Bacteremia: ED Presentations, Evaluation, and Management
- Feb 20th, 2023
- Mary E. Lewis
Authors: Mary E. Lewis, MD (EM Resident Physician, Medical College of Wisconsin); Shannon Burke, MD (Assistant Professor of EM, Medical College of Wisconsin) // Reviewed by: Summer Chavez, DO, MPH, MPM (EM Physician, University of Houston); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit); Marina Boushra, MD (EM-CCM Physician, Cleveland Clinic Foundation)
A 36-year-old female with no significant past medical history presents to the ED as directed by her physician because she had blood cultures sent yesterday that resulted positive today. They have not completed sensitivities yet and her doctor recommended she return to the ED for further treatment as she is still symptomatic. She is currently on cephalexin for pyelonephritis and has been taking it as prescribed. She had been experiencing 5 days of right-sided flank pain, dysuria, and urinary frequency prior to her presentation yesterday. At this time, she has mild back pain, but her dysuria is improving. She states she is still experiencing fevers and chills. She denies any upper respiratory symptoms, chest pain, shortness of breath, or rashes. She has been feeling somewhat fatigued and had to miss work. Vital signs include an oral temperature of 99.5° F, heart rate 85 bpm, respiratory rate 16 breaths per minute, a saturation of 99% on room air, and blood pressure 110/70 mm Hg. Her physical exam is notable for costovertebral angle tenderness on the right flank.
Bacteremia is a clinical syndrome defined by the presence of bacteria in the blood.1, 7, 8, 9, 14, 17 Bacteria can become introduced into the bloodstream via multiple mechanisms including medical procedures, indwelling catheters, trauma, burns, and ulceration of the skin.1,2, 3, 13, 15 Hematogenous spread of bacteria into the bloodstream from a primary source such as the urinary tract or respiratory tract can also occur.1, 2, 3, 13 It is the body’s response to the introduction of bacteria into the blood that ultimately determines whether a patient has a persistent bloodstream infection.1, 2
There are multiple definitions and categories of bacteremia:
- Asymptomatic bacteremia occurs when there is a transient presence of bacteria in the blood and the immune system can appropriately respond to eliminate the bacteria. This can occur after simple medical procedures. In asymptomatic bacteremia, the clinical signs and symptoms of bacteremia are absent.1
- Intermittent bacteremia results from seeding of the blood due from a source outside of the vascular system. Intermittent bacteremia is present for a defined period. This can be caused by manipulation of body tissues such as dental cleanings.
- Persistent bacteremia develops when the site is within the vascular system such as in endocarditis, suppurative thrombophlebitis, infected aneurysm, or intravascular foreign body.2
- Complicated bacteremia is the presence of bacteria in the bloodstream with a comorbid factor. Comorbid factors include endocarditis, indwelling lines or devices, persistently positive blood cultures despite therapy, persistent fever despite antimicrobial treatment for at least 72 hours, and signs of metastatic infection.11
- Occult bacteremia is that which is found on positive blood cultures, that are determined not to be contaminated, in patients who were appeared clinically well enough for discharge.8,9
Bacteremia encompasses a vast range of clinical syndromes. Ultimately, the most concerning syndrome is the development of sepsis and septic shock. While the goal of this discussion is not to review sepsis, it is important to acknowledge the consequences of bacteremia. Further discussion of sepsis and septic shock can be found here: (EM Cases – Sepsis and Septic Shock – What Matters from EM Cases Course: emdocs.net/em-cases-sepsis-and-septic-shock-what-matters-from-em-cases-course,Surviving Sepsis Campaign: 2021 Updates: emdocs.net/surviving-sepsis-campaign-2021-updates, Early Sepsis: Why Do We Miss It And How Do We Improve:emdocs.net/early-sepsis-why-do-we-miss-it-and-how-do-we-improve, The EM Educator Series: Sepsis in the ED: emdocs.net/em-educator-series-sepsis-ed, So you think it is sepsis: considerations beyond lung and urine in the sick patient without a source: emdocs.net/think-sepsis-considerations-beyond-lung-urine-sick-patient-without-source, Ready for the New Sepsis 3.0? emdocs.net/8419-2). Bacteremia is associated with significant morbidity and mortality, and not all patient populations are affected equally.8, 9, 12, 13, 14, 15, 19 One study found that the 30-day mortality rate for S. aureus bacteremia is 9.7%.8 Another study found that patients admitted from the ED with bacteremia had a 28-day mortality of 13.5-15.2%.12 Bacteremia resulting in sepsis has a worse prognosis. One study looking at sepsis associated with bacteremia in the ICU found a case fatality rate of 30%-50% when organ dysfunction was present.14 This further highlights the importance of a strong clinical understanding of bacteremia and its treatment.
