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Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.


ABSTRACT:

Background

Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.

Objectives

This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.

Methods

E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days.

Results

Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h.

Conclusions

Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

SUBMITTER: Islam K 

PROVIDER: S-EPMC9410668 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.

Islam Kamrul K   Sime Fekade B FB   Wallis Steven C SC   Bauer Michelle J MJ   Forde Brian M BM   Harris Patrick P   Shirin Tahmina T   Habib Zakir H ZH   Flora Meerjady S MS   Roberts Jason A JA  

The Journal of antimicrobial chemotherapy 20220801 9


<h4>Background</h4>Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.<h4>Objectives</h4>This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.<h4>Methods</h4>E.  ...[more]

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