Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

STI pathogens in the oropharynx: update on screening and treatment.

PURPOSE OF REVIEW: The rise in antimicrobial resistance in several STI pathogens such as Neisseria gonorrhoeae has become a public health threat as only one first-line treatment remains. Reducing screening interval for gonorrhoea and chlamydia in high-prevalence populations has been proposed to address antimicrobial stewardship, but this remains controversial. This review aimed to revisit the epidemiology of infections at the oropharynx and review the current screening recommendations and treatment guidelines in different populations. RECENT FINDINGS: Emerging evidence suggests that the oropharynx is the primary anatomical site for gonorrhoea transmission but maybe not for chlamydia transmission. Most international guidelines recommend 3-monthly oropharyngeal gonorrhoea and chlamydia screening for high-prevalence populations (e.g. men who have sex with men) but not low-prevalence populations (e.g. heterosexuals) given the clinical and public health benefits of screening in low-prevalence populations are still unclear. Doxycycline remains the first-line treatment for oropharyngeal chlamydia in most guidelines. However, some countries have moved from dual therapy (ceftriaxone and azithromycin) to monotherapy (ceftriaxone) for oropharyngeal gonorrhoea treatment to address antimicrobial stewardship. SUMMARY: The transmission of gonorrhoea and chlamydia is still not fully understood. Further work will be required to evaluate the benefits and harms of reducing screening in high-prevalence populations.

Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125-1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea.

BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125-1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea. METHODS: Gonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC < 0.002 mg/L), R (ceftriaxone-resistant, MIC = 0.5 mg/L), Z (ceftriaxone-resistant, MIC = 0.5 mg/L) and X (ceftriaxone-resistant, MIC = 2 mg/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125-1 g single-dose intramuscular regimens were conducted. RESULTS: Ceftriaxone 0.125-1 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments. CONCLUSIONS: Ceftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (±azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.

Moving Toward Online-Based Sexually Transmitted Infection Testing and Treatment Services for Young People: Who Will Use It and What Do They Want?

BACKGROUND: The market for online sexually transmitted infection (STI) services is rapidly expanding. Online health services often have unequal uptake among different demographics of the population. There is a need to understand how different online delivery options for STI testing may appeal to different groups of young people, particularly young people who have higher rates of STI diagnoses. METHODS: An online survey of young Australians aged 16 to 29 years was conducted to understand service preferences regarding consultation (telehealth, fully automated questionnaire), testing (electronic pathology form, at-home self-sampling), and treatment (e-prescriptions, mailed oral tablets). Multivariable multinomial logistic regression examined associations between user characteristics and service preferences, and adjusted relative risk ratios (aRRRs) and 95% confidence intervals (CIs) are presented. RESULTS: Among 905 respondents, rural youth were more likely to prefer fully automated questionnaires (aRRR, 1.9; 95% CI, 1.0-3.5) over telehealth consultations, whereas culturally and linguistically diverse (CALD) youth were less likely (aRRR, 0.4; 95% CI, 0.2-0.7). Rural youth preferred at-home self-sampling kits (aRRR, 1.9; 95% CI, 1.3-2.7) over electronic forms for on-site collection at pathology centers, with the opposite for CALD youth (aRRR, 0.7; 95% CI, 0.5-1.0). Receiving oral antibiotics by mail was preferred by rural youth (aRRR, 2.3; 95% CI, 1.1-4.6) over for in-clinic treatment, but not for CALD youth (aRRR, 0.5; 95% CI, 0.4-0.8). CONCLUSIONS: Our findings suggest that rural youth tend to prefer self-navigated and automated options, whereas CALD prefer options with greater provider engagement. Online STI service providers should consider how different service options may affect equitable uptake across the population and implications for addressing disparities in testing and treatment.

Can a cup a day keep cancer away? A systematic review exploring the potential of coffee constituents in preventing oral squamous cell carcinoma.

