BMFL1 Staphylococci 23KOC.pptx

Leading the world to better health RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: BMFML1 Staphylococci Class: Year 1 Course: Undergraduate Medicine Lecturer: Prof. Manaf Al-Qahtani Date: 9th November 2023 LEARNING OUTCOMES By the end of the lecture yo...

Leading the world to better health RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: BMFML1 Staphylococci 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 staphylococci 2. Describe the pathogenesis of infections caused by clinically important staphylococci 3. Recognise and describe the clinical features and complications of infections caused by clinically important staphylococci 4. Outline the laboratory diagnosis of infections caused by clinically important staphylococci 5. Choose the appropriate antimicrobial agents to treat infections caused by clinically important staphylococci 6. Discuss the epidemiology of clinically important staphylococci 7. Use the appropriate measures to prevent the acquisition and spread of infections caused by clinically important staphylococci STAPHYLOCOCCI: BASIC FEATURES • Staphylococcus is a genus of Gram-positive bacteria • They appear spherical (cocci) and form in clumps / clusters • They are facultative anaerobes • Traditionally divided into 2 groups based on their ability to clot blood plasma (the coagulase reaction / test) 1. Coagulase-positive staphylococci (S. aureus) • Can colonise nasal passages and other moist skin areas (ex. axilla, groin) 2. Coagulase-negative staphylococci (>30 other species) • Common human skin commensals (ex. S. epidermidis) COAGULASE TEST • A laboratory test used to differentiate S. aureus (coagulase +ve) from other staphylococci (negative) • Coagulase is an enzyme that can cause blood clot formation (converting fibrinogen to fibrin) – Allows bacteria to coat its surface with fibrin & possibly resist phagocytosis CATALASE TEST • Used to differentiate staphylococci from streptococci (also a Gram-positive coccus) Staphylococci = CATALASE + • Presence of catalase (an enzyme) is determined by the ability of the bacteria to reduce hydrogen peroxide into water and oxygen – this results in the production of bubbles CLINICAL CASE 1 • A 19 year old male presents to your general practice with a painful, red lump on his neck WHICH ONE OF THE FOLLOWING BESTS DESCRIBES THIS LUMP? A. Acne B. Blister C. Carbuncle D. Cold sore E. Furuncle WHICH ONE OF THE FOLLOWING STAPHYLOCOCCI IS THE MOST LIKELY CAUSATIVE PATHOGEN? A.Staphylococcus aureus B.Staphylococcus capitis C.Staphylococcus epidermidis D.Staphylococcus hominis E.Staphylococcus saprophyticus IS THE INFECTION EXOGENOUS OR ENDOGENOUS? A.Exogenous B.Endogenous DOES THIS INFECTION REQUIRE ANY FURTHER MANAGEMENT? A.Yes B.No 1. Staphylococcus aureus • Found in moist skin folds, mucosal surfaces, nasopharynx – 20 – 40% healthy humans colonised – Increased if: • Diabetes mellitus • Injecting drug use • Where a foreign body/implant is present • Distinguished as being methicillin-sensitive (MSSA) or resistant (MRSA) – Resistance to usual treatment results from production of an altered penicillin-binding protein (PBP2a) – Usually a healthcare-associated infection, elderly also higher risk • colonisation vs infection – Can also be resistant to other antimicrobial classes – In hospital: isolate / cohort with contact precautions S. aureus: Pathogenesis Portal of entry: 1. Ingestion 2. Penetration a) A break in the skin b) Entry through the mucous membranes allowing access to adjoining tissues Attaches to cells: 1. Surface proteins – Facilitate attachment 2. Capsule – Inhibits chemotaxis, phagocytosis – Facilitates adherence to implants 3. Fibrin/fibrinogen binding protein (clumping factor) – Attachment to blood clots & traumatised tissue 4. Matrix-binding proteins – Ex. adhesin – promotes collagen attachment – found in strains that cause osteomyelitis or septic arthritis S. aureus: pathogenesis Defeating/ evading the immune system: • Inhibition of phagocytosis with survival within phagocytes • Production of extracellular substances that promote invasion – Invasins – Enzymes S. aureus: pathogenesis S. aureus: pathogenesis Damage to host cells: • Direct damage – peptidogycan wall • Enzymes (see previous slides) • Toxins – EXOtoxins: Superantigens • Toxic shock syndrome toxin (TSST-1) • Enterotoxins – 8 antigenic types (A-E, G-I) – Cause