RISK FACTORS AND OUTCOMES FOR INEFFECTIVE EMPIRIC TREATMENT IN GRAM-NEGATIVE SEPSIS: STRATIFICATION BY ONSET OF INFECTION [PublishAheadOfPrint]

Sepsis and septic shock remain serious infections with reported mortality rates in excess of forty percent. Timely antibiotic therapy in sepsis and septic shock is recognized as an important determinant of outcome. However, the administration of ineffective empiric treatment (IET) (an initial antibiotic regimen that is not active against the identified pathogen(s) based on in vitro susceptibility testing) is associated with excess mortality compared to effective empiric treatment (EET). We examined all hospitalized patients between January 2010 and October 2015 at Barnes-Jewish Hospital with the presence of a sterile site (blood, or pleural, abdominal, cerebrospinal, synovial, and pericardial fluid) culture positive for Gram-negative (GN) bacteria combined with primary or secondary ICD-9-CM codes for severe sepsis (995.92) or septic shock (785.52). Variables significantly associated with early-onset (< 48 hours of hospitalization) IET of GN sterile site sepsis and septic shock included age, recent hospitalization and prior intravenous antibiotics. Late-onset IET was associated with increasing hospitalization days before infection onset and prior intravenous antibiotic administration. For patients with early-onset infection we found no difference in survival between patients receiving IET and EET. However, patients receiving IET in the late-onset infection group had a statistically lower survival compared to those receiving EET. These data suggest that risk factors and outcomes for IET can vary based on the onset of infection. Our results also highlight the importance of prior intravenous antibiotic exposure as a risk factor for IET in GN bacterial infections regardless of the onset on infection.

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