β-Lactam activity against resistant pneumococcal strains is enhanced by the immune system

Author:

Casal J.1,Giménez M. J.2,Aguilar L.2,Yuste J.1,Jado I.1,Tarragó D.1,Fenoll A.1

Affiliation:

1. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Majadahonda-Pozuelo, km. 2, 28220 Majadahonda, Madrid

2. Medical Department, GlaxoSmithKline, Tres Cantos, Madrid, Spain

Abstract

Abstract Pandemic resistance in Streptococcus pneumoniae is compromising antibiotic activity. Antibiotics that act on the cell wall, such as β-lactams, may have a combined effect with the immune system against S. pneumoniae , since both act on the bacterial envelope. This combined effect can be studied in vitro or in vivo with respect to bacterial killing, since lysis is the end-point of both β-lactams and the immune system. We review here the in vitro increase in the bactericidal activity of aminopenicillins by non-specific immunity (complement and polymorphonuclear leucocytes). Few data are available on the collaboration of specific immunity and β-lactams. We also review the effect of the presence of specific antibodies on the in vivo T > MIC needed for the therapeutic efficacy of amoxicillin, and on blood bacterial clearance in animal models. The effect that immunity has on pharmacodynamic parameters, such as T > MIC, in non-human studies may be used as a tool to predict the effect of these pharmacodynamic variations in overcoming resistance and its selection, in the context of increasing the use of pneumococcal conjugated vaccines.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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