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Antimicrobial resistance in the sexually transmitted bacterium Neisseria gonorrhoeae is compromising the management and control of gonorrhea globally. Optimized use and enhanced stewardship of current antimicrobials and development of novel antimicrobials are imperative. The first in class zoliflodacin (spiropyrimidinetrione, DNA Gyrase B inhibitor) is a promising novel antimicrobial in late-stage clinical development for gonorrhea treatment, i.e., the phase III randomized controlled clinical trial (ClinicalTrials.gov Identifier: NCT03959527) was recently finalized, and zoliflodacin showed non-inferiority compared to the recommended ceftriaxone plus azithromycin dual therapy. Doxycycline, the first-line treatment for chlamydia and empiric treatment for non-gonococcal urethritis, will be frequently given together with zoliflodacin because gonorrhea and chlamydia coinfections are common. In a previous static in vitro study, it was indicated that doxycycline/tetracycline inhibited the gonococcal killing of zoliflodacin in 6-h time-kill curve analysis. In this study, our dynamic in vitro hollow-fiber infection model (HFIM) was used to investigate combination therapies with zoliflodacin and doxycycline. Dose-range experiments using the three gonococcal strains WHO F (susceptible to relevant therapeutic antimicrobials), WHO X (extensively drug-resistant, including ceftriaxone-resistant; zoliflodacin-susceptible), and SE600/18 (zoliflodacinsusceptible strain with GyrB S467N substitution) were conducted simulating combination therapy with a single oral dose of zoliflodacin 0.5-4 g combined with a doxycycline daily oral dose of 200 mg administered as 100 mg twice a day, for 7 days (standard dose for chlamydia treatment). Comparing combination therapy of zoliflodacin (0.5-4 g single dose) plus doxycycline (200 mg divided into 100 mg twice a day orally, for 7 days) to zoliflodacin monotherapy (0.5-4 g single dose) showed that combination therapy was slightly more effective than monotherapy in the killing of N. gonorrhoeae and suppressing emergence of zoliflodacin resistance. Accordingly, WHO F was eradicated by only 0.5 g single dose of zoliflodacin in combination with doxycycline, and WHO X and SE600/18 were both eradicated by a 2 g single dose of zoliflodacin in combination with doxycycline; no zoliflodacin-resistant populations occurred during the 7-day experiment when using this zoliflodacin dose. When using suboptimal (0.5-1 g) zoliflodacin doses together with doxycycline, gonococcal mutants with increased zoliflodacin MICs, due to GyrB D429N and the novel GyrB T472P, emerged, but both the mutants had an impaired biofitness. The present study shows the high efficacy of zoliflodacin plus doxycycline combination therapy using a dynamic HFIM that more accurately and comprehensively simulate gonococcal infection and their treatment, i.e., compared to static in vitro models, such as short-time checkerboard experiments or time-kill curve analysis. Based on our dynamic in vitro HFIM work, zoliflodacin plus doxycycline for the treatment of both gonorrhea and chlamydia can be an effective combination. [ABSTRACT FROM AUTHOR]

Rectal lymphogranuloma venereum (LGV) has reemerged as a sexually transmitted infection among men who have sex with men (MSM), particularly those who are HIV-positive. We undertook a systematic review and meta-analysis to determine the efficacy of doxycycline (100 mg 2×/d for 21 days) for rectal LGV in MSM. Nine studies were included: 4 prospective, 4 retrospective, and 1 combined retrospective and prospective. In total, 282 MSM with rectal LGV were included in the studies. All studies reported using nucleic acid amplification tests to assess microbial cure. Most patients (>80%) had symptomatic rectal infection. The fixed-effects pooled efficacy for doxycycline was 98.5% (95% CI 96.3%-100%, I (2)  = 0%; p = 0.993). Doxycycline at 100 mg twice daily for 21 days demonstrated a high microbial cure rate. These data support doxycycline at this dosage and duration as first-line therapy for rectal LGV in MSM. [ABSTRACT FROM AUTHOR]

