Mycoplasma genitalium Diseases Characterized by Vulvovaginal Itching, Burning, Irritation,

performed simultaneously among neonates with gonococcal infection (see Chlamydial Infection Among Neonates). Follow-up examination is not required. Management of Mothers and Their Sex Partners

Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea (see Gonococcal Infection Among Adolescents and Adults).

Gonococcal Infection Among Infants and Children

Sexual abuse is the most frequent cause of gonococcal infection among infants and children (see Sexual Assault or Abuse of Children). For preadolescent girls, vaginitis is the most common manifestation of this infection; gonococcalassociated PID after vaginal infection can be less common among preadolescents than adults. Among sexually abused children, anorectal and pharyngeal infections with N. gonorrhoeae are frequently asymptomatic. Diagnostic Considerations

Culture can be used to test urogenital and extragenital sites for girls and boys. NAAT can be used to test for N. gonorrhoeae from vaginal and urine specimens from girls and urine for boys (see Sexual Assault or Abuse of Children). Although data regarding NAAT from extragenital sites (rectum and pharynx) among children are more limited, and performance is test dependent, no evidence supports that performance of NAAT for detection of N. gonorrhoeae among children differs from that among adults (553). Because of the implications of a N. gonorrhoeae diagnosis in a child, only validated FDA-cleared NAAT assays should be used with extragenital specimens. Consultation with an expert is necessary before using NAAT to minimize the possibility of cross-reaction with nongonococcal Neisseria species and other commensals (e.g., N. meningitidis, Neisseria sicca, Neisseria lactamica, Neisseria cinerea, or M. catarrhalis) and to ensure correct interpretation of results.

Gram stains are inadequate for evaluating prepubertal children for gonorrhea and should not be used to diagnose or exclude gonorrhea. If evidence of DGI exists, gonorrhea culture and antimicrobial susceptibility testing should be obtained from relevant clinical sites (see Disseminated Gonococcal Infection).

Recommended Regimen for Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis Among Infants and Children Weighing ≤45 kg

Ceftriaxone 25–50 mg/kg body weight IV or IM in a single dose, not to exceed 250 mg IM Recommended Regimen for Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis Among Children Weighing >45 kg

Treat with the regimen recommended for adults (see Gonococcal Infections)

Recommended Regimen for Bacteremia or Arthritis Among Children Weighing ≤45 kg

Ceftriaxone 50 mg/kg body weight (maximum dose: 2 g) IM or IV in a single dose daily every 24 hours for 7 days

Recommended Regimen for Bacteremia or Arthritis Among Children Weighing >45 kg

Ceftriaxone 1 g IM or IV in a single dose daily every 24 hours for 7 days

Other Management Considerations

Follow-up cultures are unnecessary. Only parenteral cephalosporins (i.e., ceftriaxone) are recommended for use among children. All children identified as having gonococcal infections should be tested for C. trachomatis, syphilis, and HIV (see Sexual Assault or Abuse of Children).

Mycoplasma genitalium

M. genitalium causes symptomatic and asymptomatic urethritis among men and is the etiology of approximately 15%–20% of NGU, 20%–25% of nonchlamydial NGU, and 40% of persistent or recurrent urethritis (697,909,910). Infection with C. trachomatis is common in selected geographic areas (911–913), although M. genitalium is often the sole pathogen. Data are insufficient to implicate M. genitalium infection with chronic complications among men (e.g., epididymitis, prostatitis, or infertility). The consequences of asymptomatic infection with M. genitalium among men are unknown.

Among women, M. genitalium has been associated with cervicitis, PID, preterm delivery, spontaneous abortion, and infertility, with an approximately twofold increase in the risk for these outcomes among women infected with M. genitalium (766). M. genitalium infections among women are also frequently asymptomatic, and the consequences associated with asymptomatic M. genitalium infection are unknown.

M. genitalium can be detected among 10%–30% of women with clinical cervicitis (767,770,772,914–916). The existing evidence between M. genitalium and cervicitis is mostly supportive of a causal association. Elevated proinflammatory cytokines have been demonstrated among women with M. genitalium, with return to baseline levels after clearance of the pathogen (917).

M. genitalium is identified in the cervix or endometrium of women with PID more often than in women without PID (918–924). Prevalence of M. genitalium among women with PID ranges from 4% to 22% (925,926) and was reported as 60% in one study of women with postabortal PID (918). The association with PID is supported by early studies among nonhuman primates that determined that endosalpingitis develops after inoculation with M. genitalium (927). Recent studies evaluating the lower and upper genital tract using highly sensitive M. genitalium NAAT assays or the role of M. genitalium in histologically defined endometritis have reported significantly elevated risk for PID (928). However, most studies of M. genitalium and PID, even those that controlled extensively for other infections and behavioral and biologic risk, are cross-sectional. The few prospective studies that have evaluated the role of M. genitalium in establishing subsequent PID demonstrated increased PID risk; however, these were not statistically significant associations, often because of a lack of statistical power. No clinical trial data are available that demonstrate that treating M. genitalium cervical infection prevents development of PID or endometritis. Although data regarding the benefits of testing women with PID for M. genitalium and the importance of directing treatment against this organism are limited, the associations of M. genitalium with cervicitis and PID in cross-sectional studies using NAAT testing are consistent (928).

Data from case-control serologic studies (929–931) and a meta-analysis of clinical studies (766) indicate a potential role in causing infertility. However, seroassays are suboptimal and inconclusive. Similarly, evidence for a role for M. genitalium infection during pregnancy as a cause of perinatal complications, including preterm delivery, spontaneous abortion, or low birthweight, are conflicting because evidence is insufficient to attribute cause (766,932–934). Data are limited regarding ectopic pregnancy and neonatal M. genitalium infection (935,936).

Rectal infection with M. genitalium has been reported among 1%–26% of MSM (937–940) and among 3% of women (941). Rectal infections often are asymptomatic, although higher prevalence of M. genitalium has been reported among men with rectal symptoms. Similarly, although asymptomatic M. genitalium has been detected in the pharynx, no evidence exists of it causing oropharyngeal symptoms or systemic disease.

Urogenital M. genitalium infection is associated with HIV among both men and women (942–944); however, the data are from case-control and cross-sectional studies. Risk for HIV infection is increased among women with M. genitalium, and evidence indicates that HIV shedding occurs more often among persons with M. genitalium and HIV infection who are not taking ART than among persons without M. genitalium (942,944).

Antimicrobial Resistance

Resistance to azithromycin has been rapidly increasing and has been confirmed in multiple studies. Prevalence of molecular markers for macrolide resistance, which highly correlates with treatment failure, ranges from 44% to 90% in the United States, Canada, Western Europe, and Australia (697,702,945–953). Treatment with azithromycin alone has been reported to select for resistance (705,954,955), with treatment of macrolide-susceptible infections with a 1-g dose of azithromycin resulting in selection of resistantstrain populations in 10%–12% of cases. The prevalence of quinolone resistance markers is much lower (697,956–959). The first clinical treatment failures after moxifloxacin were associated specifically with the S83I mutation in the parC gene (954,960). Prevalence of the S83I mutation in the United States ranges from 0% to 15% (947); however, correlation with fluoroquinolone treatment failure is less consistent than that with mutations associated with macrolide resistance (953,961,962). Clinically relevant quinolone resistance often is associated with coexistent macrolide resistance (954).

Diagnostic Considerations

M. genitalium is an extremely slow-growing organism. Culture can take up to 6 months, and technical laboratory capacity is limited to research settings. NAAT for M. genitalium is FDA cleared for use with urine and urethral, penile meatal, endocervical, and vaginal swab samples (https://www.hologic.com/packageinserts/diagnostic-products/aptima-mycoplasma-genitaliumassay). Molecular tests for macrolide (i.e., azithromycin) or quinolone (i.e., moxifloxacin) resistance markers are not commercially available in the United States. However, molecular assays that incorporate detection of mutations associated with macrolide resistance are under evaluation.

Men with recurrent NGU should be tested for M. genitalium using an FDA-cleared NAAT. If resistance testing is available, it should be performed and the results used to guide therapy. Women with recurrent cervicitis should be tested for M. genitalium, and testing should be considered among women with PID. Testing should be accompanied with resistance testing, if available. Screening of asymptomatic M. genitalium infection among women and men or extragenital testing for M. genitalium is not recommended. In clinical practice, if testing is unavailable, M. genitalium should be suspected in cases of persistent or recurrent urethritis or cervicitis and considered for PID.