Wk 3 Blood and CV JW Intro (1).pdf

MD3012 Infectious Diseases Week 3 Blood, sepsis and cardiovascular infection Dr Jeffrey Warner A/Professor Microbiology...

MD3012 Infectious Diseases Week 3 Blood, sepsis and cardiovascular infection Dr Jeffrey Warner A/Professor Microbiology Biomedicine College of Public Health, Medical and Veterinary Sciences Room 87-004 Tel: 47816375 [email protected] Week 3: Infections of the blood and cardiovascular system Key Words Learning Outcomes Introductory Session Guided Learning Session Synthesising Session By the end of this week, you This session will introduce The GLS will focus primarily We will use a clinical case to superantigen should be able to: blood stream infections, on the Staphylococci and explore the microbiological endotoxin focussing on the progression Streptococci, and their factors associated with a LPS from bacteraemia to shock, associated toxins. You will patient presenting with exotoxin including the clinical and look at bacterial factors shock. septicaemia bacteraemia microbiological factors, which enable evasion of the sepsis including virulence host response, in addition to septic shock mechanisms. We will also the interactions occurring endocarditis look at endocarditis as an between the microbes and prosthetic valve example of a specific CV the host which result in the cytokine storm infection. pathology of cardiovascular rheumatic fever infections. rheumatic heart disease Describe the role of LPS in √ √ √ Readings the development of sepsis Describe the role of √ √ √ Mims 6th Ed superantigens in the Chap 18: p173-5 development of sepsis Chap 30: Fever of unknown Illustrate the burden of RHD √ origin in northern Australia and describe the management Sepsis-induced Apply a process to identify √ √ immunosuppression: from the infectious cause of cellular dysfunctions to sepsis immunotherapy Apply a process to identify √ the infectious cause of Tissue-Engineered Heart endocarditis Valve: Future of Cardiac Define the virulence factors √ √ Surgery and pathogenic mechanisms of the organisms within the Rheumatic heart disease: Genera Staphylococcus and infectious disease origin, Streptococcus chronic care approach. Review EM Wk 5 LO 5.2; 5.3  A few definitions… Bacteraemia: the presence of viable bacteria in the bloodstream Septicaemia: the persistence and invasion of pathogenic organisms in the bloodstream Septic Shock: the presence of bacteria and their toxins in the bloodstream, characterised by decreased blood flow to organs and tissues, hypotension, organ dysfunction and often multiple organ failure The bloodstream as a home for microbes Favourable conditions: Contains oxygen, water & nutrients Has a neutral pH Has an appropriate temperature Unfavourable conditions: Constantly moving Antimicrobial defence mechanisms Blood recirculates through spleen & liver Conditions required for infection 1. Organisms must be released in large numbers 2. Anatomical defect facilitating colonisation 3. Organisms overcome host defences 4. Impaired host defence  Safe havens for bacteria Anatomical abnormality – Damaged heart valves Bio-films on foreign material – Catheters, IV lines – Prosthetic valves, joints  At risk patients 1. Disruption or penetration of anatomical barriers - wounds, IV catheters, contaminated IV drugs 2. Devitalised tissue - necrotic tissue has no blood supply 3. Defective granulocyte function - chemotherapy, diabetes 4. Complement defects/deficiency 5. Splenic malfunction/absence  Bacteraemia to sepsis Sepsis is a blood stream infection plus evidence of a systemic response to the infection It is a clinical diagnosis, not a laboratory one Severe sepsis is associated with organ dysfunction, hypoperfusion or hypotension  Initiation of sepsis May be direct introduction of microbes into the bloodstream – eg, IV line and other device-associated infections Skin and soft tissue, respiratory, intra-abdominal infection Bacteraemia due to bacteriuria (urosepsis) may complicate cystitis in compromised hosts/elderly Overwhelming pneumococcal infection in patients with impaired or absent splenic function Pathophysiology is complex – Symptoms result from the effects of circulating bacterial products caused by sustained bacteraemia and cytokine release  Thinking of sepsis Does the patient have a potential source of infection? - likely an endogenous source Pneumonia Empyema UTI Acute abdomen Meningitis Infective endocarditis Bone or joint infection Skin or soft tissue infection Wound infection Other… Does the patient have new signs or symptoms of infection? Does the patient have evidence of organ dysfunction?  