title: Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.
abstract: BACKGROUND
  Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.
  
  
  RESULTS
  This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.
  
  
  CONCLUSIONS
  MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.
authors.affiliation: Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital, Harrow, Middlesex, United Kingdom.
authors.forename: Philly
authors.initials: P
authors.lastname: O'Riordan
authors.forename: Uli
authors.initials: U
authors.lastname: Schwab
authors.forename: Sarah
authors.initials: S
authors.lastname: Logan
authors.forename: Graham
authors.initials: G
authors.lastname: Cooke
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Robert N
authors.initials: RN
authors.lastname: Davidson
authors.forename: Paul
authors.initials: P
authors.lastname: Bassett
authors.forename: Robert
authors.initials: R
authors.lastname: Wall
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pasvol
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D012319:RNA Polymerase II / Q000235:genetics; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology*; D012306:Risk; D012307:Risk Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission
chemical_list: D000904:Antibiotics, Antitubercular; D012319:RNA Polymerase II; D012293:Rifampin
references.citation: Thorax. 2006 Feb;61(2):158-63
references.pmid: 16254056
references.citation: J Clin Microbiol. 1995 Nov;33(11):2994-8
references.pmid: 8576360
references.citation: Am J Respir Crit Care Med. 2008 Apr 1;177(7):787-92
references.pmid: 18202343
references.citation: Thorax. 2000 Nov;55(11):962-3
references.pmid: 11050268
references.citation: Ann N Y Acad Sci. 2001 Dec;953:138-45
references.pmid: 11795406
references.citation: Lancet. 2007 Oct 20;370(9596):1453-7
references.pmid: 18064739
references.citation: Clin Infect Dis. 1997 Jan;24 Suppl 1:S121-30
references.pmid: 8994791
references.citation: Thorax. 2002 Feb;57(2):152-6
references.pmid: 11828046
references.citation: J Clin Microbiol. 1998 Jul;36(7):1969-73
references.pmid: 9650946
references.citation: Thorax. 2002 Sep;57(9):810-6
references.pmid: 12200527
references.citation: Lancet. 2006 Dec 16;368(9553):2142-54
references.pmid: 17174706
references.citation: Tuberculosis (Edinb). 2003;83(1-3):44-51
references.pmid: 12758188
references.citation: Emerg Infect Dis. 2006 May;12(5):752-9
references.pmid: 16704831
references.citation: Ann N Y Acad Sci. 2001 Dec;953:185-91
references.pmid: 11795411
references.citation: J Infect. 1998 Jul;37(1):39-40
references.pmid: 9733376
references.citation: Int J Tuberc Lung Dis. 2004 Aug;8(8):1012-6
references.pmid: 15305486
references.citation: J Infect. 2006 Jul;53(1):5-11
references.pmid: 16310855
references.citation: BMJ. 1993 Dec 11;307(6918):1539-40
references.pmid: 8274925