Assessment of new therapies for infection due to the mycobacterium avium complex: Appropriate use of in vitro and in vivo testing

Jacques H. Grosset

Research output: Contribution to journalArticle

Abstract

Laboratory testing is a prerequisite to predictions about the potential value of human clinical trials-the gold standard for the assessment of new therapies for infection with the Mycobacterium avium complex (MAC).These laboratory assessments must be made in the proper sequence, with appropriate models and methodology used to obtain data valid in determining whether clinical trials are warranted. In vitro testing permits measurements of minimal inhibitory and minimal bactericidal concentrations, identification of the synergism or antagonism of various agents, definition of an agent’s pharmacokinetic properties (e.g., hydrophilicity or lipophilicity), and evaluation of a drug's intracellular penetration and activity against intracellular organisms. The most appropriate animal model for in vivo testing of activity against MAC is the beige mouse.Experiments in this model provide important data on an agent's minimal effective dose and on its optimal dose, dosing frequency, and route(s) of administration. Evaluations in the beige mouse also document whether the agent is bactericidal or bacteriostatic, whether it selects drug-resistant mutants, and whether its use in combination with other agents is beneficial.

Original languageEnglish (US)
Pages (from-to)S233-S236
JournalClinical Infectious Diseases
Volume18
DOIs
StatePublished - Apr 1994

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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