眼科抗生素和抗菌药物耐药性：一项接受玻璃体内注射患者的随机对照研究。
Ophthalmic antibiotics and antimicrobial resistance a randomized, controlled study of patients undergoing intravitreal injections.
机构信息
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN, USA.
出版信息
Ophthalmology. 2011 Jul;118(7):1358-63. doi: 10.1016/j.ophtha.2010.12.014. Epub 2011 Mar 21.
PURPOSE
To determine whether repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics promotes antimicrobial resistance in patients undergoing intravitreal injections for choroidal neovascularization (CNV).
DESIGN
Prospective, randomized, controlled, clinical trial.
PARTICIPANTS
Forty-eight eyes of 24 patients undergoing unilateral intravitreal injections for CNV.
METHODS
Patients were assigned randomly to 1 of 4 ophthalmic antibiotics (azithromycin 1%, ofloxacin 0.3%, gatifloxacin 0.3%, moxifloxacin 0.5%) to be used after each injection in the treatment eye only. Bilateral conjunctival and unilateral nasopharyngeal cultures on the treatment side were obtained at baseline and were repeated at each subsequent visit for 1 year. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Genetic analysis of bacteria strains was performed using pulse-field gel electrophoresis.
MAIN OUTCOME MEASURES
Changes in antibiotic susceptibility patterns of conjunctival and nasopharyngeal flora over time and emergence of resistant strains.
RESULTS
Eight subjects (33%) grew Staphylococcus aureus from the nasopharynx and 1 subject (13%) showed emergence of a resistant strain. Coagulase-negative staphylococci (CNS) cultured from eyes repeatedly exposed to fluoroquinolone antibiotics demonstrated significantly increased rates of resistance to third- and fourth-generation fluoroquinolones compared with untreated eyes. Resistance to ofloxacin and levofloxacin was roughly 85% (P = 0.003), and resistance to gatifloxacin and moxifloxacin approached 67% (P = 0.009) and 77% (P<0.001), respectively. In contrast, CNS isolated from eyes repeatedly exposed to azithromycin demonstrated significantly increased resistance (94%) to erythromycin and azithromycin when compared with control eyes (P = 0.009) and decreased resistance to third-generation (P<0.03) and fourth-generation (P<0.001) fluoroquinolones when compared with eyes exposed to fluoroquinolones.
CONCLUSIONS
Repeated exposure of ocular and nasopharyngeal flora to ophthalmic antibiotics selects for resistant strains.
目的
确定眼部和鼻咽部菌群反复接触眼用抗生素是否会促进接受眼内注射脉络膜新生血管（CNV）治疗的患者产生抗菌药物耐药性。
设计
前瞻性、随机、对照临床试验。
参与者
24 例单侧 CNV 行眼内注射治疗的患者的 48 只眼。
方法
患者随机分配至 4 种眼科抗生素（阿奇霉素 1%、氧氟沙星 0.3%、加替沙星 0.3%、莫西沙星 0.5%）组，仅在治疗眼于每次注射后使用。在基线时获得治疗侧双侧结膜和单侧鼻咽培养物，并在随后的每次就诊时重复培养 1 年。使用 Kirby-Bauer 纸片扩散技术对所有细菌分离株进行 16 种不同抗生素的药敏性测试。使用脉冲场凝胶电泳对细菌株进行基因分析。
主要观察指标
随时间推移，结膜和鼻咽菌群的抗生素敏感性模式变化情况，以及耐药菌株的出现情况。
结果
8 例患者（33%）从鼻咽部培养出金黄色葡萄球菌，1 例患者（13%）出现耐药菌株。反复暴露于氟喹诺酮类抗生素的眼部培养出的凝固酶阴性葡萄球菌（CNS）对第三代和第四代氟喹诺酮类药物的耐药率显著高于未治疗的眼部。对氧氟沙星和左氧氟沙星的耐药率约为 85%（P = 0.003），对加替沙星和莫西沙星的耐药率分别接近 67%（P = 0.009）和 77%（P<0.001）。相比之下，反复暴露于阿奇霉素的 CNS 对红霉素和阿奇霉素的耐药性显著增加（94%），与对照眼相比（P = 0.009），对第三代（P<0.03）和第四代（P<0.001）氟喹诺酮类药物的耐药性降低。
结论
眼部和鼻咽部菌群反复接触眼用抗生素会选择耐药菌株。
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