Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

BACKGROUND: Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. METHODS: Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5-10 days post-treatment. RESULTS: Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5-100%). CONCLUSIONS: Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. CLINICAL TRIALS REGISTRATION: NCT02961751.

A multisite implementation of a real-time polymerase chain reaction assay to predict ciprofloxacin susceptibility in Neisseria gonorrhoeae.

There are no commercially available Food and Drug Administration-cleared rapid tests for Neisseria gonorrhoeae antimicrobial susceptibility testing. This study evaluated the performance of a laboratory-developed real-time polymerase chain reaction assay for genotyping the gyrA gene to determine antimicrobial susceptibility to ciprofloxacin. Validation and clinical performance of the gyrA assay were evaluated across 3 geographic locations (Los Angeles, San Francisco, Philadelphia). Following validation, clinical specimens were collected in Aptima Combo2® CT/NG transport medium from asymptomatic persons who tested positive for Neisseria gonorrhoeae and evaluated for assay percent reportable (i.e., proportion of N. gonorrhoeae-positive specimens that yielded a gyrA genotype). The percentage of gyrA genotyping results differed by laboratory and specimen type. The proportion of specimens that were reportable was best for urine/genital specimens (genotyped = 76.4% (95% confidence interval, 69.9-82%)) followed by rectal (genotyped = 67.2% (95% confidence interval, 63.4-70.6%)) and then pharyngeal specimens (genotyped = 36.1%, (95% confidence interval, 31.9-40.5%)). Overall, asymptomatic patients with N. gonorrhoeae yielded an interpretable genotype 57.2% (784/1370) of the time, of which 480 were wild-type gyrA, resulting in 61% (480/784) being potentially treatable with ciprofloxacin.

The Frequency of Discordant Gyrase A Genotypes Among Cases of Multiple Neisseria gonorrhoeae Infections at Different Anatomic Sites.

Gyrase A genotyping reliably predicts Neisseria gonorrhoeae susceptibility to ciprofloxacin. It is unknown whether concurrent infections at different anatomic sites harbor different susceptibility profiles. We found a 3.2% frequency of discordant gyrase A genotypes among concurrent but anatomically separate N. gonorrhoeae infections diagnosed at 2 laboratories in Los Angeles.

Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.

International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

HIV testing frequency among men who have sex with men attending sexually transmitted disease clinics: implications for HIV prevention and surveillance.

OBJECTIVES: To describe trends in the occurrence and frequency of HIV testing among men who have sex with men (MSM) receiving care in 4 US sexually transmitted disease (STD) clinics and to define factors associated with HIV testing frequency and positivity. STUDY DESIGN: Routine clinical encounters during 57,131 visits by MSM to STD clinics in 4 cities (Seattle-King County, San Francisco, Denver, and District of columbia), 2002-2006, were examined. RESULTS: From 2002 to 2006, a city-specific median of 69.1% of presumptive HIV-uninfected MSM were tested for HIV, of which, a median of 86.7% had previously tested (4.5% unknown) and a median of 3.9% were newly diagnosed with HIV. Between 2002 and 2006, the median percentage of tested MSM who reported no previous HIV testing decreased from 9.4% to 5.4% (P = 0.01) and the city-specific median intertest interval decreased from 302 to 243 days (P = 0.03). Among MSM with newly diagnosed HIV, the median intertest interval decreased from 531 days in 2002 to 287 days in 2006 (P = 0.001). Predictors of newly diagnosed HIV infection included the following: younger age, longer intertest interval, black or Hispanic race/ethnicity, clinic in San Francisco, and concurrent diagnosis with a bacterial STD. CONCLUSIONS: In MSM seen at 4 STD clinics, the percentage of never previously HIV tested is decreasing and MSM are testing more frequently.