title: Comparison of antimicrobial in vitro activities against Streptococcus pneumoniae independent of MIC susceptibility breakpoints using MIC frequency distribution curves, scattergrams and linear regression analyses.
abstract: Comparing in vitro activities of antimicrobial agents against Streptococcus pneumoniae using per cent susceptible to recommended MIC breakpoints is not optimal. In this study, MICs of penicillin G, ampicillin/sulbactam, ceftriaxone, cefuroxime, erythromycin, tetracycline, trimethoprim/sulfamethoxazole, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin were determined for 646 strains. Drug activities were compared using MIC frequency distribution curves, scattergrams and linear regression analyses of MICs (log2). MIC frequency distributions did not always correspond to recommended breakpoints for distinguishing susceptible, intermediate and resistant strains. Penicillin G, ampicillin/sulbactam and ceftriaxone had similar activities and were each c. 1-1.5 dilution steps more active than cefuroxime. For all beta-lactam drug pairs, there was a high correlation of MICs with regression line slopes (a approximately equal to 1) and coefficients of determination (R(2) = 0.90-0.97). Although beta-lactam-resistant strains were more likely to be resistant to erythromycin, tetracycline and/or trimethoprim/sulfamethoxazole than were beta-lactam-susceptible strains, MIC correlations were relatively poor (R(2) = 0.14-0.46), as they were when the non-beta-lactam drugs were compared with each other (R(2) = 0.10-0.25). Trovafloxacin and moxifloxacin were each c. 2.5 dilution steps more active than ciprofloxacin and levofloxacin. There was no correlation of quinolone MICs with MICs of any other drug class (R(2) 0.02). Among the quinolones, however, there was a high correlation of MICs with a approximately equal to 1 and R(2) = 0.81-0.92. With the quinolone drug pairs, lines of best fit were second-order polynomial equations, consistent with a dissociation of low level resistance mechanisms. In summary, beta-lactam and quinolone MICs were predictable within drug classes and testing multiple derivatives within each class is probably not necessary. Although there was some relationship between beta-lactam, erythromycin, tetracycline and trimethoprim/sulfamethoxazole MICs, predictability of MICs between drug classes was poor. There was no relationship between quinolone MICs and MICs of any of the other drugs tested.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA. fass.1@osu.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Fass
authors.forename: J
authors.initials: J
authors.lastname: Barnishan
mesh_terms: D042462:4-Quinolones; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000502:physiology; D006801:Humans; D007769:Lactams; D016014:Linear Models; D008826:Microbial Sensitivity Tests / Q000592:standards / Q000706:statistics & numerical data*; D016011:Normal Distribution; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D007769:Lactams