ABSTRACT
BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Tuberculosis, Multidrug-Resistant/microbiology , Drug Resistance, Multiple, Bacterial/genetics , Mutation/genetics , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Antitubercular Agents/pharmacology , Socioeconomic Factors , Brazil , Microbial Sensitivity Tests , Extensively Drug-Resistant Tuberculosis/microbiology , Middle Aged , Mycobacterium tuberculosis/isolation & purificationABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Clavulanic Acid/administration & dosage , Extensively Drug-Resistant Tuberculosis/drug therapy , Imipenem/administration & dosage , Linezolid/administration & dosage , beta-Lactamase Inhibitors/administration & dosage , Adolescent , Adult , Anti-Bacterial Agents/adverse effects , Brazil , Clavulanic Acid/adverse effects , Drug Therapy, Combination , Female , Humans , Imipenem/adverse effects , Linezolid/adverse effects , Male , Middle Aged , Referral and Consultation , Retrospective Studies , Treatment Outcome , Young Adult , beta-Lactamase Inhibitors/adverse effectsABSTRACT
XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group V drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreomycin, moxifloxacin, linezolid, clofazimine, high-dose isoniazid, PAS, and bedaquiline in 1 case, were retrospectively analysed. Ten patients were treated, 9 with an extensive pattern of resistance to at least 6 drugs, and 1 because of adverse reactions and drug interactions leading to a similar situation. Eight of the 10 patients treated achieved bacteriological sputum conversion (2 consecutive negative monthly cultures) over a period of 2-7 months, while 2 died. No adverse reactions attributable to prolonged administration of MPC were observed.
Subject(s)
Antitubercular Agents/therapeutic use , Clavulanic Acid/therapeutic use , Extensively Drug-Resistant Tuberculosis/drug therapy , Thienamycins/therapeutic use , Adult , Antitubercular Agents/classification , Antitubercular Agents/pharmacology , Argentina/epidemiology , Clavulanic Acid/pharmacology , Drug Therapy, Combination , Extensively Drug-Resistant Tuberculosis/epidemiology , Female , Humans , Male , Meropenem , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Peru/ethnology , Retrospective Studies , Sputum/microbiology , Thienamycins/pharmacology , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Uruguay/ethnology , Young AdultABSTRACT
In this article the author reviews the evolution of the approach to multidrug-resistant tuberculosis (MDR-TB) in Brazil following the introduction of rifampicin associated to isoniazid and pyrazinamide (RHZ). It shows Brazil was one of the world's first countries to use the RHZ regimen within a treatment system, with a first line regimen, another one specific for meningo-encephalic forms, for re-treatment of recurrences or of patients who returned with active tuberculosis after abandoning treatment, and a reserve regimen. The system was applied nationwide with guaranteed cost-free provision of medication, and self-administered. The author evaluates the growth of drug resistance, the emergence of multidrug-resistance and how management of this form of the disease has been organised.
ABSTRACT
Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.
Subject(s)
Humans , Male , Middle Aged , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/diagnosis , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Pulmonary/diagnosis , Extensively Drug-Resistant Tuberculosis/drug therapy , Fatal Outcome , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/drug therapyABSTRACT
Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem. The extent and burden of MDR-TB varies significantly from country to country and region to region. Globally, about three per cent of all newly diagnosed patients have MDR-TB and the proportion is higher in patients who had previously received anti-tuberculosis (anti-TB) treatment reflecting the failure of programs designed to ensure complete cure of patients with tuberculosis. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services and implementation of DOTS-Plus strategy.
ABSTRACT
Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem. The extent and burden of MDR-TB varies significantly from country to country and region to region. Globally, about three per cent of all newly diagnosed patients have MDR-TB and the proportion is higher in patients who had previously received anti-tuberculosis (anti-TB) treatment reflecting the failure of programs designed to ensure complete cure of patients with tuberculosis. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services and implementation of DOTS-Plus strategy.
ABSTRACT
Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem. The extent and burden of MDR-TB varies significantly from country to country and region to region. Globally, about three per cent of all newly diagnosed patients have MDR-TB and the proportion is higher in patients who had previously received anti-tuberculosis (anti-TB) treatment reflecting the failure of programs designed to ensure complete cure of patients with tuberculosis. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services and implementation of DOTS-Plus strategy.