Extent and origin of resistance to antituberculosis drugs in the Netherlands, 1993 to 2011.

The elimination of tuberculosis (TB) is threatened by an apparent increase in the level of resistance in Mycobacterium tuberculosis. In the Netherlands, where the majority of TB patients are migrants, resistance may also be increasing. We conducted a retrospective study, using 18,294 M. tuberculosis isolates from TB cases notified between 1993 and 2011. We investigated the trends in antituberculosis drug resistance, focusing on the country of birth of the patients and whether resistance had developed during treatment or was the result of transmission of resistant M. tuberculosis strains. For both scenarios, we determined whether this had happened in or outside the Netherlands. Antituberculosis drug resistance was found in 13% of all cases analysed and showed an increasing trend among patients who had been born in the Netherlands (p<0.001) and a decreasing trend among foreign-born (p=0.02) over the study period. Since 2005, the proportion of M. tuberculosis resistant strains among all strains tested has increased in both groups (p=0.03 and p=0.01, respectively). Overall, we found a significantly increasing trend when excluding streptomycin resistance (p<0.001). The trend was most markedly increased for isoniazid resistance (p = 0.01). Although resistance was mainly due to transmission of resistant strains, mostly outside the Netherlands or before 1993 (when DNA fingerprinting was not systematically performed), in some cases (n=45), resistance was acquired in the Netherlands. We conclude that antituberculosis drug resistance is increasing in the Netherlands, mostly related to migration from high TB-incidence countries, but also to domestic acquisition.

Susceptibility of clinical Mycobacterium tuberculosis isolates to a potentially less toxic derivate of linezolid, PNU-100480.

Susceptibility of clinical Mycobacterium tuberculosis isolates to PNU-100480 and linezolid was evaluated by the MGIT 960 system. The isolates had various susceptibilities to isoniazid (INH), rifampin, ethambutol, and streptomycin. The mean MIC for PNU-100480 was 3.2 times lower than that for linezolid. Therefore, PNU-100480 is a promising candidate to be developed further as an adjunct in the treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB).

Analysis of the population structure of Mycobacterium tuberculosis in Ethiopia, Tunisia, and The Netherlands: usefulness of DNA typing for global tuberculosis epidemiology.

The genetic heterogeneity among Mycobacterium tuberculosis isolates from 501 patients in Ethiopia, Tunisia, and the Netherlands was compared by analysis of DNA polymorphism driven by insertion element IS6110. The percentage of isolates displaying two or more identical patterns differed greatly in the three countries: It was highest among Tunisian isolates and lowest in Dutch isolates. In contrast to isolates from Dutch subjects infected with M. tuberculosis, the majority of strains from Ethiopia and Tunisia were from a few families of genetically highly related strains. Furthermore, little overlap was observed among isolates from the three countries, indicating strict isolation of the bacterial reservoirs in the countries. A few strains from the Netherlands matched strains from Ethiopia and Tunisia. Those strains were invariably isolated from refugees, immigrants, or persons who visited Ethiopia or Tunisia.