Hsu Donald I, Okamoto Mark P, Murthy Rekha, Wong-Beringer Annie
School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
J Antimicrob Chemother. 2005 Apr;55(4):535-41. doi: 10.1093/jac/dki026. Epub 2005 Feb 22.
Resistance among Pseudomonas aeruginosa has risen dramatically and parallels the increase in fluoroquinolone (FQ) prescribing in recent years. Risk factors for FQ resistance in P. aeruginosa and its impact on outcomes need to be well characterized.
A case-control study was carried out on hospitalized adult patients from whom FQ-resistant (case) and FQ-susceptible (control) P. aeruginosa were isolated.
A total of 177 patients with positive cultures (91 cases and 86 controls) and 119 with documented infections (65 cases, 54 controls) were included in risk factor and outcomes analysis, respectively. Independent risk factors for FQ resistance were: FQ exposure (OR 12.6, CI 4.95-32), nosocomial acquisition (OR 8.6, CI 3.5-20.7), and diabetes mellitus (OR 6.4, CI 2.1-19.3). An FQ agent was prescribed in 59% of patients receiving an 'antipseudomonal' empirical regimen. Compared with controls, FQ-resistant cases had a median delay to receiving effective therapy of 3.5 days versus 1 day and poorer outcomes: (i) lower complete response rate (45% versus 63%, P=0.04); (ii) longer time to achieve clinical stability (8 days versus 3 days, P=0.005); and (iii) higher infection-related mortality (21% versus 7%; OR = 2.9, 0.9-9.4). Empirical FQ use (OR 4.6, CI 1.5-14.3), FQ resistance (OR 3.6, CI 1.0-13.1), and high APACHE II score (OR 1.1, CI 1.0-1.2) were independent risk factors for increased mortality.
FQ exposure from widespread prescribing is a modifiable risk factor for FQ resistance in P. aeruginosa. FQ empirical therapy for Pseudomonas infections may be associated with significant delays in administering effective therapy resulting in adverse outcomes.
近年来,铜绿假单胞菌的耐药性急剧上升,且与氟喹诺酮(FQ)类药物处方量的增加同步。需要充分明确铜绿假单胞菌对FQ耐药的危险因素及其对治疗结果的影响。
对住院成年患者开展了一项病例对照研究,这些患者分离出了对FQ耐药(病例组)和对FQ敏感(对照组)的铜绿假单胞菌。
分别将177例培养结果为阳性的患者(91例病例组和86例对照组)和119例有感染记录的患者(65例病例组、54例对照组)纳入危险因素及治疗结果分析。FQ耐药的独立危险因素为:暴露于FQ(比值比12.6,置信区间4.95 - 32)、医院获得性感染(比值比8.6,置信区间3.5 - 20.7)和糖尿病(比值比6.4,置信区间2.1 - 19.3)。在接受“抗假单胞菌”经验性治疗方案的患者中,59%的患者使用了FQ类药物。与对照组相比,对FQ耐药的病例组接受有效治疗的中位延迟时间为3.5天,而对照组为1天,且治疗结果更差:(i)完全缓解率较低(45%对63%,P = 0.04);(ii)达到临床稳定的时间更长(8天对3天,P = 0.005);(iii)感染相关死亡率更高(21%对7%;比值比 = 2.9,0.9 - 9.4)。经验性使用FQ(比值比4.6,置信区间1.5 - 14.3)、FQ耐药(比值比3.6,置信区间1.0 - 13.1)和高急性生理学与慢性健康状况评分系统II(APACHE II)评分(比值比1.1,置信区间1.0 - 1.2)是死亡率增加的独立危险因素。
广泛使用FQ导致的FQ暴露是铜绿假单胞菌对FQ耐药的一个可改变的危险因素。针对假单胞菌感染的FQ经验性治疗可能与有效治疗的显著延迟相关,从而导致不良后果。