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Modulatory activity of piperine on clarithromycin against rapidly growing mycobacteria.

Title: Modulatory activity of piperine on clarithromycin against rapidly growing mycobacteria.
Authors: Palomo CT; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, Brazil. Electronic address: trevisollicarolina@gmail.com.; Murase LS; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, Brazil.; Alexandre de Oliveira R; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, Brazil.; Pereira da Silva GK; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, Brazil.; Bonone GL; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Paraná, Brazil.; Nascimento N; Postgraduate Program in Nursing, State University of Maringá, Maringá, Paraná, Brazil.; Meneguello JE; Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil.; Caleffi-Ferracioli KR; Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil.; Bertin de Lima Scodro R; Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil.; Cardoso RF; Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil.
Source: Microbial pathogenesis [Microb Pathog] 2025 Jun; Vol. 203, pp. 107494. Date of Electronic Publication: 2025 Mar 21.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE
Imprint Name(s): Original Publication: London ; Orlando : Academic Press, c1986-
MeSH Terms: Polyunsaturated Alkamides*/pharmacology ; Benzodioxoles*/pharmacology ; Piperidines*/pharmacology ; Alkaloids*/pharmacology ; Clarithromycin*/pharmacology ; Anti-Bacterial Agents*/pharmacology ; Nontuberculous Mycobacteria*/drug effects ; Nontuberculous Mycobacteria*/growth & development; Macrophages/microbiology ; Macrophages/drug effects ; Mycobacterium Infections, Nontuberculous/microbiology ; Mycobacterium Infections, Nontuberculous/drug therapy ; Microbial Sensitivity Tests ; Humans ; Drug Synergism ; Animals
Abstract: 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.; (Copyright © 2025 Elsevier Ltd. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Adjuvant compound; Clarithromycin; Fast-growing non-tuberculous mycobacteria; Mycobacteriosis; Piperine; Treatment
Substance Nomenclature: 0 (Polyunsaturated Alkamides); U71XL721QK (piperine); 0 (Benzodioxoles); 0 (Piperidines); 0 (Alkaloids); H1250JIK0A (Clarithromycin); 0 (Anti-Bacterial Agents)
Entry Date(s): Date Created: 20250323 Date Completed: 20250410 Latest Revision: 20250410
Update Code: 20260130
DOI: 10.1016/j.micpath.2025.107494
PMID: 40122412
Database: MEDLINE

Journal Article