Author: Adrianna Levesque (EM Senior Resident at SAUSHEC, US Army) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)

It is essential for Emergency Physicians to know the standard of care for sexually transmitted infection (STI) treatments, as patients often present to Emergency Departments for evaluation and treatment shortly after exposure to these diseases. The Emergency Department provides patients with rapid screening, diagnosis, treatment regimens, and access to outpatient follow up. The CDC has updated the recommendations in 2015 and can be found at http://www.cdc.gov/std/tg2015/. This article is aimed to provide the pertinent updates and recommendations applicable to the Emergency Department.

Updated treatment recommendations regarding the most common pathogens with increasing resistance rates of antibiotic resistance

Urethritis and cervicitis

Although Neisseria gonorrhoeae and Chlamydia trachomatis are well established as the most common infectious causes of urethritis and cervicitis, Mycoplasma genitalium has also been associated with these diagnoses, and less commonly, prostatitis. While M. genitalium has been found to be the sole pathogen detected in a majority of patients with urethritis and cervicitis, co-infection with C. trachomatis is common. The diagnosis of N gonorrhoeae and C trachomatis is made with nucleic acid amplification tests (NAATs). NAAT can be used for detection of M. genitalium, but there is no FDA approved test available in the U.S.

Patients with presumed infection of both N gonorrhoeae and C trachomatis should be treated with ceftriaxone 500mg intramuscularly once plus azithromycin 1g orally once. This is generally the most appropriate strategy in the ED, particularly in high-risk patients and in those for whom follow-up is uncertain or NAATs are not obtained.

Chlamydial infections may be treated with azithromycin 1g orally once or doxycycline 100mg orally twice daily for 7 days. Alternative treatments include erythromycin base 500mg orally four times daily for 7 days, erythromycin ethylsuccinate 800mg orally four times a day for 7 days, levofloxacin 500mg orally once daily for 7 days, or ofloxacin 300mg orally twice a day for 7 days. Doxycycline treatment is contraindicated in pregnant patients.

Monotherapy with 2g oral azithromycin has been proven to be effective in patients with noncomplicated gonorrheal infections, but this is no longer recommended because of concerns of resistance to macrolides and documented treatment failures. Cefixime has also been shown to have increased resistance and is no longer recommended as first line therapy for gonorrhea. Given the growing resistance patterns of gonorrhea, dual antibiotic therapy is recommended for treatment. First line recommendations for uncomplicated gonococcal infection of the vagina, cervix or rectum are ceftriaxone 500mg IM once plus azithromycin 1g orally once. In cases of gonococcal conjunctivitis or disseminated gonococcal infections, the dose of ceftriaxone should be increased to 1g IM single dose plus 1g oral azithromycin once.

In children with uncomplicated gonococcal infections weighing <45kg, the dose of ceftriaxone is 25-50mg/kg IM/IV not to exceed 250mg IM. Children weighing <45kg with disseminated gonococcal infection should receive ceftriaxone 50mg/kg IM/IV (max 1g) daily for 7 days.

Azithromycin has been shown to be more effective than doxycycline against M. genitalium. However, in some settings, azithromycin resistance has emerged and moxifloxacin has been used to treat men and women with previous treatment failures when M. genitalium is suspected.

Pelvic inflammatory disease (PID)

Given the serious sequelae related to undiagnosed PID, providers should have a low threshold for making this diagnosis. In patients with lower abdominal pain or pelvic pain with no other illness identified as a cause, one or more of the following criteria should be used to make the diagnosis of PID: cervical motion tenderness, uterine tenderness, or adnexal tenderness. The specificity is increased if a patient has one of the following: oral temp >101°F (>38.3°C), cervical mucopurulent discharge or cervical friability, increased WBC on microscopy of vaginal fluid, elevated CRP, elevated ESR, or laboratory documentation of infection with N gonorrhoeae or C trachomatis; however, this second set of criteria is not required to make the diagnosis of PID.

