Association of Phylogenomic Relatedness among Neisseria gonorrhoeae Strains with Antimicrobial Resistance, Austria, 2016-2020.
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SUBMITTER: Schaeffer J
PROVIDER: S-EPMC9328923 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Association of Phylogenomic Relatedness among Neisseria gonorrhoeae Strains with Antimicrobial Resistance, Austria, 2016-2020.
Schaeffer Justine J Lippert Kathrin K Pleininger Sonja S Stöger Anna A Hasenberger Petra P Stadlbauer Silke S Heger Florian F Eigentler Angelika A Geusau Alexandra A Indra Alexander A Allerberger Franz F Ruppitsch Werner W
Emerging infectious diseases 20220801 8
We investigated genomic determinants of antimicrobial resistance in 1,318 Neisseria gonorrhoeae strains isolated in Austria during 2016-2020. Sequence type (ST) 9363 and ST11422 isolates had high rates of azithromycin resistance, and ST7363 isolates correlated with cephalosporin resistance. These results underline the benefit of genomic surveillance for antimicrobial resistance monitoring. ...[more]
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Project description:Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.
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Project description:Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.
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Project description:The emergence of Neisseria gonorrhoeae strains that are resistant to azithromycin and extended-spectrum cephalosporins represents a public health threat, that of untreatable gonorrhea infections. Multivariate regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to the overall antimicrobial MICs for ceftriaxone, cefixime, azithromycin, tetracycline, ciprofloxacin, and penicillin. A training data set consisting of 1,280 N. gonorrhoeae strains was used to generate regression equations which were then applied to validation data sets of Canadian (n = 1,095) and international (n = 431) strains. The predicted MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) were fully explained by 5 amino acid substitutions in PenA, A311V, A501P/T/V, N513Y, A517G, and G543S; the presence of a disrupted mtrR promoter; and the PorB G120 and PonA L421P mutations. The correlation of predicted MICs within one doubling dilution to phenotypically determined MICs of the Canadian validation data set was 95.0% for ceftriaxone, 95.6% for cefixime, 91.4% for azithromycin, 98.2% for tetracycline, 90.4% for ciprofloxacin, and 92.3% for penicillin, with an overall sensitivity of 99.9% and specificity of 97.1%. The correlations of predicted MIC values to the phenotypically determined MICs were similar to those from phenotype MIC-only comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics to better monitor the dynamics of N. gonorrhoeae.
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Project description:BackgroundAntimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high.MethodsA population-level study of N. gonorrhoeae in New Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS data were obtained for 398 isolates. Relatedness was inferred using phylogenetic trees, and pairwise core SNPs. Mutations and genes known to be associated with resistance were identified, and correlated with phenotype.ResultsEleven clusters were identified. In six of these clusters, >25% of isolates were from females, while in eight of them, >15% of isolates were from females. Drug resistance was common; 98%, 32% and 68% of isolates were non-susceptible to penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates (cefixime MICs ≥ 0.12 mg/L, ceftriaxone MICs ≥ 0.06 mg/L). Only nine isolates had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all had mutations in mtrR or its promoter.ConclusionsThe high proportion of females in clusters suggests transmission is not exclusively among MSM in New Zealand; re-assessment of risk factors for transmission may be warranted in this context. As elevated MICs of ESCs and/or azithromycin were found in closely related strains, targeted public health interventions to halt transmission are urgently needed.
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Project description:Among 114 clinical Neisseria gonorrhoeae isolates collected in Vietnam during 2019-2020, we detected 15 of subclone sequence type 13871 of the FC428 clonal complex. Fourteen sequence type 13871 isolates with mosaic penA allele 60.001 were ceftriaxone or cefixime nonsusceptible, and 3/14 were azithromycin nonsusceptible. Emergence of this subclone threatens treatment effectiveness.
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