Assessment of new therapies for infection due to the Mycobacterium avium complex: appropriate use of in vitro and in vivo testing.
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.
Grosset
J H
JH
Department of Bacteriology and Virology, Groupe Hospitalier, Paris, France.
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003470:Culture Media; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D003470:Culture Media