BioProject

Background: Ideally, treatment of drug resistant Mycobacterium tuberculosis (Mtb) should be based on detailed high-quality drug susceptibility test (DST) information to secure optimal treatment and outcome. More...

Background: Ideally, treatment of drug resistant Mycobacterium tuberculosis (Mtb) should be based on detailed high-quality drug susceptibility test (DST) information to secure optimal treatment and outcome. However, it can be challenging to acquire good information in areas with high rates of Mtb resistance. We aimed to compare the quality of conventional DST performed in Minsk, Belarus (a country with high burden of Mtb resistance) with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, and to relate the DST results to treatment regimens and survival for TB patients with HIV coinfection. Methods: 30 Mtb culture positive TB/HIV-patients from Minsk from 2011 through 2013 were included. Descriptive statistics was applied to compare DST results and analyze treatment regimens and outcomes.Results: Only 10 (33,3%) HIV/TB-patients had drug sensitive Mtb, 2 (6,7%) Isoniazid mono-resistance; 8 (26,7%) MDR-TB, 5 (16,7%) pre-XDR-TB, and 5 (16,7%) XDR-TB. There was DST agreement between Minsk and Copenhagen for Rifampicin (R) and Isoniazid (H) for 27 (90%) patients. For 2nd-line drugs, discrepancies were more pronounced: 14 (46,7%) had disagreement for at least one 2nd-line drug, and 4 (13%) additional patients could be classified as preXDR-TB in Copenhagen. All patients started a TB-treatment regimen based on RH and pyrazinamide (Z), which were suitable for 40% patients only. Patients with drug resistant TB changed to 2nd-line drugs after median of 1,5 months (IQR 1-2) to a median of 4 active drugs (IQR 3-5). Median treatment duration after regimen change was 8 months (IQR 2-11). Sixteen (53%) patients died within 24 months of follow-up, and only 4 (22%) patients received treatment for >18 months.Conclusions: We found high concordance for R and H DST between Minsk and Copenhagen, whereas discrepancies for 2nd line drugs were more pronounced. For patients with drug resistant TB, treatment was often insufficient and relevant treatment adjustment delayed. Better accessibility to rapid molecular DSTs and 2nd-line drugs may potentially lead to more potent and individualized treatment regimens, ultimately improving outcome and reducing resistant Mtb transmission. Less...