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

Abstract

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.

• Authors: I I Belianin, E I Shmelev
• Journal: Problemy tuberkuleza i boleznei legkikh (Probl Tuberk Bolezn Legk) Issue 2 Pg. 31-8 ( 2007) ISSN: 1728-2993 [Print] Russia (Federation)
• PMID: 17419333 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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