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Background: Differences in opinion concerning the contribution of M. genitalium to pelvic inflammatory disease (PID) has resulted in inconsistencies across global testing and treatment guidelines. We conducted a systematic review and meta-analysis to determine the association between M. genitalium and PID and M. genitalium positivity within PID cases to provide a contemporary evidence base to inform clinical practice (PROSPERO registration: CRD42022382156)., Methods: PubMed, Embase, Medline and Web of Science were searched to Dec 1, 2023 for studies that assessed women for PID using established clinical criteria and used nucleic acid amplification tests to detect M. genitalium. We calculated summary estimates of the 1) association of M. genitalium with PID (pooled odds ratio [OR]) and 2) proportion of PID cases with M. genitalium detected (pooled M. genitalium positivity in PID), using random-effects meta-analyses, with 95% confidence intervals (CI)., Results: Nineteen studies were included: 10 estimated M. genitalium association with PID, and 19 estimated M. genitalium positivity in PID. M. genitalium infection was significantly associated with PID (pooled OR=1.67 [95%CI: 1.24-2.24]). The pooled positivity of M. genitalium in PID was 10.3% [95%CI: 5.63-15.99]. Subgroup and meta-regression analyses showed that M. genitalium positivity in PID was highest in the Americas, in studies conducted in both inpatient and outpatient clinic settings, and in populations at high risk of sexually transmitted infections., Conclusions: M. genitalium was associated with a 67% increase in odds of PID and was detected in about one in ten clinical diagnoses of PID. These data support testing women for M. genitalium at initial PID diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Although single nucleotide polymorphisms (SNPs) in Mycoplasma genitalium parC contribute to fluoroquinolone treatment failure, data are limited for the homologous gene, gyrA. This study investigated the prevalence of gyrA SNPs and their contribution to fluoroquinolone failure., Methods: Samples from 411 patients (male and female) undergoing treatment for M. genitalium infection (Melbourne Sexual Health Centre, March 2019-February 2020) were analyzed by Sanger sequencing (gyrA and parC). For patients treated with moxifloxacin (n = 194), the association between SNPs and microbiologic treatment outcome was analyzed., Results: The most common parC SNP was G248T/S83I (21.1% of samples), followed by D87N (2.3%). The most common gyrA SNP was G285A/M95I (7.1%). Dual parC/gyrA SNPs were found in 8.6% of cases. One third of infections harboring parC G248T/S83I SNP had a concurrent SNP in gyrA conferring M95I. SNPs in gyrA cooccurred with parC S83I variations. Treatment failure was higher in patients with parC S83I/gyrA dual SNPs when compared with infections with single S83I SNP alone from analysis of (1) 194 cases in this study (81.2% vs 45.8%, P = .047), and (2) pooled analysis of a larger population of 535 cases (80.6% vs 43.2%; P = .0027), indicating a strong additive effect., Conclusions: Compared with parC S83I SNP alone, M. genitalium infections with dual mutations affecting parC/gyrA had twice the likelihood of failing moxifloxacin. Although antimicrobial resistance varies by region globally, these data indicate that gyrA should be considered as a target for future resistance assays in Australasia. We propose a strategy for the next generation of resistance-guided therapy incorporating parC and gyrA testing., Competing Interests: Potential conflicts of interest . C. S. B., D. M. W., E. L. S. and G. L. M. report receiving funding support and diagnostic kits from Speedx Pty Ltd for research on Mycoplasma genitalium. G. L. M. also reports that his laboratory has received diagnostic kits from TibMolBiol unrelated to this study. C. S. B. has advised a number of industries over the years including Nabriva, GSK, and Roche Pty Ltd but has not received payment for this advisory role. S. M. G. reports grants or contracts as an human papillomavirus (HPV) Advisory Board member for Merck, as well as payment or honoraria received as an HPV consultant for Merck. C. S. B. reports a leadership or fiduciary role in the ISSTDR Board. