Development of Institution-Specific Sepsis Guidelines for Double Coverage of Gram-Negative Infections

Background:

Empiric antibiotic coverage for gram-negative organisms (GNO) is often directed at Pseudomonas aeruginosa. At Virginia Commonwealth University Medical Center (VCU), levofloxacin is the most common agent added to provide double coverage. The gram-negative bacilli most commonly responsible for infections at VCU Health are Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa with reported levofloxacin susceptibility of 74%, 94%, and 75%, respectively.

Methods:

We performed a retrospective electronic health record review of adult patients admitted to VCU from 1/1/2014 to 12/31/2014. Patients admitted with a diagnosis of sepsis, severe sepsis, or septic shock and an infection documented by positive culture with a GNO were identified. The primary objective of this study was to determine the adequacy of various empiric antibiotic combinations for each positive culture.

Results:

A total of 1,862 patients were identified. 54% (1,000) were randomly selected for review. A total of 219 patients met the inclusion criteria. 11% of patients did not receive antibiotics within 12 hours of cultures. For patients who received antibiotics targeting multi-drug resistant GNOs, 56% received a single agent; only 21% received 2 antibiotics. 84% of GNOs were susceptible to piperacillin-tazobactam. The addition of levofloxacin did not result in increased susceptibilities when used in combination with cefepime and meropenem, but did provide an approximately 8% increase in coverage when used in combination with piperacillin-tazobactam. The addition of gentamicin resulted in only about a 3% increase in coverage for cefepime and meropenem, but provided an additional 13% of coverage when used in combination with piperacillin-tazobactam.

Conclusion:

In this cohort of septic patients at VCU, gentamicin provided broader gram-negative coverage when compared to levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.