BMFL2 Streptococci 23 NR.pptx

Leading the world to better health RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: BMFML2 Streptococci Class: Year 1 Course: Undergraduate Medicine Lecturer: Prof. Manaf Al-Qahtani Date: 9th November 2023 LEARNING OUTCOMES By the end of the lectur...

Leading the world to better health RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: BMFML2 Streptococci Class: Year 1 Course: Undergraduate Medicine Lecturer: Prof. Manaf Al-Qahtani Date: 9th November 2023 LEARNING OUTCOMES By the end of the lecture you will be able to……… 1. Outline the basic laboratory features of clinically important streptococci 2. Discuss the epidemiology of clinically important streptococci 3. Describe the pathogenesis of infections caused by clinically important streptococci 4. Recognise & describe the clinical features and complications of infections caused by clinically important streptococci 5. Outline the diagnosis of infections caused by clinically important streptococci 6. Choose the appropriate antimicrobial agents to treat infections caused by clinically important streptococci 7. Use the appropriate measures to prevent the acquisition and spread of streptococcal infections INTRODUCTION • Streptococci represent a diverse group of gram positive organisms • Many normally colonize mucosal membranes – Predominant component of respiratory, gastrointestinal and genital tract – Many of low virulence – However may also invade normally sterile body sites, causing significant disease STREPTOCOCCI: BASIC LABORATORY FEATURES • Gram-positive cocci – Chains (long or short) or pairs (diplococci) • Optimal growth media supplemented with blood – May cause haemolysis on blood agar • Catalase* negative • Most are facultative anaerobes – Some are strict (obligate) anaerobes *For more on catalase see Staphylococci lecture CLASSIFICATION SYSTEMS Most commonly used classification systems: 1. Based on their actions on blood-containing agar (Haemolysis) 2. Based on antigens contained in their cell walls (Lancefield classification) 3. Molecular classification (newer) - based on emm gene (encodes for M protein) Some clinically important streptococci often referred to by both Lancefield group and haemolysis pattern Streptoco cci  haemolyti c Reduce Hb and cause a greenish discolouration of blood agar  haemolyti c Lyse blood cells & cause complete clearing of blood agar in the vicinity of their growth γ haemolyti c No change in blood agar LANCEFIELD CLASSIFICATION • • • • Serological system of grouping streptococci Based on specific antigens present in their cell walls Groups A-G of most clinical significance Basis of test: – Antibody / antigen reaction – Positive if agglutination is detected CLINICAL CASE 1 • A 10yo male attends his GP with a sore throat • On examination he has swollen, erythematous tonsils with exudate. Cervical lymph nodes are swollen & tender Which one of the following is the most likely diagnosis in this instance? A. Bloodstream infection B. Cellulitis C. Erysipelas D. Pharyngitis E. Scarlet fever A throat swab is taken and following culture, Gram staining and microscopy, the following is seen. Which one of the following best describes this Gram stain? A. Gram-negative cocci in chains B. Gram-negative diplococci C. Gram-positive coccobacilli D. Gram-positive cocci in chains E. Gram-positive diplococci Which one the following is most likely causing this infection? A. Corynebacterium diptheriae B. Streptococcus pneumoniae C. Staphylococcus aureus D. Streptococcus pyogenes E. Staphylococcus epidermidis Streptococcus pyogenes displays which one of the following haemolytic patterns on blood agar? A. Alpha haemolysis B. Beta Haemolysis C. Gamma haemolysis Beta-Haemolytic Strep are further classified using which one of the following classifications systems? A. Biofilm formation ability B. Catalase production C. Coagulase production D. Lancefield grouping E. O antigen classification CLINICALLY IMPORTANT STREPTOCOCCI 1. 2. 3. 