Modulatory activity of piperine on clarithromycin against rapidly growing mycobacteria

The treatment of mycobacteriosis depends on the species causing the disease and its susceptibility to drugs. Clarithromycin represents the cornerstone of regimens for fast-growing non-tuberculous mycobacteria, due to its antimicrobial and immunomodulatory properties. Coadministration with an adjuvant compound could decrease the minimum inhibitory concentration of antimicrobials in cases of resistant bacilli. Our focus was to combine clarithromycin with piperine, a natural compound with several biological activities already described. We determined the in vitro extra- and intracellular activity of clarithromycin, piperine and the combination against clinical isolates of fast-growing non-tuberculous mycobacteria. Piperine was shown to modulate the activity of the antimicrobial in vitro by up to 16 times at the extracellular level, including against clinical isolates phenotypically resistant to clarithromycin. The bacteriostatic activity of clarithromycin was prolonged when combined with piperine for 96 h in the time-kill curve assay. Furthermore, in an intramacrophage environment, there was a modest improvement in the activity of the combination which could be explained by the fact that the action of piperine facilitates the entry of the antimicrobial into macrophages. This leads us to believe that the use of piperine as a possible candidate for adjuvant therapy with clarithromycin for the treatment of mycobacteriosis caused by fast-growing species could prevent the appearance of resistant isolates and thus increase the chances of curing these patients.