Efficacy of piperacillin-tazobactam and cefotaxime against Escherichia coli hyperproducing TEM-1 in a mouse peritonitis infection model
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 629 KB, PDF-dokument
Objectives: Piperacillin-tazobactam (TZP) is a frequently prescribed antibiotic in hospital settings. Reports suggest in vivo efficacy of TZP, despite in vitro resistance of isolates susceptible to cephalosporins. Escherichia coli (E. coli) isolates hyperproducing TEM-1 β-lactamase possess this phenotype. This study investigated the influence of tazobactam (TAZ) concentration on piperacillin (PIP) inhibition of such isolates and compared the in vivo efficacy of TZP with cefotaxime (CTX) in an infection model. Methods: The PIP MICs for E. coli isolates, either hyperproducing TEM-1 because of promoter substitutions (n = 4) or because of gene amplification (n = 2) or producing an inhibitor-resistant TEM-35 (IRT) (n = 1), were determined using increasing concentrations of TAZ in a checkerboard setup. Furthermore, the efficacy of TZP and CTX against the isolates was investigated in a mouse peritonitis model using antibiotic exposures mimicking human conditions. Isolates producing either OXA-48 or CTX-M-15 β-lactamases were included as controls. Results: Using TAZ concentrations ≤ 64 mg/L, one isolate hyperproducing TEM-1 had a PIP MIC of 8 at TAZ 16 mg/L and two additional isolates at TAZ 64 mg/L. In the mouse peritonitis infection model, reduction of bacterial load in the peritoneum was larger for TZP than CTX only for the CTX-M-15-producing isolate. Larger reductions in bacterial load were observed after CTX treatment than TZP treatment for seven of the eight remaining test isolates. Conclusions: Piperacillin-tazobactam treatment of E. coli isolates hyperproducing TEM-1 was less effective than CTX treatment and may, for some isolates, be comparable with TZP treatment of isolates producing established resistance markers as IRT or OXA-48.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 106543 |
Tidsskrift | International Journal of Antimicrobial Agents |
Vol/bind | 59 |
Udgave nummer | 4 |
Antal sider | 5 |
ISSN | 0924-8579 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
No funding. None to declare. All animal experiments were approved by the Danish Animal Experimentation Inspectorate (license no. 2017-15-0201-01274) and performed according to institutional guidelines. All authors contributed to the study conception and design. The first draft of the manuscript was written by FBH, MRA and KS; FBH, NFM and SRA performed animal experiments; MRA, KHH and LJ provided MIC data; KLN provided sequence data and bioinformatic analysis; FBH, NFM and KS contributed data analysis; LJ, NFM and KS supervised the work. All authors contributed to the preparation of the final manuscript. We thank Eva Greibe, PhD, Department of Clinical Biochemistry, Aarhus University Hospital for assistance with measuring piperacillin concentrations in murine serum. Eva Johansen and Louise Thomsen are thanked for expert technical assistance.
Publisher Copyright:
© 2022 The Authors
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 320049020