SYNERGISM EFFECT OF SILVER NANOPARTICLES AND CEFOTAXIME TO TREAT BIOFILM FORMATION OF STAPHYLOCOCCUS AUREUS CLINICAL ISOLATED
DOI: http://dx.doi.org/10.30970/sbi.1902.833
Abstract
Background. Staphylococcus aureus, is a major pathogen causing infections in both hospital and community settings. Multi-drug-resistant strains, particularly Methicillin-resistant Staphylococcus aureus (MRSA), complicate treatment, as these strains can evade antibiotics. Biofilm formation by S. aureus protects bacterial cells from immune responses and antibiotics, making infections difficult to treat. This study evaluates the synergistic effect of silver nanoparticles (AgNPs) and cefotaxime in inhibiting biofilm formation by clinical S. aureus isolates, especially multi-drug-resistant strains.
Materials and Methods. Thirty clinical S. aureus isolates were obtained from patients with skin infections. Identification was confirmed using biochemical tests and the VITEK2 system. Antimicrobial susceptibility testing was performed using the disk diffusion method on antibiotics including ciprofloxacin, imipenem, amoxicillin-clavulanic acid, cefotaxime, and chloramphenicol. Minimum inhibitory concentrations (MICs) were also determined. Biofilm formation was quantified using crystal violet staining. Silver nanoparticles (AgNPs) were synthesized using sodium borohydride and characterized by atomic force microscopy (AFM) and field emission scanning electron microscopy (FE-SEM).
Results. All isolates were susceptible to ciprofloxacin and imipenem. Ninety percent were susceptible to amoxicillin-clavulanic acid, while 70% were susceptible to cefotaxime. All isolates were resistant to chloramphenicol. Biofilm formation assays showed variability in biofilm production. AgNPs alone demonstrated superior efficacy in inhibiting biofilm formation. The combination of AgNPs and cefotaxime exhibited the strongest inhibition, suggesting a synergistic effect.
Conclusion. This study suggests that AgNPs alone are more effective than cefotaxime in inhibiting biofilm formation. The combination of AgNPs and cefotaxime showed the most potent effect, providing a promising strategy for treating multi-drug-resistant S. aureus infections. AgNPs may serve as an adjunct to antibiotics in overcoming biofilm-associated infections.
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| Agnihotri, S., Mukherji, S., & Mukherji, S. (2013). Immobilized silver nanoparticles enhance contact killing and show the highest efficacy: elucidation of the mechanism of bactericidal action of silver. Nanoscale, 5(16), 7328-7340. doi:10.1039/c3nr00024a Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Aldridge, K. E. (1995). Cefotaxime in the treatment of staphylococcal infections: comparison of in vitro and in vivo studies. Diagnostic Microbiology and Infectious Disease, 22(1-2), 195-201. doi: 10.1016/0732-8893(95)00051-b Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Ali, Z. A., Yahya, R., Sekaran, S. D., & Puteh, R. (2016). Green synthesis of silver nanoparticles using apple extract and its antibacterial properties. Advances in Materials Science and Engineering, 2016(1), 4102196. doi:10.1155/2016/4102196 Crossref ● Google Scholar | ||||
| ||||
| Amirulhusni, A. N., Palanisamy, N. K., Mohd-Zain, Z., Ping, L. J., & Duraira, R. (2012). Antibacterial effect of silver nanoparticles on multi-drug resistant Pseudomonas aeruginosa. International Journal of Medical Science and Public Health, 6(7), 291-294. doi:10.5281/zenodo.1329578 Crossref ● Google Scholar | ||||
| ||||
| Aryal, S. (2016). Mannitol salt agar for the isolation of Staphylococcus aureus. Microbiology Info. 5-8. Google Scholar | ||||
| ||||
| Atta, S. E., Ghannawi, L., Shakir, O. Y., & Gharab, K. M. (2023). Molecular investigation of gyrA mutations in clinical isolates of methicillin-resistant Staphylococcus aureus derived from diverse sources. Al-Rafidain Journal of Medical Sciences, 5(1), S64-S70. doi:10.54133/ajms.v5i1S.282 Crossref ● Google Scholar | ||||
| ||||
