Prevention and control of biofilm-based medical-device-related infections

Prevention and control of biofilm-based medical-device-related infectionsAlvin Coda, PGY-1Loma Linda University Medical CenterEffects of catheter-related infections~1.8 million patients develop healthcare-associated infections (HAI)Bloodstream, urinary tract, and surgical site infections>98,000 associated deaths annually

Central venous catheters = MCC of HAI blood infectionsProlong hospital staysIncrease healthcare costs

Urinary tract = MC site of nosocomial infectionSurgical site infections1-3% hip implant failures due to infection (2.7-18% associated M&M)

Role of biofilms in catheter-related infectionsMicrobial biofilms provide suitable environment to amplify antibiotic- resistance.Slow/incomplete antibiotic penetrationPhysiologic response of microorganisms to heterogeneous chemical environment Subpopulations of dormant, non-dividing bacterial cellsPolymicrobial (fungal and bacterial) communitiesProduces fitness advantage (e.g. S. aureus and C. albicans)Biofilms represent an ideal niche for plasmid exchange among bacteria. In fact, the conjugation frequency appears to be higher in bacteria growing in the sessile mode than in the planktonic mode. Thus, because some plasmids contain genes coding for multidrug resis- tance, microbial biofilms provide a suitable environment to amplify both naturally occurring and induced antibiotic- resistance phenomena.

In fact, in vitro studies on polymi- crobial biofilms comprising Candida albicans and Staphylococcus epidermidis demonstrated an altered sensitivity of each species to antimicrobial agents as a result of their mutual interaction: the S. epidermidis extracellular polymer inhibited fluconazole penetration, while C. albicans ap- peared to protect S. epidermidis against vancomycin (Adam et al., 2002).3Role of biofilms in catheter-related infectionsMechanism of biofilm formation

Francolini et al 2010Stage 1: microbial adhesion to the surface. Stage 2: exopolysaccharide production andthree-dimensional biofilm development. Stage 3: detachment frombiofilm of single and clustered cells.4Antibiofilm strategies?

Inhibition of microbial adhesion to the surface (a) and of colonization (b) Hyaluronic acid, poly-N-vinylpyrrolidone, and heparin coatingsSilver alloy, nitrofurazone-coated silicon, gentaicin-coated polymethylmethacrylateInterference with the signal molecules modulating biofilm developmentDisaggregation of the biofilm matrix.Francolini et al 2010Microbial adhesion is a dynamic and biphasic process involving an early stage in which microorganisms reversibly interact with the device surface by van der Waals forces and H-bonds, and a second step with irreversible microbial adhesion mediated by specific adhesins able to recognize the host proteins (fibronectin, fibrin, etc.) layered as a conditioning film on the device surface. Once adhered, microorganisms duplicate and develop as microcolonies over the entire surface, these representing the building blocks of the biofilm.5Antimicrobial-coated CVCsMost only effective in short-term (5-8 days)Chlorhexidine/silversulphadiazine (CH/SSD)Questionable efficacy in reducing blood infectinoSilver impregnatedNo gram + actionsRifampicin-miconazole CVCsStatistically significant reduction (short-term)Minocycline-rifampicin-coated CVCs Most efficacious; up to 60 days in some casesNot active vs P. aeruginosa or Candida spp.Decreased coag-negative Staph, increased Candida sppPitfalls:Burst release of antibiotics (hrs), slow release @ very low [Abx]

Newest Antimicrobial-coated CVCsPore-forming polymers: PEG and AlbuminConsistent, controlled release over timeEx. PEG + cefamandole + rifampicin active vs rifampicin-resistant S. aureus for up to 23 days

Prevention of biofilm formationQuorum sensingDiffusible molecular signaling involved in modulation of: Specific enzymes/resistance developmentVirulence factorsMetabolitesQS Inhibitors:Usnic acid: inhibits P. aeruginosa biofilm formation (not growth)RNAIII-inhibiting peptide (RIP): S. aureus bacteriostasis and synergy w/ antibiotics, as well as biofilm inhibition.

Dispersin B: prevents Staph spp. glucosamine formation and accumulationDecentralized process of coordinating behaviors8Biofilm present; Now what?Stand-alone agents: Daptomycin, minocycline, & tigecyclineCombination therapies: Staph biofilms: Vanco/Linezolid + Rifampicin Staph spp.Silver + Cipro S. epidermidisAnprocide + bacitracin/oxacillin Staph spp.Dispersin B + cefamandole S. epidermidisP. aeruginosa biofilms: AGs + fosfomycinTobramycin + furanone (QS-interference)Candidal biofilmsAntifungal + high-dose doxy C. albicansBiofilm present; Now what?Novel In-vitro studiesBioelectric effectUltrasound + gentamicinPhotodynamic therapyNanoparticles (iron-oxide based)Dispersin B bacteriophages Staph and PseudomonalQuestions?ReferencesAppelgren P, Ransjo U, Bindslev L, Espersen F & Larm O (1996) Surface heparinization of central venous catheters reduces microbial colonization in vitro and in vivo: results from a prospective, randomized trial. Crit Care Med 24: 14821489.Aslam S (2008) Effect of antibacterials on biofilms. Am J Infect Control 36: S175.e911.Casey AL, Mermel LA, Nightingale P & Elliott TS (2008)Antimicrobial central venous catheters in adults: a systematic review and meta-analysis. Lancet Infect Dis 8: 763776. I. Francolini, G. Donelli, Prevention and control of biofilm-based medical-device-related infections, FEMS Immunol Med Microbiol, 59 (2010) 227-238.Lorente L, Lecuona M, Ramos MJ, Jimenez A, Mora ML & Sierra A (2008) The use of rifampicin-miconazole-impregnated catheters reduces the incidence of femoral and jugular catheter-related bacteremia. Clin Infect Dis 47: 11711175.