title: Effectiveness and safety of imipenem/clavulanate and linezolid to treat multidrug and extensively drug-resistant tuberculosis at a referral hospital in Brazil.
abstract: Evidence on effectiveness, safety, and tolerability of imipenem/clavulanate (IC) and linezolid containing regimens to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) is scarce. The aim of this observational study is to evaluate the therapeutic contribution of IC and linezolid to manage MDR/XDR-TB cases at the reference centre of São Paulo state, Brazil. Twelve patients (9 males, 1 HIV positive in antiretroviral treatment, 4 MDR, 8 XDR) were treated with IC, 11 of them within linezolid-containing regimens. They all were previously treated with treatment failure, for a median (IQR, interquartile range) of 4.5 (2-6.5) times, having a severe resistance pattern (median number of resistances: 7 (5-8)) and being sputum smear and culture positive. IC and linezolid were prescribed at the dose of 1000mg/day and 600mg/day, respectively. The overall exposure was (median (IQR)) 419 (375.5-658) days for IC and 678 (392-720) days for linezolid. All of them converted their sputum (time to sputum conversion; 60 (37.5-90) days) and culture (75 (60-135) days), and 7 were cured while 5 are still on treatment with a gradually improving clinical picture. While no adverse events were reported for IC, 2 minor side effects, only, were attributed to linezolid (17%); in both cases the drug was re-started without further problems. Our study suggests that IC and linezolid-containing regimens can be used safely and with satisfactory outcomes in reference centres to treat MDR/XDR-TB patients.
authors.affiliation: University Center of Araraquara, Sao Paulo, Brazil; Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Arbex
authors.affiliation: University Center of Araraquara, Sao Paulo, Brazil; Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
authors.forename: E H
authors.initials: EH
authors.lastname: Bonini
authors.affiliation: Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Kawakame Pirolla
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy; Public Health Consulting Group, Lugano, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: D'Ambrosio
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Centis
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy. Electronic address: giovannibattista.migliori@fsm.it.
authors.forename: G B
authors.initials: GB
authors.lastname: Migliori
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001938:Brazil; D019818:Clavulanic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000009:adverse effects; D000069349:Linezolid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012017:Referral and Consultation; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D015378:Imipenem; D000069349:Linezolid
keywords: Effectiveness; Imipenem; Linezolid; MDR-TB; Safety; Tolerability; XDR-TB