NCCLS perspectives in changing susceptibility breakpoints for antimicrobial drugs

Abstract

The spread of resistance to many antimicrobial agents in various microbial species has been highlighted by the World Health Organisation and many government agencies around the world. The reasons for this increase and spread are complex and are discussed. A number of surveillance studies has monitored the increase in resistance among isolates of Streptococcus pneumoniae to various important classes of antimicrobials. These results are discussed with particular reference to penicillins, macrolides and fluoroquinolones. Although there is evidence that in vitro resistance to macrolides and more recently to fluoroquinolones may be associated with a reduced clinical efficacy, there is no such clear association with resistance to β-lactams and lack of clinical efficacy in non-meningeal infections. Resistance or susceptibility to an antimicrobial agent is based on breakpoints and these are set in the US by the National Committee of Clinical and Laboratory Standards. In response to these recent clinical studies showing that non-meningeal pneumococcal infections with strains classified as resistant in vitro still responded well to treatment with various β-lactams, new breakpoints have been set. Results are presented showing that using these breakpoints, the levels of resistance to the third generation cephalosporins, ceftriaxone and cefotaxime against a range of non-meningeal pneumococcal isolates were lower than those obtained using the previous breakpoints. The excellent pharmacokinetic and pharmacodynamic properties of these agents are believed to contribute to their good activity in the clinic.