Wild-Type MIC Distribution for Re-evaluating the Critical Concentration of Anti-TB Drugs and Pharmacodynamics Among Tuberculosis Patients From South India

Frontiers in Microbiology
Azger DusthackeerRajesh Mondal

Abstract

The World Health Organization (WHO) has developed specific guidelines for critical concentrations (CCs) of antibiotics used for tuberculosis (TB) treatment, which is universally followed for drug susceptibility testing (DST) of clinical specimens. However, the CC of drugs can differ significantly among the mycobacterial species based on the population, geographic location, and the prevalence of the infecting strain in a particular area. The association between CC and the minimal inhibitory concentration (MIC) of anti-TB drugs is poorly understood. In this study, we assessed the MICs of anti-TB drugs, including isoniazid (INH), rifampicin (RMP), moxifloxacin (MXF), ethambutol (ETH), and p-aminosalicylic acid (PAS) on drug-sensitive Mtb isolates from pulmonary TB patients in South India. The MIC assays performed using solid- and liquid-growth media showed changes in the CC of a few of the tested antibiotics compared with the WHO-recommended levels. Our observation suggests that the WHO guidelines could potentially lead to overdiagnosis of drug-resistant cases, which can result in inappropriate therapeutic decisions. To evaluate the correlation between drug-resistance and CC, we performed the whole-genome sequencing for 16 mycobac...Continue Reading

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Citations

Jan 21, 2021·Clinical Pharmacology : Advances and Applications·Tesemma SileshiEleni Aklillu

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Datasets Mentioned

BETA
SUB6703345
PRJNA596377

Methods Mentioned

BETA
PCR

Software Mentioned

SAMtools
TBProfiler
Freebayes2
Python script
VCF
FastQC
R package
SnpEff
GTN
Free Bayes Genome Analysis Tool Kit ( GATK )

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