Monte Carlo simulation of Fluoroquinolone treatment for urinary tract infection caused by Escherichia coli: Analysis of Canadian versus U.S isolates

Ahmed Noreddin


This study aimed to assess the probability of Ciprofloxacin (Cipro) compared to Gatifloxacin (Gati) and Levofloxacin (Levo) achieving favorable activity for bacterial eradication and prevention of resistance development in E.coli. Cipro 500mg BID along with various doses of Gati and Levo were simulated, and target attainment potential was estimated in hospitalized patients. Previously described and validated population pharmacokinetic (PK) models of Cipro, Gati and Levo in hospitalized patients were utilized to simulate Cipro, Gati and Levo PKs. Free-drug Area Under the Concentration (AUC 0-24) was simulated in Plasma (P) using Cipro 500mg BID, Gati 200mg and 400mg OD as well as Levo 500mg, 750mg and 1000mg OD. E.coli susceptibility data were obtained from the North American Urinary Tract Infection Surveillance Study (NAUTICA). The NAUTICA study collected 2000 outpatient urinary isolates (1142 E.coli) from all geographic regions in Canada and USA. Use of Monte Carlo Simulation allowed for the full variability of susceptibility data and AUC 0-24 data for all patients. In hospitalized patients, Cipro 500mg BID, Gati 400mg OD and Levo 750mg OD showed high probability for target attainment of free AUC0-24/MIC of 125 or 250 against E.coli. Compared to Canada, U.S isolates showed lower probability of achieving a favorable outcome.


Pharmodynamics; Escherichia Coli; Monte Carlo Simulation

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