Prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021-2022.

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia.

Systematic review and meta-analysis of the association between Mycoplasma genitalium and Pelvic inflammatory disease (PID).

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.

Bacterial vaginosis after menopause: factors associated and women's experiences: a cross-sectional study of Australian postmenopausal women.

Background Bacterial vaginosis (BV) is the most common cause of vaginal discharge in reproductive age women; however, little is known about it after menopause. We aimed to learn more about BV in Australian postmenopausal women. Methods We conducted an online survey (July-September 2021). Participants were recruited via social media and professional networks and asked about demographic characteristics, sexual history and BV experiences. Outcomes of interest were the proportion who had heard of BV, had BV ever, or had BV after menopause. Factors associated with these outcomes were assessed using logistic regression. Results Of 906 participants, 83% were included in the analysis. Overall, 37.9% had heard of BV, 11.0% reported having a BV diagnosis ever, 6.3% reported having a BV diagnosis after menopause and 4.4% reported having a BV diagnosis only after menopause. Multivariable analysis found that among all women the odds of having a BV diagnosis after menopause were increased for those who had BV before menopause, had douched in the past 12months, or had a previous STI diagnosis. Among those in a sexual relationship, a BV diagnosis after menopause was associated with a BV diagnosis before menopause, or being in a sexual relationship of 5years or less in duration. About half who reported BV after menopause described recurrences, distress, and a detrimental effect on sexual relationships. Conclusions BV in postmenopausal women is associated with sexual activity, and impacts negatively on their lives. Research into BV should not be limited to reproductive age women.

Prevotella and Gardnerella Are Associated With Treatment Failure Following First-line Antibiotics for Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common vaginal dysbiosis that often recurs following first-line antibiotics. We investigated if vaginal microbiota composition was associated with BV recurrence. METHODS: We analyzed samples and data from 121 women who participated in 3 published trials evaluating novel interventions for improving BV cure, including concurrent antibiotic treatment of regular sexual partners (RSPs). Women diagnosed with BV received first-line antibiotics and self-collected vaginal swabs pretreatment and the day after finishing antibiotics (immediately posttreatment). 16S rRNA gene sequencing was performed on vaginal samples. Logistic regression explored associations between BV recurrence and features of the vaginal microbiota pre- and posttreatment. RESULTS: Sixteen women (13% [95% confidence interval {CI}, 8%-21%]) experienced BV recurrence within 1 month of treatment. Women with an untreated RSP were more likely to experience recurrence than women with no RSP (P = .008) or an RSP who received treatment (P = .011). A higher abundance of Prevotella pretreatment (adjusted odds ratio [AOR], 1.35 [95% CI, 1.05-1.91]) and Gardnerella immediately posttreatment (AOR, 1.23 [95% CI, 1.03-1.49]) were associated with increased odds of BV recurrence. CONCLUSIONS: Having specific Prevotella spp prior to recommended treatment and persistence of Gardnerella immediately posttreatment may contribute to the high rates of BV recurrence. Interventions that target these taxa are likely required to achieve sustained BV cure.

gyrA Mutations in Mycoplasma genitalium and Their Contribution to Moxifloxacin Failure: Time for the Next Generation of Resistance-Guided Therapy.

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.

Comparison of Seegene AnyPlexTM II STI-7e with standard-of-care diagnostic methods for the detection of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

The AnyPlexTM II STI-7e panel assay (Seegene) detects seven sexually transmitted organisms (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum, U. parvum, and Trichomonas vaginalis). This study compared the performance of AnyPlexTM II STI-7e with standard-of-care diagnostic methods. Samples (cervical or vaginal swabs, or urine) from 1330 women were tested on standard-of-care assays; 83/1318 (6.3%) tested positive for M. genitalium (ResistancePlus® MG), 99/1317 (7.5%) positive for C. trachomatis and 11/1316 (0.8%) positive for N. gonorrhoeae (Hologic® Aptima Combo 2®), and 6/689 (0.9%) positive for T. vaginalis (wet mount microscopy). AnyPlexTM II STI-7e had good agreement for the detection of M. genitalium [Cohen's kappa of 0.80, 95% confidence intervals (CI) 0.74-0.87] and C. trachomatis (kappa of 0.87, 95% CI 0.82-0.92), with positive and negative % agreement >96% for both infections. There was lower agreement for the detection of N. gonorrhoeae (kappa of 0.37, 95%CI 0.19-0.55) and T. vaginalis (kappa of 0.521, 95%CI 0.25-0.80). In summary, the test performed well in this comparison for M. genitalium and C. trachomatis detection, but results were less conclusive for N. gonorrhoeae and T. vaginalis due to low prevalence in the population.

Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure.

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.

parC Variants in Mycoplasma genitalium: Trends over Time and Association with Moxifloxacin Failure.

Prevalence, trends, and treatment outcome estimates were generated for parC variants in macrolide-resistant Mycoplasma genitalium. Among 539 cases, the most common amino acid change was S83I, which increased from 13% in 2012 to 2013, to 23% in 2019 to 2020 (Ptrend = 0.046). From 381 moxifloxacin treatments, failure occurred in 58.7% (95% confidence interval [CI], 46.7 to 69.9) of cases with S83I. Other changes affecting S83 or D87 were uncommon and minor contributors to failure. The absence of S83I was highly predictive of moxifloxacin cure (96.4%; 95% CI, 93.7 to 98.2), highlighting diagnostic potential.

Impact of 16S rRNA Single Nucleotide Polymorphisms on Mycoplasma genitalium Organism Load with Doxycycline Treatment.

Doxycycline targets the 16S rRNA and is widely used for the treatment of sexually transmitted infections. While it is not highly effective at eradicating Mycoplasma genitalium infections, it can reduce organism load. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of M. genitalium and change in organism load. M. genitalium samples were collected from 56 men prior to commencing doxycycline and at a median of 13 of 14 doses. These were sequenced for the 16S rRNA, and the association between 16S rRNA SNPs and change in organism load was determined. 16S rRNA sequences were available for 52/56 (92.9%) M. genitalium-infected men, of which 20 (38.5%) had an undetectable load, 26 (50.0%) had a decrease in M. genitalium load (median change of 105-fold), and 6 (11.5%) had an increase in load (median change of 5-fold). The most common SNPs identified were A742G (10/52 [19.2%]), GG960-961TT/C (7/52 [13.5%]), and C1435T (28/52 [53.8%]) (M. genitalium numbering). None were associated with a change in organism load (P = 0.76, 0.16, and 0.98, respectively). Using pooled published data from 28 isolates, no clear relationship between the SNPs and doxycycline MIC was identified. In conclusion, the low efficacy of doxycycline against M. genitalium does not appear to be due to variation in the 16S rRNA gene.

Chlamydia trachomatis and Mycoplasma genitalium prevalence and associated factors among women presenting to a pregnancy termination and contraception clinic, 2009-2019.

BACKGROUND: Risk of pelvic inflammatory disease associated with Chlamydia trachomatis and Mycoplasma genitalium is increased after termination of pregnancy (TOP) and may be increased after insertion of intrauterine devices (IUDs). Screening prior to these procedures is recommended only for C. trachomatis. We examined C. trachomatis and M. genitalium prevalence and associated factors among women presenting to a pregnancy termination and contraception service over 10 years. METHODS: Retrospective analysis of clinical data collected from 17 573 women aged 15-45 years in 2009-2019 and for 266 M. genitalium positive women tested for macrolide resistance-associated mutations in 2016-2019. RESULTS: C. trachomatis and M. genitalium prevalence was 3.7% and 3.4%, respectively. In multivariable analyses, shared risk factors were younger age (p<0.001, for both C. trachomatis and M. genitalium), socioeconomic disadvantage (p=0.045 and p=0.008, respectively) and coinfection (p<0.001, for both sexually transmitted infections), with 10.1% of C. trachomatis positive women also positive for M. genitalium. Additional risk factors were earlier year of visit (p=0.001) for C. trachomatis and for M. genitalium residing outside a major city (p=0.013). The proportion of M. genitalium infections tested between 2016 and 2019 with macrolide resistance-associated mutations was 32.7%. CONCLUSIONS: Given the high level of antimicrobial resistance and the prevalence of coinfection, testing C. trachomatis positive women for M. genitalium could be considered in this setting to prevent further spread of resistant infections. Further research is required into the causal link between M. genitalium and pelvic inflammatory disease in women undergoing TOP and IUD insertion.

The clinical indications for testing women for Mycoplasma genitalium.

