Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance

Abstract

BackgroundSerotonin reuptake inhibitors were recently reported to possess antimicrobial potentials, potentiate activity of several antibiotics, reverse multidrug resistant phenotypes of bacteria and make them susceptible to previously resistant drugs. We investigated antimicrobial potentials of sertraline (SR) against ATCC strains, clinical isolates of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa alone and in-combination with seven antibiotics. Antifungal activity was investigated against four fungal strains including Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Fusarium solani. Intrinsic antibacterial action and Minimum Inhibitory Concentrations (MICs) were determined using well assay, nutrient broth and agar dilution techniques. Disk diffusion and nutrient broth methods were used to study bacterial susceptibility to SR. Minimum Fungicidal Concentrations (MFCs) of SR were determined using Sabouraud dextrose Agar (SDA).ResultsSertraline possesses strong intrinsic antibacterial, antifungal activities and has augmented the antibacterial activities of antibiotics. For S. aureus ATCC 6538, E. coli ATCC 8739 and P. aeruginosa ATCC 9027, the MICs of SR were 20, 40 and 60 μg ml−1, respectively, whereas 55.5% clinical isolates of S. aureus and 50% of E. coli strains were inhibited at 20 and 60 μg ml−1 of SR, respectively. Among the tested fungi, 60% of A. niger and A. fumigatus were inhibited at 40 and 80 μg ml−1, respectively. MFCs were 60 and 80 μg ml−1 for A. flavus and F. solani, respectively. Antibacterial activities of all antibiotics were significantly increased (p < 0.001) with the addition of SR 100 μg ml−1 against all tested bacteria.ConclusionCombination study revealed that SR had significantly increased the activity of antibiotics, and some previously resistant strains were made susceptible. Thus antidepressants are potential sources of resistance modifying agents when used in combination.

Chemical profiling, antimicrobial and insecticidal evaluations of Polygonum hydropiper L

“…The emergence of multidrug resistant (MDR) pathogens and life-threatening infections caused by these microorganisms is a global challenge for scientific community and some scientists speculate that we are going back to the pre-antibiotic era [1, 2]. The prevalence of microbial infections due to opportunistic pathogens, frequently characterized by high mortality rates, has increased during the past two decades [3].…”

Antimicrobial Properties on Non-Antibiotic Drugs in the Era of Increased Bacterial Resistance

“…(MIC 20-30 µg/mL), Escherichia coli and Salmonella spp. (MIC 100 µg/mL) [18,19]. Numerous studies report the antibacterial activity of phenothiazines such as chlorpromazine, levomepromazine, promethazine, trifluoperazine, methdilazine and thioridazine against strains of Mycobacterium tuberculosis, with MICs that vary between different studies.…”

“…Concentrations needed for these activities greatly exceed the highest achievable level in plasma (0.5 µg/mL). [19] Consequently, these compounds cannot stand as antibacterials on their own. However, they're able to enhance the activity of antibiotic agents [17,19].…”

Sertraline demonstrates fungicidal activity in vitro for Coccidioides immitis

“…The mechanism of fungicidal action of sertraline may include both inhibition of intracellular vesicular transport (Rainey et al 2010) and inhibition of protein translation (Zhai et al 2012). Interestingly, sertraline and other serotonin reuptake inhibitors are also being actively investigated for both intrinsic antimicrobial activity and combination treatment of antibiotic-resistant bacteria (Ayaz et al 2015a, 2015b). …”