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We compared the rapid plasma reagin (RPR) titer on the day of initial presentation with that on the day of syphilis treatment to inform clinical practice as to whether a repeated RPR test should be recommended., Methods: We undertook a retrospective study between 1 March 2011 and 31 December 2020 at the Melbourne Sexual Health Centre in Australia among individuals who underwent syphilis serology on the day of initial presentation and the day of treatment, if the latter were within 14 days after initial presentation. We calculated the percentage of individuals with a ≥4-fold change in RPR titer, stratified by the time between initial presentation and treatment and by syphilis stage., Results: Among the 766 included syphilis cases, the median duration between initial presentation and treatment was 6 days (interquartile range, 5-7 days). Of these cases, 14.8% (n = 113) had a ≥4-fold increase or decrease during this interval. The number of cases with a ≥4-fold increase or decrease in RPR titer increased with increasing time between initial presentation and treatment, from 5.7% (n = 6) 1-3 days after initial presentation to 26.2% (n = 27) at 10-14 days (Ptrend < .001). There was no significant difference in the number of cases with a ≥4-fold increase or decrease in RPR titer between syphilis stages (P = .66)., Conclusions: Our data support the recommendation of repeating the RPR titer if the day of initial presentation and the day of treatment are different, even when treatment is within a few days after initial presentation., Competing Interests: Potential conflicts of interest. M. Y. C. reports NHMRC Partnership Project Grant APP2003399. C. S. B. received NHMRC Leadership Grant 1173361 and is a board member for the International Society for STD Research and an unpaid consultant to the World Health Organization. J. J. O. reports investigator grants from the NHMRC and is the board director of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine, Australian Federation of AIDS Organisation and an Executive Committee member for the Royal Australian College of Physicians Chapter of Sexual Health Medicine. E. T. A. reports a Research Training Program Scholarship from Monash University and a Research Entry scholarship from the Chapter of Sexual Health Medicine, Royal Australasian College of Physicians. E. P. F. C. reports an NHMRC Emerging Leadership Grant (GNT1172873) and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from CSL Seqirus and MSD, all paid to the institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options., Methods: This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019-December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline + azithromycin (1 g, day 1; 500 mg, days 2-4) and macrolide-resistant infections combination doxycycline + moxifloxacin (400 mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14-28 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections., Results: Of 100 patients with macrolide-susceptible MG treated with doxycycline + azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1-97.1). Of 247 patients with macrolide-resistant MG receiving doxycycline + moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0-89.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83/D87 was associated with 98.3% cure (95% CI, 93.9-99.8) following doxycycline + moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8-77.3). Side effects were common (40%-46%) and predominantly mild and gastrointestinal., Conclusions: Combination doxycycline + azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline + moxifloxacin cured only 85%. Infections that were wild-type for S83/D87 experienced high cure following doxycycline + moxifloxacin, supporting the use of a parC-resistance/susceptibility testing strategy in clinical care., Competing Interests: Potential conflicts of interest. Melbourne Sexual Health Centre has received institutional funding to support research nurse salary time to support independent investigator-led research on Mycoplasma genitalium from Speedx Pty Ltd, and has received diagnostic kits from Speedx Pty Ltd, Hologic Pty Ltd, and Cepheid Pty Ltd. D. M. W. and J. S. J. report funding or support from SpeeDx Pty Ltd, Hologic Pty Ltd, and/or Cepheid Pty Ltd. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: There is limited evidence supporting an association between Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum with symptoms or disease in nonpregnant women. However, testing and reporting of these organisms frequently occurs, in part due to their inclusion in multiplex-PCR assays for sexually transmitted infection (STI) detection. We investigated if M. hominis, U. urealyticum, and U. parvum were associated with symptoms and/or signs in nonpregnant women attending a sexual health service., Methods: Eligible women attending the Melbourne Sexual Health Centre completed a questionnaire regarding sexual practices and symptoms. Symptomatic women underwent examination. Women were assessed for bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), and tested for M. hominis, U. urealyticum, and U. parvum, and 4 nonviral STIs using a commercial multiplex-PCR., Results: 1272 women were analyzed. After adjusting for STIs and VVC, M. hominis was associated with abnormal vaginal discharge (aOR = 2.70, 95%CI:1.92-3.79), vaginal malodor (aOR = 4.27, 95%CI:3.08-5.91), vaginal pH > 4.5 (aOR = 4.27, 95%CI:3.22-5.66), and presence