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针对常见的与导管相关感染有关的当代细菌病原体测试五盐酸奥米加南的抗菌活性。

Antimicrobial activity of omiganan pentahydrochloride tested against contemporary bacterial pathogens commonly responsible for catheter-associated infections.

作者信息

Fritsche Thomas R, Rhomberg Paul R, Sader Helio S, Jones Ronald N

机构信息

JMI Laboratories, North Liberty, IA 52317, USA.

出版信息

J Antimicrob Chemother. 2008 May;61(5):1092-8. doi: 10.1093/jac/dkn074. Epub 2008 Feb 29.

Abstract

OBJECTIVES

Omiganan pentahydrochloride is a cidal cationic peptide with a broad antimicrobial spectrum, including yeast, currently in development as a topical agent for the prevention of catheter-associated infections. We evaluated the spectrum and potency of omiganan against pathogens commonly associated with such infections.

METHODS

A recent (2005-06) collection of bacterial isolates originating from patients with bloodstream, respiratory tract, and skin and skin structure infections in US medical centres was evaluated by reference broth microdilution methods against omiganan and comparator agents.

RESULTS

All tested gram-positive (390) and -negative (167) isolates were inhibited by < or = 128 and < or = 1024 mg/L, respectively, of omiganan. The agent was the most active against coagulase-negative staphylococci (range 1-8 mg/L; MIC(50/90), 4 mg/L) and inhibited all Staphylococcus aureus at < or = 32 mg/L (MIC(50/90), 16 mg/L). Omiganan was 16-fold more active against Enterococcus faecium than Enterococcus faecalis (MIC(50/90) results, 4/8 versus 64/128 mg/L, respectively). MIC ranges and MIC(50) potencies were unaffected by methicillin resistance in staphylococci, vancomycin resistance in enterococci, and penicillin resistance in streptococci. Omiganan potency was also unaffected by extended-spectrum beta-lactamase (ESBL) production in Escherichia coli when compared with wild-type strains (MIC(50) values 32 mg/L), although a 4-fold increase was noted among ESBL-positive Klebsiella spp. (128 versus 32 mg/L, respectively). Wild-type Enterobacter spp. displayed higher omiganan MIC(50/90) results (64/512 mg/L) compared with AmpC-hyperproducing strains (32/64 mg/L). Carbapenem-susceptible and -resistant P. aeruginosa strains exhibited omiganan MIC(50/90) values of 128/256 mg/L.

CONCLUSIONS

At a 1% (10 000 mg/L) topical gel formulation, omiganan can be expected to inhibit all clinically relevant bacterial species producing catheter-associated infections (all MIC values, < or = 1024 mg/L), including those with antimicrobial-resistant phenotypes.

摘要

目的

五盐酸奥米加南是一种具有广泛抗菌谱的杀菌性阳离子肽,包括对酵母菌,目前正在开发作为预防导管相关感染的局部用药。我们评估了奥米加南对通常与此类感染相关的病原体的抗菌谱和抗菌效力。

方法

采用参考肉汤微量稀释法,对美国医疗中心近期(2005 - 2006年)收集的来自血流、呼吸道、皮肤及皮肤结构感染患者的细菌分离株进行了针对奥米加南及对照药物的评估。

结果

所有测试的革兰氏阳性(390株)和阴性(167株)分离株分别被≤128 mg/L和≤1024 mg/L的奥米加南抑制。该药物对凝固酶阴性葡萄球菌活性最强(范围为1 - 8 mg/L;MIC50/90为4 mg/L),并能在≤32 mg/L(MIC50/90为16 mg/L)时抑制所有金黄色葡萄球菌。奥米加南对粪肠球菌的活性比对屎肠球菌高16倍(MIC50/90结果分别为4/8与64/128 mg/L)。葡萄球菌中的耐甲氧西林、肠球菌中的耐万古霉素以及链球菌中的耐青霉素情况均不影响奥米加南 MIC范围和MIC50效力。与野生型菌株相比(MIC50值为32 mg/L),奥米加南对大肠杆菌中产生超广谱β-内酰胺酶(ESBL)的菌株的效力也未受影响,不过在产ESBL的克雷伯菌属中观察到MIC增加了4倍(分别为128与32 mg/L)。与高产AmpC酶的阴沟肠杆菌菌株(32/64 mg/L)相比,野生型阴沟肠杆菌菌株显示出更高的奥米加南MIC50/90结果(64/512 mg/L)。对碳青霉烯敏感和耐药的铜绿假单胞菌菌株的奥米加南MIC50/90值为128/256 mg/L。

结论

在1%(10000 mg/L)的局部凝胶制剂中,预计奥米加南可抑制所有引起导管相关感染的临床相关细菌种类(所有MIC值≤1024 mg/L),包括那些具有抗菌耐药表型的细菌。

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