De-escalation of Broad Spectrum Antibiotics Following Negative Cultures in Pneumonia: Rates and Outcomes

Abstract

Background. For patients at risk for multidrug resistant organisms, IDSA/ATS guidelines recommend empiric therapy with 1 agent against methicillin-resistant Staphylococcus aureus (MRSA) and another against Pseudomonas. Following negative cultures, guidelines are unclear regarding antibiotic de-escalation. We assessed de-escalation and associated outcomes in a cohort of pneumonia patients with negative cultures. Methods. We included adults admitted with pneumonia from 2010- 2015 to 168 US hospitals if they had blood/respiratory cultures and received vancomycin together with an antipseudomonal drug other than a quinolone by hospital day 1. We excluded patients with positive cultures, death or discharge by day 4. De-escalation was defined as stopping both drugs by day 4, but continuing another antibiotic. Patients were matched on propensity for de-escalation and compared on late deterioration, inpatient mortality, length of stay (LOS), cost and 30-day readmission. The propensity model included demographics, co-morbidities and treatments on day 4, which served as proxies for clinical severity. We also compared adjusted outcomes across hospital quartile of de-escalation. Results. Of 22,400 patients included, 4121 (18.4 %) had both drugs stopped within 4 days. Median age was 72 years, 56% were female, and 39% were admitted to the intensive care unit (ICU). Compared with patients without de-escalation, those de-escalated had similar demographics, but fewer co-morbidities and less severe disease at days 1 and 4. After propensity-matching, there were no significant differences in 83 variables. In the matched sample, de-escalated patients had lower odds of inpatient mortality (OR 0.71, 95% CI 0.60 - 0.83), subsequent transfer to ICU (OR 0.31; 95% CI 0.19 - 0.52), LOS (OR 0.79, 95% CI 0.77 - 0.80) and lower costs (OR 0.79, 95% CI 0.77 - 0.80). Hospital rates of de-escalation ranged from 0-67%. Hospital de-escalation quartile was not significantly associated with any outcome. Conclusion. In a sample of US hospitals, <20% of pneumonia patients had antibiotic coverage de-escalated following negative cultures, but it varied widely by hospital. Hospitals with high rates of de-escalation did not have worse outcomes. Following negative cultures, de-escalation appears safe in selected patients.