973

Abstract

Introduction: Infection is a frequent complication in patients undergoing lung transplantation (LTx). Moreover, some of these patients are already colonized by Pseudomonas aeruginosa (PA) before surgery and need an adequate antibiotic prophylaxis to avoid further infection. Although acute, critically illness induce large changes in antibiotic pharmacokinetics and may result in inadequate drug concentrations to treat PA, no data are available on β-lactams levels after LTx. We hypothesized that β-lactams concentrations could be inadequate to treat PA in the early phase after LTx. Methods: We reviewed all patients in whom broad-spectrum β-lactams levels (ceftzidime or cefepime, CEF; meropenem, MEM; piperacillin; TZP) were measured after LTx from April 2010 to November 2012. Drug concentrations were measured after 2 hours from the onset of a 30-min perfusion and just before (trough, C0) the next dose. Drug regimens were adapted in case of cystic fibrosis. Creatinine clearance (CrCl) was calculated on the 24-hour urine collection on the day of the drug dosing. β-lactams concentrations were considered as insufficient if drug levels remained below 4 times the clinical breakpoint of the minimal inhibitory concentration (MIC) for PA at 70% (CEF), 40% (MEM) or 50% (TZP) of the dose interval. Clinical breakpoints were defined according to EUCAST guidelines and were as follows: 8 mg/L for CEF, 2 mg/L for MEM and 16 mg/L for TZP. Results: A total of 44 drug levels (7=CEF; 18=MEM; 19=TZP) were obtained in 22 patients (median age 48 [36-62] years; 8/22 male gender; median APACHE II score on ICU admission 15 [11-18]); 6 of them had cystic fibrosis. Median time from antibiotic initiation to drug dosing was 2 [1-5] days. Insufficient drug concentrations were found in 2/7 (29%) dosing for CEF, 7/18 (38%) for MEM and 12/19 (63%) for TZP (p=0.18). Only 1/10 drug dosing was found to be insufficient in patients with cystic fibrosis when compared to others (20/34, p=0.006). The proportion of patients with insufficient drug concentrations increased from 7/19 if CrCl < 40 ml/min to 4/10 if CrCl 40-120 and 10/12 if CrCl >120 ml/min (p=0.03). Conclusions: β-lactams levels are often insufficient to treat PA after LTx. Augmented renal clearance is an important determinant of insufficient drug levels.