Recent studies suggest that the proportion of PID cases attributable to N. gonorrhoeae or C. trachomatis is decreasing. Of women who received a diagnosis of acute PID, <50% test positive for either of these organisms. Organisms that comprise normal vaginal flora (e.g., anaerobes, G. vaginalis, Haemophilus influenzae, enteric Gram-negative rods, and Streptococcus agalactiae) have been shown as causative agents for PID. Additionally, cytomegalovirus (CMV), M. hominis, U. urealyticum, and M. genitalium may also be the cause of some PID cases.

Providers should strongly consider hospitalizing patients with severe illness to include high fevers and vomiting or patients with signs of sepsis. If a tubo-ovarian abscess is suspected or cannot be excluded or another surgical emergency cannot be excluded (i.e. appendicitis), patients should be observed with serial abdominal examinations for 24 hours. Pregnant patients with PID should also be admitted for observation. Hospitalization should also be considered for patients who are unable to tolerate oral outpatient treatment regimen and for patients with failure of prior antibiotic treatment.

The recommended treatment regimen of mild to moderate PID is Ceftriaxone 500mg IM plus Doxycycline 100mg twice daily for 14 days with or without Metronidazole 500mg orally twice daily for 14 days OR Cefoxitin 2gm IM and Probenecid 1gm orally once plus Doxycycline 100mg twice daily for 14 days with or without Metronidazole 500mg orally twice daily for 14 days. The addition of metronidazole adds effective treatment against anaerobes and can also effectively treat BV, which can also be etiologies of PID.

Alternative treatments for N. gonorrhea: what if pts are allergic to cephalosporins?

In patients with documented penicillin reactions, allergic reactions to first-generation cephalosporins occur in <2.5% of patients. Further, allergy to third generation cephalosporins is uncommon in penicillin-allergic patients. Use of ceftriaxone or cefixime is contraindicated if the documented allergy was anaphylaxis, Stevens Johnson syndrome, or toxic epidermal necrolysis. There is limited data regarding alternative regimens for treating gonorrhea among people who have a cephalosporin or severe penicillin allergy. Potential options are dual treatment with single doses of oral gemifloxacin 320mg plus oral azithromycin 2g or dual treatment with single doses of intramuscular gentamicin 240mg plus oral azithromycin 2g. Spectinomycin for treatment of urogenital and anorectal gonorrhea can be considered when available. When treating gonorrhea in patients allergic to cephalosporins, providers should consider consulting an infectious disease specialist.

In patients with cephalosporin allergy in a community where prevalence of gonorrhea is low and patient follow up is likely, PID can be treated with oral fluoroquinolones for 14 days (levofloxacin 500mg once daily, ofloxacin 500mg twice daily, or moxifloxacin 400mg once daily) WITH metronidazole 500mg twice daily for 14 days. The patient should have diagnostic results of gonorrhea testing available at follow up to ensure proper treatment is given.

Treatment of your patient’s partner(s) with gonorrhea and/or chlamydia

Expedited Partner Therapy (EPT) is the practice of treating the sex partner(s) of the person who has been diagnosed with Chlamydia or gonorrhea by providing the patient with a prescription for their partner(s). As per the CDC, medical providers should routinely offer EPT to heterosexual patients with chlamydia or gonorrhea infection when the provider cannot confidently ensure that all of a patient’s sex partners from the prior 60 days will be treated. EPT should be provided in accordance with the local laws and regulations. As of June 2015, only four states (Florida, Kentucky, Ohio, and West Virginia) prohibit EPT. The legal status of the particular state you practice can be found at http://www.cdc.gov/std/ept/legal/default.htm.

Syphilis

Patients with primary or secondary syphilis should be treated for early syphilis. Those who have had sexual contact with a person diagnosed with primary, secondary, or early latent syphilis within 90 days of diagnosis should be treated presumptively for early syphilis. If a person has had sexual contact with someone with primary, secondary, or early syphilis diagnosed greater than 90 days where serologic test results are not readily available should also be treated empirically for early syphilis and follow up should be recommended for all of these patients to obtain reevaluation and HIV testing. These patients should be treated with 2.4 million units IM single dose of Benzathine penicillin. Patients with late latent syphilis (which is defined as diagnosis of syphilis without evidence of primary, secondary, or tertiary disease symptoms) or syphilis for unknown duration should be treated with 7.2 million units total of Benzathine penicillin IM, with three total doses of 2.4 million units at one week intervals.

