Support for higher ciprofloxacin AUC24/MIC targets in treating Enterobacteriaceae bloodstream infection

Abstract

Objectives: Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Patients and methods: Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Results: Significant factors with regard to treatment failure were low ciprofloxacin AUC24/MIC (P<0.0001), high MIC (P=0.001), male sex (P=0.002) and low AUC24 (P=0.01). AUC24/MIC (P=0.012) and MIC (P=0.019) were significant variables in multivariate analyses; however, only the former remained significant (P=0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC24/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P=0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC24/MIC ≥250 (P=0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC24/MIC ≥250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). Conclusions: This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC24/MIC ≥250, rather than the conventional target of ≥125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range. © The Author 2010.