In vitro and in vivo activity of piperacillin, a new broad-spectrum semisynthetic penicillin.

Piperacillin sodium is a novel semisynthetic penicillin with broad spectrum activity against Gram-negative and -positive bacteria including anaerobes. In agar dilution tests with 522 clinical isolates, it inhibited at least 70-90% of each group of organisms at 16 mcg/ml with the exception of the Serratia group which required 64 mcg/ml to inhibit 70% of the isolates. Piperacillin was more potent than carbenicillin, ticarcillin and ampicillin against Klebsiella, Pseudomonas, Enterobacter and Serratia. Against Gram-positive cocci it was generally comparable to carbenicillin and ticarcillin except in the case of enterococci where it was significantly more potent. Piperacillin exhibited a broader spectrum than the cephalosporins which lacked antipseudomonal activity. It was more potent than cephalothin, cefamandole and cefoxitin against indole-positive Proteus, Acinetobacter and enterococci. Piperacillin is bactericidal; minimal bactericidal concentrations were within four-fold of the minimal inhibitory concentrations. Its activity was not significantly altered by pH, media or serum, but was reduced when inoculum size was increased from 105 to 107 CFU/ml. Synergistic effects were observed when piperacillin was combined with gentamicin or amikacin. Piperacillin was effective against both acute lethal infections and chronic kidney infections in mice. Our results indicate that piperacillin has a spectrum of activity that spans those of other semisynthetic penicillins and cephalosporins.