BACKGROUND: Coffee is one of the most consumed beverages in the world. Containing an abundance of bioactive molecules including polyphenols and flavonoids, the constituents of this beverage may exert antiproliferative, antioxidant and anti-inflammatory effects. METHODS: We conducted a systematic review to summarise the available evidence on the anticancer effects of coffee constituents and their potential therapeutic use for oral squamous cell carcinoma (OSCC). Studies were identified through a comprehensive search of OVID MEDLINE, OVID EMBASE and Web of Science, including articles from any year up to 15 May 2023. RESULTS: Of the 60 reviewed papers, 45 were in vitro, 1 was in silico and 8 were in vivo exclusively. The remaining studies combined elements of more than one study type. A total of 55 studies demonstrated anti-proliferative effects, whilst 12 studies also investigated migration and invasion of neoplastic cells. The constituents studied most frequently were quercetin and epigallocatechin gallate (EGCG), demonstrating various cytotoxic effects whilst also influencing apoptotic mechanisms in cancer cell lines. Dose-dependent responses were consistently found amongst the studied constituents. CONCLUSION: Whilst there was heterogeneity of study models and methods, consistent use of specific models such as SCC25 for in vitro studies and golden hamsters for in vivo studies enabled relative comparability. The constituents of coffee have gained significant interest over the last 30 years, particularly in the last decade, and present an area of interest with significant public health implications. Currently, there is a paucity of literature on utilization of active coffee constituents for the therapeutic treatment of oral cancers.

Web-Based STI/HIV Testing Services Available for Access in Australia: Systematic Search and Analysis.

BACKGROUND: Sexually transmitted infection (STI) rates continue to rise in Australia, and timely access to testing and treatment is crucial to reduce transmission. Web-based services have been viewed as a way to improve timely access to STI/HIV testing and have proliferated in recent years. However, the regulation of these services in Australia is minimal, leading to concerns about their quality. The purpose of this review was to systematically identify web-based STI/HIV testing services available in Australia and assess them on aspects of quality, reliability, and accessibility. OBJECTIVE: We aim to systematically identify and assess web-based STI/HIV testing services available in Australia. METHODS: A Google search of Australian web-based services was conducted in March 2022 and repeated in September 2022 using Boolean operators and search terms related to test services (eg, on the internet or home), STIs (eg, chlamydia or gonorrhea), and test type (eg, self-test). The first 10 pages were assessed, and services were categorized as self-testing (ST; test at home), self-sampling (SS; sample at home and return to laboratory), or self-navigated pathology (SNP; specimens collected at pathology center). Website reliability was assessed against the Health on the Net Foundation code of conduct, and service quality was assessed using a scorecard that was developed based on similar reviews, Australian guidelines for in-person services, and UK standards. Additionally, we looked at measures of accessibility including cost, rural access, and time to test results. RESULTS: Seventeen services were identified (8 ST, 2 SS, and 7 SNP). Only 4 services offered recommended testing for all 4 infections (chlamydia, gonorrhea, syphilis, and HIV) including genital, anorectal, and oropharyngeal sites, and 5 offered tests other than those recommended by Australian testing guidelines (eg, Ureaplasma). Nine services (1 SNP, 8 self-test) had no minimum age requirements for access. Reliability scores (scale 0-8) were similar between all services (range 4.75-8.0). Quality weighted scores (scale 0-58) were similar between SNP and SS services (average 44.89, SD 5.56 and 44.75, SD 1.77, respectively) but lower for ST services (22.66, SD 8.93; P=.002). Government-funded services were of higher quality than private services (43.54, SD 6.71 vs 29.43, SD 13.55; P=.03). The cost for services varied between SNP (Aus $0-$595; ie, US $0-$381.96), self-sample (Aus $0; ie, US $0), and ST (Aus $0-$135; ie, US $0-$86.66). The time to test results was much shorter for SNP services (~4 days) than for SS (~12 days) and ST (~14 days). CONCLUSIONS: This review identified considerable variability in the quality and reliability of the web-based STI/HIV testing services in Australia. Given the proliferation and use of these services will likely increase, it is imperative that Australia develops national standards to ensure the standard-of-care offered by web-based STI/HIV testing services is appropriate to protect Australian users from the impact of poorly performing and inappropriate tests.

Rectal chlamydia infections: implications for reinfection risk, screening, and treatment guidelines.

