Prevention and treatment of clinical biofilms Flashcards
Prevention of biofilms
porphylactic antibiotics
early aggressive antibiotics
antibiofilm surfaces
Treatment of biofilms
chronic suppressive antibiotic therapy, debridement (wound care to remove non-viable tissue, foreign material, and biofilm from the wound bed.), device removal
Pseudomonas aeruginosa biofilms in Cystic Fibrosis - treatment of intermittent infections
Isolation and hygienic measures. Early aggressive eradication therapy: Oral ciprofloxacin and nebulised colistin 3 weeks - 3 months, Nebulised monotherapy using tobramycin, nebulised DNase (pulmozyme). Cost effective & delays development of chronic infections in CF children.
Pseudomonas aeruginosa biofilms in Cystic Fibrosis - treatment of chronic infections
Chronic Infections:
CI: Persistent for 6 months, and/or rise in antibodies against P. aeruginosa. Chronic suppressive antibiotic therapy: Daily nebulised Colisitn or tobramycin for life, combined with: 2-week courses IV antibiotics every 3 months
or adhoc IV therapy as needed. suppressive therapy slows decline of pulmonary function prolonging life but has side effects: allergy- immediate or developed antimicrobial resistance
Quorum sensing
- Communication system used by many bacteria to coordinate gene expression , regulating various bacterial behaviours including pathogenic factor production/ biofilm formation, antibiotic resistance.
- Targeting Quorjum sensing mechanisms to develop antimicrobial strategies.
Bacterial Communities - Quorum sensing for bacterial survival
- Difference in gram neg vs gram pos
Bacteria spend most of their time free living in environment
Can find themselves suddenly in a different environment – communicate to find more bacteria around them increasing chance of building a colony and living. QS targeted in antimicrobial stratergies.
Quorum sensing:
mediated by autoinducers
Gram-positive bacteria: peptides
Gram-negative bacteria: mostly N-acyl-L-homoserine lactones (AHL)
Quorum sensing inhibitors (QSI)
What is used in Cystic Fibrosis?
Antibiotics inhibit QS when used at sub-MIC concentrations: Ceftazidime, Ciprofloxacin , Azithromycin, Clarithromycin. Azithromycin continuous treatment improves lung function in people with CF- risks development of macrolide resistance in other potential pathogens e.g., S. aureus. Usually just used to kill bacteria but theres growing interest in its effects on QS. Naturally occurring QSIs in garlic & ginseng
Quorum sensing inhibitors in P. aeruginosa ( Cystic Fibrosis)
P. aeruginosa has multiple QS systems
las: master QS regulator: transcriptional regulator protein allowing for cell-tocell communication to coordinate gene expression in response to population density.
Controls expression of genes involved in virulence factor production in P.aeruginosa
LasR inhibitors: LasR: regulator, Binds the AI. Inhibit LasR-AI( associated auntoinducer)-> inhibit QS: QSI binds LasR in active site, Impaired biofilm formation
Prevention and treatment of biofilms
New strategies needed
quorum sensing inhibitors, attachment blockers, molecules to dissolve biofilm matrices, bacteriophage
Inhibition of curli fibres and type I pili
- Bacteria use amyloid fibres on their surfaces to interact with biofilm
Peptide drugs e.g. FN075 block formation of fibres: anti-biofilm and anti-virulence activities. Green tea: anti-biofilm properties
Attachment blockers - dental plaque
- Streptococcus mutants part of dental plaque
-Streptococcus mutants capable of synthesising EPS
-Glucosyltransferases (three different types): GtfB – insoluble with many 1.3 linkages, GftD – soluble, GtfC – amalgam of soluble and insoluble
-Carbohydrate derivatives (6-Deoxy sucrose and Trichloro-galactosucrose) identified as the most promising GtfC inhibitors
-Attachment blockers studied to prevent attachment of Fusobacterium necrophorum in dental plaque
Bacteriophage therapy - Preventing formation of biofilms and quorum sensing
Bacteriophages: Viruses that infect and kill bacteria, used to treat bacterial infections.
Primarily targets bacterial growth and viability but potentially disrupts bacterial communication systems and prevent biofilm formation. Types: Genetically Modified Phage, Phage Lysin Depolymerases or Phage Derived Enzymes, Combination of Phage and Antibiotics, Mono Phage Therapy, Phage Cocktail
Foreign Body Infections
Diagnosis: may be culture negative: sonication of indwelling devices/PCR-based detection
Foreign body infections - treatment & prevention
Treatment: Long term treatment with high doses & combinations of antibiotics. Replacement would be good. Life-long suppressive therapy
Prevention Biomaterial approaches e.g plastics impregnated/ coated with antibiotics, silver, guranones, anti-adhesive surface properties. Chelating agents ( Mg 2+ and Ca2+ are important in biofilm formation)
Antibiofilm surfaces for medical devices ( materials)
- Use of a phage cocktail to prevent S. aureus biofilm formation (crystal violet assay) - https://enviromicro-journals.onlinelibrary.wiley.com/doi/abs/10.1111/j.1472-765X.2012.03205.x .
Good review of types of materials developed to inhibit biofilm formation: Metal, Polymers, Antiadhesive surface modifications, Incorporation of antimicrobials into materials.
