Pharmacodynamic Modelling of Risk Factors for Ciprofloxacin Resistance in Pseudomonas Aeruginosa. J. Hyatt, Millard Fillmore Hospital
Pharmacodynamic principles were explored to evaluate risk factors of ciprofloxacin resistance in Pseudomonas aeruginosa. Patients with cultures positive for P aeruginosa, susceptible to ciprofloxacin, between January of 1993 and December of 1996 were identified. 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 using logistic regression. Factors considered included: length of stay prior to initial P aeruginosa culture, isolation site, initial MIC, antibiotic area under the 24-hour concentration vs time curve (AUC24), total area under the 24-hour inhibitory concentration curve, antibiotic(s) used as dichotomous variables (yes/no) and use of monotherapy or combination therapy. Of 635 patients, 43 (7%) subsequently had ciprofloxacin-resistant P aeruginosa isolated. Four significantly-differing patient groups were identified. The observed percent 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 (g•h/mL)/g/mL had the highest resistance (17%). At AUIC24 >110 (g•h/mL)/g/mL, resistance was decreased to 11%, a rate similar to that seen in respiratory isolates not exposed to ciprofloxacin (7%). 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.
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