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DOI: 10.1055/a-2244-7698
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Potentielle Nephrotoxizität der Kombinationstherapie von Vancomycin und Piperacillin-Tazobactam: Empfehlungen der AG ABS der DGPI unter Beteiligung von Experten der GPN

Potential Nephrotoxicity of Combination of Vancomycin and Piperacillin-Tazobactam: Recommendations from the AG ABS of the DGPI supported by experts of the GPN
Luise Martin
1   Klinik für Pädiatrie m.S. Pneumologie, Immunologie und Intensivmedizin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
,
Alenka Pecar
2   Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität München, München, Germany
,
Yeliz Baltaci
3   Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Germany
,
Arne Simon 
3   Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Germany
,
Stefan Kohl
4   Klinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Kindernephrologie, Uniklinik Köln, Köln, Germany
,
Dominik Müller
5   Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
,
Johannes Forster
6   Institut für Hygiene und Mikrobiologie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
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Zusammenfassung

Die Kombination von Vancomycin und Piperacillin/Tazobactam (V+P/T) kommt in der empirischen Therapie von schweren Infektionen zum Einsatz, insbesondere, wenn patientenseitige Risikofaktoren wie Immunsuppression oder Kolonisation mit multiresistenten Erregern vorliegen. Die Nephrotoxizität von Vancomycin ist bekannt, das Risiko der Nephrotoxizität wird durch adaptierte Dosierungen sowie therapeutisches Drug-Monitoring vermindert. Piperacillin/Tazobactam (P/T) kann sehr selten eine interstitielle Nephritis auslösen. Die Resultate retrospektiver Kohortenstudien bei Kindern zeigen überwiegend eine geringe, klinisch wenig relevante, additive Nephrotoxizität (definiert als Kreatinin-Anstieg im Serum) beider Substanzen. Präklinische Studien und eine prospektive Studie mit erwachsenen Patienten, die weitere Nierenretentionsparameter sowie das klinische Outcome untersuchten, zeigten keinen Zusammenhang zwischen einer Therapie mit V+P/T und akuter Nierenfunktionseinschränkung. Aufgrund der Limitationen der vorhandenen Publikationen sprechen sich die Arbeitsgruppe ABS der DGPI und die Experten der GPN nicht gegen den Einsatz von P/T plus Vancomycin aus. Dennoch sollte durch den zeitlich restriktiven Einsatz der Kombination V+P/T die Exposition gegenüber V+P/T und ein mögliches Nephrotoxizitätsrisiko minimiert werden. Auch die alternativ infrage kommenden Substanzen sind dabei sowohl im Hinblick auf ihr antimikrobielles Spektrum, auf mögliche Nebenwirkungen sowie auf den durch sie ausgeübten Selektionsdruck kritisch zu hinterfragen. Indikationen für den empirischen sowie gezielten Einsatz von P/T und V+P/T sollten in Zusammenarbeit mit dem lokalen ABS-Team in hausinternen Leitlinien festgelegt werden. Wird die Kombinationstherapie V+P/T verwendet, sollte eine über das Serum-Kreatinin hinausgehende sowohl laborchemische (BGA, Cystatin C) als auch klinische Überwachung (Bilanzierung, Blutdruck) der Nierenfunktion erfolgen.

Abstract

The combination of vancomycin and piperacillin/tazobactam (V+P/T) is used for empirical antibiotic treatment of severe infections, especially in immunocompromised patients and those colonized with multidrug-resistant bacteria. Nephrotoxicity is a frequently observed adverse effect of vancomycin. Its risk can be reduced by therapeutic drug monitoring and adjusted dosing. Piperacillin/tazobactam (P/T) rarely causes interstitial nephritis. The results of retrospective cohort studies in children predominantly show a low, clinically irrelevant, additive nephrotoxicity (defined as an increase in creatinine in the serum) of both substances. Due to the limitations of the existing publications, the ABS working group of the DGPI and experts of the GPN do not recommend against the use of P/T plus vancomycin. Preclinical studies and a prospective study with adult patients, which evaluated different renal function tests as well as clinical outcomes, do not support previous findings of additive nephrotoxicity. Time-restricted use of V+P/T can minimize exposure and the potential risk of nephrotoxicity. Local guidelines, developed in collaboration with the antibiotic stewardship team, should define the indications for empirical and targeted use of P/T and V+P/T. When using combination therapy with V+P/T, kidney function should be monitored through clinical parameters (volume status, balancing, blood pressure) as well as additional laboratory tests such as serum creatinine and cystatin C.

Schlüsselwörter

Vancomycin - Nephrotoxizität - Antibiotic stewardship - Piperacillin-Tazobactam

Keywords

vancomycin - nephrotoxicity - antibiotic stewardship - piperacillin-tazobactamArtikel online veröffentlicht 2024

Zusätzliches Material



Publication History

Article published online:
08 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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