Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates.
Antimicrobial Activity of a Triple Antibiotic Combination Toward Ocular Pseudomonas aeruginosa Clinical Isolates.
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DOI：
10.1167/tvst.11.5.26
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发表时间：
2022-05-02
影响因子：
3
通讯作者：
Wozniak, Rachel A. F.
中科院分区：
文献类型：
--
作者：
Mei, Jia A.;Johnson, William;Kinn, Bailey;Laskey, Emily;Nolin, Lydia;Bhamare, Pratham;Stalker, Charlotte;Dunman, Paul M.;Wozniak, Rachel A. F.
铜绿假单胞菌是角膜感染的主要病因。近期，我们发现了一种抗菌药物组合，多粘菌素B/甲氧苄啶（PT）+利福平，在体外和体内研究中对铜绿假单胞菌都显示出令人瞩目的疗效。因此，通过测试该组合对多种铜绿假单胞菌临床分离株的疗效，进一步评估了这种组合作为一种潜在的角膜炎治疗方法。
测定了154株眼部临床铜绿假单胞菌分离株对莫西沙星、左氧氟沙星、红霉素、妥布霉素、PT、多粘菌素B（单独）、甲氧苄啶（单独）和利福平的最小抑菌浓度（MIC），其中90%的分离株来自角膜刮片。此外，利用部分抑菌浓度（FIC）测试评估了PT +利福平的疗效。
虽然100%的分离株对红霉素（平均MIC为224 ± 110 µg·mL⁻¹）和甲氧苄啶（单独）（206 ± 67.3 µg·mL⁻¹）有耐药性，但一般发现抗生素耐药性较低：莫西沙星（2%的分离株耐药；平均MIC为1.08 ± 1.61 µg·mL⁻¹）、左氧氟沙星（3.9%；1.02 ± 2.96 µg·mL⁻¹）、妥布霉素（1%；0.319 ± 1.31 µg·mL⁻¹）、多粘菌素B（0%；0.539 ± 0.206 µg·mL⁻¹）、PT（0%；0.416 ± 0.135 µg·mL⁻¹）和利福平（0%；23.4 ± 6.86 µg·mL⁻¹）。此外，FIC测试显示PT +利福平根除了100%的分离株，在95%的分离株中表现出相加或协同作用（平均FIC指数为0.701 ± 0.132）。
PT +利福平的药物组合对大量临床相关的铜绿假单胞菌菌株有效，因此，可能是铜绿假单胞菌角膜炎一种有前景的治疗方法。
这项工作促进了一种用于治疗角膜感染（细菌性角膜炎）的新型抗生素组合的临床前开发。
Pseudomonas aeruginosa is a leading cause of corneal infections. Recently, we discovered an antimicrobial drug combination, polymyxin B/trimethoprim (PT) + rifampin, that displayed impressive efficacy toward P. aeruginosa in both in vitro and in vivo studies. As such, this combination was further evaluated as a potential keratitis therapeutic through testing the combination's efficacy against a diverse set of P. aeruginosa clinical isolates. Minimum inhibitory concentrations (MICs) of moxifloxacin, levofloxacin, erythromycin, tobramycin, PT, polymyxin B (alone), trimethoprim (alone), and rifampin were determined for 154 ocular clinical P. aeruginosa isolates, 90% of which were derived from corneal scrapings. Additionally, the efficacy of PT + rifampin was evaluated utilizing fractional inhibitory concentration (FIC) testing. While 100% of isolates were resistant to erythromycin (average MIC 224 ± 110 µg·mL−1) and trimethoprim (alone) (206 ± 67.3 µg·mL−1), antibiotic resistance was generally found to be low: moxifloxacin (2% of isolates resistant; average MIC 1.08 ± 1.61 µg·mL−1), levofloxacin (3.9%; 1.02 ± 2.96 µg·mL−1), tobramycin (1%; 0.319 ± 1.31 µg·mL−1), polymyxin B (0%; 0.539 ± 0.206 µg·mL−1), PT (0%; 0.416 ± 0.135 µg·mL−1), and rifampin (0%; 23.4 ± 6.86 µg·mL−1). Additionally, FIC testing revealed that PT + rifampin eradicated 100% of isolates demonstrating additive or synergistic activity in 95% of isolates (average FIC index 0.701 ± 0.132). The drug combination of PT + rifampin was effective against a large panel of clinically relevant P. aeruginosa strains and, as such, may represent a promising therapeutic for P. aeruginosa keratitis. This work furthers the preclinical development of a novel antibiotic combination for the treatment of corneal infections (bacterial keratitis).
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影响因子：
8.1
作者：
Asbell, Penny A.;Sanfilippo, Christine M.;DeCory, Heleen H.
通讯作者：
DeCory, Heleen H.
影响因子：
14.2
作者：
Magiorakos, A. -P.;Srinivasan, A.;Monnet, D. L.
通讯作者：
Monnet, D. L.
影响因子：
4.9
作者：
Chojnacki, Michaelle;Philbrick, Alesa;Wozniak, Rachel A. F.
通讯作者：
Wozniak, Rachel A. F.
影响因子：
2.3
作者：
Price, FW;Dobbins, K;Zeh, W
通讯作者：
Zeh, W
影响因子：
3.6
作者：
Alter, Sherman J.;Sanfilippo, Christine M.;DeCory, Heleen H.
通讯作者：
DeCory, Heleen H.