of clue cells (aOR = 8.08, 95%CI:5.68-11.48). Ureaplasma spp. were not associated with symptoms/signs. Bacterial vaginosis was strongly associated with M. hominis (aOR = 8.01, 95%CI:5.99-10.71), but was not associated with either Ureaplasma spp. In stratified analyses, M. hominis was associated with self-reported vaginal malodor and clinician-recorded vaginal discharge in women with BV, but not with symptoms/signs in women without BV., Conclusions: Only M. hominis was associated with symptoms/signs, and these were manifestations of BV. Importantly, M. hominis was not associated with symptoms/signs in women without BV. These findings do not support routine testing for M. hominis, U. urealyticum, and U. parvum in nonpregnant women., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Macrolide resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions, and quinolone resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5 g azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We present data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend data on the efficacy of doxycycline-2.5 g azithromycin and de novo macrolide resistance., Methods: Patients attending Melbourne Sexual Health Centre between 2017 and 2018 with sexually transmitted infection syndromes were treated with doxycycline for 7 days and recalled if MG-positive. Macrolide-susceptible cases received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and resistant cases moxifloxacin (400 mg daily, 7 days). Test of cure was recommended 14-28 days post-antimicrobials., Results: There were 383 patients (81 females/106 heterosexual males/196 men who have sex with men) included. Microbial cure following doxycycline-azithromycin was 95.4% (95% confidence interval [CI], 89.7-98.0) and doxycycline-moxifloxacin was 92.0% (95% CI, 88.1-94.6). De novo macrolide resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n = 186) yielded a pooled cure of 95.7% (95% CI, 91.6-97.8). ParC mutations were present in 22% of macrolide-resistant cases., Conclusions: These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for 2.5 g azithromycin and presumptive use of doxycycline. These data provide an evidence base for current UK, Australian, and European guidelines for the treatment of MG., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Syphilis control among men who have sex with men (MSM) would be improved if we could increase the proportion of cases who present for treatment at the primary stage rather than at a later stage, as this would reduce their duration of infectivity. We hypothesized that MSM who practiced receptive anal intercourse were more likely to present with secondary syphilis, compared to MSM who did not practice receptive anal intercourse., Methods: In this retrospective analysis of MSM diagnosed with primary or secondary syphilis at Melbourne Sexual Health Centre between 2008 and 2017, we analyzed associations between the stage of syphilis (primary vs secondary) and behavioral data collected by computer-assisted self-interviews., Results: There were 559 MSM diagnosed with primary (n = 338) or secondary (n = 221) syphilis. Of these, 134 (24%) men reported not practicing receptive anal sex. In multivariable logistic regression analysis, MSM were more likely to present with secondary rather than primary syphilis if they reported practicing receptive anal intercourse (adjusted odds ratio 3.90; P < .001) after adjusting for age, human immunodeficiency virus status, and condom use. MSM with primary syphilis who did not practice receptive anal intercourse almost always (92%) had their primary syphilis lesion on their penis., Conclusions: The finding that MSM who practiced receptive anal intercourse more commonly presented with secondary syphilis-and hence, had undetected syphilis during the primary stage-implies that anorectal syphilis chancres are less noticeable than penile chancres. These men may need additional strategies to improve early detection of anorectal chancres, to reduce their duration of infectivity and, hence, reduce onward transmission.Men who practiced receptive anal intercourse (AI) were more likely to present with secondary syphilis, compared to men who exclusively practiced insertive AI. Hence, men who practice receptive AI may need additional strategies to detect anal chancres, to reduce transmission., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay., Methods: In mid-2016, Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100 mg twice daily for 7 days) for nongonococcal urethritis, cervicitis, and proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRMs) by polymerase chain reaction. Directly after doxycycline, MRM-negative infections received 2.5 g azithromycin (1 g, then 500 mg daily for 3 days), and MRM-positive infections received sitafloxacin (100 mg twice daily for 7 days). Assessment of test of cure and reinfection risk occurred 14-90 days after the second antibiotic., Results: Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRMs were detected in 167 (68.4% [95% confidence interval {CI}, 62.2%-74.2%]). Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n = 56; P < .0001). Microbiologic cure occurred in 73 of 77 MRM-negative infections (94.8% [95% CI, 87.2%-98.6%]) and in 154 of 167 MRM-positive infections (92.2% [95% CI, 87.1%-95.8%]). Selection of macrolide resistance occurred in only 2 of 76 (2.6% [95% CI, .3%-9.2%]) macrolide-susceptible infections., Conclusions: In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Background: We evaluated the impact of extended azithromycin (1.5g over 5 days) on selection of macrolide resistance and microbiological cure in men with Mycoplasma genitalium urethritis during 2013-2015 and compared this to cases treated with azithromycin 1g in 2012-2013., Methods: Microbiological cure was determined for men with M. genitalium urethritis treated with azithromycin 1.5g using quantitative polymerase chain reaction specific for M. genitalium DNA on samples 14-100 days post-treatment. Pre- and post-treatment macrolide resistance mutations were detected by sequencing the 23 S gene., Results: There was no difference in proportions with microbiological cure between azithromycin 1.5g and 1g: 62/106 (58%; 95% confidence interval [CI], 49%, 68%) and 56/107 (52%; 95%CI 42-62%), P = .34, respectively. Also, there was no difference in the proportion of wild-type 23 S rRNA (presumed macrolide sensitive) infections cured after 1.5g and azithromycin 1g: 28/34 (82%; 95%CI 65-92%) and 49/60 (82%; 95%CI 70-90%), P=1.0, respectively. There was no difference between 1.5g and 1g in the proportions of wild-type infections with post-treatment resistance mutations: 4/34 (12%; 95%CI 3-27%) and 11/60 (18%; 95%CI 10-30%), respectively, P = .40. Pre-treatment resistance was present in 51/98 (52%; 95%CI 42-62%) cases in 2013-2015 compared to 47/107 (44%; 95%CI 34-54%) in 2012-2013, P = .25., Conclusions: Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Mycoplasma genitalium (MG) is associated with nongonococcal urethritis in men and cervicitis in women. Current guidelines recommend treatment with 1 gram of azithromycin; however, treatment failure has increasingly been reported. This meta-analysis estimates treatment efficacy following treatment with 1 gram of azithromycin., Methods: Electronic databases were searched for articles published to the end of February 2015 using the following search terms: (Mycoplasma genitalium) AND (azithromycin OR zithromax OR [treatment efficacy]). Studies were included if they were English language, had participants aged ≥12 years diagnosed with urogenital MG, and had microbial cure measured within 12 months of treatment. Treatment efficacy was measured as microbial cure at last follow-up after treatment., Results: A total of 21 studies, including 1490 participants, fulfilled the inclusion criteria. Most studies were observational, with only 5 controlled trials identified. The random-effects pooled microbial cure was 77.2% (95% confidence interval [CI], 71.1%-83.4%; I(2) = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%-88.3%; I(2) = 19.7%, P = .25); for the 9 studies conducted since the beginning of 2009, pooled microbial cure was 67.0% (CI, 57.0%-76.9%; I(2) = 80.9%, P < .01)., Conclusions: The efficacy of a single dose of 1 gram of azithromycin for the treatment of urogenital MG has decreased to approach 60%. Even though most of the available evidence is based on observational studies that have considerable variability in sample size and timing of microbial cure, this low efficacy is of considerable concern. It is vital that new treatment options for MG are investigated., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium-infected participants, and factors associated with azithromycin failure., Methods: Consecutive eligible M. genitalium-infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multivariable analysis was used to examine associations with azithromycin failure., Results: Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%-69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%-43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%-94%]; adjusted odds ratio, 47.0 [95% CI, 17.1-129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%-94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment., Conclusions: We report a high azithromycin failure rate (39%) in an M. genitalium-infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and quinolone-resistant strains., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Female same-sex partnerships provide a unique opportunity to study the pathogenesis and transmissibility of bacterial vaginosis (BV) because it can be diagnosed in both members of the partnership. We conducted a nationwide community-enrolled cohort study of