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Journal ArticleDOI: 10.1016/S1473-3099(20)30704-0

Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial

04 Mar 2021-Lancet Infectious Diseases (Elsevier)-Vol. 21, Iss: 5, pp 647-656
Abstract: Summary Background To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotene mouthwashes for preventing gonorrhoea among men who have sex with men (MSM). Methods The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16–24 years. They were randomly assigned to receive Listerine (intervention) or Biotene (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471). Findings Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotene group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotene group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotene group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI −1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI −1·4 to 7·7). Interpretation Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotene. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission. Funding Australian National Health and Medical Research Council.

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Topics: Population (51%)

11 results found

Open accessJournal ArticleDOI: 10.1038/S41598-020-76184-1
Eric P F Chow1, Eric P F Chow2, Kate Maddaford, Jane S Hocking2  +7 moreInstitutions (3)
09 Nov 2020-Scientific Reports
Abstract: New treatments for oropharyngeal gonorrhoea are required to address rising antimicrobial resistance. We aimed to examine the efficacy of a 14-day course of mouthwash twice daily compared to standard treatment (antibiotic) for the treatment of oropharyngeal gonorrhoea. The OMEGA2 trial was a parallel-group and open-labelled randomised controlled trial among men with untreated oropharyngeal gonorrhoea that was conducted between September 2018 and February 2020 at Melbourne Sexual Health Centre in Australia. Men were randomised to the intervention (rinsing, gargling and spraying mouthwash twice daily for 14 days) or control (standard treatment) arm and followed for 28 days. Participants in both arms were advised to abstain from sex and kissing with anyone for 14 days after enrolment. Oropharyngeal swabs were collected at baseline, Day 14 and Day 28 and tested for Neisseria gonorrhoeae by nucleic acid amplification test (NAAT) and culture. The primary outcome was the detection of oropharyngeal N. gonorrhoeae by NAAT at Day 14 after treatment. This trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12618001380280). This trial stopped early due to a high failure rate in the mouthwash arm. Twelve men were randomly assigned to either mouthwash (n = 6) or standard treatment (n = 6). Of the 11 men who returned at Day 14, the cure rate for oropharyngeal gonorrhoea in the mouthwash arm was 20% (95% CI 1-72%; 1/5) and in the standard treatment arm was 100% (95% CI 54-100%; 6/6). A 14-day course of mouthwash failed to cure a high proportion of oropharyngeal gonorrhoea cases.

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Topics: Standard treatment (54%)

9 Citations

Journal ArticleDOI: 10.1016/S1473-3099(20)30778-7
Abstract: BACKGROUND: Bacterial sexually transmitted infections (STIs) are highly prevalent among men who have sex with men who use HIV pre-exposure prophylaxis (PrEP), which leads to antimicrobial consumption linked to the emergence of antimicrobial resistance. We aimed to assess use of an antiseptic mouthwash as an antibiotic sparing approach to prevent STIs. METHODS: We invited people using PrEP who had an STI in the past 24 months to participate in this single-centre, randomised, double-blind, placebo-controlled, AB/BA crossover superiority trial at the Institute of Tropical Medicine in Antwerp, Belgium. Using block randomisation (block size eight), participants were assigned (1:1) to first receive Listerine Cool Mint or a placebo mouthwash. They were required to use the study mouthwashes daily and before and after sex for 3 months each and to ask their sexual partners to use the mouthwash before and after sex. Participants were screened every 3 months for syphilis, chlamydia, and gonorrhoea at the oropharynx, anorectum, and urethra. The primary outcome was combined incidence of these STIs during each 3-month period, assessed in the intention-to-treat population, which included all participants who completed at least the first 3-month period. Safety was assessed as a secondary outcome. This trial is registered with, NCT03881007. FINDINGS: Between April 2, 2019, and March 13, 2020, 343 participants were enrolled: 172 in the Listerine followed by placebo (Listerine-placebo) group and 171 in the placebo followed by Listerine (placebo-Listerine) group. The trial was terminated prematurely because of the COVID-19 pandemic. 151 participants completed the entire study, and 89 completed only the first 3-month period. 31 participants withdrew consent, ten were lost to follow-up, and one acquired HIV. In the Listerine-placebo group, the STI incidence rate was 140·4 per 100 person-years during the Listerine period, and 102·6 per 100 person-years during the placebo period. In the placebo-Listerine arm, the STI incidence rate was 133·9 per 100 person-years during the placebo period, and 147·5 per 100 person-years during the Listerine period. We did not find that Listerine significantly reduced STI incidence (IRR 1·17, 95% CI 0·84-1·64). Numbers of adverse events were not significantly higher than at baseline and were similar while using Listerine and placebo. Four serious adverse events (one HIV-infection, one severe depression, one Ludwig's angina, and one testicular carcinoma) were not considered to be related to use of mouthwash. INTERPRETATION: Our findings do not support the use of Listerine Cool Mint as a way to prevent STI acquisition among high-risk populations. FUNDING: Belgian Research Foundation - Flanders (FWO 121·00).