| Benson, H. J. (2002). Microbiological applications: a laboratory manual in general microbiology. McGraw-Hill. Google Scholar | ||||
| ||||
| Boucher, H. W., & Corey, G. R. (2008). Epidemiology of methicillin-resistant Staphylococcus aureus. Clinical Infectious Diseases, 46(5), S344-S349. doi:10.1086/533590 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Bruna, T., Maldonado-Bravo, F., Jara, P., & Caro, N. (2021). Silver nanoparticles and their antibacterial applications. International Journal of Molecular Sciences, 22(13), 7202. doi:10.3390/ijms22137202 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Centers for Disease Control and Prevention (CDC). (2003). Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections - Los Angeles County, California, 2002-2003. MMWR. Morbidity and Mortality Weekly Report, 52(5), 88. PubMed ● Google Scholar | ||||
| ||||
| Chen, Q., Xie, S., Lou, X., Cheng, S., Liu, X., Zheng, W., Zheng, Z., & Wang, H. (2020). Biofilm formation and prevalence of adhesion genes among Staphylococcus aureus isolates from different food sources. MicrobiologyOpen, 9(1), e00946. doi:10.1002/mbo3.946 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Chhibber, S., Gondil, V. S., Sharma, S., Kumar, M., Wangoo, N., & Sharma, R. K. (2017). A novel approach for combating Klebsiella pneumoniae biofilm using histidine functionalized silver nanoparticles. Frontiers in Microbiology, 8, 1104. doi:10.3389/fmicb.2017.01104 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Daphedar, A., & Taranath, T. C. (2018). Characterization and cytotoxic effect of biogenic silver nanoparticles on mitotic chromosomes of Drimia polyantha (Blatt. & McCann). Toxicology Reports, 5, 910-918. doi:10.1016/j.toxrep.2018.08.018 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| El-Fouly, M. Z., Sharaf, A. M., Shahin, A. A. M., El-Bialy, H. A., & Omara, A. M. A. (2015). Biosynthesis of pyocyanin pigment by Pseudomonas aeruginosa. Journal of Radiation Research and Applied Sciences, 8(1), 36-48. doi:10.1016/j.jrras.2014.10.007 Crossref ● Google Scholar | ||||
| ||||
| Frei, A., Verderosa, A. D., Elliott, A. G., Zuegg, J., & Blaskovich, M. A. T. (2023). Metals to combat antimicrobial resistance. Nature Reviews Chemistry, 7(3), 202-224. doi:10.1038/s41570-023-00463-4 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Hemati, S., Sadeghifard, N., Ghafurian, S., Maleki, F., Mahdavi, Z., Hassanvand, A., Valadbeigi, H., Hemati, S., & Hatami, V. (2016). The association of biofilm formation and sub-minimal inhibitory concentrations of antimicrobial agents. Journal of Basic Research in Medical Sciences, 3(1), 26-30. Google Scholar | ||||
| ||||
| Iravani, S., Korbekandi, H., Mirmohammadi, S. V., & Zolfaghari, B. (2014). Synthesis of silver nanoparticles: chemical, physical and biological methods. Research in Pharmaceutical Sciences, 9(6), 385-406. PubMed ● PMC ● Google Scholar | ||||
| ||||
| Jaber, G. S., Dhaif, S. S., Abdul Hussian, T. A., Ibrahim, N. A., & Arifiyanto, A. (2023). Enhancing the prodigiosin pigment by adding Ag/TiO2 synergism for antibacterial activity. Biocatalysis and Agricultural Biotechnology, 54, 102900. doi:10.1016/j.bcab.2023.102900 Crossref ● Google Scholar | ||||
| ||||
| Kowalska-Krochmal, B., & Dudek-Wicher, R. (2021). The minimum inhibitory concentration of antibiotics: methods, interpretation, clinical relevance. Pathogens, 10(2), 165. doi:10.3390/pathogens10020165 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Malawong, S., Thammawithan, S., Sirithongsuk, P., Daduang, S., Klaynongsruang, S., Wong, P. T., & Patramanon, R. (2021). Silver nanoparticles enhance antimicrobial efficacy of antibiotics and restore that efficacy against the melioidosis pathogen. Antibiotics, 10(7), 839. doi:10.3390/antibiotics10070839 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Najim, R. S., Risan, M. H., & Al-Ugaili, D. N. (2024). Antimicrobial efficacy of quercetin against biofilm production by Staphylococcus aureus. Al-Mustansiriyah Journal of Science, 35(3), 74-80. doi:10.23851/mjs.v35i3.1367 Crossref ● Google Scholar | ||||
| ||||
