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Genomic Epidemiology of Azithromycin-Nonsusceptible Neisseria gonorrhoeae, Argentina, 2005-2019.

ABSTRACT: Azithromycin-nonsusceptible Neisseria gonorrhoeae strains are an emerging global public health threat. During 2015-2018, the prevalence of azithromycin-nonsusceptible gonococcal infection increased significantly in Argentina. To investigate the genomic epidemiology and resistance mechanisms of these strains, we sequenced 96 nonsusceptible isolates collected in Argentina during 2005-2019. Phylogenomic analysis revealed 2 main clades, which were characterized by a limited geographic distribution, circulating during January 2015-November 2019. These clades included the internationally spreading multilocus sequence types (STs) 1580 and 9363. The ST1580 isolates, which had MICs of 2-4 μg/mL, had mutations in the 23S rRNA. The ST9363 isolates, which had MICs of 2-4 or >256 μg/mL, had mutations in the 23S rRNA, a mosaic mtr locus, or both. Identifying the geographic dissemination and characteristics of these predominant clones will guide public health policies to control the spread of azithromycin-nonsusceptible N. gonorrhoeae in Argentina.

SUBMITTER: Gianecini RA

PROVIDER: S-EPMC8386799 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genomic Epidemiology of Azithromycin-Nonsusceptible Neisseria gonorrhoeae, Argentina, 2005–2019

Project description:Genomic Epidemiology of Azithromycin-Nonsusceptible Neisseria gonorrhoeae, Argentina, 2005–2019

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Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014.

Project description:The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM(r)) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM(r) strains. The genomes of 213 AZM(r) and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM(r) (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZM(r) collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZM(r) (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZM(r) was also associated with mtrR promoter mutations, including the -35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM(r) strains arise independently and can then rapidly expand clonally in a region through local sexual networks.

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Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand.

Project description:Background:Antimicrobial-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. Methods:A 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. Results:Eleven 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. Conclusions:The 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:Genomic epidemiology of Neisseria gonorrhoeae

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Genomic epidemiology and population structure of Neisseria gonorrhoeae in Norway, 2016-2017.

Project description:This study presents the nationwide epidemiology of Neisseria gonorrhoeae, using whole-genome sequencing of all culture-positive cases, which comprise roughly 40 % of all cases of gonorrhea reported in Norway from 2016 to 2017. Isolates were assigned to sequence types and Bayesian analysis clusters and variation in genes coding for antibiotic resistance was linked to phenotypic resistance data. The study also included isolates taken from the same patients from different anatomical sites at one or more time points. Comparing these isolates allows for observation of patterns of infections, i.e. multiple reinfections of genetically related clones vs. reinfections of genetically distant clones, and quantification of the genomic variation of closely related isolates from samples taken from a patient within the same day. Demographically, the patients in the study could be split into two groups; one group of patients from the capital with a high proportion of men who have sex with men (MSM), and another consisting of young adults with transmission primarily between males and females from outside the capital. Some clusters of N. gonorrhoeae were restricted to one of these two demographic groups. Pairwise comparison of multiple isolates from the same patients revealed that most were reinfected with different clones. Observations of frequent reinfections in patients is a concern and should be taken into account in the development of improved information and treatment guidelines.

| S-EPMC7276708 | biostudies-literature

Emergence and Genomic Characterization of Neisseria gonorrhoeae Isolates with High Levels of Ceftriaxone and Azithromycin Resistance in Guangdong, China, from 2016 to 2019.

Project description:Currently, antibiotic resistance (especially ceftriaxone and azithromycin dual resistance) in Neisseria gonorrhoeae is the main obstacle affecting the efficacy of treatment. As analysis of drug sensitivity, molecular features, and dissemination of dual-resistant strains is important for gonococcal prevention and control, MIC, genotyping, and genome analysis were conducted to reveal the molecular characteristics and phylogeny of N. gonorrhoeae isolates. During 2016 to 2019, 5 out of 4,113 strains were defined as dual-resistant clones, with ceftriaxone MICs of 0.25 to ≥1 mg/L and azithromycin MICs of 2 to ≥2,048 mg/L. In particular, two strains with a ceftriaxone MIC above 0.5 mg/L were characterized as penA-60.001 FC428-related clones, and two isolates with a high-level azithromycin MIC above 1,024 mg/L featuring a 23S rRNA mutation were identified. Furthermore, phylogenetic analysis confirmed that the dual-resistant strains were closer to the evolutionary origin of F89 in France, global FC428-related clones, and high-level dual-resistant clones in Australia and the United Kingdom. Dual-resistant strains, including FC428-related clones and high-level azithromycin-resistant clones, have circulated in Guangdong, China. The ability of laboratories to perform real-time drug susceptibility and genetic analyses should be strengthened to monitor the spread of threatening strains. IMPORTANCE Here, we report five sporadic dual-resistant isolates, including FC428-related ceftriaxone-resistant clones with MICs of ≥0.5 mg/L and high-level azithromycin resistance with MICs of ≥1,024 mg/L. This study highlights that dual-resistant clones with the same evolutionary origin as FC428, A2735, and F89 have circulated in Guangdong, China, which suggests that the capacity for antibiotic resistance testing and genome analysis should be strengthened in daily epidemiological surveillance.

| S-EPMC9769569 | biostudies-literature

Analysis of Neisseria gonorrhoeae azithromycin susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013.

Project description:Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144 N. gonorrhoeae isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC50 was 0.25 μg/ml, and the MIC90 was 0.5 μg/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 μg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States, and the prevalence of reduced azithromycin susceptibility remains low. These findings support the continued use of azithromycin in a combination therapy regimen for gonorrhea.

| S-EPMC4335827 | biostudies-literature

Sustained Transmission of Neisseria gonorrhoeae Strains with High-Level Azithromycin Resistance (MIC ≥ 256 μg/mL) in Argentina, 2018 to 2022.

Project description:Azithromycin combined with ceftriaxone is the recommended dual therapy for uncomplicated gonorrhea in many countries. Nevertheless, the increasing prevalence of azithromycin resistance compromises the effectiveness of this treatment strategy. From 2018 to 2022, we collected 13 gonococcal isolates with high-level azithromycin resistance (MIC ≥ 256 μg/mL) across Argentina. Whole-genome sequencing revealed that these isolates were mainly represented by the internationally spreading Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup G12302, containing the 23S rRNA A2059G mutation (in all four alleles) together with mosaic mtrD and mtrR promoter 2 loci. This information is important to develop targeted public health policies to control the spread of azithromycin-resistant N. gonorrhoeae in Argentina and internationally. IMPORTANCE Azithromycin resistance in Neisseria gonorrhoeae has been increasing in numerous populations worldwide, which is of concern, as azithromycin is part of the recommended dual treatment in many countries. Here, we report 13 N. gonorrhoeae isolates with high-level azithromycin resistance (MIC ≥ 256 μg/mL). This study observed that high-level azithromycin-resistant gonococcal strains have shown sustained transmission in Argentina and are related to the successful international clone NG-MAST G12302. Genomic surveillance together with real-time tracing and data-sharing networks will be crucial in controlling the spread of azithromycin resistance in gonococcus.

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| S-EPMC7179607 | biostudies-literature

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Project description:Rising azithromycin nonsusceptibility among Neisseria gonorrhoeae isolates threatens current treatment recommendations, but the cause of this rise is not well understood. We performed an ecological study of seasonal patterns in macrolide use and azithromycin resistance in N. gonorrhoeae, finding that population-wide macrolide use is associated with increased azithromycin nonsusceptibility. These results, indicative of bystander selection, have implications for antibiotic prescribing guidelines.

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