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Pharmacodynamic Modeling of Risk Factors for Ciprofloxacin Resistance in Pseudomonas aeruginosa

Published online by Cambridge University Press:  02 January 2015

Judith M. Hyatt  and
Jerome J. Schentag
Judith M. Hyatt*
Affiliation:
The Clinical Pharmacokinetics Laboratory, Buffalo, New York
Jerome J. Schentag
Affiliation:
The Clinical Pharmacokinetics Laboratory, Buffalo, New York
*
The Clinical Pharmacokinetics Laboratory, Millard Fillmore Health System, 3 Gates Cir, Buffalo, NY 14209
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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.

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 21 , Issue S1 , January 2000 , pp. S9 - S11
Copyright
Copyright © The Society for Healthcare Epidemiology of America 2000

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