Combination antibiotic-phytochemical effects on resistance adaptation in Staphylococcus aureus

Emergence and rapid spread of antibiotic resistance has become one of the leading causes of treatment failures in case of bacterial infections. Antibiotic combinations are generally used to enhance the overall efficacy of therapy with the aim to generate synergistic outcomes. It further helps in reduction of total antibiotic dosage. Phytochemicals are known to have multiple bacterial targets that modulate or modify resistance in bacteria. In the present study, a microchannel-based device and monitoring system was used to demonstrate and investigate short and long term effects of antibiotic-phytochemical combinations in different proportions on Staphylococcus aureus as test organism. Novel and unconventional combinations of antibiotic ciprofloxacin with the phytochemicals, quercetin, rutin, protocatechuic acid and ethyl gallate, were tested. Based on the experimental results, the strains exposed the antibiotic, generated resistant strains in four days, with 8 to 64 fold increase in their minimum inhibitory concentration (MIC) from the parent strain. The strains exposed to antibiotic-phytochemical combinations, however, showed no resistance causing mutations. The results were verified by standard laboratory practices such as disk-diffusion, mutation frequency, population profiling and molecular studies on the exposed strains. The phytochemicals were able to potentiate antibiotic activity; thereby, increasing the antibacterial efficacy and time span of the treatment with a common antibiotic.    Key words: Antibiotic combination therapy, antibiotic resistance, ciprofloxacin, microfluidic-device, phytochemical, potentiation, Staphylococcus aureus.