Activities of various beta-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis

Abstract

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.

Changing susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the clinical use of newer antibiotics

“…Patterns of increasing resistance to aztreonam and ceftazidimie may lead to the use of these agents in combination treatment regimens. Although the rate of in vitro synergy between ceftazidime and the aminoglycosides appears to be low (17), the rate for aztreonam-aminoglycoside combinations is comparable to that observed for aminoglycosides combined with various penicillin derivatives (2,6). It should be noted, however, that clinical response to antibiotic combinations has not been clearly shown to be superior to that obtained with singleagent therapy (6).…”

Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis

“…The agent has in vitro activity against gram-negative bacilli comparable to that of other new cephalosporin derivatives but is more active against Pseudomonas aeruginosa (9,13). It is also active against 1-lactamasepositive and -negative Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis (3,5), the principal pathogens of meningitis of infancy and early childhood.…”

Bactericidal and synergistic activity of moxalactam alone and in combination with gentamicin against Pseudomonas aeruginosa

“…This assessment has, with a single exception (18), been based on the results of microdilution test procedures with inoculum sizes and subculture volumes which have been insufficient for an accurate determination of 99.9% killing (2,19). At the same time, assessments of the interaction of moxalactam and aminoglycosides have been based almost entirely on their inhibitory activities alone and in combination (9,12,15,17,21).…”