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 2.5g-azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance. Methods Patients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded. Results A total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4% (95% CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0%(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% (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22% of macrolide-resistant cases at baseline. Conclusion These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.

Background The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. Methods To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 failures) or doxycycline-sitafloxacin (126 patients, including 13 failures). Results The parC G248T/S83I mutation was more common among patients who failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, p<0.001) and doxycycline-sitafloxacin (50% failures vs 16.8% cures, p = 0.014). Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the ParC S83I mutation. Infections with a ParC S83I were more likely to fail treatment with a concurrent gyrA mutation (M95I or D99N) (for doxycycline- moxifloxacin group p = 0.067, for doxycycline-sitafloxacin group p = 0.0093), suggesting an additive effect. Conclusions This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae at the pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Combining the three individual-site samples into a single pooled sample could result in significant cost savings, provided there is no significant sensitivity reduction. The aim of this study was to examine the sensitivity of pooled samples for detecting chlamydia and gonorrhea in asymptomatic MSM using a nucleic acid amplification test. Asymptomatic MSM who tested positive for chlamydia or gonorrhoea were invited to participate. Paired samples were obtained from participants prior to administration of treatment. To form the pooled sample, the anorectal swab was agitated in the urine specimen transport tube and then discarded. The pharyngeal swab and 2 ml of urine sample were then added to the tube. The difference in sensitivity between testing of pooled samples and individual-site testing was calculated against an expanded gold standard, where an individual is considered positive if either pooled-sample or individual-site testing returns a positive result. All samples were tested using the Aptima Combo 2 assay. A total of 162 MSM were enrolled in the study. Sensitivities of pooled-sample testing were 86% (94/109; 95% confidence interval [CI], 79 to 92%]) for chlamydia and 91% (73/80; 95% CI, 83 to 96%) for gonorrhea. The sensitivity reduction was significant for chlamydia (P = 0.02) but not for gonorrhea (P = 0.34). Pooling caused 22 infections (15 chlamydia and 7 gonorrhoea) to be missed, and the majority were single-site infections (19/22). Pooling urogenital and extragenital samples from asymptomatic MSM reduced the sensitivity of detection by approximately 10% for chlamydia but not for gonorrhea.

M ycoplasma genitalium is a sexually transmitted bacterium with marked capacity for developing antimicrobial resistance (1). Macrolides and 4th-generation fluroquinolones, such as moxifloxacin, have been the main agents displaying efficacy against M. genitalium. However, macrolide resistance has increased to >50% in many nations, and quinolone resistance is increasing (2-6). In Australia, 16% of M. genitalium strains are reported to have dual-class resistance (5), and Japan reports dual-class resistance of up to 25% (2), resulting in infections that often cannot be cured with current recommended therapies. Sequential monotherapy with doxycycline followed by moxifloxacin (7-9) is currently first-line therapy for macrolide-resistant M. genitalium in guidelines in Australia and the United Kingdom and achieves cure in 92% of cases (95% CI 88.1%-94.6%

ObjectivesReports of rising herpes simplex virus type 1 (HSV-1) genital infections relative to HSV-2 have been published up to 2006 in Australia. These changes have been attributed to declining childhood immunity to HSV-1. We described the temporal trends of HSV-1 and HSV-2 up to 2017 in Melbourne, Australia, to determine if the earlier trend is continuing.MethodsWe conducted a retrospective review of the medical records of 4517 patients who were diagnosed with first episode of anogenital HSV infection at the Melbourne Sexual Health Centre, Australia, between January 2004 and December 2017. HSV-1 and HSV-2 were calculated as a proportion of all first episode of anogenital HSV infections. The change in the proportions of HSV-1 and HSV-2 over time was assessed by a χ2 trend test. Risk factors associated with HSV-1 were examined using a multivariable logistic regression model.ResultsThe proportion of first episode of anogenital herpes due to HSV-1 increased significantly over time in women (from 45% to 61%; ptrend<0.001) and heterosexual men (from 38% to 41%; ptrend=0.01) but not in men who have sex with men (MSM) (ptrend=0.21). After adjusting for condom use, partner number and age, the annual increase remained significant only in women (OR 1.08, 95% CI 1.03 to 1.13, p<0.001). In MSM, HSV-1 caused up to two-thirds of anogenital herpes in most years and HSV-1 was more likely to be diagnosed at an anal site than genital site (OR 1.69, 95% CI 1.23 to 2.32, p<0.001). Younger age (<28 years) was an independent risk factor for HSV-1 in all groups.ConclusionsThe proportion of first-episode anogenital herpes due to HSV-1 has been rising in women since 2004. HSV-1 has become the leading cause of anogenital herpes in younger populations, women and MSM.

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caused by masturbation from 3.9% (95%CI 2.0 to 6.8) to 7.8% (95%CI 4.3 to 15.6) which was primarily due to solo masturbation (estimates of 3.5% (95%CI 1.7 to 6.1) to 7.1% (95%CI 4.0 to 13.1)) with little contribution from partnered masturbation (estimates of 0.3% (95%CI 0.0 to 1.5) to 0.7% (95%CI 0.1 to 4.0)). Conclusions Our model suggests that saliva use as a lubricant for solo/partnered masturbation plays a negligible a role in chlamydia transmission in MSM.

Men who have sex with men (MSM) living with HIV have a high prevalence and incidence of anal high-risk human papillomavirus (hrHPV) and anal cancer. We conducted an open-label, single-arm pilot study to examine the tolerability of imiquimod cream among MSM aged ≥18 years, living with HIV, who tested positive for anal hrHPV at Melbourne Sexual Health Centre between April 2018 and June 2020. We instructed men to apply 6.25 mg imiquimod intra-anally and peri-anally 3 doses per week for 16 weeks (period 1) and then one dose per week for a further 48 weeks (period 2). Twenty-seven MSM enrolled in period 1 and 24 (86%) applied at least 50% of doses. All men reported adverse events (AEs), including 39.5% grade 1, 39.5% grade 2, and 21% grade 3 AEs on at least one occasion. Eighteen MSM (67%) temporarily stopped using imiquimod during period 1, most commonly due to local AEs (n = 11) such as irritation and itching. Eighteen MSM continued in period 2 and all applied at least 50% of doses with no treatment-limiting AEs reported. Imiquimod 3 doses per week caused local AEs in most men and was not well tolerated. In contrast, once-a-week application was well tolerated over 48-weeks with no treatment-limiting AEs.