Mah Francis S, Romanowski Eric G, Kowalski Regis P, Yates Kathleen A, Gordon Y Jerold
Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Cornea. 2007 Jun;26(5):585-8. doi: 10.1097/ICO.0b013e318033a6f2.
Whereas gatifloxacin, a newer fluoroquinolone, was engineered to increase its Gram-positive potency, we assessed whether it still retained significant Gram-negative activity in vivo. Specifically, we compared the efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the New Zealand White (NZW) rabbit keratitis model.
A total of 30 NZW rabbits each were intrastromally inoculated in both eyes with approximately 1000 CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs; microg/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control. One drop was instilled in both eyes every 15 minutes for 5 doses and then every 30 minutes for 14 doses. One hour after the final treatment, the animals were euthanized, and bacterial colony counts from the corneas were determined.
For SM, Zymar and Ciloxan significantly reduced (P < 0.001, ANOVA) the colony counts compared with tobramycin and saline control. Zymar was more effective than Ciloxan (P < 0.001, ANOVA). For PA, all antibiotics reduced equivalently the colony counts compared with the saline control (P = 0.005, ANOVA).
The enhanced Gram-positive activity of gatifloxacin is not associated with any decreased Gram-negative activity in vivo. Zymar may prove useful for SM and PA keratitis.
加替沙星是一种新型氟喹诺酮类药物,其设计目的是增强对革兰氏阳性菌的抗菌效力,我们评估了它在体内是否仍保留显著的革兰氏阴性菌活性。具体而言,我们比较了Zymar(0.3%加替沙星)、Ciloxan(0.3%环丙沙星)和强化妥布霉素(14mg/mL)在新西兰白兔角膜炎模型中治疗粘质沙雷氏菌(SM)和铜绿假单胞菌(PA)引起的实验性革兰氏阴性菌感染的疗效。
总共30只新西兰白兔,每只兔子的双眼基质内接种约1000CFU的SM和PA。通过E试验,SM的最低抑菌浓度(MICs;μg/mL)分别为加替沙星(0.125)、环丙沙星(0.047)和妥布霉素(1.5),PA的分别为加替沙星(0.125)、环丙沙星(0.19)和妥布霉素(0.5)。16小时后,将兔子分为4个治疗组:(1)Zymar组,(2)Ciloxan组,(3)强化妥布霉素组,(4)生理盐水对照组。每15分钟双眼各滴入一滴,共滴5次,然后每30分钟滴入一滴,共滴14次。最后一次治疗后1小时,对动物实施安乐死,并测定角膜上的细菌菌落计数。
对于SM,与妥布霉素和生理盐水对照组相比,Zymar和Ciloxan显著降低了菌落计数(P<0.001,方差分析)。Zymar比Ciloxan更有效(P<0.001,方差分析)。对于PA,与生理盐水对照组相比,所有抗生素等效地降低了菌落计数(P=0.005,方差分析)。
加替沙星增强的革兰氏阳性菌活性与体内革兰氏阴性菌活性的任何降低均无关。Zymar可能对SM和PA角膜炎有用。