Missed phenotypic drug resistance in pediatric tuberculosis: A cause of concern in a resource-limited setting

Indian J Tuberc. 2023:70 Suppl 1:S59-S64. doi: 10.1016/j.ijtb.2023.04.004. Epub 2023 Apr 11.

Abstract

Background: Multi-drug resistance (MDR) in pediatric tuberculosis (TB) is a growing global threat. Unavailability of conventional or molecular drug susceptibility test (DST) in resource-limited settings often impede the determination of the extent of first line anti-tubercular drugs deployed in national programs.

Materials and method: Pulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to first-line anti-TB was detected by 1% proportion method. KatG315 and inhA-15 genes were amplified by PCR and detection of mutations were done by sequencing. Genotypic resistance for rifampicin was detected by Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, California).

Results: Fifty-one cases of pediatric tuberculosis were confirmed microbiologically. Resistance to isoniazid, streptomycin, rifampicin and ethambutol were 5 (14%), 4 (11%), 2 (5.5%) and 2 (5.5%) respectively by 1% proportion method. Genotypic Rifampicin and isoniazid resistance was found in 2 (5.5%) and 7 (14%) samples respectively.

Conclusion: Existing genotypic methods, detect targeted mutations conferring rifampicin resistance, however isoniazid (INH) resistance often go undetected. Since the resistance to pivotal anti-TB drugs are often encoded by multiple genes which may not be targeted by widely available molecular tests, discrepancies in molecular and culture-based DST reports should be interpreted with caution.

Keywords: Culture; Isoniazid; Mutations; Resistance; Rifampicin; Tuberculosis.

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Child
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis* / genetics
  • Resource-Limited Settings
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Tuberculosis* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / diagnosis

Substances

  • Rifampin
  • Isoniazid
  • Antitubercular Agents