Chapter 15 - Murine Thigh Infection Model

Abstract

This chapter focuses on murine thigh infection model, which provides a sensitive experimental infection for evaluation of antimicrobial efficacy and allows for easily reproducible determination of antimicrobial-microbe interactions and the simultaneous measurement of antimicrobial pharmacokinetics in the serum and/or tissue of the infected animal. This model was first described by Eagle and co-workers, who in the late 1940s used a murine thigh infection to examine the effect of penicillin G in a single dose on the growth of various streptococci. It has been used by several investigators for further study of the in-vivo postantibiotic effect (PAE) and to examine various pharmacokinetic and dynamic parameters and their correlation with efficacy against a number of different organisms, both when used singly and in combinations for 24 hours. Any strain of Swiss mice can probably be used in the neutropenic model, but a pilot study to determine the growth rate of untreated organisms and the optimal inoculum is advisable. All antimicrobial classes currently used have been evaluated in the neutropenic murine thigh infection model, including penicillins, cephalosporins, carbapenems, glycopeptides, aminoglycosides, fluoroquinolones, macrolides, tetracyclines, lincosamines, rifamycins and streptogramins. Single-dose antimicrobial pharmacokinetics need to be determined either before or simultaneously with treatment. This model is suitable for screening of new antimicrobial agents, particularly in regards to the association of antibacterial effect with the pharmacological variables prior to clinical trials. Experience with aminoglycosides attests to the predictive ability of this model. Moreover, it is simple, accurate and cheap and it needs neither special housing (except for standard animal facilities) nor special equipment, and is thus suitable for practically every researcher in the field of microbiology and infectious diseases.