In vitro microbiological properties of mezlocillin compared with four cephalosporins

The intrinsic activity, antibacterial spectrum and beta-lactamase stability of mezlocillin were determined and compared with that of four other beta-lactams: ceftriaxone, ceftizoxime, cefotaxime, cefuroxime. These parameters were studied by determining the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against 397 gram-negative bacteria including Pseudomonas sp. and 124 gram-positive cocci, utilizing 10(5) and 10(7) CFU/ml bacterial concentrations. The sensitivity to ten different standard beta-lactamases was determined by a spectrophotometric method that utilizes the velocity of cytochrome c reduction. Mezlocillin was hydrolyzed, at different degrees, by all the beta-lactamases under examination (TEM 1, TEM 2, OXA1, OXA2, OXA3, S + A, P99, STH4, SHV1, K1) but such hydrolysis did not affect its bactericidal activity which was similar to that of the other beta-lactamase-stable beta-lactams. In addition MBC/MIC ratios were very low and the differences of MIC values at different bacterial inocula were not significant. We also studied the stimulation of inducible beta-lactamases by subinhibitory doses of antibiotics, the eventual changes of antibiotic susceptibility after these stimulations and, finally, the frequency of spontaneous resistant mutants. Mezlocillin stimulated the production of inducible beta-lactamases in 50% of the bacteria examined, but in contrast with the other drugs tested, no increase of MICs occurred nor did mezlocillin select resistant mutants.