4. Strep. pyogenes (Group A,  -haemolytic) Strep. agalactiae (Group B,  -haemolytic) Other  -haemolytic streptococci  -haemolytic streptococci - “viridans” streptococci - Strep. pneumoniae (pneumococcus) 5. Enterococci (Group D,  - or non-haemolytic) 6. Peptostreptococcus (anaerobic or non-haemolytic) 1. STREPTOCOCCUS PYOGENES (GROUP A,  -HAEMOLYTIC STREPTOCOCCI) • Beta-haemolytic streptococci • Possess the Lancefield group A antigen • Commonly colonise oropharynx of children & young adults – Colonisation is transient – Influenced by acquired immunity & competition from other organisms in the oropharynx • Among the most prevalent of human bacterial pathogens • Major cause of bacterial pharyngitis GROUP A STREPTOCOCCI: IRISH EPIDEMIOLOGY • Invasive group A strep = notifiable disease Pathogen Number laboratoriesbyyear-end %Coverage of population 2016 2017 Year 2018 38 97% 37 99% 39 100% 38 100% 36 93% 118 117 110 93.2% 7.0% 111 110 89 80.2% 4.7% 110 102 95 86.4% 2.9% 85 84 77 90.6% 4.9% 30 29 23 76.7% 13.3% 2019 2020* Group A streptococci Number of isolates of which notified to publichealth Number emm-typed %emm-typed %Erythromycin-R* Source: HPSC %Trends2016-2020 GROUP A, HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS Several virulence factors involved in causing disease: • Structural components: • Capsule: resists phagocytosis • Cell wall: peptidoglycan can activate alternative complement pathway • M-proteins : • >80 types, mediate attachment to cells, anti-phagocytic • Major virulence factors – some types associated with greater severity of disease • M-like proteins…. Bind IgG/ IgM GROUP A, HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS Cytolysins: • Streptolysin O/S exotoxins – ASOT titre • Hyaluronidase – Tissue destruction, allowing spread of infection • Leucocidin • Haemolysins • Streptokinase Pyrogenic (erythrogenic) exotoxins • Responsible for rash, fever • Potent activators of immune system (toxic shock syndrome) • Activation of T-cells leads to increased secretion of proinflammatory cytokines • Produced by both antigen presenting cells and T lymphocytes PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) 1. Droplet spread 2. Direct contact with e.g., infected wounds Get in – Portal of Entry Get out and spread further M proteins Exotoxins Haemolysins Hyaluronidase Leucocidin Streptokinase Cause damage to host cells Colonises oropharynx Invades epithelial cells Attach to cells Defeat/evade the immune system M protein Capsule = resists phagocytosis CLINICAL INFECTIONS • Suppurative infection: 1. Pharyngitis 2. Scarlet fever 3. Erysipelas, cellulitis, necrotising fasciitis 4. Toxic shock syndrome, bloodstream infection • Post-Infectious immune-mediated complications: – Rheumatic fever* • May later develop rheumatic heart disease – Glomerulonephritis *(Note GAS a very unusual case of infective endocarditis (IE) – but RHD predisposes to IE by other organisms later on) (Commonly confused by students) 1. STREPTOCOCCAL PHARYNGITIS • One of the most common bacterial infections of childhood • Occasionally due to Group C or G • Spread: Person-to-person via droplets (saliva or nasal secretions) • Facilitated by overcrowding • Incubation period: • History: 2-4 days • Sore throat • Fever, headache • Nausea + vomiting (especially children) 1. STREPTOCOCCAL PHARYNGITIS • On examination: • Redness, oedema, lymphoid hyperplasia • Enlarged tonsils with exudate, enlarged tender lymph nodes • Fever • Laboratory findings • positive throat culture • immunological (antibody) response (anti-streptolysin O titre, ASOT) Hyperaemic, enlarged tonsils with exudate Slide: A Colour Atlas of Infectious Diseases, Emond COMPLICATIONS 1. Suppurative complications: – Quinsy – peritonsillar abscess – Otitis media – Acute mastoiditis 2. Non-suppurative (immunological) sequelae: – Acute glomerulonephritis – Acute rheumatic fever Main reason for antibiotic treatment is to prevent rheumatic fever A FOUR YEAR OLD GIRL PRESENTS TO THE GP WITH AN ERYTHEMATOUS, PAPULAR, BLANCHING RASH ON HER ARMS AND TRUNK THAT HAS A “SANDPAPER” FEEL. WHICH OF THE FOLLOWING IS THE MOST LIKELY INFECTION? A. B. C. D. E. Cellulitis Erysipelas Impetigo Necrotising fasciitis Scarlet fever 2. SCARLET FEVER ‘Scarletina’ • Delayed-type skin reactivity to pyrogenic toxin produced by the organism • Pharyngitis + rash • May also occur following impetigo 3. SKIN AND SOFT TISSUE INFECTION • • • • Impetigo Erysipelas