Comparison of the Pharmacokinetic and Pharmacodynamic Activity of Piperacillin and Mezlocillin

Study Objective. To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ). Design. Open‐label, randomized, three‐way crossover study. Setting. Hartford Hospital Clinical Research Center. Patients. Nine healthy volunteers. Interventions. Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg. Measurements and Main Results. Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2‐ to 3‐fold higher peak serum bactericidal activity at the end of infusion and 4‐ to 5‐fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g. Conclusion. Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.