Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden

Background Neisseria gonorrhoeae has developed resistance to most antimicrobials used for treatment. Worryingly, treatment failures with oral extended-spectrum cephalosporins (ESCs) have been reported, especially in the WHO Western Pacific Region, and susceptibility to all ESCs (oral and injectable), the last remaining treatment options in many settings, is decreasing globally. Objectives To examine the emergence, spread and characteristics of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Sweden. Methods All available Swedish isolates from 1998-2009, collected from many countries worldwide, displaying decreased susceptibility to cefixime and/or ceftriaxone (minimum inhibitory concentration (MIC) >= 0.032 mg/l; n=331) were examined using antibiograms, full-length porB gene sequencing, N gonorrhoeae multi-antigen sequence typing (NO-MAST), and sequencing of ESC resistance determinants (penA, mtrR and porB1b (penB alteration)). Results Based on EUCAST breakpoints, 30 (9.1%) and one (0.3%) of the isolates displayed in vitro resistance to cefixime and ceftriaxone, respectively. penA mosaic alleles and penA A501 alteration were detected in 24% and 11%, respectively, of the isolates, and in increasing prevalence over the years. Moreover, among these isolates 38 NO-MAST sequence type (STs) were detected, with ST1407 (n=29), ST1103 (n=9) and ST3378 (n=8) being most common. Conclusions The proportions of N gonorrhoeae isolates with decreased susceptibility and resistance to ESCs have substantially increased over the years in Sweden. Both penA mosaic alleles and the penA A501 alteration, together with mtrR and penB, are important for the decreased susceptibility and resistance to ESCs. At least one gonococcal penA mosaic strain (ST1407), including its evolving subtypes, with decreased susceptibility/resistance to ESCs circulates worldwide.