Resistance to fluoroquinolones and second-line injectable drugs: Impact on multidrug-resistant TB outcomes
European Respiratory Journal
Stop TB Dept., World Health Organization, Geneva, Switzerland; Divisions of General Internal Medicine, Infectious Diseases and Epidemiology, Albert Einstein College of Medicine, New York, NY; Dept. of Global Health and Social Medicine, Harvard Medical School, Boston, MA; School of Medicine, University of California Davis, Davis, CA, United States; World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate; Dept. of Biomedical Sciences, University of Sassari, Sassari, Italy; Médecins Sans Frontières, Cape Town, South Africa; US Centers for Disease Control and Prevention, HIV/STD Research Program, Bangkok, Thailand; Clinical Infectious Diseases, Tuberculosis Center Borstel, Borstel, Germany; Dept. of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC; Montreal Chest Institute, McGill University, Montreal, QC, Canada; Long Island City, NY, United States; Lantana, FL, United States; Toronto, ON, Canada; Rochester, MN, United States; Montreal, QC, Canada; Boston, MA, United States; Albuquerque, NM, United States; Tradate, Italy; Denver, CO, United States; Taipei City, Taiwan; Cape Town, South Africa; Haren, Netherlands; Davis, CA, United States; Paris, France; Geneva, Switzerland; Fajara, Gambia; Richmond, CA, United States; Bronx, NY, United States; Cuernavaca, Mexico; Atlanta, GA, United States; San Francisco, CA, United States; Seoul, South Korea; Pretoria, South Africa; Borstel, Germany; Upeslejas, Latvia; Hong Kong, Hong Kong; New York, NY, United States; Seattle, WA, United States; London, United Kingdom; Buenos Aires, Argentina; Masan City, South Korea; Madrid, Spain; Aguascalientes, Mexico; Mexico City, Mexico; Makati, Philippines; Tygerberg, South Africa; Tokyo, Japan; Sassari, Italy; Tehran, Iran; Groningen, Netherlands; Tallinn, Estonia
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. Copyright © ERS 2013.
amikacin; aminosalicylic acid; capreomycin; ciprofloxacin; cycloserine; ethambutol; ethionamide; gatifloxacin; isoniazid; kanamycin; levofloxacin; moxifloxacin; ofloxacin; pyrazinamide; quinoline derived antiinfective agent; rifampicin; sparfloxacin; streptomycin; terizidone; amikacin; amoxicillin plus clavulanic acid; azithromycin; capreomycin; clarithromycin; clofazimine; imipenem; kanamycin; levofloxacin; linezolid; macrolide; protionamide; quinoline derived antiinfective agent; rifampicin; roxithromycin; streptomycin; thioacetazone; unindexed drug; adult; antibiotic resistance; antibiotic sensitivity; article; bacterial strain; cause of death; disease association; dose response; drug effect; drug treatment failure; extensively drug resistant tuberculosis; female; human; low drug dose; major clinical study; male; meta analysis; multicenter study (topic); multidrug resistant tuberculosis; priority journal; relapse; secondary health care; treatment duration; treatment outcome; Article; death; drug megadose; drug response; extensively drug resistant tuberculosis; methodology; multidrug resistance; multidrug resistant tuberculosis; observational study