women who have sex with women, including women coenrolled with their regular female sexual partner (FSP), to investigate the BV incidence rate and factors associated with incident BV., Methods: Women who have sex with women, without prevalent BV in a cross-sectional study, were enrolled in a 24-month cohort study involving 3-monthly questionnaires and self-collected vaginal swabs that were scored by the Nugent method. We assessed the BV incidence rate per 100 woman-years (WY) and used univariate and multivariable Cox regression analysis to establish factors associated with BV acquisition., Results: Two hundred ninety-eight participants were enrolled in the cohort; 122 were coenrolled with their regular FSP. There were 51 incident cases of BV (rate, 9.75/100 WY; 95% confidence interval [CI], 7.41-12.83). Incident BV was associated with exposure to a new sexual partner (adjusted hazard ratio [AHR], 2.51; 95% CI, 1.30-4.82), a partner with BV symptoms (AHR, 3.99; 95% CI, 1.39-11.45), receptive oral sex (AHR, 3.52; 95% CI, 1.41-8.79), and onset of BV symptoms (AHR, 2.80; 95% CI, 1.39-5.61). Women coenrolled with their BV-negative partner had a greatly reduced risk of incident BV (AHR, 0.26; 95% CI, .11-.61), and high concordance of Nugent category (74%), which was predominantly normal vaginal flora throughout follow-up., Conclusions: These data highlight the strong influence of sexual relationships and behaviors on BV acquisition and the vaginal microbiota. They provide epidemiological evidence to support exchange of vaginal bacterial species between women and the concept that BV is sexually transmitted., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: To guide interpretation of gonorrhea tests of cure using nucleic acid amplification testing, this study examined the persistence of Neisseria gonorrhoeae DNA following treatment for pharyngeal and rectal gonorrhea., Methods: Men who had sex with men diagnosed with pharyngeal or rectal gonorrhea underwent swabbing from the pharynx or rectum 7 and 14 days following treatment. Repeat testing for N. gonorrhoeae was undertaken using real-time polymerase chain reaction (PCR) assays targeting the opa gene and porA pseudogene., Results: One hundred pharyngeal and 100 rectal gonorrhea infections in 190 men were included. For pharyngeal gonorrhea, positivity of N. gonorrhoeae DNA on both PCR assays was present at days 7 or 14 in 13% (95% confidence interval [CI], 6.4%-19.6%) and 8% (95% CI, 2.7%-13.3%), respectively. For rectal gonorrhea, DNA positivity was present in 6% (95% CI, 1.4%-10.7%) and 8% (95% CI, 2.7%-13.3%), respectively. Among 200 baseline pharyngeal and rectal isolates, there were 10 with ceftriaxone minimum inhibitory concentration (MIC) ≥0.06 mg/L and azithromycin MIC ≥0.5 mg/L, of which 3 (30%) had DNA detected at day 14; among the 190 isolates with lower ceftriaxone and azithromycin MICs, only 13 (7%) had persistent DNA (odds ratio, 5.8 [95% CI, 1.3-25.4]; P = .019). One man initially infected with N. gonorrhoeae multiantigen sequence type 2400 had type 4244 infection at day 14, indicating reinfection., Conclusions: Pharyngeal and rectal gonorrhea DNA persisted in 8% of men 14 days after treatment. Persistence was associated with elevated ceftriaxone and azithromycin MICs. Persistence can also reflect reinfection., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) that is potentially associated with reproductive tract sequelae in women. This study aimed to estimate MG incidence and treatment failure and provide estimates of organism load in infection., Methods: 1110 women aged 16-25 years were recruited from primary care clinics in Australia. Women were tested for MG at baseline, 6 months, and 12 months, and MG organism load was measured by quantitative polymerase chain reaction (PCR). MG-positive cases were screened for MG 23S ribosomal RNA (rRNA) gene point mutations shown to confer azithromycin resistance using high-resolution melt following PCR., Results: MG incidence rate was 1.3 per 100 person-years (n=14; 95% confidence interval [CI], .8-2.3); women reporting 3 or more sex partners in the last 12 months had an increased rate of incident infection (rate ratio [RR], 5.1; 95% CI, 1.3-19.6]). There were 3 cases of MG reinfection (0.8 per 100 person-years [95% CI, .1-.9]. Organism load was higher for prevalent than incident infection (P=.04). There were 3 cases of treatment failure (9.4% [95% CI, 2.0-25.0]); organism load was higher in cases with treatment failure than in successfully treated cases (P<.01). An MG 23S rRNA mutation was detected in 5 cases (3 cases of treatment failure and 2 successfully treated)., Conclusions: Although MG incidence was relatively low, testing should be recommended for women considered to be at increased risk based on sexual history. Our results also suggest that organism load might be important in azithromycin treatment failure.

