De-escalation of Empiric Antibiotics Following Negative Cultures in Hospitalized Patients with Pneumonia: Rates and Outcomes

BACKGROUND: For patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized pneumonia patients with negative cultures. METHODS: We included adults admitted with pneumonia in 2010-2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity-adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS) and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles. RESULTS: Of 14,170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2%-35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were < 50%. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to ICU (adjusted odds ratio 0.38; 95%CI 0.18-0.79); LOS (adjusted ratio of means 0.76, 95% CI 0.75-0.78) and costs (0.74, 95%CI 0.72-0.76). CONCLUSIONS: A minority of eligible pneumonia patients had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice.