Snydman D R, McDermott L A, Jacobus N V
Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA.
J Chemother. 2005 Dec;17(6):614-21. doi: 10.1179/joc.2005.17.6.614.
The interactions of daptomycin with gentamicin and 5 beta-lactam agents were determined by checkerboard and timed-kill studies. Eighty isolates were tested by checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and VRE. Checkerboard results showed highest frequency of synergistic effects against VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a modest effect with most combinations against VRE and MRSA (5-20%); and indifference with daptomycin and most agents against MSSA (0-5%); except with daptomycin with oxacillin where 10-20% synergy was observed. Synergistic interaction was confirmed by time kill studies in seven of ten isolates where checkerboard suggested synergy. A bactericidal effect was exerted in 5/7 synergistic combinations. The in vitro data suggest that daptomycin combined with other antibiotics may be microbiologically beneficial and not antagonistic.
通过棋盘法和时间杀菌研究确定了达托霉素与庆大霉素及5种β-内酰胺类药物的相互作用。用棋盘法检测了80株菌株：耐甲氧西林金黄色葡萄球菌（MRSA）、甲氧西林敏感金黄色葡萄球菌（MSSA）、万古霉素敏感粪肠球菌（VSEF）和万古霉素耐药肠球菌（VRE）各20株。对8株选定的菌株进行了时间杀菌曲线实验：MRSA、MSSA、VSEF和VRE各2株。棋盘法结果显示，达托霉素与头孢曲松、头孢吡肟或亚胺培南联合使用时，对VSEF的协同效应频率最高（35%-75%）；对大多数VRE和MRSA组合有中等效应（5%-20%）；达托霉素与大多数药物对MSSA无相互作用（0%-5%）；但达托霉素与苯唑西林联合使用时观察到10%-20%的协同作用。在棋盘法提示有协同作用的10株菌株中，有7株通过时间杀菌研究证实了协同相互作用。在5/7的协同组合中发挥了杀菌作用。体外数据表明，达托霉素与其他抗生素联合使用可能在微生物学上有益且无拮抗作用。
