[Virulence of rifampicin and quinolone resistant mutants of strains of plague microbe with Fra+ and Fra- phenotypes].

Experiments with 15 highly virulent antigenically typical strains (Fra+) and 3 fraction-free strains (Fra-) of the plague microbe were conducted. It was demonstrated that a single exposure of the plague microbe to rifampicin or nalidixic acid (100 micrograms/ml) resulted in the formation of mutants (Rifr or Nalr) resistant to the drugs. The mutation frequency was 10(-10)-10(-8). All the Nalr mutants showed cross resistance to ciprofloxacin, a 3rd generation quinolone. A comparative study of the virulence of the clones in the population of the initial strains of the plague microbe and the cultures of the Rifr and Nalr mutants revealed that the predominating majority of the variants resistant to rifampicin and the quinolone preserved their high virulence. The resistance level of the mutants was sufficient for inducing the infection development in the albino mice at the background of the therapy with rifampicin, nalidixic acid or ciprofloxacin: no statistically significant differences in the values of the LD50 of the culture for the treated and nontreated animals were recorded. The Rifr and Nalr variants of the fraction-free strains of the plague microbe preserved their ability to overcome the specific immunity in the albino mice. The experimental data indicated that the rifampicin or quinolone monotherapy required a caution and the combined etiotropic therapy was more advantageous since it decreased the risk of the complications due to the drug resistant virulent variants of the plague microbe forming during the treatment.