Measurement of piperacillin plasma concentrations in cancer patients with suspected infection.

Abstract

Piperacillin (PIP) in combination with tazobactam is commonly used for anti-infective treatment in cancer patients. PIP exerts a time-dependent killing. Thus, the maintenance of plasma concentrations above a pre-defined target concentration for a pre-defined time may be relevant for optimal efficacy. It is assumed that PIP-plasma concentrations above the clinical breakpoint of the target pathogen [Pseudomonas aeruginosa, clinical breakpoint at minimal inhibitory concentration (MIC) 16mg/L] should be reached for 100% of the dosing interval or>4xMIC (64mg/L) for 50% of the dosing interval. Whereas studies in the intensive-care setting have shown underdosing in patients with sepsis, little is known about PIP-plasma concentrations in cancer patients. Data of 56 cancer patients who received piperacillin/tazobactam (PIP/TAZ, 4.5g three times daily) as empiric therapy for suspected infection were analysed at baseline and 4h after the infusion. Median trough concentrations in steady state [median 3days (IQR 3-5) after start of PIP/TAZ] were 4.6mg/L (95% CI 0.3-136.3) and median PIP-plasma concentrations 4h after infusion were 46.2mg/L (95% CI 10.1-285.6). A second evaluation 5days (IQR 4-7) after start of PIP/TAZ confirmed these results: trough concentrations were 2.7mg/L (95% CI 0.5-6.3), concentrations after 4h 28.0mg/L (95% CI 1.7-47.3). A good renal function was associated with lower plasma concentrations (r=-0.388, p<0.003). Detailed pharmacokinetic measurements in six patients showed low maximum plasma concentration (median 165mg/L) and a rapid decline of plasma concentrations (median plasma half time 1.38h). In conclusion, piperacillin plasma concentrations in cancer patients are below target levels warranting prospective trials to investigate therapeutic drug monitoring.