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

Abstract

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 (↑FEV1) between pre- and posttreatment. Meropenem pharmacodynamic indices (fT > MIC, fAUC/MIC, fCmin/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 ↑FEV1 was 18.8% ± 11.3% posttreatment. The mean (range) fT > MIC exposure was 63% (0–100%). An Emax model determined a significant relationship between fT > MIC and ↑FEV1 (r2 = 0.8, P < 0.0004). 65% fT > MIC was a significant predictor of response; the median (25th, 75th %) ↑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 ↑FEV1. Larger studies are required to confirm this exposure threshold.