Tag Archives: infectious disease

Must Know Antimicrobial Regimens – Adults

Authors: Marina N. Boushra, MD (EM Resident Physician, Vidant Medical Center) and Cassandra Bradby, MD (EM Attending Physician, Vidant Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

A 75-year-old man with a history of diabetes, hypertension, and dementia presents to the emergency department with a complaint of altered mental status. His nursing home caretaker endorses a dry cough for one week that has recently become productive and fevers with a Tmax of 38.9 ºC. She notes that he is not “acting like himself,” and elaborates that he is sleeping more, talking less, and has had multiple episodes of urinary incontinence, which is unusual for him. His vitals on arrival are T 38.5º C, HR 110, RR 30, BP 100/70. His exam is notable for somnolence, increased work of breathing with accessory muscle use, coarse rales at the base of the right lung, tachycardia, and dry mucus membranes.

Bacterial infections are a common diagnosis in the emergency department, and emergency physicians are often tasked with providing antibiotics for outpatient management or beginning antibiotics prior to admission. Antibiotic treatment is not without side effects, and treatment started in the emergency department is frequently empiric. Therefore, an understanding of the most likely causative organisms as well as local patterns of susceptibility and resistance is paramount to adequate treatment, appropriate antibiotic selection, and responsible antibiotic stewardship. Important historical details to elicit include allergies, recent antibiotic use, prior antibiotic failure, dialysis use, use of immunosuppressants or history of immunocompromise, culture results of prior infections, and contact with healthcare facilities, including recent hospitalization, living in a care facility, or recent invasive procedures such as ureteral catheterizations or intubation. These details offer vital information regarding possible bacterial resistance or the presence of opportunistic infection. Because multiple empiric regimens exist for infectious disease in the emergency department, contacting the hospital pharmacy about the local antibiogram may help tailor the empiric regimen to local microbial susceptibilities. Please keep this in mind with the recommendations discussed in each table. The following is a discussion of the most common or most emergent ED-diagnosed bacterial infections, their most likely causative organisms, and current recommendations for empiric treatment.

Pneumonia

Pneumonia is infection of the pleural parenchyma and can be broadly divided into community-acquired (CAP) and hospital-acquired pneumonia (HAP). A third category of pneumonia, healthcare-associated pneumonia, is discussed in more detail later in this paper. The majority of pneumonia is community-acquired but historical details such as recent hospitalization, intubation, or ventilator dependence should raise concern for HAP and multi-drug resistant organisms (MDROs). Travel history may be important for more rare causes of pneumonia. In patients with known or suspected HIV or AIDS, pneumocystis pneumonia should be strongly considered.

Community-Acquired Pneumonia (CAP)

CAP can be caused by a variety of pathogens, with the most common bacterial cause being Streptococcus pneumonia1–3. Other common organisms include respiratory viruses, Haemophilus influenza, and Mycoplasma pneumoniae1–3. In patients requiring ICU admission, S. pneumoniae is still common, but there is increased prevalence of Legionella pneumophila, Staphylococcus aureus, gram-negative bacilli, and influenza4. It is important to remember these differences in etiology and to cover adequately for these serious organisms in patients requiring ICU admission. Patients with risk factors for aspiration pneumonia should receive additional anaerobic coverage. Treatment for CAP has become increasingly more complicated due to rising resistance to antibiotics. Risk factors for drug resistance include age >65, alcoholism, medical comorbidities, immunosuppressive illness or medication use, and use of beta-lactam, macrolide, or fluoroquinolone antibiotics in the last 3-6 months5,6.

Treatment should be initiated as soon as a diagnosis of CAP is made to prevent decompensation. CAP can often be treated on an outpatient basis. Studies have shown that physicians often use inconsistent criteria when making the decision to admit patients for the treatment of CAP and overestimate short-term patient mortality, leading to an increased rate of unnecessary hospitalizations7. The 2007 guidelines for the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS) recommend using the CURB-65 score or Pneumonia Severity Index (PSI), both well validated prediction rules and decision aids, to aid in the risk stratification of patients and making the decision to admit for inpatient treatment7–9. Interestingly, a recent article investigating oral vs. intravenous fluoroquinolones for non-critically ill patients with CAP showed no difference in mortality, ICU transfers, or need for vasopressors or intubation10. Studies have shown shorter time to treatment and shorter hospital stays for patients started on oral rather than intravenous antibiotics11. As such, it is important to consider oral therapy in non-critically ill patients with CAP who are being admitted for treatment but are able to tolerate oral medication.

Studies have shown similar efficacy in CAP for fluoroquinolones and macrolides plus a penicillin or cephalosporin12. Importantly, there is a high rate of macrolide resistance in S. pneumoniae in the United States; as such, macrolides should not be used as empiric monotherapy in areas where resistance to macrolides is >25%5,13–15. Recommended regimens are outlined in the Table 1 below. The IDSA is expected to publish new guidelines for the treatment of CAP that better reflect current trends in resistance in the summer of 2017.

Hospital-Acquired (nosocomial) Pneumonia (HAP)

Pneumonia patients with recent hospitalizations present a challenge in antibiotic selection. While the pneumonia may be caused by an MDRO picked up in the healthcare environment, it is also possible that the patient has a simple community-acquired organism. The multi-drug resistant (MDR) score assesses a particular patient’s risk for infection with an MDRO16,17. Patients with a high MDR score should be presumed to have a pneumonia due to a resistant organism and treated accordingly with broad-spectrum coverage as outlined in Table 1 below. Patients with low MDR scores can be treated with the more narrow-spectrum coverage used for CAP, with the possibility of widening the spectrum in the event of treatment failure. The Shorr score is a similar scoring tool to assess the risk of infection by an MDR and tailor empiric coverage appropriately18.  Antibiotic treatment for presumed HAP should cover for Staphylococcus aureus and Pseudomonas aeruginosa19. Local antimicrobial prevalence and susceptibility, especially within the hospital, is helpful to determining a regimen, but can often be deferred to the judgement of the admitting team. Empiric regimens as recommended in the 2016 IDSA/ATS guidelines for empiric management of HAP are outlined in Table 1 below.

Healthcare-Associated Pneumonia (HCAP)

Healthcare-associated pneumonia (HCAP) refers to pneumonia that may have been acquired in healthcare facilities such as nursing homes and dialysis centers. It was formerly grouped with HAP due to presumed increased susceptibility to MDROs. Several studies, however, have shown no increased susceptibility to MDROs in patient with HCAP, and it is conspicuously missing from the IDSA/ATS guidelines on the management of HAP19–24. As such, in the absences of other historical susceptibilities to MDROs such as comorbidities or severe illness, patients with HCAP may be treated as CAP19–24.

Table 1: Empiric Treatment of Pneumonia based on type, setting, and patient-specific factors8,19

Type Setting Patient Factors Regimen
CAP Outpatient No recent antibiotics, co-morbidities, high-rate of resistance -Doxycycline 100mg bid for five days

-Azithromycin 500mg on day 1 followed by 250mg for four days.*

-Clarithromycin 500mg bid for seven days*

Recent antibiotics, co-morbidities, high-rate of resistance -Levofloxacin 750mg daily for five days

-Moxifloxacin 400mg daily for five days

-Gemifloxacin 320mg daily for five days

-Combination therapy with a beta-lactam (amoxicillin 1g tid, amoxicillin-clavulanate 2g bid, cefpodoxime 200mg bid, or cefuroxime 500mg bid) PLUS either a macrolide (azithromycin 500mg on day 1, followed by 250mg for four days, or clarithromycin 500mg bid for five days) or doxycycline 100mg bid for five days.

Inpatient Mild-Moderate disease, managed on general floor -Levofloxacin 750mg IV or po

-Moxifloxacin 400mg IV or po

-Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a macrolide (azithromycin 500mg IV, or clarithromycin 500mg orally)

Severe disease requiring ICU admission -Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a respiratory fluoroquinolone (levofloxacin 750mg IV, or moxifloxacin 400mg IV) OR azithromycin 500mg IV.

-If penicillin allergic, a respiratory fluoroquinolone PLUS aztreonam 1g

-If MRSA suspected, add vancomycin 15-20mg/kg IV

HAP Inpatient Combination therapy is warranted, with one from each of the following 3 categories:

1) Piperacillin-tazobactam 4.5 g IV, Cefepime 2 g IV, Ceftazidime 2g IV, Imipenem/cilastatin 500mg IV

2) Azithromycin 500mg IV, Ciprofloxacin 400mg IV, Levofloxacin 750mg IV, or Gentamicin 5-7mg/kg IV

3) Vancomycin 15-20mg/kg IV, Linezolid 600mg IV

*Macrolide antibiotics should not be used as empiric monotherapy in areas of known S. pneumoniae resistance >25% to macrolides. If such resistance exists, pair with a beta-lactam as shown in the table above.

Urinary Tract Infection

Urinary tract infections can involve the lower urinary tract (cystitis) or the upper tract (pyelonephritis). Urinary tract infections are very common in women, with sexually active women being at higher risk. Risk factors for urinary tract infections include recent sexual intercourse, prior urinary tract infections, and recent spermicide use25. When present in men, urinary tract infections are typically associated with underlying anatomical anomalies, recent catheterization, or other risk factors. While not all urinary tract infections in males are necessarily complicated, a search for these risk factors should be conducted when a male is diagnosed with a urinary tract infection.

Uncomplicated Cystitis

Urinary tract infections in women begin by bacterial colonization of the vagina by fecal bacteria, which may ascend via the urethra to infect the bladder and kidneys. Uncomplicated cystitis and pyelonephritis in women is typically caused by Escherichia coli, though Proteus mirabilis, Klebsiella pneumoniae, and Streptococcus saprophyticus are occasionally found26,27. Empiric treatment for uncomplicated urinary tract infections is best tailored to the regional E. coli sensitivities and is outlined in Table 328. Of note, this table may be modified based on local resistance patterns. Sterile pyuria should raise concern for a possible sexually-transmitted infection (STI) and patients who fail to improve despite appropriate antibiotic treatment should be tested for STI.

Complicated Urinary Tract Infection

A complicated urinary tract infection is one which is associated with a condition that increases the risk for therapeutic failure, as outlined in Table 2. The microbial spectrum of complicated UTI is more broad, including not only the typical organisms associated with uncomplicated UTI but also more varied and resistant pseudomonal, staphylococcal, and Serratia species as well as fungi29,30. Complicated lower urinary tract infections may be managed as an outpatient, but indications for hospitalization include inability to tolerate oral therapy or suspected/ documented infection with a resistant organism such as extended-spectrum beta-lactamase producing organisms (ESBLs). Complicated pyelonephritis is the progression of infection resulting in emphysematous pyelonephritis, corticomedullary or perinephric abscess, or papillary necrosis. Complicated pyelonephritis is an indication for admission and intravenous antibiotic treatment.

Table 2: Conditions that increase the risk of treatment failure in UTI (complicated UTI)

Diabetes
Pregnancy
Renal failure
Hospital-acquired infection
Immunosuppression
Renal transplantation
Anatomic abnormality of the urinary tract
Symptoms >7 days prior to presentation
Presence of an indwelling foreign body (ureteral catheter, nephrostomy tube, ureteral stent)
Ureteral calculus

UTI and Asymptomatic Bacteriuria in the Pregnant Patient

Urinary tract infection and colonization in pregnant patients are worth special mention. While asymptomatic bacteriuria in a non-pregnant female does not warrant treatment, studies have shown a high rate of progression to symptomatic cystitis and pyelonephritis in pregnant patients31. As such, current recommendations suggest that any bacteriuria in a pregnant patient should be treated with antibiotics32. Additionally, although urinary tract infection in a pregnant woman is, by definition, complicated, fluoroquinolones, the first-line treatment for complicated cystitis, are a pregnancy class C medication and should be avoided33. Mild urinary tract infections in pregnant females are treated similarly to uncomplicated UTIs, as shown in Table 3 below. Follow-up cultures for resolution are important in this patient population34.

Table 3: Empiric treatment of uncomplicated and complicated urinary tract infections28,31,35.

Urinary Tract Infection Recommended regimen
Uncomplicated cystitis -Nitrofurantoin 100mg bid for five days*

-Trimethoprim-sulfamethoxazole 160/800mg bid for three days

-Cephalexin 500mg BID for 3-7 days

-Fosfomycin 3g in a single dose*

-Ciprofloxacin 250mg bid or Levofloxacin 250mg once per day for three days**

Complicated cystitis Outpatient:

-Ciprofloxacin 500mg bid or 1000mg daily for five to ten days

-Levofloxacin 750mg daily for five to ten days

Inpatient:

-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

-Tobramycin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

Uncomplicated Pyelonephritis

 

 

Outpatient:

-Ciprofloxacin 500mg po bid for seven days or 1000mg daily for seven days

-Levofloxacin 750mg po daily for five to seven days

Inpatient:

-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV

-Tobramycin 3-5mg/kg IV

Complicated Pyelonephritis – Inpatient, mild-moderate disease:

-Ceftriaxone 1g IV

-Ciprofloxacin 400mg IV

-Levofloxacin 750 mg IV

-Aztreonam 1g IV

Inpatient, severe disease:

-Cefepime 2g IV

-Ampicillin 1g IV four times per day plus Gentamicin 5mg/kg IV daily

-Piperacillin-tazobactam 3.375g IV

-Meropenem 500mg IV

-Imipenem 500mg IV

-Doripenem 500mg IV

Asymptomatic bacteriuria and acute cystitis in the pregnant patient -Nitrofurantoin 100mg po bid for five to seven days (in second or third trimester)*

-Trimethoprim-sulfamethoxazole 160/800 mg po bid for three days****

-Fosfomycin 3g po in a single dose*

-Amoxicillin-clavulanate 500mg po tid for three to seven days

-Cephalexin 500mg po bid for three to seven days

-Cefpodoxime 100mg po bid for three to seven days

*Fosfomycin and nitrofurantoin should be avoided if there is concern for early pyelonephritis.

**Fluoroquinolones, if possible, should be reserved for other important uses to avoid resistance against this class of antibiotics.

***Adding ampicillin provides Enterococcus coverage

****Should be avoided in first trimester and at term

Cellulitis and Soft-Tissue Infection

Cellulitis and Erysipelas

Cellulitis and erysipelas are bacterial skin infections that differ in that erysipelas involves the upper dermis and superficial lymphatics while cellulitis involves the deeper dermis and subcutaneous fat tissue. Both manifest with localized skin erythema, edema, warmth, and pain. Because of the more superficial nature of erysipelas, these lesions are typically more raised and better demarcated than cellulitis. Erysipelas also presents more acutely and with more systemic symptoms such as fevers and chills. The most common pathogens in cellulitis are beta-hemolytic streptococci and S. aureus, including methicillin-resistant S. aureus (MRSA)36–38. Beta-hemolytic streptococci are the most common cause of erysipelas36,39.

Lesions consistent with cellulitis should be examined closely for the presence of a drainable abscess. History is particularly important in the patient with possible cellulitis as cellulitis associated with human or animal bites or with water exposure needs different coverage than uncomplicated cellulitis. The presence of an indwelling device near the region of cellulitis is also important, as it is an indication of device infection.

The treatment of uncomplicated cellulitis is based on whether or not there is associated purulence. Current guidelines group erysipelas with non-purulent cellulitis in terms of treatment, as the lesions are often difficult to distinguish from each other and are caused by a similar spectrum of organisms. Patients with purulent cellulitis should receive empiric coverage for MRSA pending culture results40. Patients with non-purulent cellulitis or erysipelas should receive empiric coverage for beta-hemolytic streptococcus and MSSA, although patients with systemic symptoms, recurrent infection, or prior infection with MRSA should receive additional MRSA coverage36. Cellulitis can typically be managed as an outpatient; patients with signs of systemic toxicity, rapid progression, indwelling devices, or failure of outpatient management should be admitted for parenteral antibiotics. In addition to antibiotics, elevation of the affected area is an important aspect of treatment as it helps promotes drainage of edema and inflammatory substances, speeding symptomatic improvement36.

Table 4: Empiric treatment of cellulitis and erysipelas36

Infection Recommended regimen
Uncomplicated nonpurulent cellulitis without MRSA risk factors or erysipelas Outpatient -Dicloxacillin 500mg po qid for 5-10 days

-Cephalexin 500mg po qid for 5-10 days

-Clindamycin 450mg po tid for 5-10 days

Inpatient -Cefazolin 1-2g IV tid

-Ceftriaxone 1g IV every 24 hours

-Oxacillin or nafcillin IV every 4 hours

-Clindamycin 600-900mg IV tid

Uncomplicated purulent cellulitis or nonpurulent cellulitis with MRSA risk factors

 

Outpatient -Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Skin abscesses

Skin abscesses are most commonly due to S. aureus (MRSA or MSSA), although polymicrobial infection with flora from the skin or adjacent mucosal tissues is also common36,40–42. Risk factors for MRSA infection include recent hospitalization or antibiotic use, contact with healthcare environments, institutionalization, HIV infection, intravenous drug use, and diabetes. Source control, in the form of warm compresses to promote drainage or incision and drainage, is important. The role of antibiotics following source control is debated. Studies have shown a slightly increased cure rate with the use of antibiotics following incision and drainage of uncomplicated abscesses, but also a higher rate of diarrhea and adverse effects43,44. Antibiotics should be started for large (>2cm) or multiple abscesses, extensive surrounding cellulitis, systemic symptoms, immunocompromise or co-morbidities, the presence of an indwelling device, or in cases where incision and drainage alone fails to achieve adequate clinical response36. Hospitalization and parenteral antibiotics should be considered for patients with extensive skin involvement or signs of systemic toxicity.

Table 5: Empiric antibiotic treatment of abscesses following source control36

Outpatient If suspicion for MRSA:

-Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg po bid for 5-7 days

If no suspicion for MRSA:

-Dicloxacillin 500mg po bid for 5-7 days

-Cephalexin 500mg po bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Sexually-Transmitted and Vulvovaginal Infections

Sexually transmitted infections (STI) are a diagnosis of immense public health importance. While the results of lab testing are often not available in the emergency department, physicians should have a low threshold for the initiation of treatment in patients with presentations consistent with STI. Treatment for common STIs is outlined in Table 6 below45. Counseling patients about safe sex practices and urging them to inform their partners is paramount to infection control.

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is infection of the upper genital tract (uterus, endometrium, fallopian tubes, ovaries) in women. PID may extend to involve adjacent structures, causing periappendicitis, pelvic peritonitis, and perihepatitis (Fitz-Hugh-Curtis syndrome). The majority of PID is caused by ascending sexually-transmitted infections (STI), with Neisseria gonorrhea and Chlamydia trachomatis being the most commonly implicated pathogens in PID45. The diagnosis of PID is often a presumptive one based on presentation. Due to the risk for tubal scarring leading to infertility or risk of ectopic pregnancy, even minimal symptoms without an alternative diagnosis warrant the start of antibiotic therapy to reduce the risk of serious complications due to delay of therapy. Mild to moderate disease can be treated as an outpatient. Indications for hospitalization and intravenous antibiotics include pregnancy, clinically severe disease, complicated PID (pelvic abscess), and intolerance to, noncompliance with, or failure of oral antibiotics. Empiric coverage for inpatient and outpatient management of pelvic inflammatory disease are outlined in Table 646,47.

Table 6: Recommended treatment regimens for select genitourinary infections45–47

Chlamydia -Azithromycin (1g po in one dose)

-Doxycycline (100mg bid for 7 day)

Gonorrhea* -Ceftriaxone (250mg IM or IV in one dose) plus azithromycin (1g po in one dose) or doxycycline (100mg bid for 7 days)
Trichomonas -Metronidazole (2g po in a single dose or 500mg bid for seven days)

-Tinidazole (2g po in a single dose)

Bacterial Vaginosis -Metronidazole (500mg  po bid for seven days)

-Metronidazole vaginal gel 0.75% (5g intravaginally for five days)

-Clindamycin vaginal gel 2% (5g intravaginally for seven days)

Candida Vulvovaginitis Fluconazole (150mg po in one dose)
Pelvic Inflammatory

Disease

Outpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

Inpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

*Patients with gonorrhea should also be treated for chlamydia due to high rates of concomitant infection.

Bacterial meningitis

While meningitis is not as common an emergency department diagnosis as the bacterial infections discussed above, patients with meningitis are often quite ill, and knowledge of appropriate antibiotic coverage can speed time to therapy. The most common causes of community-acquired meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, in older adults, Listeria monocytogenes48,49. Empiric treatment should be initiated as soon as meningitis is suspected. Empiric regimens should include ceftriaxone (2g every 12 hours) or cefotaxime (2g every 4-6 hours) for coverage of N. meningitidis and S. pneumoniae as well as vancomycin due to increasing rates of S. pneumoniae resistance to third-generation cephalosporins50,51. In patients >50 years of age or with immunocompromise, ampicillin (2g every 4 hours) should be added to provide coverage for L. monocytogenes49.

Adverse Effects of Antibiotic Use

A discussion of antibiotic use in the emergency department would be remiss without mention of the adverse effects of antibiotics commonly used in the ED. While the use of certain antibiotics may be unavoidable due to patient allergies or susceptibility patters, knowledge of the adverse effects of antibiotics may help guide therapeutic choices and inform or temper patient expectations.

Clostridium difficile infection should always be a consideration when starting antibiotics. Clindamycin is the most common culprit in antibiotic-associated C. difficile infection, but cephalosporins, penicillins, and fluoroquinolones are also common causes52–56. Aminoglycosides, tetracyclines, metronidazole, and vancomycin are rarely associated with C. difficile infection, though any antibiotic use increases the risk for C. difficile infection57. Other important adverse effects include QT prolongation with arrhythmia associated with macrolide and fluoroquinolone use and the risk of peripheral neuropathy and (the uncommon, but oft-cited) tendon rupture with fluoroquinolone use. Common or serious side effects of antibiotics used in the emergency department are summarized in Table 7 below.

Table 7: Common and serious adverse effects of commonly used antibiotics

Antibiotic Common Adverse Effects Serious Adverse Effects Comments
Beta-lactams C. diff infection, diarrhea Hypersensitivity reactions High risk of C. diff, especially with broader coverage and with ampicillin
Macrolides Diarrhea, nausea, vomiting, abdominal pain QT prolongation (especially with erythromycin)
Clindamycin C. diff infection, diarrhea Serious hypersensitivity reactions Most common cause of C. diff
Fluoroquinolones Anorexia, nausea, vomiting, abdominal pain Tendon rupture, peripheral neuropathy, QT prolongation High C. diff risk
Tetracyclines Nausea, diarrhea, photosensitivity Inhibition of bone growth and tooth discoloration (a concern in children) Low C. diff risk
Vancomycin Abdominal pain, nausea Nephrotoxicity, ototoxicity, Red man syndrome, hypotension Red man syndrome can be prevented with pretreatment with antihistamines
Aminoglycosides Nephrotoxicity, ototoxicity Need frequent monitoring of drug levels
Metronidazole Headache, dizziness, metallic taste Disulfiram-like reaction Low C. diff risk
  • Summary

Table 8: Common and serious bacterial infections and recommended empiric treatment

Infection Important organisms to cover Recommended Regimens
Community-acquired pneumonia S. pneumoniae CAP outpatient: doxycycline, macrolide +/- penicillin or cephalosporin

CAP inpatient, mild: respiratory fluoroquinolone, macrolide + penicillin or cephalosporin

S. pneumoniae, L. pneumophila, S. aureus CAP inpatient, severe: penicillin or cephalosporin+ fluoroquinolone OR azithromycin
Hospital-acquired pneumonia S. pneumoniae, MRSA, P. aeruginosa HAP inpatient: anti-pseudomonal penicillin or cephalosporin, or fluoroquinolone, or carbapenem + vancomycin/linezolid
Uncomplicated cystitis E. coli Nitrofurantoin or fosfomycin or TMP/SMX or ciprofloxacin

 

Complicated cystitis or uncomplicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Outpatient: Fluoroquinolone

Inpatient: Fluoroquinolone or aminoglycoside or third-generation cephalosporin or carbapenem

Complicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Inpatient, mild-moderate: third-generation cephalosporin or monobactam

Inpatient, severe: anti-pseudomonal penicillin or cephalosporin, carbapenem

Asymptomatic bacteriuria or simple cystitis in the pregnant patient E. coli Nitrofurantoin or TMP/SMX or fosfomycin, or penicillin or cephalosporin with gram-negative coverage
Nonpurulent cellulitis or abscess without MRSA risk factors, erysipelas Beta-hemolytic streptococcal species, MSSA Outpatient and inpatient: staphylococcal penicillin or cephalosporin
Purulent cellulitis, nonpurulent cellulitis or abscess with MRSA risk factors Beta-hemolytic streptococcal species, MSSA, MRSA Outpatient: Clindamycin or TMP/SMX or doxycycline

Inpatient: Vancomycin or clindamycin

Chlamydia C. trachomatis Azithromycin or doxycycline
Gonorrhea N. gonorrhea AND C. trachomatis Ceftriaxone plus azithromycin or doxycycline
Trichomonas Trichomonas vaginalis Metronidazole or tinidazole
Bacterial vaginosis Polymicrobial, anaerobic gram-negative rods Metronidazole oral or intravaginal gel or clindamycin
Candida Vulvovaginitis C. albicans, C. glabrata Fluconazole
Pelvic Inflammatory Disease N. gonorrhea, C. trachomatis Inpatient and outpatient: third generation cephalosporin plus doxycycline
Bacterial meningitis S. pneumoniae, N. meningitidis, L. monocytogenes (if >50 years or immunocompromised) Vancomycin plus third generation cephalosporin +/- ampicillin if age >50 or immunocompromised

 

 References / Further Reading

  1. Johansson, N., Kalin, M., Tiveljung-Lindell, A., Giske, C. G. & Hedlund, J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin. Infect. Dis. 50, 202–9 (2010).
  2. Jain, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N. Engl. J. Med. 373, 415–27 (2015).
  3. Gadsby, N. J. et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin. Infect. Dis. 62, 817–23 (2016).
  4. Cillóniz, C. et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 66, 340–6 (2011).
  5. Vanderkooi, O. G. et al. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin. Infect. Dis. 40, 1288–97 (2005).
  6. Ramsdell, J., Narsavage, G. L. & Fink, J. B. Management of Community-Acquired Pneumonia in the Home: An American College of Chest Physicians Clinical Position Statement. Chest 127, 1752–1763 (2005).
  7. Fine, M. J. et al. The hospital admission decision for patients with community-acquired pneumonia. Results from the pneumonia Patient Outcomes Research Team cohort study. Arch. Intern. Med. 157, 36–44 (1997).
  8. Mandell, L. A. et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 44 Suppl 2, S27-72 (2007).
  9. Lim, W. S. et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58, 377–82 (2003).
  10. Belforti, R. K. et al. Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia. Clin. Infect. Dis. 63, 1–9 (2016).
  11. Cyriac, J. M. & James, E. Switch over from intravenous to oral therapy: A concise overview. J. Pharmacol. Pharmacother. 5, 83–7 (2014).
  12. Ruhe, J. & Mildvan, D. Does Empirical Therapy with a Fluoroquinolone or the Combination of a β-Lactam Plus a Macrolide Result in Better Outcomes for Patients Admitted to the General Ward? Infect. Dis. Clin. North Am. 27, 115–132 (2013).
  13. Low, D. E. What Is the Relevance of Antimicrobial Resistance on the Outcome of Community-Acquired Pneumonia Caused by Streptococcus pneumoniae? (Should Macrolide Monotherapy Be Used for Mild Pneumonia?). Infect. Dis. Clin. North Am. 27, 87–97 (2013).
  14. Daneman, N., McGeer, A., Green, K., Low, D. E. & Toronto Invasive Bacterial Diseases Network. Macrolide resistance in bacteremic pneumococcal disease: implications for patient management. Clin. Infect. Dis. 43, 432–8 (2006).
  15. Jones, R. N., Sader, H. S., Moet, G. J. & Farrell, D. J. Declining antimicrobial susceptibility of Streptococcus pneumoniae in the United States: report from the SENTRY Antimicrobial Surveillance Program (1998-2009). Diagn. Microbiol. Infect. Dis. 68, 334–6 (2010).
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Evaluation of Fever in the Emergency Department

Authors: Sarah Dewitt, MD (EM Resident Physician, Virginia Tech-Carilion), Summer Chavez, DO/MPH (EM Resident Physician, Virginia Tech-Carilion), and Jack Perkins, MD (EM Assistant Program Director, Virginia Tech-Carilion) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case:  A 61 y/o male is brought to the Emergency Department (ED) by his family for complaints of dyspnea, subjective fever, and chest pain. He has no past medical history, and his VS include temperature 100.6°F, heart rate of 110, blood pressure 130/80, respiratory rate of 26, and pulse oxygenation 90% on room air.  His examination reveals a well-developed male who is in mild distress, but the cardiac and pulmonary examinations are non-contributory.  Your initial concerns focus around suspicion of pneumonia, although your resident quickly points out this could also be the presentation of a pulmonary embolus.  Does the fever help you differentiate between the two, or would have a lack of fever altered your clinical evaluation?  How does the presence of fever shape the differential diagnosis in the ED, and in those patients where an infectious etiology is suspected, should the absence of fever reassure the provider?

Introduction: The pathophysiology of fever

The hypothalamus controls body temperature by balancing inputs from the peripheral nerves that utilize warm/cold receptors in the skin and also analyze the temperature of blood in the surrounding area.1 Fever itself is typically caused by a pyrogen, simply defined as a chemical substance that provokes fever. One such example is exogenous pyrogens, such as those seen in gram-positive bacteria (Staphylococcus aureus enterotoxins) and the superantigens associated with Group A streptococcus and Group B streptococcus microbial infections.1 Many bacteria and fungi can trigger the production and release of cytokines, small proteins that trigger the inflammatory cascade. These cytokines lead to prostaglandin-2 release in peripheral tissues, raising the hypothalamic temperature set point through cAMP release. Central nervous system cytokines are responsible for the hyperpyrexia seen in neurologic trauma and infection.1

Table 1: Differential diagnosis of fever in the ED (note: table not inclusive of all possible causes of fever)

Infectious Causes of Fever   Non-Infectious Causes of Fever 
Bacterial Infections 

•      UTI 

•      Pneumonia 

•      Meningitis 

•      Intra-abdominal 

•      Skin/soft-tissue 

•      Osteomyelitis  

Malignancy (e.g. leukemia, lymphoma, pheochromocytoma)
Viral Infections 

•      URI, pharyngitis  

•      Gastroenteritis 

•      Aseptic meningitis  

•      HIV 

•      Influenza

Autoimmune (e.g. rheumatoid arthritis, systemic lupus erythematosus)
Parasitic Infection 

•      Malaria

•      Toxoplasmosis

•      Giardiasis

Drug Reaction

•      Allergic reaction to, or metabolic consequences of drug

Arthropod Infections 

•      Lyme

•      Rocky Mountain Spotted fever

•      Babesiosis

Seizure
Fungal Infections 

•      Candidiasis

•      Blastomycosis

•      Histoplasmosis

 

Environmental Fever

•      High external temperatures, or excess exercise

  Hyperthyroidism
  Neurologic

•      Subarachnoid hemorrhage

  Embolic vs. Thrombosis vs. Infarction

•      MI

•      Renal infarct

•      PE

  Blood Transfusion Reaction
  Factitious Fever

•      Munchausen’s vs. Munchausen’s by proxy

How do I proceed to determine if the fever in front of me is from an infectious vs. non-infectious source?

