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Mycoplasma Genitalium is a sexually transmitted infection causing symptoms like urethritis and pelvic pain. It can be diagnosed and treated.
In 2015, the Centers for Disease Control and Prevention (CDC) classified Mycoplasma genitalium infection as an "emerging issue" in its Sexually Transmitted Diseases Treatment Guidelines. First identified in the 1980s, M. genitalium is increasingly acknowledged as a significant contributor to various sexually transmitted infections (STIs), including urethritis in men and cervicitis in women. Notably, M. genitalium is responsible for more STIs than Neisseria gonorrhoeae and ranks as the second most common STI after Chlamydia trachomatis. Despite its prevalence, diagnosing and treating M. genitalium infections can be challenging.
Infectious Disease Advisor spoke with Dr. Oluwatosin Jaiyeoba Goje from the Ob/Gyn & Women's Health Institute at Cleveland Clinic in Ohio, and Dr. Amesh Adalja, spokesperson for the Infectious Diseases Society of America and Senior Associate at Johns Hopkins Center for Health Security in Baltimore, Maryland, about the difficulties in diagnosing and managing M. genitalium infections.
M. genitalium infection is a widespread cause of STIs globally, with prevalence rates ranging from 0.4% among young adults in the United States to 4.5% in the Netherlands. In Sweden, up to 6.3% of patients at a sexually transmitted diseases (STD) clinic were found to have M. genitalium. Despite variations in prevalence between countries, M. genitalium remains the most common STI, second only to Chlamydia trachomatis.
“The prevalence of M. genitalium is particularly alarming because most infected individuals are unaware of their condition,” Dr. Goje noted. “Symptoms can be vague or absent, and if left untreated, M. genitalium can lead to serious health issues, including urethritis, cervicitis, and pelvic inflammatory disease.”
Even when patients do exhibit symptoms, healthcare providers may not consider M. genitalium as a potential cause. “Clinicians are generally less familiar with M. genitalium than with other more commonly treated STIs that they learned about in medical school,” Dr. Adalja explained. “However, M. genitalium is prevalent enough in certain situations that it shouldn't be overlooked.”
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Early Symptoms:
Importance of Early Detection:
If you suspect exposure to Mycoplasma genitalium or experience symptoms, consulting a healthcare provider for timely testing and treatment is important.
Dr. Adalja emphasizes that M. genitalium infection should be considered in men displaying symptoms of urethritis, which are similar to those of chlamydia and gonorrhea. “M. genitalium is the second most common cause of urethritis, and it has been thoroughly studied in men. Testing is particularly important for those who do not improve after their first course of antibiotics, as M. genitalium often shows resistance to commonly used STI treatments,” he explained.
Dr. Goje also recommends testing for M. genitalium in women experiencing persistent cervicitis symptoms, especially in those who have not responded to empirical antibiotic treatment for chlamydia and gonorrhea and who have tested negative for these pathogens.
However, testing for M. genitalium can be challenging and time-consuming due to the slow growth of the organism. “Isolating and culturing M. genitalium is impractical when immediate antimicrobial treatment is necessary,” Dr. Goje noted.
“Although there is no FDA-approved test for M. genitalium, the nucleic acid amplification test (NAAT) is the preferred method,” Dr. Goje stated. NAAT employs polymerase chain reaction (PCR) and can be conducted on various sample types, including urethral, vaginal, and cervical swabs, as well as urine and endometrial biopsies.
However, NAAT for M. genitalium is based on assays developed for research purposes, meaning it is typically only available in reference labs, usually at large university hospitals. “If you’re at a smaller hospital, it’s crucial to know where testing can be done and which facilities are conducting it in research contexts,” Dr. Adalja explained. “It’s not a test that is readily accessible.”
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Significant antimicrobial resistance poses a major challenge in treating M. genitalium infections. Since M. genitalium lacks a cell wall, antibiotics that target cell wall biosynthesis, such as beta-lactams (e.g., penicillins and cephalosporins), are ineffective against this organism, Dr. Goje explained.
Dr. Adalja noted that patients with urethritis often receive an empirical course of doxycycline, which is effective against C. trachomatis but has high treatment failure rates for M. genitalium infections. “More than half of patients with M. genitalium treated with doxycycline may experience microbiological failure,” he said.
Dr. Goje added that patients who do not respond to an initial course of doxycycline typically need a second round of antibiotics, usually consisting of azithromycin for at least five days. However, resistance to azithromycin occurs in up to 50% of M. genitalium cases. In instances where azithromycin fails, the preferred regimen is moxifloxacin 400 mg daily for 7 to 14 days. “Initial reports indicate cure rates with moxifloxacin are 100%, although more research is needed,” Dr. Goje stated.
