Hanne S. Harbison

The Efficacy and Safety of Gentamicin Plus Azithromycin and Gemifloxacin Plus Azithromycin as Treatment of Uncomplicated Gonorrhea

BACKGROUND Ceftriaxone is the foundation of currently recommended gonorrhea treatment. There is an urgent need for backup treatment options for patients with cephalosporin allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of 2 combinations of existing noncephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. METHODS We conducted a randomized, multisite, open-label, noncomparative trial in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland, and Pennsylvania. Patients aged 15-60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10-17 days after treatment among 401 participants in the per protocol population. RESULTS Microbiological cure was achieved by 100% (lower 1-sided exact 95% confidence interval [CI] bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower 1-sided exact 95% CI bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection; gemifloxacin/azithromycin cured 15 of 15 pharyngeal and 5 of 5 rectal infections. Gastrointestinal adverse events were common in both arms. CONCLUSIONS Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. Clinical Trials Registration. NCT00926796.

A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea

BACKGROUND Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. METHODS We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. RESULTS A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. CONCLUSIONS Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. CLINICAL TRIALS REGISTRATION NCT01591447.

Sexual partnership characteristics of African American women who have sex with women; impact on sexually transmitted infection risk.

Background African American women who have sex with women (WSW) are emerging as a population at risk for sexually transmitted infections (STIs). The objectives of this study were to explore partnership characteristics for a cohort of African American WSW and evaluate those characteristics as potential risk factors for STIs. In addition, we aimed to determine STI diagnoses and identify predictors of STI infection. Methods Women who have sex with women presenting to a sexually transmitted disease clinic in Birmingham, AL, completed a questionnaire and were tested for bacterial vaginosis, trichomoniasis, chlamydia, gonorrhea, Mycoplasma genitalium, syphilis, HIV, and herpes simplex virus type 2. Results A total of 163 women were enrolled: 78 WSW and 85 women who have sex with women and men (WSWM) (based on report of past year sexual behavior). Both WSW and WSWM reported similar numbers of female partners over the lifetime, past year, and past month; however, WSWM reported significantly more lifetime male partners, thus having a higher overall number of sexual partners. Women who have sex with women and men were more likely to report new or casual partner(s), group sex, history of STIs, and sex with partner(s) known to have STIs. Overall, WSWM were more likely to have a current diagnosis of bacterial vaginosis, a current diagnosis of a curable STI, or a diagnosis of a noncurable STI (85% vs. 56%, P < 0.01). Conclusions African American WSW are not a homogeneous group, and their sexual health may be directly or indirectly influenced by male partners. A better understanding of the distinctions and differences between African American WSW and WSWM will enable health care providers to improve the quality of care provided.

Sexual behaviors, perception of sexually transmitted infection risk, and practice of safe sex among southern African American women who have sex with women.

Background Women who have sex with women (WSW) and women who have sex with women and men (WSWM) are frequently perceived to be at low risk for sexually transmitted infections (STIs), although data show that their STI rates are similar to heterosexual women. Little research has examined sexual behaviors, perceptions of STI risk, and practice of safe sex among African American WSW/WSWM living in the Southern United States, a population of women likely to be at high risk for STIs. Methods Focus group discussions were conducted with African American WSW/WSWM living in Birmingham, Alabama, to explore their sexual behaviors with women, perceptions of STI risk from female (and male) sexual partners, and practice of safe sex. Digital audio-recordings were transcribed and analyzed using HyperRESEARCH software. Results Seven focus groups were conducted between August 2011 and March 2012, with 29 total participants. Women reported a broad range of sexual behaviors with female partners. They were more aware of their risk for STI acquisition from male partners than from female partners and felt that their best options for safe sex in their relationships with women were practicing good hygiene and requiring proof of STI testing results. Conclusions African American WSW/WSWM in this study were aware of their STI risk, more so with regard to men, and desired accurate information on safer sex options in their sexual relationships with women. Health care providers can assist these women by helping them apply their existing knowledge of heterosexual STI transmission to their female sexual partnerships.

Characteristics of Women Reporting Multiple Recent Sex Partners Presenting to a Sexually Transmitted Disease Clinic for Care

Background: Sexually transmitted disease (STD) clinic attendees are considered to be at higher risk of sexually transmitted infections (STIs) than the general population. However, little is known about STD clinic subpopulations and their unique risks for STIs. The goal of this project was to begin to characterize an important STD clinic subpopulation, the small proportion of women reporting a recent history of multiple sex partners. Methods: Screening of electronic medical records from 2007 identified 347 (7%) women with ≥4 partners in the last 12 months. Records for women with ≥4 sex partners were matched with women reporting 1 sex partner in the last 12 months. Demographic, sexual history, STI history, and laboratory diagnosis(es) were extracted from the electronic medical record and compared using a case-control study design. Results: Approximately 5000 women presented to our STD clinic in 2007; 7.0% reported ≥4 sex partners. Women with ≥4 sex partners were less often black and on average younger than women with single partners (Median age, 24 vs. 29). They reported more nonvaginal sex, more same-sex contacts, but more consistent condom use than women with single partners. Dyspareunia, genital lesions, abdominal pain, and skin findings were more commonly reported by women with ≥4 sex partners. Women with multiple partners were also more likely to report ever having had ≥3 STIs and were more likely to report a history of gonorrhea or syphilis. They were also more likely to be diagnosed at presentation with chlamydia, gonorrhea, or syphilis. Conclusion: Women reporting multiple sex partners are an important minority among STD clinic attendees. Understanding the antecedents to high risk sexual behavior as determined by partner number is an important step in reducing STIs in this group.

