Intracellular habitat of pathogenic microorganisms: implications for antimicrobial chemotherapy

A few pathogenic bacteria have developed various strategies to live in particular intracellular compartments. Within such specific niches the conditions for antibiotic activities may be quite different from the milieu given in the laboratory for in vitro testing of antimicrobial susceptibility according to recommended procedures such as EUCAST or CLSI. There are some examples when intracellular pathogens are not affected by an antimicrobial agent, although they are susceptible in vitro, namely Listeriae are in vitro susceptible to vancomycin but this antibiotic does not work on intracellular Listeria. On the other hand, it could happen that in the intracellular bacteria are susceptible to an agent which is ineffective under recommended in vitro test conditions, namely Listeriae are generally resistant to fosfomycin in vitro but fosfomycin is active against intracellular Listeriae. Prerequisites for effective treatment are: the microorganism is vulnerable, i.e. not refractory, during the intracellular living, the drug gets access to the site of residence (some drugs do not penetrate and some others are exported by efflux pumps) and the drug remains active under these particular conditions. Furthermore, the help of the host's own defense system is required. Therefore, antimicrobial therapy of infections with intracellular microorganisms should respect these aspects