The efficacies of these regimens have not been fully evaluated in prospective trials in HIV-positive subjects and we recommend 12 months of rifampicin and ethambutol with pyrazinamide also given in the first 2 months (2REZ/10RE).
If INH resistance is only discovered at 2 months of initial four-drug treatment then one can either continue with rifampicin and ethambutol for 10 months or continue rifampicin, ethambutol and pyrazinamide for a total of 6 months. In patients Ivacaftor datasheet with extensive disease, one might continue both ethambutol and pyrazinamide with rifampicin for 9–12 months or even use rifampicin and ethambutol with a quinolone. TB resistance to at least isoniazid and rifampicin is known as MDR-TB and isolates are at high risk of further acquired drug resistance. Risk factors for MDR-TB include: previous TB treatment; All such patients should be referred to regional treatment centres, regardless of HIV infection status. There is a web-based discussion forum that
can be used by the physician managing such cases. Further details are available on the BTS website at http://www.brit-thoracic.org.uk/tuberculosis.aspx Although patients BIBW2992 in vivo with strains resistant to rifampicin alone have a better prognosis than those with MDR-TB, they are also at increased risk of treatment failure and further resistance and should be managed in consultation with an expert. There are no definitive randomized or controlled studies to define the best regimens for MDR-TB. In principle, patients should be given four drugs to which the organism is susceptible. Recommendations are therefore
based on the resistance profile and expert opinion. The optimum duration of treatment of MDR-TB in HIV-infected patients has also not been established, but many patients are treated for at least 18 months to 2 years after cultures revert to negative. The drugs used to treat MDR-TB include the second-line and other drugs that are listed Protein kinase N1 in Table 3. There are no formal data regarding interactions between these drugs and antiretrovirals but a review of the subject has been published [117]. Ethionamide has significant interactions because it is metabolized by the CYP450 system, although by which isoenzyme is unknown. There is no guidance about dose adjustment but TDM may be useful. There is a potential for renal toxicity with aminoglycosides and tenofovir but there are few data on drug interactions between antiretrovirals and second-line anti-tuberculous treatment except for clarithromycin. Expert advice should be sought through the expert physicians network (http://www.brit-thoracic.