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.

Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges

“…Studies among XDR-TB patients receiving imipenem containing regimens have shown relatively high sputum conversion (72%) and treatment success rates (60%) [8,9]. Though the success rates are encouraging, the regimen requires multiple intravenous injections and hence, the hospitalization for treatment [10].…”

Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis

“…All patients showed sputum and culture conversion within 180 days. No adverse events were reported for imipenem-clavulanate (52). In a large observational study, the clinical outcomes of 84 patients, treated with 500 mg imipenem-clavulanate four times a day, were compared with results from 168 controls.…”

Cardiac safety of bedaquiline: a systematic and critical analysis of the evidence

“…The treatment of multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) remains a challenge for clinicians for several reasons, including the large number of drugs required, the cost, the tolerability of single drugs and their combinations, and the effectiveness and long treatment duration [1][2][3][4][5][6]. Therefore, fresh attention has recently been paid to new and repurposed anti-TB drugs [4,5,[7][8][9][10][11][12][13][14][15][16][17][18].…”