Neisseria gonorrhoeae and emerging resistance to extended spectrum cephalosporins

Abstract

Antibiotic resistance in Neisseria gonorrhoeae poses on-going problems for individual case management and disease control for gonorrhoea. Considerable reliance is now placed on third-generation cephalosporins for the treatment of gonorrhoea following the loss of efficacy of penicillins and quinolones. Current clinical and laboratory perspectives on N. gonorrhoeae with decreased susceptibility to third-generation cephalosporins are provided. Treatment failures following therapy with the oral third-generation cephalosporins cefixime and ceftibuten have been reported, but not with the injectable ceftriaxone. The gonococci involved have raised minimal inhibitory concentrations to these agents, including to ceftriaxone. The presence of multiple chromosomal changes form the basis for this 'resistance', prominent among which is a mosaic penicillin-binding protein 2 found in association with additional known and unknown mutations in other genes. The imprecise nature of laboratory criteria for detecting these gonococci means that the distribution and prevalence of these strains is also uncertain. Concerns regarding the appearance of gonococci associated with treatment failure with oral cephalosporins are increasing. The origins, causes and patterns of spread of these clinically resistant gonococci are reminiscent of the earlier experiences with quinolone-resistant gonococci. Preventive measures require simultaneous implementation of disease-control principles, coupled with those for antimicrobial resistance.