Investigations Blood culture (off antibiotics) – ID = Gram stain, catalase, coagulase Urine for microscopy, culture and sensitivity (MCS) Do not delay treatment as mortality increases by 7% per hour for the first 6 hours that treatment is inadequate (up to 42%) Imaging to identify foci of infection Abdominal CT scan of a 17-year- old boy showing two abscess cavities in the spleen  Gram negative bacteraemia Gram negative diplo-cocci: Neisseria meningitidis – Colonise nasopharyngeal region in ~25% population Gram negative rods: Pseudomonas (opportunistic) Escherichia coli – Colonise GI tract Klebsiella pneumoniae – Colonise GI tract Serious issues with emerging antimicrobial resistance  Pathogenesis of sepsis Gram negative bacteria LPS (endotoxin) IL-2 IFN- T lymphocyte gamma macrophage Superantigen Exotoxin IL-1 TNF-alpha Gram positive bacteria Activities of endotoxin Mims Figure 18.4 Gram positive cell wall Staphylococcus aureus Streptococcus pyogenes  Cardiovascular infections Infection of implantable devices – permanent pacemakers, implantable cardioverter defibrillators Endocarditis –infection of the endocardium (including heart valves) Pericarditis - inflammation of the heart lining (pericardium) – Cause often unknown, typically viral (Coxsackie B virus), generally mild and resolves on its own Myocarditis - inflammation of the heart muscle (myocardium) – Ranges from asymptomatic to severe heart failure – Usually viral cause – diffuse inflammation; Coxsackie B virus, enteroviruses – If bacterial or fungal – focal infection, secondary to seeding from bloodstream or extension from adjacent organs – Serum troponin is a useful clinical biomarker  Risk Factors for CIED infections Host related Procedure related Congestive heart failure Lack of antibiotic Diabetes prophylaxis Warfarin therapy Operator experience Renal insufficiency Implantation technique History of implant replacement Infection occurs via: *1: Contamination during time of implantation, erosion of device through intact skin 2: Haematogenous seeding of device from distant focus of infection  Endocarditis Inflammation of the endocardium - usually associated with the valves Likely pathogen depends on: 1) Condition of valve (abnormal, prosthetic) - RHD↓, heart disease↑ 2) IV drug user -highest incidence at 1-5%/yr 3) Healthy patient - no underlying conditions - relatively uncommon - requires organism of high virulence  Clinical Presentation Type of clinical presentation has implications for aetiology 1. Sub-acute endocarditis (~60% Streptococci: viridans, Group D, Enterococci, Coxiella/Q Fever in Australia - Poorly defined onset - Symptoms lasting weeks/months 2. Acute endocarditis (~60% S. aureus – native and PV) - acute onset of symptoms - symptoms occurring days before presentation *  Pathogenesis of IE Adherence of Abnormal heart Fibrin and bacteria and valve platelet production of deposition vegetations Mitral valve vegetations  Causative organisms Abnormal/damaged IV drug user: valve: Staphylococcus aureus Staphylococcus aureus Oral streptococci Oral streptococci Enterococcus Coag neg Staphylococcus Gram neg (enteric) bacteria Enterococus Group D streptococci  Causative organisms cont. Prosthetic valve (2m): Coagulase neg staphylococci Staphylococcus aureus Staphylococcus aureus Coagulase neg staphylococci Gram neg (enteric) bacteria Oral streptococci Oral streptococci Enterococcus Gram neg (enteric) bacteria  Diagnosis of IE Based on a combination of clinical, microbiologic and ECG findings Modified Duke criteria is useful – 2 major or 1 major + 3 minor criteria – Q-fever serology indicative of chronic disease is now included as a major criteria Relies on multiple +ve blood cultures with usual pathogens, ECG evidence of vegetation or abscess, and predisposing cardiac valvular disease  Treatment of IE Antibiotic therapy – Oral Strep: IV PenG for 4 weeks – MSSA: beta-lactamase resistant penicillin – PVE: β-lactam + gentamicin + rifampin Cardiac surgery on valve – Early if infection is uncontrolled and life-threatening – Late if valve damage is progressive Prevention - Prophylactic antibiotics for at risk patients (?)  Microbial virulence factors contributing to infection 1: Microbial adherence Surface proteins; capsular polysaccharides; fibrinogen binding proteins; pili 2: Biofilm formation Polysaccharide intercellular adhesins 3: Microbial persistence Immune evasion Bacterial attachment & biofilms Biofilm formation is universal for all device related infections Type 1 pilus-mediated bacterial attachment to the bladder epithelium  Gram positive cocci Clusters Chains Staphylococci/catalase +ve Streptococci/catalase -ve Haemolysis patterns Beta–haemolysis (Effect on red blood cells) (complete) Alpha-haemolysis (partial) Gamma–haemolysis = no haemolysis  Staphylococcus Gram positive cocci in clusters Mix of high and low virulence species in genus Separated on basis of coagulase production Staphylococcus Coagulase positive Coagulase negative (CoNS) Staphylococcus aureus Staphylococcus epidermidis + others  Oral Streptococci Viridans streptococci – Streptococcus mutans Normal flora of the oral cavity Alpha–haemolytic streptococci Transmitted to bloodstream via dental work, poor oral hygiene Low virulence organisms  Streptococcus pyogenes (GAS) Gram positive coccus in chains Beta-haemolytic Cause of rheumatic fever/RHD Cross reaction of Ab between M protein on GAS and heart valve tissue GAS & Rheumatic heart disease