Alexander Mischnik1, Christoph Lübbert2, Nico T Mutters3. 1. Klinik für Infektiologie und Mikrobiologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Deutschland. alexander.mischnik@uksh.de. 2. Fachbereich Infektions- und Tropenmedizin, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Deutschland. 3. Institut für Infektionsprävention und Krankenhaushygiene, Universitätsklinikum Freiburg, Freiburg, Deutschland.
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.
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.
Entities:
Keywords:
Avibactam, ceftazidime drug combination; Carbapenemase; Ceftolozane, tazobactam drug combination; β-Lactamase inhibitors; β-Lactamases, extended spectrum
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