PURPOSE OF REVIEW: Rectal chlamydia is a prevalent sexually transmissible infection in both men who have sex with men (MSM) and in women. Screening is recommended for MSM but remains controversial for women. The optimal treatment for rectal chlamydia is now conclusive but interpreting and managing positive results remains challenging. Infections among MSM are increasing and strategies are needed to reduce incident infections. This review summarizes recent developments for the screening and management of rectal chlamydia and its implications on reinfection. RECENT FINDINGS: Reinfections in MSM may be occurring due to resumption of sex soon after treatment whereas repeat infections in women may occur due to autoinoculation in the absence of sex. Doxycycline is now first-line treatment but its role in chemoprophylaxis remains unclear. False positive results remain an issue, but the development of viability assays may prove useful in future to determine true infections. SUMMARY: Doxycycline is the first-line treatment for rectal chlamydia and in women may prevent infections at the urogenital site. Viability assays can help to reduce antibiotic use once developed. The role of routine screening of rectal chlamydia in women remains unclear and this debate may soon include asymptomatic infections in MSM.

Comparison of gastrointestinal side effects from different doses of azithromycin for the treatment of gonorrhoea.

OBJECTIVES: Azithromycin is commonly used to treat Neisseria gonorrhoeae. We compared its gastrointestinal side effects using 1 g single, 2 g single or 2 g split (i.e. 1 g plus 1 g 6-12 h later) dosing, representing our clinic's changing guidelines over the study period. METHODS: We recruited consecutive sexual health clinic patients who received azithromycin (and 500 mg ceftriaxone) for uncomplicated gonorrhoea. Each patient received a text message 48 h after their attendance to complete a questionnaire. RESULTS: Patients received 1 g single (n = 271), 2 g single (218) or 2 g split (105) doses. Vomiting was less common for 1 g versus 2 g single dose [1.1% versus 3.7%; risk difference (RD): -2.6%; 95% CI: -0.2 to -5.4] and 2 g split versus 2 g single dose (0.9% versus 3.7%; RD: -2.8%; 95% CI: -0.3 to -5.8). Nausea was less common for 1 g versus 2 g single dose (13.7% versus 43.1%; RD: -29.5%; 95% CI: -21.7 to -37.2) and 2 g split versus 2 g single dose (16.4% versus 43.1%; RD: -26.8; 95% CI: -17.2 to -36.3). Diarrhoea was less common for 1 g versus 2 g single dose (25.5% versus 50.9%; RD: -25.5%; 95% CI: -17.0 to -33.9) and 2 g split versus 2 g single dose (30.9% versus 50.9%; RD: -20.0; 95% CI: -9.1 to -30.9). Almost all were willing to retake the same dosing for gonorrhoea in the future: 97% for 1 g single; 94% for 2 g single; and 97% for 2 g split dose. CONCLUSIONS: Azithromycin 2 g split dose for gonorrhoea resulted in significantly less vomiting, nausea and diarrhoea than a 2 g single dose.

What do young people in high-income countries want from STI testing services? A systematic review.

BACKGROUND: There are upward trends of STI rates among young people in most high-income countries. We reviewed the literature to provide a summary of information to support health services with the aim of increasing testing of STIs among young people living in high-income countries. METHODS: We conducted a systematic review (Prospero: CRD42020179720) using PubMed, Embase, PsychINFO and CINAHL. The search was performed on 10 January 2020 for studies between January 2000 and 10 January 2020. Two reviewers independently screened articles, and any discrepancies were resolved by a third reviewer. Studies were included if they were performed in high-income countries and contained data on both young people (<26 years) and STI testing preferences. Data regarding the characteristics of STI testing services that young people preferred was extracted. We categorised these characteristics using the framework of a social-ecological model. RESULTS: We identified 1440 studies, and 63 studies were included in the final review. We found 32 studies that addressed individual factors, 62 studies that addressed service factors and 17 studies that addressed societal factors. At an individual level, we identified eight attributes including the need for improved sexual health education. At a service level, 14 attributes were identified including preferences from different subgroups of young people (such as sexual and ethnic minorities) for the types of services. At a societal level, we identified two attributes including the need to address stigma associated with STIs. CONCLUSION: We provide an overview of the growing body of literature capturing the preferences of young people for STI testing services. To optimise the uptake of STI testing among young people, factors from all socioecological levels should be considered. In addition, understanding and accounting for distinct preferences from subgroups of young people could increase demand for STI testing services for those at greatest need.

