title: Phenotypic and genetic characterization of the first two cases of extended-spectrum-cephalosporin-resistant Neisseria gonorrhoeae infection in South Africa and association with cefixime treatment failure.
abstract: OBJECTIVE
  To describe the phenotypic and genetic characteristics of the first two cases of extended-spectrum cephalosporin (ESC)-resistant Neisseria gonorrhoeae in South Africa, one of which was associated with verified cefixime treatment failure.
  
  
  METHODS
  Two ESC-resistant N. gonorrhoeae isolates were cultured from the urethral discharge of two men who have sex with men (MSM). One man reported a persistent urethral discharge that had failed to respond to previous therapy with oral cefixime. Agar dilution MICs were determined for eight antibiotics. β-Lactam-associated resistance mutations were identified through PCR-based amplification and sequencing for several key genes: penA, mtrR and its promoter, porB1b (penB), ponA and pilQ. For molecular epidemiological characterization, full-length porB gene sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) were performed.
  
  
  RESULTS
  Both isolates were resistant to cefixime, ciprofloxacin, penicillin and tetracycline and intermediate/resistant to azithromycin, but susceptible to ceftriaxone, gentamicin and spectinomycin. Both isolates had the type XXXIV penA mosaic allele in addition to previously described resistance mutations in the mtrR promoter (A deletion), porB1b (penB) (G101K and A102N) and ponA1 (L421P). Both isolates had an identical NG-MAST sequence type (ST4822) and MLST sequence type (ST1901).
  
  
  CONCLUSIONS
  Both isolates were resistant to cefixime and possessed a number of identical mutations in key genes contributing to ESC resistance in N. gonorrhoeae. The two isolates contained the type XXXIV penA mosaic allele and belonged to a successful international MSM-linked multidrug-resistant gonococcal clone (MLST ST1901) associated with several cefixime treatment failures in Europe and North America.
authors: Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, National Health Laboratory Service, 1 Modderfontein Road, Sandringham 2192, South Africa. davidl@nicd.ac.za
authors: David A
authors: DA
authors: Lewis
authors: Charlotte
authors: C
authors: Sriruttan
authors: Etienne E
authors: EE
authors: Müller
authors: Daniel
authors: D
authors: Golparian
authors: Lindy
authors: L
authors: Gumede
authors: Donald
authors: D
authors: Fick
authors: Johan
authors: J
authors: de Wet
authors: Venessa
authors: V
authors: Maseko
authors: Jennifer
authors: J
authors: Coetzee
authors: Magnus
authors: M
authors: Unemo
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015373:Bacterial Typing Techniques; D020682:Cefixime / Q000627:therapeutic use*; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000494:pharmacology; D018550:Cephalosporin Resistance / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D005798:Genes, Bacterial / Q000235:genetics; D006069:Gonorrhea / Q000188:drug therapy* / Q000382:microbiology*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013019:South Africa; D017211:Treatment Failure; D047568:Unsafe Sex; D000097623:Cefpodoxime
chemical_list: D000900:Anti-Bacterial Agents; D020682:Cefixime; D015296:Ceftizoxime; D004269:DNA, Bacterial; D000097623:Cefpodoxime
keywords: cefpodoxime; ceftriaxone; gonorrhoea; mosaic penA genes