Delays in appropriate antibiotic therapy for gram-negative bloodstream infections: a multicenter, community hospital study

Abstract

Background: Gram-negative bacterial bloodstream infection (BSI) is a serious condition with estimated 30% mortality. Clinical outcomes for patients with severe infections improve when antibiotics are appropriately chosen and given early. The objective of this study was to estimate the association of prior healthcare exposure on time to appropriate antibiotic therapy in patients with gram-negative BSI.

Method: We performed a multicenter cohort study of adult, hospitalized patients with gram-negative BSI using time to event analysis in nine community hospitals from 2003-2006. Event time was defined as the first administration of an antibiotic with in vitro activity against the infecting organism. Healthcare exposure status was categorized as community-acquired, healthcare-associated, or hospital-acquired. Time to appropriate therapy among groups of patients with differing healthcare exposure status was assessed using Kaplan-Meier analyses and multivariate Cox proportional hazards models.

Results: The cohort included 578 patients with gram-negative BSI, including 320 (55%) healthcare-associated, 217 (38%) community-acquired, and 41 (7%) hospital-acquired infections. 529 (92%) patients received an appropriate antibiotic during their hospitalization. Time to appropriate therapy was significantly different among the groups of healthcare exposure status (log-rank p=0.02). Time to first antibiotic administration regardless of drug appropriateness was not different between groups (p=0.3). The unadjusted hazard ratios (HR) (95% confidence interval) were 0.80 (0.65-0.98) for healthcare-associated and 0.72 (0.63-0.82) for hospital-acquired, relative to patients with community-acquired BSI. In multivariable analysis, interaction was found between the main effect and baseline Charlson comorbidity index. When Charlson index was 3, adjusted HRs were 0.66 (0.48-0.92) for healthcare-associated and 0.57 (0.44-0.75) for hospital-acquired, relative to patients with community-acquired infections.

Conclusions: Patients with healthcare-associated or hospital-acquired BSI experienced delays in receipt of appropriate antibiotics for gram-negative BSI compared to patients with community-acquired BSI. This difference was not due to delayed initiation of antibiotic therapy, but due to the inappropriate choice of antibiotic.

Figure 1. Cumulative hazard of receiving appropriate antibiotic therapy or any antibiotic therapy based on Kaplan-Meier analysis.

Cumulative hazards among healthcare exposure categories of patients with Gram-negative bloodstream infections in community hospitals, 2003-2006. Healthcare exposure categories include community-acquired (dashed dark-gray line), healthcare-associated (solid light-gray line), and hospital-acquired (dotted light-gray line). For all analyses, the origin of the risk period was defined as starting 24 hours prior to blood culture collection. A. The cumulative hazard of receiving the first dose of an appropriate antibiotic, log-rank test p=0.02. B. The cumulative hazard of receiving the first dose of any antibiotic, log-rank test p=0.3.

Figure 2. Probability of remaining on inappropriate antibiotic therapy based on Cox proportional hazards model.

Healthcare exposure categories include community-acquired (dashed dark-gray line), healthcare-associated (solid light-gray line), and hospital-acquired (dotted light-gray line). Model inputs to produce these curves were the following: Charlson index of 0, malignancy=none, age >65, Medicare/Medicaid=yes, dependent in >3 activities of daily living=yes.