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首页> 外文期刊>Cytokine >IFN-gamma enhances killing of methicillin-resistant Staphylococcus aureus by human monocytes more effectively than GM-CSF in the presence of daptomycin and other antibiotics.
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IFN-gamma enhances killing of methicillin-resistant Staphylococcus aureus by human monocytes more effectively than GM-CSF in the presence of daptomycin and other antibiotics.

机译:在达托霉素和其他抗生素存在下,IFN-γ比GM-CSF更有效地增强人单核细胞对耐甲氧西林金黄色葡萄球菌的杀伤力。

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摘要

Because cytokines have been utilized in treatment of sepsis in neonates, we studied the effects of interferon-gamma (IFN-gamma) and GM-CSF on killing of intracellular methicilin-resistant Staphylococcus aureus (MRSA) by human monocyte derived macrophages (MDM) in the presence of daptomycin (Dap), rifampin (Rif), gentamicin (Gen), and combinations of these drugs. MDM infected with MRSA were treated with Dap (1 x MIC), Gen (0.5 x MIC), or Rif (1 x MIC), singly or in combination, with or without cytokines. MDM were lysed and viable bacteria counted. With antibiotics, MDM activated by IFN-gamma had a more rapid and prolonged bacterial killing effect than MDM activated by GM-CSF. This effect was most obvious with the triple-drug combination. In contrast, GM-CSF reduced intracellular killing under most experimental conditions compared to the effect of antibiotics alone. Dap alone and two- and three-drug combinations demonstrated significant killing effect for the 48 h of the assay. IFN-gamma enhanced rapid intracellular killing of MRSA in the presence of triple-drug treatment or Dap alone. GM-CSF in combination with the antibiotics reduced killing under most conditions studied. Further studies to confirm these observations with IFN-gamma-activated MDM and other MRSA strains are needed to support clinical trials for difficult-to-treat MRSA infections.
机译:由于细胞因子已被用于治疗新生儿败血症,因此我们研究了干扰素-γ(IFN-γ)和GM-CSF对人单核细胞衍生巨噬细胞(MDM)杀灭细胞内耐甲氧西林的金黄色葡萄球菌(MRSA)的作用。达托霉素(Dap),利福平(Rif),庆大霉素(Gen)以及这些药物的组合的存在。用Dap(1 x MIC),Gen(0.5 x MIC)或Rif(1 x MIC)将MRSA感染的MDM单独或组合使用或不使用细胞因子进行治疗。裂解MDM并计数活菌。对于抗生素,与GM-CSF激活的MDM相比,IFN-γ激活的MDM具有更快,更长时间的细菌杀灭作用。对于三药组合,这种效果最为明显。相反,与单独使用抗生素的效果相比,在大多数实验条件下,GM-CSF减少了细胞内杀伤力。单独使用Dap以及两种和三种药物的组合在48小时的试验中显示出了显着的杀伤作用。在三重药物治疗或单独使用Dap的情况下,IFN-γ增强了MRSA的快速细胞内杀伤作用。在大多数研究条件下,GM-CSF与抗生素联合使用可减少杀伤力。需要进一步的研究来证实IFN-γ激活的MDM和其他MRSA菌株的这些观察结果,以支持难以治疗的MRSA感染的临床试验。

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