Journal Article

Effect of opsonophagocytosis mediated by specific antibodies on the co-amoxiclav serum bactericidal activity against <i>Streptococcus pneumoniae</i> after administration of a single oral dose of pharmacokinetically enhanced 2000/125 mg co-amoxiclav to healthy volunteers

Luis Alou, Lorenzo Aguilar, David Sevillano, María-José Giménez, Beatriz Laguna, Olatz Echeverría, Antonio Carcas, Rubin Lubomirov, Julio Casal and José Prieto

in Journal of Antimicrobial Chemotherapy

Volume 55, issue 5, pages 742-747
Published in print May 2005 | ISSN: 0305-7453
Published online May 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki071
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

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  • Medical Oncology
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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 β-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 × h/mL). The AUKC of the control growth curve of S. pneumoniae in Hanks' balanced salt solution (AUKCK) was used as control. The effect of the presence of complement and/or PMN was evaluated by the difference in the AUKCK and the different AUKCs obtained in the presence of inactivated serum (AUKCIS), active serum (AUKCS), inactivated serum plus PMN (AUKCIS+PMN) and active serum plus PMN (AUKCS+PMN).

Results: Significant differences were found in all cases between the bactericidal activity of active serum+PMN (AUKCK – AUKCS+PMN) and that of inactivated serum (AUKCK – AUKCIS) 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.

Keywords: β-lactams; Phase I study; polymorphonuclear neutrophils; ex vivo killing curves

Journal Article.  3605 words. 

Subjects: Medical Oncology ; Critical Care

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