| Rasigade, J.-P., & Vandenesch, F. (2014). Staphylococcus aureus: a pathogen with still unresolved issues. Infection, Genetics and Evolution, 21, 510-514. doi:10.1016/j.meegid.2013.08.018 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Rasool K, H., Abad, W. K., & Abd, A. N. (2025). Preparation of ZnO nanoparticles from Juglans regia dry husk extract for biomedical applications. Journal of Biosafety and Biosecurity, 7(1), 1-8. doi:10.1016/j.jobb.2024.10.004 Crossref ● Google Scholar | ||||
| ||||
| Selim, S. A., Adam, M. E., Hassan, S. M., & Albalawi, A. R. (2014). Chemical composition, antimicrobial and antibiofilm activity of the essential oil and methanol extract of the Mediterranean cypress (Cupressus sempervirens L.). BMC Complementary and Alternative Medicine, 14(1), 179. doi:10.1186/1472-6882-14-179 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Shariati, A., Noei, M., Askarinia, M., Khoshbayan, A., Farahani, A., & Chegini, Z. (2024). Inhibitory effect of natural compounds on quorum sensing system in Pseudomonas aeruginosa: a helpful promise for managing biofilm community. Frontiers in Pharmacology, 15, 1350391. doi:10.3389/fphar.2024.1350391 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Sharma, S., Mohler, J., Mahajan, S. D., Schwartz, S. A., Bruggemann, L., & Aalinkeel, R. (2023). Microbial biofilm: a review on formation, infection, antibiotic resistance, control measures, and innovative treatment. Microorganisms, 11(6), 1614. doi:10.3390/microorganisms11061614 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Siddique, M. H., Aslam, B., Imran, M., Ashraf, A., Nadeem, H., Hayat, S., Khurshid, M., Afzal, M., Malik, I. R., Shahzad, M., Qureshi, U., Khan, Z. U. H., & Muzammil, S. (2020). Effect of silver nanoparticles on biofilm formation and EPS production of multidrug-resistant Klebsiella pneumoniae. BioMed Research International, 2020(1), 6398165. doi:10.1155/2020/6398165 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Swolana, D., & Wojtyczka, R. D. (2022). Activity of silver nanoparticles against Staphylococcus spp. International Journal of Molecular Sciences, 23(8), 4298. doi:10.3390/ijms23084298 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Taraszkiewicz, A., Fila, G., Grinholc, M., & Nakonieczna, J. (2013). Innovative strategies to overcome biofilm resistance. Biomed Research International, 2013(1), 150653. doi:10.1155/2013/150653 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Tong, S. Y., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015). Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clinical Microbiology Reviews, 28(3), 603-661. doi:10.1128/cmr.00134-14 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Vladár, A. E., & Hodoroaba, V.-D. (2020). Characterization of nanoparticles by scanning electron microscopy. In: V.-D. Hodoroaba, W. E. S. Unger, & A. G. Shard (Eds.), Characterization of nanoparticles (pp. 7-27). Elsevier. doi:10.1016/b978-0-12-814182-3.00002-x Crossref ● Google Scholar | ||||
| ||||
| Wayne, P. A. (2015). Clinical and laboratory standards institute (CLSI) performance standards for antimicrobial susceptibility testing. Google Scholar | ||||
| ||||
| Yin, I. X., Zhang, J., Zhao, I. S., Mei, M. L., Li, Q., & Chu, C. H. (2020). The antibacterial mechanism of silver nanoparticles and its application in dentistry. International Journal of Nanomedicine, 15, 2555-2562. doi:10.2147/ijn.s246764 Crossref ● PubMed ● PMC ● Google Scholar | ||||
| ||||
| Yonathan, K., Mann, R., Mahbub, K. R., & Gunawan, C. (2022). The impact of silver nanoparticles on microbial communities and antibiotic resistance determinants in the environment. Environmental Pollution, 293, 118506. doi:10.1016/j.envpol.2021.118506 Crossref ● PubMed ● Google Scholar | ||||
| ||||
| Zhao, A., Sun, J., & Liu, Y. (2023). Understanding bacterial biofilms: from definition to treatment strategies. Frontiers in Cellular and Infection Microbiology, 13, 1137947. doi:10.3389/fcimb.2023.1137947 Crossref ● PubMed ● PMC ● Google Scholar | ||||
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