Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth

Abstract

Production of exotoxins by staphylococci and streptococci may lead to the development of toxic shock syndrome (TSS). Because clindamycin inhibits exotoxin production, its use has been advocated for the treatment of TSS. However, the bacteriostatic action of clindamycin might be a disadvantage for the treatment of overwhelming infections. We investigated the effects of flucloxacillin and gentamicin on exotoxin production, because incubation with these antibiotics combines bactericidal action with protein synthesis inhibition. Staphylococcus aureus during the logarithmic and stationary phases of growth was incubated with either clindamycin, flucloxacillin, or a combination of flucloxacillin and gentamicin at concentrations of 2 or 10 times the MIC. In logarithmic-phase cultures clindamycin had a static effect on bacterial growth. After incubation with flucloxacillin, either alone or in combination with gentamicin, a rapid and large reduction in the number of viable bacteria was demonstrated. In stationary-phase cultures none of the antibiotics significantly changed the number of viable bacteria. TSS toxin 1 (TSST-1) production during logarithmic-phase growth was inhibited by > or =95% by all antibiotics. In stationary-phase cultures, clindamycin, flucloxacillin, and the combination of flucloxacillin and gentamicin inhibited TSST-1 production by 95, 30, and 75%, respectively, compared with the level of exotoxin production in the controls. The present results indicate that clindamycin inhibits TSST-1 production and exerts bacteriostatic activity in both bacterial growth phases. Because the combination of flucloxacillin and gentamicin combines the inhibition of exotoxin production with high bactericidal activity at least in logarithmic-phase cultures, it should be considered an alternative to clindamycin for the treatment of exotoxin-mediated diseases, especially in patients with overwhelming infections.