Mycoplasma Genitalium (M. gen) is a bacterium that has gained attention as a sexually transmitted infection (STI) because it often presents without noticeable symptoms. The infection is curable, but achieving eradication is complex. This complexity stems from the bacterium’s significant development of resistance to antibiotics traditionally used to treat STIs. Precise and often sequential therapy is necessary to manage an M. gen infection successfully.
Understanding Mycoplasma Genitalium
Mycoplasma Genitalium (M. gen) is a microscopic bacterium that infects the urinary and genital tracts. Unlike many common bacteria, M. gen lacks a rigid cell wall, a critical feature that influences its treatment. This absence means that antibiotics like penicillin, which target cell walls, are entirely ineffective against it.
The infection is primarily transmitted through sexual contact, including vaginal and anal intercourse. M. gen is a recognized cause of several genitourinary conditions. In men, it causes non-gonococcal urethritis, leading to symptoms like discharge or burning during urination. In women, M. gen is linked to cervicitis, pelvic pain, and potentially more severe complications.
The Standard Approach to Curing M. gen
The standard strategy for curing M. gen has shifted away from single-drug regimens due to concerns about treatment failure and resistance. Current guidelines recommend a two-step, sequential therapy as the preferred initial approach. This regimen begins with a seven-day course of doxycycline, typically taken twice daily.
Doxycycline is not highly effective on its own, but its role is to significantly reduce the overall bacterial load. Following this course, an extended course of the macrolide antibiotic azithromycin is administered. This sequential strategy improves cure rates, especially when the M. gen strain is still susceptible to azithromycin. Patient adherence to the full multi-day course of both medications is paramount for complete eradication.
Treating all sexual partners is essential, as reinfection is a common cause of treatment failure. Partners should be tested and treated simultaneously to prevent the infection from being passed back and forth. If the infecting strain is susceptible to macrolides, this two-drug sequence is the most effective way to eliminate the infection.
Navigating Antibiotic Resistance
The primary hurdle in treating M. gen is the high prevalence of antibiotic resistance, particularly to azithromycin. In many settings, the rate of macrolide resistance now exceeds 50%. This widespread resistance means the standard sequential therapy often fails, requiring specialized second-line treatments.
When first-line treatment fails, clinicians often assume macrolide resistance is present. Ideally, this situation calls for resistance-guided therapy, using molecular testing to detect mutations in the M. gen genome. If macrolide resistance is confirmed or strongly suspected, the protocol shifts to a different class of antibiotics.
The alternative second-line treatment involves a sequential regimen: the initial seven-day course of doxycycline followed by a seven-day course of moxifloxacin. Moxifloxacin belongs to the fluoroquinolone class and is highly effective against most macrolide-resistant strains. However, resistance to fluoroquinolones is also emerging, reported in 15% to 20% of cases in some areas.
The incorrect or single-drug use of macrolides primarily drives the selection of highly resistant M. gen strains. For infections that fail both azithromycin and moxifloxacin, treatment options become extremely limited. These cases sometimes require third-line agents like pristinamycin or minocycline.
Why Confirmation of Cure is Essential
Successfully completing the antibiotic regimen does not automatically confirm eradication due to the high risk of treatment failure. Therefore, a “Test of Cure” (TOC) is a non-negotiable step in the management of M. gen. This follow-up test uses a nucleic acid amplification test (NAAT) to check for the presence of the bacterium’s genetic material.
The timing of the TOC is important; current guidelines recommend waiting at least three to four weeks after the final antibiotic dose. Testing too soon can result in a false-positive because fragments of dead bacteria can linger and still be detected by the NAAT. A positive TOC indicates treatment failure, signaling the need to initiate a second-line therapy.
Failure to confirm a cure carries significant health risks. In women, persistent M. gen can lead to serious complications, including pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, or infertility. Men can develop epididymitis, a painful inflammation of the tube at the back of the testicle.