Empiric Antibiotic De-escalation Needed After Negative Cultures for Pneumonia

Researchers assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized patients with pneumonia who have negative cultures.

Fewer than 1 in 7 eligible patients with pneumonia had their empiric antibiotic coverage de-escalated following negative cultures, according to a retrospective cohort study published in Clinical infectious Diseases.

Investigators studied patients 18 years and older admitted with pneumonia to a hospital participating in the Premier Healthcare Database between 2010 and 2015. Patients with positive culture isolates, positive urine antigen tests, or positive polymerase chain reaction assays were excluded from participation. All patients received an empiric anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) drug and at least 1 antipseudomonal agent (excluding quinolones). De-escalation was defined as discontinuing both broad-spectrum empiric antimicrobial agents on hospital day 4 while continuing other antibiotics.

Associations of de-escalation on hospital day 4 were measured with the following outcomes: all-cause in-hospital mortality from hospital day 5 to 14; day 5 or later intensive care unit (ICU) transfer; invasive mechanical ventilation; vasopressor use; Clostridioides difficile infection or a positive laboratory test for it; length of stay; and cost.

Antibiotic re-escalation was defined as resumption of anti-MRSA or antipseudomonal therapy by day 7 after de-escalation and was measured.

A total of 14,710 eligible patients met the initial criteria. In general, anti-MRSA therapy was noted to be de-escalated earlier than antipseudomonal therapy. By day 4, 77 patients had died and 12,786 patients were on a broad-spectrum empiric antibiotic. By day 4, 1924 patients (13%) discontinued the empiric agents. By day 10, approximately 65% of patients had treatment de-escalated or were discharged.

De-escalation occurred more frequently larger hospitals (9.7%) compared with smaller hospitals (5.9%), in teaching hospitals (9.7%) compared with others (6.3%), and in urban hospitals (8.2%) compared with rural hospitals (6.9%).

The study authors found the following to be significantly associated with de-escalation:

  • Less frequent late ICU admission (odds ratio [OR], 0.38; 95% CI, 0.18-0.79);
  • Late invasive mechanical ventilation (OR, 0.25; 95% CI, 0.09-0.66);
  • Late vasopressor use (OR, 0.13; 95% CI, 0.04-0.44);
  • Shorter length of stay (risk-adjusted ratio of means, , 0.76; 95% CI, 0.75-0.78); and
  • Lower hospitalization cost (risk-adjusted ratio of means, 0.74; 95% CI, 0.72-0.76).

De-escalation was not significantly associated with 14-day mortality (OR, 0.65; 95% CI, 0.39-1.08) or developing C difficile infection (OR, 1.33; 95% CI, 0.40-4.47).

Re-escalation to broad-spectrum drugs occurred in 13 patients (1.4%) during their hospitalization.

“Looking at de-escalation rates across hospitals (2-35%) demonstrates that there is substantial room for improvement. In particular, the low rates of de-escalation among low-risk culture-negative patients highlight an easy target for antimicrobial stewardship, since close to 100% of such patients should be de-escalated,” the investigators stated.

Limitations of this study include some residual confounding by indication and a lack of clinical data that were needed to directly measure clinical severity.

“Since antibiotics are not benign and antimicrobial stewardship programs should emphasize de-escalation following negative cultures as an opportunity to reduce exposure to broad-spectrum antibiotics, improving both antimicrobial stewardship and medication safety by substitution of lower-toxicity agents,” study authors concluded.

Disclosure: Some authors have disclosed affiliations with biotech, pharmaceutical, device, and/or other companies. Please see the original reference for a full list of authors’ disclosures.


Deshpande A, Richter SS, Haessler S, et al. De-escalation of empiric antibiotics following negative cultures in hospitalized patients with pneumonia: rates and outcomes. Clin Infect Dis. 2021;72(8):1314-1322. doi:10.1093/cid/ciaa212