Methods: Plasma samples were collected at steady-state at timed intervals after a single 400mg IV dose from burn patients receiving ciprofloxacin q12h or q8h, and ICU trauma patients dosed q12h (N=3, 3, and 8). Drug levels were determined by HPLC. PK parameters were estimated by non-compartmental analysis using WinNonLin (Certara, Inc.). A 10,000 subject Monte Carlo simulation was performed using EUCAST MIC distributions to determine the cumulative fraction of response (CFR) for A. baumannii, P. aeruginosa, K. pneumoniae, E. cloacae, and E. coli (Crystal Ball, Oracle).
Results: PK and demographic parameters did not differ significantly between the groups, nor did presumed augmented renal clearance (eGFR>120 ml/min/1.73m2) significantly affect weight-based clearance, volume of distribution or AUC24. The maximum MIC at which a ratio of AUC:MIC ≥125 could be achieved was 0.373 ±0.375 µg/mL, 0.539±0.429 µg/mL, and 0.344 ±0.113 µg/mL for burn patients dosed q12h, q8h, and non-burn trauma ICU patients dosed q12h, respectively. Using EUCAST MICs, Monte Carlo simulation revealed a CFR ranging from 56.7% in burn q12h patients with A. baumannii to 100% in all groups with E. cloacae.
Conclusion: Neither q12h nor q8h ciprofloxacin dosing achieved the optimal AUC:MIC ratio of ≥125 in critically ill burn or non-burn patients up to the susceptible breakpoint of 1 µg/mL for Enterobacteriaceae. More frequent dosing or larger doses could achieve optimal PK-PD at higher MICs, potentially improving ciprofloxacin efficacy in critically ill burn and trauma patients.
See more of: Poster Abstract Session