Preventing New Gram-negative Resistance Through Beta-lactam De-escalation in Hospitalized Patients With Sepsis: A Retrospective Cohort Study
Open accessAbstract
Background: Whether antibiotic de-escalation reduces the risk of subsequent antibiotic resistance is uncertain. We sought to determine if beta-lactam (BL) antibiotic de-escalation is associated with decreased incidence of new Gram-negative resistance in hospitalized patients with sepsis. Methods: In a retrospective cohort study, patients with sepsis who were treated with at least 3 consecutive days of BL antibiotics, the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7 were enrolled. Patients were grouped into three categories: (1) de-escalation of beta-lactam spectrum score (BLSS), (2) no change in BLSS, or (3) escalation of BLSS. The primary outcome was the isolation of a new drug-resistant Gram-negative bacteria from a clinical culture within 60 days of cohort entry. Fine-Gray proportional hazards regression modeling while accounting for in-hospital death as a competing risk was performed. Findings: Six hundred forty-four patients of 7742 (8.3%) patients developed new gram-negative resistance. The mean time to resistance was 23.7 days yielding an incidence rate of 1.85 (95% confidence interval [CI]: 1.71–2.00) per 1000 patient-days. The lowest incidence rate was observed in the de-escalated group 1.42 (95% CI: 1.16–1.68) per 1000 patient-days. Statistically significant reductions in the development of new gram-negative resistance were associated with BL de-escalation compared to no-change (hazards ratio (HR) 0.59 [95% CI: .48–.73]). Conclusions: De-escalation was associated with a decreased risk of new resistance development compared to no change. This represents the largest study to date showing the utility of de-escalation in the prevention of antimicrobial resistance.
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Fast de-escalation was shown to be associated with a decreased risk.
“and a fast de-escalation was shown to be associated with a decreased risk [26, 27].”
From Lab efficiency and improvements in the management of bloodstream infections: a before and after study (2025) · cites this paper as [27]
The Outcomes section reports that beta-lactam de-escalation was associated with less new gram-negative resistance than no change (HR 0.59, 95% CI 0.48–0.73). But the Discussion says patients were classified using their entire beta-lactam exposure, not just the early treatment phase; the paper therefore does not establish the added claim about *fast* de-escalation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAntibiotic resistance is correlated with antibiotic use.
“Antibiotic resistance being correlated with antibiotic use, in terms of antimicrobial stewardship, it is crucial that antibiotics are only used when indicated”
From Lab efficiency and improvements in the management of bloodstream infections: a before and after study (2025) · cites this paper as [27]
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Kam, K. Q., Chen, T., Kadri, S. S., Lawandi, A., Yek, C., Walker, M., Warner, S., Fram, D., Chen, H.-C., Shappell, C. N., et al. (2025) · Clinical Infectious Diseases · doi:10.1093/cid/ciae591 · Cited by 29 · see citing works
Optimal antibiotic use in the intensive care unit
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- Authors
- Teshome, B. F., Park, T., Arackal, J., Hampton, N., Kollef, M. H., & Micek, S. T.
- Affiliations
- University of Health Sciences and Pharmacy (US)
- St. John's University (US)
- BJC HealthCare (US)
- Washington University in St. Louis (US)
- Corresponding author
- Micek, Scott T
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-06-06
- Volume
- 79
- Issue
- 4
- Pages
- 826-833
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- OpenAlex
- W4399392886
- Cited by
- 39
- References
- 4
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 5
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- sepsis, antimicrobial resistance prevention, hospitalized patients
- MeSH terms
- Aged, Aged, 80 and over, Anti-Bacterial Agents, Female, Gram-Negative Bacteria, Hospitalization, Humans, Male, Middle Aged, Retrospective Studies, Incidence, Gram-Negative Bacterial Infections, Sepsis, beta-Lactams
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