New insight into the molecular characterization of isoniazid and rifampicin resistant Mycobacterium tuberculosis strains from Saudi Arabia.
Data on the genetic variation of isolates of Mycobacterium tuberculosis and spectrum of mutations determining resistance to principal anti-tuberculosis drugs isoniazid (INH) and rifampicin (RIF) have not yet been studied in Saudi Arabia. One hundred and fifty-one clinical isolates of M. tuberculosis from different regions in the country showing resistance to RIF and INH were subjected to drug susceptibility testing, characterization of mutations conferring drug resistance and genotyping. Phenotypically 17 (11.3%) isolates were resistance to RIF, 75 (49.6%) were resistant to INH and 59 (39.1%) were resistant to both RIF and INH, respectively. Sixteen (10.6%), 74 (49%) and 56 (37.1%) were determined as resistant to RIF, INH and to both by line probe assay. High frequency of rpoB 531 mutations (67.1%) in RIF resistant strains and katG 315 mutations (65.2%) in INH resistant strains were found. Mutations responsible for INH resistance, katG 315 (P value<0.001, odds ratio: 1.81, 95% CI [1.51, 2.18]) and inhA-15 (P value - 0.004, odds ratio: 1.48, 95% CI [1.22, 1.8]) were predominant among the newly diagnosed cases. Beijing strains were significantly associated with multi drug resistance and mutations in combination of rpoB531 and katG315 (P value - <0.001, odds ratio: 6.83, 95% CI [2.65, 17.58]). In addition multi drug resistance was significantly associated with treatment history (P value<0.001, odds ratio: 3.16, 95% CI [2.14, 4.67]). Furthermore, a higher rate (39.3%) of clustering among the multidrug resistant strains particularly with Beijing family (52.9%) was observed. Saudi Arabia harbors highly diverse drug resistant M. tuberculosis population with an ongoing transmission which needs to be immediately managed.
Tuberculosis Research Section, Department of Infection and Immunity, MBC-03, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. bvarghese99@kfshrc.edu.sa
Bright
B
Varghese
Andreas
A
Hillemann
Dian Rachma
DR
Wijayanti
Mohammed
M
Shoukri
Fahad
F
Al-rabiah
Ruba
R
Al-Omari
Sahal
S
Al-Hajoj
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016017:Odds Ratio; D012293:Rifampin / Q000494:pharmacology*; D012529:Saudi Arabia / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology; D055815:Young Adult
D001426:Bacterial Proteins; D004269:DNA, Bacterial; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin