EM Lit Review: CDC Update to Sexually Transmitted Infection (STI) Treatment
Does the evidence support the new guidelines?
By Joshua Easter, MD, MSc
University of Virginia Health System emergency physician and UVA School of Medicine associate professor
Case: A 25 year-old-male presents with yellowish discharge from his penis for the past three days. It is associated with a burning pain with urination. He has no testicular pain, abdominal pain, fever, rash, or vomiting. He is sexually active with three partners in the last three months, and he occasionally employs barrier protection. You suspect a sexually transmitted infection, and the patient prefers empiric antibiotic treatment in the ED, while awaiting results of his urine nucleic acid amplification testing for gonorrhea and chlamydia. What medications do you administer?
In December, the Centers for Disease Control and Prevention (CDC) updated their recommendations for the management of gonococcal and chlamydial infection (St Cyr, 2020). Most salient to us as emergency physicians is that the CDC now recommends administering ceftriaxone 500 mg IM for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. In addition, if chlamydia infection has not been excluded, they recommend administering doxycycline 100 mg PO for 7 days. These represent changes from the prior standard of administering 250 mg IM ceftriaxone for gonococcus and 1 g PO azithromycin or doxycycline 100 mg PO for 7 days for chlamydia (CDC, 2015).
FIGURE. Percentage of Neisseria gonorrhoeae isolates with elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, and azithromycin — Gonococcal Isolate Surveillance Project, United States, 2009–2018 Source: CDC. Sexually Transmitted Disease Surveillance 2018. https://www.cdc.gov/std/stats18/default.htm. * Elevated MIC = ceftriaxone ≥0.125 µg/mL; cefixime ≥0.25 µg/mL; azithromycin ≥2.0 µg/mL.
Gonococcus is developing increased resistance to antibiotics. The Gonococcal Isolate Surveillance Project tests urethral isolates from 25 symptomatic men in 25-30 STD clinics monthly to determine susceptibility to various antibiotics. It has detected increased resistance to quinolones and azithromycin (FIGURE). Only ceftriaxone continues to show excellent effectiveness against gonococcus, and therefore the CDC does not recommend quinolones or macrolides to treat gonorrhea. While co-administration of azithromycin with ceftriaxone may mitigate resistance of gonococcus to ceftriaxone, it increases the risk of patients developing overall resistance to macrolides.
In terms of ceftriaxone dosing, mounting evidence indicates a larger dose is required than previously recommended. In animal models the lowest ceftriaxone dose that universally eradicated gonococcus at 48 hours was 5 mg/kg body weight. As a result, the previously recommended dose of 250 mg would be inadequate for patients weighing >50 kg. In addition, the amount of ceftriaxone reaching the pharynx is variable, and so larger doses are often required to treat pharyngeal infections. As a result, the CDC now recommends 500 mg IM for patients <150 kg and 1 g IM for patients weighing ³ 150 kg.
Remarkably, there is limited discussion in the CDC’s update about their decision to recommend doxycycline and not azithromycin for chlamydia infection. Previously the CDC had considered a single dose of azithromycin 1 g orally as an alternate regimen for the treatment of chlamydia. The CDC briefly states that the change is based on concern about antibiotic resistance from macrolides. However, this stems from one study in children showing azithromycin is associated with changes in the gut’s resistome that may increase both macrolide and non-macrolide resistance (Doan, 2020; Doan, 2019). There is limited low quality data comparing doxycycline to azithromycin, suggesting a small 2-3% increase in efficacy with doxycycline (Kong, 2014). Meanwhile, a Cochrane review found no significant differences in efficacy between doxycycline and azithromycin for the management of pelvic inflammatory disease (Savaris, 2017). These studies were done in a controlled setting and also do not consider the potential for non-compliance with a 1 week course of doxycycline.
Medication non-compliance is a significant problem that the CDC did not address in their update. One ED based study found less than 60% of patients filled their prescription for STI treatment (Lieberman, 2019). The high frequency of adverse effects, such as dyspepsia and photosensitivity, with doxycycline may further reduce compliance. Chlamydia infection is often asymptomatic and this may also reduce compliance. Given the minimal increase in efficacy with a one week course of doxycycline over azithromycin coupled with the substantial increased risk of non-compliance with doxycycline, it seems reasonable to continue to provide a single dose of azithromycin 1 g PO in the ED for chlamydia.
After talking with the patient, you are concerned for STI. He weighs 100 kg and therefore you administer 500 mg IM ceftriaxone in the ED. As chlamydia has not been excluded, you discuss the risks and benefits of azithromycin versus doxycycline with your patient, and together you all decide to treat him with 1g PO azithromycin.
About the VACEP EM Lit Review: Every month, VACEP members will share their readings of the latest medical literature. Submit yours to us by emailing Executive Director Sarah Marshall.
