■要测试头孢地洛,一种铁载体-头孢菌素抗生素,用于实验性广泛耐药(XDR)铜绿假单胞菌角膜炎的局部单药治疗。
■临床前研究。
■鉴定的铜绿假单胞菌角膜炎分离株,眼药水爆发的XDR铜绿假单胞菌,兔子,盐水,头孢地洛50毫克/毫升,环丙沙星0.3%,和妥布霉素14mg/ml。
■头孢地醇对铜绿假单胞菌角膜炎分离株(n=135)的抗菌活性通过最小抑制浓度(MIC)测试进行评估。用实验兔模型在体内测试眼毒性/耐受性和抗菌功效。使用生物测定法评估角膜浓度和稳定性。
■敏感性的最小抑制浓度分析,眼部毒性/耐受性分级试验,细菌负荷的菌落形成单位(CFU)分析,角膜头孢地洛浓度。
■100%的铜绿假单胞菌角膜炎分离株对头孢地洛敏感(n=135),MIC90为0.125μg/ml,包括XDR分离物(MIC=0.125μg/ml)。外用头孢地洛50mg/ml对眼表毒性最小,耐受性良好。对于XDR铜绿假单胞菌分离物,外用头孢地洛50毫克/毫升,与环丙沙星相比,角膜CFU显着降低0.3%,妥布霉素14毫克/毫升,和盐水。此外,妥布霉素14mg/ml比盐水对照更有效。平均头孢多醇角膜浓度比铜绿假单胞菌角膜炎分离株的MIC90高191倍。冷藏的头孢地醇在1个月的时间内保持了抗菌活性。
这些结果表明,头孢地洛对兔角膜具有良好的耐受性,并且在体外对铜绿假单胞菌角膜炎分离株有效,并且在体内对兔角膜炎模型中的XDR分离株有效。鉴于最近由这种XDR铜绿假单胞菌引起的角膜炎的爆发,头孢地洛是一种有前途的额外抗生素,应进一步评估用于抗生素耐药性铜绿假单胞菌引起的角膜炎的局部治疗。
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UNASSIGNED: To test cefiderocol, a siderophore-cephalosporin antibiotic for topical monotherapy treatment of experimental extensively drug-resistant (XDR) Pseudomonas aeruginosa keratitis.
UNASSIGNED: Preclinical study.
UNASSIGNED: Deidentified P. aeruginosa keratitis isolates, XDR P. aeruginosa from eye drop outbreak, rabbits, saline, cefiderocol 50 mg/ml, ciprofloxacin 0.3%, and tobramycin 14 mg/ml.
UNASSIGNED: Cefiderocol antibacterial activity against P. aeruginosa keratitis isolates (n = 135) was evaluated by minimum inhibitory concentration (MIC) testing. Ocular toxicity/tolerability and antibacterial efficacy were tested in vivo with experimental rabbit models. Corneal concentrations and stability were assessed using a bioassay.
UNASSIGNED: Minimum inhibitory concentration analysis for susceptibility, graded tests for ocular toxicity/tolerability, colony-forming unit (CFU) analysis for bacterial burden, corneal cefiderocol concentrations.
UNASSIGNED: One hundred percent of P. aeruginosa keratitis isolates were susceptible to cefiderocol (n = 135), the MIC90 was 0.125 μg/ml including the XDR isolate (MIC = 0.125 μg/ml). Topical cefiderocol 50 mg/ml was minimally toxic to the ocular surface and was well tolerated. For the XDR P. aeruginosa isolate, topical cefiderocol 50 mg/ml, significantly decreased corneal CFU compared with ciprofloxacin 0.3%, tobramycin 14 mg/ml, and saline. In addition, tobramycin 14 mg/ml was more effective than the saline control. Mean cefiderocol corneal concentrations were 191× greater than the MIC90 of the P. aeruginosa keratitis isolates. Refrigerated cefiderocol maintained antimicrobial activity over a 1-month period.
UNASSIGNED: These results demonstrate that cefiderocol is well tolerated on rabbit corneas and is effective against P. aeruginosa keratitis isolates in vitro and was effective in vivo against an XDR isolate in a rabbit keratitis model. Given the recent outbreak of keratitis caused by this XDR P. aeruginosa, cefiderocol is a promising additional antibiotic that should be further evaluated for topical treatment of keratitis caused by antibiotic resistant P. aeruginosa.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.