RESUMEN
BACKGROUND: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid-based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC. METHODS: In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9-12; safety was assessed at TOC and day 21-30. RESULTS: One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%). CONCLUSIONS: TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials. CLINICAL TRIALS REGISTRATION: NCT02866227.
Asunto(s)
Antiinfecciosos/uso terapéutico , Boratos/uso terapéutico , Ácidos Bóricos/uso terapéutico , Candidiasis Vulvovaginal/tratamiento farmacológico , Ácido Edético/análogos & derivados , Ácido Edético/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Adolescente , Adulto , Antiinfecciosos/farmacología , Boratos/farmacología , Ácidos Bóricos/farmacología , Ácido Edético/farmacología , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts. Methods: Using gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014-2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes. Results: In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014-2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug. Conclusions: Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea.
Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Susceptibilidad a Enfermedades/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Neisseria gonorrhoeae/efectos de los fármacos , Adulto , Ceftriaxona/uso terapéutico , Resistencia a las Cefalosporinas , Farmacorresistencia Bacteriana , Homosexualidad Masculina , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Minorías Sexuales y de Género , Washingtón/epidemiologíaRESUMEN
Substance use disorders (SUDs) are thought to predict care discontinuity, though magnitude and substance-specific variance of effects are unclear. This report of analytic work undertaken with a multi-regional American cohort of 9153 care enrollees addresses these gaps. Care retention was computed from 24-month post-linkage clinic visit documentation, with SUD cases identified from patient-report screening instruments. Two generalized estimating equations tested binary and hierarchial SUD predictors of retention, and potential effect modification by patient age-group, sex, and care site. Findings demonstrate: (1) detrimental SUD effect, equivalent to a nine percentage-point decrease in retention, with independent effects of age-group and care site; (2) substance-specific effect of marijuana UD associated with lower retention; and (3) age-modification of each effect on care discontinuity, with SUDs serving as a risk factor among 18-29 year-olds and protective factor among 60+ year-olds. Collective findings document patient attributes as influences that place particular subgroups at-risk to discontinue care.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/epidemiología , Retención en el Cuidado , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The Centers for Disease Control and Prevention guidelines for pharyngeal gonorrhea treatment recommend dual therapy with intramuscular ceftriaxone and either azithromycin or doxycycline. Few clinical data exist to support this recommendation. METHODS: We conducted a retrospective analysis of patients diagnosed with pharyngeal gonorrhea during 1993-2011, at a sexually transmitted disease clinic in Seattle, Washington, and compared the proportion of repeat positive tests for pharyngeal gonorrhea 7-180 days following treatment among persons receiving different drug regimens. Associations of treatment regimens were assessed using relative risks through Poisson regression models with log link and robust standard errors. RESULTS: A total of 1440 cases of pharyngeal gonorrhea were diagnosed during the study period, 25% of which (n = 360) underwent retesting. Among retested patients, the risk of repeat positive test was lowest among persons receiving an oral cephalosporin and azithromycin (7%, reference group), and highest among those receiving an oral cephalosporin alone (30%; relative risk [RR], 3.98; 95% confidence interval [CI], 1.70-9.36) or in combination with doxycycline (33%; RR, 4.18; 95% CI, 1.64-10.7). The risk of repeat test positivity did not significantly differ between persons treated with an oral cephalosporin and azithromycin and those treated with ceftriaxone alone (9.1%; RR, 0.81; 95% CI, .18-3.60) or ceftriaxone combined with azithromycin or doxycycline (11.3%; RR, 1.20; 95% CI, .43-3.33). CONCLUSIONS: In this retrospective study, dual therapy with an oral third-generation cephalosporin and azithromycin was comparable to ceftriaxone-based regimens in the treatment of pharyngeal gonorrhea. Combination oral therapy with doxycycline was associated with an elevated risk of persistent or recurrent infection.