Promising Antituberculosis Activity of Piperine Combined with Antimicrobials: A Systematic Review.

Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown promising activity as efflux pump (EP) inhibitor and as adjunct in treatment of tuberculosis (TB). The present systematic review investigated scientific studies of the activity of piperine against mycobacteria, with a focus on its mechanism of action, drug interactions, and antimycobacterial activity. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement. We considered studies that were published up to December 1, 2017. Google Scholar was also searched to increase the number of publications. We searched for articles using the search terms "piperine" and "Mycobacterium spp." The search yielded a total of 225 articles. After removing duplicate publications, 208 publications remained. Of these, we evaluated the full text of 13 articles. After applying the inclusion criteria, eight studies were included in the present systematic review. The results of the systematic review showed that piperine has promising anti-TB activity, mainly when combined with antimicrobials, and plays an important role as an EP inhibitor.

Combinatory activity of linezolid and levofloxacin with antituberculosis drugs in Mycobacterium tuberculosis.

SETTING: The increase of multidrug and extensively drug resistant Mycobacterium tuberculosis strains turns the search for new tuberculosis (TB) treatment options of paramount importance. OBJECTIVE: In this sense, the present study evaluates the in vitro activity of isoniazid (INH)/rifampicin (RIF)/levofloxacin (LVX) and INH/RIF/linezolid (LNZ) combinations in resistant M. tuberculosis. DESIGN: The activities of the combinations were evaluated with M. tuberculosis H37Rv, susceptible and 10 resistant clinical isolates by three-dimensional checkerboard. LVX and LNZ were used as the third drug at fixed ½ and » minimum inhibitory concentration (MIC). INH and RIF were tested at concentrations ranging from 0.0009 µg/mL to 50 µg/mL and 0.0009 µg/mL to 800 µg/mL, respectively. The combinatorial effects were determined by the Fractional Inhibitory Concentration Index (FICI). FICI values ≤ 0.75, 0.75-4 and ≥4 were considered as synergism, indifferent and antagonism, respectively. RESULTS: MIC ranged from 0.03 - 6.25 µg/mL for INH, 0.008-100 µg/mL for RIF, 0.12-0.25 µg/mL for LVX and 0.25-0.5 µg/mL for LNZ in the H37Rv and all clinical isolates. INH/RIF/LVX and INH/RIF/LNZ synergisms were observed in 40 and 50% of the resistant M. tuberculosis clinical isolates and better observed for INH and RIF combined to LVX or LNZ at » MIC. CONCLUSION: The present study calls attention for the potential use of INH/RIF/LVX and INH/RIF/LNZ combinations in the treatment of resistant TB.