Penicillin allergic non-pregnant patients: can alternatively be prescribed doxycycline 100mg orally twice daily for 14 days or tetracycline 400mg four times daily for 14 days. A single dose of 2 g oral azithromycin has been documented to successfully treat primary and secondary syphilis in some cases but resistance has been documented in many areas of the U.S. and this treatment is recommended only if penicillin and doxycycline regimens are not feasible. The use of azithromycin for syphilis is contraindicated in men who have sex with men (MSM), patients with HIV, and pregnant patients. If alternative treatments are used, patients should have clinical and serological follow up.

Pregnant patients: Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin and should be evaluated closely by obstetrics and immunology.

Children: ≥1 month diagnosed with latent syphilis should be managed by a pediatric infectious-disease specialist. Those with acquired latent syphilis should be evaluated for sexual abuse (e.g., through consultation with child protection services). Evaluation should include CSF analysis (VDRL, cell count and protein), CBC with differential and platelet count. Sexual and physical assault should be considered in evaluation and other examination options may include long-bone radiographs, chest radiographs, liver-function tests, neuroimaging and ophthalmologic exam.

Patients <1 year with primary, secondary or latent syphilis should be treated with benzathine penicillin G 50,000 units IM once (maximum dose of 2.4 million units). Children >1 year with latent syphilis should be treated with benzathine penicillin G 50,000 units IM (maximum dose of 2.4 million units) for 3 doses at one week intervals.

Trichomoniasis

This is the most prevalent nonviral STI in the U.S. and most patients lack symptoms, although symptoms may include urethritis, epididymitis, prostatitis, or malodorous yellow-green vaginal discharge with or without vulvar irritation. Wet mount is only 51-65% sensitive in diagnosis and NAAT is 95-100% sensitive for detection of T. vaginalis. Treatment options are 2g oral metronidazole once or oral tinidazole 2g once. Alternatively, patients may take metronidazole 500mg oral twice daily for 7 days.

What are recommendations when a patient comes in after sexual assault and just wants treatment after their exposure? What do we treat against exactly?

Trichomoniasis, BV, gonorrhea, and chlamydial infection are the most frequently diagnosed infections among women who have been sexually assaulted. Such conditions are prevalent and detection of these infections after an assault does not necessarily imply acquisition during the assault.

If a patient chooses to forego a criminal investigation, examination should include NAAT for gonorrhea and chlamydia, KOH and Wet prep to evaluate for BV and candidiasis, serum samples for HIV, Hepatitis B and syphilis. Serum samples may be obtained outside of the Emergency Department if the patient is able to establish close follow up; however, compliance with follow up in patients surviving sexual assault is poor.

Empiric treatment against chlamydia, gonorrhea, and trichomonas should be considered. Emergency contraception should be offered to the patient in cases that pregnancy might be the result of assault.  Treatment regimen recommendation is ceftriaxone 500mg IM once, azithromycin 1g orally once, and metronidazole 2g orally once (or alternatively tinidazole 2g orally once). If alcohol has been recently consumed, the metronidazole or tinidazole may be given to take at home to avoid adverse reactions.

Postexposure Hepatitis B vaccine should be offered if the patient has not been vaccinated and the assailant’s immunization status is not known. If Hepatitis B vaccine is given at the time of assault, the patient will need to complete the vaccination series. If patients have not been previously vaccinated against HPV, the HPV vaccination can be offered to patients aged 9-26 years and patients will need to complete this vaccination series.

Recommendations for Postexposure HIV Risk Assessment of Adolescent and Adult Survivors Within 72 Hours of Sexual Assault

• Assess risk for HIV infection in the assailant, and test that person for HIV whenever possible.
  • High-risk encounters include exposure of vagina, rectum, eye, mouth or other mucous membrane with nonintact skin or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or other blood-contaminated body fluid in a known HIV-infected assailant.
  • If the HIV status of the assailant is unknown, there should be a case-by-case determination for nPEP
• If the survivor appears to be at risk for acquiring HIV from the assault, discuss nPEP, including benefits and risks.
• Consult with a specialist in HIV treatment if nPEP is being considered.
• If the survivor chooses to start nPEP, provide enough medication to last until the follow-up visit at 3-7 days after initial assessment and assess tolerance to medications.
• If nPEP is started, perform CBC and serum chemistry at baseline.
• Perform an HIV antibody test at original assessment. The patient will need repeat antibody test at 6 weeks, 3 months, and 6 months.

