[In vivo bactericidal activity of an oxacillin-netilmicin combination against Staphylococcus aureus. Influence of the rhythm of netilmicin administration]

Abstract

The bactericidal activity of two regimens of netilmicin (8 mg/kg/day) given intravenously once a day (od) or thrice daily (tid) both alone and in combination with oxacillin (200 mg/kg/day) was compared using a model of fibrin clots infected with a strain of Staphylococcus aureus (10(7) CFU/g) sensitive to methicillin and netilmicin (clinical isolate) and implanted subcutaneously in rabbit. This study shows that: 1) Netilmicin given alone as both single and divided doses results in early bacterial killing but does not exert a bactericidal effect after 24 hours because of a significant late increase of the number of bacterial. 2) The netilmicin-oxacillin combinations are more bactericidal at 1 h, 2 h and 24 h than oxacillin alone (P less than 0.001). 3) The oxacillin-netilmicin combination appears to be better for bacterial killing when netilmicin is given thrice daily (P less than 0.001). It is hard to draw a clinical inference from such an experimental study but it seems that 8-hour divided doses intervals should be better for administration of netilmicin than single daily dose during the acute period of staphylococcal infections.