food poisoning (will be covered in GIHEP module) – Exfoliative toxins • Scalded skin syndrome – Other • Cytotoxins (alpha, beta, leukocidin, etc) Gets out & spreads further: • Person-to-person – direct contact via skin carriage, especially hands • Environment – shed on to surfaces CLASSIFICATION OF STAPHYLOCOCCAL INFECTIONS 1. Skin & soft tissue Discussed briefly here, please also see the lecture ‘Skin and Soft Tissue Infections’ 2. Systemic – invasive 3. Toxin-mediated a) Food Poisoning / Gastroenteritis a) b) b) c) Short incubation period, self-limiting Covered in GIHEP module Scalded Skin Syndrome Toxic Shock Syndrome Spectrum of S. aureus infections 2. SYSTEMIC S. AUREUS INFECTIONS • Bloodstream infection (BSI) • Endocarditis – Usually secondary to BSI – Will be covered in more detail in cardiovascular module • Bone/joint infections – Ex. septic arthritis, osteomyelitis – Please see lecture on bone & joint infections for more detail • Deep abscesses, e.g. brain, spine, psoas muscle • Pneumonia – Risk factors: viral respiratory infection, cystic fibrosis, ventilation, aspiration – Will be discussed further in respiratory module 3. Toxin-mediated: Scalded Skin Syndrome • Spectrum of superficial blistering skin disorders – Localized blisters – Generalized exfoliation of entire body surface – Mucous membranes usually spared • Exfoliative toxins – Toxins spread haematogenously from a localised source – Split intracellular bridges in skin layer (middle layers) • Most common in children < 6 yrs – Mainly in neonates – Immunosuppressed adults / renal failure • Contagious ++ • Mortality: • Children <3% / Adults up to 60% Scalded Skin Syndrome Clinical: • Skin extremely painful • Large patches of necrotic epidermis slide off the underlying layers at the slightest pressure – Nikolsky’s sign • Complications usually due to sepsis / secondary infection / dehydration Management: • Rehydration • Wound care • Antimicrobial treatment 3. Toxin-Mediated: Staphylococcal Toxic Shock Syndrome (TSS) • TSS toxin-1 acts as a superantigen*  massive cytokine release • Historically associated with high absorbency tampons • Rapid, dramatic & fulminant onset: – Pyrexia, hypotension – Rash with subsequent desquamation, especially on palms and soles • Other organ involvement: – Renal failure – CNS (disorientation without focal neurological signs) – Muscular (severe myalgia, increase in CK) *Superantigens? Check on the Pathogenesis of bacterial infection lecture Desquamation of skin in TSS (Dr E Brown, Bristol) Laboratory Diagnosis Day 0 Patient specimen (e.g. blood culture) • Incubate at 37oC Day 1+ Positive signal • • • • 24 hours later Culture results • Read agar culture plates • Coagulase test • Phone team/patient reviewed 24 hours later Antibiotic susceptibility results • Alter empiric antibiotic therapy as appropriate • If MRSA – infection control precautions & decolonisation Gram stain; bunches of grapes Set up culture plates in lab Team reviews patient ? PCR for earlier confirmation MANAGEMENT OF S. AUREUS INFECTION 1. History, especially timing and presentation of symptoms 2. Clinical exam a) Focus on a possible source or evidence of the spread of infection if systemically unwell b) Be sure to examine: a) Skin: IV line sites or other indwelling devices, surgical wounds, soft tissue infections or abscesses a) Remember scars can indicate implantable devices or joint or valve replacements b) CVS: evidence of known or new / changed murmur on auscultation c) Musculoskeletal: new bone or joint pain, reduced range of motion or limp, swelling, loss of function c) Always consider the possibility of deep-seated infection Management of S. aureus infection 3. Investigations: (depends on the clinical presentation) • General bloods: FBC, U&E, CRP, lactate • Microbiological (specimen will depend on infection site) – – – – – – Abscess - pus or tissue better than skin swab BSI – blood cultures Pneumonia – sputum, broncho-alveolar lavage (BAL) Septic arthritis – joint fluid TSS (next slide) Food poisoning – food (not stool) • Other investigations (as relevant): – Imaging (ex. CXR, CT or MRI scans, Echocardiogram) TSS – Investigations & Management Investigations: • Blood cultures if febrile or systemically unwell – Rarely positive • Wound swab for culture if skin lesion • Other swabs for culture: – Abscess – Cervix/vagina Management: 1. Recognise it quickly 