Association Between Delayed Broad-Spectrum Gram-negative Antibiotics and Clinical Outcomes: How Much Does Getting It Right With Empiric Antibiotics Matter?

• Published in: Clinical infectious diseases Vol. 80; no. 5; p. 949
• Main Authors: Baghdadi, Jonathan D, Goodman, Katherine E, Magder, Laurence S, Claeys, Kimberly C, Sutherland, Mark E, Harris, Anthony D
• Format: Journal Article
• Language: English
• Published: United States 04.06.2025
• Subjects: Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Female; Gram-Negative Bacteria - drug effects; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - mortality; Humans; Male; Middle Aged; Patient Readmission - statistics & numerical data; Retrospective Studies; Treatment Outcome; United States; United States; inpatient antibiotic utilization; gram-negative antibiotics; clinical outcomes; antibiotic stewardship; empiric therapy
• ISSN: 1537-6591
• DOI: 10.1093/cid/ciaf039

Clinicians often start unnecessarily broad-spectrum empiric gram-negative antibiotics out of the concern that delaying effective therapy could lead to a worse clinical outcome. This study examined the consequences of delayed initiation of broad-spectrum gram-negative antibiotics. In a retrospective cohort of adult inpatients from 928 US hospitals, we compared clinical outcomes after (1) empiric narrow-spectrum antibiotics escalated to broad-spectrum antibiotics (delayed broad-spectrum therapy [DBT]) and (2) empiric broad-spectrum antibiotics continued as post-empiric therapy (early broad-spectrum therapy [EBT]) using Win Ratios. DBT and EBT patients were matched on hospital, admitting diagnosis, and propensity scores incorporating 28 clinical variables. The outcome of interest was a ranked composite of mortality, readmission, and adverse drug events. Out of 746 880 inpatients, 82 276 (11%) received DBT and 664 604 (89.0%) received EBT. Among the 67 046 with DBT who were matched to 67 046 with EBT, mortality was 8.7% after DBT and 9.5% after EBT (P = .022), readmission was 10.5% after DBT and 11.8% after EBT (P < .0001), and the rate of adverse drug events was 8.4% after DBT and 7.2% after EBT (P < .0001). Among matched patients, clinical outcomes were superior after DBT compared with EBT (win-ratio 1.06; P < .0001). On average, among a large sample of adult inpatients who ultimately received broad-spectrum antibiotic therapy, delaying initiation of a broad-spectrum antibiotic was not associated with worse outcomes. Although broad-spectrum empiric therapy is undoubtedly sometimes warranted, this finding challenges the common belief that is it safer to err towards overly broad-spectrum empiric antibiotic therapy.