β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: Time for a reappraisal in the era of few antibiotic options?

Harris, Patrick N. A., Tambyah, Paul A. and Paterson, David L. (2015) β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: Time for a reappraisal in the era of few antibiotic options?. The Lancet Infectious Diseases, 15 4: 475-485. doi:10.1016/S1473-3099(14)70950-8


Author Harris, Patrick N. A.
Tambyah, Paul A.
Paterson, David L.
Title β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: Time for a reappraisal in the era of few antibiotic options?
Journal name The Lancet Infectious Diseases   Check publisher's open access policy
ISSN 1473-3099
1474-4457
Publication date 2015-01-01
Year available 2015
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/S1473-3099(14)70950-8
Open Access Status Not yet assessed
Volume 15
Issue 4
Start page 475
End page 485
Total pages 11
Place of publication London, United Kingdom
Publisher Lancet Publishing Group
Language eng
Subject 2725 Infectious Diseases
Abstract The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin-tazobactam or amoxicillin-clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin-tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic-pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies. Prospective cohort data and a meta-analysis suggest that BLBLIs are non-inferior to carbapenems in the treatment of bloodstream infections caused by ESBL producers. We examine why BLBLIs are perceived as inferior in the treatment of infection with ESBL producers, and discuss data that suggest these concerns might not be strongly supported by clinical evidence.
Formatted abstract
The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin–tazobactam or amoxicillin–clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin–tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic–pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies. Prospective cohort data and a meta-analysis suggest that BLBLIs are non-inferior to carbapenems in the treatment of bloodstream infections caused by ESBL producers. We examine why BLBLIs are perceived as inferior in the treatment of infection with ESBL producers, and discuss data that suggest these concerns might not be strongly supported by clinical evidence.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
 
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