Misperceptions regarding protective barrier method use for safer sex among African-American women who have sex with women.

BACKGROUND Barrier methods for HIV and sexually transmissible infection (STI) prevention among women who have sex with women (WSW) are available, although their effectiveness has not been systematically investigated. These methods are infrequently used by WSW. As part of a larger study on STI risk perceptions and safer sex among African-American WSW, we discovered several misperceptions regarding barrier methods that may be associated with their limited use. METHODS Participants were recruited from the Jefferson County Health Department STI Clinic and through word of mouth in Birmingham, Alabama, for focus group discussions exploring perceptions of STI risk and safer sex. RESULTS Seven focus groups with 29 participants were conducted (age range: 19-43 years). Several misperceptions regarding barrier methods were identified, notably the conflation of dental dams and female condoms. Descriptions of the use of barrier methods were qualified with phrases suggesting their hypothetical, rather than actual, use. Additional evidence that barrier methods are not actually used came from beliefs that dental dams and female condoms are available in major grocery stores or department store chains. CONCLUSIONS Those providing sexual health services to WSW should be cautious in assuming that WSW have accurate information regarding barrier methods for safer sex. Sexual health services provided to WSW should include an accurate description of what barrier methods are, how to distinguish them from barrier methods more commonly used during heterosexual sex (female and male condoms), and how to use them correctly. Future studies are needed to address how effectively these measures reduce transmission of STIs among WSW.

O02.5 A Phase II, Dose Ranging Study to Evaluate the Efficacy and Safety of Single-Dose Oral Solithromycin (CEM-101) For Treatment of Patients with Uncomplicated Urogenital Gonorrhoea

Objectives Emerging resistance to available treatment creates an urgent need for new therapies for uncomplicated gonorrhoea. Solithromycin, a new 4th generation macrolide with 3 ribosomal targets, is highly active against most antibiotic-resistant strains of Neisseria gonorrhoeae. A Phase II, dose ranging study to evaluate the efficacy and safety of single-dose oral solithromycin for uncomplicated urogenital gonorrhoea was conducted. Methods Consenting participants with suspected Neisseria gonorrhoeae infection were cultured at the urethra/cervix, rectum, and pharynx at enrollment and Day 7 . The primary outcome was bacterial eradication (conversion from positive baseline N. gonorrhoeae urethral/cervical culture to negative) at Day 7. Secondary outcomes included eradication of rectal or pharyngeal gonorrhoea and the eradication of gonococcal and chlamydial nucleic acids. Initially, eligible patients received a single 1200 mg oral dose of solithromycin; following demonstration of bacteriologic efficacy, a second cohort was treated with a single 1000 mg dose. Results Of 41 (19 M, 22 F) participants enrolled, 28 were treated with a 1200 mg dose and, to date, 13 with 1000 mg. Gonococcal eradication rates in 22 evaluable 1200 mg patients were 100% (22/22) for urethral/cervical, pharyngeal (5/5), and rectal (2/2) infections. Of 9 evaluable 1000 mg patients enrolled to date, gonococcal eradication rates have been 100% (9/9) for urethral/cervical, pharyngeal (2/2), and rectal (1/1) infections. Susceptibility data from 25 isolates show the median MIC (range) for solithromycin was 0.06 µg/mL (0.015–0.125) and for azithromycin was 0.125 µg/mL (0.06–0.5). Solithromycin was generally well-tolerated with mild dose-related gastrointestinal AEs (68%; 28/41). The most common AE was mild diarrhoea, occurring in 61% (17/28) of patients receiving the 1200 mg dose and 15% (2/13) of patients receiving the 1000 mg dose. Conclusions A single dose of 1200 or 1000 mg solithromycin appears to be well-tolerated and effective in eradicating N. gonorrhoeae.

YI.3 Sexually Transmitted Infections (STIs) Vary Among African American Women Who Have Sex with Women Based on Exposure to Male Sexual Partners

Introduction Little is known about partner characteristics or rates of STIs among African American women who have sex with women (AAWSW). Methods African American women aged ≥ 16 years attending a Health Department STD clinic were enrolled in this ongoing study if they reported sexual activity with a female partner during the preceding year. Participants completed a study questionnaire and were tested for curable (trichomoniasis, Chlamydia, gonorrhoea, and syphilis) and non-curable (HSV-2, HIV) STIs. Results Of 128 participants reporting female partners during the preceding year, 52% (67/128) also reported sex with men during the same interval (WSWM). WSW and WSWM did not differ with regards to age, lifetime number of female partners, or number of female partners during the preceding year. WSWM reported increased numbers of lifetime male partners compared to WSW ( p = 0.01). During the 30 days preceding enrollment, WSWM reported a median of 2 sexual partners (interquartile (IQR) range 0–4) while WSW reported a median of 1 sexual partner (IQR 0–2). WSWM were significantly more likely than WSW to report new or casual female partners within 30 days preceding enrollment (46% vs. 28%; p = 0.03) while WSW were more likely to report regular female partners (75% vs. 34%; p = 0.01). Additionally, 39% (26/67) of WSWM reported new or casual male partners within 30 days preceding enrollment. Although not statistically significant, diagnosis of all curable STIs (trichomoniasis, Chlamydia, gonorrhoea, and syphilis) was more common among WSWM than WSW (30% vs. 16%; p = 0.07). Similarly, seropositivity for HIV and HSV-2 was more than twice as common among WSWM as WSW. Conclusions AAWSW in this study were at high risk for STIs. AAWSWM, as a subgroup, may demonstrate heightened STI rates compared to exclusive AAWSW, perhaps influenced by partnership characteristics. Sexual health services for AAWSW should take into account partner gender heterogeneity when screening for STIs.