Bacteria in Dairy Products in Baggage of Incoming Travelers, Brazil

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 20, No. 11, November 2014 1933 to low concentrations of rifampin. To confirm that this effect was a result of persistence rather than generation of resistant mutants, we transferred the colonies growing after transient rifampin exposure of Beijing strain 1585 to a medium containing 8 mg/L rifampin. Their growth was completely inhibited, and molecular analysis did not detect any of the most prevalent rifampin resistance–associated mutants (data not shown). We believe that these results provide a possible explanation for the otherwise unrealistically high (apparent) mutation frequency reported by de Steenwinkel et al. (2). If these strains are capable of persisting at low concentrations of rifampin, this extended period would provide a window for the generation of mutants during or after exposure. Stress may also play a role; rpoB gene mutants have shown to exhibit a stringent-like response (7), and defective rpoB activity as a result of low-level rifampin exposure could induce a similar response. If rifampin induces a stress response, the situation may be analogous to the high mutation rates seen after quinolone exposure (8). In summary, our data show that the high apparent M. tuberculosis strain mutation frequency reported by de Steenwinkel et al. (2) may be a result of the higher tolerance to rifampin of some Beijing strains. This tolerance likely results in a specific window of rifampin concentrations that, possibly combined with subsequent error-prone replication/outgrowth, enables the generation and selection of new mutants, rather than the selection of preexisting mutants. When interpreted in the light of our observations, the unexpected results of de Steenwinkel et al. could help explain the association of Beijing genotype strains with drug resistance and relapse (9,10). Drug levels achieved during treatment may be much more critical in preventing the accumulation of rifampin-resistant mutants for these strains than for other genotypes. This study was financially supported by NanonextNL project 03E.07.