Factors associated with rectal pH among men who have sex with men.

Background Rectal chlamydia treatment failures up to 22% with azithromycin 1 g have been reported, but low tissue concentrations are unlikely to be the cause. Anecdotally, low rectal pH could reduce rectal azithromycin concentrations, with in vitro studies reporting higher minimum inhibitory concentrations (MICs) with lower pHs for antibiotics used to treat sexually transmissible infections (STIs). Leucocytes arising from an inflammatory immune response could also lower pH and efficacy. We examined factors that may alter rectal pH and potentially influence treatment outcomes. METHODS: We recruited consecutive men who have sex with men (MSM) from a Dutch STI clinic between October 2016 and July 2018 who had not used antibiotics in the past fortnight. Rectal mucus collected under anoscopy using a cotton swab was used to wet a pH indicator strip. Logistic regression was used to examine the association of pH <8.0 to demographic, dietary, sexual health and behaviour data, recent medication use and STI diagnosis. RESULTS: In total, 112 MSM were recruited (median age 37 years). It was found that 45% and 39% of men were HIV positive or had a rectal infection, respectively. And 50% had a rectal pH <8.0, with 27% reporting a pH between 6.0 and 6.5 where treatment failure is thought to occur for azithromycin. The adjusted odds ratio (OR) of a pH <8.0 showed that being aged 36-45 years (OR 6.7; 95%CI: 1.9-23.4) or having high rectal leucocytes in a Gram smear (OR 0.3; 95%CI: 0.1-0.7) were significantly associated with a low and high rectal pH, respectively. CONCLUSIONS: Lower rectal pH among MSM is associated with older age and could influence the rectal pharmacokinetics of azithromycin and other drugs influenced by pH and may therefore affect treatment outcomes.

Development of New Antimicrobials for Urogenital Gonorrhea Therapy: Clinical Trial Design Considerations.

Gonorrhea remains a major public health challenge, and current recommendations for gonorrhea treatment are threatened by evolving antimicrobial resistance and a diminished pipeline for new antibiotics. Evaluations of potential new treatments for gonorrhea currently make limited use of new understanding of the pharmacokinetic and pharmacodynamic contributors to effective therapy, the prevention of antimicrobial resistance, and newer designs for clinical trials. They are hampered by the requirement to utilize combination ceftriaxone/azithromycin therapy as the comparator regimen in noninferiority trials designed to seek an indication for gonorrhea therapy. Evolving gonococcal epidemiology and clinical trial design constraints hinder the enrollment of those populations at the greatest risk for gonorrhea (adolescents, women, and persons infected with antibiotic-resistant Neisseria gonorrhoeae). This article summarizes a recent meeting on the evaluation process for antimicrobials for urogenital gonorrhea treatment and encourages the consideration of new designs for the evaluation of gonorrhea therapy.

Treatment efficacy for pharyngeal Neisseria gonorrhoeae: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Rising gonorrhoea rates require highly effective treatments to reduce transmission and prevent development of antimicrobial resistance. Currently the most effective treatments for pharyngeal gonorrhoea remain unclear. This review aimed to estimate treatment efficacy for pharyngeal gonorrhoea. METHODS: Online bibliographic databases were searched for the period 1 January 2000 to 17 September 2019 for treatments of gonorrhoea. All randomized controlled trials (RCTs) with data on pharyngeal gonorrhoea among participants aged 15 years or above, published in English, were included. Meta-analyses (random effects) were used to estimate the treatment efficacy, defined as microbiological cure, among currently recommended monotherapies and dual therapies, previously recommended but no longer used regimens and emerging drugs under evaluation. Side effects were also summarized. The study protocol was registered on PROSPERO (CRD42020149278). RESULTS: There were nine studies that included 452 participants studying 19 treatment regimens. The overall treatment efficacy for pharyngeal gonorrhoea was 98.1% (95% CI: 93.8%-100%; I2 = 57.3%; P < 0.01). Efficacy was similar for single (97.1%; 95% CI: 90.8%-100.0%; I2 = 15.6%; P = 0.29) and dual therapies (98.0%; 95% CI: 91.4%-100%; I2 = 79.1%; P < 0.01). Regimens containing azithromycin 2 g or ceftriaxone were similarly efficacious. The summary efficacy estimate for emerging drugs was 88.8% (95% CI: 76.9%-97.5%; I2 = 11.2%; P = 0.34). Small sample sizes in each trial was a major limitation. CONCLUSIONS: Regimens containing ceftriaxone or azithromycin 2 g, alone or as part of dual therapies are the most efficacious for pharyngeal gonorrhoea. Further pharyngeal-specific RCTs with adequate sample sizes are needed.