Cellulitis Necrotising fasciitis These will be covered in more detail in the ‘Skin and Soft Tissue Infections Lecture’ 4. OTHER SERIOUS INFECTIONS • Streptococcal toxic shock syndrome • Soft tissue inflammation followed by pain, fever, chills, multi-organ failure • Pyrogenic exotoxin production • Rapidly progressive • Bloodstream infection • Mortality approaches 40% COMPLICATIONS: RHEUMATIC FEVER & GLOMERULONEPHRITIS Post-streptococcal auto-immune complications • Affect a minority of people who have group A streptococcal infection • Immune reaction: Development of antibodies to some fraction of the organism – In rheumatic fever: the antibodies cross-react with cardiac tissue  immune complex deposition on the heart – In post-streptococcal glomerulonephritis: immune complexes are deposited on the glomerular basement membrane – Molecular mimicry ACUTE RHEUMATIC FEVER • • • • Associated with streptococcal pharyngitis but NOT with streptococcal skin infections Occurs 2-3 weeks later Fever, joint pains and carditis • With recovery, affected heart valves become thickened and deformed • • May also get neurological involvement (Syndenham’s chorea) Antibiotic prophylaxis required if undergoing procedure that may put patient at risk of endocarditis Diagnosis is based on the Jones Criteria • Documented evidence of a recent GAS infection and clinical findings ACUTE GLOMERULONEPHRITIS • • • • Associated with streptococcal pharyngitis AND sometimes with streptococcal skin infections Oedema, puffy face, swollen extremities • Due to sodium and water retention Hypertension • With albumin and blood in the urine Majority of young patients recover completely • • • However, may lead to permanent renal damage May warrant lifelong dialysis or renal transplantation Or may be fatal 2. STREPTOCOCCUS AGALACTIAE (GROUP B,  -HAEMOLYTIC STREPTOCOCCI) • Colonise the lower GI and GU tract • 10-40% women intermittently carry S. agalactiae in vagina • May be carried in the throat • Important cause of neonatal sepsis • Neonatal colonization usually occurs via the mother’s genital tract • Risk factors: • Maternal colonisation • Premature delivery / Premature rupture of membranes • Prolonged labour • Low birth rate • Intra-partum fever GROUP B STREPTOCOCCI: IRISH EPIDEMIOLOGY Pathogen Number laboratoriesby year-end %Coverage of population Group Bstreptococci (from 1st January 2019) Number of isolates %Erythromycin-R* 2016 2017 Year 2018 38 97% 37 99% 39 100% 38 100% 36 93% † † † † † † 176 41.9% 102 31.9% † No data; data collection for this pathogen commenced in 2019 Source: HPSC *2020 data missing from 2 laboratories 2019 2020* GROUP B -HAEMOLYTIC STREPTOCOCCI: VIRULENCE MECHANISMS • Capsule polysaccharide – Different serotypes based on capsular polysaccharides – Types Ia, III to V most commonly associated with colonisation and disease • Haemolysins • Hyaluronidase • Surface proteins - adhesins You will learn more about Group B streptococci and neonatal sepsis in SC1 3. OTHER  -HAEMOLYTIC STREPTOCOCCI • Can cause similar diseases as Group A streptococcus • But without the immunological complications • Group C streptococci • Puerperal fever • Tonsillitis • Wound sepsis • Group G streptococci • Upper respiratory tract infections • Endocarditis 4.  -HAEMOLYTIC STREPTOCOCCI A. “viridans” streptococci B. Streptococcus pneumoniae (‘pneumococcus’) 4A:“VIRIDANS” STREPTOCOCCI • Oropharynx, GIT & GU tract • Most lack Lancefield antigens • Exception S. bovis (Group D) • Clinical infection: • Several associated with dental caries and endocarditis • Invasive disease often related to breech in mucosal surfaces • Strep. sanguis • Strep. mitis • Commonest viridans strep • Tooth biofilm • Infective endocarditis • Strep. mutans • Dental caries • Strep. anginosus (milleri) • Purulent infections: brain & liver abscesses • Strep. bovis • Linked to colon cancer • Infective endocarditis CLINICAL CASE 2 • An 80yo female presents with: – – – – Productive cough Shortness of breath Pleuritic chest pain Fever • One week previously she was diagnosed with influenza. WHICH ONE OF THE FOLLOWING STREPTOCOCCI IS THE MOST LIKELY CAUSATIVE PATHOGEN? A. S. agalactiae B. S. mitis C. S. oralis D. S. pneumoniae E. S. pyogenes