Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin

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Abstract
We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins—ticarcillin, mezlocillin and piperacillin alone and in combination with 80mg gentamicin in normal volunteers. Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin. Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l. Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin–gentamicin combination However, except for the mezlocillin–gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin–gentamicin regimes were > 1·8 at zero and 2 h after the infusion against the organisms tested. It is unlikely that these differences in the three penicillin–gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.