BACKGROUND: While the contribution of Mycoplasma genitalium (MG) to symptoms in men is well described, less is known about its association with common genital symptoms in women. We aimed to determine the prevalence of MG and macrolide resistance, and its association with common genital symptoms in women attending a sexual health service, to inform indications for testing and clinical practice. METHODS: We undertook a cross-sectional study of symptomatic and asymptomatic women attending Melbourne Sexual Health Centre (MSHC), between April 2017 and April 2019. Women were tested for MG and macrolide resistance, Chlamydia trachomatis (CT), Neisseria gonorrhoeae, Trichomonas vaginalis, bacterial vaginosis and vulvovaginal candidiasis. Women completed a questionnaire on symptoms, and symptomatic women underwent examination. The prevalence of MG (and macrolide resistance) and other genital infections was calculated with 95% CIs, and associations between these outcomes and specific genital symptoms were examined using logistic regression. RESULTS: Of 1318 women, 83 (6%, 95% CI: 5% to 8%) had MG, of which 39 (48%, 95% CI: 36% to 59%) had macrolide-resistant MG; 103 (8%, 95% CI: 6% to 9%) women had CT. MG prevalence was similar in asymptomatic (10 of 195; 5%) and symptomatic (73 of 1108; 7%) women, p=0.506. MG was associated with mucopurulent cervicitis on examination (adjusted OR=4.38, 95% CI: 1.69 to 11.33, p=0.002), but was not associated with other specific genital symptoms or signs. CONCLUSIONS: MG was as common as CT among women attending MSHC. MG was not associated with genital symptoms, but like CT, was significantly associated with cervicitis. These data provide evidence that routine testing for MG in women with common genital symptoms is not indicated. The presence of macrolide resistance in 48% of women supports use of resistance-guided therapy.

Positivity and Risk Factors for Trichomonas vaginalis Among Women Attending a Sexual Health Clinic in Melbourne, 2006 to 2019.

BACKGROUND: Trichomonas vaginalis is not a notifiable disease in Australia in most states, resulting in limited Australian epidemiological studies. This study aimed to examine the positivity of T. vaginalis in women attending the Melbourne Sexual Health Centre (MSHC) and identify associated factors. METHODS: All women 16 years or older who were tested for T. vaginalis at MSHC from 2006 to 2019 were included. The diagnostic method changed from culture to nucleic acid amplification test in August 2018. The annual positivity of T. vaginalis was calculated. Because of the data completeness, we performed a generalized estimating equations multivariable logistic regression using data from 2011 to 2019 to examine factors associated with T. vaginalis positivity. RESULTS: From 2006 to 2019, 69,739 tests for T. vaginalis were conducted, and 294 tested positive (0.42%; 95% confidence interval [CI], 0.37%-0.47%). Approximately 60% of women tested reported symptoms. After adjusting for potential confounders including the change in diagnostic method, there was a 21% (95% CI, 12%-31%) annual increase in T. vaginalis positivity between 2011 and 2019. Women with concurrent syphilis had the highest odds of testing positive for T. vaginalis (adjusted odds ratio [aOR], 21.55; 95% CI, 6.96-66.78), followed by women who had injected drugs in the last 12 months (aOR, 6.99; 95% CI, 4.11-11.87), were 35 years or older (aOR, 3.47; 95% CI, 2.26-5.35), or had concurrent chlamydia (aOR, 1.77; 95% CI, 1.05-2.99). CONCLUSIONS: The rising positivity of T. vaginalis at MSHC irrespective of change in diagnostic method suggests a concurrent community-wide rise in Melbourne. Given the rising positivity, testing informed by risk factors should be considered.

Drug and Alcohol Use with Condomless Anal Sex among Men Who Have Sex with Men in Melbourne, Australia: A Retrospective Data Analysis from 2011 to 2017.

Rises in condomless anal sex among men who have sex with men (MSM) have been reported over the last decade but there is less certainty about the role that drugs, alcohol, play in this change. We examined the changes in drug and alcohol use among 22,255 MSM reporting condomless anal sex at Melbourne Sexual Health Centre in 2011-2017. There was a 7% annual increase in using drugs before and/or during condomless anal sex but a 3% annual reduction in condomless anal sex while drunk. MSM taking PrEP were more likely to report condomless anal sex with drug use (AOR: 1.21; 95%CI: 1.07-1.37) and alcohol use (AOR: 1.29; 95%CI: 1.14-1.46) compared with MSM not taking PrEP.

Patterns of Sexual Practices, Sexually Transmitted Infections and Other Genital Infections in Women Who Have Sex with Women Only (WSWO), Women Who Have Sex with Men Only (WSMO) and Women Who Have Sex with Men and Women (WSMW): Findings from a Sexual Health Clinic in Melbourne, Australia, 2011-2019.

