Duration of exposure to antipseudomonal β-lactam antibiotics in the critically ill and development of new resistance.
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Study Objective: Minimizing the duration of broad‐spectrum antimicrobial exposure in the critically ill is a commonly used strategy aimed at preventing resistance. Our objective was to correlate the duration of exposure to antipseudomonal β‐lactam antibiotics with the development of new resistance in critically ill patients. Design: Single‐center, retrospective cohort study. Setting: A large, academic, tertiary care hospital. Patients: A total of 7118 adults with a discharge diagnosis of severe sepsis or septic shock who received at least one dose of cefepime, meropenem, or piperacillin‐tazobactam during their hospitalization between 2010 and 2015. Measurements and Main Results: Cohort entry was defined as the first day of any antipseudomonal β‐lactam initiation, and exposure was defined as the cumulative days of any antipseudomonal β‐lactam exposure during the 60‐day follow‐up period. The primary outcome was development of new resistance to any antipseudomonal β‐lactam > 3 days after cohort entry. New resistance was defined as detection of resistance to any antipseudomonal β‐lactam not identified within 180 days before cohort entry. Patients without an outcome (i.e., did not develop new resistance) or who died by day 60 were censored. Cox proportional hazards models were performed to assess the risk of development of new resistance to any antipseudomonal β‐lactam with each additional day of exposure. Analyses of each individual antipseudomonal β‐lactam were evaluated as secondary outcomes. Each additional day of exposure to any antipseudomonal β‐lactam resulted in an adjusted hazard ratio (aHR) of 1.04 (95% confidence interval [CI] 1.04–1.05) for new resistance development. The risk of developing new resistance to cefepime, meropenem, and piperacillin‐tazobactam for each additional day of exposure resulted in an aHR of 1.08 (95% CI 1.07–1.09), 1.02 (95% CI 1.01–1.03), and 1.08 (95% CI 1.06–1.09), respectively. Conclusion: Among critically ill patients who receive antipseudomonal β‐lactam antibiotics, each additional day of exposure to cefepime, meropenem, and piperacillin‐tazobactam is associated with an increased risk of new resistance development.
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Potential harms of unnecessary antimicrobials include allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, Clostridioides difficile infection, and antimicrobial resistance.
“These include a range of adverse events such as allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, Clostridioides difficile infection, and antimicrobial resistance [101–106].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [106]
The increasing emphasis on administering immediate antibiotics to all patients with possible sepsis may be driving increased use of unnecessarily broad-spectrum antibiotics, antibiotic-associated adverse events, and antimicrobial resistance without benefitting patients.
“The increasing emphasis on administering immediate antibiotics to all patients with possible sepsis may therefore be driving increased use of unnecessarily broad-spectrum antibiotics, antibiotic-associated adverse events, and antimicrobial resistance without benefitting patients.”
From Trends in empiric broad-Spectrum antibiotic use for suspected community-onset Sepsis in US hospitals (2024) · cites this paper as [17]
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- Authors
- Teshome, B. F., Vouri, S. M., Hampton, N., Kollef, M. H., & Micek, S. T.
- Affiliations
- University of Health Sciences and Pharmacy (US)
- University of Florida Health (US)
- BJC HealthCare (US)
- Washington University in St. Louis (US)
- Corresponding author
- Micek, Scott T.
- Venue
- Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Publisher
- Wiley
- Published
- 2019-01-07
- Volume
- 39
- Issue
- 3
- Pages
- 261-270
- ISSN
- 0277-0008 (ISSN-L)
- 1875-9114
- PMC
- PMC6507412
- OpenAlex
- W2902532896
- Cited by
- 190
- References
- 14
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 33 · 2023: 33 · 2022: 37 · 2021: 16 · 2020: 21 · 2019: 9
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for Barnes-Jewish Hospital
- National Center for Advancing Translational Sciences (KL2TR000450)
- Institute of Clinical and Translational Sciences (UL1TR000448)
- 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
- antimicrobial resistance, critically ill patients, sepsis, septic shock, cefepime, meropenem, piperacillin-tazobactam, broad-spectrum antibiotics, resistance development, antibiotic stewardship, intensive care unit, nosocomial infections, carbapenem resistance, extended-spectrum beta-lactamase, metallo-beta-lactamase, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Klebsiella oxytoca, Klebsiella aerophila
- MeSH terms
- Aged, Anti-Bacterial Agents, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Shock, Septic, Time Factors, Cohort Studies, Critical Illness, Sepsis, Drug Resistance, Multiple, Bacterial, beta-Lactams, Tertiary Care Centers
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