Killing of Intraleukocytie Staphylococcus aureus by Rifampin: In-Vitro and In-Vivo Studies

Abstract

Many virulent Staphylococcus aureus phagocytized by polymorphonuclear neutrophils (PMN) remain viable. Human PMN were mixed with S. aureus aerobically and anaerobically, and it was observed that many intracellular bacteria survived incubation with high concentrations of nine commonly used antistaphylococcal agents. In marked contrast to this, low concentrations of rifampin completely killed intraleukocytic bacteria. Experiments were then performed to evaluate the efficacy of rifampin in staphylococcal infections in mice. Treatment with penicillin or methicillin of mice that had been given intraperitoneal injections of S. aureus was only minimally effective in reducing mortality (93.1% in untreated mice, 83% in penicillin-treated mice, and 70% in methicillin-treated mice). In contrast to this, treatment with rifampin reduced mortality to 27.1% (P < .0005). In other experiments, rifampin alone prevented the formation of abscesses resulting from subcutaneous inoculation of staphylococci. The mechanism for this marked activity of rifampin in the treatment of experimental staphylococcal infections may be the unique ability of this antibiotic to kill intracellular staphylococci.