Despite rises in sexually transmitted infection (STI) notifications among Australian women in the last decade, limited STI surveillance data exist specifically for women who have sex with women. This study aimed to compare differences in sexual practices and positivity for STIs and other genital infections among women who have sex with men only (WSMO), women who have sex with women only (WSWO), and women who have sex with men and women (WSMW), and whether these changed over time. In this retrospective repeated cross-sectional study, women attending the Melbourne Sexual Health Centre for the first time between 2011 and 2019 were categorized as "WSMW," "WSWO," or "WSMO" according to self-reported sexual practices in the previous 12 months. Demographic information, sexual practices, and positivity for STIs and other genital infections were compared between the three groups and over time. A total of 36,147 women (2618 WSMW, 534 WSWO, and 32,995 WSMO) were included. WSMW reported more sexual partners (median = 6; IQR = 4-10) than WSMO (median = 3; IQR = 2-5) and WSWO (median = 2; IQR = 1-4) (p < .001). A higher proportion of WSMW always used condoms with casual male partners compared to WSMO (20.4% vs 15.9%; p < .001). The proportion of women who always used condoms with casual male partners decreased over time in WSMO, (19.9% in 2011 to 15.2% in 2019, ptrend < .001) but not in WSMW. Bacterial vaginosis was more common in WSWO (14.8%) than in WSMW (11.8%) and WSMO (7.7%) (p < .001). Chlamydia was more common in WSMO (9.3%) than in WSMW (6.6%) and WSWO (1.2%) (p < .001). Syphilis was more common in WSMO (1.0%) than in WSMW (0.3%) and WSWO (0.0%) (p = .004). Over time, chlamydia positivity in WSWO increased (from 0.0% to 2.7%, ptrend = .014), and syphilis positivity in WSMW increased (from 0.0% to 0.7%, ptrend = .028); however, positivity of these STIs did not change in other groups. Sexual practices and positivity for STIs and other genital infections differed according to the sex of women's partners in the previous 12 months. Knowledge of these differences is important to account for future changes in STI trends that may occur in these subpopulations.

Prevalence of bacterial vaginosis in postmenopausal women: a systematic review and meta-analysis.

Bacterial vaginosis (BV), the most common cause of vaginal discharge in women of reproductive age, is associated with considerable reproductive and gynaecological sequelae and increases the risk of acquiring sexually transmissible infections including HIV. Although we understand the burden of BV in women of reproductive age, much less is known about the burden of BV in postmenopausal women. We undertook this systematic review and meta-analysis to estimate the prevalence of BV in postmenopausal women. The electronic databases PubMed, EMBASE, Web of Science, and The Cochrane Library were searched for English-language papers reporting on the prevalence of BV in postmenopausal women and published up until the end of July 2020. Search terms included: (prevalence OR survey OR proportion) AND 'bacterial vaginosis'. Meta-analysis was used to calculate pooled estimates of prevalence. We identified 2461 unique references and assessed 328 full-text articles for eligibility, with 13 studies included in the meta-analysis. The prevalence of BV ranged from 2.0 to 57.1%, with a summary estimate of 16.93% (95% CI: 8.5-27.4; I 2 =97.9). There was considerable heterogeneity between studies and quality varied considerably. Further research is needed to provide a better understanding of the condition in postmenopausal women and understand its effect on their lives.

Are Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum Associated With Specific Genital Symptoms and Clinical Signs in Nonpregnant Women?

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.

Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment.

Bacterial vaginosis (BV) is the most common vaginal dysbiosis to affect women globally, yet an unacceptably high proportion of women experience BV recurrence within 6 months of recommended antibiotic therapy. The low rate of sustained cure highlights our limited understanding of the pathogenesis of BV recurrence, which has been attributed to possible persistence and re-emergence of BV-associated bacteria (BVAB) or a BV-associated biofilm following antimicrobials and/or reinfection occurring from sexual partners.There is a robust body of evidence to support the exchange of bacteria between partners during sexual activity, and while the hypothesis that women treated for BV are subsequently reinfected with BVAB following sex with an untreated sexual partner is not new, failure of past partner treatment trials has eroded confidence in this concept. If reinfection is a key driver of recurrence, current antimicrobial regimens directed to women alone are unlikely to achieve a high level of sustained cure, and the approach of partner treatment to reduce reinfection is justified. In this manuscript, we present the molecular and epidemiological evidence that underlies the hypothesis that BV is sexually transmitted, and summarise why research that continues to consider sexual partnerships is necessary. We also outline the significant barriers and challenges that we have identified while undertaking partner treatment studies, and we discuss the factors that impact on our ability to determine their effectiveness.Ultimately, the pathogenesis of BV recurrence is likely to be multifaceted and not attributable to a single mechanism in all women. If we are to achieve sustained cure for women, it is likely that combined and individualised approaches to eradicate BVAB, support an optimal vaginal microbiome, and prevent reinfection from partners will be required.

