Optimal duration of antimicrobial therapy for uncomplicated Gram-negative bloodstream infections

Optimal antimicrobial treatment duration for Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined effectiveness of short (7-10 days) and long (> 10 days) courses of antimicrobial therapy for uncomplicated Gram-negative BSI. Hospitalized adults with uncomplicated Gram-negative BSI at Palmetto Health hospitals in Columbia SC, USA from January 1, 2010 to December 31, 2013 were identified. Multivariate Cox proportional hazards regression with propensity score adjustment was used to examine risk of treatment failure in the two groups. During the study period, 117 and 294 patients received short and long courses of antimicrobial therapy for uncomplicated Gram-negative BSI, respectively. Overall, the median age was 67 years, 258 (63%) were women, 282 (69%) had urinary source of infection, and 271 (66%) had BSI due to Escherichia coli. The median duration of antimicrobial therapy was 8.5 and 13.3 days in the short and long treatment groups, respectively. After adjustment for the propensity to use a short course of therapy, risk of treatment failure was higher in patients receiving short compared to long courses of antimicrobial agents (HR 2.60, 95% CI: 1.20-5.53, p = 0.02). Other risk factors for treatment failure included liver cirrhosis (HR 5.83, 95% CI: 1.89-15.02, p = 0.004) and immune compromised status (HR 4.30, 95% CI: 1.57-10.80, p = 0.006). Definitive antimicrobial therapy with intravenous or highly bioavailable oral agents was associated with reduced risk of treatment failure (HR 0.33, 95% CI: 0.14-0.73, p = 0.006). The current results support common clinical practice of 2 weeks of antimicrobial therapy for uncomplicated Gram-negative BSI.