High risk and rapid appearance of multidrug resistance during tuberculosis treatment in Moldova

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a serious problem in the former Soviet Union and may appear during TB treatment. We aimed to estimate the prevalence of, timing of and factors associated with MDR-TB diagnosis during TB treatment in Moldova, which was part of the former Soviet Union. We analysed data on 3 754 confirmed non-MDR-TB cases (between January 1, 2007 and December 31, 2010) in the Moldovan TB surveillance database, where patients provided sputum specimens for drug-susceptibility testing, multiple times, during treatment. We estimated the percentage of individuals with confirmed baseline non-MDR-TB that were diagnosed with MDR-TB during treatment, documented the time at which MDR-TB was diagnosed, and used a failure-time model to identify factors associated with MDR-TB diagnosis. Between 7.2% and 9.2% of initially non-MDR-TB cases were diagnosed with MDR-TB during treatment. Half of these MDR-TB diagnoses occurred with 3 months of the initial diagnosis. An increased MDR-TB risk during treatment was associated with baseline resistance to first-line TB drugs (linear increase in risk per additional drug), previous incarceration and HIV co-infection. MDR can appear rapidly during TB treatment. Policy considerations should emphasise management during early treatment by increasing ambulatory TB treatment to prevent nosocomial transmission, and ensuring universal rapid diagnostics access to prevent acquisition and transmission of drug resistance.

FIGURE 1

Flow chart of inclusions and exclusions for the study. All outcomes (or lack of outcome) are as recorded in the Moldovan national tuberculosis (TB) database as of July 2011. MDR: multidrug resistant. ^#: the total number includes patients whom initiated treatment abroad and, therefore, are not in either new or previously treated categories; ^¶: poor outcome includes died, defaulted on treatment and failed treatment.

FIGURE 2

Cumulative percentage of non-multidrug-resistant tuberculosis (non-MDR-TB) cases in whom MDR-TB appeared (n=237) during the first year of treatment by a) time after initial diagnosis at which MDR-TB is detected, and b) time after initial diagnosis at which the first follow-up sputum collection occurred. Data are shown separately for new cases (solid line, n=145) and previously treated cases (dotted line, n=92). Straight lines indicate in a) the days after initial diagnosis at which 50% of cases had been diagnosed with MDR-TB (87 days for new cases and 99 days for previously treated cases), and in b) the percentage of cases where sputum had been collected for follow-up testing by 90 days after initial diagnosis (70% of new cases and 46% of previously treated cases). ^#: The number of days after initial TB diagnosis that MDR-TB diagnosis was made; ^¶: the number of days after initial TB diagnosis that first follow-up sputum collection occurred.