The inhibitory and bactericidal activities of carbenicillin, ticarcillin, moxalactam, cefoperazone, azlocillin, piperacillin, ceftazidime, and three aminoglycosides, alone and in various combinations, were determined against 60 isolates of Pseudomonas aeruginosa from the sputum of patients with cystic fibrosis. Ceftazidime was the most active ,B-lactam, with minimum inhibitory and bactericidal concentrations for 90o of isolates of 4 ,ug/ml. Moxalactam was the least active of the new -lactams, with activity equivalent to that of carbenicillin; each had a minimum inhibitory concentration for 90% of isolates of 64 ,ug/ml and a minimum bactericidal concentration for 90% of isolates of 128 p.g/ml. Of the recently introduced 3-lactam derivatives, azlocillin, cefoperazone, ceftazidime, moxalactam, and piperacillin have a higher order of activity than their predecessors against not only the Enterobacteriaceae but also against Pseudomonas aeruginosa (2,10,13,15,18). Thus, they might be useful in the treatment ofP. aeruginosa pulmonary infections which are currently difficult to manage in patients with cystic fibrosis (CF). This possibility led to the current study of the activities of these new 3-lactams, alone and in combination with each other or gentamicin, tobramycin, and amikacin, against 60 isolates of P. aeruginosa from the sputum of patients with CF.
MATERIALS AND METHODSA total of 60 isolates of P. aeruginosa, including mucoid and nonmucoid strains, was identified by standard microbiological methods. The organisms were then stored on tryptic soy agar slants and were checked for purity and subcultured monthly.Moxalactam (Eli Lilly & Co.), piperacillin (Lederle Laboratories), carbenicillin (Roerig-Pfizer Co.), azlocillin (Delbay Research Corp.), ticarcillin (Beecham Laboratories), cefoperazone (Pfizer Inc.), ceftazidime (Glaxo Research Group), gentamicin (Schering Corp.), tobramycin (Eli Lilly), and amikacin (Bristol Laboratories) were furnished as dry powders. Stock solutions were prepared from these powders and were used immediately or stored at -70°C for no longer than 2 weeks.Minimum inhibitory concentrations (MICs) were determined by microbroth dilution, and combination studies were done by microbroth checkerboard methods. Mueller-Hinton broth was used for all determinations. Mueller-Hinton broth was adjusted to optimal calcium and magnesium concentrations and a pH of 7.2 to 7.4 (6). The preparation and inoculation of microbroth plates were accomplished with the MIC-2000 system (Dynatech Corp.). Plates were used immediately or stored at -70°C for no longer than 2 weeks. Microbroth plates received an inoculum consisting of a 10' dilution of a log-phase culture adjusted to the density of a 0.