Carbapenem Therapeutic Drug Monitoring in Critically Ill Adult Patients and Clinical Outcomes: A Systematic Review with Meta-Analysis

Drug monitoring is one strategy of antibiotic stewardship to face antimicrobial resistance. This strategy could have a determinant role in critically ill patients treated with carbapenems to overcome pharmacokinetic variability, reduce the risk of subtherapeutic dosage or toxicity, and reduce the risks inherent to treatment. However, the effectiveness of therapeutic drug monitoring (TDM) is unknown. This paper aims to identify TDM effectiveness in critically ill patients treated with carbapenems. English and ClinicalTrials.gov databases were searched to identify relevant studies evaluating carbapenem TDM. Randomized controlled trials (RCTs) and comparative cohort studies were selected for inclusion if they compared carbapenem TDM to standard care in adult critically ill or sepsis/septic shock patients. The primary outcome was mortality. Secondary outcomes included morbidity, clinical cure, microbiological eradication, antimicrobial resistance, drug-related side effects, and achievement of target plasma concentrations. Overall, performing carbapenem TDM was not associated with a decrease in mortality. However, it could be evidence for a relationship with clinical cure as well as target attainment. Some studies found favorable outcomes related to clinical and microbiological responses, such as lower procalcitonin levels at the end of the monitored therapy compared to standard care. For the primary and secondary outcomes analyzed, strong evidence was not identified, which could be due to the size, risk of bias, and design of selected studies.

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Therapeutic Drug Monitoring of Fluconazole in Critically Ill Patients

Case Medical Research ◽

10.31525/ct1-nct04252027 ◽

2020 ◽

Author(s):

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug

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How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients?

BMC Infectious Diseases ◽

10.1186/1471-2334-14-288 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 51

Author(s):

Gloria Wong ◽

Fekade Bruck Sime ◽

Jeffrey Lipman ◽

Jason A Roberts

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Severe Infections

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Barriers and facilitators in the clinical implementation of beta-lactam therapeutic drug monitoring in critically ill patients

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000937 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Alan Abdulla ◽

Puck van den Broek ◽

Tim M.J. Ewoldt ◽

Anouk E. Muller ◽

Henrik Endeman ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Barriers And Facilitators ◽

Therapeutic Drug ◽

Clinical Implementation ◽

Beta Lactam

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Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

Journal of Applied Bioanalysis ◽

10.17145/jab.18.021 ◽

2018 ◽

Vol 4 (5) ◽

pp. 166-174

Author(s):

Nora J mabelis ◽

Kimberly N. Shudofsky ◽

Joost J. van Raaij ◽

Sjoerd D. Meenks ◽

Thomas Havenith ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Bacterial Infections ◽

Therapeutic Drug

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Personalized Antibiotic Therapy for the Critically Ill: Implementation Strategies and Effects on Clinical Outcome of Piperacillin Therapeutic Drug Monitoring—A Descriptive Retrospective Analysis

Antibiotics ◽

10.3390/antibiotics10121452 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1452

Author(s):

Schrader Nikolas ◽

Riese Thorsten ◽

Kurlbaum Max ◽

Meybohm Patrick ◽

Kredel Markus ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Antibiotic Therapy ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Implementation Strategy ◽

Care Staff ◽

Therapeutic Drug ◽

Health Care Staff ◽

Standard Operating

Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians’ alertness.

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