Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria
Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria
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DOI：
10.1093/jac/dkz225
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发表时间：
2019-09-01
影响因子：
5.2
通讯作者：
Spellberg, Brad
中科院分区：
文献类型：
--
作者：
Luna, Brian M.;Ershova, Ksenia;Spellberg, Brad
背景：需要新的策略来减缓细菌病原体中抗生素耐药性的出现。特别是，社会正在经历由革兰氏阴性细菌病原体引起的耐药性感染的危机，迫切需要新的治疗方法来对抗这些疾病。从宿主获得铁几乎是微生物病原体（包括革兰氏阴性菌）引起感染的普遍需要。我们以前曾报道，脱辅基转铁蛋白，目的：明确脱铁转铁蛋白在体外抑制肺炎克雷伯菌和鲍曼不动杆菌（革兰氏阴性菌）生长，减少抗生素耐药性的产生的潜力。方法：研究了脱辅基转铁蛋白单独或与美罗培南、环丙沙星联合应用对克雷伯氏杆菌的疗效。肺炎链球菌和A.结果：证明脱铁转铁蛋白对两种致病菌的MIC均为可检测的。脱铁转铁蛋白介导的添加剂的抗菌作用，这两种抗生素对多个菌株的时间杀灭试验。最后，加入脱辅基转铁蛋白，环丙沙星或美罗培南减少了耐药突变体的出现，在20天的连续传代的两个species.Conclusions：这些结果表明，脱辅基转铁蛋白可能有希望抑制耐药突变体的出现时，治疗革兰氏阴性菌引起的感染。
Background: New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gramnegative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens-including Gramnegative bacteria-to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.Objectives: To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.Methods: The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time-kill assay and assays for the selection of resistant mutants.Results: We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apotransferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time-kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.Conclusions: These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.