Fever is a common finding in patients presenting to the ED. The differential diagnosis of fever is broad and not limited to infectious etiologies. A key clinical question is deciding whether infection is likely enough to warrant antimicrobial administration. A detailed history and physical exam, the past medical history, current medications (e.g. chemotherapy, glucocorticoids), and recent use of antibiotics may help shape the pre-test probability of an infectious source of fever.  However, it is common to need adjunctive laboratory testing or radiographic imaging to further evaluate the source of the fever.  Basic testing in the ED often involves a complete blood count (CBC), urinalysis, and a Chest X-ray (CXR).  The emergency provider (EP) may deem it appropriate to send a urine culture, blood cultures, and add viral antigen testing in select cases.  For example, blood cultures may not be necessary in cases of UTI or pneumonia in patients being discharged; however, they would be useful in cases of severe sepsis or septic shock, as these patients will be admitted and the inpatient team will need this information.  It may also be necessary to look further through other serologic testing such as C-reactive protein (CRP), sedimentation rate (ESR), and Procalcitonin.

CRP is an acute phase reactant that becomes elevated in response to inflammatory stimuli. Serum CRP levels surge within 4-6 hours after stimulation, double every 8 hours, and peak after 35-60 hours. It is therefore going to be a more beneficial marker of infection after 12 hours of fever. However, in patients who present with fever at more than 12 hours after onset, it has been shown that serum CRP is elevated significantly in patients with bacterial infections.3  Initially, the measurement of CRP was quantitative and positive in almost all disease states, making it a poor test of choice for diagnosing.  Since then, labs have created a specific monoclonal antibody and immunological methods of measurement that have made the CRP test used today very accurate and reproducible.  It is quick, and its sensitivity is within 0.04mg/L.4  The value of a single CRP measurement in sepsis diagnosis has been investigated and has been found to be useful in the diagnosis of sepsis.4  In a review published in Intensive Care Med 2002, different studies found that CRP cutoffs between 40-100 mg/L had sensitivity for detecting sepsis between 71-100%, and specificity between 40-85.5%.4  CRP is non-specific, however, and may be elevated in numerous other conditions such as malignancy, rheumatologic disease, and chronic vascular disease among other conditions.  It is used most frequently when the provider needs adjunctive information in the search for more unusual sources of infection such as osteomyelitis.

Much like CRP, an ESR is occasionally sent in the ED often as an adjunctive piece of information when searching for more unusual causes of infection such as osteomyelitis or a septic prosthetic joint. It suffers from the same lack of specificity, especially in the older population with numerous comorbid conditions.

Procalcitonin (PCT) is a 116-amino acid peptide that is elevated mainly in response to infectious etiologies.  It is much more likely to be elevated in bacterial as opposed to viral infections.5, 6 Serum procalcitonin levels increase significantly in severe systemic infections.5 While PCT has been studied extensively in the inpatient setting to de-escalate antibiotic therapy and to determine utility of empiric antibiotics in COPD exacerbations, its role in the ED has yet to be defined.  Currently its use is not widespread, and it has not been well enough studied in the ED to support its use in determining antibiotic deployment in patients with severe sepsis or septic shock.

In sum, it may take a considerable amount of time to make a decision in the ED as to whether the febrile patient truly has an infectious etiology and what antibiotics are most appropriate.  In the sickest patient cohort (e.g. shock), empiric antibiotics are clearly indicated when sepsis is high on the differential. However, we are obligated to proceed cautiously in those stable febrile patients in whom infection is not readily apparent.  Indiscriminate use of antibiotics is fraught with consequences for the patient and the healthcare system.  Keep in mind it may still be unclear after a few hours in the ED as to whether the source of the patient fever is infectious, even after robust use of ancillary testing and a thorough history and physical examination.

How often does sepsis present without a fever?

The SIRS criteria embrace hyperthermia and hypothermia as part of the various parameters to help identify potential sepsis.  These criteria have come under scrutiny in recent years, and there is no better example as to the pitfalls of the SIRS criteria than the potential for the septic patient who is afebrile.  In the elderly and the immunocompromised patient (e.g. HIV/AIDS, cancer, cirrhosis, diabetes mellitus systemic corticosteroid use, organ transplant, use of immunosuppressant medications), the febrile response to infection might be absent. Some sources report that 20-30% of elderly patients may either remain afebrile or mount a blunted response to infection.8 In fact, some studies postulate that patients who do not mount a febrile response to infection often have more adverse clinical outcomes.  A study by Fernandes et al highlighted this risk in elderly patients with bacterial meningitis.9 They found that factors that were independently associated with adverse clinical outcome were older age, absence of fever at ICU admission, and lower GCS score.9

Caterino et al reported that only absence of fever on initial presentation to the ED and initial serum bicarbonate level were independently predictive of patient decompensation after admission to a floor bed as defined by a transfer to the ICU within 48 hours of admission.10 One potential conclusion from this study suggests that the diagnosis of sepsis, subsequent treatment, and assessment of severity of illness are all made more complex in the afebrile patient who truly has sepsis.11  The literature also supports atypical presentations (i.e. afebrile, non-specific complaints such as weakness) of the elderly patients who are bacteremic.12

In sum, do not dismiss the potential for sepsis simply because fever is not present.  The older patient and those who are immunocompromised should be expected to present in atypical fashion, and sepsis should be on many differentials regardless of whether fever is documented.

How accurate are oral temperatures compared to other core temperatures?

Oral temperatures are much more convenient that core temperatures in the ED. However, the evidence does not support the accuracy of oral temperatures. A 2015 meta-analysis determined that the accuracy of peripheral temperatures was unacceptable for making clinical decisions.1 Seventy-five studies were included that compared a gold standard core temperature to peripheral temperatures. The authors used ± 0.5 °C as the accepted limit of agreement.13 In patients with hyperthermia, the limits of agreement were -1.44 °C to 1.46 °C, and in hypothermia, -2.07 °C to 1.90 °C.13 The calculated sensitivity was only 64% [95% CI: 55-72%], but specificity performed better at 96% [95% CI: 93-97%].13

In conclusion, if the patient has a fever or is hypothermic by oral temperature, it does not need to be repeated. However, if the patient is normothermic by an oral temperature and the result would change provider management (e.g. sepsis is high on the differential), a core temperature is strongly recommended, either by a rectal thermometer or temperature sensing foley catheter.

Is there any harm in not treating a fever?

While some authors argue that fever places physiologic stress on patients, other data supports that fever enhances the immune system and curbs bacterial growth.14 Additional data from observational studies concluded that a higher early fever was linked to lower mortality rates in ICU patients admitted due to infectious causes.14  The results from a 2015 randomized controlled clinical trial that studied the benefit of treating fever in ICU patients were published in the New England Journal of Medicine.14 Seven hundred ICU patients with fever were randomized to receive either 1000 mg of acetaminophen or placebo.14 There was no statistical significance in number of ICU-free days, 28-day mortality, or 90-day mortality between either group.14 While this one RCT showed no true benefit to treating fever, clinical judgment is important as some patients may be distressed by the fever and appreciate anti-pyretic therapy.

Does the degree of fever help in narrowing the differential in terms of infectious vs. non-infectious etiology? 

Fever > 106.7° F is considered to be hyperpyrexia.1 While this can happen in septic patients, this is more common in those with intracranial hemorrhage, neuroleptic malignant syndrome, and heat stroke.1, 15 Additionally, there is a marked difference between hyperthermia and fever. Hyperthermia is treated differently and does not respond to typical anti-pyretics, as there are no pyrogenic molecules.1 Consider what the patient was doing immediately before presentation, such as long exposure in hot temperatures consistent with heat stroke.1 Even rarer are those patients who have pathology of their hypothalamus affecting their set point, such as tumor, trauma or hemorrhage—termed “hypothalamic fever.1

When you have a patient that presents with undifferentiated hyperpyrexia, think about the following differential to help guide your diagnostic evaluation.  A thorough review of the history and current medications is paramount, as serotonin syndrome, heat stroke, sepsis, and thyroid storm have specific treatments and high associated mortality.

Hyperpyrexia Differential in the ED
•      Sepsis
•      Heat Exposure (spectrum of illness)
•      Neuroleptic Malignant Syndrome
•      Medication Side Effects
•      Serotonin Syndrome
•      Thyroid Storm

Adapted from: McGugan EA. Hyperpyrexia in the emergency department. Emergency Medicine 2001;13(1):116.

In pediatric patients, it is often assumed that the degree of temperature elevation helps distinguish between a viral and bacterial etiology.  However, the literature does not support this assumption.16  In one study, neither maximum temperature, age, or leukocytosis was predictive of an underlying bacterial etiology.16

If I suspect sepsis, should I draw blood cultures in the ED each time the patient spikes a fever > 101?

It is incumbent upon emergency providers to try and obtain blood cultures on patients with severe sepsis or septic shock prior to initiation of antibiotics in a reasonable time frame. However, if the patient ends up in the ED for hours, is there utility in repeating blood cultures every time the patient is febrile?  Riedel et al did not find an increased likelihood of documenting bacteremia by employing this technique, and there is always the risk of false positive blood cultures.23 At this time it is recommended to only draw the initial set of blood cultures prior to antibiotic administration. Blood cultures are not recommended in patients who will be discharged, have uncomplicated infectious disease presentations (i.e. cellulitis admitted to a non-ICU setting), or in situations where the results of the cultures will not change management (i.e. community-acquired pneumonia admitted to a non-ICU setting).

How often does fever accompany a PE?

Two historical studies from the 1970’s reported fever in 50% (>37.5°C) and 57.1% (>38°C) of patients with pulmonary embolism respectively.16 The landmark Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study reported a much lower rate of fever in their patients with PE.  They found that 14% of patients with fever (≥ 100.0°F) had no identifiable source of that  fever other than pulmonary embolus.18 The incidence of pulmonary hemorrhage or infarction was not statistically significant higher in those with fever.18 Calvo-Romero et.al performed a retrospective review of 154 patients with acute pulmonary embolism and found 18.2% had fever (>37°C) without any other known causes.19

Fever is commonly seen in pulmonary embolism, especially low-grade fever, but any clinical significance remains to be determined. A high-grade fever (≥ 101°F) was present in only 6% of the study group in the PIOPED trial.18 In the Calvo-Romero study, 27 of 28 patients had a low-grade fever (temperature between 37°C and 39°C).1 In this study, compared to patients with PE without fever, EKG findings, mortality rates, and chest XR findings were similar.1 In the PIOPED study, 37% of patients who died with a pulmonary embolism had a low-grade fever.18 Higher-grade fevers were more likely to be associated with secondary pneumonitis or widespread pulmonary infarction in the PIOPED group.18 Unfortunately it is not uncommon for the EP to be faced with the dilemma of whether a febrile patient with respiratory complaints has a pulmonary embolus or is septic from pneumonia.  The clinician must vigorously examine the history, exam, past medical hisotry, and any ancillary testing (e.g. CXR) to help narrow the differential diagnosis. There are certianly circumstances when advanced imaging such as a CTA may be required to differentiate sepsis from pulmonary embolus, especially if the CXR is non-diagnostic.

Takeaways:

  • Not all fever is from an infectious source. Keep a broad differential and narrow based on a detailed history, a thorough physical exam, and lab/imaging results.
  • Blood cultures are not a routine part of the evaluation of fever and should be deployed in clinical scenarios which are evidence-based (e.g. septic shock) or when the results would affect patient care.
  • CRP, PCT, and ESR can be helpful in certain patient care scenarios as adjunctive information when trying to establish the source of a fever as infectious in etiology. Lack of specificity for each of these makes the clinical pre-test probability paramount prior to ordering these tests.
  • Not all septic patients have fever! Those without fever have been shown to have worse in-hospital outcomes.
  • Oral temperatures can be used for clinical decision making if a fever is documented. However, the poor sensitivity of oral temperatures mandates that a core temperature be obtained if the result would change management.  Bottom line: if you suspect sepsis and the patient is afebrile orally, get a core temperature.
  • Use your clinical judgment when deciding whether to treat a fever—not all fevers need to be treated with anti-pyretics.
  • Do not dismiss the diagnosis of pulmonary embolus because the patient is febrile.

 

References / Further Reading

  1. Dinarello CA, Porat R. Fever [Internet]. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill Education; 2015 [cited 2016 Oct 29]. Available from: http://mhmedical.com/content.aspx?aid=1120874671
  2. Morris F, Fletcher A. ABC Of Emergency Differential Diagnosis [Internet]. West Sussex, UK: Blackwell Publishing; [cited 2016 Nov 9]. Available from: https://www.google.com/search?client=safari&rls=en&q=Fletcher_C000.indd+-+ABC+Of+Emergency+Differential+Diagnosis+2009.pdf&ie=UTF-8&oe=UTF-8
  3. Lee C-C, Hong M-Y, Lee N-Y, Chen P-L, Chang C-M, Ko W-C. Pitfalls in using serum C-reactive protein to predict bacteremia in febrile adults in the ED. Am J Emerg Med 2012;30(4):562–9.
  4. Povoa P. C-reactive protein: a valuable marker of sepsis. Intensive Care Med 2002;28:235–43.
  5. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med 2008;36(3):941–52.
  6. Mat-Nor MB, Ralib A, Abdulah NZ, Pickering JW. The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. J Crit Care 2016;33:245–51.
  7. Puskarich MA, Jones AE. Sepsis [Internet]. In: Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM, editors. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill Education; 2016 [cited 2016 Nov 9]. Available from: http://mhmedical.com/content.aspx?aid=1121510693
  8. Moran D. Infections in the elderly. Top Emerg Med 2003;25(2):174–81.
  9. Fernandes D, Gonçalves-Pereira J, Janeiro S, Silvestre J, Bento L, Póvoa P. Acute bacterial meningitis in the intensive care unit and risk factors for adverse clinical outcomes: retrospective study. J Crit Care 2014;29(3):347–50.
  10. Caterino JM, Jalbuena T, Bogucki B. Predictors of acute decompensation after admission in ED patients with sepsis. Am J Emerg Med 2010;28(5):631–6.
  11. Burlaud A, Mathieu D, Falissard B, Trivalle C. Mortality and bloodstream infections in geriatrics units. Arch Gerontol Geriatr 2010;51(3):e106–9.
  12. Wester AL, Dunlop O, Melby KK, Dahle UR, Wyller TB. Age-related differences in symptoms, diagnosis and prognosis of bacteremia. BMC Infect Dis 2013;13:346–346.
  13. Niven DJ, Gaudet JE, Laupland KB, Mrklas KJ, Roberts DJ, Stelfox HT. Accuracy of peripheral thermometers for estimating temperature: a systematic review and meta-analysis. Ann Intern Med 2015;163(10):768–77.
  14. Young P, Saxena M, Bellomo R, et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med 2015;373(23):2215–24.
  15. McGugan EA. Hyperpyrexia in the emergency department. Emerg Med 2001;13(1):116.
  16. Trautner BW, Caviness AC, Gerlacher GR, Demmler G, Macias CG. Prospective evaluation of the risk of serious bacterial infection in children who present to the emergency department with hyperpyrexia (temperature of 106 degrees F or higher). Pediatrics 2006;118(1):34–40.
  17. Nucifora G, Badano L, Hysko F, Allocca G, Gianfagna P, Fioretti P. Pulmonary Embolism and Fever. Circulation 2007;115(6):e173–6.
  18. Stein PD, Afzal A, Henry JW, Villareal CG. Fever in acute pulmonary embolism. Chest 2000;117(1):39–42.
  19. Calvo-Romero JM, Lima-Rodríguez EM, Pérez-Miranda M, Bureo-Dacal P. Low-grade and high-grade fever at presentation of acute pulmonary embolism. Blood Coagul Fibrinolysis Int J Haemost Thromb 2004;15(4):331–3.

