Impact of Check It: A Novel Community-Based Chlamydia Screening and Expedited Treatment Program for Young Black Men.

OBJECTIVES: This study aimed to estimate the impact of the Check It program, a novel community-based chlamydia seek, test, and treat program for young Black men who have sex with women, on test positivity rates for chlamydia in young Black women. METHODS: We used a synthetic control model to compare chlamydia test positivity rates in Orleans Parish (intervention site) with other similar parishes (control sites) in Louisiana. We estimated a model that used all other parishes as potential contributors to a synthetic control for Louisiana as well as a sample limited to the 40 parishes in Louisiana with the largest Black populations. RESULTS: The Check It program was associated with a 1.69-percentage-point decline in chlamydia positivity in the first full year of operation and a 2.44-percentage-point decline in chlamydia positivity in the second full year of operation compared with control sites with the largest Black populations (P = 0.05). Results were similar when the treatment site was compared with all other sites in Louisiana. CONCLUSIONS: The Check It program was associated with a significant decline in chlamydia testing positivity rates among women in Orleans Parish compared with control sites. Screening of young Black men who have sex with women can decrease rates in women living in the same community. Future recommendations for chlamydia screening of young men should be considered.

A Comparison of Single-Dose Versus Multidose Metronidazole by Select Clinical Factors for the Treatment of Trichomonas vaginalis in Women.

BACKGROUND: In a randomized controlled trial of 2 g (single-dose) metronidazole (MTZ) versus 500 mg twice daily for 7 days (multidose) for Trichomonas vaginalis treatment, multidose was superior. We examined if the effect was similar by select clinical factors to determine if treatment recommendations could be targeted. METHODS: The primary outcome was T. vaginalis repeat infection at test-of-cure (TOC) 4 weeks after completion of therapy. Analyses were stratified by T. vaginalis history, baseline genital symptoms, and concurrent diagnosis of bacterial vaginosis (BV) per Nugent score at baseline. RESULTS: Women who returned for TOC (n = 540) were included. At baseline, 52.9% had a self-reported history of T. vaginalis; 79.3%, genital symptoms; 5.8%, a gonorrhea diagnosis; and 47.5%, BV. During follow-up, 97.4% took all MTZ as instructed and 34.5% had interval condomless sex with a baseline partner. At TOC, 14.8% tested positive for T. vaginalis. In stratified analysis, women randomized to single-dose MTZ had a higher rate of TOC T. vaginalis positivity than those randomized to multidose if they were symptomatic at baseline (21.4% vs. 10.8%, P = 0.003) or had a reported history of T. vaginalis (24.1% vs. 12.6%, P = 0.01). Test-of-cure T. vaginalis positivity was higher for women receiving a single dose (18.9%) versus multidose (10.8%), irrespective of baseline BV status (P > 0.06). In multivariable analysis, only a history of T. vaginalis and single-dose MTZ were independently associated with a positive TOC for T. vaginalis. CONCLUSIONS: Although multidose MTZ is recommended for all women with T. vaginalis, it is especially important for women with a T. vaginalis history and, given high posttreatment infection rates, a TOC should be performed.

Anal and Oral Sex Behaviors Among Young Black Men Who Have Vaginal Sex: Evidence of the Need for Extragenital Testing for Chlamydia and Gonorrhea.

BACKGROUND: Unprotected oral and anal sex may result in extragenital sexually transmitted infections. The purposes of this study were to describe sexual behaviors, barrier use, and chlamydia/gonorrhea (Ct/GC) positivity among young Black men who have sex with women, and to examine the potential influence of extragenital infections on genital infections. METHODS: Young Black men who had vaginal sex were screened for Ct/GC in New Orleans, LA, from August 14, 2019, to February 29, 2020. Audio/computer-assisted self-interviews were used to collect data on demographics and sexual behaviors. χ2 /Fisher exact or t test/Wilcoxon rank tests were used to assess differences in behaviors by Ct/GC positivity. RESULTS: Among 373 men studied, 619 female partnerships were reported in the past 2 months. Vaginal sex was reported in all partnerships per study protocol, receiving fellatio in 42.7%, performing cunnilingus in 35.7%, and penile-anal sex in 5.9%. Although 31.4% of the men consistently used condoms for vaginal sex with all partners, consistent barrier use was low during cunnilingus (0.5%) and fellatio (5.1%). Urethral infection rates among all men in the sample were 12.6% for Ct and 1.6% for GC. There was no significant difference in Ct/GC rates between those using and not using condoms consistently during vaginal sex ( P = 0.38). CONCLUSIONS: Unprotected oral sex with female partners was common. The high rate of genital infection among men who used condoms consistently for vaginal sex suggests that oral infections could be serving as a reservoir of genital infection. Testing at all sites of exposure for youth who engage in heterosexual sex is merited.

