Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study

Abstract

SummaryBackgroundThe emergence of Neisseria gonorrhoeae with decreased susceptibility to extended spectrum cephalosporins raises the prospect of untreatable gonorrhoea. In the absence of new treatments, efforts to slow the increasing incidence of resistant gonococcus require insight into the factors that contribute to its emergence and spread. We assessed the relatedness between isolates in the USA and reconstructed likely spread of lineages through different sexual networks.MethodsWe sequenced the genomes of 236 isolates of N gonorrhoeae collected by the Centers for Disease Control and Prevention's Gonococcal Isolate Surveillance Project (GISP) from sentinel public sexually transmitted disease clinics in the USA, including 118 (97%) of the isolates from 2009–10 in GISP with reduced susceptibility to cefixime (cefRS) and 118 cefixime-susceptible isolates from GISP matched as closely as possible by location, collection date, and sexual orientation. We assessed the association between antimicrobial resistance genotype and phenotype and correlated phylogenetic clustering with location and sexual orientation.FindingsMosaic penA XXXIV had a high positive predictive value for cefRS. We found that two of the 118 cefRS isolates lacked a mosaic penA allele, and rechecking showed that these two were susceptible to cefixime. Of the 116 remaining cefRS isolates, 114 (98%) fell into two distinct lineages that have independently acquired mosaic penA allele XXXIV. A major lineage of cefRS strains spread eastward, predominantly through a sexual network of men who have sex with men. Eight of nine inferred transitions between sexual networks were introductions from men who have sex with men into the heterosexual population.InterpretationGenomic methods might aid efforts to slow the spread of antibiotic-resistant N gonorrhoeae through augmentation of gonococcal outbreak surveillance and identification of populations that could benefit from increased screening for aymptomatic infections.FundingAmerican Sexually Transmitted Disease Association, Wellcome Trust, National Institute of General Medical Sciences, and National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance

“…The average size of the recombination regions identified was 360 base pairs. The estimate for the ratio of effects of recombination and mutation (r/m) for our strain set was 2.2, a relatively high value for bacterial species (Didelot & Maiden, 2010) (Fig S3, and quite similar to the r/m estimate of 1.9 based on the whole genome alignment on a less genetically diverse group of N. gonorrhoeae strains reported by Grad et al (Grad et al, 2014).…”

“…Recent multi-genome studies have focused on either a restricted geographic region (Vidovic et al, 2014) (genomes also included in present studies or on a small subset of the N. gonorrhoeae population (Grad et al, 2014). Hence, there is a need for studies aimed at understanding the global N.…”

“…Our approach in this study builds on recent multi-genome studies (Grad et al, 2014;Vidovic et al, 2014), with the goal of using whole genome analysis to elucidate two processes: 1) the population structure and dynamics of Neisseria gonorrhoeae and 2) the correlation between this population differentiation and AMR evolution in gonococci. Our genome analysis of strains from multiple sites across the world offers a geographic diversity of N. gonorrhoeae isolates, providing more depth in genome-wide studies of this pathogen and identifying possible sub-populations impacting AMR and evolution within the species.…”

Sexually transmitted infections: challenges ahead

“…Effective STI control will require the political will to prioritise and invest in new 150 rapid molecular methods for predicting AMR (for AMR surveillance but ideally also to inform individualized treatment), [190][191][192] rapid point of care tests for diagnosis of gonorrhoea (ideally with combined prediction of AMR); 190,191 ideal phylogenomics of gonococci and their AMR (also in non-cultured samples); 159,457,[459][460][461][462][463][464] and appropriate models for pharmacokinetics/ pharmacodynamics (urogenital and extragenital sites) and prediction of AMR induction/selection, evolution and biological fitness. -Data are for principal diagnosis, recorded using the ICD-9-CM from 1993-94 to 1997-98, and recording using the ICD-10-AM (Australian modification) from 1998-99.…”

Challenges with antimicrobial susceptibility testing forNeisseria gonorrhoeaein the era of extensively drug-resistant gonorrhoea — molecular antimicrobial resistance testing crucial

“…for rapid point-of-care tests), treatment and vaccine; and even find associations with pathogenesis (tissue tropism, type and severity of infection, etc.). 8,9 …”