Tobias Rachow1,2, Verena Schlüter3, Sibylle Bremer-Streck4, Udo Lindig3, Sebastian Scholl3, Peter Schlattmann5, Michael Kiehntopf4, Andreas Hochhaus3, Marie von Lilienfeld-Toal3,6,7. 1. Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany. tobias.rachow@med.uni-jena.de. 2. Center for Sepsis Care and Control (CSCC), Universitätsklinikum Jena, Jena, Germany. tobias.rachow@med.uni-jena.de. 3. Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany. 4. Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Jena, Germany. 5. Institut für Medizinische Statistik, Informatik und Dokumentation, Universitätsklinikum Jena, Jena, Germany. 6. Center for Sepsis Care and Control (CSCC), Universitätsklinikum Jena, Jena, Germany. 7. Leibnitz-Insitut für Naturstoffforschung und Infektionsbiologie e.V., Hans-Knöll-Institut, Jena, Germany.
Abstract
BACKGROUND: 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) 16 mg/L] should be reached for 100% of the dosing interval or >4xMIC (64 mg/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. METHODS: Data of 56 cancer patients who received piperacillin/tazobactam (PIP/TAZ, 4.5 g three times daily) as empiric therapy for suspected infection were analysed at baseline and 4 h after the infusion. RESULTS: Median trough concentrations in steady state [median 3 days (IQR 3-5) after start of PIP/TAZ] were 4.6 mg/L (95% CI 0.3-136.3) and median PIP-plasma concentrations 4 h after infusion were 46.2 mg/L (95% CI 10.1-285.6). A second evaluation 5 days (IQR 4-7) after start of PIP/TAZ confirmed these results: trough concentrations were 2.7 mg/L (95% CI 0.5-6.3), concentrations after 4 h 28.0 mg/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 165 mg/L) and a rapid decline of plasma concentrations (median plasma half time 1.38 h). CONCLUSION: In conclusion, piperacillin plasma concentrations in cancer patients are below target levels warranting prospective trials to investigate therapeutic drug monitoring.
BACKGROUND:Piperacillin (PIP) in combination with tazobactam is commonly used for anti-infective treatment in cancerpatients. 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) 16 mg/L] should be reached for 100% of the dosing interval or >4xMIC (64 mg/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 cancerpatients. METHODS: Data of 56 cancerpatients who received piperacillin/tazobactam (PIP/TAZ, 4.5 g three times daily) as empiric therapy for suspected infection were analysed at baseline and 4 h after the infusion. RESULTS: Median trough concentrations in steady state [median 3 days (IQR 3-5) after start of PIP/TAZ] were 4.6 mg/L (95% CI 0.3-136.3) and median PIP-plasma concentrations 4 h after infusion were 46.2 mg/L (95% CI 10.1-285.6). A second evaluation 5 days (IQR 4-7) after start of PIP/TAZ confirmed these results: trough concentrations were 2.7 mg/L (95% CI 0.5-6.3), concentrations after 4 h 28.0 mg/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 165 mg/L) and a rapid decline of plasma concentrations (median plasma half time 1.38 h). CONCLUSION: In conclusion, piperacillin plasma concentrations in cancerpatients are below target levels warranting prospective trials to investigate therapeutic drug monitoring.
Entities:
Keywords:
Cancer patients; Piperacillin; Plasma concentrations; Therapeutic drug monitoring
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