Check It: A Community-Based Chlamydia Seek, Test, and Treat Program for Young Black Men Who Have Sex With Women in New Orleans, Louisiana.

BACKGROUND: Check It is a novel, bundled, community-based seek, test, and treat Chlamydia trachomatis (Ct) screening program for 15- to 24-year-old Black men in New Orleans who have sex with women. The program design addressed barriers and facilitators to Ct screening/treatment by enlisting trusted community partners, incorporating participant input, providing free index/partner expedited treatment, developing relatable marketing materials and an educational Web site, encouraging peer referral, and providing a modest monetary incentive. METHODS: Areas of high poverty were identified using census data; ethnographic/key informant interviews identified sites in those areas where the target population congregated. Black youth informed Web site design and social marketing. Content was inspirational/educational/amusing and endorsed recruitment and brand awareness. A community advisory board, participant interviews, community partner feedback, and recruitment staff involvement in the process evaluation helped refine the program in an ongoing manner. RESULTS: During formative stages, 41 key informant/community advisory board members informed program refinement. Community partners provided venue locations (n = 65) and participant referrals. Between May 22, 2017, and February 28, 2020, 1890 men were enrolled (acceptance rate, 96.0%) with Ct infection rate of 10.2%. Overall study treatment was provided to 86.1% (71.4%-90.9%) of participants who tested positive and 28.5% (14.5%-41.5%) of their partners. Findings from in-depth interviews with participants (n = 43) led to increased treatment uptake. CONCLUSIONS: C. trachomatis community screening of young Black men was successful through collaboration with trusted community partners, by tailoring implements/marketing with participant input, reducing barriers to treatment, and providing modest monetary incentives. The Check It program can serve as a roadmap for reducing health disparities in this population.

Adapting Index/Partner Services for the Treatment of Chlamydia Among Young African American Men in a Community Screening Program.

BACKGROUND: Screening for asymptomatic Chlamydia trachomatis (Ct) among men has not been recommended because feasibility and efficacy are unknown. Check It is a seek-test-treat community-based Ct screening program for African American men who have sex with women and who are 15 to 24 years of age. This is an evaluation of adaptations made to the program aimed at improving index/partner notification and treatment rates. METHODS: The original Check It intervention included free testing and treatment, contact tracing performed by a third party, expedited index therapy, and expedited partner therapy via pharmacy pickup. The intervention was adapted after a series of in-depth interviews eliciting information to refine the program. Changes included continuity of testing, notification, and treatment by the same staff; expanded hours; and patient-delivered partner therapy with a medication mail-delivery option. Rates of index male and partner treatment were compared using log-binomial models and generalized estimating equations. RESULTS: Men in the adapted intervention (n = 85) were more likely than men in the original intervention (n = 99) to be contacted (relative risk [RR], 1.14; 95% confidence interval [CI], 1.02-1.27), make a treatment plan (RR, 1.14; 95% CI, 1.01-1.27), and complete treatment (RR, 1.45; 95% CI, 1.20-1.75). Female sexual partners were significantly more likely to complete treatment in postadaptation (n = 153) compared with preadaptation (n = 161; RR, 3.02; 95% CI, 1.81-5.05). CONCLUSIONS: Compared with third-party notification and expedited index therapy/expedited partner therapy available by pharmacy pickup only, patient-delivered partner therapy with mail-delivery option, staff available at nontraditional hours, and staff continuity across testing, notification, and treatment significantly improved index and partner treatment completion.

In Silico and Experimental Evaluation of Primer Sets for Species-Level Resolution of the Vaginal Microbiota Using 16S Ribosomal RNA Gene Sequencing.