History and Physical
History may reveal fever, chills, and rigors.1, 12, 18 Shaking chills have been shown to have a greater likelihood ratio for bacteremia (LR 4.7) when compared with tachycardia (LR 1.4) or fever (LR 1.9).3,20 Additional signs present as patients get sicker; patients can develop altered mental status, acute respiratory distress syndrome, and acute kidney injury.1 Vital signs may demonstrate fever, hypothermia, or hypotension.1, 3, 12, 15 However, it is important to maintain suspicion for bacteremia despite normal vital signs if the clinical picture fits. One study found that 33% of patients with positive blood cultures had a normal temperature.9 Patients should be assessed for possible infectious sources on history and physical exam.
The differential diagnosis for bacteremia is broad and should be developed based on the concern for potential sources of infection.1, 3, 11 Additionally it is important to consider past medical history that could complicate bacteremia, including structural heart disease, history of device implantation, recent surgery, instrumentation, intravenous drug use, or prosthesis.1, 11, 21
Triage models have been developed for early identification of bacteremia based on initial presentation. Early identification may help to initiate treatment earlier, which may improve morbidity and mortality.4, 5, 6, 9, 12, 13 Additionally, patients with a low risk of bacteremia can be identified and excluded from further workup, potentially reducing costs and hospital length of stay.6 Examples of triage models include Triage XGB, Triage RF, Triage LR, Triage qSOFA, and SIRS.6 The Triage XGB, Triage RF, and Triage LR models are machine-learning algorithms using 10 triage variables: age, ambulance use, chief complaint, initial mental status, triage level, time from symptom onset to ED visit, systolic blood pressure in triage, diastolic blood pressure in triage, heart rate in triage, and body temperature in triage.6 One study demonstrated that the XGB, Triage RF, and Triage LR models performed better in the identification of bacteremia relative to the SIRS criteria or qSOFA models.6 The XGB model had a sensitivity of 97% for bacteremia. While further investigation is needed, these models have the potential to impact clinical care.
Blood cultures are the gold standard for confirming suspected bacteremia.1, 5, 8, 10, 18 When drawing blood cultures, 2-3 sets of cultures should be drawn from different sites.1,2 If indwelling lines are present, at least one set of blood cultures should be drawn off those lines.18 If a central line is removed, the tip of the line may also be cultured. The clinical utility of catheter tip cultures is debated, given the possibility of contamination during the removal of the line. 1, 18
Clinical suspicion dictates when to perform blood cultures. Certain features, like the presence of central lines and certain primary sources have a high likelihood of bacteremia, so blood cultures should be drawn when these conditions are suspected or confirmed.2,3 Below is a chart (Table 1) detailing different sources of infection and the pretest probability of bacteremia:
Table 1: Pretest Probability of Bacteremia in Common Clinical Scenarios3
Additionally, it is important to obtain cultures even if the likelihood of bacteremia is lower but the patient’s comorbidities are such that if bacteremia were missed the consequences would be severe.3 These articles provide further information on when to obtain blood cultures:
(“So, Blood Cultures… or No?” – Use of Blood Cultures in the ED, Blood cultures: when do they make a meaningful impact on clinical care?)
Which bacteria do blood cultures commonly produce?
Gram-positive bacteria are the most common type of bacteria isolated, of which S. aureus is the most common.1, 3, 13, 15 S. aureus infections are associated with higher rates of hospital admission, organ failure, septic shock, ICU admission, and 30-day mortality.8 The most common gram-negative organism, and the second most common cause of bacteremia, is E. coli.1, 13 Gram- negative bacteremia is associated with need for vasopressor use in the ED, bandemia, and urinary sources of infection.7 Common contaminants in blood cultures include coagulase-negative staphylococci and Bacillus and Corynebacterium species.14, 18 Bacteria with high case fatality rates include S. aureus, S. pyogenes, S. pneumoniae, and E. coli.12, 16 The identification of specific organisms is an important factor in tailoring treatment and understanding the potential severity.
Other molecular adjuncts to cultures, including PNA-FISH, MALDI-TOF, and PCR (GeneXpert, FilmArray, Verigene) have been developed to rapidly identify specific bacteria and susceptibilities. Depending on the assay, these molecular adjuncts may result between 10 minutes to 2.5 hours, so there may be potential to tailor antibiotic therapy in the ED.4,5 While not widely integrated yet, these adjuncts can aid in antimicrobial stewardship, improved clinical outcomes, decreased lengths of stays, and lower healthcare costs.4,5, 22
Blood cultures have been drawn – so, what else?
