Antibiotic additive and synergistic action of rutin, morin and quercetin against methicillin resistant Staphylococcus aureus

Abstract

BackgroundTo determine the effect of flavonoids in conjunction with antibiotics in methicillin resistant Staphylococcus aureus (MRSA) a study was designed. The flavonoids included Rutin, Morin, Qurecetin while antibiotics included ampicillin, amoxicillin, cefixime, ceftriaxone, vancomycin, methicillin, cephradine, erythromycin, imipenem, sulphamethoxazole/trimethoprim, ciprofloxacin and levolfloxacin. Test antibiotics were mostly found resistant with only Imipenem and Erythromycin found to be sensitive against 100 MRSA clinical isolates and S. aureus (ATCC 43300). The flavonoids were tested alone and also in different combinations with selected antibiotics.MethodsAntibiotics and flavonoids sensitivity assays were carried using disk diffusion method. The combinations found to be effective were sifted through MIC assays by broth macro dilution method. Exact MICs were determined using an incremental increase approach. Fractional inhibitory concentration indices (FICI) were determined to evaluate relationship between antibiotics and flavonoids is synergistic or additive. Potassium release was measured to determine the effect of antibiotic-flavonoids combinations on the cytoplasmic membrane of test bacteria.ResultsAntibiotic and flavonoids screening assays indicated activity of flavanoids against test bacteria. The inhibitory zones increased when test flavonoids were combined with antibiotics facing resistance. MICs of test antibiotics and flavonoids reduced when they were combined. Quercetin was the most effective flavonoid (MIC 260 μg/ml) while morin + rutin + quercetin combination proved most efficient with MIC of 280 + 280 + 140 μg/ml. Quercetin + morin + rutin with amoxicillin, ampicillin, cephradine, ceftriaxone, imipenem, and methicillin showed synergism, while additive relationship was indicated between morin + rutin and amoxicillin, cephradine, ceftriaxone, imipenem, and methicillin. Quercetin alone had an additive effect with ampicillin, cephradine, ceftriaxone, imipenem, and methicillin. Potassium leakage was highest for morin + rutin + quercetin that improved further in combination with imipenem. Morin and rutin alone had no activity but in combination showed activity against test bacteria.ConclusionsThe flavonoids when used in combination with antibiotics were found to increase each other activity against test bacteria. The relationship between the flavonoids and antibiotics in most of the cases was additive. However in a few cases synergism was also observed. Flavonoids alone or in combinations also damaged bacterial cell membrane.

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus

“…Virulence factors of S. aureus represent an important aspect in pathogenesis, toxins in particular. Luteolin decreased α-toxin production by S. aureus and exhibited activity against MRSA isolates [11], in agreement with previous reports [12,13]. …”

“…In our previous study, an additive effect [13] was observed for quercetin in combination with antibiotics, with FICI <1. In the present report, additive effect is also found for Q + L with AMP, CEPH and MET (FICI ≤ 1).…”

Antioxidant, Antimicrobial and Cytotoxic Properties as Well as the Phenolic Content of the Extract from Hancornia speciosa Gomes

“…Amin et al [22] found that quercetin derivatives, such as those present in the EEHS, were active against methicillin-resistant S . aureus strains.…”

“…These compounds also have antimicrobial activities [22]. These properties have attracted scientific interest because 60% of the antimicrobial drugs discovered in the past few decades are of natural origin [23].…”

Annona glabra Flavonoids Act As Antimicrobials by Binding to Pseudomonas aeruginosa Cell Walls

“…Another compound identified in SF32-33 is quercetin (3,3′,4′,5,7-pentahydroxyflavone). Reports have shown a potential use for this compound when combined with either epigallocatechin-3-gallate c, against drug-resistant Mycobacterium tuberculosis (Dey et al, 2015), or oxacillin, causing damage in the cell walls of multi-resistant Staphylococcus aureus (Amin et al, 2015). It is possible that all the compounds identified herein act synergistically, contributing to the antimicrobial effects of SF32-33.…”