Abstract
In order to exploit the potential benefits of antimicrobial combination therapy, we need a better understanding of the circumstances under which pharmacodynamic interactions expected. In this study, Pharmacodynamic interactions between silver nanoparticle (SNP) and topical antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) were investigated using the MIC test, Combination assay followed by Fractional Inhibitory concentration Index and Agar well diffusion method. SNP + MUP, SNP + NEO, SNP + VAN combinations showed Synergism (SN) and SNP + CEF, SNP + GEN, SNP + TET showed Partial synergism (PS) against Staphylococcus aureus. Four combinations (SNP + CEF, SNP + MUP, SNP + GEN, SNP + VAN) showed SN, SNP + TET showed PS and Indifferent effect (ID) were observed for SNP + NEO against Pseudomonas aeruginosa. SN was observed for SNP + CEF, SNP + GEN, SNP + NEO, SNP + TET and SNP + MUP showed ID, SNP + VAN showed PS against Escherichia coli. In addition, we elucidated the possible mechanism involved in the pharmacodynamic interaction between SNP-topical antibiotics by increased ROS level, membrane damage following protein release, K+ leakage and biofilm inhibition. Thus, our findings support that conjugation of the SNP with topical antibiotics have great potential in the topical formulation when treating complex resistant bacterial infections and where there is a need of more concentration to kill pathogenic bacteria.
Highlights
Pharmacodynamic interactions are those where the effects of one drug are changed by the presence of another drug at its site of action
Vancomycin found to be more susceptible than other antibiotics tested and neomycin showed no activity against P. aeruginosa ATCC 25619
Our findings revealed that silver nanoparticle (SNP) and combinations caused significant level potassium leakage due to membrane damage as compared to the control treated against S. aureus, P. aeruginosa, E. coli
Summary
Pharmacodynamic interactions are those where the effects of one drug are changed by the presence of another drug at its site of action. The use of Silver nanoparticles can be exploited in various fields, medical and pharmaceutical due to their low toxicity to human cells, high thermal stability and low volatility[3] This has resulted in a broad array of studies in which Silver nanoparticles have played a role as drug and as well as superior antimicrobial agent and even has shown to prevent HIV binding to host cells[4]. The present study aims to evaluate any pharmacodynamic interactions such as synergistic, additive, antagonistic effect of SNPs when conjugate with the commonly used topical deliverable antibiotics such as Cefazolin (CEF), Mupirocin (MUP), Gentamycin (GEN), Neomycin (NEO), Tetracycline (TET), Vancomycin (VAN) against major causes of wound, burn bacterial infections. To the best of the authors’ knowledge, this is the first report on the possible pharmacodynamic interaction of several topical antibiotics and SNPs
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