Workup, including imaging choices, should be tailored to clinical suspicion for a primary source based on the history and physical exam.1 Inflammatory markers, including procalcitonin, ESR, and CRP have been studied extensively in bacteremia and sepsis. Generally, these markers have been thought to be nonspecific markers of inflammation that do not necessarily differentiate between infection and other inflammatory responses.23-25 The utility of procalcitonin specifically has been a topic of debate. It should not be used as a decision tool for the initiation of antibiotics in cases of suspected bacteremia.18 However, it has been shown to predict bacteremia, especially in ICU patients.11 Additionally, data suggests that procalcitonin may be helpful in differentiating line colonization rather than invasive infection and may allow for discontinuation of antibiotics in this setting.18
ED Management: How to treat suspected bacteremia in the ED
In the ED, physicians rarely have access to blood culture results or rapid confirmation of bacteria in the blood. If there is suspicion for bacteremia, then empiric, broad-spectrum antibiotics should be initiated as soon as possible, preferably after blood cultures are drawn.1, 6, 12 Coverage for bacteria such as MRSA and pseudomonas should be considered in the right clinical context, including recent hospitalization or antibiotic use. Early initiation of treatment has been associated with reduced morbidity and mortality.6, 12 Additionally, data suggests that inappropriate antibiotics are a very important factor in affecting the outcome of patients admitted to the ICU for community-acquired bacteremia.16
Patients presenting with positive blood cultures
Blood culture contamination is also important to consider when managing bacteremia. Only 5-10% of blood cultures are positive, half of which are contaminated.6 Results are more likely to be due to a contaminant if only one is positive. Again, common contaminants include coagulase negative staphylococci and Bacillus and Corynebacterium species. 14,18
Pharmacists and infectious disease physicians may help guide decisions regarding antibiotic therapy, especially for patients with a prior history of multi-drug resistant infections, severe allergies or dosing adjustments in the setting of liver/renal impairment.
The patient is covered empirically within antibiotics for a urinary source and was admitted to the hospital for blood culture monitoring and further treatment. Several hours later, the patient was found to have a Verigene positive for E. coli. This allowed for narrowing of the selected antibiotics to target E. coli. This case demonstrates the utility of rapid identification of bacteremia using molecular models and the importance of considering occult bacteremia in patients with a known primary source.
- Bacteremia has significant morbidity and mortality.
- High-risk factors for development of bacteremia include the presence of central venous catheter, discitis, vertebral osteomyelitis, spinal epidural abscess, acute non-traumatic native septic joint, meningitis, septic shock, and ventriculoatrial shunt infections.
- Rapid identification of potential bacteremia and the initiation of broad-spectrum antibiotics is important. In the ED, physicians should always treat empirically when bacteremia is suspected, even when the specific bacteria is not confirmed.
- Triage tools may be useful for identifying patients at risk for bacteremia, but clinical judgment should supersede these scores.
- Molecular models may be a useful adjunct to blood cultures for the rapid identification of pathogens and susceptibilities but are not always readily available.
- Smith DA, Nehring SM. Bacteremia. StatPearls. 2022.
- Doern GV. Detection of bacteremia: Blood cultures and other diagnostic tests. In: Post TW, ed. UpToDate. UptoDate; 2022.
