Piperacillin, a new penicillin active against many bacteria resistant to other penicillins

Abstract

The in vitro activity of piperacillin, a new semisynthetic piperazine penicillin derivative, was evaluated against 626 clinical isolates and compared with the activity of other β-lactam antibiotics. At a concentration of 0.1 μg/ml, piperacillin inhibited all streptococci except enterococci. Non-β-lactamase-producing producing staphylococci were inhibited by 1.6 μg or less per ml. Both β-lactamase- and non-β-lactamase-producing Haemophilus were inhibited by 0.1 μg/ml. Piperacillin inhibited non-β-lactamase-producing Escherichia coli, Salmonella and Shigella at concentration of 6.3 μg/ml but 20% of strains of these species containing type III β-lactamase were not inhibited by 100 μg/ml. Piperacillin at 25 μg/ml inhibited 83% of Citrobacter, 58% of Klebsiella, 88% of Enterobacter, and 50% of indolepositive Proteus, Acinetobacter, and Providencia. At 25 μg/ml, piperacillin inhibited 95% of Pseudomonas aeruginosa and 78% of Bacteroides fragilis. The minimal inhibitory concentration of piperacillin against Pseudomonas was affected by increasing the inoculum size and by pH. Minimum bactericidal concentrations against Pseudomonas and Serratia often were eightfold greater than the minimum inhibitory concentrations. Piperacillin was equal in activity to ampicillin against enterococci. It was more active than carbenicillin against E. coli, Klebsiella, Enterobacter, and Bacteroides. It was the most active penicillin against Pseudomonas and inhibited many strains of Pseudomonas for which the MICs of carbenicillin were above 200 μg/ml. Piperacillin was hydrolyzed by many different β-lactamases. Synergistic activity of piperacillin was demonstrated when it was combined with amikacin, gentamicin, and cefazolin against P. aeruginosa and members of the Enterobacteriaceae. No antagonism was observed when piperacillin was combined with aminoglycosides; however, antagonism was observed rarely against E. coli when piperacillin was combined with cefazolin.