Meropenem time above the MIC exposure is predictive of response in cystic fibrosis children with acute pulmonary exacerbations

Meropenem exposures from 15 children (8-17 years old) with cystic fibrosis (CF) acute pulmonary exacerbation were analyzed to define the pharmacodynamic threshold required for a positive response. The primary endpoint was the relative increase in forced expiratory volume in 1 s (up arrow FEV1) between pre- and posttreatment. Meropenem pharmacodynamic indices UT > MIC, fAUC/MIC, fC(min)/MIC) over the first 24 h were estimated for each participant based on their individual parameter estimates and the isolated pathogen with the highest meropenem MIC. Pseudomonas aeruginosa was the most common pathogen (n = 11/15). The mean SD up arrow FEV1 was 18.8% +/- 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0-100%). An E-max, model determined a significant relationship between fT > MIC and up arrow FEV1 (r(2) = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) up arrow FEV1 was 28.5% (22.2%, 31.7%) in those patients who achieved above 65% fT > MIC and 7.8% (1.1%, 12.6%) in those at or below 65% fT > MIC (P = 0.001). This is the first study in CF children to link meropenem exposure with a positive response as measured by up arrow TEV1. Larger studies are required to confirm this exposure threshold. (C) 2018 Elsevier Inc. All rights reserved.