Background: Identification of bacteria in human vaginal specimens is commonly performed using 16S ribosomal RNA (rRNA) gene sequences. However, studies utilize different 16S primer sets, sequence databases, and parameters for sample and database clustering. Our goal was to assess the ability of these methods to detect common species of vaginal bacteria. Methods: We performed an in silico analysis of 16S rRNA gene primer sets, targeting different hypervariable regions. Using vaginal samples from women with bacterial vaginosis, we sequenced 16S genes using the V1-V3, V3-V4, and V4 primer sets. For analysis, we used an extended Greengenes database including 16S gene sequences from vaginal bacteria not already present. We compared results with those obtained using the SILVA 16S database. Using multiple database and sample clustering parameters, each primer set's ability to detect common vaginal bacteria at the species level was determined. We also compared these methods to the use of DADA2 for denoising and clustering of sequence reads. Results: V4 sequence reads clustered at 99% identity and using the 99% clustered, extended Greengenes database provided optimal species-level identification of vaginal bacteria. Conclusions: This study is a first step toward standardizing methods for 16S rRNA gene sequencing and bioinformatics analysis of vaginal microbiome data.

Mycoplasma genitalium Infections in Women Attending a Sexually Transmitted Disease Clinic in New Orleans.

BACKGROUND: Mycoplasma genitalium has been significantly and nonsignificantly associated with cervicitis, urethritis, or vaginal discharge. This study examined the associations of M. genitalium with selected sexually transmitted infections (STIs) and demographic, behavioral, and clinical factors among women attending a sexually transmitted disease (STD) clinic in New Orleans. METHODS: Women aged ≥18 years who presented to the New Orleans STD clinic provided sociodemographic data and sexual behavior; STI, obstetric, and gynecologic history; and urine, vaginal, endocervical, and rectal specimens. Specimens were tested for M. genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis, Ureaplasma species, and yeast. Bacterial vaginosis (BV) was diagnosed by Nugent score, and cervicitis was defined as ≥30 polymorphonuclear leukocytes per high-power microscopic field on a cervical Gram stain or yellow mucopus on an endocervical swab. RESULTS: Among 400 women studied, M. genitalium was independently significantly associated with age <25 years (P < .03) and with ≥2 sexual partners in the last 12 months (P < .003). Neisseria gonorrhoeae (adjusted odds ratio [AOR], 1.75; P = .103), C. trachomatis (AOR, 1.43; P = .247), and T. vaginalis (AOR, 1.60; P = .120) independently increased the odds of infection with M. genitalium. Controlling for other STIs and BV, there was a positive trend for M. genitalium to predict cervicitis (AOR, 3.18 [95% confidence interval, .99-10.2]; P = .05). CONCLUSIONS: Mycoplasma genitalium in our study displayed the clinical features of C. trachomatis and N. gonorrhoeae, the 2 organisms that drive research agendas in diagnosis, treatment, and prevention of bacterial STIs.

Trichomonas vaginalis Virus Among Women With Trichomoniasis and Associations With Demographics, Clinical Outcomes, and Metronidazole Resistance.

BACKGROUND: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kilo-base pair (kbp), double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine the TVV prevalence in US Trichomonas vaginalis isolates and TVV's associations with patient demographics, clinical outcomes, and metronidazole resistance. METHODS: Archived T. vaginalis isolates from the enrollment visits of 355 women participating in a T. vaginalis treatment trial in Birmingham, Alabama, were thawed and grown in culture. Their total RNA was extracted using a Trizol reagent. Contaminating, single-stranded RNA was precipitated using 4.0 M Lithium Chloride and centrifugation. The samples were analyzed by gel electrophoresis to visualize a 4.5 kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates obtained from the women's test of cure visits. RESULTS: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV-positive (TVV+) isolates were significantly older (P = .01), more likely to smoke (P = .04), and less likely to report a history of gonorrhea (P = .04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infections with TVV+ isolates (P = .14 and P = .44, respectively). Of 25 test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance, while 2/15 TVV-negative isolates demonstrated mild to moderate resistance (P = .23). CONCLUSIONS: Of 355 T. vaginalis isolates tested for TVV, T. vaginalis isolates tested for TVV, the prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be commensal to T. vaginalis.