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Topics: Men who have sex with men (52%), Population (51%)

7 Citations

Open accessJournal ArticleDOI: 10.3390/ANTIBIOTICS10020103
21 Jan 2021-Antibiotics
Abstract: While antimicrobial resistance (AMR) is seen in both Neisseria gonorrhoeae and Neisseria meningitidis, the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways leading to the development of AMR. This review highlights the growing research interest in developing anti-virulence therapies (AVTs) which are directed towards inhibiting virulence factors to prevent infection. By targeting virulence factors that are not essential for gonococcal survival, it is hypothesized that this will impart a smaller selective pressure for the emergence of resistance in the pathogen and in the microbiome, thus avoiding AMR development to the anti-infective. This review summates the current basis of numerous anti-virulence strategies being explored for N. gonorrhoeae.

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Topics: Neisseria gonorrhoeae (51%)

1 Citations

Journal ArticleDOI: 10.1097/QCO.0000000000000793
Abstract: PURPOSE OF REVIEW Antimicrobial resistance in sexually acquired infection (STI) pathogens is an important global public health threat. There is an urgent need for novel STI treatment and prevention strategies to tackle the rising incidence of STIs in high-income settings and the static progress in low- and middle-income settings over the past decade. The purpose of this review was to describe the research outlining the emergence of resistance in common STI pathogens and new strategies for their treatment and prevention. RECENT FINDINGS Rates of STIs have dramatically increased over the past decade. Further, antimicrobial resistance to first-line agents among key STI pathogens continues to emerge globally. Recent findings demonstrate promising results regarding the efficacy of novel antimicrobial treatment strategies for these pathogens, including several new, repurposed and unique combinations of antimicrobials. In addition, a number of new biomedical prevention strategies, such as antibacterial mouthwash and doxycycline chemoprophylaxis, are being investigated as novel prevention strategies for bacterial STIs. SUMMARY Significant progress has been made in the development of novel antimicrobials for the treatment of antimicrobial-resistant sexually acquired pathogens. However, due to the rapid development of resistance to antimicrobials demonstrated by these pathogens in the past, further research and development of effective prevention strategies should be prioritized.

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Topics: Antibiotic resistance (51%)

