Towards precision antibiotic therapy: predictors and outcomes of meropenem target attainment

This study aimed to measure meropenem trough concentrations, assess their association with outcomes, and develop a clinical prediction score for optimal drug levels.

In this retrospective single centre cohort study, we analysed 543 meropenem concentrations from 331 patients. Targets were defined as 100% fT>MIC (duration of time the drug concentration remains above the minimum inhibitory concentration) and 100% fT>4×MIC. A predictive scoring system was developed using logistic regression and validated via receiver operating characteristic (ROC) analysis. Propensity score matching (PSM) and inverse probability treatment weighting were applied.

The target was reached in 73.8% of measurements for 100% fT>MIC and 48.8% for 100% fT>4×MIC. While the clinical cure rates were not different in patients with pharmacokinetic/pharmacodynamic (PK/PD) target attainment, microbiological cure rates were higher in case of achieving 100% fT>MIC and 100% fT>4×MIC (p<0.001). According to the multivariate logistic regression analysis, the best predictors of achieving the meropenem PK/PD target of 100% fT>MIC and >4×MIC were 6 g/24 hour loading dose, estimated glomerular filtration rate (eGFR) and age. While a 6 g/24 hour loading dose and older age were associated with higher target attainment, elevated eGFR correlated with lower serum levels. The prediction score derived by using these parameters had a sensitivity of 71.2%, specificity of 67.6%, positive predictive value of 86.1%, negative predictive value of 45.5% and accuracy of 70.2%. There is a trend towards clinical cure and target attainment according to PSM analysis.

Three-quarters of the measurements achieved the PK/PD target of 100% fT>MIC, while half achieved the more stringent target of 100% fT>4×MIC, highlighting the need for optimised dosing strategies. Target achievement rates can be improved with therapeutic drug monitoring and personalised dosing approaches are needed.