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

Clin Infect Dis. 2021 Apr 26;72(8):1314-1322. doi: 10.1093/cid/ciaa212.


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 patients with pneumonia 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, .38; 95% CI, .18-.79), LOS (adjusted ratio of means, .76; .75-.78), and costs (.74; .72-.76).

Conclusions: A minority of eligible patients with pneumonia 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.

Keywords: antimicrobial stewardship; community-acquired pneumonia; de-escalation; negative cultures.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents*
  • Hospital Mortality
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Pneumonia* / drug therapy
  • Retrospective Studies


  • Anti-Bacterial Agents
  • Anti-Infective Agents