Incidence and duration of incident oropharyngeal gonorrhoea and chlamydia infections among men who have sex with men: prospective cohort study.

OBJECTIVES: This prospective cohort study aimed to determine the natural history and incidence of oropharyngeal gonorrhoea and chlamydia among a cohort of men who have sex with men (MSM) over a 12-week period, and to examine risk factors associated with incident oropharyngeal infections. METHODS: MSM either aged ≥18 years and had a diagnosis of oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the past 3 months or aged 18-35 years who were HIV-negative taking pre-exposure prophylaxis (PrEP) were eligible for this study. Enrolled men were followed up for 12 weeks. Oropharyngeal swabs were collected at week 0 (baseline) and week 12 (end of study). Between these time points, weekly saliva specimens and the number of tongue kissing, penile-oral and insertive rimming partners were collected by post. Oropharyngeal swabs and saliva specimens were tested by NAAT for Neisseria gonorrhoeae and Chlamydia trachomatis. Poisson regression was performed to examine the risk factors (weekly number of partners) associated with incident oropharyngeal gonorrhoea. RESULTS: A total of 100 MSM were recruited. The incidence of oropharyngeal gonorrhoea and chlamydia was 62 (95% CI 37 to 105) and 9 (95% CI 2 to 35)/100 person-years, respectively. The median duration of incident oropharyngeal infection with gonorrhoea was 28 days (IQR=21-36, n=7). The incidence rate ratio (IRR) for oropharyngeal gonorrhoea increased with an increased number of kissing partners (IRR=1.08; 95% CI 1.03 to 1.12) an increased number of penile-oral sex partners (IRR=1.07, 95% CI 1.01 to 1.14) but not with an increased number of insertive rimming partners (IRR=1.11, 95% CI 0.96 to 1.29) or other demographic factors. The IRR and duration of incident oropharyngeal chlamydia were not calculated due to the small number of cases (n=2). CONCLUSIONS: MSM have a high incidence of oropharyngeal gonorrhoea and the median duration of infection was less than 3 months.

Gardnerella vaginalis Clade Distribution Is Associated With Behavioral Practices and Nugent Score in Women Who Have Sex With Women.

BACKGROUND: Gardnerella vaginalis is detected in women with and without bacterial vaginosis (BV). Identification of 4 G. vaginalis clades raised the possibility that pathogenic and commensal clades exist. We investigated the association of behavioral practices and Nugent Score with G. vaginalis clade distribution in women who have sex with women (WSW). METHODS: Longitudinal self-collected vaginal specimens were analyzed using established G. vaginalis species-specific and clade-typing polymerase chain reaction assays. Logistic regression assessed factors associated with detection of G. vaginalis clades, and multinomial regression assessed factors associated with number of clades. RESULTS: Clades 1, 2, and 3 and multiclade communities (<2 clades) were associated with Nugent-BV. Clade 1 (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.65-6.84) and multiclade communities (relative risk ratio [RRR], 9.51; 95% CI, 4.36-20.73) were also associated with Lactobacillus-deficient vaginal microbiota. Clade 4 was neither associated with Nugent-BV nor Lactobacillus-deficient microbiota (OR, 1.49; 95% CI, 0.67-3.33). Specific clades were associated with differing behavioral practices. Clade 1 was associated with increasing number of recent sexual partners and smoking, whereas clade 2 was associated with penile-vaginal sex and sharing of sex toys with female partners. CONCLUSIONS: Our results suggest that G. vaginalis clades have varying levels of pathogenicity in WSW, with acquisition occurring through sexual activity. These findings suggest that partner treatment may be an appropriate strategy to improve BV cure.

Resistance-Guided Antimicrobial Therapy Using Doxycycline-Moxifloxacin and Doxycycline-2.5 g Azithromycin for the Treatment of Mycoplasma genitalium Infection: Efficacy and Tolerability.

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.