Weighing Potential Benefits and Harms of Mycoplasma genitalium Testing and Treatment Approaches Associations with Disease Syndromes

Male Urethritis

MGen is consistently and strongly associated with acute, persistent, and recurrent urethritis and is an accepted cause of male urethritis. No new data have emerged to change this conclusion.

Epididymitis

Evidence to determine whether MG causes epididymitis remains insufficient. Only case reports have been published, and no new studies have compared MG prevalence in men with and without epididymitis.

Male Infertility

Limited available evidence does not support the role of MG as a cause of male infertility. Although an increasing number of studies have investigated this possibility, many have evaluated sperm quality rather than documented infertility. Studies enrolling fertile and infertile men have reported no association.

Female Cervicitis

Earlier evidence on the relationship between MG and cervicitis was somewhat conflicting, partly because of varying definitions of cervicitis, but generally supported an association. This inconsistency remained the case in 4 newer cross-sectional studies. Of those studies, 2 demonstrated increased risk, 1 demonstrated increased risk only among a subset of persons, and 1 reported no increased risk.

Pelvic Inflammatory Disease

Data remain conflicting on the association of MG with PID, as reflected in the 2 published meta-analyses. Studies published since 2014 continued this trend, demonstrating a statistically significant 2-fold increased risk for histologic endometritis (29), a nonsignificant ≈3-fold increase in risk for incident PID, and no association. No randomised trials have been conducted to test whether screening and treatment of Mycoplasma Genitalium reduces PID incidence. In the absence of such trials, there are no population-based screening recommendations.

Female Infertility

In vitro inoculation of MG into fallopian tube tissue damages and destroys cilia, suggesting that MG might impair female fertility. Consistent with this finding is the 2-fold increased risk for infertility in the meta-analysis, especially among studies accounting for other microbial causes of infertility. More recent studies have reported mixed results. In 2 studies, serologic testing was used to detect antibodies indicative of previous infection; 1 observed a significantly longer time to conception, whereas the other reported no association with tubal factor infertility. Three studies used nucleic acid amplification testing (NAAT), which typically detects active infection, and found that MG infection was more common among infertile than fertile women.

Preterm Delivery

Evidence remains insufficient on the relationship between MG infection and preterm delivery. An earlier meta-analysis demonstrated a 2-fold increased risk for preterm delivery, stronger among studies accounting for other infections. However, 2 more recent studies observed low MG prevalence (0%–1%) and could not evaluate an association. In a third study, M. genitalium infection was more common in women in Australia who experienced a preterm birth than in those who did not (15.4% vs. 2.3%), but this difference was not statistically significant. Adequately powered studies are needed.

Other Perinatal Outcomes

Evidence for an association between MG infection and spontaneous abortion is conflicting. An initial meta-analysis reported significantly increased risk in MG infected persons, but subsequent studies did not. Using NAAT, MG has been detected in the endotrachea of neonates (47), bronchoalveolar lavage samples from children 0–5 years, and ocular samples from infants born to infected mothers, suggesting that transmission of MG during vaginal delivery might occur. However, positive NAATs might only reflect residual DNA; larger studies are needed to determine the extent of maternal-to-child transmission.

Who Should Be Tested for M. genitalium?

Screening, diagnostic testing, and tests for cure each have different goals. Screening tests are undertaken in asymptomatic persons to provide treatment, limit sequelae, and prevent transmission. Diagnostic tests are performed in symptomatic persons to direct treatment at a specific pathogen and eliminate the organism. Tests of cure are undertaken to confirm the eradication of pathogens. Recommendations for each type of testing are typically grounded in a robust body of evidence. As with MG, potential benefits must be weighed against potential harms when there is less robust evidence.

Screening

Screening at-risk women for gonorrhoea and chlamydia is recommended in the United States because infections are frequently asymptomatic; robust data exist on risk for sequelae from untreated infections; effective treatment is readily available; and, for chlamydia, data from a randomised trial demonstrated decreased risk for PID in persons screened and treated. MG meets only 1 of these criteria: infections are frequently asymptomatic (≈30%–60% in clinic populations). Data on the risk for sequelae from untreated MG infections in women are less robust than data for chlamydia.

Prospective studies of sequelae in women are limited, challenging our ability to infer cause. There is no evidence of adverse sequelae in men, although such data are sparse. Given the high rates of macrolide resistance and the advent of fluoroquinolone treatment failures, effective treatment is not readily available for all infected persons (see section on antimicrobial therapies). Finally, randomised controlled trials evaluating whether screening and treating MG infections could prevent PID and perinatal complications are costly; none have been undertaken despite the articulated need. Some population subgroups have a higher risk for PID, and screening and treatment in those subgroups might yield greater benefits, but this possibility has not been assessed.

Benefits of Screening for M. genitalium

Screening and effectively treating asymptomatic persons for MG could reduce transmission and population-level prevalence. However, reductions in prevalence after implementing screening programs for sexually transmitted infections do not always occur, as demonstrated by increasing chlamydia prevalence in the United States. Some declines in PID have offset this increase, although PID rates have slightly increased in recent years. If identified infections could be effectively treated while minimising the selection of resistance, screening could reduce the likelihood of transmitted resistance, leading to subsequent reductions in the population-level prevalence of antimicrobial resistance.

Harms of Screening

If asymptomatic infections do not cause sequelae, screening and treatment will result in unnecessary antibiotic exposure. On an individual level, antibiotics might disrupt a person’s microbiota and lead to other health conditions. And adverse effects associated with antibiotics are occasionally serious. On a population level, more widespread antibiotic use speeds the emergence. And spread of antimicrobial resistance, and multidrug-resistant MG infections are often refractory to treatment. Anecdotal reports suggest that treatment-refractory infections can lead to anxiety and depression that would not occur in the absence of screening. Consistent with earlier assessments, screening asymptomatic persons for M. Gen is not recommended in the 2021 CDC Sexually Transmitted Infections Treatment Guidelines.