Can’t Miss Surgical Emergencies – Part 2

Authors: Sarah Brubaker, MD (EM Resident at SAUSHEC, US Army) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

This is the second in a two-part series discussing can’t-miss diagnoses that may require emergent surgical intervention. Part 1 (http://www.emdocs.net/cant-miss-surgical-emergencies-part-1/) included ruptured ectopic pregnancy, ruptured AAA, and aortic dissection. In this article, we will explore three more disease processes that can be easy to miss, though delay in diagnosis and treatment can lead to long-term sequelae and even death. So, without further ado, let’s jump right in to discuss three more surgical emergencies.

Case 1:

A 63-year-old male with a history of insulin-dependent diabetes, CHF, and stage II CKD presents with a painful “rash” on his left thigh. He noticed it for the first time this morning. On exam, he is slightly tachycardic, normotensive, and has a fever of 101.0 ͒F. He has an area of warm, mildly tender erythema in the inner left thigh.

NECROTIZING FASCIITIS

Epidemiology and Risk Factors

Necrotizing soft tissue infection is a rare but deadly clinical entity. According to a large cohort study in Texas, the incidence of necrotizing fasciitis has increased in the past decade (1), perhaps due to increased clinical suspicion and awareness. In this study, 72% of patients had one or more comorbidities, and the most prevalent risk factor was diabetes (48%), followed by obesity (15%). Another study found that patients with diabetes and obesity are also more likely to die as a result of necrotizing infection (2). Other risk factors include chronic alcoholism, peripheral vascular disease, heart disease, renal failure, decubitus ulcers, chronic skin infections, intravenous drug abuse, and immunocompromised states such as HIV or cancer (3,4). However, necrotizing fasciitis can also present in young, healthy individuals!

Even with prompt diagnosis and optimal treatment, necrotizing fasciitis portends high morbidity and mortality (5).  Mortality rates are classically described as 25-35%, but they have been steadily decreasing, and mortality is currently estimated to be approximately 10% in the United States (1,4).  Despite declining mortality rates, more patients are discharged to long-term facilities with debilitating conditions (1).

Pathophysiology

Most necrotizing infections are secondary infections–they develop from an initial break in the skin, usually related to accidental or iatrogenic trauma (3). According to IDSA guidelines, 80% of necrotizing skin infections result from the extension of an initial, often minor, skin lesion. These small lesions, caused from external trauma such as IV injection, surgical incision, abscess, insect bite, or decubitus ulcer, lead to direct invasion of the subcutaneous tissue that results in a rapidly spreading necrotizing process (1). The remaining 20% have no visible skin lesion, and while spontaneous development of necrotizing fasciitis is rare, patients with diabetes and malignancy are at increased risk (3).

Spread of infection below the subcutaneous tissue leads to thrombosis of the capillary beds under the skin. However, a large number of capillary beds must thrombose before dermal involvement becomes apparent, so physical exam findings do not accurately represent the extent of necrotizing infection. An ischemic tissue environment promotes bacterial growth, propagating the process and resulting in rapid spread of infection. Thus, infection can spread as quickly as one inch per hour (4)! As the disease progresses, widespread gangrene of the skin, subcutaneous tissue, fascia, and even skeletal muscle may occur. These are late findings that portend poor prognosis, so it is important to diagnose necrotizing infection long before these findings become apparent.

Necrotizing skin infections can be categorized into three groups: polymicrobial (type I), monomicrobial due to Strep or Staph species (type II), and infection due to Vibrio vulnificus (which some refer to as type III), more common in cirrhotics) . Polymicrobial infections are more common than monomicrobial. They occur after surgery or in patients with peripheral vascular disease, diabetes, decubitus ulcers, or mucosal tears of GI/GU tract (i.e. Fournier’s gangrene). Cases of necrotizing fasciitis that arise after varicella infection or after trivial injuries like minor scratches/insect bites are almost always monomicrobial, caused by Strep pyogenes. The mortality in this group is high, approaching 50-70% in patients with hypotension and organ failure (3).

Clinical presentation

The classic presentation of necrotizing fasciitis is a patient with severe pain, anxiety, and diaphoresis, sometimes with systemic symptoms such as fever and nausea (3). However, the clinical presentation for patients with necrotizing fasciitis is very non-specific. Patients may present with only a small area of cellulitis, which can rapidly spread in a short amount of time. Patients often describe excruciating pain at the site of infection. Only 10-45% of patients report trauma or a break in the skin prior to onset of symptoms (3). The most important historical clue is the rate of spread of infection. Therefore, it is important to inquire about how quickly the symptoms have progressed, how quickly the cellulitis has spread, and whether the patient has already been diagnosed with cellulitis but has failed antibiotic management.

Physical exam

Because necrotizing fasciitis spreads so quickly, it can initially be difficult to distinguish between cellulitis and necrotizing infection. Patients often present with abnormal vital signs, such as tachycardia and fever, in addition to disorientation or lethargy. Exam features that suggest deep infection include severe, constant pain, bullae (related to occlusion of deep blood vessels that traverse the fascia or muscle compartments), skin necrosis or ecchymosis that precede skin necrosis, gas in the soft tissues (detected by palpation or imaging), edema that extends beyond the margin of erythema, cutaneous anesthesia, systemic toxicity (manifested by fever, leukocytosis, delirium, and renal failure), and rapid spread, especially despite antibiotic therapy (6).

The classic description of necrotizing fasciitis is excruciating pain associated with only a small area of cellulitis, with tenderness beyond the area of erythema. Thus, the catch-phrase for necrotizing fasciitis is “pain out of proportion to exam findings.” However, as the condition develops, the affected areas may become insensate. It is important to evaluate for the presence of subcutaneous emphysema at the site of infection. When anesthesia, bullae, skin sloughing, rapid progression, or crepitus are present, emergent surgical evaluation is necessary (1,3,6). However, the only signs present in more than half of patients with necrotizing fasciitis are erythema, tenderness, and marked edema beyond the area of redness. Crepitus occurs in only 13-31% of patients (3).

Diagnosis

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is the most popular tool used to risk-stratify patients with suspected necrotizing fasciitis. Points are assigned based on lab values: CRP, WBC, hemoglobin, serum creatinine, and glucose. A score greater than six indicates high risk for necrotizing fasciitis. The initial study reported a positive predictive value of 94% and a negative predictive value of 96% in patients with scores higher >6 (7). Patients with a score higher than six also have a higher rate of mortality and amputation (8). However, despite its widespread use, the LRINEC score has never been validated, and it was originally retrospectively derived. In addition, several studies have questioned its sensitivity (which, at best, is 80%) (9,10,11) and its specificity (65% in the initial study) (7).

Infectious Diseases Society of America (IDSA) guidelines recommend the following tests for evaluation of a patient with suspected necrotizing fasciitis: blood cultures with drug susceptibility testing, CBC with differential, creatinine, bicarbonate, creatine phosphokinase, and CRP (12). Hospitalization should be considered in patients with hypotension, elevated creatinine, low sodium bicarbonate, elevated creatine phosphokinase (2-3 times the upper limit of normal), marked WBC left shift, or CRP greater than 13 mg/L. These patients also warrant aggressive diagnostic measures, usually surgical exploration.

It is important to note that necrotizing fasciitis is a clinical diagnosis. Laboratory values are nonspecific and minimally helpful in making the diagnosis. The most helpful finding on Xray is subcutaneous emphysema, but this only found in up to 25% of cases of confirmed necrotizing fasciitis (13). In addition, CT and MRI also have poor sensitivity in identifying and characterizing necrotizing soft tissue infection (12). Necrotizing fasciitis may not present with any abnormalities on CT imaging, but it may be visible as edema extending along the fascial plane, with or without emphysema. Obtaining advanced imaging is often unhelpful, and it may delay appropriate treatment and referral to a surgeon.

Ultrasound is emerging as a potential diagnostic modality. Several case studies have detailed incidences in which ultrasound was able to identify and characterize necrotizing infections missed by CT but subsequently confirmed in the OR (14).

Surgery is the most important diagnostic and therapeutic modality! Necrotizing fasciitis spreads incredibly rapidly, so prompt treatment should not be delayed by obtaining labs and imaging. If there is a high suspicion for necrotizing fasciitis, but the diagnosis cannot be confirmed, the patient should be brought to the operating room for an exploratory incision with the potential for further debridement.

Treatment

Early diagnosis and intervention are essential because mortality is directly associated with time to initial intervention (15). Even with optimal treatment, necrotizing soft tissue infections portend significant morbidity and have mortality rates of 25-35%.  If a patient presents with a history and physical exam concerning for necrotizing fasciitis, initiate antibiotic therapy immediately. Because necrotizing infections are often polymicrobial, broad-spectrum coverage is necessary; the preferred antibiotics are vancomycin or linezolid plus piperacillin-tazobactam or a carbapenem; or ceftriaxone plus metronidazole (12). Clindamycin should be added due to its effects on toxin inhibition. If concern for Vibrio is present, doxycycline is required. However, the tissue ischemia associated with deep infection prevents adequate delivery of oxygen and antibiotics to the damaged tissue. Thus, antibiotics alone are not an effective treatment, and emergent surgical consult is necessary.

Case 2:

A 13-year-old boy presents with severe, vague abdominal pain that woke him from his sleep approximately 1 hour ago. He feels slightly nauseated and has vomited once. His vitals and physical exam are within normal limits.

TESTICULAR TORSION

Epidemiology and Risk Factors

Although the incidence of testicular torsion in only 4.5 in 100,000 males aged 1 to 25 years (16), testicular torsion is the third most common cause of malpractice lawsuits in adolescent males aged 12 to 17 years (17). This is because it is misdiagnosed in up to 12.5% of initial encounters (18). The most common misdiagnosis is epididymitis.

Testicular torsion occurs in a bimodal distribution. The first, which only includes a small number of cases, occurs in the neonatal period. The second curve, which accounts for 65% of all torsions (19), occurs in the peripubertal period. Predisposing factors include congenital anatomic abnormalities. It is important to note that previous orchiopexy does not significantly decrease future risk of torsion, so do not lower your suspicion of torsion in a patient with prior testicular surgery.

Pathophysiology

Each testis is surrounded by a layer of tissue called the tunica vaginalis, which consists of both a visceral and a parietal layer. In most cases, the testis is posteriorly anchored to the tunica. However, in 12% of males, the testis is suspended freely within the tunical cavity via the spermatic cord, so the testes are prone to rotate along the axis of its cord. This congenital predisposition to testicular torsion is known as the “bell-clapper deformity” (19).

The pathophysiology of testicular torsion varies slightly depending on whether the event happens during the neonatal period versus the peripubertal period. In newborns, the testes and their surrounding tissue are extremely mobile, so the cord and the tunica vaginal twist as a unit, resulting in “extravaginal torsion.” As males age and the tunica becomes less mobile, the testis is more prone to twist within its covering. This is known as “intravaginal torsion.”

Torsion usually occurs in the absence of a preceding event. It commonly occurs during sleep, when unilateral cremasteric muscle contraction results in asymmetric movement of the testis within the tunica vaginalis (20). Because the cremasteric muscle fibers are wrapped around the spermatic cord, they are able to move the testis up and out of the scrotum. If the torsion results in twisting of cremasteric fibers, the cremasteric reflex will be absent on that side (21). In addition, testicular torsion leads to reflex stimulation of the celiac ganglion, which results in significant nausea and vomiting.

Testicular torsion is a surgical emergency because the twisted spermatic cord results in obstruction of both the venous and arterial vessels. This lack of blood flow can lead to rapid necrosis of the testicle; thus, any male (especially pubertal/prepubertal) with testicular pain or swelling must be regarded as torsion until proven otherwise (22)!

Clinical Presentation

Testicular torsion classically presents with acute testicular pain, nausea, and vomiting. Sudden onset pain is highly suggestive of testicular torsion, but remember that other etiologies, such as epididymitis, may present with pain that is similar in onset and character. In addition, up to 16% of patients with testicular torsion experience a gradual onset of pain (23). Pain may be localized to the testis, but it may also be generalized abdominal pain, especially in patients with an undescended testis. In a study of 597 patients, 5% of patients with testicular torsion and a fully descended testicle did not describe any scrotal pain, and 22% had abdominal pain that preceded and exceeded the scrotal pain (27). Approximately 36% of patients had a history of previous unilateral or bilateral testicular pain or swelling (27).

The pain associated with testicular torsion is usually unprovoked. One study found that injury was implicated in only 4% of cases, recent exercise in 7%, and bicycle riding in 3% (19). Close to 11% were woken from sleep with the pain.

Nausea and vomiting is present in up to 70% of patients with testicular torsion (24), and the combination of scrotal pain or swelling and nausea or vomiting increases likelihood of testicular torsion compared to similar etiologies, like epididymitis or torsion of a testicular appendage. Dysuria and other urinary symptoms are rare in testicular torsion (5%) and are more consistent with epididymitis.

Several studies suggest that presence of pain of duration less than 24 hours, nausea/vomiting, high position of the testis, and abnormal cremasteric reflex have a high positive prognostic value for testicular torsion (20,21,28). One study found that all of the patients with testicular torsion had at least one of the four risk factors, while none of the children with the absence of the four risk factors were diagnosed with torsion (17). Testicular appendageal torsion presents similarly to testicular torsion but usually lacks the systemic symptoms of nausea and vomiting (20).

Because testicular torsion has a relatively nonspecific clinical presentation, and because young boys are often unable to accurately characterize their pain, testicular torsion may present with vague symptoms, sometimes in a manner similar to gastroenteritis (19). Thus, always consider testicular torsion in the differential diagnoses of any male presenting with abdominal pain or vomiting!

Physical Exam

Vital signs are often normal in patients presenting with early testicular torsion. In fact, mild fever and tachycardia are late signs, associated with low testicular salvage rates (19).

The most common physical exam finding is swelling and erythema of the affected hemiscrotum, which is seen in up to 80% of cases (21). Testicular tenderness (60%) and a high-riding testis (50%) with a “transverse lie” (30%) are other common findings (21,19). Although absent cremasteric reflex is an element of the classic description of testicular torsion, the prevalence in the literature ranges from 21% (21) to 100% (22). Therefore, absent cremasteric reflex is not sensitive enough to be a reliable physical exam finding. In addition, up to 30% of males with normal testicles lack a cremasteric reflex.

Another potentially misleading physical exam finding is epididymal tenderness, which may be present in approximately 16% of patients with confirmed testicular torsion (29). The physical exam can be deceptively consistent with epididymitis, which is why it is important to maintain a high level of suspicion for any male with testicular pain, especially in adolescent boys with abdominal, scrotal, or testicular pain.

Diagnosis

It is not possible to consistently and accurately differentiate testicular torsion from epididymitis and other scrotal pathologies by physical exam alone (22). In addition, lab tests are usually not useful in the diagnosis of testicular torsion. It is reasonable to obtain a urine sample in patients with suspected torsion, because a urinalysis is almost always normal in testicular torsion. Evidence of infection or pyuria is more consistent with other etiologies of scrotal pain (21).

Ultrasound with color-flow duplex is the imaging modality of choice to diagnose testicular torsion. Findings that indicate the presence of torsion include reduced or absent blood flow to the affected testicle. Absence of blood flow is diagnostic for torsion, with specificity close to 100%. However, the sensitivity ranges from 69-90% (23), and several recent studies found sensitivities of approximately 82% (24). There are several reasons for this. First, a partial torsion may reveal falsely reassuring blood flow. Additionally, in a testicle with torsion-detorsion pathology, the blood flow may actually appear normal or increased.  Three aspects of the US should be evaluated: gray scale appearance (desiring similar findings between the testicles), visualizing arterial and venous blood flow, and finding low resistance in arterial Doppler.