Background: Single-dose azithromycin is recommended over multi-dose doxycycline as treatment for chlamydial infection. However, even with imperfect adherence, doxycycline is more effective in treating genital and rectal infection. Recently, it has been suggested that autoinoculation from the rectum to the genitals may be a source of persistent chlamydial infection in women. We estimated the impact autoinoculation may have on azithromycin and doxycycline effectiveness. Methods: We estimate treatment effectiveness using a simple mathematical model, incorporating data on azithromycin and doxycycline efficacy from recent meta-analyses, and data on prevalence of rectal infection in women with genital chlamydial infection. Results: When the possibility of autoinoculation is taken into account, we calculate that doxycycline effectiveness may be 97% compared to just 82% for azithromycin. Conclusions: Consideration should be given to re-evaluating azithromycin as the standard treatment for genital chlamydia in women. [ABSTRACT FROM AUTHOR]

Background: Chlamydia trachomatis is the most common notifiable disease in Australia, mainly affecting those aged 15 to 29 years. Testing rates are low in Australia and considerably lower in rural areas, with access and confidentiality of sexual health services being problematic in rural and regional areas. This study aimed to determine the feasibility of establishing a pilot chlamydia testing outreach program among 16-25 year old males and females in rural Victoria (Australia) undertaken at local sporting clubs and to determine the prevalence of chlamydia and acceptability of the program in this population. Methods: We aimed to recruit young people from the Loddon Mallee region of Victoria, Australia between May and September 2007. After a night of sporting practice, participants provided a first pass urine sample, completed a brief questionnaire regarding risk taking behaviour and were then provided with condoms and health promotion materials about sexually transmitted infections (STIs). Those positive for chlamydia were managed by telephone consultation with a practitioner from Melbourne Sexual Health Centre. Results: A total of 709 young people participated (77% male, 23% female), 77% being sexually active. All provided a urine sample and completed the questionnaire. Participation rate on recruitment nights was over 95%. Overall chlamydia prevalence in those sexually active was 5.1% (95%CI: 3.4-7.3), 7.4% in females (95%CI: 3.5-13.6) and 4.5% in males (95%CI: 2.7-6.9). Conclusion: Sporting clubs represent a feasible, acceptable and innovative community based setting to screen, treat and educate young people in a rural and regional setting, especially for males. [ABSTRACT FROM AUTHOR]

