Infective Endocarditis by Biofilm-Producing Methicillin-Resistant -Pathogenesis, Diagnosis, and Management

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2025 Jan 8

PMID 39766522

Authors

Ashlesha Kaushik

Helen Kest

Mangla Sood

Corey Thieman

Bryan W Steussy

Michael Padomek

Sandeep Gupta

Affiliations

Soon will be listed here.

Abstract

Infective endocarditis (IE) is a life-threatening condition with increasing global incidence, primarily caused by , especially methicillin-resistant strains (MRSA). Biofilm formation by is a critical factor in pathogenesis, contributing to antimicrobial resistance and complicating the treatment of infections involving prosthetic valves and cardiovascular devices. Biofilms provide a protective matrix for MRSA, shielding it from antibiotics and host immune defenses, leading to persistent infections and increased complications, particularly in cases involving prosthetic materials. Clinical manifestations range from acute to chronic presentations, with complications such as heart failure, embolic events, and neurological deficits. Diagnosis relies on the Modified Duke Criteria, which have been updated to incorporate modern cardiovascular interventions and advanced imaging techniques, such as PET/CT (positron emission tomography, computed tomography), to improve the detection of biofilm-associated infections. Management of MRSA-associated IE requires prolonged antimicrobial therapy, often with vancomycin or daptomycin, needing a combination of antimicrobials in the setting of prosthetic materials and frequently necessitates surgical intervention to remove infected prosthetic material or repair damaged heart valves. Anticoagulation remains controversial, with novel therapies like dabigatran showing potential benefits in reducing thrombus formation. Despite progress in treatment, biofilm-associated resistance poses ongoing challenges. Emerging therapeutic strategies, including combination antimicrobial regimens, bacteriophage therapy, antimicrobial peptides (AMPs), quorum sensing inhibitors (QSIs), hyperbaric oxygen therapy, and nanoparticle-based drug delivery systems, offer promising approaches to overcoming biofilm-related resistance and improving patient outcomes. This review provides an overview of the pathogenesis, current management guidelines, and future directions for treating biofilm-related MRSA IE.

Citing Articles

Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts.

Almatroudi A Biology (Basel). 2025; 14(2).

PMID: 40001933 PMC: 11852148. DOI: 10.3390/biology14020165.

References

Karaolis D, Rashid M, Chythanya R, Luo W, Hyodo M, Hayakawa Y . c-di-GMP (3'-5'-cyclic diguanylic acid) inhibits Staphylococcus aureus cell-cell interactions and biofilm formation. Antimicrob Agents Chemother. 2005; 49(3):1029-38. PMC: 549248. DOI: 10.1128/AAC.49.3.1029-1038.2005. View

Otto C, Nishimura R, Bonow R, Carabello B, Erwin 3rd J, Gentile F . 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2020; 143(5):e72-e227. DOI: 10.1161/CIR.0000000000000923. View

Akturk E, Oliveira H, Santos S, Costa S, Kuyumcu S, Melo L . Synergistic Action of Phage and Antibiotics: Parameters to Enhance the Killing Efficacy Against Mono and Dual-Species Biofilms. Antibiotics (Basel). 2019; 8(3). PMC: 6783858. DOI: 10.3390/antibiotics8030103. View

Kostakioti M, Hadjifrangiskou M, Hultgren S . Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med. 2013; 3(4):a010306. PMC: 3683961. DOI: 10.1101/cshperspect.a010306. View

Mu H, Guo F, Niu H, Liu Q, Wang S, Duan J . Chitosan improves anti-biofilm efficacy of gentamicin through facilitating antibiotic penetration. Int J Mol Sci. 2014; 15(12):22296-308. PMC: 4284708. DOI: 10.3390/ijms151222296. View

