[Reduced mycobacterial resistance to antituberculous drugs in the experiment and clinic: immediate and long-term results]

Probl Tuberk Bolezn Legk. 2007;(2):31-8.
[Article in Russian]


A suspension of multidrug resistant clinical Mycobacterium tuberculosis (MBT) strain, at a concentration of 1 x 10(8) microbes per ml, resistant to streptomycin (S), rifampicin (R), isoniazid (I), and kanamycin (K), was in vitro treated for 60 minutes with dissolved ozone (pO3) at a concentration of 0.5-4 microg/ml). Then it was placed in the Lowenstein-Jensen media containing various concentrations of S, I, R, and K. Following 3 months, drug susceptibility was determined by the number of cultured colonies and MBT was used to prepare a suspension at the same concentration, which was again treated with pO3 by the same procedure and placed to the media containing the drugs. A session was thrice repeated. After each pO3 treatment, MBT resistance to I decreased and it completely disappeared after triple treatment. Each pO3 treatment caused a reduction in MBT resistance to R, but it was high (640 microg/ml). After double pO3 treatment MBT resistance to S decreased, but it was recovered after its third ozone treatment. All pO3-untreated control cultures showed a growth of more than 100 colonies. Sixty-eight BALC/s mice were in vivo inoculated via intravenous injections of the clinical MBT strain resistant to S, I, R, and K. The mice were divided into 5 groups: 1) intact mice; 2) those inoculated and untreated; 3) those treated with 1; 4) those treated with I and peritoneally given pO3, 0.5-4 microg/ml); and 5) those given pO3. The animals began dying at month 4 of inoculation. By month 5, all mice, other than intact and pO3-treated ones, died. Passage of MBT from the month by month 4 showed a reduction in their resistance to I in the groups treated with pO3. When the mice were treated with I alone, damages to their livers and spleens were greater than when they were untreated. With co-administration of I and pO3, the damage was least. Treatment provoked a rapid change of MBT to granular and L-forms and MBT was undetectable in its typical form after 1-2-month therapy. The altered MBT formed an untypical histological pattern of tuberculous inflammation in mice in the presence of characteristic cellular cooperation. Clinical studies indicated that 1-6-month concurrent use of chemotherapy and pO3 in patients with drug-resistant tuberculosis eliminated drug resistance of isolated MBT to one of the drugs (I, R, K) in 97.3%, MBT became at once susceptible to I, R, and K in 47.2%. I and/or R were successfully used in the treatment of more than a third of the patients. The studies have demonstrated that most patients with drug-resistant pulmonary tuberculosis can be treated with the most effective drugs provided that systemic intravenous injection of pO3 is made.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / pharmacology
  • Antibiotics, Antitubercular / therapeutic use
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use*
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • Injections, Intravenous
  • Isoniazid / administration & dosage
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Kanamycin / administration & dosage
  • Kanamycin / pharmacology
  • Kanamycin / therapeutic use
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Ozone / administration & dosage
  • Ozone / pharmacology*
  • Radiography, Thoracic
  • Rifampin / administration & dosage
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Streptomycin / administration & dosage
  • Streptomycin / pharmacology
  • Streptomycin / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Pulmonary / diagnostic imaging
  • Tuberculosis, Pulmonary / drug therapy*


  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Kanamycin
  • Ozone
  • Isoniazid
  • Rifampin
  • Streptomycin