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DOI: 10.1055/s-0043-110504
Neue Antibiotika für die Therapie von multiresistenten gramnegativen Bakterien
New Antibiotics for Treatment of Highly Resistant Gram-negative BacteriaPublication History
Publication Date:
23 July 2018 (online)
![](https://www.thieme-connect.de/media/ains/20180708/lookinside/thumbnails/10-1055-s-0043-110504_ai3579266-1.jpg)
Zusammenfassung
Die stetige Zunahme an bakteriellen Resistenzen und von multiresistenten Erregern (MRE) – vor allem im gramnegativen Bereich – ist ein weltweites Problem. Die Entwicklung neuer Wirkstoffe gegen Infektionen mit multiresistenten gramnegativen Erregern (MRGN) besitzt daher höchste Priorität. Im Folgenden werden kürzlich zugelassene oder in der fortgeschrittenen klinischen Prüfung befindliche Antibiotika mit Wirksamkeit gegen MRGN vorgestellt.
Abstract
New β-lactam/β-lactamase inhibitor (BLI) combinations (ceftolozan/tazobactam, ceftazidim/avibactam, meropenem/vaborbactam, imipenem/relebactam, aztreonam/avibactam) are the focus of newly approved antibiotics or those currently in advanced clinical testing. In contrast to the BLI currently available, the new inhibitors avibactam, vaborbactam and relebactam are not structurally β-lactams.
The combination with a BLI protects β-lactam from degradation by broad-spectrum β-lactamases from gram-negative pathogens. The main indications for the new substances are therefore infections with multi-resistant gram-negative bacteria.
In clinical use, it should be noted that the BLI does not close efficacy gaps in the β-lactam/BLI combination (e.g. no effect of cephalosporin/BLI combinations on anaerobes or enterococci).
Cefiderocol is the first representative of the siderophore cephalosporin antibiotic group to enter phase II clinical testing.
Eravacyclin (tetracycline derivative) and plazomicin (aminoglycoside) are new non-β-lactam antibiotics in advanced clinical testing (phase III).
In order to maintain the efficacy of new reserve antibiotics for as long as possible, a prescription should only be made if an additional benefit in comparison to established substances has been proven, e.g. by a resistance test.
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Der Schwerpunkt der neu zugelassenen bzw. in der fortgeschrittenen klinischen Prüfung befindlichen Antibiotika sind neue β-Laktam/β-Laktamase-Inhibitor-Kombinationen (Ceftolozan/Tazobactam, Ceftazidim/Avibactam, Meropenem/Vaborbactam, Imipenem/Relebactam, Aztreonam/Avibactam).
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Im Gegensatz zu den bisher verfügbaren β-Laktamase-Inhibitoren (BLI) sind die neuen Inhibitoren Avibactam, Vaborbactam und Relebactam strukturell keine β-Laktame.
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Durch die Kombination mit einem BLI wird das β-Laktam vor dem Abbau durch Breitspektrum-β-Laktamasen von gramnegativen Erregern geschützt. Der Indikationsschwerpunkt der neuen Substanzen sind daher Infektionen mit multiresistenten gramnegativen Bakterien.
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Bei der klinischen Anwendung ist zu berücksichtigen, dass generelle Wirklücken des in den β-Laktam/BLI-Kombinationen enthaltenen β-Laktams durch den BLI nicht geschlossen werden (z. B. keine Wirkung von Cephalosporin/BLI-Kombinationen auf Anaerobier oder Enterokokken).
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Cefiderocol befindet sich als erster Vertreter der Antibiotikagruppe der Siderophor-Cephalosporine in der Phase II der klinischen Prüfung.
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Neue Nicht-β-Laktam-Antibiotika in der fortgeschrittenen klinischen Prüfung (Phase III) sind Eravacyclin (Tetrazyklinderivat) und Plazomicin (Aminoglykosid).
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Um die Wirksamkeit neuer Reserveantibiotika möglichst lange zu erhalten, sollten sie nur verordnet werden, wenn ein Zusatznutzen im Vergleich zu etablierten Substanzen belegt wurde, z. B. durch eine Resistenztestung.
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