Clinical Outcomes of combination antimicrobial therapy in Patients with biofilm-associated infection
DOI:
https://doi.org/10.5281/zenodo.22812793Keywords:
biofilm, combination therapy, antimicrobial resistance, device-associated infection, clinical outcomesAbstract

Background: Biofilm formation is a major driver of treatment failure in chronic and device-associated bacterial infections, and combination antimicrobial regimens are increasingly used to overcome the reduced antibiotic penetration and heightened tolerance that biofilms confer.
Objective: This study evaluated clinical outcomes of combination antimicrobial therapy compared with monotherapy in patients with culture-confirmed biofilm-associated infection.
Methods: We conducted a retrospective cohort analysis of adult patients with biofilm-associated infections, including prosthetic joint infection, catheter-related bloodstream infection, and chronic wound infection, comparing clinical cure, relapse, and time to resolution between combination and monotherapy groups.
Results: Combination therapy was associated with a higher rate of clinical cure and a lower rate of relapse at 90 days than monotherapy, with the largest absolute benefit observed in prosthetic-device-associated infections and in regimens that paired a biofilm-active agent such as rifampicin with a companion antibiotic.
Conclusions: Combination antimicrobial therapy improves clinical outcomes in biofilm-associated infection relative to monotherapy, supporting its use particularly where source control is incomplete or a retained device cannot be removed.
References
Costerton, J.W., Stewart, P.S., Greenberg, E.P. (1999) Bacterial biofilms: a common cause of persistent infections. Science, 284(5418): 1318-1322. DOI: 10.1126/science.284.5418.1318
Hall-Stoodley, L., Costerton, J.W., Stoodley, P. (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews Microbiology, 2(2): 95-108. DOI: 10.1038/nrmicro821
Stewart, P.S., Costerton, J.W. (2001) Antibiotic resistance of bacteria in biofilms. Lancet, 358(9276): 135-138. DOI: 10.1016/S0140-6736(01)05321-1
Mah, T.F., O'Toole, G.A. (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends in Microbiology, 9(1): 34-39. DOI: 10.1016/S0966-842X(00)01913-2
Flemming, H.C., Wingender, J. (2010) The biofilm matrix. Nature Reviews Microbiology, 8(9): 623-633. DOI: 10.1038/nrmicro2415
Hoiby, N., Bjarnsholt, T., Givskov, M., Molin, S., Ciofu, O. (2010) Antibiotic resistance of bacterial biofilms. International Journal of Antimicrobial Agents, 35(4): 322-332. DOI: 10.1016/j.ijantimicag.2009.12.011
Zimmerli, W., Trampuz, A., Ochsner, P.E. (2004) Prosthetic-joint infections. New England Journal of Medicine, 351(16): 1645-1654. DOI: 10.1056/NEJMra040181
Tande, A.J., Patel, R. (2014) Prosthetic joint infection. Clinical Microbiology Reviews, 27(2): 302-345. DOI: 10.1128/CMR.00111-13
Raad, I., Hanna, H., Maki, D. (2007) Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lancet Infectious Diseases, 7(10): 645-657. DOI: 10.1016/S1473-3099(07)70235-9
Mermel, L.A., Allon, M., Bouza, E., Craven, D.E., Flynn, P., O'Grady, N.P., et al. (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 49(1): 1-45. DOI: 10.1086/599376
James, G.A., Swogger, E., Wolcott, R., Pulcini, E., Secor, P., Sestrich, J., et al. (2008) Biofilms in chronic wounds. Wound Repair and Regeneration, 16(1): 37-44. DOI: 10.1111/j.1524-475X.2007.00321.x
Bjarnsholt, T., Kirketerp-Moller, K., Jensen, P.O., Madsen, K.G., Phipps, R., Krogfelt, K., et al. (2008) Why chronic wounds will not heal: a novel hypothesis. Wound Repair and Regeneration, 16(1): 2-10. DOI: 10.1111/j.1524-475X.2007.00283.x
Wolcott, R.D., Rhoads, D.D., Bennett, M.E., Wolcott, B.M., Gogokhia, L., Costerton, J.W., et al. (2010) Chronic wounds and the medical biofilm paradigm. Journal of Wound Care, 19(2): 45-53. DOI: 10.12968/jowc.2010.19.2.46966
Zimmerli, W., Widmer, A.F., Blatter, M., Frei, R., Ochsner, P.E. (1998) Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. JAMA, 279(19): 1537-1541. DOI: 10.1001/jama.279.19.1537
