Open AccessEffects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model
Author(s) -
J. Casal,
Lorenzo Aguilar,
Isabel Jado,
José Yuste,
Marı́a José Giménez,
J. Prieto,
Asunción Fenoll
Publication year - 2002
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.46.5.1340-1344.2002
Subject(s) - streptococcus pneumoniae , cefotaxime , pharmacodynamics , antibody , penicillin , sepsis , amoxicillin , antibiotics , pharmacokinetics , pharmacology , microbiology and biotechnology , medicine , pneumococcal infections , in vivo , immunology , biology
A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of beta-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-beta-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain. The rate of mortality was 100% in nontreated animals in the absence of specific antibodies. A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates. In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively. These doses produced times that the levels in serum remained above the MIC (deltaT > MICs) approximately 30% of the dosing interval. When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg ( approximately 8 times lower), with the deltaT > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively. This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance.