French G L
Department of Infection, King's College London, St Thomas' Hospital, London SE1 7EH, UK.
J Antimicrob Chemother. 2006 Dec;58(6):1107-17. doi: 10.1093/jac/dkl393. Epub 2006 Oct 13.
Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens. These strains are often multiresistant to several antibiotic classes and are a major cause of serious hospital- and now community-acquired infections and associated morbidity and mortality. As a result of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are widely used as first-line therapy for serious MRSA infections. However, the emergence of glycopeptide tolerance and resistance has complicated treatment and there remains a clinical need for new antibiotics with suitable pharmacokinetic properties with activity against MRSA and other gram-positive pathogens. Infections caused by MRSA and other bacteria usually respond as well to bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence that rapid bacterial killing has potential clinical advantages over bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic lipopeptides, shows rapid bactericidal activity against S. aureus, including strains tolerant or resistant to other agents. This review outlines the methods by which bactericidal and bacteriostatic properties are defined and tested, discusses the potential importance of bactericidal therapy in MRSA and other infections and examines the potential role of daptomycin in treatment.
在过去十年中,耐甲氧西林金黄色葡萄球菌(MRSA)菌株已成为严重的病原体。这些菌株通常对多种抗生素类具有多重耐药性,是严重医院感染以及现在社区获得性感染及相关发病率和死亡率的主要原因。由于抗菌耐药性增加,糖肽类药物,如万古霉素,被广泛用作严重MRSA感染的一线治疗药物。然而,糖肽类药物耐受性和耐药性的出现使治疗变得复杂,临床上仍然需要具有合适药代动力学特性且对MRSA和其他革兰氏阳性病原体有活性的新型抗生素。由MRSA和其他细菌引起的感染通常对抑菌剂和杀菌剂的反应相同。然而,有证据表明,在某些感染中,快速杀灭细菌相对于抑菌治疗具有潜在的临床优势。达托霉素是首个环脂肽类药物对金黄色葡萄球菌具有快速杀菌活性,包括对其他药物耐受或耐药的菌株。本综述概述了定义和测试杀菌和抑菌特性的方法,讨论了杀菌治疗在MRSA和其他感染中的潜在重要性,并探讨了达托霉素在治疗中的潜在作用。