利奈唑胺治疗多重耐药革兰阳性细菌性心内膜炎的研究进展

利奈唑胺是新型噁唑烷酮类抗生素,可口服,也可静脉应用.其口服生物利用度为100%,组织穿透能力强,即使在心脏瓣膜或赘生物上其局部浓度亦高.利奈唑胺与其他抗生素无交叉耐药性.虽然体外试验表明利奈唑胺主要是抑菌性的,但其对多重耐药革兰阳性菌,如凝血酶阴性葡萄球菌(CNS)、耐甲氧西林金葡菌(MRSA)、耐万古霉素肠球菌(VRE)等均有抗菌活性.已经证实,利奈唑胺能有效治疗动物模型实验性IE.利奈唑胺治疗人类IE时,既有成功也有失败的报道.一般来说,利奈唑胺耐受性好.长期治疗偶可引起可逆性骨髓抑制,如贫血及血小板减少.最近美国心脏学会(AHA)公布的指南建议,虽然利奈唑胺不作为IE治疗的一线药物,但对多重耐药革兰阳性菌株引起的IE,尤其对"标准疗法"有禁忌证或治疗失败,或不能耐受糖肽类抗生素者来说,还是一个重要的治疗选择.

Progress in Linezolid Treatment of Infective Endocarditis Caused by Multidrug-resistant Gram-positive Bacteria

Linezolid, a new oxazolidinone antibiotic that demonstrates a hundred percent of oral bioavailability, has been clinically available in both oral and intravenous formulation. It possesses a characteristic of high tissue penetration, even in cardiac valves and vegetations, which allows high local concentration of the antibiotic to be achieved. Linezolid has no cross-resistance with other classes of antibiotics. Despite in vitro the drug appears to be predominantly bacteriostatic, it shows activity against multidrug-resistant gram-positive organisms, including coagulase-negative staphylococci, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. It has shown the efficacy for infective endocarditis (IE) in animal models, but both successes and failures have been reported for human IE cases treated with linezolid. Overall, linezolid is well tolerated. Rare complications, such as reversible myelosuppression with anemia and thrombocytopenia, have been associated with prolonged linezolid therapy. The guidelines published recently by the American Heart Association (AHA) recommend linezolid as an important therapeutic option for the treatment of IE caused by multidrug-resistant gram-positive organisms, especially for the treatment of those patients who can not tolerate glycopeptides, or to whom standard therapy is contra-indicated or unsuccessful. However, it should not be regarded as first-line treatment.