Ostergaard L, Lauridsen T, Iversen K, Bundgaard H, Sondergaard L, Ihlemann N . Infective endocarditis in patients who have undergone transcatheter aortic valve implantation: a review. Clin Microbiol Infect. 2020; 26(8):999-1007. DOI: 10.1016/j.cmi.2020.01.028. View

Cesta N, Di Luca M, Corbellino M, Tavio M, Galli M, Andreoni M . Bacteriophage therapy: an overview and the position of Italian Society of Infectious and Tropical Diseases. Infez Med. 2020; 28(3):322-331. View

Wang G, Hanke M, Mishra B, Lushnikova T, Heim C, Thomas V . Transformation of human cathelicidin LL-37 into selective, stable, and potent antimicrobial compounds. ACS Chem Biol. 2014; 9(9):1997-2002. PMC: 4168778. DOI: 10.1021/cb500475y. View

Wu H, Moser C, Wang H, Hoiby N, Song Z . Strategies for combating bacterial biofilm infections. Int J Oral Sci. 2014; 7(1):1-7. PMC: 4817533. DOI: 10.1038/ijos.2014.65. View

10.

Manosalva N, Tortella G, Diez M, Schalchli H, Seabra A, Duran N . Green synthesis of silver nanoparticles: effect of synthesis reaction parameters on antimicrobial activity. World J Microbiol Biotechnol. 2019; 35(6):88. DOI: 10.1007/s11274-019-2664-3. View

11.

Loughrey P, Armstrong D, Lockhart C . Classical eye signs in bacterial endocarditis. QJM. 2015; 108(11):909-10. DOI: 10.1093/qjmed/hcv055. View

12.

Belfield K, Bayston R, Hajduk N, Levell G, Birchall J, Daniel M . Evaluation of combinations of putative anti-biofilm agents and antibiotics to eradicate biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother. 2017; 72(9):2531-2538. DOI: 10.1093/jac/dkx192. View

13.

Li S, Zhu C, Fang S, Zhang W, He N, Xu W . Ultrasound microbubbles enhance human β-defensin 3 against biofilms. J Surg Res. 2015; 199(2):458-69. DOI: 10.1016/j.jss.2015.05.030. View

14.

Patrulea V, Borchard G, Jordan O . An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections. Pharmaceutics. 2020; 12(9). PMC: 7560145. DOI: 10.3390/pharmaceutics12090840. View

15.

Di Martino P . Extracellular polymeric substances, a key element in understanding biofilm phenotype. AIMS Microbiol. 2019; 4(2):274-288. PMC: 6604936. DOI: 10.3934/microbiol.2018.2.274. View

16.

Batoni G, Maisetta G, Esin S . Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria. Biochim Biophys Acta. 2015; 1858(5):1044-60. DOI: 10.1016/j.bbamem.2015.10.013. View

17.

Shahrour H, Ferrer-Espada R, Dandache I, Barcena-Varela S, Sanchez-Gomez S, Chokr A . AMPs as Anti-biofilm Agents for Human Therapy and Prophylaxis. Adv Exp Med Biol. 2019; 1117:257-279. DOI: 10.1007/978-981-13-3588-4_14. View

18.

Siddhardha B, Pandey U, Kaviyarasu K, Pala R, Syed A, Bahkali A . Chrysin-Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity against . Pathogens. 2020; 9(2). PMC: 7168315. DOI: 10.3390/pathogens9020115. View

19.

Zhang Y, Cheng M, Zhang H, Dai J, Guo Z, Li X . Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci. Appl Environ Microbiol. 2018; 84(15). PMC: 6052257. DOI: 10.1128/AEM.00886-18. View

20.

Adelaide M, Salnikov E, Ramos-Martin F, Aisenbrey C, Sarazin C, Bechinger B . The Mechanism of Action of SAAP-148 Antimicrobial Peptide as Studied with NMR and Molecular Dynamics Simulations. Pharmaceutics. 2023; 15(3). PMC: 10051583. DOI: 10.3390/pharmaceutics15030761. View