In Vitro Activity of Piperacillin Compared with That of Carbenicillin, Ticarcillin, Ampicillin, Cephalothin, and Cefamandole Against Pseudomonas aeruginosa and Enterobacteriaceae

Abstract

Piperacillin (T-1220), a semisynthetic derivative of aminobenzylpenicillin, was more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa; over 60% of isolates were inhibited at a concentration of 6.3 ug/ml. Piperacillin was bactericidal for 84% of Pseudomonas strains at 100 ,ug/ml, carbenicillin killed 60%, and ticarcillin killed 68% at that concentration. Piperacilhin was also more active than the other penicillins against isolates of Escherichia coli, Enterobacter, and Proteus mirabilis. The combination of piperacillin and tobramycin, demonstrating synergistic inhibition of 87% of strains of P. aeruginosa, was the most active of the penicillin-aminoglycoside combinations tested for synergism.Piperacillin sodium (T-1220) is a new semisynthetic penicillin with a broad spectrum of activity against gram-negative bacteria. In recent studies, many isolates of Pseudomonas aeruginosa and members of the Enterobacteriaceae were noted to be more susceptible to piperacillin than to carbenicillin (6,14,15). In the current study, the in vitro activity of piperacillin was compared with that of carbenicillin and ticarcillin against P. aeruginosa, and with that of carbenicillin, ticarcillin, ampicillin, cephalothin, and cefamandole against various Enterobacteriaceae. In addition, we compared combinations of piperacillin or carbenicillin with gentamicin or tobramycin for synergistic activity against P. aeruginosa. MATERIALS AND METHODSBacterial isolates. Fifty isolates each of Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, and P. aeruginosa, 37 of Enterobacter spp., 28 indolepositive Proteus, 13 Providencia stuartii, and 5 Serratia marcescens constituted the 283 bacterial isolates obtained from the diagnostic microbiology laboratory of the Royal Victoria Hospital. The identity of all isolates was confirmed by standard methods (3, 9). Not more than one isolate of a given species per patient was included.Culture medium. Mueller-Hinton broth was supplemented with calcium chloride and magnesium chloride (12). The final calcium concentration was 5.4 to t Present address: Division of Virology, New Addenbrooke's Hospital, Cambridge, England.6.0 mg/dl, and the magnesium concentration was 2.2 to 2.5 mg/dl in the various batches used.Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A microtitration broth dilution technique similar to that described by Harwick et al. was employed (8). Stock solutions of piperacillin, carbenicillin, and ticarcillin were prepared in Mueller-Hinton broth at a concentration of 533 ,g/ml. After appropriate dilutions in Mueller-Hinton broth and addition of the bacterial inoculum, the antibiotic concentrations ranged from 400 to 0.8 ,ug/ml, in a final volume of 200 ,ul. For ampicillin, cephalothin, and cefamandole, stock solutions were prepared at a concentration of 266 ,ug/ml, yielding antibiotic concentrations of 200 to 0.4 'Ug/ml.

Comparative In Vitro Appraisal of Piperacillin, Including Its Activity Against Salmonella typhi

“…This is in accordance with the findings of other workers (3,7,11,16,22). Although synergy was also demonstrated against the majority of Klebsiella and Proteus strains when piperacillin was combined with aminoglycosides or cephalothin, the results were not as consistently good.…”

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

“…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.…”

Early synergistic interaction between semisynthetic penicillins and aminoglycosidic aminocyclitols against Enterobacteriaceae

“…and Klebsiella pneumoniae (4,11). In addition, several investigators have demonstrated in vitro synergism between piperacillin and aminoglycosides against members of the Enterobacteriaceae (5,8,12), Pseudomonas aeruginosa (2,8,13,17), and other nonfermentative, gramnegative bacteria (3).…”

“…Piperacillin is a new semisynthetic penicillin which has demonstrated greater in vitro activity than carbenicillin or ticarcillin against Pseudomonas aeruginosa and members of the Enterobacteriaceae (1,5,13,15,16,19,20 Antibiotic synergism. The interaction between each of the three semisynthetic penicillins and each of the two aminoglycosides was evaluated by time-kill curves in Mueller-Hinton broth as described previously (6).…”