Pharmacodynamic Modeling of Risk Factors for Ciprofloxacin Resistance in Pseudomonas aeruginosa

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Abstract
Objective: To determine risk factors for ciprofloxacin resistance in Pseudomonas aeruginosa.Methods: Patients with cultures (any site) positive for P aeruginosa, susceptible to ciprofloxacin, between January 1993 and December 1996 were identified using a computerized database. Factors predictive of emergence of ciprofloxacin resistance in P aeruginosa strains isolated from the same cultured site, within 21 days of the initial culture, were determined. Factors considered included length of stay prior to initial P aeruginosa culture, isolation site, initial minimum inhibitory concentration (MIC), antibiotic area under the 24-hour concentration curve (AUC24), total area under the 24-hour inhibitory concentration curve ([AUIC24] AUC24/MIC summed for all active drugs), antibiotic(s) used as dichotomous variables (yes/no), and use of monotherapy or combination therapy.Results: Of 635 patients, 43 (7%) subsequently had ciprofloxacin-resistant P aeruginosa isolated. Four significantly differing patient groups were identified: group 1, P aeruginosa isolates from all sites other than the respiratory tract, treated with any drugs; group 2, respiratory tract isolates treated with drugs other than ciprofloxacin; group 3, respiratory tract isolates treated with ciprofloxacin at AUIC24 > 110 (μg·h/mL)/μg/mL; and group 4, respiratory tract isolates treated with ciprofloxacin at AUIC24 ≤110 (μg·h/mL)/μg/mL. The observed percentage resistant was a continuous function of prior length of stay in all four groups. Respiratory tract isolates had higher rates of ciprofloxacin resistance (12%) than isolates from other infection sites (4%). Respiratory tract isolates exposed to ciprofloxacin at AUIC24 ≤110 (μg·h/mL)/μg/mL had the highest resistance (17%). At AUIC24 >110 (μg·h/mL)/μg/mL, resistance was decreased to 11%, a rate similar to that seen in respiratory isolates not exposed to ciprofloxacin (7%).Conclusions: Application of pharmacokinetic and pharmacodynamic principles to dosing of ciprofloxacin may reduce the risk of ciprofloxacin resistance to the level seen in isolates exposed to other agents.