Defining multidrug-resistant tuberculosis: correlating GenoType MTBDRplus assay results with minimum inhibitory concentrations.
This study correlates MICs of rifampicin (RIF) and isoniazid (INH) with GenoType MTBDRplus assay results for drug-resistant Mycobacterium tuberculosis (MTB) clinical isolates. MICs of RIF and INH were established for 84 and 90 isolates, respectively, testing 7 concentrations of each drug. Genotypic resistance to each drug was determined by GenoType MTBDRplus assay with 50 representative mutations confirmed by pyrosequencing, with mutations in the rpoB gene associated with RIF resistance and mutations in the katG and/or inhA genes associated with INH resistance. Based upon the correlation of MICs with specific genetic profiles, relative resistance levels were established for each isolate. Results indicate that MTB phenotypic resistance, currently based upon the testing of isolate susceptibility to a single drug concentration, may be more accurately profiled via quantitative MICs, and therefore, the correlation of molecular diagnostic results with specific MICs may allow for more optimal treatment of infections.
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Priti
P
Kambli
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Kanchan
K
Ajbani
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Meeta
M
Sadani
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Chaitali
C
Nikam
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Anjali
A
Shetty
Pulmonology Section, Department of Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Zarir
Z
Udwadia
Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Sophia B
SB
Georghiou
Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Timothy C
TC
Rodwell
Department of Medicine, University of California, San Diego, San Diego, CA, USA.
Antonino
A
Catanzaro
Microbiology Section, Department of Laboratory Medicine, P.D. Hinduja National Hospital and Medical Research Center, Mumbai, India. Electronic address: dr_crodrigues@hindujahospital.com.
Camilla
C
Rodrigues
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics; D010641:Phenotype; D012293:Rifampin / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D007538:Isoniazid; D012293:Rifampin
Drug susceptibility testing; Level of resistance; Multidrug-resistant tuberculosis; Mutations