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.