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Measurement of piperacillin plasma concentrations in cancer patients with suspected infection

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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.

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Funding

The study has received no funding. Data from patients were generated as part of the routine work in the University Hospital Jena, Germany.

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Authors and Affiliations

  1. Klinik für Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany

    Tobias Rachow, Verena Schlüter, Udo Lindig, Sebastian Scholl, Andreas Hochhaus & Marie von Lilienfeld-Toal

  2. Institut für Klinische Chemie und Laboratoriumsdiagnostik, Universitätsklinikum Jena, Jena, Germany

    Sibylle Bremer-Streck & Michael Kiehntopf

  3. Institut für Medizinische Statistik, Informatik und Dokumentation, Universitätsklinikum Jena, Jena, Germany

    Peter Schlattmann

  4. Center for Sepsis Care and Control (CSCC), Universitätsklinikum Jena, Jena, Germany

    Tobias Rachow & Marie von Lilienfeld-Toal

  5. Leibnitz-Insitut für Naturstoffforschung und Infektionsbiologie e.V., Hans-Knöll-Institut, Jena, Germany

    Marie von Lilienfeld-Toal

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  1. Tobias Rachow
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Correspondence to Tobias Rachow.

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TR received lecture fees from Pfizer.

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Rachow, T., Schlüter, V., Bremer-Streck, S. et al. Measurement of piperacillin plasma concentrations in cancer patients with suspected infection. Infection 45, 629–636 (2017). https://doi.org/10.1007/s15010-017-1026-z

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  • DOI: https://doi.org/10.1007/s15010-017-1026-z

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