title: Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes.
abstract: A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95% CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95% CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95% CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95% CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.
authors.affiliation: Stop TB Dept, World Health Organization, Geneva, Switzerland.
authors.forename: Dennis
authors.initials: D
authors.lastname: Falzon
authors.forename: Neel
authors.initials: N
authors.lastname: Gandhi
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Migliori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Helen S
authors.initials: HS
authors.lastname: Cox
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Holtz
authors.forename: Maria-Graciela
authors.initials: MG
authors.lastname: Hollm-Delgado
authors.forename: Salmaan
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Kathryn
authors.initials: K
authors.lastname: DeRiemer
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
authors.forename: Lia
authors.initials: L
authors.lastname: D'Ambrosio
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Lange
authors.forename: Melissa
authors.initials: M
authors.lastname: Bauer
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D003625:Data Collection; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D064887:Observational Studies as Topic; D017211:Treatment Failure; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D024841:Fluoroquinolones