Silver Carboxylate as an Antibiotic-Independent Antimicrobial: A Review of Current Formulations, in vitro Efficacy, and Clinical Relevance A Review of Current Formulations and Clinical Relevance

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Makena Mette Liam Connolly Neel Vishwanath Sai Allu Colin Whitaker Benjamin K Stone Drew Clippert Valentin Antoci Christopher Born Dioscaris Garcia


The increasing prevalence of multi-drug resistant pathogens has led to a renewed focus on the use of silver as an antibiotic-independent antimicrobial. Unfortunately, the use of many silver formulations may be limited by an uncontrolled release of silver with the potential for significant cytotoxic effects. Silver carboxylate (AgCar) has emerged as an alternative formulation of silver with the potential to mitigate these concerns while still displaying significant bactericidal activity. This article reviews the efficacy of silver carboxylate formulations as a promising novel antibiotic-independent antimicrobial.
This study was conducted through a search of five electronic databases (PubMed, Embase, MEDLINE, Cochrane Library, and Web of Science) for relevant studies up to September 2022. Searches were conducted for types of “silver carboxylate” formulations. Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. A review of the antimicrobial activity and cytotoxicity of silver carboxylate was compiled based on this search.   
Current body of data suggests that silver carboxylate shows promise as an emerging antibiotic-independent antimicrobial, with significant bactericidal effects while minimizing cytotoxicity. Silver carboxylate addresses several of the limitations of more primitive formulations, including controlled dosing and fewer negative effects on eukaryotic cell lines. These factors are concentration-dependent and largely rely on the vehicle system used to deliver it. Although several silver carboxylate-based formulations like titanium dioxide/ polydimethylsiloxane (TiO2/PDMS) matrix-eluting AgCar have shown promising results in vitro, and could potentially be utilized independently or in conjunction with current and future antimicrobial therapies, there is a need for further in vivo studies to validate their overall safety and efficacy profile.

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METTE, Makena et al. Silver Carboxylate as an Antibiotic-Independent Antimicrobial: A Review of Current Formulations, in vitro Efficacy, and Clinical Relevance. Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 19 june 2024. doi:
Review Articles


