Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models.

Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models.
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DOI:
10.1111/j.1755-3768.2010.01897.x
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发表时间:
2010-06
影响因子:
3.4
通讯作者:
Gordon YJ
Gordon YJ
中科院分区:
医学3区
文献类型:
--
作者:
Kowalski RP;Romanowski EG;Mah FS;Shanks RM;Gordon YJ

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目的:确定1.5%左氧氟沙星局部应用能否成功治疗兔角膜炎模型中对左氧氟沙星耐药和敏感的金黄色葡萄球菌(SA)和铜绿假单胞菌(PA)。32只新西兰大白兔分别对左氧氟沙星耐药和敏感的SA进行骨髓腔内注射1000个集落形成单位(CFU)。4小时后,取8只兔的角膜匀浆,测定起始CFU/ml,24只兔分为3组:左氧氟沙星、万古霉素(头孢唑林为左氧氟沙星敏感的SA)和生理盐水。在5小时内给药21滴。治疗1小时后取角膜匀浆,取角膜匀浆,分别对左氧氟沙星耐药组和敏感组32只新西兰兔进行角膜基质内注射1000CFU。16小时后,取8只兔角膜匀浆,取CFU/ml。24只兔随机分为3组:左氧氟沙星、妥布霉素(环丙沙星为左氧氟沙星敏感PA)和生理盐水。在8小时内给药19滴。治疗1h后,取角膜匀浆,取CFU/ml数据进行灭菌处理和非参数分析。与万古霉素相比,1.5%左氧氟沙星对左氧氟沙星耐药的SA显著降低(p<0.05);对于左氧氟沙星敏感的SA,左氧氟沙星相当于头孢唑林(p>0.05);对于左氧氟沙星耐药的PA,相当于妥布霉素;对于左氧氟沙星敏感的PA,相当于环丙沙星;与生理盐水和发病相比,更多的SA和PA显著降低。在对左氧氟沙星敏感的PA组(32/32)和对左氧氟沙星敏感的SA组(16/16)中,1.5%的左氧氟沙星对角膜有灭菌作用,而对左氧氟沙星耐药的SA组(0/16)则不灭菌。1.5%左氧氟沙星可有效降低兔角膜炎模型的SA和PA,而不受体外耐药性的影响。
To determine whether topical levofloxacin 1.5% will successfully treat both levofloxacin-resistant and susceptible Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) in rabbit keratitis models. For levofloxacin-resistant and susceptible SA, respectively, 32 New Zealand White (NZW) rabbits were intrastromally injected with 1000 colony-forming units (CFU). After 4 hr, the corneas of eight rabbits were homogenized to determine onset CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, vancomycin (cefazolin for levofloxacin-susceptible SA) and saline. Twenty-one drops were administered over 5 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. For levofloxacin-resistant and susceptible PA, respectively, 32 NZW rabbits were intrastromally injected with 1000 CFU. After 16 hr, the corneas of eight rabbits were homogenized for CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, tobramycin (ciprofloxacin for levofloxacin-susceptible PA) and saline. Nineteen drops were administered over 8 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. The CFU/ml data were analysed for sterilization and non-parametrically for reduction. Levofloxacin 1.5% significantly reduced more (p < 0.05) levofloxacin-resistant SA than vancomycin; was equivalent to cefazolin (p > 0.05) for levofloxacin-susceptible SA; was equivalent to tobramycin for levofloxacin-resistant PA; was equivalent to ciprofloxacin for levofloxacin-susceptible PA; and significantly reduced more SA and PA than saline and onset. Levofloxacin 1.5% sterilized the corneas in the levofloxacin-resistant and susceptible PA groups (32/32) and levofloxacin-susceptible SA group (16/16), but not the levofloxacin-resistant SA group (0/16). Levofloxacin 1.5% was effective for reducing SA and PA in the rabbit keratitis models regardless of in vitro resistance.