Because ultrasound is not a reliable diagnostic tool, many investigators have researched alternative methods for diagnosing testicular torsion. In the TWIST (Testicular workup for ischemia and suspected torsion) study, Barbosa and colleagues attempted to make a scoring system to risk-stratify for testicular torsion (30). The score assigns points to physical exam findings and historical factors: nausea/vomiting (1 point), presence of testicular swelling (2 points), hard testicle (2 points), absent cremasteric reflex (1 point), and high-riding testis (1 point). According to this study a score greater than 5 is highly indicative of testicular torsion and the patient should go straight to the OR without imaging. Per the study, a patient with a score less than two has low risk for torsion and thus does not require ultrasound. Patients with a score between 2 and 5 are considered “indeterminate” and require ultrasound. The TWIST score reduces ultrasound use by 20%, and it is 100% sensitive for testicular torsion. However, it is not widely accepted, in part because it has not been validated. Nonetheless, it emphasizes an important point: because ultrasound lacks sensitivity for testicular torsion, the diagnosis is largely clinical! Do not delay surgical intervention to obtain confirmatory imaging (20).

Treatment

The most definitive diagnostic and treatment modality for testicular torsion is detorsion of the affected testicle.

If clinical suspicion for torsion is high, you may attempt to manually detorse in the emergency department (25). Most testicular torsions occur in a lateral-to-medial direction, so the “open-book method” is preferred. This involves rotating the affected testicle 1½ full rotations medial-to-lateral. The endpoint of successful detorsion is resolution of pain. If pain increases with rotation, it is likely that you are worsening the torsion, so attempt the same maneuver in the lateral-to-medial direction. Consult urology regardless of whether manual detorsion appears successful.

If torsion is suspected and manual detorsion is unsuccessful, consult urology for emergent surgical intervention. The classic “golden window” for surgical intervention of testicular torsion is six-hours (19), because testicular preservation rates were once thought to rapidly decline after six hours of torsion symptoms. However, recent literature suggests that viability may extend well-beyond this window. Thus, do not lessen the urgency of your surgical consult if symptoms have persisted for 8, 12, or even 24 hours! Many pediatric urologists advocate for aggressive surgical intervention in suspected testicular torsion, as the risks of missing a torsion include infertility, sepsis, and death; however, the risks of performing an unnecessary surgery are comparatively low (31).

Case 3:

A 24-year-old female presents with sudden-onset, right lower quadrant abdominal pain with associated nausea but no fever, vomiting, or diarrhea. Her vital signs are normal, and her exam is remarkable for right lower quadrant tenderness to palpation. Pelvic exam is unremarkable except for mild right adnexal tenderness.

OVARIAN TORSION

Epidemiology and Risk Factors

The exact prevalence and incidence of ovarian torsion are unknown. However, up to 3% of women who present to the emergency department with acute abdominal pain have adnexal torsion (32). While infantile and childhood torsion is possible, it is very rare in the prepubertal period. Nearly ¾ of all cases of ovarian torsion present during the reproductive years, from 20-40 years old (33). Risk factors include ovulation induction, ovarian hyperstimulation syndrome, history of adnexal torsion, PCOS, previous tubal ligation, and pregnancy (34). Malignancy may be associated with ovarian torsion in 1.1-2% of adult patients, and the incidence of malignancy in children is even lower (33). In a retrospective chart review involving 87 women with diagnosed ovarian torsion, 35% had prior pelvic surgery (21% of these were tubal ligation), and 22% had a known history of ovarian cyst (35).

The most significant risk factor for ovarian torsion is the presence of a large ovarian cyst or mass, which predisposes the ovary to twisting. In adults, a causative finding for adnexal torsion is found in 64-82% of cases (38,39). In pediatric patients, the incidence of underlying ovarian pathology ranges from 51-84% (36,37).  The risk of ovarian torsion correlates with the size of an ovarian cyst. The risk is higher for cysts greater than 4-5 cm in diameter (33).

However, adnexal torsion may occur in patients with no underlying adnexal pathology (38). One study found that up to 46% of torsion cases involve normal-appearing ovaries (41).

Pathophysiology

Whether due to ovarian enlargement, cyst, or just an over-mobile ovary, ovarian torsion occurs when the ovary twists along the axis of the adnexa (40). This leads to the blockage of venous return, which results in congestion and ultimately decreased arterial blood flow. Once the arterial blood flow is compromised, the ovary is in danger of ischemia and necrosis.

Ovarian torsion is significantly more likely to occur on the right side, with a ratio of approximately 3:2 (42). This may be due to a longer utero-ovarian ligament on the right side, or the presence of the sigmoid colon on the left side, which limits mobility of the adnexa (33).

Clinical Presentation

Ovarian torsion classically presents with sudden-onset pain, concomitant with the onset of nausea and vomiting, followed by persistent colicky pain (33,40). Up to 90% of patients report acute onset abdominal pain, usually isolated to one side (44). The pain may be constant, or (in the case of torsion/detorsion) intermittent. One meta-analysis found the pain in ovarian torsion to be sudden onset (59%), sharp or stabbing (70%), and radiating to flank, back, or groin (51%) (33). If prompted, most patients report a history of similar pain, suggesting the possibility of intermittent ovarian torsion.

Other symptoms include nausea (70%), vomiting (45%), and fever (20%). If an adnexa becomes necrotic, the patient may exhibit peritoneal signs, which are both rare and a poor prognostic indicator (42).

Children with ovarian torsion have less severe symptoms and are less likely to present with nausea and vomiting (33). In addition, because the ovaries are relatively higher and intra-abdominal in girls compared to women, the clinical presentation is often vague in children.

Thus, it is important to consider ovarian torsion in all female patients presenting with abdominal or pelvic pain, nausea, and vomiting. Sounds easy enough, right? Because nothing else presents with those symptoms. Except appendicitis, diverticulitis, nephrolithiasis, incarcerated hernia, mesenteric adenitis, gastroenteritis, ruptured ovarian cyst, PID, tubo-ovarian abscess, ectopic pregnancy…and the list goes on. The vague symptoms and extensive differential diagnosis for ovarian torsion are two reasons that ovarian torsion is a commonly missed diagnosis! One study found that ovarian torsion was considered in the admitting differential in only 47% of patients with confirmed ovarian torsion. Other studies demonstrate that adnexal torsion was diagnosed preoperatively in only 37-50% of cases (44,45). Despite the diagnostic conundrum that ovarian torsion provides, there are no scoring systems or risk stratifying tools that help make the diagnosis (46). Maintain a high clinical suspicion for all women with undifferentiated abdominal or pelvic pain.

Physical Exam

Unfortunately, the physical exam does not help make the diagnosis more obvious. Vital signs are usually normal, with a low-grade fever (18%) in some cases, and perhaps slight tachycardia with elevated blood pressure if the pain is severe (42).

The rest of the exam is also non-specific. The most common finding is unilateral lower abdominal tenderness. However, up to 30% of patients may have no pain on exam (35)! The pelvic exam may reveal a palpable adnexal mass, but up to 75% of patients with proven adnexal torsion do not have a palpable mass (43).

Diagnosis

Labs are useful when considering ovarian torsion, only because they may offer a suitable alternative diagnosis. Obtain a urinalysis, pregnancy test, CBC, and electrolyte panel. Urinalysis may demonstrate sterile pyuria, and up to 50% of patients with ovarian torsion have slight leukocytosis on CBC (46).

Ultrasound is currently the most utilized diagnostic tool. “Positive” findings include a significant (greater than 4 cm) ovarian mass, free fluid in the cul-de-sac, unilateral ovarian enlargement, and decreased blood flow in the affected ovary (46). However, just as ultrasound is specific but not sensitive in diagnosing testicular torsion, the diagnostic yield is questionable in ovarian torsion. Specificity is as high as 92%, but sensitivity is likely as low as 40% (47). Normal Doppler flow is present in 45-61% of cases (26).

Ultrasound has traditionally been preferred over CT imaging in the case of suspected ovarian or endometrial pathology. However, recent research has focused on the use of CT in this setting. One review article posits that CT is more sensitive than ultrasound for detecting underlying adnexal masses, and just as sensitive as ultrasound in finding torsion (48). The data on this topic are conflicting: some studies demonstrate a distinct advantage of ultrasound over CT, some an advantage of CT over ultrasound, and still other studies demonstrate equal efficacy for both imaging modalities. Regardless of which imaging modality is superior, ovarian torsion is sometimes diagnosed by CT scans ordered for suspected appendicitis or other diagnoses. CT has a high enough specificity that when CT demonstrates findings of ovarian torsion, and the performance of another imaging exam (i.e. US) that delays therapy is unlikely to improve preoperative diagnostic yield.

Treatment

The only effective treatment for ovarian torsion is surgical intervention. Laparoscopic surgical evaluation of the ovaries is also the golden standard for diagnosis, because diagnostic imaging is considered unreliable. Unlike surgery for testicular torsion, which often cannot salvage the affected testicle, urgent surgical detorsion successfully preserves ovarian function in over 90% of cases (49).

Summary

This is the second in a two-part series on surgical emergencies: conditions that require quick disposition and potentially time-sensitive emergent surgery. These diseases include ruptured ectopic pregnancy, AAA, aortic dissection, necrotizing fasciitis, and ovarian / testicular torsion. You must maintain a high index of suspicion for these diseases, as delay in treatment can lead to substantial increases in morbidity and mortality. In all of these disease processes, hemodynamic instability = emergent surgical consultation.

 

NECROTIZING FASCIITIS

-Consider this diagnosis in any patient with cellulitis, but especially in patients with diabetes and obesity.

-Laboratory testing and imaging do not have high enough sensitivity to reliably exclude the diagnosis, so this is truly a clinical diagnosis!

-Necrotizing fasciitis spreads as quickly as 1 inch per hour. Its mortality is as high as 35% and is directly related to time-to-treatment.

Antibiotics should be initiated immediately, but antibiotics alone are not an effective treatment; emergent surgical exploration is necessary.
TESTICULAR TORSION

-Must consider in any peripubertal male with abdominal pain +/- nausea and vomiting.

-Classic exam findings include swelling and erythema of the affected hemiscrotum, with unilateral loss of the cremasteric reflex, and testicular tenderness.

-The most common imaging modality to diagnose testicular torsion is Doppler ultrasonography, but this is an unreliable diagnostic tool, so if your suspicion for testicular torsion is high, then act quickly regardless of ultrasound results!

-You may attempt to manually detorse in the ED by rotating the testicle in a medial-to-lateral direction. Resolution of pain is an indicator of successful detorsion.

-Even if manual detorsion is successful, an emergent urology consult is necessary!

 

OVARIAN TORSION

Maintain a high clinical suspicion for all women with undifferentiated abdominal or pelvic pain.

-Most common in the reproductive years (20-40 years old).

-Ovarian torsion classically presents with sudden-onset, unilateral pain, concomitant with the onset of nausea and vomiting.

Ultrasound is the most commonly used imaging modality, but CT or MRI may be equally efficacious. Ovarian torsion may not be detectable by any imaging if there is torse/detorse pathology.

-The only effective treatment is surgical intervention, which successfully preserves function in 90% of cases.

 

References/Further Reading:

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  2. Arif N, Yousfi S, Vinnard C. Deaths from necrotizing fasciitis in the United States, 2003–2013. Epidemiology and infection 2016; 144(6): 1338-1344.
  3. Stevens DL et al. Practice Guidelines for the diagnosis and management of skin and soft-tissue infections: IDSA Guidelines. Clinical Infectious Diseases 2005; 41: 1373-1406.
  4. Kelley EW and Magilner D. Soft tissue infections. In Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. New York: McGraw-Hill, 2016. 1034-1036.
  5. Park SJ, Kim DH, Choi CI, Yun SP, Kim JH, Seo H, J HJ, Jun TY, Necrotizing soft tissue infection: analysis of the factors related to mortality in 30 cases of a single institution for 5 years. Ann Surg Treat Res 2016 Jul; 91(1): 45-50.
  6. Hakkarainen TW, Kopari NM, Pham TN, et al. Necrotizing soft tissue infections: review and current concepts in treatment, systems of care, and outcomes. Current Problems in Surg. 2014; 51: 344-362.
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  8. Su YC, Chen HW, Hong YC, Chen CT, Hsiao CT, Chen IC. Laboratory Risk indicator for necrotizing fasciitis score and the outcomes. Anz Journal of Surgery Nov 2008; 78(11): 968-972.
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  10. Raam R, Moran GJ, Jhun P, Herbert M. Worms and Flesh-Eating Bacteria? The Worst Day of Your Life. Annals of Emergency Medicine 2016 Aug; 68(2): 245-8.
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  12. DL Stevens et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical Infectious Diseases 2014; 59: e10–52.
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  32. Lentz GM, Lobo RA, Gershenson D, et al. Comprehensive Gynecology. 6th ed. Philadelphia, PA: Mosby, Inc. 383–432.
  33. Cass DL. Ovarian torsion. Seminars in Pediatric Surgery 2005: 14(2): 86-92.
  34. Boswell K, Silverberg KM. Recurrence of ovarian torsion in a multiple pregnancy: conservative management via transabdominal ultrasound-guided ovarian cyst aspiration. Fertil Steril. 2010; 94: 1910.e1–1910.e3.
  35. Houry D, Abbott JT. Ovarian torsion: a fifteen-year review. Ann Emerg Med 2001; 38: 156-9.
  36. Bagolan P, Giorlandino C, Nahom A, et al. The management of fetal ovarian cysts. J Pediatr Sur 2002; 37: 25-30.
  37. Mittermayer C, Blaicher W, Grassauer D, et al. Fetal ovarian cysts: development and neonatal outcome. Ultraschall Med 2003; 24: 21-6.
  38. Dunnihoo DR, Wolff J. Bilateral torsion of the adnexa: a case report and a review of the world literature. Obstet Gynecol 1984;64:55S-59S.
  39. Anspach B. The torsion of tubal enlargements with special reference to pyosalpinx. Am J Obstet Gynecol 1912; 66: 553-95.
  40. Heniff M and Fleming HRB. Abdominal and pelvic pain in the nonpregnant female. In Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. New York: McGraw-Hill, 2016. 628-629.
  41. Pansky M, Smorgick N, Herman A, Schneider D, Halperin R. Torsion of normal adnexa in postmenarchal women and risk of recurrence. Obstet Gynecol 2007; 109: 355–359.
  42. Shadinger L, Andreotti R, Kurian R. Preoperative sonographic and clinical characteristics as predictors of ovarian torsion. J Ultrasound Med 2008; 27: 7–13.
  43. Moore C, Meyers AB, Cotasto J, Bokhari J. Prevalence of abnormal CT findings in patients with proven ovarian torsion and a proposed triage schema. Emerg Radiol 2009; 16: 115–120.
  44. Spigland N, Ducharme JC, Yazbeck S. Adnexal torsion in children. J Pediatric Surg 1989; 24: 974-976.
  45. Mordehai J, Mares AJ, Barki Y, et al. Torsion of uterine adnexa in neonates and children: a report of 20 cases. J Pediatric Surg 1991; 26: 1195-1199.
  46. Sasaki KJ, Miller CE. Adnexal torsion: Review of the literature. JMIG 2014; 21(2): 196-202.
  47. Bar-On S, Maschiach R, Stockheim, D. Emergency laparoscopy for suspected ovarian torsion: are we too hasty to operate? Fertil Steril 2010; 93: 2012-15.
  48. Swenson DW, Lourenco AP, Beaudoin FL, Grand DJ, Killelea AG, McGregor AJ. Ovarian torsion: case-control study comparing the sensitivity and specificity of ultrasonography and computed tomography for diagnosis in the emergency department. European Journal of Radiology 2014; 83: 733-738.
  49. Oelsner G, Cohen SB, Soriano D, Admon D, Mashiach S, Carp H. Minimal surgery for the twisted ischaemic adnexa can preserve ovarian function. Hum Reprod 2003;18:2599–602.

