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BMC Infect Dis. 2018 Dec 5;18(1):625. doi: 10.1186/s12879-018-3524-8.

A systematic review of the association between delayed appropriate therapy and mortality among patients hospitalized with infections due to Klebsiella pneumoniae or Escherichia coli: how long is too long?

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Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Global Health Economics and Outcomes Research, Allergan plc, Madison, NJ, USA.
Meta Research, Evidera, Bethesda, MD, USA.
Global Health Economics and Outcomes Research, Allergan plc, 2525 Dupont Drive, Irvine, CA, 92612, USA.



Temporal relationships between the time to appropriate antibiotic therapy and outcomes are not well described.


A systematic literature review and meta-analysis was performed to examine this relationship in patients hospitalized with Klebsiella pneumoniae or Escherichia coli infections.


Twenty identified studies contained data for patients who received delayed appropriate therapy (DAT) versus appropriate antibiotic therapy for these pathogens. Of the 20 included studies, the majority (19/20) focused on patients with bloodstream infections, and only 1 study evaluated patients with pneumonia. When all DAT results were combined (any delay > 24 h from culture collection or any delay after culture and susceptibility reporting [C& SR]), there was an increased risk of mortality (odds ratio [OR], 1.60 [95% CI, 1.25-2.50]). The risk of mortality was greater when DAT > 48 h from culture collection or DAT > C&SR results were combined (OR, 1.76 [95% CI, 1.27-2.44]).


Our findings suggest there is a need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early, relatively aggressive and comprehensive, antibiotic therapy, especially among patients with bloodstream infections due to K. pneumoniae or E. coli.


Delayed treatment; Escherichia coli; Gram-negative infection; Klebsiella pneumoniae; Mortality

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