- Fabre V, Sharara SL, Salinas AB, Carroll KC, Desai S, Cosgrove SE. Does This Patient Need Blood Cultures? A Scoping Review of Indications for Blood Cultures in Adult Nonneutropenic Inpatients. Clinical Infectious Diseases. 2020;71(5):1339-1347. doi:10.1093/cid/ciaa039
- Box MJ, Sullivan EL, Ortwine KN, et al. Outcomes of Rapid Identification for Gram-Positive Bacteremia in Combination with Antibiotic Stewardship at a Community-Based Hospital System. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2015;35(3):269-276. doi: https://doi.org/10.1002/phar.1557
- Kothari A, Morgan M, Haake DA. Emerging Technologies for Rapid Identification of Bloodstream Pathogens. Clinical Infectious Diseases. 2014;59(2):272-278. doi:10.1093/cid/ciu292
- Choi DH, Hong KJ, Park JH, et al. Prediction of bacteremia at the emergency department during triage and disposition stages using machine learning models. The American Journal of Emergency Medicine. 2022/03/01/ 2022;53:86-93. doi: https://doi.org/10.1016/j.ajem.2021.12.065
- Chase M, Klasco RS, Joyce NR, Donnino MW, Wolfe RE, Shapiro NI. Predictors of bacteremia in emergency department patients with suspected infection. The American Journal of Emergency Medicine. 2012/11/01/ 2012;30(9):1691-1697. doi: https://doi.org/10.1016/j.ajem.2012.01.018
- Fu C-M, Tseng W-P, Chiang W-C, et al. Occult Staphylococcus aureus Bacteremia in Adult Emergency Department Patients: Rare but Important. Clinical Infectious Diseases. 2012;54(11):1536-1544. doi:10.1093/cid/cis214
- Seigel TA, Cocchi MN, Salciccioli J, et al. Inadequacy of Temperature and White Blood Cell Count in Predicting Bacteremia in Patients with Suspected Infection. Journal of Emergency Medicine. 2012;42(3):254-259. doi: 10.1016/j.jemermed.2010.05.038
- Riedel S, Carroll KC. Early Identification and Treatment of Pathogens in Sepsis: Molecular Diagnostics and Antibiotic Choice. Clinics in Chest Medicine. 2016/06/01/ 2016;37(2):191-207. doi: https://doi.org/10.1016/j.ccm.2016.01.018
- Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine. 2017;45(3)
- Andersson H, Axelsson C, Larsson A, et al. The early chain of care in bacteraemia patients: Early suspicion, treatment and survival in prehospital emergency care. The American Journal of Emergency Medicine. 2018/12/01/ 2018;36(12):2211-2218. doi: https://doi.org/10.1016/j.ajem.2018.04.004
- Weinstein MP, Towns ML, Quartey SM, et al. The Clinical Significance of Positive Blood Cultures in the 1990s: A Prospective Comprehensive Evaluation of the Microbiology, Epidemiology, and Outcome of Bacteremia and Fungemia in Adults. Clinical Infectious Diseases. 1997;24(4):584-602. doi:10.1093/clind/24.4.584
- Hugonnet S, Harbarth S, Ferrière K, Ricou B, Suter P, Pittet D. Bacteremic sepsis in intensive care: temporal trends in incidence, organ dysfunction, and prognosis. Critical care medicine. 2003/02// 2003;31(2):390-394. doi: 10.1097/01.ccm.0000045026.81584.6f
- Diekema DJ, Beekmann SE, Chapin KC, Morel KA, Munson E, Doern GV. Epidemiology and Outcome of Nosocomial and Community-Onset Bloodstream Infection. Journal of Clinical Microbiology. 2003;41(8):3655-3660. doi: 10.1128/JCM.41.8.3655-3660.2003
- Vallés J, Rello J, Ochagavía A, Garnacho J, Alcalá MA. Community-Acquired Bloodstream Infection in Critically Ill Adult Patients: Impact of Shock and Inappropriate Antibiotic Therapy on Survival. CHEST. 2003;123(5):1615-1624. doi:10.1378/chest.123.5.1615
- Walls R, Hockberger R, Gausche-Hill M, Erickson TB, Wilcox SR. Rosen’s Emergency Medicine: Concepts and Clinical Practice: 2-Volume Set. Elsevier Health Sciences; 2022.
- Farkas J. Line infection. Internet Book of Critical Care https://emcrit.org/ibcc/line/#persistent_bacteremia Published July 20, 2021. Accessed 12/29/2022.
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2021;49(11)
- Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? [published correction appears in JAMA. 2013 Jan 23;309(4):343]. JAMA. 2012;308(5):502-511. doi:10.1001/jama.2012.8262
- Rapoport AB, Fischer LS, Santibanez S, Beekmann SE, Polgreen PM, Rowley CF. Infectious Diseases Physicians’ Perspectives Regarding Injection Drug Use and Related Infections, United States, 2017. Open Forum Infect Dis. 2018 Jun 8;5(7):ofy132. doi: 10.1093/ofid/ofy132. PMID: 30018999; PMCID: PMC6041812.
- Scerbo MH, Kaplan HB, Dua A, et al. Beyond Blood Culture and Gram Stain Analysis: A Review of Molecular Techniques for the Early Detection of Bacteremia in Surgical Patients. Surg Infect (Larchmt). 2016;17(3):294-302. doi:10.1089/sur.2015.099
- Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013;50(1):23-36. doi:10.3109/10408363.2013.764490
- Biron BM, Ayala A, Lomas-Neira JL. Biomarkers for Sepsis: What Is and What Might Be?. Biomark Insights. 2015;10(Suppl 4):7-17. Published 2015 Sep 15. doi:10.4137/BMI.S29519
- Samraj RS, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock. 2013;40(5):358-365. doi:10.1097/SHK.0b013e3182a66bd6