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

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Abstract
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 .mu./ml with the exception of the Serratia group which required 64 .mu./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 4-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[colony-forming units]/ml. Synergistic effects were observed when piperacillin was combined with gentamicin or amikacin. Piperacillin was effective against acute lethal infections and chronic kidney infections in mice. Piperacillin has a spectrum of activity that spans those of other semisynthetic penicillins and cephalosporins.