M. genitalium was first identified in the early 1980s (249) and has become recognized as a cause of male urethritis, responsible for approximately 15%–20% of nongonococcal urethritis (NGU) cases, 20%–25% of nonchlamydial NGU, and approximately 30% of persistent or recurrent urethritis (250). In most settings, it is more common than N. gonorrhoeae but less common than C. trachomatis. While M. genitalium is often the sole pathogen detected, coinfection with C. trachomatis is not uncommon in selected areas (251-253).
Although strong and consistent evidence has linked M. genitalium to urethritis in men, it remains unknown whether this infection can cause male infertility or other male anogenital tract disease syndromes. The organism has been detected in men with epididymitis in a limited number of cases, but this has not been extensively investigated. Similarly, M. genitalium has been found in the rectum, but detection is infrequently accompanied by rectal symptoms, and its presence does not appear to cause a syndrome of clinical proctitis.
The pathogenic role of M. genitalium is less definitive in women than it is in men. M. genitalium can be found in the vagina, cervix, and endometrium and, like chlamydial and gonococcal infections, M. genitalium infections in women are commonly asymptomatic. M. genitalium can be detected in 10%–30% of women with clinical cervicitis, and most (253-259) studies have found that this organism is more common among women with cervicitis than those without this syndrome (251,260,261).
M. genitalium is found in the cervix and/or endometrium of women with PID more often than in women without PID (262-271), and endosalpingitis develops in nonhuman primates after inoculation with M. genitalium, suggesting that this organism can cause PID. M. genitalium has been detected in 2%–22% of PID cases (median: 10%) depending on the setting, but the frequency with which M. genitalium-infected women experience PID has been under studied. Although one study in Sweden reported a substantial increase in risk for postabortal PID among women with M. genitalium (262), the proportion of M. genitalium-positive women who subsequently experienced PID in two other studies was relatively low (<5%) (272,273), and evidence from serologic studies assessing the association of PID with antibody to M. genitalium is inconsistent. Overall, evidence suggests that M. genitalium can cause PID, but that this occurs less frequently than it does with C. trachomatis (271, 273).
A few seroepidemologic studies have found that women with tubal factor infertility are more likely to have antibodies to M. genitalium than fertile women, suggesting that this organism might cause female infertility. However, more research is needed. On the basis of certain reports, M. genitalium was uncommonly identified in women who experience adverse pregnancy outcomes, but was associated with increased risk for preterm delivery in one U.S. and another Peruvian study (274,275). Data are scarce regarding M. genitalium and ectopic pregnancy.
M. genitalium is a slow-growing organism. Culture can take up to 6 months, and only a few laboratories in the world are able to recover clinical isolates. Therefore, NAAT is the preferred method for M. genitalium detection. In research settings, M. genitalium is diagnosed by NAAT testing of urine, urethral, vaginal, and cervical swabs and through endometrial biopsies, typically using in-house PCR or assays intended for research use only. NAAT tests (polymerase chain reaction or transcription mediated amplification) for M. genitalium are available in some large medical centers and commercial laboratories, but there is no diagnostic test for M. genitalium that is cleared by the FDA for use in the United States. In the absence of validated tests, M. genitalium should be suspected in cases of persistent or recurrent urethritis and may be considered in persistent or recurrent cases of cervicitis and PID.
M. genitalium lacks a cell wall, and thus antibiotics targeting cell-wall biosynthesis (e.g., beta-lactams including penicillins and cephalosporins) are ineffective against this organism. Given the diagnostic challenges, treatment of most M. genitalium infections will occur in the context of syndromic management for urethritis, cervicitis, and PID.
The 7-day doxycycline regimen recommended for treatment of urethritis is largely ineffective against M. genitalium with a median cure rate of approximately 31% (276-278). The 1-g single dose of azithromycin was significantly more effective against M. genitalium than doxycycline in two randomized urethritis treatment trials (276,277) and is preferred over doxycycline. However, resistance to azithromycin appears to be rapidly emerging. The median cure rate for both men and women is approximately 85%, but was only 40% in the most recent trial (278). Persons with treatment failures after the 1-g azithromycin regimen frequently have macrolide-resistant strains, suggesting that single-dose azithromycin therapy might select for resistance. A longer course of azithromycin (an initial 500-mg dose followed by 250 mg daily for 4 days) might be marginally superior to the single dose regimen (279-281). However, in some settings, approximately 50% of all M. genitalium infections are caused by organisms that are already resistant to azithromycin (282), and persons who do not respond to the 1-g azithromycin regimen generally do not benefit from retreatment with the extended dose regimen.
Moxifloxacin (400 mg daily x 7, 10 or 14 days) has been successfully used to treat M. genitalium in men and women with previous treatment failures, with cure rates of 100% in initial reports (280, 283). However, moxifloxacin has been used in only a few cases, and the drug has not been tested in clinical trials. Although generally considered effective, studies in Japan, Australia, and the United States have reported moxifloxacin treatment failures after the 7 day regimen (284-287).
Recommended PID treatment regimens are based on antibiotics that are not effective against M. genitalium. Therefore, clinicians might consider M. genitalium in cases that do not respond to therapy within 7–10 days. Where validated M. genitalium testing is available, clinicians might test women with PID for M. genitalium. When M. genitalium is detected, a regimen of moxifloxacin 400 mg/day for 14 days has been effective in eradicating the organism (288). Nevertheless, no data have been published that assess the benefits of testing women with PID for M. genitalium, and the importance of directing treatment against this organism is currently unknown.
In settings where validated M. genitalium testing is available, persons with persistent urethritis, cervicitis, or PID accompanied by persistent detection of M. genitalium might be treated with moxifloxacin. However, routine tests-of-cure in asymptomatic persons are not recommended.
Sex partners should be managed according to guidelines for patients with nongonococcal urethritis (NGU), cervicitis, and PID. In settings with access to validated M. genitalium tests, partner testing and treatment of identified infections might be considered.
Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative. Treatment of most M. genitalium infections will occur in the context of syndromic management for urethritis, cervicitis, and PID (See Mycoplasma genitalium, Treatment).