Pelvic Inflammatory Disease: Pearls and Pitfalls

Authors: Marina N. Boushra, MD (EM Resident Physician, Vidant Medical Center) and Cassandra Bradby, MD (EM Attending Physician, Vidant Medical Center) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 24-year-old female with no significant past medical history presents to the emergency department (ED) with lower abdominal pain for five days. The pain has been associated with decreased appetite and nausea but no vomiting. It is exacerbated by sexual intercourse. Her last menstrual was period five days ago, and while she typically gets cramping, she states that this pain is more severe. Her vitals on arrival are temperature 101.2º Fahrenheit (F), heart rate (HR) 80 beats per minute (bpm), respiratory rate (RR) 14/minute, blood pressure (BP) 115/70 mmHg. Her physical examination is notable for diffuse tenderness to palpation of the abdomen, scant blood in the vaginal vault, yellow discharge from the cervical os, and severe bilateral adnexal tenderness on bimanual examination.

Background

Pelvic inflammatory disease (PID) is infection of the upper genital tract (uterus, endometrium, fallopian tubes, ovaries) in women. PID may extend to involve adjacent structures, causing periappendicitis, pelvic peritonitis, and perihepatitis (Fitz-Hugh-Curtis syndrome). The majority of PID is caused by ascending sexually-transmitted infections (STI). Neisseria gonorrhea and Chlamydia trachomatis are the most commonly implicated pathogens in PID1. However, PID can also be caused by bacterial-vaginosis related organisms or, more rarely, enteric or respiratory pathogens that have colonized the lower genital tract1. Even more rarely, a chronic form of PID may be seen with tuberculosis in endemic areas or Actinomyces in women who have intrauterine devices2,3.

Any sexually active woman is at risk for PID but women with multiple sexual partners are at the highest risk4. Other risk factors include age younger than 25 years, herpes infection, HIV infection, a partner with an STI, prior PID, or prior STI. Barrier contraception is protective5. Pregnancy also decreases the risk of PID due to the mucus plug that can prevent ascending infection from the lower to the upper genital tract. Note, however, that PID can still develop in the first 12 weeks of pregnancy6. The spectrum of PID symptoms is wide with some patients going undiagnosed until they develop sequelae such as tubal factor infertility or an ectopic pregnancy. In symptomatic patients, lower abdominal pain, typically bilateral, is often the presenting symptom1. Dyspareunia and/or an onset of pain with, or shortly after, menstruation should also raise suspicion for PID7. A history of abnormal uterine bleeding, such as menorrhagia, metrorrhagia, or post-coital bleeding, is seen in one third of patients with PID8. Physical examination typically reveals lower abdominal pain, which may be unilateral or bilateral, although diffuse abdominal pain may also be seen. Cervical motion tenderness and the classic “chandelier sign” – severe pain with cervical motion such that the patient “jumps for the chandelier” on examination – may be present. Fever, rebound tenderness, and/or hypoactive bowel sounds are indicative of more severe disease and should increase suspicion for a pelvic abscess. Associated right upper quadrant pain is concerning for Fitz-Hugh-Curtis syndrome inflammation of the hepatic capsule. The most common cause of death in PID is rupture of a tubo-ovarian abscess (TOA), which has a mortality rate of 5-10%6. Serious complications include tubal factor infertility, tubal scarring leading to ectopic pregnancy, and chronic pelvic pain.

Differential Diagnosis

The differential diagnosis for pelvic and lower abdominal pain is extremely broad and varies by age. The differential in pre-menopausal women includes ectopic pregnancy, a complicated intrauterine pregnancy, ovarian cyst, ovarian torsion, endometriosis, urinary tract pathologies, appendicitis, and irritable bowel syndrome. Laboratory evaluation should include a pregnancy test in any pre-menopausal woman. In post-menopausal women, many of the gastrointestinal and urinary pathologies are still possible but there is lower risk for ovarian torsion and endometriosis. Diagnoses such as ovarian masses, endometrial cancer, and colon cancer should be considered.

Diagnosis

There is no specific lab value, physical examination finding, or imaging study that is diagnostic of PID. The diagnosis of PID is often presumptive based on clinical findings. The clinical diagnosis is only 65-90% specific, but the addition of the criteria in Table 1 increases the specificity of the clinical diagnosis1,5,9. In patients with known or suspected PID, testing for STIs, including syphilis and HIV, should be obtained. Other helpful laboratory tests include a white blood cell count, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR). A positive urinalysis does not exclude the diagnosis of PID, as inflammation in the pelvis can cause white blood cells in the urine6.

 Table 1: Findings suggestive of PID1

Oral temperature >101°F (>38.3°C)
Abnormal cervical or vaginal mucopurulent discharge
Cervical friability
Abundant white blood cells on saline microscopy of vaginal secretions
Documented infection with of N. gonorrhoeae or C. trachomatis

Imaging with pelvic ultrasound may be helpful in excluding other causes of pelvic pain, including ectopic pregnancy, ovarian cysts, and ovarian torsion. It is also helpful in the diagnosis of TOA. Computed tomography (CT) or magnetic resonance imaging (MRI) may also be used, with MRI being particularly useful in characterizing complicated soft-tissue masses as would be seen with TOA6.

Management

While the clinical diagnosis is only 65-90% specific, even minimal symptoms without an alternative diagnosis warrant antibiotic therapy to reduce the risk of potentially serious complications due to the delay of or withholding therapy1. Women with IUDs do not need to have them removed prior to the start of treatment because they are rarely the cause of PID1. If symptoms fail to improve in 48-72 hours, removal of the IUD should be considered1.

Antibiotic selection should cover for N. gonorrhea and C. trachomatis. The importance of anaerobic coverage is controversial, since no trial has demonstrated improved outcomes and there is concern that the gastrointestinal side effects associated with metronidazole will lead to noncompliance10. There is currently an ongoing study on the role of anaerobic coverage in PID (Clinical Trials.gov, identifier NCT01160640).

Anaerobic coverage should be added, however, in patients who have a history of gynecologic instrumentation in the prior two to three weeks. Possible antibiotic regimens for inpatient and outpatient management are listed in Table 2.

 There has been a trend towards outpatient management of patients with mild to moderate disease. The Pelvic Inflammation Disease Evaluation Clinical Health Trial (PEACH Trial) showed similar short-term clinical and microbiologic and long-term reproductive outcomes between the inpatient and outpatient arms of the trial, with the inpatient arm experiencing high rates of phlebitis from IV doxycycline administration12.

Table 2: Inpatient and Outpatient Treatment Regimens1

Outpatient management Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)
Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)
Inpatient management Cefoxitin (2g IV q6 hours) plus doxycycline (100mg po bid for 14 days)
Cefotetan (2g IV q12 hours) plus doxycycline (100mg po bid for 14 days)
Clindamycin (900mg IV q8 hours) plus gentamicin (2mg/kg loading dose then 1.5 mg/kg q8 hours IV)

Indications for hospitalization and IV antibiotics include pregnancy, clinically severe disease, complicated PID (pelvic abscess), and intolerance to, noncompliance with, or failure of oral antibiotics1.

If a patient is treated as an outpatient, follow up in 72 hours should be arranged. Patient education is paramount, especially in adolescents where the risk of recurrence is higher and the time to pregnancy is shorter than in adult patients. Partner notification, evaluation and treatment should be encouraged. Patients should be educated about the use of barrier contraception and safe sex practices and instructed to remain abstinent from sexual activity until one week after the completion of treatment for them and their partner.

Pearls

  • Even though the presumptive clinical diagnosis is only 65-90% specific, symptoms suggestive of PID should be treated with antibiotics immediately to avoid the risk of serious sequelae, including permanent scarring that may lead to infertility and ectopic pregnancy.
  • Obtain a pelvic ultrasound to assess for TOA in patients with asymmetrical pelvic findings or clinical signs of toxicity.
  • Fluoroquinolones should not be used in known or suspected gonorrhea infection due to increasing rates of resistance.
  • IUDs do not need to be removed prior to treatment of PID.
  • Antibiotics should cover both gonorrhea and C. trachomatis.
  • Anaerobic coverage is only suggested if there has been recent gynecologic instrumentation.

 Pitfalls

  • Dismissing the pelvic pain associated with PID for dysmenorrhea.
  • Assuming a positive UA excludes the diagnosis of PID (beware sterile pyuria)
  • Failing to do a pelvic exam and STI testing on a woman with lower abdominal pain.

References / Further Reading

  1. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  2. Namavar Jahromi B, Parsanezhad ME, Ghane-Shirazi R. Female genital tuberculosis and infertility. Int J Gynaecol Obstet 2001; 75:269.
  3. Kim YJ, Youm J, Kim JH, Jee BC. Actinomyces-like organisms in cervical smears: the association with intrauterine device andpelvic inflammatory  Obstet Gynecol Sci. 2014 Sep;57(5):393-6.
  4. Lee NC, Rubin GL, Grimes DA. Measures of sexual behavior and the risk of pelvic inflammatory disease. Obstet Gynecol 1991; 77:425.
  5. Ross, Johnson. Pelvic Inflammatory Disease: pathogenesis, microbiology, and risk factors. UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 12 October 2016.
  6. Shepherd SM, Weiss B, Shoff WH. Pelvic Inflammatory Disease in Tintinalli, Judith E., Gabor D. Kelen, and J. Stephan Stapczynski. Emergency Medicine: A Comprehensive Study Guide. New York: McGraw-Hill, Medical Pub. Division, 2016. Ch 103:668-672.
  7. Korn AP, Hessol NA, Padian NS, et al. Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis. Am J Obstet Gynecol 1998; 178:987.
  8. Wiesenfeld HC, Sweet RL, Ness RB, et al. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 2005; 32:400.
  9. Peipert JF, Boardman LA, Sung CJ. Performance of clinical and laparoscopic criteria for the diagnosis of upper genital tract infection. Infect Dis Obstet Gynecol 1997; 5:291.
  10. Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis 2007; 44 Suppl 3:S111.
  11. Wiesenfeld, HC. Pelvic Inflammatory Disease: Treatment. UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Accessed 12 October 2016.
  12. Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol 2002; 186:929.

Lyme disease ED Presentations / Management Pearls and Pitfalls

Authors: Oleg Uryasev, MD (EM Resident Physician, Virginia Tech Carilion Emergency Medicine Residency) and Jack Perkins, MD (Assistant Program Director, Virginia Tech Carilion Emergency Medicine Residency) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

 Background

The first case of Lyme disease was documented more than 5000 years ago. (1) Today, it is the most commonly reported vector borne disease with ~30,000 cases per year in the United States. The vast majority of cases are found in the Northeast and in the upper Midwest, but there is distribution nationally. (2,3) Lyme is a manifestation of infection by the spirochete Borrelia burgdorferi. This spirochete is harbored by the deer tick Ixodes scapularis and Ixodes pacificus.

The chance of Lyme transmission depends on the duration of tick attachment. If an infected tick is attached for less than 24 hours, then there is an almost zero percent chance of transmission. However, the tick has been attached for more than 72 hours, there is an almost one hundred percent chance of disease transmission. (4) It is important to keep in mind that patients with tick bites are at risk for many other tick borne illnesses such as Babesiosis, Rocky Mountain Spotted Fever, Southern Tick-associated Rash Illness, Ehrlichiosis, Anaplasmosis and Tularemia.

Case Presentations and Discussion:

Case 1:

13 year-old male presents after a camping trip with reports of tick bite and subsequent rash. He is otherwise healthy and has no medical or surgical history. Vital signs are unremarkable. His examination is normal except for a target-like lesion with central clearing on his abdomen which is pruritic and mildly painful.

What are some manifestations of early Lyme Disease?

Presentation of Lyme depends on the degree of systemic dissemination. Early on, when locally contained, the manifestation tends to be dermatologic. Erythema migrans (EM), an isolated, circumscribed, target like lesion with central clearing, is present in 70-80% of patients and usually erupts on the lower extremities or the trunk within 3-30 days of tick bite.  Atypical presentations can have multiple EM lesions, associated vesicles or necrosis, no central clearing, or be located in an unusual location such as the scalp. Some individuals with Lyme disease will never manifest a rash. Borrelial lymphocytoma, a reddish-blue nodule located on the nipple or ear is an extremely rare, and predominantly European dermatologic presentation for Lyme. (5, 6, 7) Pediatric presentations for all stages tends to mimic adult presentations. (8)

As the disease progresses, systemic symptoms occur and may mimic a viral illness that lacks respiratory or gastrointestinal complaints. Fatigue, myalgias, arthralgias, fevers, anorexia, headache and neck stiffness are the hallmarks of this stage. Conjunctivitis can occur as well. (9, 10)

Which antibiotics should I choose when treating Lyme disease?

In early infections or indolent infections with arthritis as a preliminary manifestation, oral doxycycline is sufficient. In cases where doxycycline is contraindicated, such as in children under <8 years old and pregnant patients, amoxicillin and cefuroxime axetil are acceptable alternatives. For advanced cases requiring inpatient management, (e.g. neurological or cardiac involvement) intravenous (IV) ceftriaxone is recommended. Duration of therapy depends on degree of disease progression but it usually is for 14-28 days. (4)

Case 2:

A 40 year-old female presents for facial droop. The droop started in the right side of her face several days ago and is progressively worsening. She reports having a viral illness the month prior with myalgias, fevers and a headache. Her examination is remarkable for right facial nerve palsy, otherwise unremarkable.

When should I suspect Lyme as the causative agent for Bell’s Palsy?

Bell’s Palsy is the most common cranial neuropathy associated with Lyme. Lyme can cause neuropathy in any cranial nerve, but the facial nerve is the most commonly affected. Cranial neuropathies can happen weeks to months after initial infection. In order to have neurological symptoms, the spirochetes must be disseminated in the nervous system. Lyme should be suspected as the causative agent when a cranial neuropathy occurs in the setting of symptoms consistent with disseminated Lyme such as myalgias/arthralgias, fevers, headache or meningismus.  (11)

Should I be testing/treating all patients with Bell’s Palsy for Lyme?

When caused by Lyme, it is rare to have an isolated cranial nerve palsy without any other symptoms of disseminated disease. For this reason, routine testing and treatment with an isolated Bell’s palsy with no other symptoms consistent with Lyme is low yield and should not be done. (12) In cases where Lyme is the suspected culprit of a cranial nerve deficit, the patient should be treated empirically without waiting for titers to be completed.

 Case 3:

21 year-old female presents to the ED for altered mental status. Her family reports she has not been feeling well for the last several months and now is not acting like herself. She is febrile and tachycardic. On examination she is ill-appearing, answers questions inappropriately, has meningismus and her skin is hot and dry.

When should I suspect Lyme as the cause of meningitis? What should the CSF analysis show?

Clinically, Lyme progressing to meningitis should demonstrate the regular prodrome of early disseminated disease. Patients will have fevers, myalgias, arthralgias, and rash prior to central nervous system (CNS) involvement of Lyme. On occasion, a history may be difficult to obtain, or your patient may have had an atypical presentation of early Lyme. Thus, the making the diagnosis of CNS Lyme meningitis may be very difficult. A lumbar puncture should be performed to confirm presence of meningitis.  Once patients develop meningitis, the presence of a cranial nerve palsy in conjunction with meningitis makes the diagnosis of Lyme slightly more likely. (13) Cerebral spinal fluid (CSF) findings will be almost indistinguishable from viral meningitis. (14)

If I suspect Lyme meningitis, how should I tailor ED management and antibiotic choices?

