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Impact of surfactants and other body fluids on in vitro activity of a novel β-lactamase inhibitor enmetazobactam in combination with cefepime against clinical isolates of Klebsiella pneumoniae

The Journal of Antibiotics volume 76, pages 183–189 (2023)Cite this article

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Abstract

Surfactants might impact treatment of lower respiratory tract infections. Moreover, other body fluids, such as urine or serum, could impact antibacterial activity as well. Therefore, the impact of surfactants, urine, and serum on the antibacterial activity of the novel β-lactam/β-lactamase inhibitor combination of cefepime-enmetazobactam (FPE) was determined. Ten clinical isolates of Klebsiella pneumoniae, and the quality control strains K. pneumoniae ATCC 700603 and Escherichia coli NCTC 13353, were tested. Minimal Inhibitory Concentration (MIC) determinations (all strains) and Time Kill Curves (TKC) (one clinical isolate) were determined for FPE and piperacillin-tazobactam (TZP) with and without surfactant formulations Survanta® (SUR; 1%v/v) and Curosurf® (CUR; 1 mg ml−1). Determination of daptomycin MIC against Staphylococcus aureus ATCC 29213 in the presence and absence of surfactants was used as a positive control. Additionally, the impact of growth media supplemented with pooled human urine or serum were also evaluated by MIC testing. Expectedly, media supplemented with SUR increased the daptomycin MIC against S. aureus ATCC 29213. In contrast, the surfactants had no impact on the antibacterial activity of FPE against the tested Enterobacterales isolates. TKC experiments also revealed no impact of CUR on the antibacterial activity of FPE. These results demonstrate that the antibacterial activity of FPE is unaffected in the presence of lung surfactant. Moreover, FPE was not impacted by media supplemented with urine or serum.

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Acknowledgements

We would like to thank Juan Quevedo, representative of Advanz Pharma, for administrative support. Moreover, we would like to thank (Allecra Therapeutics), especially A. Belley and P. Knechtle for funding the in vitro experiments.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

    Alina Nussbaumer-Pröll, Sabine Eberl & Markus Zeitlinger

  2. Allecra Therapeutics SAS, Saint-Louis, France

    Adam Belley & Philipp Knechtle

  3. JMI Laboratories, Iowa City, IA, USA

    Michael D. Huband & Holly K. Huynh

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  1. Alina Nussbaumer-Pröll
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  2. Sabine Eberl
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  3. Adam Belley
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Correspondence to Markus Zeitlinger.

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Nussbaumer-Pröll, A., Eberl, S., Belley, A. et al. Impact of surfactants and other body fluids on in vitro activity of a novel β-lactamase inhibitor enmetazobactam in combination with cefepime against clinical isolates of Klebsiella pneumoniae. J Antibiot 76, 183–189 (2023). https://doi.org/10.1038/s41429-022-00592-w

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