Abstract

Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73-5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.

Highlights

  • Reducing the rates of Gram-negative bacteraemia (GNB) and antimicrobial resistance (AMR) are public health priorities, with a major focus on reducing antibiotic prescribing given the undeniable link between prescribing and AMR

  • A larger proportion of women had Escherichia coli bacteraemia (ECB) (55.7%), but this trend was reversed for Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB), where men accounted for 59.8% and 61.4%, respectively

  • Urinary source bacteraemia was identified in 652 patients (47.3% of patients overall), with proportions varying by organism: 51.4% for ECB, 34.9% for KPB and 21.6% for PsAB

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Summary

Introduction

Reducing the rates of Gram-negative bacteraemia (GNB) and antimicrobial resistance (AMR) are public health priorities, with a major focus on reducing antibiotic prescribing given the undeniable link between prescribing and AMR. Evidence regarding the effect on clinical outcomes of empirical antibiotic therapy to which the bacteraemia organism is resistant in-vitro (discordant antibiotic treatment) is conflicting. The relationship may be confounded by illness severity and the results may not be generally applied to all patients with community-onset GNB. This notion is supported by findings from a systematic review, which highlighted methodological limitations of studies assessing mortality risk associated with antibiotic treatment in bloodstream infections and the importance of controlling for disease severity [11]. Source of bacteraemia has been posited as an important predictor of patient outcomes, with several studies finding lower mortality in patients with a urinary compared with non-urinary source ECB [5, 12,13,14]

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