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.