title: Phenotypic and genotypic diversity in a multinational sample of drug-resistant Mycobacterium tuberculosis isolates.
abstract: OBJECTIVE
  To develop and evaluate rapid, molecular-based drug susceptibility testing (DST) for extensively drug-resistant tuberculosis (XDR-TB), we assembled a phenotypically and genotypically diverse collection of Mycobacterium tuberculosis isolates from patients evaluated for drug resistance in four high-burden countries.
  
  
  METHODS
  M. tuberculosis isolates from India (n = 111), Moldova (n = 90), the Philippines (n = 96), and South Africa (n = 103) were selected from existing regional and national repositories to maximize phenotypic diversity for resistance to isoniazid, rifampin (RMP), moxifloxacin, ofloxacin, amikacin, kanamycin, and capreomycin. MGIT™ 960 was performed on viable isolates in one laboratory using standardized procedures and drug concentrations. Genetic diversity within drug resistance phenotypes was assessed.
  
  
  RESULTS
  Nineteen distinct phenotypes were observed among 400 isolates with complete DST results. Diversity was greatest in the Philippines (14 phenotypes), and least in South Africa (9 phenotypes). Nearly all phenotypes included multiple genotypes. All sites provided isolates resistant to injectables but susceptible to fluoroquinolones. Many patients were taking drugs to which their disease was resistant.
  
  
  CONCLUSIONS
  Diverse phenotypes for XDR-TB-defining drugs, including resistance to fluoroquinolones and/or injectable drugs in RMP-susceptible isolates, indicate that RMP susceptibility does not ensure effectiveness of a standard four-drug regimen. Rapid, low-cost DST assays for first- and second-line drugs are thus needed.
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: R S
authors: RS
authors: Garfein
authors: University of Arkansas, Department of Biological Sciences, Fayetteville, Arkansas, USA.
authors: D G
authors: DG
authors: Catanzaro
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: T C
authors: TC
authors: Rodwell
authors: Department of Family Medicine and Public Health, University of California, San Diego, California, USA.
authors: E
authors: E
authors: Avalos
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: R L
authors: RL
authors: Jackson
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: J
authors: J
authors: Kaping
authors: Tropical Disease Foundation, Inc, Philippine Institute of Tuberculosis Building, Makati City, Philippines.
authors: H
authors: H
authors: Evasco
authors: Hinduja National Hospital, Mumbai, India.
authors: C
authors: C
authors: Rodrigues
authors: Microbiology and Morphology Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova.
authors: V
authors: V
authors: Crudu
authors: California Department of Public Health, Richmond, California, USA.
authors: S-Y G
authors: SY
authors: Lin
authors: E
authors: E
authors: Groessl
authors: Department of Family Medicine and Public Health, University of California, San Diego, California, USA.
authors: E
authors: E
authors: Groessel
authors: Department of Family Medicine and Public Health, University of California, San Diego, California, USA.
authors: N
authors: N
authors: Hillery
authors: Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
authors: A
authors: A
authors: Trollip
authors: Department of Family Medicine and Public Health, University of California, San Diego, California, USA.
authors: T
authors: T
authors: Ganiats
authors: Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
authors: T C
authors: TC
authors: Victor
authors: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: K
authors: K
authors: Eisenach
authors: University of Arkansas, Department of Biological Sciences, Fayetteville, Arkansas, USA.
authors: F
authors: F
authors: Valafar
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: J
authors: J
authors: Channick
authors: Department of Microbiology, University of Hawaii, Honolulu, Hawaii, USA.
authors: L
authors: L
authors: Qian
authors: Department of Medicine, University of California, San Diego, California, USA.
authors: A
authors: A
authors: Catanzaro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008966:Moldova; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification*; D010641:Phenotype; D010679:Philippines; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents