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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. Plasmid-mediated 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.

SUBMITTER: Mehta SD

PROVIDER: S-EPMC3147659 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Emergence of quinolone resistance and cephalosporin MIC creep in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009.

Mehta Supriya D SD Maclean Ian I Ndinya-Achola Jeckoniah O JO Moses Stephen S Martin Irene I Ronald Allan A Agunda Lawrence L Murugu Ruth R Bailey Robert C RC Melendez Johan J Zenilman Jonathan M JM

Antimicrobial agents and chemotherapy 20110523 8

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 μg/ml; a ciprofloxacin MIC of ≥1.0 μg/ml; and a spectinomycin MIC of ≥128.0 μg/ml. Susceptibility t ...[more]

PMID: 21606224

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Project description:BackgroundQuinolone-resistant Neisseria gonorrhoeae has swiftly emerged in Canada. We sought to determine its prevalence in the province of Ontario and to investigate risk factors for quinolone-resistant N. gonorrhoeae infection in a Canadian setting.MethodsWe used records from the Public Health Laboratory of the Ontario Agency for Health Protection and Promotion in Toronto, Ontario, and the National Microbiology Laboratory in Winnipeg, Manitoba, to generate epidemic curves for N. gonorrhoeae infection. We extracted limited demographic data from 2006 quinolone-resistant N. gonorrhoeae isolates and from a random sample of quinolone-susceptible isolates. We also extracted minimum inhibitory concentrations for commonly tested antibiotics.ResultsBetween 2002 and 2006, the number of N. gonorrhoeae infections detected by culture decreased by 26% and the number of cases detected by nucleic acid amplification testing increased 6-fold. The proportion of N. gonorrhoeae isolates with resistance to quinolones increased from 4% to 28% over the same period. Analysis of 695 quinolone-resistant N. gonorrhoeae isolates and 688 quinolone-susceptible control isolates from 2006 showed a higher proportion of men (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.3-4.1) and patients over 30 years of age (OR 3.1, 95% CI 2.4-3.8) in the quinolone-resistant group. The proportion of men who have sex with men appeared to be relatively similar in both groups (OR 1.4, 95% CI 1.1-1.8). Quinolone-resistant strains were more resistant to penicillin (p < 0.001), tetracycline (p < 0.001) and erythromycin (p < 0.001). All isolates were susceptible to cefixime, ceftriaxone, azithromycin and spectinomycin.InterpretationDuring 2006 in Ontario, 28% of N. gonorrhoeae isolates were resistant to quinolones. Infections in heterosexual men appear to have contributed significantly to the quinolone resistance rate. Medical practitioners should be aware of the widespread prevalence of quinolone-resistant N. gonorrhoeae and avoid quinolone use for empiric therapy.

Project description:BACKGROUND:Phenotypic fluoroquinolone resistance was first reported in Western Kenya in 2009 and later in Coastal Kenya and Nairobi. Until recently gonococcal fluoroquinolone resistance mechanisms in Kenya had not been elucidated. The aim of this paper is to analyze mutations in both gyrA and parC responsible for elevated fluoroquinolone Minimum Inhibitory Concentrations (MICs) in Neisseria gonorrhoeae (GC) isolated from heterosexual individuals from different locations in Kenya between 2013 and 2017. METHODS:Antimicrobial Susceptibility Tests were done on 84 GC in an ongoing Sexually Transmitted Infections (STI) surveillance program. Of the 84 isolates, 22 resistant to two or more classes of antimicrobials were chosen for analysis. Antimicrobial susceptibility tests were done using E-test (BioMerieux) and the results were interpreted with reference to European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. The isolates were sub-cultured, and whole genomes were sequenced using Illumina platform. Reads were assembled de novo using Velvet, and mutations in the GC Quinolone Resistant Determining Regions identified using Bioedit sequence alignment editor. Single Nucleotide Polymorphism based phylogeny was inferred using RaxML. RESULTS:Double GyrA amino acid substitutions; S91F and D95G/D95A were identified in 20 isolates. Of these 20 isolates, 14 had an additional E91G ParC substitution and significantly higher ciprofloxacin MICs (p?=?0.0044*). On the contrary, norfloxacin MICs of isolates expressing both GyrA and ParC QRDR amino acid changes were not significantly high (p?=?0.82) compared to MICs of isolates expressing GyrA substitutions alone. No single GyrA substitution was found in the analyzed isolates, and no isolate contained a ParC substitution without the simultaneous presence of double GyrA substitutions. Maximum likelihood tree clustered the 22 isolates into 6 distinct clades. CONCLUSION:Simultaneous presence of amino acid substitutions in ParC and GyrA has been reported to increase gonococcal fluoroquinolone resistance from different regions in the world. Our findings indicate that GyrA S91F, D95G/D95A and ParC E91G amino acid substitutions mediate high fluoroquinolone resistance in the analyzed Kenyan GC.

Project description:BACKGROUND:Treatment of gonorrhea is complicated by the development of antimicrobial resistance in Neisseria gonorrhoeae (GC) to the antibiotics recommended for treatment. Knowledge on types of plasmids and the antibiotic resistance genes they harbor is useful in monitoring the emergence and spread of bacterial antibiotic resistance. In Kenya, studies on gonococcal antimicrobial resistance are few and data on plasmid mediated drug resistance is limited. The present study characterizes plasmid mediated resistance in N. gonorrhoeae isolates recovered from Kenya between 2013 and 2018. METHODS:DNA was extracted from 36 sub-cultured GC isolates exhibiting varying drug resistance profiles. Whole genome sequencing was done on Illumina MiSeq platform and reads assembled de-novo using CLC Genomics Workbench. Genome annotation was performed using Rapid Annotation Subsystem Technology. Comparisons in identified antimicrobial resistance determinants were done using Bioedit sequence alignment editor. RESULTS:Twenty-four (66.7%) isolates had both ?-lactamase (TEM) and TetM encoding plasmids. 8.3% of the isolates lacked both TEM and TetM plasmids and had intermediate to susceptible penicillin and tetracycline MICs. Twenty-six (72%) isolates harbored TEM encoding plasmids. 25 of the TEM plasmids were of African type while one was an Asian type. Of the 36 isolates, 31 (86.1%) had TetM encoding plasmids, 30 of which harbored American TetM, whereas 1 carried a Dutch TetM. All analyzed isolates had non-mosaic penA alleles. All the isolates expressing TetM were tetracycline resistant (MIC>?1?mg/L) and had increased doxycycline MICs (up to 96?mg/L). All the isolates had S10 ribosomal protein V57M amino acid substitution associated with tetracycline resistance. No relation was observed between PenB and MtrR alterations and penicillin and tetracycline MICs. CONCLUSION:High-level gonococcal penicillin and tetracycline resistance in the sampled Kenyan regions was found to be mediated by plasmid borne blaTEM and tetM genes. While the African TEM plasmid, TEM1 and American TetM are the dominant genotypes, Asian TEM plasmid, a new TEM239 and Dutch TetM have emerged in the regions.

Dataset Information

Emergence of quinolone resistance and cephalosporin MIC creep in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009.

Publications

Emergence of quinolone resistance and cephalosporin MIC creep in Neisseria gonorrhoeae isolates from a cohort of young men in Kisumu, Kenya, 2002 to 2009.

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