Evaluation of Synergism between the Aminoglycoside Antibiotic Streptomycin and the Cardiovascular Agent Amlodipine

Abstract

Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in vitro against 504 bacterial strains belonging to both Gram positive and Gram negative genera, as well as in vivo against a mouse-virulent bacterium. Based on such findings, the present study was undertaken to determine whether the efficacy of this non-antibiotic drug could be enhanced in the presence of any antibiotic. Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics, viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline, erythromycin and ciprofloxacin were chosen. Disc diffusion test with amlodipine and streptomycin revealed marked synergism between the combination, compared with their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergy, the checkerboard analysis was performed. The fractional inhibitory concentration (FIC) index of this combination turned out to be 0.24, which confirmed synergism. This antibiotic-non-antibiotic pair was then administered to mice, challenged with S. typhimurium to determine whether this was effective in vivo. Statistical analysis of the mouse protection tests suggested that the combination was highly synergistic (p<0.001), according to Student's t-test. This synergistic drug combination may help us in enhancing the scope of prolonged antibiotic therapy in various types of infections, and might open a new therapeutic approach to combat drug resistance in bacterial diseases.

Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China

“…The inhibitory concentrations of AML against most of the strains tested ranged from 25 to 200 μg/ml, but its effects on P. aeruginosa , E. coli , and K. pneumoniae were limited, and the inhibitory concentrations were >800, >800, and 400 μg/ml, respectively. A further study demonstrated that AML in combination with streptomycin had a synergistic effect [10]. In addition to its in vitro and in vivo activity against Gram-positive and Gram-negative bacteria, AML showed a two- to eightfold reduction in its MIC when combined with streptomycin, and vice versa [10].…”

“…A further study demonstrated that AML in combination with streptomycin had a synergistic effect [10]. In addition to its in vitro and in vivo activity against Gram-positive and Gram-negative bacteria, AML showed a two- to eightfold reduction in its MIC when combined with streptomycin, and vice versa [10]. Similarly, when paired with levofloxacin, AML showed potential synergistic effects in the eradication of P. aeruginosa biofilms [11].…”

“…All of the broth preparations used in the microdilution testing and the Mueller Hinton broth were freshly prepared and used within 24 hours. The checkerboard procedure [10] was used to determine the combined effects of AML and imipenem. Synergy was determined by calculating the fractional inhibitory concentration (FIC) index as follows: FIC index = FICA + FICB = [A]/MICA + [B]/MICB, where [A] is the concentration of drug A; FICA is the FIC of drug A; and [B], MICB, and FICB are defined in the same manner for drug B.…”

Zinc Lactate and Sapindin Act Synergistically with Lactocin 160 Against Gardnerella vaginalis

“…The interactions between two antimicrobials were investigated using a microplate reader-based checkerboard assay described by Asok et al [28] and Badaoui Najjar et al [27]. Briefly, the aqueous solutions of each pair of antimicrobials were prepared separately.…”

Cystic fibrosis infections: treatment strategies and prospects

“…Combinations of different antimicrobial agents with nonantibiotic compounds have been tested in vitro as alternative therapies against P. aeruginosa and B. cepacia , with mixed results. Nonantibiotics tested included polyethylenimine (Khalil et al , 2008), theophylline and theobromine (Rajyaguru & Muszynski, 1998), bismuth‐thiols (Veloira et al , 2003), the sodium channel blocker amiloride (Cohn et al , 1988; Middleton et al , 2005; Treerat et al , 2008), the calcium channel blocker verapamil (Cohn et al , 1995), the bronchodilator salbutamol (Vaisman et al , 1987; Brand, 2000; Ramagopal & Lands, 2000), the cardiovascular drug amlodipine (Asok Kumar et al , 2004), the amiloride homologues ( N,N ‐hexamethylene)amiloride, ( N ‐methyl‐ N ‐isobutyl)amiloride, and benzamil (Cohn et al , 1992; Treerat et al , 2008), gallium (Kaneko et al , 2007), and farnesol (Jabra‐Rizk et al , 2006).…”