Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea: the relationship between antibiotic MIC and clinical outcome.

OBJECTIVES: To investigate the relationship between MIC and clinical outcome in a randomized controlled trial that compared gentamicin 240 mg plus azithromycin 1 g with ceftriaxone 500 mg plus azithromycin 1 g. MIC analysis was performed on Neisseria gonorrhoeae isolates from all participants who were culture positive before they received treatment. METHODS: Viable gonococcal cultures were available from 279 participants, of whom 145 received ceftriaxone/azithromycin and 134 received gentamicin/azithromycin. Four participants (6 isolates) and 14 participants (17 isolates) did not clear infection in the ceftriaxone/azithromycin and gentamicin/azithromycin arms, respectively. MICs were determined by Etest on GC agar base with 1% Vitox. The geometric mean MICs of azithromycin, ceftriaxone and gentamicin were compared using logistic and linear regression according to treatment received and N. gonorrhoeae clearance. RESULTS: As the azithromycin MIC increased, gentamicin/azithromycin treatment was less effective than ceftriaxone/azithromycin at clearing N. gonorrhoeae. There was a higher geometric mean MIC of azithromycin for isolates from participants who had received gentamicin/azithromycin and did not clear infection compared with those who did clear infection [ratio 1.95 (95% CI 1.28-2.97)], but the use of categorical MIC breakpoints did not accurately predict the treatment response. The geometric mean MIC of azithromycin was higher in isolates from the pharynx compared with genital isolates. CONCLUSIONS: We found that categorical resistance to azithromycin or ceftriaxone in vitro, and higher gentamicin MICs in the absence of breakpoints, were poorly predictive of treatment failure.

Home interventions and light therapy for the treatment of vitiligo (HI-Light Vitiligo Trial): study protocol for a randomised controlled trial.

INTRODUCTION: Vitiligo is a condition resulting in white patches on the skin. People with vitiligo can suffer from low self-esteem, psychological disturbance and diminished quality of life. Vitiligo is often poorly managed, partly due to lack of high-quality evidence to inform clinical care. We describe here a large, independent, randomised controlled trial (RCT) assessing the comparative effectiveness of potent topical corticosteroid, home-based hand-held narrowband ultraviolet B-light (NB-UVB) or combination of the two, for the management of vitiligo. METHODS AND ANALYSIS: The HI-Light Vitiligo Trial is a multicentre, three-arm, parallel group, pragmatic, placebo-controlled RCT. 516 adults and children with actively spreading, but limited, vitiligo are randomised (1:1:1) to one of three groups: mometasone furoate 0.1% ointment plus dummy NB-UVB light, vehicle ointment plus NB-UVB light or mometasone furoate 0.1% ointment plus NB-UVB light. Treatment of up to three patches of vitiligo is continued for up to 9 months with clinic visits at baseline, 3, 6 and 9 months and four post-treatment questionnaires.The HI-Light Vitiligo Trial assesses outcomes included in the vitiligo core outcome set and places emphasis on participants' views of treatment success. The primary outcome is proportion of participants achieving treatment success (patient-rated Vitiligo Noticeability Scale) for a target patch of vitiligo at 9 months with further independent blinded assessment using digital images of the target lesion before and after treatment. Secondary outcomes include time to onset of treatment response, treatment success by body region, percentage repigmentation, quality of life, time-burden of treatment, maintenance of response, safety and within-trial cost-effectiveness. ETHICS AND DISSEMINATION: Approvals were granted by East Midlands-Derby Research Ethics Committee (14/EM/1173) and the MHRA (EudraCT 2014-003473-42). The trial was registered 8 January 2015 ISRCTN (17160087). Results will be published in full as open access in the NIHR Journal library and elsewhere. TRIAL REGISTRATION NUMBER: ISRCTN17160087.

Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

BACKGROUND: Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. METHODS/DESIGN: This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. DISCUSSION: The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.