Antibiotic resistance of bacterial biofilms

Høiby, Niels; Bjarnsholt, Thomas; Givskov, Michael; Molin, Søren; Ciofu, Oana

doi:10.1016/j.ijantimicag.2009.12.011

Cited by 2,761 publications

(2,218 citation statements)

References 110 publications

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“…The degradation of β-lactam antibiotics by β-lactamases, the binding of aminoglycoside antibiotics to the alginate matrix of mucoid P. aeruginosa biofilms and the inhibition of the activity of tobramycin by lung mucus in cystic fibrosis patients are all examples of unwanted interactions of the antimicrobial agent with the biofilm or the surrounding tissue. [20,40,41] Mugabe et al evaluated the antimicrobial activity of three different liposomes (DMPC:Chol, DPPC:Chol, DSPC:Chol) encapsulating gentamycin against biofilms of several clinical strains of P. aeruginosa. [42] All liposomes showed a significantly higher antimicrobial activity compared to the free antibiotic.…”

Section: Protection Of the Antimicrobial Agentmentioning

confidence: 99%

“…In addition, if lipid-based nanoparticles bind to bacteria, fusion with the bacterial wall may be induced, allowing antibiotic delivery directly into the cytoplasm (see section 2.1.1). [20,120] A classic way to determine the amount of liposomes adsorbed to the biofilm is to calculate the percentage apparent monolayer coverage (%amc). This is done by radioactive labeling of the liposomes and scintillation counting of a biofilm which is exposed to the liposomes and rinsed to remove non adhered liposomes.…”

Section: Studying the Interaction And Transport Of Nanoparticles In Bmentioning

confidence: 99%

“…Several mechanisms of antimicrobial resistance and tolerance have been suggested such as limited diffusion of antimicrobial agents in the biofilm matrix, deactivation of the antimicrobial agent in the outer layers of the biofilm via binding to matrix components or enzymatic modification and the occurrence of niches in the biofilm with less sensitive cells, including starved cells and persister cells. [15,17,[19][20][21] There is an urgent need for innovative strategies that are able to overcome these mechanisms of resistance. One possible approach which is gaining considerable interest is the use of nanoparticles for antimicrobial drug delivery.…”

Section: Introductionmentioning

confidence: 99%

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Lipid and polymer nanoparticles for drug delivery to bacterial biofilms

Forier

Raemdonck

Smedt

et al. 2014

Journal of Controlled Release

370

320

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Biofilms are matrix-enclosed communities of bacteria that show increased antibiotic resistance and the capability to evade the immune system. They can cause recalcitrant infections which cannot be cured with classical antibiotic therapy. Drug delivery by lipid or polymer nanoparticles is considered a promising strategy for overcoming biofilm resistance. These particles are able to improve the delivery of antibiotics to the bacterial cells, thereby increasing the efficacy of the treatment. In this review we give an overview of the types of polymer and lipid nanoparticles that have been developed for this purpose. The antimicrobial activity of nanoparticle encapsulated antibiotics compared to the activity of the free antibiotic is discussed in detail. In addition, targeting and triggered drug release strategies to further improve the antimicrobial activity are reviewed. Finally, ample attention is given to advanced microscopy methods that shed light on the behavior of nanoparticles inside biofilms, allowing further optimization of the nanoformulations. Lipid and polymer nanoparticles were found to increase the antimicrobial efficacy in many cases. Strategies such as the use of fusogenic liposomes, targeting of the nanoparticles and triggered release of the antimicrobial agent ensured the delivery of the antimicrobial agent in close proximity of the bacterial cells, maximizing the exposure of the biofilm to the antimicrobial agent. The majority of the discussed papers still present data on the in vitro anti-biofilm activity of nanoformulations, indicating that there is an urgent need for more in vivo studies in this field.

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Section: Protection Of the Antimicrobial Agentmentioning

confidence: 99%

Section: Studying the Interaction And Transport Of Nanoparticles In Bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lipid and polymer nanoparticles for drug delivery to bacterial biofilms

Forier

Raemdonck

Smedt

et al. 2014

Journal of Controlled Release

370

320

View full text Add to dashboard Cite

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“…Conversely, chronic infections are where there is a delay in the healing process (an inability of the injured site to restore anatomical and functional integrity), consistent with the severity of the injury [9]. The presence of biofilms and their innate ability to tolerate antibiotics up to 1000 times greater than planktonic cells, is thought to delay wound restoration [10][11][12][13]. Cells assuming the biofilm phenotype are commonly observed in patients with various underlying conditions, which can be system wide in the case of immunodeficiency and diabetes, or more focused in the case of venous leg ulcers and cystic fibrosis (CF).…”

Section: Introductionmentioning

confidence: 99%

“…In the case of CF, chronic biofilm infections have been known to persist in the airways for over 30 years. Therefore, chronic infections are an ever increasing problem due to their recalcitrance towards extensive antibiotic treatment regimes and persistence under sustained attack from the host's innate and adaptive immune response systems [10,14].…”

Section: Introductionmentioning

confidence: 99%

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

Roberts

Kragh

Bjarnsholt

et al. 2015

Journal of Molecular Biology

Self Cite

173

153

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We have become increasingly aware that during infection, pathogenic bacteria often grow in multicellular biofilms which are often highly resistant to antibacterial strategies. In order to understand how biofilms form and contribute to infection, in vitro biofilm systems such as microtitre plate assays and flow cells, have been heavily used by many research groups around the world. Whilst these methods have greatly increased our understanding of the biology of biofilms, it is becoming increasingly apparent that many of our in vitro methods do not accurately represent in vivo conditions. Here we present a systematic review of the most widely used in vitro biofilm systems, and we discuss why they are not always representative of the in vivo biofilms found in chronic infections. We present examples of methods that will help us to bridge the gap between in vitro and in vivo biofilm work, so that our bench-side data can ultimately be used to improve bedside treatment.

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