Guay David R P
Institute for the Study of Geriatric Pharmacotherapy, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Pharmacotherapy. 2004 Jan;24(1):58-68. doi: 10.1592/phco.24.1.58.34808.
The advent of multidrug-resistant gram-positive aerobes such as Staphylococcus aureus, Streptococcus pneumoniae, and the enterococci, which are resistant to beta-lactams, vancomycin, and a host of other commonly used antimicrobials, has complicated our approach to antibiotic therapy. Despite marketing of the first oxazolidinone, linezolid, and the streptogramin combination, quinupristin-dalfopristin, an urgent need exists for more agents to combat these pathogens. Two such agents, the glycopeptide oritavancin (LY333328) and the glycylcycline tigecycline (GAR-936), are in phase III clinical trials. These agents, which require parenteral administration, exhibit substantial in vitro activity against a variety of gram-positive aerobes and anaerobes, including the multidrug-resistant organisms listed previously. Only tigecycline demonstrates useful activity against gram-negative organisms. Combination therapy of these agents with ampicillin or aminoglycosides frequently leads to synergistic in vitro activity against multidrug-resistant staphylococci and streptococci. These agents are also active in a variety of animal models of systemic and localized infections. Few published efficacy and tolerability data are available in humans. If controlled clinical trial data verify these agents' efficacy and tolerability, both drugs should become welcome additions to the available antimicrobials. However, restricting their use to the treatment of infections caused by bacteria resistant to other antimicrobials, especially multidrug-resistant staphylococci and streptococci, may prolong their clinical utility by retarding the development of resistance. Careful surveillance of bacterial sensitivity to these agents should be undertaken to assist clinicians in the decision whether or not to use these agents empirically to treat infections caused by suspected multidrug-resistant gram-positive pathogens.
耐多药革兰氏阳性需氧菌的出现，如对β-内酰胺类、万古霉素及许多其他常用抗菌药物耐药的金黄色葡萄球菌、肺炎链球菌和肠球菌，使我们的抗生素治疗方法变得复杂。尽管首个恶唑烷酮类药物利奈唑胺以及链阳菌素组合药物奎奴普丁-达福普汀已上市，但仍迫切需要更多药物来对抗这些病原体。两种此类药物，即糖肽类药物奥利万星（LY333328）和甘氨酰环素类药物替加环素（GAR-936），正处于III期临床试验阶段。这些药物需要胃肠外给药，对多种革兰氏阳性需氧菌和厌氧菌具有显著的体外活性，包括之前列出的耐多药菌。只有替加环素对革兰氏阴性菌显示出有效的活性。这些药物与氨苄西林或氨基糖苷类药物联合治疗，常常会对耐多药葡萄球菌和链球菌产生协同体外活性。这些药物在各种全身性和局部感染的动物模型中也具有活性。关于这些药物在人体中的疗效和耐受性的公开数据很少。如果对照临床试验数据证实这些药物的疗效和耐受性，那么这两种药物都将成为现有抗菌药物中受欢迎的补充药物。然而，将它们的使用限制于治疗由对其他抗菌药物耐药的细菌引起的感染，尤其是耐多药葡萄球菌和链球菌引起的感染，可能通过延缓耐药性的发展来延长它们的临床效用。应仔细监测细菌对这些药物的敏感性，以协助临床医生决定是否凭经验使用这些药物来治疗由疑似耐多药革兰氏阳性病原体引起的感染。
