Background Repeated C. trachomatis infections are common among young sexually active women. The relative frequency of re-infection and antibiotic treatment failure is undefined. Methods Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessment every 3 months, including amplification tests for C. trachomatis, ompA genotyping and interviews and diary entries to document partner-specific coitus and event-specific condom use. Repeated infections were classified as re-infection or treatment failure using an algorithm. All infections with treatment outcomes were used to estimate antibiotic use-effectiveness. Results We observed 478 infection episodes among 210 participants; 176 women remained uninfected. Incidence rate was 34 per 100-woman years. Of those infected, 121 had ≥1 repeat infections forming 268 episode pairs; 183 pairs had complete data and were classified with the algorithm. Of repeated infections, 84.2% were definite, probable or possible re-infections, 13.7% were probable or possible treatment failures and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated a 92.2% treatment use-effectiveness. Conclusions Most repeat chlamydial infections in this high incidence cohort were re-infections, but treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

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BACKGROUNDAntibiotic-resistant Neisseria gonorrhoeae has prompted the development of new therapies. Zoliflodacin is a new antibiotic that inhibits DNA biosynthesis. In this multicenter, phase 2 trial, zoliflodacin was evaluated for the treatment of uncomplicated gonorrhea. METHODSWe randomly assigned eligible men and women who had signs or symptoms of uncomplicated urogenital gonorrhea or untreated urogenital gonorrhea or who had had sexual contact in the preceding 14 days with a person who had gonorrhea to receive a single oral dose of zoliflodacin (2 g or 3 g) or a single 500-mg intramuscular dose of ceftriaxone in a ratio of approximately 70:70:40. A test of cure occurred within 6±2 days after treatment, followed by a safety visit 31±2 days after treatment. The primary efficacy outcome measure was the proportion of urogenital microbiologic cure in the microbiologic intention-to-treat (micro-ITT) population. RESULTSFrom November 2014 through December 2015, a total of 179 participants (167 men and 12 women) were enrolled. Among the 141 participants in the micro-ITT population who could be evaluated, microbiologic cure at urogenital sites was documented in 55 of 57 (96%) who received 2 g of zoliflodacin, 54 of 56 (96%) who received 3 g of zoliflodacin, and 28 of 28 (100%) who received ceftriaxone. All rectal infections were cured in all 5 participants who received 2 g of zoliflodacin and all 7 who received 3 g, and in all 3 participants in the group that received ceftriaxone. Pharyngeal infections were cured in 4 of 8 participants (50%), 9 of 11 participants (82%), and 4 of 4 participants (100%) in the groups that received 2 g of zoliflodacin, 3 g of zoliflodacin, and ceftriaxone, respectively. A total of 84 adverse events were reported: 24 in the group that received 2 g of zoliflodacin, 37 in the group that received 3 g of zoliflodacin, and 23 in the group that received ceftriaxone. According to investigators, a total of 21 adverse events were thought to be related to zoliflodacin, and most such events were gastrointestinal. CONCLUSIONSThe majority of uncomplicated urogenital and rectal gonococcal infections were successfully treated with oral zoliflodacin, but this agent was less efficacious in the treatment of pharyngeal infections. (Funded by the National Institutes of Health and Entasis Therapeutics; ClinicalTrials.gov number, NCT02257918.

In this phase 2 study, single oral doses of gepotidacin were ≥95% effective for bacterial eradication in culture-proven uncomplicated urogenital gonorrhea. New antibiotics for drug-resistant Neisseria gonorrhoeae are urgently needed. With additional evaluation, gepotidacin may provide an alternative therapeutic option.

The incidence of T. vaginalis infection is high among adolescent women; untreated infections may last undetected for 3 months or longer. Reinfection is common. Treatment with oral metronidazole is effective, and T. vaginalis DNA disappears rapidly after treatment.

Background Some screening and treatment programs implemented to control genital Chlamydia trachomatis infections and their complications have shown initial reductions in infection prevalence followed by rises to pre-program levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity and thereby increases risk of re-infection. Methods A literature review was undertaken to assess evidence supporting the concept of protective immunity, its characteristics and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April, 2008. Results Definitive human studies are not available, but cross-sectional studies show chlamydia prevalence, organism load and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome upon re-exposure, similar to what is found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity following resolution of untreated infection. In longitudinal studies of African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon gamma production by peripheral blood mononuclear cells in response to chlamydial heat shock protein 60 was associated with low risk of incident infection. In cross-sectional studies, relevant Th1 type responses are found in infected persons, paralleling the studies in animal models. Conclusions The data support the concept that some degree of protective immunity against re-infection develops following human genital infection, although it appears at best partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs. Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations, frequent biological and behavioral sampling and special cohorts to help control for exposure.

These findings support public health messages of reducing the number of sexual partners, promoting routine condom use, and frequent sexually transmitted infection screening that may be beneficial with HPV infections.