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

Internist (Berl). 2018 Dec;59(12):1335-1343. doi: 10.1007/s00108-018-0508-0.
[Article in German]

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.

Keywords: Avibactam, ceftazidime drug combination; Carbapenemase; Ceftolozane, tazobactam drug combination; β-Lactamase inhibitors; β-Lactamases, extended spectrum.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria
  • Gram-Negative Bacterial Infections* / drug therapy
  • Humans
  • beta-Lactamase Inhibitors* / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors