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Prior to choosing an initial tuberculosis (TB) treatment regimen, clinicians should assess all patients for risk factors for drug-resistant TB.
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Rapid molecular tests to predict rifampin resistance (and, ideally, isoniazid resistance) should be performed for every patient, with results used to guide treatment. Rapid molecular tests are especially important for patients with risk factors for drug-resistant TB.
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For the optimal management of drug-resistant TB, particularly multidrug-resistant (MDR-TB), providers should have access to: (i) state-of-the-art drug susceptibility testing for all drugs that will be used; (ii) an uninterrupted supply of quality-assured first- and second-line anti-TB drugs; (iii) directly observed therapy and other components of a patient-centered comprehensive management program; and (iv) a team experienced in the management of drug-resistant TB that includes physicians, nurses and pharmacists.
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Isolates from all TB patients diagnosed with rifampin resistance or multidrug resistance should undergo phenotypic drug susceptibility testing for all anti-TB medicines currently recommended to treat MDR-TB.
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Federal and provincial government agencies, and pharmaceutical companies operating in Canada, should facilitate timely access to second-line drugs for MDR and extensively drug-resistant (XDR)-TB.
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In patients with mono-isoniazid resistance, a treatment regimen including a later generation fluoroquinolone (levofloxacin is preferred), rifampin, ethambutol and pyrazinamide should be given for 6 months.
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For the treatment of isoniazid-resistant TB, in patients with less extensive disease (eg, noncavitary), and especially if there is increased risk of liver toxicity, pyrazinamide should be given for the first 2 months only; in the final 4 months, rifampin, ethambutol and the fluoroquinolone should be given.
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For the treatment of MDR-TB, treatment should include:
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use of regimens that include bedaquiline, for all patients;
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use of regimens that include linezolid, for all patients; and
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use of regimens that include either levofloxacin or moxifloxacin, for all patients.
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For the treatment of MDR-TB, drugs that the infecting strain has proven resistance to through drug susceptibility testing should not be used.
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For the treatment of MDR-TB, the initial regimen should include levofloxacin or moxifloxacin AND bedaquiline AND linezolid AND clofazimine AND cycloserine.
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For the treatment of MDR-TB, 5 to 7 months after culture conversion occurs, the total number of drugs in the regimen can be reduced to 4.
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For the treatment of MDR-TB, a total treatment duration of 18 to 20 months, modified based on response to therapy, is appropriate.
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For the treatment of pre-extensively drug-resistant or extensively drug-resistant TB, or in situations where one or more of the Group A and B drugs cannot be used due to side effects, contra-indications, unavailability or resistance, one or more Group C drugs can be added, to ensure at least 5 drugs are in the regimen. The order of preference for the addition of Group C drugs is (from most to least preferred): ethambutol, pyrazinamide, delamanid, amikacin, imipenem-cilastatin or meropenem (plus clavulanic acid), ethionamide and p-aminosalicylic acid.
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In patients with MDR-TB, partial lung resection (lobectomy, segmentectomy or wedge resection) in carefully selected patients can be an adjunct to optimized medical therapy. The optimal timing of surgical resection appears to be after culture conversion is achieved.
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