SYNERGISM EFFECT OF SILVER NANOPARTICLES AND CEFOTAXIME TO TREAT BIOFILM FORMATION OF STAPHYLOCOCCUS AUREUS CLINICAL ISOLATED

Safiya Saad Dhaif, Dhuha Badr Mahmood, Ghufran Salman Jawad, Lujain Ali Ghannawi, Haidar Fadhil Al-Rubaye


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.


Keywords


Staphylococcus aureus, biofilm, silver nanoparticles (AgNPs), Cefotaxime

Full Text:

PDF

References


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
CrossrefPubMedGoogle 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
CrossrefPubMedGoogle 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
CrossrefGoogle 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
CrossrefGoogle 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
CrossrefGoogle 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
CrossrefPubMedGoogle 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
CrossrefPubMedPMCGoogle 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.
PubMedGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefGoogle 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
CrossrefPubMedPMCGoogle 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.
PubMedPMCGoogle 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
CrossrefGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefGoogle 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
CrossrefPubMedGoogle 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
CrossrefGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefGoogle 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
CrossrefPubMedPMCGoogle 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
CrossrefPubMedGoogle 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
CrossrefPubMedPMCGoogle Scholar


Refbacks

  • There are currently no refbacks.


Copyright (c) 2025 Safiya Saad Dhaif, Dhuha Badr Mahmood, Ghufran Salman Jawad, Lujain Ali Ghannawi, Haidar Fadhil Al-Rubaye

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.