Alou Luis, Aguilar Lorenzo, Sevillano David, Giménez María-José, Laguna Beatriz, Echeverría Olatz, Carcas Antonio, Lubomirov Rubin, Casal Julio, Prieto José
Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain.
J Antimicrob Chemother. 2005 May;55(5):742-7. doi: 10.1093/jac/dki071. Epub 2005 Mar 10.
To measure the effect of opsonophagocytosis mediated by complement activated by specific antibodies on the co-amoxiclav serum bactericidal activity against Streptococcus pneumoniae strains with reduced susceptibility to beta-lactams (amoxicillin MICs of 2, 4, 8 and 16 mg/L).
An open Phase I study measuring ex vivo bactericidal activity after anti-pneumococcal vaccination and an oral dose of 2000/125 mg sustained-release co-amoxiclav was carried out. The ex vivo bactericidal activity was investigated through killing curves over 3 h [assuring polymorphonuclear neutrophil (PMN) viability] with serum samples collected 1.5 h and 5 h after dosing. Global killing was measured as the area under the killing curve (AUKC; log cfu x h/mL). The AUKC of the control growth curve of S. pneumoniae in Hanks' balanced salt solution (AUKC(K)) was used as control. The effect of the presence of complement and/or PMN was evaluated by the difference in the AUKC(K) and the different AUKCs obtained in the presence of inactivated serum (AUKC(IS)), active serum (AUKC(S)), inactivated serum plus PMN (AUKC(IS+PMN)) and active serum plus PMN (AUKC(S+PMN)).
Significant differences were found in all cases between the bactericidal activity of active serum+PMN (AUKC(K) - AUKC(S+PMN)) and that of inactivated serum (AUKC(K) - AUKC(IS)) with therapeutic indexes ranging from 0.56 to 3.04. At 1.5 h after dosing, a significantly higher bactericidal activity of co-amoxiclav was obtained when opsonophagocytosis occurred (samples with active serum and PMN) than when not occurring (killing curves with inactivated serum and without PMN), for all amoxicillin non-susceptible strains.
The results of this ex vivo study suggest that the collaboration of co-amoxiclav and complement-mediated opsonophagocytosis activated by specific antibodies may lay new approaches to overcome in vivo amoxicillin non-susceptibility.
测定特异性抗体激活补体介导的调理吞噬作用对复方阿莫西林血清杀菌活性的影响，该活性针对对β-内酰胺类药物敏感性降低的肺炎链球菌菌株（阿莫西林的最低抑菌浓度为2、4、8和16mg/L）。
开展一项开放性I期研究，测定抗肺炎球菌疫苗接种及口服一剂2000/125mg缓释复方阿莫西林后的体外杀菌活性。通过给药后1.5小时和5小时采集的血清样本，在3小时内绘制杀菌曲线（确保多形核中性粒细胞（PMN）的活力）来研究体外杀菌活性。总体杀菌率通过杀菌曲线下面积（AUKC；log cfu×h/mL）来衡量。将肺炎链球菌在汉克斯平衡盐溶液中的对照生长曲线的AUKC（AUKC(K)）用作对照。通过AUKC(K)与在灭活血清（AUKC(IS)）、活性血清（AUKC(S)）、灭活血清加PMN（AUKC(IS+PMN)）和活性血清加PMN（AUKC(S+PMN)）存在下获得的不同AUKC之间的差异，评估补体和/或PMN存在的影响。
在所有情况下，活性血清+PMN的杀菌活性（AUKC(K) - AUKC(S+PMN)）与灭活血清的杀菌活性（AUKC(K) - AUKC(IS)）之间均存在显著差异，治疗指数范围为0.56至3.04。给药后1.5小时，对于所有阿莫西林不敏感菌株，当发生调理吞噬作用时（活性血清和PMN的样本），复方阿莫西林的杀菌活性显著高于未发生时（灭活血清且无PMN的杀菌曲线）。
这项体外研究结果表明，复方阿莫西林与特异性抗体激活的补体介导的调理吞噬作用之间的协同作用可能为克服体内阿莫西林不敏感性提供新方法。
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