Open accessJournal ArticleDOI: 10.3389/FMICB.2021.776909
Abstract: Objectives Chlorhexidine digluconate (chlorhexidine) and Listerine mouthwashes are being promoted as alternative treatment options to prevent the emergence of antimicrobial resistance in Neisseria gonorrhoeae. We performed in vitro challenge experiments to assess induction and evolution of resistance to these two mouthwashes and potential cross-resistance to other antimicrobials. Methods A customized morbidostat was used to subject N. gonorrhoeae reference strain WHO-F to dynamically sustained Listerine or chlorhexidine pressure for 18 days and 40 days, respectively. Cultures were sampled twice a week and minimal inhibitory concentrations (MICs) of Listerine, chlorhexidine, ceftriaxone, ciprofloxacin, cefixime and azithromycin were determined using the agar dilution method. Isolates with an increased MIC for Listerine or chlorhexidine were subjected to whole genome sequencing to track the evolution of resistance. Results We were unable to increase MICs for Listerine. Three out of five cultures developed a 10-fold increase in chlorhexidine MIC within 40 days compared to baseline (from 2 to 20 mg/L). Increases in chlorhexidine MIC were positively associated with increases in the MICs of azithromycin and ciprofloxacin. Low-to-higher-level chlorhexidine resistance (2-20 mg/L) was associated with mutations in NorM. Higher-level resistance (20 mg/L) was temporally associated with mutations upstream of the MtrCDE efflux pump repressor (mtrR) and the mlaA gene, part of the maintenance of lipid asymmetry (Mla) system. Conclusions Exposure to sub-lethal chlorhexidine concentrations may not only enhance resistance to chlorhexidine itself but also cross-resistance to other antibiotics in N. gonorrhoeae. This raises concern regarding the widespread use of chlorhexidine as an oral antiseptic, for example in the field of dentistry.

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Topics: Chlorhexidine (58%)


29 results found

Open accessJournal ArticleDOI: 10.1093/AJE/KWP440
Abstract: There is increasing interest in estimating and drawing inferences about risk or prevalence ratios and differences instead of odds ratios in the regression setting. Recent publications have shown how the GENMOD procedure in SAS (SAS Institute Inc., Cary, North Carolina) can be used to estimate these parameters in non-population-based studies. In this paper, the authors show how model-adjusted risks, risk differences, and risk ratio estimates can be obtained directly from logistic regression models in the complex sample survey setting to yield population-based inferences. Complex sample survey designs typically involve some combination of weighting, stratification, multistage sampling, clustering, and perhaps finite population adjustments. Point estimates of model-adjusted risks, risk differences, and risk ratios are obtained from average marginal predictions in the fitted logistic regression model. The model can contain both continuous and categorical covariates, as well as interaction terms. The authors use the SUDAAN software package (Research Triangle Institute, Research Triangle Park, North Carolina) to obtain point estimates, standard errors (via linearization or a replication method), confidence intervals, and P values for the parameters and contrasts of interest. Data from the 2006 National Health Interview Survey are used to illustrate these concepts.

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Topics: Survey sampling (55%), Logistic regression (53%), Population (53%) ... read more

352 Citations

Open accessJournal ArticleDOI: 10.1016/S1473-3099(17)30310-9
Abstract: WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

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Topics: Pelvic inflammatory disease (53%), Bacterial vaginosis (52%), Sexual transmission (52%) ... read more

350 Citations

Open accessJournal ArticleDOI: 10.1177/1536867X1301300304
01 Sep 2013-Stata Journal
Abstract: In this article, we explain how to calculate adjusted risk ratios and risk differences when reporting results from logit, probit, and related nonlinear models. Building on Stata�s margins command, we create a new postestimation command, adjrr, that calculates adjusted risk ratios and adjusted risk differences after running a logit or probit model with a binary, a multinomial, or an ordered outcome. adjrr reports the point estimates, delta-method standard errors, and 95% confidence intervals and can compute these for specific values of the variable of interest. It automatically adjusts for complex survey design as in the fit model. Data from the Medical Expenditure Panel Survey and the National Health and Nutrition Examination Survey are used to illustrate multiple applications of the command.

