Carbapenem-associated multidrug-resistant Acinetobacter baumannii are sensitised by aztreonam in combination with polyamines.
Carbapenem-associated multidrug-resistant Acinetobacter baumannii are sensitised by aztreonam in combination with polyamines.
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DOI：
10.1016/j.ijantimicag.2012.08.009
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发表时间：
2013-01
影响因子：
10.8
通讯作者：
Kwon DH
中科院分区：
文献类型：
--
作者：
Malone L;Kwon DH
碳青霉烯类多重耐药鲍曼不动杆菌（MDR-Ab）在全球临床分离株中很常见，是一个主要的治疗挑战。以前的研究表明，外源性多胺（精胺和亚精胺）增强了铜绿假单胞菌对β-内酰胺类药物的敏感性，但诱导了对多粘菌素的耐药性。本研究旨在探讨外源性多胺治疗碳青霉烯类药物相关MDR-Ab的可能性。研究了多胺对A.测定了鲍曼不动杆菌、抗生素的最小抑菌浓度（MIC）以及时间杀灭和棋盘测定。脂多糖（LPS）和β-内酰胺酶活性对A.还评估鲍曼不动杆菌的多胺效应。A.单独使用4 mM精胺和16 mM亚精胺时鲍曼不动，但亚抑制浓度的氨曲南（AZT）（8 μg/mL）和这些浓度的多胺可显著抑制鲍曼不动。在所有碳青霉烯类相关MDR-Ab中，AZT单药（≥128 μg/mL）与多胺联合给药的MIC降至0.25-8 μg/mL。对青霉素的MIC也显著降低，但对头孢他啶和美罗培南的MIC没有显著降低，而对其他抗生素的MIC，包括多粘菌素B，在与多胺联合使用时，对所有测试的A均不受影响。鲍曼不动杆菌。多胺对AZT的影响与杀菌活性具有强烈的协同作用，并在5 mM MgCl 2（或CaCl 2）或200 mM NaCl的浓度下保留。排除了LPS和β-内酰胺酶在多胺效应中的作用。总体结果表明，AZT联合多胺可能有助于治疗碳青霉烯类药物相关的MDR-Ab。
Carbapenem-associated multidrug-resistant Acinetobacter baumannii (MDR-Ab) are common among clinical isolates worldwide and are a major therapeutic challenge. Previously it was shown that exogenous polyamines (spermine and spermidine) enhanced susceptibility to β-lactams but induced resistance to polymyxins in Pseudomonas aeruginosa. This study aimed to explore the possible availability of exogenous polyamines in treating carbapenem-associated MDR-Ab. The effects of polyamines on the growth rate of A. baumannii, minimal inhibitory concentrations (MICs) of antibiotics, and time–kill and checkerboard assays were determined. Roles of lipopolysaccharide (LPS) and β-lactamase activity of A. baumannii were also assessed for the polyamine effects. Growth of A. baumannii was unaffected at 4 mM spermine and 16 mM spermidine alone, but was significantly inhibited by a subinhibitory concentration of aztreonam (AZT) (8 μg/mL) and those concentrations of the polyamines. MICs to AZT alone (≥128 μg/mL) were reduced to the range 0.25–8 μg/mL in combination with polyamines in all carbapenem-associated MDR-Ab. MICs to penicillins, but not to ceftazidime and meropenem, were also significantly reduced, whilst MICs to other antibiotics, including polymyxin B, were unaffected in combination with polyamines for all tested A. baumannii. Polyamine effects on AZT were strongly synergistic with bactericidal activity and were retained at concentrations of 5 mM MgCl2 (or CaCl2) or 200 mM NaCl. Roles of LPS and β-lactamase in the polyamine effects were excluded. Overall results suggest that AZT in combination with polyamines may be useful for the treatment of carbapenem-associated MDR-Ab.
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