Hyatt J M, Schentag J J
The Clinical Pharmacokinetics Laboratory, Millard Fillmore Health System, Buffalo, New York 14209, USA.
Infect Control Hosp Epidemiol. 2000 Jan;21(1 Suppl):S9-11. doi: 10.1086/503167.
To determine risk factors for ciprofloxacin resistance in Pseudomonas aeruginosa.
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.
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 (microg x h/mL)/microg/mL; and group 4, respiratory tract isolates treated with ciprofloxacin at AUIC24 < or =110 (microg x h/mL)/microg/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 < or =110 (microg x h/mL)/microg/mL had the highest resistance (17%). At AUIC24 >110 (microg x h/mL)/microg/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.
确定铜绿假单胞菌对环丙沙星耐药的危险因素。
利用计算机数据库识别出1993年1月至1996年12月期间培养物（任何部位）中铜绿假单胞菌呈阳性且对环丙沙星敏感的患者。确定在初始培养后21天内从同一培养部位分离出的铜绿假单胞菌菌株中出现环丙沙星耐药的预测因素。考虑的因素包括初始铜绿假单胞菌培养前的住院时间、分离部位、初始最低抑菌浓度（MIC）、24小时浓度曲线下的抗生素面积（AUC24）、24小时抑菌浓度曲线下的总面积（[AUIC24]，所有活性药物的AUC24/MIC总和）、用作二分变量的抗生素（是/否）以及使用单药治疗或联合治疗。
635例患者中，43例（7%）随后分离出对环丙沙星耐药的铜绿假单胞菌。确定了四个有显著差异的患者组：第1组，来自呼吸道以外所有部位的铜绿假单胞菌分离株，接受任何药物治疗；第2组，呼吸道分离株接受环丙沙星以外的药物治疗；第3组，呼吸道分离株接受AUIC24>110（μg·h/mL）/μg/mL的环丙沙星治疗；第4组，呼吸道分离株接受AUIC24≤110（μg·h/mL）/μg/mL的环丙沙星治疗。在所有四组中，观察到的耐药百分比是先前住院时间的连续函数。呼吸道分离株的环丙沙星耐药率（12%）高于其他感染部位的分离株（4%）。接受AUIC24≤110（μg·h/mL）/μg/mL环丙沙星治疗的呼吸道分离株耐药率最高（17%）。当AUIC24>110（μg·h/mL）/μg/mL时，耐药率降至11%，与未接受环丙沙星治疗的呼吸道分离株的耐药率（7%）相似。
将药代动力学和药效学原理应用于环丙沙星给药可能会将环丙沙星耐药风险降低至与接受其他药物治疗的分离株所见水平相当。
