Temocillin breakpoints in pyelonephritis: evaluation in a murine model due to ESBL-producing Escherichia coli clinical isolates.

Abstract

BACKGROUND:

Due to a spectrum restricted to Enterobacteriaceae and stability against ESBL and AmpC enzymes, temocillin is of major interest for the treatment of pyelonephritis. But there are still uncertainties about the optimal regimen and clinical breakpoints.

OBJECTIVES:

To study in a murine model of pyelonephritis the activity of temocillin against Escherichia coli isolates with different MICs in order to evaluate clinical breakpoints.

METHODS:

Four clinical uropathogenic E. coli isolates with temocillin MICs of 8 mg/L (Ec8), 16 mg/L (Ec16), 32 mg/L (Ec32) and 64 mg/L (Ec64) were evaluated. Antibiotic 24 h T>MIC achieved in humans was reproduced in mice with either intravenous temocillin (2 g q12h or 2 g q8h) or intravenous imipenem (1 g q8h). Efficacy was assessed by bacterial count in kidneys.

RESULTS:

Compared with controls, temocillin at 2 g q12h was highly efficient against Ec8 (-3.32 log10 cfu/g and negative cultures in 93% of mice; P < 0.001); imipenem gave similar results. Temocillin at 2 g q12h also induced high reduction of bacterial count against Ec16 (-2.92 log10 cfu/g; P < 0.001), albeit cultures were negative in only 48% of mice. In contrast, no significant effect was observed in mice infected by Ec32 (-0.01 log10 cfu/g; P = 0.981) or Ec64 (-0.55 log10 cfu/g; P = 0.523). Even temocillin at 2 g q8h failed to control Ec32 infection (-1.55 log10 cfu/g; P = 0.197).

CONCLUSIONS:

This model suggests a clinical breakpoint up to 16 mg/L for non-severe pyelonephritis treated with temocillin at 2 g q12h, a value consistent with the few previous available data.

• Authors: Kévin Alexandre, Anaïs Soares, Françoise Chau, Bruno Fantin, François Caron, Manuel Etienne
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 74 Issue 5 Pg. 1323-1326 (05 01 2019) ISSN: 1460-2091 [Electronic] England
• PMID: 30689887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Anti-Bacterial Agents
• Penicillins
• temocillin
• beta-Lactamases

Topics

• Administration, Intravenous
• Animals
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Load (drug effects)
• Colony Count, Microbial
• Disease Models, Animal
• Escherichia coli (drug effects, enzymology, growth & development)
• Escherichia coli Infections (drug therapy, microbiology)
• Female
• Humans
• Kidney (microbiology)
• Mice
• Mice, Inbred CBA
• Microbial Sensitivity Tests
• Penicillins (therapeutic use)
• Pyelonephritis (drug therapy, microbiology)
• beta-Lactamases