Optimal Timing for Trichomonas vaginalis Test of Cure Using Nucleic Acid Amplification Testing.

BACKGROUND: The optimal timing for nucleic acid amplification testing (NAAT) posttreatment for Trichomonas vaginalis has not been fully established. Testing too soon posttreatment may detect remnant nucleic acid that is not from viable organisms, falsely misclassifying person as infected. The purpose of this study was to examine how long T. vaginalis nucleic acid is detectable postmetronidazole (MTZ) treatment. METHODS: Women diagnosed with T. vaginalis treated with MTZ (2 g single-dose or 500 mg twice daily for 7 days multidose) self-collected a vaginal swab for NAAT at baseline and each week postcompletion of treatment through test of cure (TOC) at week 4, when a culture was also performed. Women who reported interim sexual exposure or who were culture positive at 4 weeks were excluded. Time to first negative NAAT was examined using Kaplan Meier analysis. RESULTS: All women receiving multidose metronidazole were NAAT-negative by 21 days and those receiving single dose by 28 days postcompletion of treatment. Though over half (60.7%) of the cohort reinitiated sex during follow-up¸ all reported using condoms during sex or that they and their partner were treated before sex. Six (6.7%) of 89 had a positive NAAT following their first negative NAAT. CONCLUSIONS: The optimal timing for T. vaginalis retesting after completion of treatment is 3 weeks for those receiving multidose MTZ and 4 weeks for those receiving single-dose, though sexual reexposure and false negatives should be considered.

Identification of Key Bacteria Involved in the Induction of Incident Bacterial Vaginosis: A Prospective Study.

Background: The sequence of events preceding incident bacterial vaginosis (iBV) is unclear. Methods: African American women who have sex with women, who had no Amsel criteria and Nugent scores of 0-3, were followed for 90 days to detect iBV (defined as a Nugent score of 7-10 on at least 2-3 consecutive days), using self-collected vaginal swab specimens. For women with iBV (cases) and women maintaining normal vaginal flora (healthy women), 16S ribosomal RNA gene sequencing targeting V4 was performed. Longitudinal vaginal microbiome data were analyzed. Results: Of 204 women screened, 42 enrolled; of these, 45% developed iBV. Sequencing was performed on 448 specimens from 14 cases and 8 healthy women. Among healthy women, Lactobacillus crispatus dominated the vaginal microbiota in 75%. In contrast, prior to iBV, the vaginal microbiota in 79% of cases was dominated by Lactobacillus iners and/or Lactobacillus jensenii/Lactobacillus gasseri. The mean relative abundance of Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type I became significantly higher in cases 4 days before (P. bivia), 3 days before (G. vaginalis), and on the day of (A. vaginae and Megasphaera type I) iBV onset. The mean relative abundance of Sneathia sanguinegens, Finegoldia magna, BV-associated bacteria 1-3, and L. iners was not significantly different between groups before onset of iBV. Conclusion: G. vaginalis, P. bivia, A. vaginae, and Megasphaera type I may play significant roles in iBV.

Mycoplasma genitalium Infection in Men.

Mycoplasmagenitalium is one of the major causes of nongonococcal urethritis (NGU) worldwide but an uncommon sexually transmitted infection (STI) in the general population. The risk of sexual transmission is probably lower than for Chlamydia trachomatis. Infection in men is usually asymptomatic and it is likely that most men resolve infection without developing disease. The incubation period for NGU caused by Mycoplasma genitalium is probably longer than for NGU caused by C. trachomatis. The clinical characteristics of symptomatic NGU have not been shown to identify the pathogen specific etiology. Effective treatment of men and their sexual partner(s) is complicated as macrolide antimicrobial resistance is now common in many countries, conceivably due to the widespread use of azithromycin 1 g to treat STIs and the limited availability of diagnostic tests for M. genitalium. Improved outcomes in men with NGU and better antimicrobial stewardship are likely to arise from the introduction of diagnostic M. genitalium nucleic acid amplification testing including antimicrobial resistance testing in men with symptoms of NGU as well as in their current sexual partner(s). The cost effectiveness of these approaches needs further evaluation. The evidence that M. genitalium causes epididymo-orchitis, proctitis, and reactive arthritis and facilitates human immunodeficiency virus transmission in men is weak, although biologically plausible. In the absence of randomized controlled trials demonstrating cost effectiveness, screening of asymptomatic men cannot be recommended.

