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Neue β‑Laktam-Antibiotika und β‑Laktamase-Inhibitoren gegen multiresistente Gram-negative Erreger

New β‑lactam antibiotics and β‑lactamase inhibitors against multidrug-resistant Gram-negative bacteria

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Zusammenfassung

Hintergrund

Die rasche Zunahme multiresistenter Gram-negativer Erreger (MRGN) ist ein drängendes und weitgehend ungelöstes globales Problem. Die Behandlungsoptionen bei diesen Erregern sind sehr stark eingeschränkt. Nur wenige neue Substanzen sind zugelassen worden oder befinden sich aktuell in klinischen Phase-II/III-Studien.

Ziel der Arbeit

Übersichtliche Vorstellung der bislang vorliegenden Daten zu den neuen β‑Laktam-Antibiotika und β‑Laktamase-Inhibitor-Kombinationen. Die neuen Makrolide, Ketolide und Aminoglykoside werden nicht adressiert.

Material und Methoden

Selektive Literaturrecherche zu den Substanzen Ceftazidim/Avibactam, Ceftolozan/Tazobactam, Imipenem/Cilastatin + Relebactam, Meropenem/Vaborbactam, Aztreonam/Avibactam und Cefiderocol unter Einbeziehung aktuell registrierter Studien mit klinischer Auswertung und Datenanalyse.

Ergebnisse

Die Entwicklung neuer Substanzen zur Therapie von Infektionen durch MRGN eröffnet neue Optionen bei Infektionen durch besonders schwierig zu behandelnde Erreger, insbesondere Erreger, die Carbapenemasen vom Klebsiella-pneumoniae-Carbapenemase (KPC) und OXA-48-Typ bilden. β‑Laktamase-Bildner werden durch die neuen Substanzen oder Kombinationen unterschiedlich stark gehemmt; allerdings fehlen noch immer ausreichende Therapieoptionen für Metallo-β-Laktamase-Bildner sowie Infektionen durch multiresistente Pseudomonas-aeruginosa- und Acinetobacter-spp.-Stämme.

Schlussfolgerung

Vielfach sind die klinischen Daten noch indifferent und stammen aus uneinheitlich definierten Patientenkollektiven. Direkte Vergleiche mit etablierten Behandlungsstrategien wie dem „Last-resort-Einsatz“ von Polymyxinen sind kaum möglich. Leider sind auch bereits Fälle einer raschen Resistenzentwicklung beschrieben. Der Stellenwert der Toxizität und optimalen Dosierung – auch bei Organversagen oder Organersatzverfahren wie Dialyse – ist vielfach noch unklar.

Abstract

Background

The worldwide spread of multidrug-resistant Gram-negative bacteria (MDR-GN) continues. Treatment options for infections caused by MDR-GN remain scarce and only few new substances are currently in clinical phase II/III studies or have already been granted market approval.

Objectives

To provide an overview about current data on new β‑lactam antibiotics and β‑lactamase inhibitor combinations, respectively. New macrolides, ketolides and aminoglycosides are not addressed.

Materials and methods

Selective literature research regarding published data on ceftazidim/avibactam, ceftolozan/tazobactam, imipenem/cilastatin + relebactam, meropenem/vaborbactam, aztreonam/avibactam and cefiderocol, as well as registered trials.

Results

The development of new antimicrobials for the treatment of MDR-GN infections offers new options for attending physicians. β‑Lactamase producers are inhibited by these new substances, though with varying efficacy; however, there are still no adequate treatment options for metallo-β-lactamase (MBL) producers.

Conclusions

Clinical data are still indifferent and come from heterogeneous patient collectives. Direct comparisons with established treatment strategies, such as the “last-resort use” of polymyxins are hardly possible. Cases of early development of resistance have already been described. Finally, the importance of toxicity and optimal dosing—in organ failure or organ replacement procedures such as dialysis—remain unclear.

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Authors and Affiliations

  1. Klinik für Infektiologie und Mikrobiologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Deutschland

    Alexander Mischnik

  2. Fachbereich Infektions- und Tropenmedizin, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

    Christoph Lübbert

  3. Institut für Infektionsprävention und Krankenhaushygiene, Universitätsklinikum Freiburg, Freiburg, Deutschland

    Nico T. Mutters

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  1. Alexander Mischnik
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Correspondence to Alexander Mischnik.

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A. Mischnik, C. Lübbert und N.T. Mutters geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Mischnik, A., Lübbert, C. & Mutters, N.T. Neue β‑Laktam-Antibiotika und β‑Laktamase-Inhibitoren gegen multiresistente Gram-negative Erreger. Internist 59, 1335–1343 (2018). https://doi.org/10.1007/s00108-018-0508-0

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