Multidrug-resistant (MDR) tuberculosis (TB) (resistance to at least isoniazid and rifampicin), with >480000 cases in 2013, 10% of them being affected by extensively drug-resistant (XDR)-TB (MDR-TB ...with additional resistance to any fluoroquinolone, and to injectable second-line drugs (SLDs) (capreomycin, kanamycin or amikacin)), continues to represent a real threat to TB control 1-4. In some high MDR-TB burden countries, the prevalence of MDR-TB among new cases exceeds 20% and among retreatment cases, reaches almost 50% 1, 5.
Highlights • The World Health Organization (WHO) 2016 guidelines for multidrug-resistant tuberculosis (MDR-TB) propose a regrouping of anti-TB drugs for the treatment of MDR-TB. • The classification ...of anti-TB drugs guides the clinician in designing an appropriate multidrug-/extensively drug-resistant TB regimen. • Discussion on possible future changes to the anti-TB drug groupings has started. • Based on recent evidence on some compounds, certain drugs are likely to increase or decrease in importance in the future. • If the efficacy and safety profile of linezolid, bedaquiline, and delamanid is confirmed, they might move up the anti-TB drug hierarchy.
Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and ...tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.
Summary Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are generally thought to have high mortality rates. However, many cases can be treated with the right combination ...and rational use of available antituberculosis drugs. This Review describes the evidence available for each drug and discusses the basis for recommendations for the treatment of patients with MDR and XDR tuberculosis. The recommended regimen is the combination of at least four drugs to which the Mycobacterium tuberculosis isolate is likely to be susceptible. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Among the first group (the oral first-line drugs) high-dose isoniazid, pyrazinamide, and ethambutol are thought of as an adjunct for the treatment of MDR and XDR tuberculosis. The second group is the fluoroquinolones, of which the first choice is high-dose levofloxacin. The third group are the injectable drugs, which should be used in the following order: capreomycin, kanamycin, then amikacin. The fourth group are called the second-line drugs and should be used in the following order: thioamides, cycloserine, then aminosalicylic acid. The fifth group includes drugs that are not very effective or for which there are sparse clinical data. Drugs in group five should be used in the following order: clofazimine, amoxicillin with clavulanate, linezolid, carbapenems, thioacetazone, then clarithromycin.
Drug-resistant strains of
pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate ...treatment of tuberculosis, as well as unchecked transmission of
, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.
Tuberculosis: are we making it incurable? Caminero, José A; Matteelli, Alberto; Loddenkemper, Robert
European respiratory journal/The European respiratory journal
42, Številka:
1
Journal Article
Drug-resistant tuberculosis (TB) has become one of the main obstacles to controlling (and eventually eliminating) this disease 1–4. The World Health Organization (WHO) reports that the number of ...patients suffering from TB with resistance to rifampicin (RR-TB) or multidrug-resistant TB (MDR-TB, resistance to at least isoniazid and rifampicin) is increasing alarmingly each year. Furthermore, the treatment success rates achieved globally are suboptimal, barely exceeding 50% 1, 2, 5. The proportion decreases to 25% in patients with extensively drug-resistant tuberculosis (XDR-TB) (MDR-TB plus resistance to at least one fluoroquinolone (FQ) and a second-line injectable (SLI) drug) and to <20% when the drug resistance profile is beyond XDR 1, 2, 5.
The adherence to long tuberculosis (TB) treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors ...associated with defaulting from or dying during antituberculosis treatment.
Prospective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up) and fatality (died vs. the rest of patients) were based on logistic regression, calculating odds ratios (OR) and 95% confidence intervals (CI).
Of the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%), completed treatment 540 (36.2%), failure 2 (0.1%), transfer-out 33 (2.2%), default 27 (1.8%), death 27 (1.8%), lost to follow-up 65 (4.4%), other 4 (0.3%). Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88), living alone (OR = 2.35; CI:1.05-5.26), residents of confined institutions (OR = 4.79; CI:1.74-13.14), previous treatment (OR = 2.93; CI:1.44-5.98), being an injecting drug user (IDU) (OR = 9.51; CI:2.70-33.47) and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98). Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01), retired (OR = 12.26;CI:1.74-86.04), HIV-infected (OR = 9.93; CI:1.48-66.34), comprehension difficulties (OR = 4.07; CI:1.24-13.29), IDU (OR = 23.59; CI:2.46-225.99) and Directly Observed Therapy (DOT) (OR = 3.54; CI:1.07-11.77).
Immigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required for patients who are retired, HIV-infected, IDU, and those with treatment comprehension difficulties.
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