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Biofilms by Mind Map: Biofilms

1. Infective Endocarditis

1.1. Annual Incidence 2-3/100,000

1.1.1. Elderly > risk,

1.1.2. Early Death 20%

1.1.3. 2/3 Abnormal valve (often unrecognised pre- IE presentation) Rheumatic fever Degenerative valve disease

1.2. Abnormalities predisposing to IE

1.2.1. Rheumatic fever (elderly or imported) Tissue destruction Strep. pyogenes, antibody cross reactivity Type II Hypersensitivty

1.2.2. Prosthesis

1.2.3. Valve surgery/prosthesis

1.2.4. Intra cardiac device Pacemaker/defibrillator

1.2.5. Mitral valve prolapse

1.3. 30 % Staphylococci (Most common cause)

1.3.1. S. aureus and coagulase negative

1.3.2. IV drug abuse, haemodialysis Tricuspid

1.3.3. Iatrogenic IV catheter related

1.3.4. Acute Large Vegetations Rapid Onset

1.4. Streptococci (decreasing in incidence)

1.4.1. Alpha-haemolytic,

1.4.2. Subacute Vegetations Gradual Onset

1.5. Detection

1.5.1. Blood culture Blood should be sterile on culture Bacteraemia Transient Continuous Intermittent

1.5.2. Blood Culture-II 1. Venipuncture into Liquid medium Aerobes, Anaerobes 2. Three samples (0, 30, 90 min (L af, R af, L/R af)) Sensitivity increases with sample volume 99% pathogens detected by 3 cultures Antibacterial blood neutralised by SPS Optimum blood:broth ratio Samples via lines if line infection 3. Growth/Processing 5 days @ 37°C Longer in IE, PUO 4. After growth, Microscopic detection, Gram stain G+ chains, probably Streptococcus 5. Full ID: culture on solid media

1.6. Diagnosis

1.6.1. Difficult variable signs and symptoms

1.6.2. Duke criteria Pathology and clinical Major Minor

1.6.3. Definite: Possible: Excluded Definite by Pathological data: microorganism in the heart Definite by Clinical data: Major/minor

1.6.4. Pathology Cardiac failure destruction of heart valve Embolism (septic) Vessel damage from inflammation of the blood vessels (Vasculitis) or Microscopic clots, which damage the small capillaries (micro-emboli) Stroke, Janeway lesion Roth Spots Immune complex disease Glomerulonephrtis, arthritis Petechiae, Osler’s nodes, Roth spots Bacteraemia Splenomegaly, anaemia

1.6.5. Transoesophageal Echocardiogram TOE (TEE)

1.6.6. Mitral Vegetation Friable – can embolise (septic embolism

1.6.7. Prosthetic valve endocarditis

1.7. IE Types and associated bacteria

1.7.1. Abnormal native valve Congenital defects (especially turbulent flow) Rheumatic fever, degenerative (calcific) disease Mitral valve prolapse (5 -10 X risk) Pathogen usually mouth/gut/urinary tract Streptococcus Enterococcus Dental issues

1.7.2. Normal valve consequence of bacteraemia Staph. aureus Strep pneumoniae Iatrogenic : cannula Self inflicted IVDA ( often tricuspid) S. aureus, Pseudomonas, Yeasts.

1.7.3. Prosthetic valve Prosthetic valve; 20% cases <2% risk, first year after surgery- 0.5 % Annual risk > 1 year out

1.7.4. Culture Negative Coxiella burnetti and Bartonella spp.

1.8. Treatment

1.8.1. Vegetation impenetrable to phagocytes Bactericidal antibiotics required

1.8.2. Synergistic combinations Combination Therapy Empirical therapy of life-threatening infection Mixed infections Avoidance of resistance e.g. TB Synergy: penicillin and aminoglycoside Antagonism : penicillin and tetracycline Toxicity sparing : amphotericin B and 5-flucytosine

1.8.3. MIC of organism is essential MIC= Minimum Inhibitory Concentration lowest concentration of antimicrobial preventing growth

1.8.4. IV min 2 weeks

1.8.5. Streptococcal endocarditis MIC = < 0.125 mg/L >0.125 mg/L

1.8.6. Enterococci/ Streptococci MIC >0.5 <4.0 mg/L Ampicillin/amoxycillin – 2 g q4h iv for 4-6 weeks Amoxycillin MIC > 4mg/L Vancomycin 1G BD & Gentamicin 1mg/kg q12h iv Vancomycin MIC > 4mg/L Difficult Linezolid, daptomycin

1.8.7. Staphylococci Methicillin sensitive Flucoxacillin- 2g every 4- 6 IV daily, 4 weeks ( 12g daily) Prosthesis (PVE): Plus Gentamicin- 1 mg/kg BD & Rifampicin for 6 weeks Methicillin resistant or allergic Vancomycin 1g BD 4 weeks, with levels plus Rifampicin 300-600 mg q12 po Prosthesis (PVE): Plus Gentamicin- 1 mg/kg q12h iv 2 weeks plus BD twice daily

1.8.8. Laboratory Monitoring Gentamicin levels - pre dose trough <1mg/L Peak dose 1 hr post dose 3-5 mg/L CRP/ESR Creatinine WCC and platelets

1.9. Something Extra



2. Bacteriaemia-from biofilm-forming bacteria

2.1. Streptococcus mutans etc viridans

2.1.1. Teeth/Oral

2.1.2. Vascular damage/ Leak promoting activity Oral manipulations Scale and Polish Root Canal Dental extraction

2.2. Staphylococcus epidermis (S.aureus)

2.2.1. Intravascular catheter

2.2.2. Colonisation

2.2.3. Fluid infusion

2.2.4. Invasive surgery

2.2.5. Coagulase Neg or Positive

2.3. Bacteraemia gives access to abnormal heart valve

3. Biofilm Infections

3.1. Oral- Dental plaque

3.1.1. Removed by flossing/brushing

3.1.2. Rapidly re-forms

3.1.3. Streptococcus mutans prominent

3.1.4. Causes gum inflammation (gingivitis)

3.1.5. Plaque Microbiome

3.2. Intravenous catheter colonisation

3.2.1. Staphylococcus epidermidis

3.2.2. (S. aureus)

3.2.3. Biofilm formed

3.2.4. Source of Bacteriaemia

3.3. Endocarditis

3.4. Prosthetic and Shunt infections

3.4.1. Neurosurgery: Shunts Important to reduce skin organism (CnS) biofilm infection of shunt

3.4.2. Cardiology: Stents

3.4.3. Urology: Urinary catheter

3.4.4. All clean Surgery apart from urinary catheters, - Skin source of infection - <5% Infection rate , except Urinary catheter

3.4.5. Orthopaedic: Joints A. Infected prosthetic joint B. Replacement of infected prosthesis by antimicrobial containing spacer C. Later insertion of prosthesis

3.5. UTI Basics

4. Learning objectives

4.1. Bacterial biofilms

4.1.1. Sessile community of bacteria Cell attachment interface/ each other substratum Matrix of Extracellular Polymeric substances Sticky Altered Phenotype Growth rate + gene transcription Mediated by Gene Regulation

4.1.2. Key concept, therapeutic relevance Antibiotic resistant Slow growing Difficult to eradicate

5. GM 1002 2017

5.1. Dr John Mac Sharry, School Of Medicine , UCC, Cork, Ireland