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Meta-Analysis
. 2022 Nov 14;75(10):1848-1860.
doi: 10.1093/cid/ciac506.

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

Rekha Pai Mangalore  1   2 , Aadith Ashok  1 , Sue J Lee  1   2 , Lorena Romero  3 , Trisha N Peel  1   2 , Andrew A Udy  4   5 , Anton Y Peleg  1   2   6
Affiliations
Meta-Analysis

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

Rekha Pai Mangalore et al. Clin Infect Dis. .

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.

Keywords: antibacterial agents; critical illness; drug concentration; pharmacodynamics; pharmacokinetics.

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Conflict of interest statement

Potential conflicts of interest. R. P. M. reports a doctorate support scholarship from the National Health and Medical Research Council of Australia (NHMRC) unrelated to this work. A. A. U. reports grant funding from the NHMRC (paid to Monash University), the Medical Research Future Fund (MRFF) Australia (paid to Monash University), and the Department of Health, Commonwealth of Australia (paid to Monash University) for research projects outside the current work and in-kind support (trial consumables) from Integra Lifesciences for a project outside the current work. A. Y. P. reports grant funding from the NHMRC (Practitioner Fellowship; paid to Monash University) for research projects outside the current work and an investigator-initiated research grant from Merck Sharp & Dohme Corp. T. N. P. reports an NHMRC Career Development Fellowship; funds for advisory board consultancy for Merck Sharp & Dohme Corp outside the scope the submitted work and paid to author’s institution; and fees from Australian Health Unity as a consultant advising on coronavirus disease 2019 preparedness in residential aged care facilities. All authors declare that they have no known conflicts of interest, financial or otherwise that could have influenced the research reported in this paper. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Flow diagram showing the number of included studies. Abbreviation: TDM, therapeutic drug monitoring.
Figure 2.
Figure 2.
Forest plot showing the risk of mortality with TDM-guided beta-lactam dosing compared with standard dosing. The blue squares represent the effect estimates from individual studies; the size of the square is proportional to the weight of the study. The horizontal lines represent the 95% CI of the study estimate. The black diamond represents the pooled effect size. Abbreviation: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel Test; RR, risk ratio; TDM, therapeutic drug monitoring.
Figure 3.
Figure 3.
Forest plot comparing subgroup target attainment (A), clinical cure (B), and microbiologic cure (C). The blue squares represent the effect estimates from individual studies; the size of the square is proportional to the weight of the study. The horizontal lines represent the 95% CI of the study estimate. The black diamond represents the pooled effect size. Abbreviation: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel Test; RR, risk ratio; TDM, therapeutic drug monitoring.
Figure 4.
Figure 4.
A, Traffic light plot with summary of risk of bias for each randomized controlled trial: low (+), some concerns (–), and high (×). B, Summary plot. Each risk of bias item is presented as percentage.
Figure 5.
Figure 5.
Funnel plot showing the assessment of publication bias. Abbreviations: RR, risk ratio; SE, standard error.
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Comment in

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