Mushtaq Shazad, Warner Marina, Johnson Alan P, Livermore David M
Antibiotic Resistance Monitoring & Reference Laboratory, Health Protection Agency Colindale, 61 Colindale Avenue, London NW9 5HT, UK.
J Antimicrob Chemother. 2004 Sep;54(3):617-20. doi: 10.1093/jac/dkh401. Epub 2004 Aug 20.
Dalbavancin is a long-half-life (9-12 days) glycopeptide, now in Phase 3 development. Its pharmacokinetics may facilitate home intravenous therapy, early discharge and long prophylaxis.
Dalbavancin and comparators were tested in vitro against staphylococci and streptococci to determine (i) activity and (ii) the comparability of agar dilution MICs by the BSAC and the NCCLS methods. The test panels comprised 92-93 isolates each of Staphylococcus aureus, coagulase-negative staphylococci (CoNS) and 'viridans' streptococci, chosen for epidemiological diversity and to over-represent strains resistant to conventional agents, including teicoplanin.
Dalbavancin MICs by the BSAC and NCCLS methods generally were identical, or else those by the BSAC method were two-fold lower. In both cases the MIC distributions of dalbavancin within species groups were unimodal, with peaks at 0.25, 0.12/0.25 and 0.12 mg/L for S. aureus, CoNS and viridans streptococci, respectively. MIC differences between the BSAC and NCCLS methods were similarly small for other glycopeptides and, generally, non-glycopeptides. Dalbavancin MICs were mostly two- to 16-fold below those of vancomycin and dalbavancin-like vancomycin-remained highly active against teicoplanin-non-susceptible staphylococci.
Dalbavancin has good activity versus streptococci and staphylococci, including teicoplanin-resistant strains. MICs by BSAC and NCCLS agar dilution methods were comparable to each other; slightly lower MIC values, nevertheless, have been recorded by broth microdilution.
达巴万星是一种半衰期长(9 - 12天)的糖肽类药物,目前正处于3期研发阶段。其药代动力学特性可能有利于家庭静脉治疗、早期出院和长期预防。
对达巴万星及其对照药物进行体外抗葡萄球菌和链球菌测试,以确定(i)活性,以及(ii)英国抗菌化疗学会(BSAC)和美国国家临床实验室标准化委员会(NCCLS)方法的琼脂稀释法最低抑菌浓度(MIC)的可比性。测试菌组分别包含92 - 93株金黄色葡萄球菌、凝固酶阴性葡萄球菌(CoNS)和“草绿色”链球菌,这些菌株的选择考虑了流行病学多样性,并使对包括替考拉宁在内的传统药物耐药的菌株占比过高。
BSAC法和NCCLS法测得的达巴万星MIC通常相同,否则BSAC法测得的MIC值低两倍。在这两种情况下,达巴万星在各菌种组内的MIC分布均为单峰,金黄色葡萄球菌、CoNS和草绿色链球菌的峰值分别为0.25、0.12/0.25和0.12 mg/L。对于其他糖肽类药物以及一般的非糖肽类药物,BSAC法和NCCLS法之间的MIC差异同样很小。达巴万星的MIC大多比万古霉素低2至16倍,且达巴万星样万古霉素对替考拉宁不敏感的葡萄球菌仍保持高活性。
达巴万星对链球菌和葡萄球菌具有良好活性,包括对替考拉宁耐药的菌株。BSAC法和NCCLS法的琼脂稀释法测得的MIC彼此可比;不过,肉汤微量稀释法记录的MIC值略低。