Totally drug-resistant tuberculosis strains: evidence of adaptation at the cellular level.

In the Eastern Mediterranean Region (EMRO), there are no accurate estimates of numbers of patients with multidrugresistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB). In 2006, we documented the existence and transmission of XDR-TB among patients with MDR-TB [1]. In a further study, we isolated more dangerous forms of bacilli, named totally drug-resistant (TDR) [2]. This group of strains showed in vitro resistance to all firstand second-line drugs tested (i.e. aminoglycosides, cyclic polypeptides, fluoroquinolones, thioamides, serine analogues and salicylic acid derivatives). TDRTB patients remained smearand culture-positive after 18 months’ median treatment with second-line drugs. Even changing the treatment to co-amoxyclav (625 mg per 8 h) or clarithromycin (1,000 mg?day), along with a high dose of isoniazid (15 mg?kg) led to no improvement [2]. In the present study, transmission electron microscopy (TEM) was used to evaluate the differences between such deadly bacilli and MDR or susceptible ones at the ultrastructural level. Furthermore, to evaluate the genotyping patterns, the strains were subjected to spoligotyping and variable number of tandem repeats (VNTR) analysis.