PubMed1997
Determination of the MIC in vitro is often used as the basis for predicting the clinical efficacy of antibiotics. Listeriae are uniformly susceptible in vitro to most common antibiotics except cephalosporins and fosfomycin. However, the clinical outcome is poor. This is partially because listeriae are refractory to the bactericidal mechanisms of many antibiotics, especially to ampicillin-amoxicillin, which still is regarded as the drug of choice. A true synergism can be achieved by adding gentamicin. Another point is that listeriae are able to reside and multiply within host cells, e.g., macrophages, hepatocytes, and neurons, where they are protected from antibiotics in the extracellular fluid. Only a few agents penetrate, accumulate, and reach the cytosol of host cells, where the listeriae are found. Furthermore, certain host cells may exclude antibiotics from any intracellular compartment. Thus, determination of the antibacterial efficacy of a drug against listeriae in cell cultures may be a better approximation of potential therapeutic value. Certain host cells may have acquired the property of excluding certain antibiotics, for example macrolides, from intracellular spaces, which might explain therapeutic failures of antibiotic therapy in spite of low MICs. Animal models do not completely imitate human listeriosis, which is characterized by meningitis, encephalitis, soft tissue and parenchymal infections, and bacteremia. Meningitis produced in rabbits is a hyperacute disease, whereby most listeriae lie extracellularly, fairly accessible to antibiotics that can cross the blood-cerebrospinal fluid barrier. In the murine model of systemic infection, Listeria monocytogenes is located mainly within macrophages and parenchymal cells of the spleen and liver, hardly accessible to certain drugs, such as ampicillin and gentimicin. The therapeutic efficacy of drugs clearly depends on the model used. Thus, for example, the combination of ampicillin with gentamicin acts synergistically in the rabbit meningitis model but not in the mouse model. Since conventional antimicrobial therapy with antibiotics is not satisfactory, particularly in the immunocompromised host (about 30% of patients with listeriosis die in spite of a rational choice of antibiotics), other possibilities must be considered for therapy as well as prevention. Indeed, listeriae are highly susceptible to several endogenous antibiotics, such as defensins. Bacteriocins produced by related bacterial species, e.g., lactobacilli and enterococci, are rapidly bactericidal. However, unfortunately, the use of such alternative measures along with immunization and immunmodulation is not yet feasible.