Pharmacodynamics and tolerability of high-dose, prolonged infusion carbapenems in adults with cystic fibrosis – A review of 3 cases

Cystic fibrosis (CF) is a disease marked by repeated acute pulmonary exacerbations of infections, often caused by Pseudomonas aeruginosa and Burkholderia cepacia. As antibiotic susceptibility declines, dose optimization must be considered to provide adequate pharmacodynamic exposure. We report three cases of CF exacerbations in adults caused by multi-drug resistant P. aeruginosa and B. cepacia. Each case required dosing strategies greater than currently recognized in package inserts: meropenem 3000 mg every 8 h (3-hour infusion) and doripenem 2000 mg every 8 h (4-hour infusion). Pharmacokinetic analyses demonstrated that targeted pharmacodynamic exposures were achieved against most of the organisms, resulting in clinical improvements despite laboratory reported resistance. The high-dose, prolonged infusion regimens were well tolerated demonstrating that pharmacodynamically optimized carbapenem regimens may be used safely and effectively in patients with limited conventional treatment options.