Treatment outcomes for isoniazid-monoresistant tuberculosis in Peru, 2012-2014.

BACKGROUND: Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing-the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Unusually, Peru has pioneered universal pre-treatment drug susceptibility testing with methods that identify isoniazid resistance and has thus identified a large number of individuals requiring tailored therapy. Since 2010, treatment in Peru for isoniazid-resistant tuberculosis without multidrug-resistant tuberculosis (Hr-TB) has been with a standardized nine-month regimen of levofloxacin, rifampicin, ethambutol and pyrazinamide. The objectives of this study were to evaluate the outcomes of treatment for patients with Hr-TB initiating treatment with this regimen between January 2012 and December 2014 and to determine factors affecting these outcomes. METHODS: Retrospective cross-sectional study; case data were obtained from the national registry of drug-resistant tuberculosis. Patients diagnosed with isoniazid resistant TB without resistance to rifampicin, pyrazinamide, ethambutol and quinolones as determined by either a rapid drug susceptibility testing (DST) (nitrate reductase test, MODS, Genotype MTBDRplus) or by the proportion method were included. FINDINGS: A total of 947 cases were evaluated (a further 403 without treatment end date were excluded), with treatment success in 77.2% (731 cases), loss to follow-up in 19.7% (186 cases), treatment failure in 1.2% (12 cases), and death in 1.9% (18 cases). Unfavorable outcomes were associated in multivariate analysis with male gender (OR 0.50, 95% CI 0.34-0.72, p<0.05), lack of rapid DST (OR 0.67, 95% CI 0.50-0.91, p = 0.01), additional use of an injectable second-line anti-tuberculous drug (OR 0.46, 95% CI 0.31-0.70, p<0.05), and treatment initiation in 2014 (OR 0.77, 95% CI 0.62-0.94, p = 0.01). INTERPRETATION: The treatment regimen implemented in Peru for isoniazid resistant TB is effective for TB cure and is not improved by addition of an injectable second-line agent. Access to rapid DST and treatment adherence need to be strengthened to increase favorable results

Effectiveness and Safety of Imipenem-Clavulanate Added to an Optimized Background Regimen (OBR) Versus OBR Control Regimens in the Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Comparison of effectiveness and safety of imipenem/clavulanate-versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases. 84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p<0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively. Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p<0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only. Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients

Effectiveness and safety of meropenem/ clavulanate-containing regimens in the treatment of MDR- and XDR-TB

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/ clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases. Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9) versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days. No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment). The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases