PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Guiding Beta-lactam antibiotics dose by therapeutic drug monitoring increases clinical cure and microbiological eradication in critically ill patients – a systematic review and meta-analysis

Text of the abstract

Introduction
Around 70% of the critically ill patients admitted to intensive care units receive antibiotics and beta-lactams are the most frequently prescribed. The pharmacokinetics of these drugs varies considerably in this patient population, causing uncertainty in the dosing of antibiotics. Therapeutic drug monitoring (TDM) is an essential tool to provide evidence for making decisions on dosing which eventually improve clinical outcomes.
Aims
This systematic review and meta-analysis examined the efficacy of beta-lactam antibiotics prescribed based on TDM by comparison with standard dosing in critically ill patients.
Methods
We performed a systematic search using 3 databases on 4 November 2021. The study protocol was pre-registered in the PROSPERO database (CRD42021285188). We collected data on outcomes reported in the eligible studies, using the patients, intervention, comparison, outcome (PICO) framework. Randomized controlled trials and observational studies were selected. The population of interest included critically ill patients admitted to the ICU. The intervention group consisted of those receiving TDM-guided beta-lactam treatment, while in the comparison group standard dosing was used. The random effects model yielded the odds ratios (OR) and mean differences (MD) with the associated 95% confidence intervals (CI). I2 value and Χ2 test evaluated statistical heterogeneity.
Results
We included in the meta-analysis 7 trials comprising 798 patients. Significantly improved clinical cure (OR 2.27; 95%CI 1.89-2.72; I2=0%), and microbiological eradication (OR 1.89; 95%CI 0.70-5.10; I2=0%) were associated with TDM-guided treatments. Nevertheless, hospital and ICU mortality (OR 0.87, 95%CI 0.50-1.50, I2=0%; OR 0.95, 95%CI 0.50-1.80, I2=0%; respectively) and length of ICU stay (MD -0.46 days; 95%CI -2.70-1.75; I2=19%) did not differ significantly between the 2 groups.
Conclusion
Our study found that TDM of beta-lactam antibiotics increases clinical cure and improves microbiological eradication in critically ill patients. We did not find a significant association between TDM and other outcomes, including ICU length of stay, ICU mortality or hospital mortality. Strictly standardized protocols and trials with greater sample size are needed to establish TDM-guided dosing of beta-lactam antibiotics.