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Topics: Logit (56%), Probit model (56%), Probit (55%) ... read more

153 Citations

Journal ArticleDOI: 10.1016/S2352-3018(18)30072-9
Martin Holt1, Toby Lea1, Toby Lea2, Limin Mao1  +11 moreInstitutions (5)
01 Aug 2018-The Lancet HIV
Abstract: Summary Background Pre-exposure prophylaxis (PrEP) has been rapidly rolled out in large, publicly funded implementation projects in Victoria and New South Wales, Australia. Using behavioural surveillance of gay and bisexual men, we analysed the uptake and effect of PrEP, particularly on condom use by gay and bisexual men not using PrEP. Methods We collected data from the Melbourne and Sydney Gay Community Periodic Surveys (GCPS), cross-sectional surveys of adult gay and bisexual men in Melbourne, VIC, and Sydney, NSW. Recruitment occurred at gay venues or events and online. Eligible participants were 18 years or older (face-to-face recruitment) or 16 years or older (online recruitment), identified as male (including transgender participants who identified as male); and having had sex with a man in the past 5 years or identified as gay or bisexual, or both. Using multivariate logistic regression, we assessed trends in condom use, condomless anal intercourse with casual partners (CAIC), and PrEP use by gay and bisexual men, controlling for sample variation over time. Findings Between Jan 1, 2013, and March 31, 2017, 27 011 participants completed questionnaires in the Melbourne (n=13 051) and Sydney (n=13 960) GCPS. 16 827 reported sex with casual male partners in the 6 months before survey and were included in these analyses. In 2013, 26 (1%) of 2692 men reported CAIC and were HIV-negative and using PrEP, compared with 167 (5%) of 3660 men in 2016 and 652 (16%) of 4018 men in 2017 (p Interpretation A rapid increase in PrEP use by gay and bisexual men in Melbourne and Sydney was accompanied by an equally rapid decrease in consistent condom use. Other jurisdictions should consider the potential for community-level increases in CAIC when modelling the introduction of PrEP and in monitoring its effect. Funding Australian Government Department of Health, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

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Topics: Homosexuality (52%), Condom (50%)

102 Citations

Open accessJournal ArticleDOI: 10.1071/SH19023
Magnus Unemo1, Monica M Lahra1, Michelle J Cole2, P Galarza3  +6 moreInstitutions (7)
23 Aug 2019-Sexual Health
Abstract: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious public health problem, compromising the management and control of gonorrhoea globally. Resistance in N. gonorrhoeae to ceftriaxone, the last option for first-line empirical monotherapy of gonorrhoea, has been reported from many countries globally, and sporadic failures to cure especially pharyngeal gonorrhoea with ceftriaxone monotherapy and dual antimicrobial therapies (ceftriaxone plus azithromycin or doxycycline) have been confirmed in several countries. In 2018, the first gonococcal isolates with ceftriaxone resistance plus high-level azithromycin resistance were identified in England and Australia. The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Program (GASP) is essential to monitor AMR trends, identify emerging AMR and provide evidence for refinements of treatment guidelines and public health policy globally. Herein we describe the WHO GASP data from 67 countries in 2015–16, confirmed gonorrhoea treatment failures with ceftriaxone with or without azithromycin or doxycycline, and international collaborative actions and research efforts essential for the effective management and control of gonorrhoea. In most countries, resistance to ciprofloxacin is exceedingly high, azithromycin resistance is present and decreased susceptibility or resistance to ceftriaxone has emerged. Enhanced global collaborative actions are crucial for the control of gonorrhoea, including improved prevention, early diagnosis, treatment of index patient and partner (including test-of-cure), improved and expanded AMR surveillance (including surveillance of antimicrobial use and treatment failures), increased knowledge of correct antimicrobial use and the pharmacokinetics and pharmacodynamics of antimicrobials and effective drug regulations and prescription policies (including antimicrobial stewardship). Ultimately, rapid, accurate and affordable point-of-care diagnostic tests (ideally also predicting AMR and/or susceptibility), new therapeutic antimicrobials and, the only sustainable solution, gonococcal vaccine(s) are imperative.

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Topics: Antimicrobial stewardship (56%), Antibiotic resistance (53%), Gonorrhea (51%) ... read more

83 Citations