Antibiotic Adjuvant 4-Hexylresorcinol Enhances the Efficiency of Antituberculosis Drugs

Bull Exp Biol Med. 2024 Feb;176(4):466-471. doi: 10.1007/s10517-024-06048-5. Epub 2024 Mar 15.

Abstract

We studied the possibility of using 4-hexylresorcinol to increase the efficiency of anti-mycobacterial chemotherapy. In an in vitro experiment, 4-hexylresorcinol increased the efficiency of rifampicin, kanamycin, and isoniazid against Mycobacterium smegmatis by 3-5 times. Experiments in sanitation of BALB/c mice infected with M. smegmatis showed the best efficacy of the isoniazid and 4-hexylresorcinol combination in comparison with isoniazid monotherapy. The growth-inhibiting activity of the combination of antibiotic rifabutin with 4-hexylresorcinol was shown on 6 strains of M. tuberculosis. A 2-fold decrease in the minimum inhibitory concentration of this antibiotic in the presence of half-minimum inhibitory concentration of 4-hexylresorcinol was demonstrated for monoresistant strain M. tuberculosis 5360/42Hr. On the mouse model of experimental tuberculosis caused by M. tuberculosis H37Rv, a 5-fold decrease in lung contamination and more rapid complete cure were achieved in animals treated with the combination of rifabutin and 4-hexylresorcinol in comparison with rifabutin monotherapy.

Keywords: Mycobacterium smegmatis; Mycobacterium tuberculosis; adjuvant 4-hexylresorcinol; isoniazid; rifabutin.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Hexylresorcinol* / pharmacology
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Mice
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis*
  • Rifabutin / pharmacology
  • Rifabutin / therapeutic use
  • Tuberculosis* / drug therapy

Substances

  • Antitubercular Agents
  • Isoniazid
  • Hexylresorcinol
  • Rifabutin
  • Adjuvants, Immunologic