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


METHODS
We 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 (cef(RS)) 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.


RESULTS
Mosaic penA XXXIV had a high positive predictive value for cef(RS). We found that two of the 118 cef(RS) isolates lacked a mosaic penA allele, and rechecking showed that these two were susceptible to cefixime. Of the 116 remaining cef(RS) isolates, 114 (98%) fell into two distinct lineages that have independently acquired mosaic penA allele XXXIV. A major lineage of cef(RS) 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.


CONCLUSIONS
Genomic 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 asymptomatic infections.
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ygrad@hsph.harvard.edu.
Yonatan H
YH
Grad
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Robert D
RD
Kirkcaldy
Centers for Disease Control and Prevention, Atlanta, GA, USA.
David
D
Trees
Wellcome Trust Sanger Institute, Hinxton, UK.
Janina
J
Dordel
Wellcome Trust Sanger Institute, Hinxton, UK.
Simon R
SR
Harris
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Edward
E
Goldstein
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Hillard
H
Weinstock
Wellcome Trust Sanger Institute, Hinxton, UK.
Julian
J
Parkhill
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
William P
WP
Hanage
Wellcome Trust Sanger Institute, Hinxton, UK; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK.
Stephen
S
Bentley
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Marc
M
Lipsitch
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D020682:Cefixime / Q000627:therapeutic use*; D018550:Cephalosporin Resistance / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics; D005838:Genotype; D006069:Gonorrhea / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics*; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D000900:Anti-Bacterial Agents; D020682:Cefixime