In Vitro Activity of Rifamycins Alone and in Combination with Other Antibiotics Against Chlamydia trachomatis

Abstract
Rifamycins are highly active against Chlamydia trachomatis, but the possible development of resistance has been of concern. The ability of rifampin, rifamide, and DL473 to induce resistance in chlamydiae and the effect of combinations of antibiotics on chlamydiae were evaluated in tissue culture. When chlamydiae were exposed to stepwise increases in the concentration of rifampin or rifamide, resistance rapidly emerged. Stepwise resistance did not emerge after exposure to DL473, although organisms resistant to one rifamycin were resistant to all three. Single-step emergence of resistance to rifampin or DL473 was also demonstrated. However, these resistant organisms were difficult to maintain in tissue culture. Combinations of ampicillin, erythromycin, or a tetracycline with rifampin or DL473 were neither synergistic nor antagonistic against chlamydiae. However, subinhibitory amounts of erythromycin or oxytetracycline prevented the emergence of resistance to rifampin. Such combinations may prove useful in therapy for chlamydial infections.