Factors Associated With Early Resumption of Condomless Anal Sex Among Men Who Have Sex With Men After Rectal Chlamydia Treatment.

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.

Prevalence of sexually transmissible infections and HIV in men attending sex-on-premises venues in Australia: a systematic review and meta-analysis of observational studies.

Background In Australia, men who have sex with men (MSM) have high rates sexually transmissible infections (STIs) and sex-on-premises venue (SOPV) patrons are at risk. This paper assesses Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV prevalence in men tested at Australian SOPVs and describes testing services. METHODS: EMBASE, Medline, PubMed and international conference proceedings were searched for articles reporting on-site SOPV testing between 1 January 2000 and 31 January 2017. Meta-analysis calculated pooled prevalence estimates of STIs by anatomical site. RESULTS: Twelve cross-sectional studies were identified. Most (8/12) were local sexual health clinics (SHC) outreach services. Participants' mean age was 41.1 years (95% confidence interval (CI) 37.0-43.3; range 17 to 84 years). Testing included CT and NG (9/12), HIV (8/12) and syphilis (5/12). CT and NG prevalence overall summary estimates were 3.4% (95% CI 1.9-5.2%, I2 = 88.7%, P < 0.01) and 1.3% (95% CI 0.7-2.2%, I2 = 75.5%, P < 0.01) respectively. CT and NG prevalence was highest in the ano-rectum and oro-pharynx respectively. The HIV and syphilis pooled estimates were 2.3% (95% CI 1.6-2.9%, I2 = 93.1%, P < 0.01) and 3.2% (95% CI 1.8-4.6%, I2 = 72.8%, P < 0.01) respectively. Participation rate varied. CONCLUSION: This review examines HIV and STI testing in Australian SOPVs before HIV pre-exposure prophylaxis (PrEP). Findings indicate a high prevalence of STIs. PrEP use and resultant condomless sex may influence STI prevalence. Further research is required to determine the effect of PrEP on the STI prevalence among SOPV patrons.

Treatment Outcomes for Rectal Lymphogranuloma Venereum in Men Who Have Sex with Men Using Doxycycline, Azithromycin, or Both: A Review of Clinical Cases.

BACKGROUND: Treatment for rectal lymphogranuloma venereum where doxycycline 100 mg twice daily for 21 days was used-either alone or together with azithromycin 1 g single dose-resulted in microbiological cure of 97%. These data support doxycycline 100 mg twice daily for 21 days as the preferred treatment for rectal lymphogranuloma venereum.

Systematic Review and Meta-Analysis of Doxycycline Efficacy for Rectal Lymphogranuloma Venereum in Men Who Have Sex with Men.

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.

The Efficacy of Azithromycin for the Treatment of Genital Mycoplasma genitalium: A Systematic Review and Meta-analysis.

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.

Treatment of rectal chlamydia infection may be more complicated than we originally thought.

Rectal chlamydia diagnoses have been increasing among MSM and may also rise among women as anal sex rates increase among heterosexuals. However, there is growing concern about treatment for rectal chlamydia with treatment failures of up to 22% being reported. This article addresses factors that may be contributing to treatment failure for rectal chlamydia, including the pharmacokinetic properties of azithromycin and doxycycline in rectal tissue, the ability of chlamydia to transform into a persistent state that is less responsive to antimicrobial therapy, the impact of the rectal microbiome on chlamydia, heterotypic resistance, failure to detect cases of lymphogranuloma venereum and the performance of screening tests. If we are to reduce the burden of genital chlamydia, treatment for rectal chlamydia must be efficacious. This highlights the need for randomized controlled trial evidence comparing azithromycin with doxycycline for the treatment of rectal chlamydia.

Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modelling the impact of autoinoculation from the gastrointestinal tract to the genital tract.

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.