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

Abstract

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.

Conflict of interest statement

Potential conflicts of interest. A. D. has received research support from The Clorox Company and is on the advisory board of Ferring Pharmaceuticals. S. S. R. has received research support from bioMerieux, BD Diagnostics, Hologic, Diasorin, Affinity Lifescale, Accelerate, OpGen, and Roche. M. D. Z. is a consultant and has received research support from Astellas, Paratek, Cleveland Clinic, Lungpacer, Nabriva, Merck, The Medicines Company, Shionogi, Pfizer, Melinta, Tetraphase, and Spero. P. B. I. has consulted with Colgate Palmolive and G.E. Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Patient selection flow chart to identify study eligible patients. Abbreviations: CT, computed tomography; ICU, intensive care unit; MRSA, methicillin-resistant Staphylococcus aureus; PCR, polymerase chain reaction.

Figure 2.

Proportions of patients remaining on an antipseudomonal agent (dashed line), anti-MRSA agent (dot-dash line), both (dotted line), or either agent (solid line) by hospital day. Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.

Figure 3.

Distribution of de-escalation rates by hospital day 4 through hospital day 10 across US hospitals with at least 100 eligible pneumonia patients with negative cultures. *Represents mean. Abbreviations: Max, maximum; Min, minimum.

Figure 4.

Bar chart of hospital rates of day 4 de-escalation (y axis), grouped by hospital de-escalation quartile and further stratified by sextiles of predicted mortality (x axis).