Cefditoren activity against nearly 1000 non-fastidious bacterial isolates and the development of in vitro susceptibility test methods

Abstract

Cefditoren (formerly ME-1206) is an investigational, orally administered cephalosporin ester with bactericidal activity against many Gram-positive and -negative organisms. Cefditoren potency against nearly 1000 non-fastidious species was determined by National Committee for Clinical Laboratory Standards (NCCLS) reference broth microdilution and standardized disk diffusion methods. Against staphylococci, usable cefditoren activity was completely correlated with oxacillin with respect to potency and susceptibility interpretation ( mec A-negative strains). Cefditoren was very active against Klebsiella spp., Proteus mirabilis, Salmonella spp., and Escherichia coli (MIC 90 range, 0.12–1 μg/ml; median zone, 23–26 mm). Cefditoren had more limited activity against Citrobacter spp., Enterobacter spp., Serratia marcescens, and indole-positive Proteae (MIC 50 range, 0.12–1 μg/ml; MIC 90, > 16 μg/ml; median zone, 18–25 mm). Against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp., and other non-fermentors, cefditoren was inactive (MIC 90, > 16 μg/ml; zone, 6 mm). Pharmacokinetic analysis of cefditoren showed that utilized dosages produce a plasma concentration that exceeds 0.5 μg/ml for 5 to 8 h and 1 μg/ml for 4 to 6 hours (T 1/2 ranges from 1.5–2 h). The following interpretive criteria were suggested: ≤ 2 μg/ml or ≥ 15 mm (susceptible) and ≥ 8 μg/ml or ≤ 11 mm (resistance) that yielded an intermethod categorical agreement of 95.8% and very major or major error rates of 0.7% and 0.3%, respectively. Alternatively, ≤ 1 μg/ml or ≥ 18 mm (susceptible) and ≥ 4 μg/ml or ≤ 14 mm (resistant) breakpoints resulted in 96.2% accuracy and combined serious errors of only 1.1%. Cefditoren was observed to be a very active cephalosporin ranking among the most potent available orally active β-lactams for use against a wide variety of pathogens.