比较贝西沙星、加替沙星和莫西沙星对兔角膜炎模型中不同喹诺酮类药物敏感性模式铜绿假单胞菌菌株的作用。

Comparison of besifloxacin, gatifloxacin, and moxifloxacin against strains of pseudomonas aeruginosa with different quinolone susceptibility patterns in a rabbit model of keratitis.

机构信息

Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.

出版信息

Cornea. 2011 Jan;30(1):83-90. doi: 10.1097/ICO.0b013e3181e2f0f3.

DOI:10.1097/ICO.0b013e3181e2f0f3

PMID:20847656

Abstract

PURPOSE

Determine the effectiveness of topical besifloxacin, gatifloxacin, and moxifloxacin in treating keratitis caused by 2 strains of Pseudomonas aeruginosa with different quinolone susceptibility profiles.

METHODS

Minimal inhibitory concentrations (MICs) were determined for each fluoroquinolone. Sequence analysis was performed on the quinolone resistance determining regions of the ciprofloxacin/levofloxacin-resistant strain. Rabbit corneas were injected with 10 colony-forming units (CFU). After 16 hours, phosphate-buffered saline, besifloxacin (6 mg/mL), gatifloxacin (3 mg/mL), or moxifloxacin (5 mg/mL) was applied topically every 15 minutes for 5 doses, then every 30 minutes for 14 doses. Eyes were examined pre- and posttreatment. Corneas were harvested for bacterial quantitation.

RESULTS

MICs against the fully susceptible strain were 0.5, 0.25, and 0.5 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. The MICs against the ciprofloxacin/levofloxacin-resistant strain were 2, 16, and 32 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. Sequence analysis revealed amino acid mutations in all 4 fluoroquinolone target genes. None of the treatments had an effect on clinical severity of eyes infected with the fully susceptible strain (P > 0.05); however, all were effective at significantly reducing the bacterial CFU in the corneas (P < 0.05). For the ciprofloxacin/levofloxacin-resistant strain, clinical scores of besifloxacin-treated eyes were significantly lower than moxifloxacin-treated eyes (P < 0.037). The quantities of ciprofloxacin/levofloxacin-resistant bacteria recovered from corneas of all treatment groups were significantly lower than those recovered from phosphate-buffered saline-treated corneas (P < 0.05). Besifloxacin-treated eyes had significantly lower CFU recovered as compared with that of gatifloxacin- and moxifloxacin-treated eyes (P < 0.05).

CONCLUSIONS

These results support clinical investigation of the effectiveness of besifloxacin in treating Pseudomonas keratitis.

摘要

目的

确定贝西沙星、加替沙星和莫西沙星治疗两种不同喹诺酮类药物敏感性表型铜绿假单胞菌角膜炎的疗效。

方法

测定每种氟喹诺酮的最小抑菌浓度（MIC）。对环丙沙星/左氧氟沙星耐药株的喹诺酮耐药决定区进行序列分析。用 10 个集落形成单位（CFU）注射兔角膜。16 小时后，用磷酸盐缓冲盐水、贝西沙星（6mg/mL）、加替沙星（3mg/mL）或莫西沙星（5mg/mL）每 15 分钟局部给药 5 次，然后每 30 分钟给药 14 次。治疗前后检查眼睛。采集角膜进行细菌定量。

结果

对完全敏感株的 MIC 分别为贝西沙星 0.5、0.25 和 0.5μg/mL，加替沙星和莫西沙星分别为 2、16 和 32μg/mL。对环丙沙星/左氧氟沙星耐药株的 MIC 分别为贝西沙星 2、16 和 32μg/mL，加替沙星和莫西沙星分别为 2、16 和 32μg/mL。序列分析显示所有 4 种氟喹诺酮靶基因均发生了氨基酸突变。治疗对完全敏感株感染的眼睛的临床严重程度均无影响（P＞0.05）；然而，所有治疗均能显著降低角膜中的细菌 CFU（P＜0.05）。对于环丙沙星/左氧氟沙星耐药株，贝西沙星治疗眼的临床评分明显低于莫西沙星治疗眼（P＜0.037）。与磷酸盐缓冲盐水治疗组相比，所有治疗组从角膜中回收的环丙沙星/左氧氟沙星耐药菌数量明显减少（P＜0.05）。与加替沙星和莫西沙星治疗组相比，贝西沙星治疗组回收的 CFU 明显减少（P＜0.05）。