Background: Bacterial vaginosis (BV) recurrence posttreatment is common. Our aim was to determine if behaviors were associated with BV recurrence in women in a randomized controlled trial (RCT)., Methods: Symptomatic 18- to 50-year-old females with BV (≥3 Amsel criteria and Nugent score [NS] = 4-10) were enrolled in a 3-arm randomized double-blind RCT Melbourne Sexual Health Centre, Australia, in 2009-2010. All 450 participants received oral metronidazole (7 days) and were equally randomized to vaginal clindamycin, lactobacillus-vaginal probiotic or vaginal placebo. At 1, 2, 3, and 6 months, participants self-collected vaginal smears and completed questionnaires. Primary endpoint was NS = 7-10. Cox regression was used to estimate hazard ratios (HRs) for risk of BV recurrence associated with baseline and longitudinal characteristics., Results: Four hundred four (90%) women with postrandomization data contributed to analyses. Cumulative 6-month BV recurrence was 28% (95% confidence interval [CI], 24%-33%) and not associated with treatment. After stratifying for treatment and adjusting for age and sex frequency, recurrence was associated with having the same pre-/posttreatment sexual partner (adjusted HR [AHR] = 1.9; 95% CI, 1.2-3.0), inconsistent condom use (AHR = 1.9; 95% CI, 1.0-3.3), and being non-Australian (AHR = 1.5; 95% CI, 1.0-2.1), and halved with use of an estrogen-containing contraceptive (AHR = 0.5; 95% CI, .3-.8)., Conclusions: Risk of BV recurrence was increased with the same pre-/posttreatment sexual partner and inconsistent condom use, and halved with use of estrogen-containing contraceptives. Behavioral and contraceptive practices may modify the effectiveness of BV treatment., Clinical Trials Registration: ACTRN12607000350426.

Background: Mycoplasma genitalium is a common cause of nongonococcal urethritis. Treatment trials have shown that doxycycline is inefficient, whereas a 5-day course of azithromycin eradicates the bacterium from 95% of infected men. The aim of the study was to establish the reason for the occasional treatment failures., Methods: Seven M. genitalium strains isolated from men who experienced azithromycin treatment failure were tested for in vitro susceptibility to macrolides with use of a cell culture-based method. The genetic basis for the drug resistance was established by sequencing parts of the 23S ribosomal RNA gene and the genes encoding the L4 and L22 proteins. Nine sets of specimens obtained before and after treatment from patients who experienced azithromycin treatment failure were examined with use of sequencing of polymerase chain reaction products., Results: The 7 strains that were isolated from patients who experienced treatment failure with azithromycin had minimum inhibitory concentrations >8 microg/mL for azithromycin and erythromycin. Three different mutations at positions 2058 and 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene were found. Of the 9 patients with specimens obtained before and after treatment, only 2 had an initial specimen in which the mutation was present, indicating that drug resistance was induced as the result of an inappropriate dosage of azithromycin., Conclusion: Development of macrolide resistance was shown to correlate with subsequent azithromycin treatment failure. The genetic basis for the drug resistance was shown to be mutations in region V of the 23S rRNA gene, which is well described in other Mollicutes. These findings raise concern about the use of single-dose azithromycin treatment of nongonococcal urethritis of unknown etiology.

We performed a systematic review and meta-analysis of the association between sexual risk factors and bacterial vaginosis (BV). Forty-three studies reported new or multiple sexual partners and condom use relative to prevalent, incident, or recurrent BV. The summary estimate of the relative risk for the association between BV new or multiple male partners was 1.6 (95% confidence interval, 1.5-1.8), between BV and any female partners was 2.0 (95% confidence interval, 1.7-2.3), and between BV and condom use was 0.8 (95% confidence interval, 0.8-0.9). This review is the first to summarize available observational data for BV. It shows that BV is significantly associated with sexual contact with new and multiple male and female partners and that decreasing the number of unprotected sexual encounters may reduce incident and recurrent infection. Investigation of sexual transmission of BV is limited by the absence of a clear microbiological etiology; however, we have shown that the epidemiological profile of BV is similar to that of established sexually transmitted infections.