Treatment of Experimental Staphylococcal Infection with Rifampin

Abstract

Bacteria surviving within leukocytes are protected from the lethal action of high concentrations of most antibiotics, which may explain, in part, the failure of bactericidal antibiotics to eradicate staphylococci from abscesses. Since rifampin is unique in its ability to kill intraleukocytic bacteria, the efficacy of this drug was tested in the treatment of staphylococcal infections in mice. Groups of mice infected intravenously with Staphylococcus aureus were treated with rifampin (20 mg/kg), procaine penicillin (937.5 mg/kg), or methicillin (200 mg/kg). All untreated mice died with disseminated visceral abscesses. After 10 days of therapy, survival in groups treated with penicillin and methicillin was 16 and 20%, respectively, whereas with rifampin it was 80% ( P < 0.0005). Antibiotic concentrations in the serum of mice treated with penicillin, methicillin, or rifampin were bactericidal for the strain of S. aureus used. Serial bacterial counts of kidney, lung, and spleen homogenates showed that neither penicillin nor methicillin was able to eradicate staphylococci, whereas rifampin completely sterilized those organs in many mice. When abscess contents and infected peritoneal washings were incubated with high concentrations of penicillin, methicillin, or rifampin, only rifampin killed all of the bacteria. The capacity of rifampin to eradicate staphylococci from pus in vitro and from abscesses in mice appears to be related to the ability of rifampin to kill intraleukocytic bacteria.