Influence of inoculum size on activity of cefoperazone, cefotaxime, moxalactam, piperacillin, and N-formimidoyl thienamycin (MK0787) against Pseudomonas aeruginosa

Abstract

Forty clinical isolates of Pseudomonas aeruginosa were tested for their susceptibility to cefoperazone, cefotaxime, moxalactam, piperacillin, N-formimidoyl thienamycin (MK0787), and gentamicin at three different inocula. At an inoculum of 5 x 10(3) colony-forming units (CFU) per ml, the minimum inhibitory concentrations (in micrograms per milliliter) for 90% of isolates (MIC90) were as follows: gentamicin, 1; N-formimidoyl thienamycin, 2; cefoperazone, 4; piperacillin, 8; moxalactam, 16; and cefotaxime, 16. When the inoculum was increased to 5 x 10(5) CFU/ml, the MIC90 for all drugs tested increased. Among the beta-lactam antibiotics, N-formimidoyl thienamycin and cefoperazone had the lowest MIC90 (8 micrograms/ml) at this inoculum. When the inoculum was increased further to 5 x 10(7) CFU/ml, an MIC90 could be determined only for gentamicin and N-formimidoyl thienamycin (4 and 8 micrograms/ml, respectively). Indeed, the MIC50 for moxalactam, cefotaxime, cefoperazone, and piperacillin was 128 micrograms/ml or more at this inoculum. The minimum bactericidal concentration for 90% of isolates (MBC90) at an inoculum of 5 x 10(5) CFU/ml ranged from 8 micrograms/ml for gentamicin and N-formimidoyl thienamycin to 128 micrograms/ml for cefotaxime. At the highest inoculum, however, whereas the MBC90 for gentamicin and N-formimidoyl thienamycin remained at 8 micrograms/ml, the MBC90 for each of the other drugs was greater than 128 micrograms/ml. N-Formimidoyl thienamycin was the only drug tested for which an MIC100 and MBC100 (MIC and MBC for 100% of isolates) could be determined, and these were not significantly different from the MIC90 and MCB90.