Mycoplasma genitalium From Basic Science to Public Health: Summary of the Results From a National Institute of Allergy and Infectious Disesases Technical Consultation and Consensus Recommendations for Future Research Priorities.

This article lays out the research priorities for Mycoplasma genitalium research agreed upon by the participants in a 2016 National Institutes of Allergy and Infectious Diseases-funded Technical Consultation focused on this organism. The state of current knowledge concerning the microbiology, epidemiology, clinical manifestations of infection, treatment, and public health significance of M. genitalium reviewed at the meeting is described in detail in the individual articles included in this supplemental edition of the Journal of Infectious Diseases. Here we summarize the points made in these articles most relevant to the formulation of the research priorities listed in this article. The most important recommendation resulting from this Technical Consultation is the initiation of clinical trials designed to determine definitively whether screening for and treatment of M. genitalium infections in women and their sexual partners improve reproductive health in women and/or prevent human immunodeficiency virus transmission.

Rate of Decline in Nontreponemal Antibody Titers and Seroreversion After Treatment of Early Syphilis.

BACKGROUND: Syphilis management is complex and demonstration of treatment response requires monitoring of nontreponemal antibody titers for a ≥ 4-fold decline and/or seroreversion to nonreactive titers. METHODS: We evaluated data from a multicenter clinical trial of syphilis treatment conducted from 2000 to 2009 involving human immunodeficiency virus (HIV)-negative patients 18 years or older with early syphilis. To assess the rate of titer decline and seroreversion after effective therapy, rapid plasma reagin (RPR) titers were analyzed at 1, 3, 6, 9, and 12 months among patients with an appropriate treatment response. We plotted the rate of RPR titer decline after treatment, estimated the frequency of seroreversion, and conducted multivariate analyses to assess characteristics associated with seroreversion. RESULTS: Among 369 (79.4%) of 465 HIV-negative patients with early syphilis who had an appropriate treatment response, 333 participants had complete RPR data over 12 months. Although the decline in RPR titers was ≥ 4-fold among 88.0% (293/333) of participants at 3 months and ≥ 8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy. Male sex (adjusted odds ratio, 4.3; 95% confidence interval, 1.8-10.5) and baseline RPR titers ≤ 1:32 (adjusted odds ratio, 14.5; 95% confidence interval, 6.8-31.2) were associated with higher odds of seroreversion compared with females and titers > 1:32, respectively. CONCLUSIONS: Despite a ≥ 4-fold RPR titer decline after treatment, the majority of HIV-negative patients with early syphilis failed to have seroreversion at 12 months. Nontreponemal antibody titers often persist despite an appropriate treatment response.

The Vaginal Microbiome: Current Understanding and Future Directions.

This article summarizes the highlights of the expert technical consultation on bacterial vaginosis (BV), sponsored by the National Institute of Allergy and Infectious Disease and held in Washington, DC, on 8-9 April 2015. Many issues touched on in this article are discussed in much greater detail in the 6 preceding articles in this supplement to The Journal of Infectious Diseases There was a consensus among the meeting attendees concerning the most important research issues in the field: the pathogenesis of the syndrome, way to optimize treatment, and the relative roles of sexual transmission and endogenous infection in BV epidemiology. This article concludes with a listing of BV and genitourinary tract research priorities that were discussed and agreed on by attendees. The most important of these included better characterization of vaginal microbiome community state subtypes, application of advanced "-omic" technologies to improve understanding of BV pathogenesis, further investigation of the relationships between the male and female genitourinary tract microbiomes, and the development of new drugs for BV treatment.

Identification of novel microbes associated with pelvic inflammatory disease and infertility.

