The antimicrobial activity of cefotaxime: comparative multinational hospital isolate surveys covering 15 years.

The "third-generation" cephalosporins (3GC) have emerged as one of the most significant therapeutic entities in the last 15 years. These 3GC compounds (using cefotaxime as a model) have generally maintained their potency and spectrum of activity against important pathogens. However, the continuing popularity of this class associated with local, regional, or national-level use or abuse has led to efficacy reduction against some organism populations associated with selection of Class I cephalosporinase, stably derepressed mutants predominantly among Citrobacter and Enterobacter spp.; emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (usually Klebsiella spp.), as well as some isolates mimicking Class I-type resistance patterns; and lastly, altered PBP-mediated resistances among pneumococci, Haemophilus influenzae and pathogenic Neisseria spp. Some of these resistance patterns had been present prior to the clinical introduction of 3GCs and have only significantly threatened their use in the last 5 years. Prudent application of these 3GC drugs should be the goal for this decade as follows: 1) use as monotherapy at appropriate doses and frequencies only for organisms with low potential for mutational events; 2) use combination therapy routinely for organisms such as Citrobacter, Enterobacter, some indole-positive protease and Pseudomonas aeruginosa, to minimize emerging resistance clones; 3) use conservatively in high risk patients to minimize "super-colonization" by emerging problem bacteria (e.g. vancomycin-resistant enterococci, Xanthomonas maltophilia etc.); 4) use only those agents among 3GCs that have documented safety, broad clinical applications to all age groups, acceptable pharmacokinetic features and clear cost-saving potential; and 5) use in prophylaxis (surgical procedure, selective decontamination), should be focused toward single-dose or short-course regimens to reduce total hospital-wide exposure to broad-spectrum beta-lactam drugs.(ABSTRACT TRUNCATED AT 250 WORDS)