By: Casey N. Pinto PhD, CRNP, MPH, The Pennsylvania State University, Department of Public health Sciences Chlamydia was discovered in 1907 but was not associated with non-gonococcal urethritis (NGU) until the 1970s. In 1988 the CDC made chlamydia a nationally notifiable disease in the US. In 1990 there were 34,000 cases documented,1,2 rising to nearly 1.6 million cases in 2020.3 Prevalence rates of chlamydia among the general population is 2.3%4 however, rates vary between 1.4% and 14% based on select social determinants and age.2,5,6 Mycoplasma genitalium (MG) was discovered in 1981 during a search for causative agents of NGU.7,8 However, since the MG bacteria took six months to grow on very specific culture mediums, clinical diagnosis was limited to clinical suspicion. The first assay for MG was approved by the FDA in the US in 2019,9 allowing for improved diagnosis and prevalence estimates. Current prevalence of MG is 1% among the general US population4 with a range of 4-38% among select population groups.10-14 Thus MG is more prevalent than gonorrhea (0.4%),4 and is quickly catching chlamydia, and surpassing in select populations. Initial symptoms of MG are mild (urethritis/cervicitis/proctitis) with limited information on long-term effects. Existing evidence is predominantly among women (endometritis, pelvic inflammatory disease, preterm birth, fetal demise, and infertility).15-17 Among men it is theorized that infertility, epididymitis, and/or prostatitis are potential long-term effects.18,19 MG screening guidelines are continually adjusted based on new evidence. Currently, screening is limited to patients who are symptomatic and includes urine, vaginal, meatal, rectal, and endocervical sites as indicated.19 Asymptomatic screening should not include MG 19 unless clinical decision making justifies screening (i.e. partner positive and unable to clear infection). Symptomatic patients who test positive for MG require treatment. Asymptomatic patients with a positive MG test should be considered for treatment based on clinical judgement, especially since there is evidence that 93% of patients will clear an MG infection without any treatment at 12 months.20 Treatment for MG initially mirrored chlamydia treatment (azithromycin 1gm PO) however, increasing macrolide resistance has been documented among MG isolates (44%-90%).19 Due to the high rate of macrolide resistance, and the lack of resistance testing in the US (currently available in other countries),21 azithromycin should be avoided as a treatment for proven or suspected MG. The current recommendations are doxycycline 100mg PO BID x 7days followed by moxifloxacin 400mg PO daily x 7 days. Doxycycline alone will not adequately treat the infection but will decrease the bacteria burden. So moxifloxacin can successfully eradicate the infection without increasing the rate of resistance among fluoroquinolones.22 While the 7-day doxycycline treatment followed by moxifloxacin is cumbersome, it does allow time for MG testing results to determine if the second antibiotic is needed. Additionally, when resistance testing is available in the US, the 7-day doxycycline window will allow time to determine the appropriate second antibiotic. MG is not only likely to be the next chlamydia, but the high likelihood of developing resistance will complicate current and future treatment. Providers should be suspicious of MG in cases of NGU to ensure appropriate and timely treatment. References Taylor-Robinson D. The discovery of Chlamydia trachomatis. Sex Transm Infect. 2017;93:10. Miller WC. Prevalence of Chlamydial and Gonococcal Infections Among Young Adults in the United States. JAMA. 2004;291(18):2229. Centers for Disease Control and Prevention. 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