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检索：刘金淑
翻译：周超群
审核: 刘金淑、陈志锦
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[/h1][h1]美国：研究人员联合使用抗菌药物首次杀灭高耐药性大肠埃希菌[/h1]
由布法罗大学道格拉斯·雷维尔（Douglas Levere）提供的研究信息，氨曲南、阿米卡星和多粘菌素B的新型组合能够杀死携带mcr-1和ndm-5基因的大肠埃希菌，这两种基因使细菌能突破最后一道抗生素防线。
抗生素的黄金时代可能即将结束。最近发现携带mcr-1和ndm-5基因的大肠埃希菌使得细菌对最后抗生素免疫，已经导致临床医生无有效的手段来治疗超级细菌。但是在一项新的研究中，布法罗大学的研究人员组合了三种抗生素，它们在一起能铲除致命细菌。这一开创性的研究最近发表在美国微生物学会杂志《mBio》上。
研究人员发现，由氨曲南、阿米卡星和被称为抗生素最后防线之一的多粘菌素B的新型组合能够在24小时内杀死携带mcr-1和ndm-5基因的大肠埃希菌，同时也能防止它们的再次生长。然而，这些抗生素的传统组合并不能杀死这种大肠埃希菌，反而导致快速耐药性。
尽管在美国已报道的携带mcr-1的大肠埃希菌病例不到24例，但随着世界各地报告的病例数的增加，细菌对可用抗生素的免疫力已使医疗界容易受到大规模感染暴发的伤害。
抗生素耐药菌的快速增长,使多粘菌素的重要性重新引起人们的关注，多粘菌素是对耐药菌有效的一类抗生素，但由于它可能对肾脏造成伤害，而被当作最后的抗生素治疗手段。
为了避免开出高剂量的多粘菌素并弥补其缺陷，研究人员决定采用新的给药策略和多种抗生素组合。研究人员研究了超过15种抗生素联合多粘菌素B的数十种组合后，发现了两种有效的治疗方法。多粘菌素B与氨曲南或阿米卡星的组合在24小时后检测不到细菌。
然而，大肠埃希菌数在96小时后能够再次达到初始水平，并且在暴露于多粘菌素B和阿米卡星组合的10天后,产生阿米卡星耐药菌株亚群。多粘菌素B和氨曲南能将大肠埃希菌抑制在持续但非复制状态。只有三联组合才能消除大肠埃希菌菌株并防止再生长。
这一重要发现有希望为mcr-1和ndm-5菌株提供可行的治疗方法。
资料来源：布法罗大学
原文:
Researchers Use Antibiotics Combo to Kill First Strain of Highly Resistant E. coli in U.S.
August 21, 2017
A novel combination of aztreonam, amikacin and polymyxin B was able to kill E. coli carrying mcr-1 and ndm-5 — genes that make the bacterium immune to last-resort antibiotics. Courtesy of Douglas Levere, University at Buffalo
The golden age of antibiotics may be drawing to a close. The recent discovery of E. coli carrying mcr-1 and ndm-5 — genes that make the bacterium immune to last-resort antibiotics — has left clinicians without an effective means of treatment for the superbug. But in a new study, University at Buffalo researchers have assembled a team of three antibiotics that, together, are capable of eradicating the deadly bacterium. The groundbreaking research was recently published in mBio, a journal for the American Society of Microbiology.
The researchers found that a novel combination of aztreonam, amikacin and polymyxin B — a last-resort antibiotic — was able to kill E. coli carrying mcr-1 and ndm-5 genes within 24 hours while also preventing regrowth. Traditional combinations of these antibiotics were unable to kill the E. coli and resulted in rapid resistance.
Fewer than two dozen cases of E. coli carrying mcr-1 have been reported in the U.S. However, with additional cases reported worldwide, the bacteria’s immunity to available antibiotics has left the medical community vulnerable to a massive outbreak of infections.
The rapid increase in antibiotic-resistant bacteria has resurrected the importance of polymyxins, a class of antibiotics that are effective but employed as a last resort because of the damage they can cause to the kidneys.
To avoid prescribing high dosages of polymyxins and to make up for the antibiotic’s weaknesses, the researchers decided to turn to new dosing strategies and multiple antibiotic combinations
After conducting studies on dozens of combinations of more than 15 antibiotics paired with polymyxin B, the researchers discovered two effective treatments. Combinations of polymyxin B with either aztreonam or amikacin resulted in undetectable bacterial counts after 24 hours.
The E. coli, however, was able to regrow to initial levels after 96 hours and a subpopulation of amikacin-resistant strains arose after 10 days when exposed to the combination of polymyxin B and amikacin. Polymyxin B and aztreonam pushed the E. coli into a persistent but nonreplicating state. Only the triple combination eliminated the E. coli strain and prevented regrowth.
“We knew that polymyxins alone couldn’t work. Only the three drugs combined were able to work synergistically to suppress and kill the bacteria,” says Bulman. “We overcame the bacteria by pushing it as far as possible with an agent that it was resistant to while simultaneously administering two other antibiotics.”
The promising finding may provide a viable treatment against mcr-1 and ndm-5 strains.
The research was funded through a $4.4 million National Institutes of Health (NIH) grant awarded to Tsuji to develop new dosing regimens for polymyxins.
rce: University at Buffalo
图文编辑：小小牧童
审稿：马嘉睿 高晓东
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发表于 2017-9-22 19:32:00