WHEN S. PNEUMONIAE IS CULTURED ON BLOOD AGAR, WHICH ONE OF THE FOLLOWING HAEMOLYTIC PATTERNS IS MOST LIKELY TO BE SEEN? 1. Alpha haemolysis 2. Beta Haemolysis 3. Gamma haemolysis 4B: S. PNEUMONIAE -haemolytic • Gram-positive cocci in chains or diplococci • Carried in nasopharynx by: – 5-10% of healthy adults – 20-40% of healthy children • Polysaccharide capsule – > 90 serotypes – Allow typing of strains – Vaccines available against some serotypes • Variety of clinical infections Gram-positive diplococci, i.e. Pneumococcus (Humphreys, Willatts & Vincent) INVASIVE PNEUMOCOCCAL DISEASE (BLOODSTREAM AND MENINGITIS) IN IRELAND VIRULENCE FACTORS & PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) Direct person to person spread via respiratory droplets Get in – Portal of Entry Get out and spread further Colonises oropharynx – mediated by adhesin Attach to cells Invasion promoted by cell wall, adhesins + cytotoxin pneumolysin Pneumolysin & cell wall polysaccharide capsule: activates complement and cytokine release Cause damage to host cells Defeat/ evade the immune system Risk factors: immunodeficiency, splenectomy, asplenia Antibiotic resistance facilitates disease Capsular polysaccharide: anti-phagocytic PNEUMOCOCCAL PNEUMONIA (MORE DETAIL LATER IN RESP MODULE) • Symptoms: • Pleuritic chest pain • Shortness of breath • Purulent sputum • Classically  “lobar” pneumonia • May cause bronchopneumonia especially in the elderly • Complications: • Parapneumonic effusion • Empyema / Lung abscess • Bacteraemia • Influenza infection a major predisposing factor SINUSITIS & OTITIS MEDIA • • • • S. pneumoniae is a common cause of acute infection of the paranasal sinuses and ear Usually preceded by upper respiratory tract infection Otitis media usually affects young children Sinusitis affects all ages PNEUMOCOCCAL MENINGITIS & BSI Meningitis: • Leading cause of meningitis in adults • How does it get to the central nervous system? • During a bacteraemia • Chronic ear infection • Sinus infections • After head trauma BSI / Bacteraemia • 25-30% of patients with pneumococcal pneumonia • May accompany meningitis • RARELY occurs with cases of sinusitis or otitis media 5. ENTEROCOCCI • 18 species: E. faecium and E. faecalis most • • • • • • common Previously classified as Group D streptococci Bowel flora – usually low virulence Facultative anaerobes Haemolytic pattern varies • Alpha or beta Grow in presence of bile salts • i.e grow on MacConkey agar Vancomycin resistance is common! VIRULENCE FACTORS & PATHOGENESIS (FROM THE BACTERIA'S PERSPECTIVE…) 1. CONTACT from hands, environment, 2. Contaminated food or water Get out and spread further Get in – Portal of Entry Cause damage to Haemolysinshost cells Most infections = endogenously (bowel flora) Attach to cells Protein and carbohydrate factors enable binding to cells Defeat/ evade the immune system Antibiotic resistance (intrinsic / acquired) facilitates survival and multiplication ENTEROCOCCAL INFECTION At-Risk Patients: • Recent surgery • Underlying disease • Malignancy • Burns or trauma • Recent antibiotics • cephalosporins or aminoglycosides • Prolonged hospitalization • Especially ICU Types of Infection: 1. Urinary tract infection a) Particularly urinary catheter-related 2. 3. 4. 5. Endocarditis Bloodstream infection Wound infections Intra-abdominal infections INFECTIVE ENDOCARDITIS (MORE IN CV MODULE IN SEMESTER 2) • Turbulent flow through the heart provides a surface for bacteria to attach • Bacteria enter blood usually after a procedure that damages epithelial barriers • e.g. dental extraction, cystoscopy • Bacteria attach to damaged valves and vegetations form Vegetation on heart valve (Slide: A Colour Atlas of Infectious Diseases, Emond) 6. ANAEROBIC STREPTOCOCCUS PEPTOSTREPTOCOCCUS • >25% of anaerobes from clinical specimens • Colonise oral cavity, GI & GU tracts, and skin • Infections include • • • • Aspiration pneumonia Sinusitis and brain abscess Intra-abdominal abscesses Pelvic infections GENERAL ASPECTS OF DIAGNOSIS OF INFECTION (THIS WOULD APPLY TO ANY STREP INFECTION) • Clinical suspicion based on clinical features • Appropriate samples sent to the laboratory based on site of infection – – – – Blood (if invasive disease suspected) CSF (meningitis) Urine Throat swab (pharyngitis) • In the laboratory: – Gram stain on sterile site sample (blood, CSF, pus) – Culture: takes 24 – 48 hours • Samples incubated aerobically and anaerobically • Blood agar (haemolysis) • MacConkey agar (enterococci) LABORATORY DIAGNOSIS • Identification • Lancefield Grouping • Bacitracin susceptibility (GAS) • Optochin sensitive (pneumococcus) • Bile solubility (enterococci) • Serology • Detect recent Group A infection in suspected rheumatic fever & glomerulonephritis i.e. ASO titres (ASOT) • PCR • Blood, CSF • Urinary antigen (for pneumococcus) S. PYOGENES LAB DIAGNOSIS Bacitracin disk • Gram-positive cocci in chains • ß-haemolytic • Catalase negative • Group A Group A ß-haemolytic streptococci showing bacitracin susceptibility (clearing around bacitracin disc) S. PNEUMONIAE LAB DIAGNOSIS • Gram-positive cocci in chains or diplococci •  -haemolytic • Catalyse negative Optochin disk Susceptible to optochin i.e. growth inhibited by optochin ANTIMICROBIAL RESISTANCE IN PNEUMOCOCCI • Pneumococci can alter the structure of penicillinbinding proteins (PBPs) that are found on their surface – β lactam antibiotics (e.g., penicillin) cannot bind to pneumococci and destroy their cell wall • Different levels/degrees of resistance – Low-level or intermediate resistance – High-level or full resistance • Important to know if patient has been in area where there is high level of resistance ANTIMICROBIAL RESISTANCE AND S. PNEUMONIAE 2020 Map downloaded from ECDC’s Surveillance Atlas on 01/12/2021 IE rank: 8/29 (17.6%) EU/EEA: 15.6%^ (population-weighted mean) ^ Increased from 13.2% in 2019 5-year trend Source: HPSC STREPTOCOCCI: ANTIBIOTIC TREATMENT Most commonly use cell wall active agents: • Penicillins – Nearly all  -haemolytic streptococci susceptible • Cephalosporins – – – – For penicillin-resistant pneumococci Used for treatment of meningitis – ceftriaxone (3rd gen) Used if rash with penicillin Do not use for enterococci (are intrinsically resistant) • Vancomycin – If  -lactam anaphylaxis – If resistance to  -lactams suspected ENTEROCOCCI ANTIBIOTIC TREATMENT • First line treatment for enterococci = amoxicillin – If resistant to this (many E. faecium are!) then vancomycin • However VRE (vancomycin resistant enterococci) problematic (i.e. can’t use vancomycin) • Patients may become colonised, +/- develop significant infection due to VRE • Limited treatment options, with significant potential side effects and interactions – Linezolid PREVENTION & CONTROL VACCINATION Pneumococcal vaccine available against some serotypes • Childhood vaccination programme • Adults > 65 years • Clinical risk groups, e.g. splenectomy Impact of pneumococcal vaccine Data source: HPSC and Irish Pneumococcal Reference Laboratory PRINCIPLES OF INFECTION PREVENTION & CONTROL 1. Immunisation a) Pneumococcal vaccine available against some serotypes i. ii. iii. Childhood vaccination programme Adults > 65 years Clinical risk groups e.g. splenectomy 2. Infection Prevention & Control a) Group A strep - isolate in a single room if iGAS confirmed until 24 hours on appropriate antimicrobial therapy b) Notifiable diseases – public health Which one of the following is a well-recognised post-infectious immune mediated complication of untreated Group A streptococcus pharyngitis? A. B. C. D. E. Blindness Deafness Gastroenteritis Meningitis Rheumatic fever YEAR 1 STUDENTS IN NEED OF ASSISTANCE • RCSI Student Assistance Programme – • RCSI Centre for Mastery: Personal, Professional & Academic Success (CoMPPAS) – – • • https://www.mercersmedicalcentre.com/rcsi-students For urgent medical advice/emergency outside regular hours contact DubDoc (Out of Hours GP) (+353) 014545607 https://www.dubdoc.ie/ – • If require urgent assistance from RCSI, or you are on campus you can contact security at 01 402 22 19. This number will not result in an in person response. Please note that in an emergency your safest action is to contact the local emergency services (112/999). If you are an International Student you should also contact your Embassy/ Sponsor to advise them of your circumstances. 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