Emergence of Quinolone Resistance and Cephalosporin MIC Creep in Neisseria gonorrhoeae Isolates from a Cohort of Young Men in Kisumu, Kenya, 2002 to 2009

Abstract

We evaluated antimicrobial resistance in Neisseria gonorrhoeae isolated from men enrolled in a randomized trial of male circumcision to prevent HIV. Urethral specimens from men with discharge were cultured for N. gonorrhoeae. MICs were determined by agar dilution. Clinical and Laboratory Standards Institute (CLSI) criteria defined resistance: penicillin, tetracycline, and azithromycin MICs of >2.0 g/ml; a ciprofloxacin MIC of >1.0 g/ml; and a spectinomycin MIC of >128.0 g/ml. Susceptibility to ceftriaxone and cefixime was shown by an MIC of <0.25 g/ml. Additionally, PCR amplification identified mutations in parC and gyrA genes in selected isolates. From 2002 to 2009, 168 N. gonorrhoeae isolates were obtained from 142 men. Plasmidmediated penicillin resistance was found in 65%, plasmid-mediated tetracycline resistance in 97%, and 11% were ciprofloxacin resistant (quinolone-resistant N. gonorrhoeae [QRNG]). QRNG appeared in November 2007, increasing from 9.5% in 2007 to 50% in 2009. Resistance was not detected for spectinomycin, cefixime, ceftriaxone, or 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 MICs were as follows: 4 g/ml (n ‫؍‬ 1), 8 g/ml (n ‫؍‬ 49), and 16 g/ml (n ‫؍‬ 1). QRNG increased rapidly and alternative regimens are required for N. gonorrhoeae treatment in this area. Amid emerging multidrug-resistant N. gonorrhoeae, antimicrobial resistance surveillance is essential for effective drug choice. High levels of plasmid-mediated resistance and increasing MICs for cephalosporins suggest that selective pressure from antibiotic use is a strong driver of resistance emergence.

Gentamicin Susceptibility among a Sample of Multidrug-Resistant Neisseria gonorrhoeae Isolates in India

“…In the present study, most (76.9%) of the isolates were within a wide MIC range of 0.5 to 4 mg/liter, while 95%, 99.7%, and 100% of European, Argentinian, and Kenyan isolates were within a more narrow MIC range of 4 to 8, 4 to 8, and 4 to 16 mg/liter, respectively (14,15,25). In comparison, only 9.1% isolates in our study had MIC values of 8 mg/liter.…”

Trends of Resistance to Antimicrobials Recommended Currently and in the Past for Management of Gonorrhea in the Apex STD Center in India and Comparison of Antimicrobial Resistance Profile Between 2002–2006 and 2007–2012

“…6 The very high occurrence of tetracycline-resistant and less susceptible strains to the extent of 74.7% in this study is comparable with reports from other countries (Kenya 97%, Thailand 82%, Indonesia 100%, Ethiopia 92.6%,). 2,22,29 Some exceptions were noted in the United States, 5 where tetracycline resistance rates were only 22.5% and rates in South America and the Caribbean decreased from a level of 61.1% of isolates tested in 2001 to 21.8% in 2010. 30 This high percentage of resistance to tetracycline indicates that this antibiotic is certainly not appropriate for gonorrhea treatment in India and other countries.…”

“…2,22,29 Throughout the study period, the contribution of PPNG isolates (47.9%) to overall penicillin resistance was higher as compared with N. gonorrhoeae isolates with chromosomally mediated penicillin resistance (5.4%). The findings are similar to those from Kenya, Thailand, South America, and the Caribbean.…”

“…The findings are similar to those from Kenya, Thailand, South America, and the Caribbean. 2,22,30 The reason for this consistency may be because of the mode of transfer of resistance determinants between N. gonorrhoeae isolates. β-Lactamase plasmid can be mobilized between N. gonorrhoeae isolates by the transfer plasmid.…”

“…Decreased susceptibility or resistance to extended-spectrum cephalosporins (ESCs), currently recommended for treatment of uncomplicated gonococcal infections, has been documented in numerous countries worldwide including Asia, Africa, Australia, the United States, and Europe. [2][3][4][5][6][7][8][9] In recent years, the extensively drug-resistant N. gonorrhoeae isolates, with ceftriaxone treatment failures, were reported posing an increasing problem in the management of gonorrhea. [10][11][12] Antimicrobial resistance surveillance is recommended to guide therapy in individual patient, monitor AMR trends, and follow the emergence and spread of new resistant strains.…”