To mitigate further development of antimicrobial resistance in M. genitalium, Dr. Adalja emphasized the importance of avoiding inappropriate initial antibiotic treatments, such as doxycycline. “Increasing awareness among clinicians that M. genitalium could be responsible for their patient's STI symptoms is crucial. Many clinicians outside the infectious diseases or STI specialties may not be familiar with M. genitalium and its role in STIs, leading them to prescribe incorrect antibiotics inadvertently.”
Dr. Goje pointed out that the challenges in diagnosing M. genitalium infections are significant barriers to effective treatment. “We cannot treat what we cannot diagnose,” she said. “Sometimes, we have no choice but to treat empirically based on signs and symptoms and to rule out other known causes of urethritis and cervicitis.”
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M. genitalium was first identified in the early 1980s and has since been recognized as a contributor to male urethritis, accounting for approximately 15%–20% of nongonococcal urethritis (NGU) cases, 20%–25% of nonchlamydial NGU, and around 30% of persistent or recurrent urethritis. In many settings, it is more prevalent than N. gonorrhoeae but less so than C. trachomatis. While M. genitalium is often the only pathogen found, coinfections with C. trachomatis are not uncommon in certain regions.
Strong and consistent evidence links M. genitalium to urethritis in men; however, its role in male infertility or other male anogenital tract diseases is still unclear. The organism has been identified in a limited number of cases involving men with epididymitis, but this has not been extensively studied. M. genitalium has also been detected in the rectum, although its presence there rarely correlates with rectal symptoms, and it does not seem to cause a clinical syndrome of proctitis.
The pathogenic role of M. genitalium in women is less well defined than in men. The organism can be found in the vagina, cervix, and endometrium, and, similar to chlamydial and gonococcal infections, M. genitalium infections in women are often asymptomatic. It can be detected in 10%–30% of women with clinical cervicitis, and most studies indicate that it is more common among those with cervicitis than among those without.
M. genitalium is found more frequently in the cervix and/or endometrium of women with pelvic inflammatory disease (PID) compared to those without. In nonhuman primates, endosalpingitis developed following inoculation with M. genitalium, suggesting its potential role in causing PID. M. genitalium has been detected in 2%–22% of PID cases (median: 10%), though the frequency of PID among M. genitalium-positive women remains underexplored. While a study in Sweden indicated a significant increase in the risk of postabortal PID among women with M. genitalium, the proportion of these women who experienced PID in two other studies was relatively low (<5%). Evidence from serological studies examining the association between PID and antibodies to M. genitalium is inconsistent. Overall, while M. genitalium is suggested to cause PID, it appears to do so less frequently than C. trachomatis.
Some seroepidemiological studies have found that women with tubal factor infertility are more likely to have antibodies to M. genitalium compared to fertile women, implying that the organism might contribute to female infertility. However, more research is necessary. Reports have indicated that M. genitalium is rarely found in women with adverse pregnancy outcomes but has been linked to an increased risk of preterm delivery in one U.S. and one Peruvian study. Data regarding M. genitalium and ectopic pregnancy is limited.
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The 7-day doxycycline regimen recommended for treating urethritis is largely ineffective against M. genitalium, with a median cure rate of only about 31%. In contrast, a single 1-g dose of azithromycin has shown significantly better efficacy against M. genitalium in two randomized trials and is preferred over doxycycline. However, resistance to azithromycin appears to be rapidly increasing. The median cure rate for both men and women is approximately 85%, but this dropped to just 40% in the most recent trial. Patients experiencing treatment failures after the 1-g azithromycin regimen often have macrolide-resistant strains, suggesting that this single-dose therapy may select for resistance. A longer azithromycin course (an initial 500-mg dose followed by 250 mg daily for 4 days) may be slightly more effective than the single dose. However, in some settings, about 50% of M. genitalium infections are caused by strains already resistant to azithromycin, and patients who do not respond to the 1-g regimen typically do not benefit from the extended dosing.
Moxifloxacin (400 mg daily for 7, 10, or 14 days) has been successfully used to treat M. genitalium in men and women with previous treatment failures, achieving cure rates of 100% in initial reports. However, moxifloxacin has been administered in only a limited number of cases and has not been evaluated in clinical trials. While generally deemed effective, studies in Japan, Australia, and the United States have reported treatment failures with moxifloxacin after the 7-day regimen.
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