Management for Lyme meningitis in the ED is identical to management for any other suspected bacterial meningitis. Antibiotic therapy should not be delayed in order to obtain a lumbar puncture since a delay in antibiotic therapy leads to worse patient outcomes. Antibiotics should be ordered immediately while the LP is being performed. If Lyme is the causative agent for meningitis, the patient will already be covered appropriately if IDSA guidelines are followed for antibiotic choices. Every patient greater than one month old should receive either ceftriaxone or cefepime, either of which will adequately treat Borrelia burgdorferi. (15)

Case 4:

32 -year-old male presents to the ED for shortness of breath and chest pain. He reports a recent illness after which he started to have chest pain and shortness of breath. He is bradycardic on examination and his EKG demonstrates a 2nd degree AV block.

How do I approach cardiovascular manifestations of Lyme?

Untreated, the disseminated late stage disease of Lyme can progress to cardiac manifestations, but this is rare. Cardiac pathology due to Lyme usually involves varying degrees of atrioventricular (AV) block. The AV block fluctuates and can rapidly progress from first degree to third degree. Approximately 1/3rd of patients with Lyme carditis will require temporary AV pacing. Almost no patients require permanent pacemakers since the heart block resolves with antibiotic treatment. Some patients develop ST segment depression or T wave inversions, most commonly in inferior leads. Lyme can present with a myocarditis or pericarditis pattern as well.

While Lyme carditis can occur in any demographic group, young males are at highest risk. (4, 16, 17) Lyme carditis is a difficult diagnosis to make in the ED due to its infrequent occurrence. Lyme carditis should be considered in patients with heart block who are not typically at risk for heart blocks in endemic regions of the country or with systemic symptoms consistent with disseminated Lyme.

Which patients should I admit for parenteral therapy?

The IDSA recommends admission and parenteral antibiotics for (4):

Symptomatic patients (e.g. syncope, dyspnea, or chest pain)

Second or third degree AV block

First degree AV block with PR interval greater than 300 milliseconds

Case 5:

17 year-old male presents with an engorged tick on his right side. He has no medical or surgical history, and currently has no symptoms. His vital signs are unremarkable. On examination, he has no rashes, but a small unidentifiable tick is seen on his right flank.

When is prophylaxis indicated?

The answer is based on the individual, history of the tick bite, and practice location. The IDSA criteria by which a provider should determine whether prophylaxis is indicated:

1) Tick identified as I. Scapularis and is present ≥ 36 hours (engorgement or by patient history)

2) Local rate of infection ≥ 20%

3) Treatment begun < 72 hours from tick removal

4) No contraindication to Doxycycline

For an updated distribution of endemic areas with Lyme visit the CDC website: http://www.cdc.gov/lyme/stats/maps.html

Prophylaxis for Lyme is a single dose of 200mg of doxycycline after a tick with high risk of infection. Amoxicillin has never been verified to be effective in prophylaxis and should not be used. (4)

When should we pursue diagnostic testing in the ED?

Sensitivity of diagnostic testing depends on degree of disease dissemination. ELISA and Western blot testing are available for IgM and IgG antibodies to Borrelia burgdorferi. Testing in the early stages of Lyme (e.g. tick exposure with or without EM rash) will likely be falsely negative due to lack of systemic reaction. (18) In the ED, testing for Lyme will not change our management since tests require several days for results. Patients should be treated empirically and dispositioned appropriately based on severity of symptoms. Testing is generally discouraged due to the delay in obtaining results and the potential for false results.

Case 6:

A 66 yo female with a history of hypertension, fibromyalgia, and anxiety presents with five years of fatigue, arthralgias and generalized weakness. She has had intermittent chills as well. She states she was tested a year ago for Lyme’s disease and this was positive. She has subsequently had three separate courses of antibiotics for her Lyme’s disease and is requesting admission for IV antibiotics for Chronic Lyme Disease resistant to oral antibiotics. Her vitals signs and a complete examination are unremarkable. EKG, laboratory tests and a recent magnetic resonance imaging (MRI) of the brain are reviewed and also unremarkable except for a positive PCR for Lyme 12 months prior.

How do we approach the patient with “Chronic Lyme Disease”?

A lot of confusion surrounds the diagnosis of “Chronic Lyme Disease.” When we say Chronic Lyme Disease (CLD) we do not mean untreated Lyme with progression to late disseminated disease, or undiagnosed Lyme with chronic arthritis or neurological manifestations. Rather, CLD is one of two broad categories:

  • Physical manifestations of the disease after successful treatment. More correctly this diagnosis should be Post-Lyme syndrome (PLS). PLS defined by fatigue, weakness, arthralgias and other symptoms of Lyme for a prolonged period after successful treatment with antibiotics. In fact, many patients require 12-24 months for all symptoms to clear. This period may even longer for those with disseminated disease.
  • Vague complaints in a patient with no true diagnosis of Lyme. The patient may have positive PCR testing but is likely false positive or positive due to a previous Lyme infection. Alternatively, he or she may have had negative PCR results but he or she may still believe that Lyme is responsible. Both of these patient groups have an alternative diagnosis causing their symptoms.

Are antibiotics indicated for Chronic Lyme Disease?

Chronic Lyme Disease is not a prolonged infection despite treatment. Antibiotics are not indicated in the Emergency Department. (19)

Conclusion

Lyme disease is the most common among a handful of uncommon tick borne illnesses and should be included in the differential of diagnoses, especially in patients who live in endemic areas. It is helpful for emergency providers to be familiar with all manifestations of Lyme disease especially since antibiotics may be curative.

 Take home points:

1) Add Lyme disease to your differential when you see a patient with a history viral illness with headache, myalgias/arthalgias and fevers, especially in endemic regions.

2) If Bell’s palsy is due to Lyme, systemic symptoms of Lyme should also be present. Testing for Lyme in isolated Bell’s palsy is not indicated.

3) Initial management for Lyme meningitis is identical to any other patient presenting to the ED for bacterial meningitis.

4) Prophylaxis is only appropriate in patients who reside in an endemic area who have had a tick attached for greater than 36 hours. Doxycycline is the only approved prophylactic antibiotic.

5) Chronic Lyme disease is not a continued spirochete infection and is often misdiagnosed when in fact a completely separate disease process (e.g. multiple sclerosis) is the underlying etiology.  Chronic Lyme disease refers to prolonged symptoms after the infectious component has been treated.

 References / Further Reading

1) http://www.livescience.com/18704-oldest-case-lyme-disease-spotted-iceman-mummy.html Last accessed 7/23/2016

2) http://www.cdc.gov/lyme/stats/ Last accessed 7/23/2016

3) Kugeler KJ, Farley GM, Forrester JD, Mead PS. Geographic distribution and expansion of human Lyme disease, United States. Emerg Infect Dis. 2015 Aug;21(8):1455-7

4) Gary P.  Wormser, Raymond J.  Dattwyler, Eugene D.  Shapiro, John J.  Halperin, Allen C.  Steere, Mark S.  Klempner, Peter J.  Krause, Johan S.  Bakken, Franc Strle, Gerold Stanek, Linda Bockenstedt, Durland Fish, J.  Stephen Dumler, and Robert B.  Nadelman. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. IDSA Guidelines 2006

5) Müllegger RR, Glatz M. Skin manifestations of lyme borreliosis: diagnosis and management. Am J Clin Dermatol 2008; 9: 355-68.

6) Biesiada G, Czepiel J, Leśniak MR, Garlicki A, Mach T. Lyme disease: review. Archives of Medical Science : AMS. 2012;8(6):978-982.

7) Steere AC, Sikand VK. The presenting manifestations of Lyme disease and the outcomes of treatment. N Engl J Med 2003; 348:2472.

8) Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med 1996; 335:1270.

9) Bitar I, Lally EV. Musculoskeletal manifestations of Lyme disease. Med Health R I 2008; 91: 213-5.

10) Nadelman RB, Nowakowski J, Forseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996; 100:502.

11) Kuiper H, Devriese PP, de Jongh BM, Vos K, Dankert J. Absence of Lyme borreliosis among patients with presumed Bell’s palsy. Arch Neurol. 1992;49(9):940–943.

12) Albers JR, Tamang S. Common questions about Bell palsy. Am Fam Physician. 2014 Feb 1;89(3):209-12.

13) Garro AC, Rutman M, Simonsen K, et al. Prospective validation of a clinical prediction model for Lyme meningitis in children. Pediatrics 2009; 123:e829.

14) Lakos A. CSF findings in Lyme meningitis. J Infect 1992; 25:155.

15) Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ, Practice Guidelines for the Management of  Bacterial Meningitis by the Infectious Diseases Society of America. IDSA Guidelines 2004

16) Forrester JD, Mead P. Third-degree heart block associated with lyme carditis: review of published cases. Clin Infect Dis. 2014 Oct;59(7):996-1000.

17) Scheffold N, Herkommer B, Kandolf R, May AE. Lyme carditis–diagnosis, treatment and prognosis. Dtsch Arztebl Int. 2015 Mar 20;112(12):202-8.

18) Steere AC, McHugh G, Damle N, Sikand VK. Prospective study of serologic tests for lyme disease. Clin Infect Dis 2008; 47:188.

19) Marques A. Chronic Lyme Disease: An appraisal. Infectious disease clinics of North America. 2008;22(2):341-360.

DIC in the ED: What can you do about it?

Author: Ashley Phipps, MD (EM Chief Resident, UTSW / Parkland Memorial Hospital // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

 Patient Case

A 67 year-old male presents to the emergency department (ED) for fevers, nausea, vomiting, and severe epigastric pain for the past 2 days. The patient has a history of alcoholism, hypertension, and diabetes. On exam, he is ill-appearing, tachycardic, and mildly tachypneic. Laboratory studies and a computed tomography (CT) abdomen/pelvis are obtained showing a lipase of 316 and pancreatic stranding making pancreatitis the most likely diagnosis. Other notable laboratories studies include leukocytosis to 22,000/microliter (uL), thrombocytopenia to 42,000/uL, hyperglycemia to 351, and a mild transaminitis. His nurse tells you that there is blood oozing around his intravenous (IV) sites. Being an astute clinician, you recognize that this patient is critically ill, and you begin to worry about disseminated intravascular coagulation (DIC).

 Background

DIC is an acquired coagulation syndrome that results in excessive clotting and clotting factor consumption, with subsequent severe bleeding in severely ill patients. Many different conditions can lead to DIC (table 1); however, the mechanism for DIC is the same in each case. In DIC, the coagulation cascade is activated and its control mechanism is lost. This leads to the formation of thrombin clots that are then deposited in capillaries and small vessels. The large amount of thrombin and fibrin clot deposition has three big consequences. First, the excessive clotting effectively consumes the body’s store of clotting factors and platelets. Next, the clot deposition in the microcirculation leads to hemolysis as red blood cells attempt to pass through. Lastly, the counter-regulatory system, the fibrinolytic system, also gets activated and starts dissolving the clots. At this point, clotting factors are depleted and significant bleeding can ensue. (1)

Table 1. Known causes of DIC

Infection (bacterial, viral, & fungal)
Trauma
Pregnancy complications (placental abruption, intrauterine fetal demise, amniotic fluid embolus, HELLP syndrome)
Acute Respiratory Distress Syndrome (ARDs)
Acute liver failure
Pancreatitis
Malignancy (most common in leukemia), chemotherapy
Vasculitis
Envenomation (rattlesnakes, vipers)
Transfusion reactions

Clinical Presentation

The clinical presentation will vary based on the precipitating cause. Patients can present with hypercoagulation, hyperfibrinolysis, or a mixed picture of both. If hypercoagulation predominates, clinical presentation can include signs of end-organ failure or gangrene in small vascular beds such as the fingers or toes. This is the most common initial presentation of DIC in septic patients. Contrastingly, if bleeding predominates, the patient may have petechiae or large ecchymosis, hematuria or hematochezia, or oozing from IV sites and any other sites of trauma. This is the most common presentation of DIC in patients with trauma, malignancy, pregnancy, or liver failure related illnesses. (2)

 Diagnostic Studies

In all severely ill patients, especially those with symptoms or signs of DIC, coagulation laboratories studies should be obtained. These include platelet count, prothrombin time (PT), and fibrinogen. Additional tests including d-dimer, fibrin degradation products, activated partial thromboplastin time (aPTT), clotting time, and specific factor assays can be helpful. (1) DIC is often associated with several characteristic laboratory findings, shown in Table 2. This disease differs from other coagulation disorders in the degree and number of laboratory abnormalities.

Table 2. Laboratory abnormalities in DIC

Platelet count
PT (INR)
Fibrinogen ↓ (can be elevated in early DIC)
D-dimer
Fibrin degradation products
aPTT
Clotting time
Specific factor assays ↓ (especially Factor II, V, VII, X)

Several scoring systems exist to determine the likelihood of DIC as well as prognosis (2). For example, the International Society on Thrombosis and Haemostasis has a scoring system that gives points for the degree of thrombocytopenia, degree of elevation in the d-dimer, degree of prolongation of the PT, and if the fibrinogen level is low or not. If that score is greater than or equal to 5, the presentation is consistent with DIC. (3) This score was then validated in a prospective study looking at 217 intensive care patients at an academic center resulting in a sensitivity of 91% and specificity of 97%. The study also showed a strong correlation between DIC and 28-day mortality (4), further illustrating how important it is to start treatment for DIC in the emergency department if it is suspected.

Treatment: What can we do about it?

  1. Treat the underlying disease. For most cases, DIC will resolve on its own if the underlying condition is appropriately treated (5).
  1. If bleeding is the main problem and there is continuing active bleeding or a high risk for more bleeding:
Lab Abnormality Treatment
Hgb <7 or active significant bleeding on exam PRBCs (packed red blood cells)
Platelets <50,000 Platelets
PT >1.5 or fibrinogen <100 FFP (fresh frozen plasma)

Vitamin K

Trauma-related bleeding TXA (tranexamic acid)

The dosing for transfusions will vary based on the exact lab values and presentation. For platelet transfusion, the platelet count should rise by 5,000/uL for each unit of platelets (6). For FFP, the initial recommended dose is 15 cc/kg (2).

If the patient cannot tolerate large volumes of fluid, small volume PCC (prothrombin complex concentrate) can be substituted for FFP. However, giving only PCC will not replenish all of the needed clotting factors, especially factor V and fibrinogen. Thus, cryoprecipitate should also be given to help replenish the patient’s depleted fibrinogen. (6)

Some patients in DIC will also continue to have low fibrinogen levels that are refractory to FFP administration. These patients require concomitant cryoprecipitate (7).

Disposition for all of these patients should be to an intensive care unit (ICU). However, depending on how long it takes to get the patient out of the ED and into the ICU, it is important to keep in mind that the DIC labs should be repeated every six hours in critically ill patients and after any interventions (7).

  1. If hypercoagulation is the main problem, consider therapeutic doses of low molecular weight heparin. A small randomized control study showed this was superior to using unfractionated heparin. The predominately hyperfibrinolytic patients are also at increased risk for venous thromboembolism and should be started on prophylactic anticoagulation with low molecular weight heparin as soon as the bleeding risk is mitigated. (5)

 Case Resolution

You reassess the patient and notice that he indeed is continuing to ooze from his two IV sites. You also notice petechiae on his lower extremities. Concerned for DIC, you immediately start treating the patient’s underlying condition of pancreatitis and a urinary tract infection. The patient is made nil per os (NPO) and given IV fluids, antiemetics, and analgesia. His hyperglycemia is controlled after fluids are started. He has known thrombocytopenia and the rest of his DIC labs show an INR of 1.8, a low fibrinogen level, and an elevated d-dimer. The patient is given two units of platelets, 15 cc/kg FFP, 10 mg IV Vitamin K and is admitted to the ICU laboratory tests are frequently checked and he is given blood products as needed. On day two, the patient begins to improve and by day eight, the patient is discharged home.

 Summary

DIC is an important clinical entity seen in critically ill patients. Laboratories studies may demonstrate low platelets, an elevated INR, an elevated d-dimer, and low fibrinogen levels. Rapid identification and treatment of the underlying cause as well as supplementation with blood products is important to reduce mortality in these patients.

