What Persons Should I Follow? Thalidomide Fanatics About Flickr

Except for fluroquinolones, no novel anti-TB antibiotic has been introduced in the last 45?years. ��-Lactams have not been considered to be useful drugs for the treatment of TB, because Mycobacterium tuberculosis naturally produces BlaC, an extended-spectrum class?A ��-lactamase [3]. However, older reports have shown that the combination of amoxycillin and clavulanic acid is bactericidal in?vitro [4], an efficacy that can be accounted for by the recent demonstration that BlaC is irreversibly inactivated by clavulanic acid [3]. Reduction of the burden of M.?tuberculosis Abiraterone in the sputum of patients treated with amoxycillin and clavulanic acid has been reported [5], but clinical assessments for the treatment of MDR TB are limited to anecdotal cases in which amoxycillin�Cclavulanic acid was used in association with second-line drugs [6]. Among the different classes of ��-lactams, very recent data concerning carbapenems have opened new avenues towards the potential use of this class in the treatment of TB, especially for MDR and XDR TB. Until recently, all ��-lactams were thought to exclusively act on the active-site serine d,d-transpeptidases, the classic penicillin-binding proteins that catalyse the final cross-linking step of peptidoglycan synthesis. We have recently shown that these d,d-transpeptidases are bypassed by a novel family of polymerases, the active-site cysteine l,d-transpeptidases (Ldts), in ��-lactam-resistant enterococci and in M.?tuberculosis [7,8]. These enzymes are promising targets for the use of carbapenems, or for the development of anti-TB drugs belonging to this class, because the Ltds are responsible for the formation Thalidomide of 80% of the cross-links in M.?tuberculosis, and these enzymes are irreversibly inactivated by carbapenems by the formation of covalent adducts [8,9]. Moreover, one of the five Ltds of M.?tuberculosis (LdtMt2) is essential for virulence in a mouse model of acute infection [9]. Carbapenems are slowly hydrolysed by the ��-lactamase BlaC [3], and one member of the carbapenem family, meropenem, has been reported to be uniformly active in?vitro in association with clavulanic acid against a panel of XDR strains (meropenem Ixazomib MIC of