Development and Assessment of a Nomogram to Propose the Initial Dosage Regimen of a Meropenem Infusion Based on Serum Creatinine and Age Using a Monte Carlo Simulation

Abstract

A conventional nomogram, based on serum creatinine (sCr) and age, was developed in order to determine the correct initial dosage regimen for meropenem (MEPM) infusions in elderly patients with severe community-acquired pneumonia (CAP), using a target minimum inhibitory concentration (MIC) of 2 mg/L. A correlation between age and actual bodyweight (BW) in a development cohort of 44 males and 45 females was performed by linear regression using the least-squares method (male: y 0.4676x 80.281, R 2 0.4888; female: y 0.4373x 77.502, R 2 0.3194). There were no significant differences between actual BW and the BW (e-BW) estimated using this equation in this cohort (male: e-BW 41.6 3.1 kg, BW 41.7 3.5 kg, p 0.93; female: e-BW 39.5 2.1 kg, BW 39.5 3.7 kg, p 0.20). By integrating these equations using the Monte Carlo simulation method, a dosage regime was calculated which would have an 80% probability of maintaining plasma drug levels above the MIC for more than 40% of the time (>40%TAM), using only the age and sCr of individual patients. This relationship was summarized as a nomogram. The nomogram was validated using an independent validation cohort (n 28) of patients. An optimized dosage regimen could be predicted in 84 patients (94.4%) in the development cohort and 25 patients (89.3%) in the validation cohort. This nomogram may be a useful tool for clinicians and pharmacists in determining an initial MEPM regimen in elderly patients with severe CAP, based only on age and sCr.

A dosing nomograph for cerebrospinal fluid penetration of meropenem applied by continuous infusion in patients with nosocomial ventriculitis

“…To date, there are several dosing nomograms available to guide continuous meropenem infusion for optimal drug exposure in critically ill patients (11)(12)(13)(14). Unfortunately, none of the nomograms target drug concentrations at the infection sites such as CSF.…”