1. Centers for Disease Control and Prevention. National and State Healthcare-Associated Infections Progress Report. Published online 2016. Accessed October 11, 2022.
2. Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224(1):59-74. doi:10.1016/j.jamcollsurg.2016.10.029
3. Peleg AY, Hooper DC. Hospital-acquired infections due to gram-negative bacteria. N Engl J Med. 2010;362(19):1804-1813. doi:10.1056/NEJMra0904124
4. Young P, Khadaroo R. Surgical site infections. Surg Clin North Am. 2014;94(6). doi:10.1016/j.suc.2014.08.008
5. Kern WV, Rieg S. Burden of bacterial bloodstream infection—a brief update on epidemiology and significance of multidrug-resistant pathogens. Clin Microbiol Infect. 2020;26(2):151-157. doi:10.1016/j.cmi.2019.10.031
6. Medina E, Pieper DH. Tackling Threats and Future Problems of Multidrug-Resistant Bacteria. Curr Top Microbiol Immunol. 2016;398:3-33. doi:10.1007/82_2016_492
7. Ibrahim S, Al-Saryi N, Al-Kadmy IMS, Aziz SN. Multidrug-resistant Acinetobacter baumannii as an emerging concern in hospitals. Mol Biol Rep. 2021;48(10):6987-6998. doi:10.1007/s11033-021-06690-6
8. WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health. Saudi Med J. 2014;35(7).
9. Rather MA, Gupta K, Mandal M. Microbial biofilm: formation, architecture, antibiotic resistance, and control strategies. Braz J Microbiol Publ Braz Soc Microbiol. 2021;52(4):1701-1718. doi:10.1007/s42770-021-00624-x
10. Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol. 2017;15(8):453-464. doi:10.1038/nrmicro.2017.42
11. Roy R, Tiwari M, Donelli G, Tiwari V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence. 2018;9(1):522-554. doi:10.1080/21505594.2017.1313372
12. Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv. 2019;37(1):177-192. doi:10.1016/j.biotechadv.2018.11.013
13. Coates ARM, Hu Y, Holt J, Yeh P. Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. Expert Rev Anti Infect Ther. 2020;18(1):5-15. doi:10.1080/14787210.2020.1705155
14. Cascioferro S, Carbone D, Parrino B, et al. Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm-Associated Infections. ChemMedChem. 2021;16(1):65-80. doi:10.1002/cmdc.202000677
15. Rao H, Choo S, Rajeswari Mahalingam SR, et al. Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies. Mol Basel Switz. 2021;26(7):1870. doi:10.3390/molecules26071870
16. Song S, Wood TK. Combatting Persister Cells With Substituted Indoles. Front Microbiol. 2020;11:1565. doi:10.3389/fmicb.2020.01565
17. Kim W, Hendricks GL, Tori K, Fuchs BB, Mylonakis E. Strategies against methicillin-resistant Staphylococcus aureus persisters. Future Med Chem. 2018;10(7):779-794. doi:10.4155/fmc-2017-0199
18. Peng J, Mishra B, Khader R, Felix L, Mylonakis E. Novel Cecropin-4 Derived Peptides against Methicillin-Resistant Staphylococcus aureus. Antibiot Basel Switz. 2021;10(1):36. doi:10.3390/antibiotics10010036
19. Ismat A, Walter N, Baertl S, et al. Antibiotic cement coating in orthopedic surgery: a systematic review of reported clinical techniques. J Orthop Traumatol Off J Ital Soc Orthop Traumatol. 2021;22(1):56. doi:10.1186/s10195-021-00614-7
20. Garcia DR, Vishwanath N, Allu S, et al. Synergistic Effects of Silver Carboxylate and Chlorhexidine Gluconate for Wound Care and Prevention of Surgical Site Infections by Cutibacterium acnes and Methicillin-Resistant Staphylococcus aureus. Surg Infect. 2022;23(3):254-261. doi:10.1089/sur.2021.237
21. Eltorai AE, Haglin J, Perera S, et al. Antimicrobial technology in orthopedic and spinal implants. World J Orthop. 2016;7(6):361-369. doi:10.5312/wjo.v7.i6.361
22. Garcia D, Gilmore A, Berns E, et al. Silver carboxylate and titanium dioxide-polydimethylsiloxane coating decreases adherence of multi-drug resistant Serratia marcescens on spinal implant materials. Spine Deform. 2021;9(6):1493-1500. doi:10.1007/s43390-021-00380-w
23. Garcia DR, Berns EM, Spake CSL, et al. Silver carboxylate-doped titanium dioxide-polydimethylsiloxane coating decreases Cutibacterium acnes adherence and biofilm formation on polyether ether ketone. Spine J Off J North Am Spine Soc. 2022;22(3):495-503. doi:10.1016/j.spinee.2021.09.011
24. Hsu JE, Bumgarner RE, Matsen FA. Propionibacterium in Shoulder Arthroplasty: What We Think We Know Today. J Bone Joint Surg Am. 2016;98(7):597-606. doi:10.2106/JBJS.15.00568
25. Caseris M, Ilharreborde B, Doit C, et al. Is Cutibacterium acnes early surgical site infection rate related to the duration of antibiotic prophylaxis in adolescent idiopathic scoliosis surgery? Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc. 2020;29(7):1499-1504. doi:10.1007/s00586-020-06427-2
26. Vishwanath N, Whitaker C, Allu S, et al. Silver as an Antibiotic-Independent Antimicrobial: Review of Current Formulations and Clinical Relevance. Surg Infect. Published online September 29, 2022. doi:10.1089/sur.2022.229
27. Lansdown ABG. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006;33:17-34. doi:10.1159/000093928
28. de Lima R, Seabra AB, Durán N. Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles. J Appl Toxicol JAT. 2012;32(11):867-879. doi:10.1002/jat.2780
29. Haglin JM, Garcia DR, Roque DL, Spake CSL, Jarrell JD, Born CT. Assessing the Efficacy of a Silver Carboxylate Antimicrobial Coating on Prosthetic Liners. JPO J Prosthet Orthot. 2020;32(4):251-257. doi:10.1097/JPO.0000000000000271
30. Tran N, Kelley MN, Tran PA, et al. Silver doped titanium oxide-PDMS hybrid coating inhibits Staphylococcus aureus and Staphylococcus epidermidis growth on PEEK. Mater Sci Eng C Mater Biol Appl. 2015;49:201-209. doi:10.1016/j.msec.2014.12.072
31. Aldabaldetrecu M, Tamayo L, Alarcon R, et al. Stability of Antibacterial Silver Carboxylate Complexes against Staphylococcus epidermidis and Their Cytotoxic Effects. Mol Basel Switz. 2018;23(7):E1629. doi:10.3390/molecules23071629
32. Tran N, Tran PA, Jarrell JD, et al. In vivo caprine model for osteomyelitis and evaluation of biofilm-resistant intramedullary nails. BioMed Res Int. 2013;2013:674378. doi:10.1155/2013/674378
33. Lu X, Ye J, Zhang D, et al. Silver carboxylate metal-organic frameworks with highly antibacterial activity and biocompatibility. J Inorg Biochem. 2014;138:114-121. doi:10.1016/j.jinorgbio.2014.05.005
34. Lintinen K, Luiro S, Figueiredo P, et al. Antimicrobial Colloidal Silver–Lignin Particles via Ion and Solvent Exchange. ACS Sustain Chem Eng. 2019;7(18):15297-15303. doi:10.1021/acssuschemeng.9b02498
35. O’Beirne C, Piatek ME, Fossen J, et al. Continuous flow synthesis and antimicrobial evaluation of NHC* silver carboxylate derivatives of SBC3 in vitro and in vivo. Met Integr Biometal Sci. 2021;13(2):mfaa011. doi:10.1093/mtomcs/mfaa011
36. Alexander JW. History of the medical use of silver. Surg Infect. 2009;10(3):289-292. doi:10.1089/sur.2008.9941