Beta-Lactam Antibiotic Therapeutic Drug Monitoring in Critically Ill Patients: A Systematic Review and Meta-Analysis

Author:

Pai Mangalore Rekha12ORCID,Ashok Aadith1,Lee Sue J12,Romero Lorena3,Peel Trisha N12,Udy Andrew A45,Peleg Anton Y126

Affiliation:

1. Department of Infectious Diseases, Alfred Hospital, Alfred Health , Melbourne, Victoria , Australia

2. Central Clinical School, Monash University , Melbourne, Victoria , Australia

3. Ian Potter Library, Alfred Hospital , Melbourne, Victoria , Australia

4. Department of Intensive Care and Hyperbaric Medicine, Alfred Hospital, Alfred Health , Melbourne, Victoria , Australia

5. School of Public Health and Preventative Medicine Australia, Monash University , Melbourne, Victoria , Australia

6. Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Melbourne, Victoria , Australia

Abstract

Abstract Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.

Funder

National Health and Medical Research Council

Australian Health Unity

Merck Sharp & Dohme Corp

Medical Research Future Fund, and Department of Health, Australia

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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