Lebeaux, D., Ghigo, J.M., Beloin, C. (2014) Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiology and Molecular Biology Reviews, 78(3): 510-543. DOI: 10.1128/MMBR.00013-14
Donlan, R.M., Costerton, J.W. (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clinical Microbiology Reviews, 15(2): 167-193. DOI: 10.1128/CMR.15.2.167-193.2002
Ceri, H., Olson, M.E., Stremick, C., Read, R.R., Morck, D., Buret, A. (1999) The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. Journal of Clinical Microbiology, 37(6): 1771-1776. DOI: 10.1128/JCM.37.6.1771-1776.1999
Anderl, J.N., Franklin, M.J., Stewart, P.S. (2000) Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrobial Agents and Chemotherapy, 44(7): 1818-1824. DOI: 10.1128/AAC.44.7.1818-1824.2000
Coenye, T., Nelis, H.J. (2010) In vitro and in vivo model systems to study microbial biofilm formation. Journal of Microbiological Methods, 83(2): 89-105. DOI: 10.1016/j.mimet.2010.08.018
Bjarnsholt, T. (2013) The role of bacterial biofilms in chronic infections. APMIS Supplementum, 121(s136): 1-58. DOI: 10.1111/apm.12099
Osmon, D.R., Berbari, E.F., Berendt, A.R., Lew, D., Zimmerli, W., Steckelberg, J.M., et al. (2013) Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases, 56(1): e1-e25. DOI: 10.1093/cid/cis803
Del Pozo, J.L., Patel, R. (2009) Infection associated with prosthetic joints. New England Journal of Medicine, 361(8): 787-794. DOI: 10.1056/NEJMcp0905029
Trampuz, A., Piper, K.E., Jacobson, M.J., Hanssen, A.D., Unni, K.K., Osmon, D.R., et al. (2007) Sonication of removed hip and knee prostheses for diagnosis of infection. New England Journal of Medicine, 357(7): 654-663. DOI: 10.1056/NEJMoa061588
Byren, I., Bejon, P., Atkins, B.L., Angus, B., Masters, S., McLardy-Smith, P., et al. (2009) One hundred and twelve infected arthroplasties treated with DAIR: antibiotic duration and outcome. Journal of Antimicrobial Chemotherapy, 63(6): 1264-1271. DOI: 10.1093/jac/dkp107
Senneville, E., Joulie, D., Legout, L., Valette, M., Dezeque, H., Beltrand, E., et al. (2011) Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus. Clinical Infectious Diseases, 53(4): 334-340. DOI: 10.1093/cid/cir402
Lynch, A.S., Robertson, G.T. (2008) Bacterial and fungal biofilm infections. Annual Review of Medicine, 59: 415-428. DOI: 10.1146/annurev.med.59.110106.132000
Del Pozo, J.L., Patel, R. (2007) The challenge of treating biofilm-associated bacterial infections. Clinical Pharmacology and Therapeutics, 82(2): 204-209. DOI: 10.1038/sj.clpt.6100247
Widmer, A.F., Frei, R., Rajacic, Z., Zimmerli, W. (1990) Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections. Journal of Infectious Diseases, 162(1): 96-102. DOI: 10.1093/infdis/162.1.96
Darouiche, R.O. (2004) Treatment of infections associated with surgical implants. New England Journal of Medicine, 350(14): 1422-1429. DOI: 10.1056/NEJMra035415
Chambers, H.F., DeLeo, F.R. (2009) Waves of resistance: Staphylococcus aureus in the antibiotic era. Nature Reviews Microbiology, 7(9): 629-641. DOI: 10.1038/nrmicro2200
Parsek, M.R., Singh, P.K. (2003) Bacterial biofilms: an emerging link to disease pathogenesis. Annual Review of Microbiology, 57: 677-701. DOI: 10.1146/annurev.micro.57.030502.090720
Fowler, V.G., Boucher, H.W., Corey, G.R., Abrutyn, E., Karchmer, A.W., Rupp, M.E., et al. (2006) Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. New England Journal of Medicine, 355(7): 653-665. DOI: 10.1056/NEJMoa053783
Trampuz, A., Widmer, A.F. (2006) Infections associated with orthopedic implants. Current Opinion in Infectious Diseases, 19(4): 349-356. DOI: 10.1097/01.qco.0000235161.85925.e8
Trampuz, A., Zimmerli, W. (2006) Antimicrobial agents in orthopaedic surgery: prophylaxis and treatment. Drugs, 66(8): 1089-1105. DOI: 10.2165/00003495-200666080-00005
Published
Issue
Section
License
Copyright (c) 2022 Divya Nair, et al.

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

