Penetration of piperacillin-tazobactam into bronchial secretions after multiple doses to intensive care patients.

The penetration of piperacillin-tazobactam in eight mechanically ventilated intensive care patients (age, 56.0 +/- 12.2 years, and weight, 76.5 +/- 15.2 kg [means +/- standard deviations]) with bacterial pneumonia was investigated. They were given intravenous doses of piperacillin (4 g) and tazobactam (0.5 g) as 30-min infusions every 6 h. The kinetic study was performed after the fourth dose on day 2 of treatment. Samples of blood and bronchial secretions (BS) were collected before the fourth dosing and 0.5, 1, 2, 4, and 6 h after the end of infusion. Drug concentrations in both sera and BS were measured by high-performance liquid chromatography. Concentrations (in micrograms per milliliter) in serum were 184.80 +/- 63.03 and 40.03 +/- 30.79 for piperacillin and 23.05 +/- 7.53 and 4.86 +/- 4.54 for tazobactam at 0.5 and 6 h, respectively, after the end of infusion. The corresponding concentrations (in micrograms per milliliter) in BS were 29.33 +/- 25.08 and 20.25 +/- 19.11 for piperacillin and 6.86 +/- 4.25 and 4.25 +/- 2.78 for tazobactam. The percentages for the extent of penetration of piperacillin and tazobactam, as defined by the BS/serum area under the curve ratio, were 35.70 and 78.42%, respectively. These data indicate good penetration of both piperacillin and tazobactam into BS. The concentrations of tazobactam in BS are persistent and high enough to exceed the values found to be effective in vitro against the tazobactam-susceptible beta-lactamases produced by the most important pathogens responsible for nosocomial pneumonia.