Alou Cervera, LuisAguilar, LorenzoSevillano Fernández, DavidGiménez, María JoséLaguna, BeatrizEcheverría, OlatzCarcas, AntonioLubomirov, RubinCasal, JulioPrieto Prieto, José2024-07-292024-07-292005-05-01Alou L, Aguilar L, Sevillano D, Giménez MJ, Laguna B, Echeverría O, Carcas A, Lubomirov R, Casal J, Prieto J. Effect of opsonophagocytosis mediated by specific antibodies on the co-amoxiclav serum bactericidal activity against Streptococcus pneumoniae after administration of a single oral dose of pharmacokinetically enhanced 2000/125 mg co-amoxiclav to healthy volunteers. J Antimicrob Chemother. 2005 May;55(5):742-7.0305-745310.1093/jac/dki071https://hdl.handle.net/20.500.14352/107183Objectives: 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). Methods: 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)). Results: 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. Conclusions: 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.engjournal article1460-2091https://doi.org/10.1093/jac/dki071https://academic.oup.com/jac/article/55/5/742/691163restricted access611.02β-lactamsPhase I studypolymorphonuclear neutrophilsex vivo killing curvesMicrobiología médica2414 Microbiología