Summary

It is essential for ED providers to know the current treatment recommendations based on antibiotic resistance. In treatment of STIs, concurrent treatment of all sex partners is critical for prevention of transmission and re-infection. Patients and partners should be advised to abstain from intercourse until they and their sexual partners have been adequately treated and all symptoms have resolved.

For a quick reference guide on the current STI treatment recommendations from the 2015 CDC guidelines, please see http://www.cdc.gov/std/tg2015/2015-wall-chart.pdf.

References/Further Reading

-Burnett, Aaron M., Christopher P. Anderson, and Michael D. Zwank. ‘Laboratory-Confirmed Gonorrhea And/Or Chlamydia Rates In Clinically Diagnosed Pelvic Inflammatory Disease And Cervicitis’. The American Journal of Emergency Medicine 30.7 (2012): 1114-1117.
-Cdc.gov. ‘2015 STD Treatment Guidelines’. N.p., 2015.
-Cdc.gov. ‘Legal Status Of Expedited Partner Therapy’. N.p., 2015.
-Cohen, C R. ‘Detection Of Mycoplasma Genitalium In Women With Laparoscopically Diagnosed Acute Salpingitis’. Sexually Transmitted Infections 81.6 (2005): 463-466.
-Haggerty, Catherine L. et al. ‘Mycoplasma Genitalium Among Women With Nongonococcal, Nonchlamydial Pelvic Inflammatory Disease’. Infectious Diseases in Obstetrics & Gynecology 2006 (2006): 1-5.
-Kirkcaldy, R. D. et al. ‘The Efficacy And Safety Of Gentamicin Plus Azithromycin And Gemifloxacin Plus Azithromycin As Treatment Of Uncomplicated Gonorrhea’. Clinical Infectious Diseases 59.8 (2014): 1083-1091.
-Liang, S. Y. et al. ‘Update of Emerging Infections: News From the Centers for Disease Control and Prevention’. Annals of Emergency Medicine 66.5 (2015): 526-7.
-Lin, J. H. ‘Clinical Outcome In The Use Of Cephalosporins In Pediatric Patients With A History Of Penicillin Allergy’. Pediatrics 130.Supplement (2012): S18-S18.
-Ness, R. B. ‘A Cluster Analysis Of Bacterial Vaginosis-Associated Microflora And Pelvic Inflammatory Disease’. American Journal of Epidemiology 162.6 (2005): 585-590.
-Ness, Roberta B. 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’. American Journal of Obstetrics and Gynecology 186.5 (2002): 929-937.
-Novalbos, A. et al. ‘Lack Of Allergic Cross-Reactivity To Cephalosporins Among Patients Allergic To Penicillins’. Clin Exp Allergy 31.3 (2001): 438-443.
-Pichichero, M et. al. ‘Safe Use Of Selected Cephalosporins In Penicillin-Allergic Patients: A Meta-Analysis’. Otolaryngology – Head and Neck Surgery 136.3 (2007): 340-347.
-Romano, Antonino et al. ‘IgE-Mediated Hypersensitivity To Cephalosporins: Cross-Reactivity And Tolerability Of Penicillins, Monobactams, And Carbapenems’. Journal of Allergy and Clinical Immunology 126.5 (2010): 994-999.
-Short, Vanessa L. et al. ‘Clinical Presentation Of Mycoplasma Genitalium Infection Versus Neisseria Gonorrhoeae Infection Among Women With Pelvic Inflammatory Disease’. Clinical Infectious Diseases 48.1 (2009): 41-47.
-Wiesenfeld, H. C. et al. ‘O04.6 Mycoplasma Genitalium- Is It A Pathogen In Acute Pelvic Inflammatory Disease (PID)?’. Sexually Transmitted Infections 89.Suppl 1 (2013): A34-A34.