Microbial resistance to currently available antibiotics is a public health problem in the\nfight against infectious diseases. Most antibiotics are characterized by numerous side effects that\nmay be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an\nalternative way to minimize the adverse effects associated with most conventional antibiotics, piperine\nand piperlongumine were screened in combination with conventional rifampicin, tetracycline, and\nitraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus\naureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index\nwas used to estimate the synergistic effects of various combination ratios of the piperamides and\nantibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed\nsynergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic\ninteraction was also observed with piperine in combination with tetracycline against S. aureus, while\nantagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the\npiperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with\nthe exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1\nrifampicin/piperine. No synergistic interaction was observed when the commercial compounds were\ncombined with itraconazole and tested against C. albicans. The results showed that piperine and\npiperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage\ncombinations of these bioactive compounds with the antibiotics used may be a better option for the\ntreatment of bacterial infections that aims to minimize the adverse effects associated with the use of\nthese conventional antibacterial drugs.
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