Introduction: Neisseria gonorrhoeae infections are common and incidence increasing. Oropharyngeal infections are associated with greater treatment failure compared with other sites and drive transmission to anogenital sites through saliva. Gonococcal resistance is increasing and new treatments are scarce, therefore, clinicians must optimise currently available and emerging treatments in order to have efficacious therapeutic options. This requires pharmacokinetic data from the oral cavity/oropharynx, however, availability of such information is currently limited., Methods and Analysis: Healthy male volunteers (participants) recruited into the study will receive single doses of either ceftriaxone 1 g, cefixime 400 mg or ceftriaxone 500 mg plus 2 g azithromycin. Participants will provide samples at 6-8 time points (treatment regimen dependent) from four oral sites, two oral fluids, one anorectal swab and blood. Participants will complete online questionnaires about their medical history, sexual practices and any side effects experienced up to days 5-7. Saliva/oral mucosal pH and oral microbiome analysis will be undertaken. Bioanalysis will be conducted by liquid chromatography-mass spectrometry. Drug concentrations over time will be used to develop mathematical models for optimisation of drug dosing regimens and to estimate pharmacodynamic targets of efficacy., Ethics and Dissemination: This study was approved by Royal Melbourne Hospital Human Research Ethics Committee (60370/MH-2021). The study results will be submitted for publication in peer-reviewed journals and reported at conferences. Summary results will be sent to participants requesting them. All data relevant to the study will be included in the article or uploaded as supplementary information., Trial Registration Number: ACTRN12621000339853., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Our aim was to determine whether exposure to the anatomical sites (oropharynx, penis, or anus) of male partners of men who have sex with men (MSM) were independent risk factors for oropharyngeal gonorrhoea after adjusting for exposures to these sites., Methods: In this cross-sectional study, we invited MSM who attended the Melbourne Sexual Health Centre (MSHC) in Victoria, Australia between 26-November 2018 and 31-December 2020 to complete a survey of their sexual practices in the past three months. We collected data on the number of male partners with whom men engaged in sexual activities that exposed their oropharynx to their partners' oropharynx (kissing), penis (fellatio), and anus (rimming or analingus). Only men who were aged ≥ 16 years, tested for oropharyngeal gonorrhoea and did not have indeterminate or invalid results were included in the final analysis. We conducted univariable and multivariable logistic regression analyses to investigate associations between oropharyngeal gonorrhoea and the three exposures to the oropharynx., Findings: The median age of the 2,322 men who completed the survey was 31 years (IQR: 26-40), and 5·2% ( n = 120) were diagnosed with oropharyngeal gonorrhoea. Our univariate analysis showed that oropharyngeal gonorrhoea was significantly associated with increasing number of kissing ( p trend <0·0001), rimming ( p trend <0·0001) and fellatio ( p trend <0·0001) partners. After adjusting for all three exposures, oropharyngeal gonorrhoea was associated with increasing number of kissing ( p trend = 0·014) and rimming partners ( p trend = 0·037) but not fellatio ( p trend = 0·61)., Interpretation: Our data suggest kissing and rimming are important practices in oropharyngeal gonorrhoea transmission in MSM Novel interventions which target the oropharynx are required for gonorrohoea prevention., Funding: Australian National Health and Medical Research Council., Competing Interests: EPFC are JJO are each supported by an Australian National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grant (GNT1172873 for EPFC and GNT1193955 for JJO). CKF and CSB are supported by an Australian NHMRC Leadership Investigator Grant (GNT1172900 for CKF and GNT1173361 for CSB). JSH is supported by an NHMRC Senior Research Fellowship (GNT1136117). ETA is supported by Australian Government Research Training Program (RTP) scholarship from Monash University and Research Entry Scholarship from the Chapter of Sexual Health Medicine, Royal Australasian College of Physician. JT is supported by Australian Government Research Training Program (RTP) Scholarship from Monash University. All other authors declare no competing interests., (© 2022 The Author(s).)

Background: The resumption of sexual activity shortly after commencing treatment for sexually transmitted infections (STIs) is poorly described despite contributing to onward transmission. With azithromycin remaining an option for rectal Chlamydia trachomatis, resuming sex too early after treatment may contribute to antimicrobial resistance because of exposure of newly acquired STIs to subinhibitory concentrations., Methods: Clinical and sexual behavioral data were collected from men participating in a trial assessing treatment efficacy for rectal chlamydia. Data were collected at recruitment and weekly for 3 weeks after commencing treatment. Outcome measures were resumption of any sexual activity or condomless receptive anal sex within 1, 2, or 3 weeks after commencing treatment. Generalized linear regression was used to calculate adjusted risk ratios (aRR) to identify associated factors., Results: Almost 1 in 10 men (9.5%; 95% confidence interval [CI], 7.2-12.1) resumed condomless receptive anal sex within 1 week of commencing treatment. This was associated with current preexposure prophylaxis use (aRR, 3.4; 95% CI, 2.5-4.8]) and having 9 or more sexual partners in the last 3 months (aRR, 3.2; 95% CI, 1.6-5.0). Most men (75.0%; 95% CI, 71.3-78.5) resumed any sexual activity within 3 weeks; this was associated with a greater number of sexual partners (4-8 partners; aRR, 1.2; 95% CI, 1.1-1.5; ≥9 partners; aRR, 1.5; 95% CI, 1.3-1.7)., Conclusions: Resuming condomless receptive anal sex early after treatment may facilitate onward transmission and promote antimicrobial resistance for STIs. Although azithromycin remains a treatment option, this analysis highlights the need for new health promotion messages regarding early resumption of sex and continued surveillance for antimicrobial resistance.