Emergence of Quinolone-Resistance and Cephalosporin MIC Creep in Neisseria 2 gonorrhoeae in a Cohort of Young Men in Kisumu, Kenya: 2002 – 2009

Abstract

Introduction: We evaluated antimicrobial resistance in Neisseria gonorrhoeae (NG) isolated from men enrolled in a randomized trial of male circumcision to prevent HIV. Methods: Urethral specimens from men with discharge were cultured for NG. Minimum inhibitory concentrations (MICs) were determined by agar dilution. Clinical Laboratory Standards Institute criteria defined resistance: MIC≥2.0 μg/ml for penicillin, tetracycline, and azithromycin; ciprofloxacin MIC≥1.0 μg/ml; spectinomycin MIC≥128.0 μg/ml. Susceptibility to ceftriaxone and cefixime was MIC<0.25 μg/ml. Additionally, PCR amplification identified mutations in parC and gyrA genes in selected isolates. Results: From 2002–2009, 168 NG isolates were obtained from 142 men. Plasmid mediated penicillin resistance was found in 65%, plasmid mediated tetracycline resistance in 97%, and 11% were ciprofloxacin resistant (QRNG). QRNG appeared November 2007, increasing from 9.5% in 2007 to 50% in 2009. Resistance was not detected for spectinomycin, cefixime, ceftriaxone, and azithromycin, but MICs of cefixime (p=0.018), ceftriaxone (p<0.001), and azithromycin (p=0.097) increased over time. In a random sample of 51 men gentamicin MIC was: 4 μg/ml (n=1), 8 μg/ml (n=49), 16 μg/ml (n=1). Discussion: QRNG increased rapidly and alternative regimens are required for NG treatment in this area. Amid emerging multi-drug resistant NG, antimicrobial resistance surveillance is essential for effective drug choice. High levels of plasmid mediated resistance and increasing MIC for cephalosporins suggest that selective pressure from antibiotic use is a strong driver of resistance emergence.