The Annals of pharmacotherapy · 2026
Meropenem Exposure, Target Attainment, and Therapeutic Drug Monitoring Practices in Critically Ill Adults Receiving Continuous Renal Replacement Therapy: A Systematic Review.
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Mohd Rozi Nazatul Adhwa, Jia Hui Lim, Saffian Shamin, Makmor-Bakry Mohd, Mohamad Yusof Aliza, Mustafar Ruslinda, M Saud Muhammad Nordin, Mohd Tahir Nor Asyikin
Аннотация
OBJECTIVE: To critically evaluate meropenem pharmacokinetics/pharmacodynamics (PK/PD) target attainment, therapeutic drug monitoring (TDM), infusion strategies, and clinical outcomes during continuous renal replacement therapy (CRRT).
DATA SOURCES: Ovid MEDLINE, PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to August 15, 2026, using meropenem, TDM, β-lactam, and CRRT terms, with adult, human, and English-language limits.
STUDY SELECTION AND DATA EXTRACTION: Thirteen reports representing 12 unique studies (2 randomized, 10 non-randomized) reporting meropenem concentration data during CRRT were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2 or ROBINS-I.
DATA SYNTHESIS: Total clearance ranged from 3.60 to 6.6 L/h. Lower or primary PK/PD target non-attainment ranged from 0% to 26.7%, while aggressive-target non-attainment ranged from 0% to 53.3% in most analyses and reached 93% in 1 study when a minimum inhibitory concentration (MIC) of 8 mg/L was assumed. Continuous or prolonged infusion may facilitate sustained exposure, but comparative evidence was limited. Four used routine TDM; only 2 implemented protocolized TDM-guided dose adjustment. Low exposure was associated with higher mortality in 1 adjusted observational analysis, but evidence for clinical outcomes was of very low certainty.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Standardized meropenem regimens cannot be assumed to provide consistent exposure during CRRT. Optimized infusion and timely, protocolized TDM may support individualized dosing when multidisciplinary expertise is available.
CONCLUSIONS: Available evidence supports a shift from standardized empirical dosing toward individualized, measurement-guided meropenem therapy in patients receiving CRRT.
DATA SOURCES: Ovid MEDLINE, PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to August 15, 2026, using meropenem, TDM, β-lactam, and CRRT terms, with adult, human, and English-language limits.
STUDY SELECTION AND DATA EXTRACTION: Thirteen reports representing 12 unique studies (2 randomized, 10 non-randomized) reporting meropenem concentration data during CRRT were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2 or ROBINS-I.
DATA SYNTHESIS: Total clearance ranged from 3.60 to 6.6 L/h. Lower or primary PK/PD target non-attainment ranged from 0% to 26.7%, while aggressive-target non-attainment ranged from 0% to 53.3% in most analyses and reached 93% in 1 study when a minimum inhibitory concentration (MIC) of 8 mg/L was assumed. Continuous or prolonged infusion may facilitate sustained exposure, but comparative evidence was limited. Four used routine TDM; only 2 implemented protocolized TDM-guided dose adjustment. Low exposure was associated with higher mortality in 1 adjusted observational analysis, but evidence for clinical outcomes was of very low certainty.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Standardized meropenem regimens cannot be assumed to provide consistent exposure during CRRT. Optimized infusion and timely, protocolized TDM may support individualized dosing when multidisciplinary expertise is available.
CONCLUSIONS: Available evidence supports a shift from standardized empirical dosing toward individualized, measurement-guided meropenem therapy in patients receiving CRRT.