References/Further Reading

  1. Tintinalli JE et al. Acquired bleeding disorders: disseminated intravascular coagulation. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 2011; 7.
  2. Wada H, Matsumoto T, Yamashit Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014; 2(1):15.
  3. Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86: 1327-30.
  4. Bakhtiari K, Meijers JC, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004; 32(12): 2416-21.
  5. Wada H, et al. Guidance for diagnosis and treatment of disseminated intravascular coagulation from harmonization of the recommendations from three guidelines. J Thrombosis & Haemostasis. 2013; 11: 761-7.
  6. Levi M, Opal SM. Coagulation abnormalities in critically ill patients. Crit Care. 2006; 10(4): 222.
  7. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009; 145(1): 24-33.

Cellulitis Antibiotic Selection: Management Updates

Authors: Josh Bucher, MD (Assistant Professor of Emergency Medicine, Rutgers – RWJMS) and Darren Cuthbert, MD, MPH (EM Resident Physician, Rutgers – RWJMS) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM staff physician at SAUSHEC, USAF)

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Introduction

The treatment of cellulitis has changed tremendously in the last ten years. With the development of community-acquired MRSA infections along with an increasing number of immunocompromised hosts, there is concern about missing MRSA if not treating cellulitis for it.1 However, the Infectious Disease Society of America (IDSA) released their skin and soft tissue guidelines in 2014, providing clear instructions for both antibiotic choice and who should be treated for suspected MRSA. We will start with four cases and then describe the IDSA recommendations.

These cases will highlight the recent updates to the Infectious Disease Society’s Practice Guidelines for the management of cellulitis and soft tissue infections. It is vital that emergency providers stay current with their clinical judgment in disposition as well as the use of appropriate antibiotic therapy.

 

Cases

Case 1 – A 47 year-old Hispanic male with a history of poorly controlled type II diabetes mellitus presents to your ED complaining of pain with redness to the distal posterior leg.  He reports an onset of 1 week with the pain progressively worsening while the area has quadrupled in size. He denies recollection of a triggering event.  He describes his pain as throbbing in quality, worsening from 1/10 at first instance, to 5/10 today, non-radiating, with mild exacerbation upon light touch and ambulation.  The patient has spent the past month living in a homeless shelter while in recovery for alcoholism. He has no primary doctor.   Visual inspection reveals a right leg with a 10” by 8” area that is red, warm, and erythematous, with sharply demarcated borders. The area is tender to touch with a negative Pratt’s or Homan’s sign.  His leg has adequate distal pulses, with no motor or sensory deficits.  He has no fever, chills, and his vital signs are within normal limits. A bedside ultrasound performed shows no fluid collection.

Case 2 – A 28 year-old Caucasian female with a 9-year history of intravenous heroin use presents to your ED complaining of fever and pain with redness to the right antecubital space. The patient states she first noticed redness surrounding an injection site 3 days prior, but continued to inject within that proximity. Yesterday she was unable to find a vein and noticed pus oozing from the site.  Over the past 24 hours the area has become more painful, and she feels what she describes as a “ball” underneath the skin within the region. Visual inspection shows a poorly demarcated area of redness in the right antecubital space that is circumferential around the elbow, spreading half way down the forearm.  The area is warm and tender to light touch, spanning approximately 4.5” by 7”. There is a smaller area in the middle with fluctuance and induration. Her temperature is 101.6, with a blood pressure and heart rate of 102/55 and 103, respectively.  She has adequate distal pulses, with no motor or sensory deficits.

Case 3 – A 25 year-old health male presents with the complaint of flank pain. He reports he scraped it a few days ago inside his house. He cleaned it, but it has progressively became more painful. On exam, he has a 4 x 4 cm area of erythema that is tender without crepitus. He is afebrile, has no medical problems, and has an appointment with his primary doctor in two days but could not wait due to pain so came in for evaluation today.

Case 4 – A 66 year-old patient with an aggressive leukemia presents with altered mental status. He last received chemotherapy 3 days ago. His family stated he has become progressively confused and noted a weird rash. On his left lower extremity there is erythema, purple discoloration, and large bullae up to the proximal thigh. He is febrile, tachycardia, and hypotensive. His sodium is 127 and his WBC is 35.

 

When approaching the management of skin in soft tissue infections in the ED, it must first be determined whether the infection is purulent or non-purulent, followed by assessing the severity.  Non purulent infections vary in form from erysipelas and cellulitis.  Purulently draining skin and soft tissue infections usually come in the form of furuncles, carbuncles, or abscesses.1 Feasibility and specification of antibiotic use, need for surgical evaluation, and need for culture and sensitivity are all dependent upon these factors.

Distinguishing the mild purulent skin and soft tissue infection from a moderate or severe infection begins with the physical exam and vital signs.  Both the moderate and severe cases show signs of systemic disease.1 In the case of skin and soft tissue infections, systemic disease is defined as a temperature >38C, tachycardia >90 bpm, respiratory rate >24, or an abnormal white blood cell count >12,000 or < 4,000.  Immunocompromised patients are also considered as having systemic disease.  A severe patient is one with systemic disease who has failed a round of antibiotic therapy or incision and drainage.1 Non-purulent infection severity is defined similarly, but rather than failing incision and drainage, which isn’t indicated for non-purulent cellulitis, a severe infection demonstrates deeper spread and systemic signs of sepsis including hypotension and other organ dysfunction.1

If no focal purulence is found, incision and drainage is not indicated, while antibiotics are.  Mild and moderate cases in a stable patient can be managed as an outpatient, with no culture and sensitivity required.  A beta-lactam, cephalosporin (with sea water exposure), or clindamycin is efficacious per the IDSA.1 Many treatment plans will depend on institution sensitivities and antibiogram, so if possible utilize these helpful resources.

In the case of a severe non-purulent infection, a necrotizing process must be ruled out.1  Necrotizing fasciitis comes in three forms: type I which is polymicrobial (most common), type II which typically occurs on the extremities and is caused by a Group A streptococcus, and type III which is caused by vibrio vulnificus via underwater sea injury.2 The most important risk factor for necrotizing fasciitis is a weakened immune system such as diabetes, cancer, or HIV.2  Suspicion for necrotizing fasciitis requires immediate surgical inspection in conjunction with empiric antibiotics (vancomycin plus piperacillin/tazobactam and clindamycin).1 The patient requires ICU admission and empiric antibiotics, along with surgical debridement.1

Purulent skin and soft tissue infections on the other hand require incision and drainage; in fact, a mild infection only requires incision and drainage without culture/sensitivity or antibiotic therapy.  Moderate and severe disease are treated with empiric antibiotics (TMP/SMX or doxycycline in moderate disease, or vancomycin or daptomycin in severe disease) pending the results of a culture and sensitivity.1

 

Case Resolutions

Case 1 – The patient is unable to obtain any outpatient follow up as he is homeless with no primary doctor. The patient agrees with the plan for admission for intravenous antibiotics, and 1 gram of cefazolin is ordered.

Case 2 – The abscess is incised with greater than 20 mL of purulent fluid expressed from the wound. An appropriate weight-based dose of vancomycin is administered, and the patient is admitted.

Case 3 – The patient is appropriately treated in the mild, non-purulent category and leaves with a prescription for penicillin VK for one week.

Case 4 – Emergent surgical consultation is obtained. The patient is administered vancomycin, piperacillin/tazobactam as well as clindamycin, and the surgical service takes the patient to the operating room for an obvious necrotizing infection.

 

Take Home Points

  1. Patients with uncomplicated cellulitis, with no co-morbidities, and without purulence, require coverage for MSSA with penicillins or first-generation cephalosporins.
  2. Patients with non-purulent cellulitis requiring admission only need coverage for MSSA and not MRSA.
  3. Purulent cellulitis requires coverage for MRSA.
  4. Necrotizing fasciitis requires broad-spectrum coverage, and, most importantly, immediate surgical consultation for debridement.
  5. Know your hospital’s antibiogram and availability of timely outpatient follow-up.

 

References / Further Reading

  1. Stevens D.L., Bisno A.L., et al. (2014). Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. Infectious Diseases Society of America: Clinical Infectious Diseases Advance Access, June 18th, 2014. (1). DOI: 10.1093/cid/ciu296
  2. Babak S., Strong M., Pascual J., Schwab W. (2009). Necrotizing Fasciitis: Current Concepts and Review of the Literature. Journal of the American College of Surgeons. 208-2 (279-288). DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2008.10.032

Brain Abscess: Pearls and Pitfalls

Author: Kristen Kann, MD (EM Staff Physician, SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Background

Brain abscesses are relatively rare compared to other CNS infections encountered by the emergency physician, such as meningitis, but are extremely important to consider and recognize due to the differences in diagnosis, treatment, and outcomes for the patient. There are approximately 2,000 cases of brain abscess in the United States annually.1 Some important risk factors include immunocompromised state (HIV/AIDS, transplant recipients, chronic alcoholism), injection drug use, and violation of the cranial or spinal spaces due to trauma or surgery.1

Pathogenesis

The most likely causative agent of a brain abscess depends on the patient and the likely source of the infection. Most CNS abscesses are bacterial, with 60% being polymicrobial.4 Immunocompromised patients will have a higher risk for fungal (Candida and Aspergillus most commonly)5 and parasitic infections. Patients in, or recently returned from, endemic areas may also be at risk for CNS tuberculosis or neurocysticercosis.  In general, Streptococci are involved in approximately 70% of CNS abscesses, and Staphylococci in approximately 20%.4

Abscesses can be primary, but are most often either from direct spread (1/3 of cases) or distant sources (1/3 of cases).2 Contiguous spread can occur from the sinuses, the middle ear, or dental infections, while the most common distant source of infection is the pulmonary system.1 Hematogenous spread appears to be increased in systemic hypoxic states such as chronic pulmonary disease or congenital heart disease.2 The remaining cases are either iatrogenic, related to trauma, or of an unknown source.

Signs/Symptoms

One of the biggest challenges for emergency physicians in the diagnosis of brain abscess is the lack of a reliable, sensitive, and specific clinical picture. Many patients presenting with brain abscess have a clinical picture consistent with meningitis, sepsis, or other infectious process, and the classic triad of fever, headache, and focal neurologic signs is present in less than one third of patients.2 Headache is the most common symptom of brain abscess, occurring in about 70% of cases, but characteristics of the headache (such as generalized vs one-sided, gradual or sudden onset) are not reliable indicators of an underlying abscess. Focal neurologic signs such as aphasia, hemiparesis, or a visual field deficit are important findings, as they are less common in other, more diffuse CNS infections such as meningitis and are contraindications to lumbar puncture. Nuchal rigidity, in the case of a CNS abscess, should increase concern for rupture of the abscess into the CSF spaces and possible impending decompensation. Fever is present in less than 50% of patients at presentation and should NOT be used to rule out CNS abscess. Seizures are the most common complication of brain abscesses but are rarely the first presenting sign.1, 2

Work Up

The work up for brain abscesses has two key features: IMAGING WITH CONTRAST, and AVOIDANCE OF LUMBAR PUNCTURE.

CT scan, while not as sensitive for MRI in the diagnosis of brain abscess, is much more widely available to the EP, and it is the most likely first imaging modality that will be obtained. IV contrast should be ordered in any patient in whom a brain abscess is suspected, including those with high risk historical features, focal neurologic signs, or a history of CNS trauma or surgery. An abscess may appear only as an area of lower density (also known as cerebritis) early in the course of illness, but as the abscess matures, encapsulation causes the characteristic “ring enhancement” on CT with contrast.

LP is contraindicated in patients with possible increased ICP caused by a space-occupying lesion such as a brain abscess.3 Clinical findings that should trigger the EP to consider deferring an LP, at least until after imaging, include focal neurologic deficit, papilledema, seizures, head trauma, or a rapid change in level of consciousness. Exam findings consistent with elevated intracranial pressure include decreased mental status, vomiting, seizures, and possibly Cushing’s Triad of increased blood pressure, decreased heart rate, and erratic respirations. Exam findings concerning for uncal herniation include unilateral third-nerve palsy (pupillary dilation and loss of light reflex) and altered mental status.

It is important to note that LP plays no role in the diagnosis of brain abscess- culturing the causative organism is unlikely, and there are no specific findings in CSF that will diagnose brain abscess. Due to the overlapping presentations of meningitis and brain abscess, however, there is some data about LP results. One study of 65 patients showed a mean protein level of 250 mg/dL (range 90 to 425 mg/dL); mean glucose level 39 mg/dL (range 11 to 58 mg/dL); and mean white cell count 4407 per microL (range 80 to 5006 per microL).6

Other laboratory tests that may be obtained include a CBC with differential, a chemistry panel (to assist with dosing of empiric antibiotics and evaluate for other causes of altered mental status), and blood cultures. Though blood cultures are only positive about 10% of the time, they may be useful to the inpatient team, especially if no specific source is suspected (in which case, direct culture of the source infection is likely to be more useful than blood cultures).

Management

ED management of brain abscess centers on diagnosis, empiric antibiotics, and consultation with neurosurgery. Almost all abscesses will need to be drained, unless there are only very small abscesses in deep brain structures that may not be amenable to drainage. If the patient is very stable and neurosurgical consultation is available with a plan for aspiration within 24 hours, an argument could be made for delay in administration of antibiotics until the abscess can be sampled for cultures. This will allow for guidance of therapy and, possibly, avoidance of some side effects of broad, long term antibiotic coverage. However, in the patient with altered mental status or unstable clinical status, empiric treatment should be started as soon as feasible in the Emergency Department.

Empiric therapy for bacterial brain abscess includes a third generation cephalosporin such as ceftriaxone plus metronidazole. Patients with recent trauma or surgery on the CNS should receive additional coverage for MRSA (usually vancomycin), and patients at risk for tuberculosis, fungal infection, or parasitic infection should receive specific treatments for those organisms in addition to empiric antibiotics. Empiric steroids are not indicated in all patients, but may be useful in patients with concern for cerebral edema. Treatment is usually continued for 6-8 weeks, with follow-up imaging to evaluate for response to treatment.5

Summary

– Brain abscesses, though rare, are important for emergency physicians to consider due to important differences in management.

– At risk patients include those with immunocompromise, violation of the CNS spaces through trauma or surgery, and those with a history of possible source infections such as dental, sinus, or middle ear infections.

– The presentation is vague, but headache and focal neurologic findings or altered mental status, with or without a fever and nuchal rigidity, should alert the EP to the possibility of a brain abscess.

– These findings necessitate imaging with IV contrast, and an LP should be avoided due to the possibility of herniation.

Empiric antibiotics such as Ceftriaxone + Metronidazole, possibly Vancomycin, and targeted treatment for patients at risk for fungal or parasitic infections, should be started as quickly as possible in ill-appearing patients.

Neurosurgery should be consulted early to assist in source control and long term treatment.

 

References / Further Reading:

  1. Meurer, W. J. (2014). Central Nervous System Infections in Rosen’s Emergency Medicine, 8th
  2. Ma O. Chapter 148. Central Nervous System and Spinal Infections in Tintinalli’s Emergency Medicine Manual, 7th
  3. Euerle, B.D. (2014). Spinal Puncture and Cerebrospinal Examination in Roberts and Hedges’ Clinical Procedures in Emergency Medicine, 6th
  4. Moorman, J. P. (2013) Acute Infections of the Central Nervous System: Meningitis and Brain Abscess in Gantz’s Manual of Clinical Problems in Infectious Disease
  5. Anderson, N.C., Koshy A.A., and Roos, K.L. (2016) Bacterial, Fungal and Parasitic Diseases of the Nervous System in Bradley’s Neurology in Clinical Practice
  6. Tattevin P et al., Bacterial Brain Abscesses: A Retrospective Study of 94 Patients Admitted to an Intensive Care Unit, Am J Med. 2003; 115(2):143