OBJECTIVES: As pelvic inflammatory disease (PID) aetiology is not completely understood, we examined the relationship between select novel bacteria, PID and long-term sequelae. METHODS: Fastidious bacterial vaginosis (BV)-associated bacteria (Sneathia (Leptotrichia) sanguinegens, Sneathia amnionii, Atopobium vaginae and BV-associated bacteria 1 (BVAB1)), as well as Ureaplasma urealyticum and Ureaplasma parvum were identified in cervical and endometrial specimens using organism-specific PCR assays among 545 women enrolled in the PID Evaluation and Clinical Health study. Risk ratios and 95% CIs were constructed to determine associations between bacteria, histologically confirmed endometritis, recurrent PID and infertility, adjusting for age, race, gonorrhoea and chlamydia. Infertility models were additionally adjusted for baseline infertility. RESULTS: Persistent detection of BV-associated bacteria was common (range 58% for A. vaginae to 82% for BVAB1) and elevated the risk for persistent endometritis (RRadj 8.5, 95% CI 1.6 to 44.6) 30 days post-cefoxitin/doxycycline treatment, independent of gonorrhoea and chlamydia. In models adjusted for gonorrhoea and chlamydia, endometrial BV-associated bacteria were associated with recurrent PID (RRadj 4.7, 95% CI 1.7 to 12.8), and women who tested positive in the cervix and/or endometrium were more likely to develop infertility (RRadj 3.4, 95% CI 1.1 to 10.4). Associations between ureaplasmas and PID sequelae were modest. CONCLUSIONS: To our knowledge, this is the first prospective study to demonstrate that S. sanguinegens, S. amnionii, BVAB1 and A. vaginae are associated with PID, failure of the Centers for Disease Control and Prevention-recommended treatment to eliminate short-term endometritis, recurrent PID and infertility. Optimal antibiotic regimens for PID may require coverage of novel BV-associated microbes.

Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis.

BACKGROUND: Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. METHODS: Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. RESULTS: The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). CONCLUSIONS: In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

Kinetics of Genetic Variation of the Mycoplasma genitalium MG192 Gene in Experimentally Infected Chimpanzees.

Mycoplasma genitalium, a human pathogen associated with sexually transmitted diseases, is capable of causing chronic infections, though mechanisms for persistence remain unclear. Previous studies have found that variation of the MgPa operon occurs by recombination of repetitive chromosomal sequences (known as MgPars) into the MG191 and MG192 genes carried on this operon, which may lead to antigenic variation and immune evasion. In this study, we determined the kinetics of MG192 sequence variation during the course of experimental infection using archived specimens from two chimpanzees infected with M. genitalium strain G37. The highly variable region of MG192 was amplified by PCR from M. genitalium isolates obtained at various time points postinfection (p.i.). Sequence analysis revealed that MG192 sequence variation began at 5 weeks p.i. With the progression of infection, sequence changes accumulated throughout the MG192 variable region. The presence of MG192 variants at specific time points was confirmed by variant-specific PCR assays and sequence analysis of single-colony cloned M. genitalium organisms. MG192 nucleotide sequence variation correlated with estimated recombination events, predicted amino acid changes, and time of seroconversion, a finding consistent with immune selection of MG192 variants. In addition, we provided evidence that MG192 sequence variation occurred during the process of M. genitalium single-colony cloning. Such spontaneous variation suggests that some MG192 variation is independent of immune selection but may form the basis for subsequent immune selection.

Efficacy of Antimicrobial Therapy for Mycoplasma genitalium Infections.

Mycoplasma genitalium has been causally linked with nongonococcal urethritis in men and cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion, and infertility in women, yet treatment has proven challenging. To inform treatment recommendations, we reviewed English-language studies describing antimicrobial susceptibility, resistance-associated mutations, and clinical efficacy of antibiotic therapy, identified via a systematic search of PubMed supplemented by expert referral. Minimum inhibitory concentrations (MICs) from some contemporary isolates exhibited high-level susceptibility to most macrolides and quinolones, and moderate susceptibility to most tetracyclines, whereas other contemporary isolates had high MICs to the same antibiotics. Randomized trials demonstrated poor efficacy of doxycycline and better, but declining, efficacy of single-dose azithromycin therapy. Treatment failures after extended doses of azithromycin similarly increased, and circulating macrolide resistance was present in high levels in several areas. Moxifloxacin remains the most effective therapy, but treatment failures and quinolone resistance are emerging. Surveillance of M. genitalium prevalence and antimicrobial resistance patterns is urgently needed.

Advances in the Understanding and Treatment of Male Urethritis.

Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting.