COMBINATION OF FLUCLOXACILLIN AND GENTAMICIN INHIBITS TOXIC-SHOCK-SYNDROME TOXIN-1 PRODUCTION BY STAPHYLOCOCCUS-AUREUS IN BOTH LOGARITHMIC AND STATIONARY PHASES OF GROWTH

Production of exotoxins by staphylococci and streptococci may lead to the development of toxic shock syndrome (TSS), Because clindamycin inh ibits exotoxin production, its use has been advocated for the treatmen t of TSS. However, the bacteriostatic action of clindamycin might be a disadvantage for the treatment of overwhelming infections. We investi gated the effects of flucloxacillin and gentamicin on exotoxin product ion, because incubation with these antibiotics combines bactericidal a ction with protein synthesis inhibition, Staphylococcus am-ens during the logarithmic and stationary phases of growth mas incubated with eit her clindamycin, flucloxacillin, or a combination of flucloxacillin an d gentamicin at concentrations of 2 or 10 times the MIG. In logarithmi c-phase cultures clindamycin had a static effect on bacterial growth. After incubation with flucloxacillin, either alone or in combination w ith gentamicin, a rapid and large reduction in the number of viable ba cteria was demonstrated. In stationary-phase cultures none of the anti biotics significantly changed the number of viable bacteria, TSS tor;i n 1 (TSST-1) production during logarithmic-phase growth was inhibited by greater than or equal to 95% by ail antibiotics, In stationary-phas e cultures, clindamycin, flucloxacillin, and the combination of fluclo xacillin 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 grow th phases. Because the combination of flucloxacillin and gentamicin co mbines the inhibition of exotoxin production with high bactericidal ac tivity 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.