Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae.
BACKGROUND
Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.


METHODS
All adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.


RESULTS
There were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23).


CONCLUSIONS
BLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.
University of Queensland Centre for Clinical Research, Brisbane, Queensland Australia ; Department of Infectious Diseases, National University Hospital, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Patrick N A
PN
Harris
Department of Infectious Diseases, National University Hospital, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Mo
M
Yin
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ; Department of Laboratory Medicine, National University Hospital, Singapore, Singapore.
Roland
R
Jureen
International Medical University, Kuala Lumpur, Malaysia.
Jonathan
J
Chew
Department of Infectious Diseases, National University Hospital, Singapore, Singapore.
Jaminah
J
Ali
School of Population Health, University of Queensland, Brisbane, QLD Australia.
Stuart
S
Paynter
University of Queensland Centre for Clinical Research, Brisbane, Queensland Australia.
David L
DL
Paterson
Department of Infectious Diseases, National University Hospital, Singapore, Singapore ; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Paul A
PA
Tambyah
Carbapenem; Enterobacteriaceae; Extended-spectrum β-lactamase; Piperacillin-tazobactam