2026-06-28T20:13:03Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1071832024-07-29T23:50:20Zcom_20.500.14352_14col_20.500.14352_15

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 Alou Cervera, Luis Aguilar, Lorenzo Sevillano Fernández, David Giménez, María José Laguna, Beatriz Echeverría, Olatz Carcas, Antonio Lubomirov, Rubin Casal, Julio Prieto Prieto, José Objectives: 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. 2024-07-29T11:56:59Z 2024-07-29T11:56:59Z 2005-05-01 journal article Alou 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. 0305-7453 10.1093/jac/dki071 https://hdl.handle.net/20.500.14352/107183 1460-2091 https://doi.org/10.1093/jac/dki071 https://academic.oup.com/jac/article/55/5/742/691163 eng restricted access Oxford University Press