2. Resuscitation & critical care input 3. Rapid IV antimicrobials 4. Source control: a) Debride infected or necrotic wounds, drain abscess etc Antibiotic Treatment • Choice, route & duration of treatment depends on the site and complexity of the infection • • • • Mild infections e.g. boil, folliculitis: no treatment Skin/soft tissue infections & respiratory tract infection: 7 days Bloodstream infection: 14 days Complicated infection (endocarditis, septic arthritis, osteomyelitis): at least four weeks, but may need longer • Flucloxacillin if susceptible (MSSA) • 1st generation cephalopsorin (e.g. cefazolin) also an option • Vancomycin or Teicoplanin (glycopeptide) if MRSA • Or alternatives (daptomycin, linezolid, tetracyclines) • If bloodstream infection – Look for the source: • ECHO, radiology & repeat blood cultures after commencing antimicrobial treatment to confirm blood is now sterile EPIDEMIOLOGY: S. AUREUS BLOODSTREAM INFECTION IN IRELAND 2018 TO 2022 Source: HPSC/EARS-Net Community-Acquired MRSA • Skin infections & necrotizing pneumonia • Younger, healthier patients • Less antibiotic resistant, but more virulent • Certain strains, e.g. USA300, still more common in North America 2. Coagulase-negative staphylococci • Natural inhabitants of human skin & mucosa • Much less virulent than S. aureus – rarely pathogenic in healthy individuals – S. epidermidis infections often associated with prosthetic devices e.g. Joint replacements, prosthetic valves, pacemakers – S. saprophyticus causes urinary infection • Will be covered again in year 2 REGUB module Staphylococcus epidermidis pathogenesis S. epidermidis infections (Devices) • Bloodstream infection often secondary to IV lines • Endocarditis: prosthetic valves • Prosthetic joint infections • Continuous ambulatory peritoneal dialysis peritonitis • Ventriculitis / shunt-associated meningitis CLINICAL CASE 2 • A 65yo male develops a fever and rigors 16 days post operation for a small bowel resection • He has a CVC in situ for parenteral nutrition, which was inserted on the day of surgery • The skin around the insertion site is erythematous • Two sets of blood cultures are sent to the laboratory for culture & susceptibility testing WHICH ONE OF THE FOLLOWING IS THE MOST LIKELY DIAGNOSIS? A.Bloodstream infection B.Cellulitis C.Necrotising fasciitis D.Meningitis E.Urinary tract infection FOLLOWING BLOOD CULTURE, THE LAB REPORTS THE FOLLOWING……. WHICH ONE OF THE FOLLOWING BEST DESCRIBES THIS GRAM-STAIN? A. B. C. D. E. Gram-positive bacilli Gram-positive coccobacilli Gram-positive cocci in clusters Gram-positive cocci in chains Gram-positive diplococci MORE LABORATORY RESULTS Microscopy: Gram-positive cocci in clusters Catalase: positive Coagualse: positive BASED ON THIS, WHICH ONE OF THE FOLLOWING IS THE MOST LIKELY CAUSATIVE PATHOGEN? A. Staphylococcus aureus B. Staphylococcus capitis C. Staphylococcus epidermidis D. Staphylococcus hominis E. Staphylococcus saprophyticus UNDERSTANDING LABORATORY RESULTS Microscopy: Gram-positive cocci in clusters Catalase: positive Plus Coagualse: positive S. aureus COULD THIS INFECTION BE CAUSED BY MRSA? A. Yes B. No Diagnosis & Management of CoNS Diagnosis Often patient not particularly systemically unwell 1. History and examination 2. Blood cultures (at least two sets) Management 3. Source control: often the prosthesis must come out for effective treatment (biofilm) 4. Culture prosthetic material 5. Coagulase-negative staphylococci often antibiotic resistant, including methicillin/flucloxacillin • Vancomycin is usual empiric treatment • Indication & duration of treatment depends on location of infection & if prosthetic material can be removed CLINICAL CASE 3 • A 72 year old female develops a fever and rigors six weeks post op for a total knee replacement • Blood cultures are sent to the laboratory and the results below are reported: Microscopy: Gram-positive cocci in clusters Catalase: positive Coagualse: negative WHICH ONE OF THE FOLLOWING IS THE MOST LIKELY CAUSATIVE PATHOGEN? A. Staphylococcus aureus B. Staphylococcus capitis C. Staphylococcus epidermidis D. Staphylococcus hominis E. Staphylococcus saprophyticus WHICH OF THE FOLLOWING VIRULENCE FACTORS IS IMPORTANT IN THE PATHOGENESIS OF DEVICE-RELATED INFECTIONS INVOLVING S. EPIDERMIDIS? A.Biofilm B.Coagulase C.Catalse D.Exfoliative toxin A E.Protein A Staphylococcal Biofilm Formation 3 1 2 MEDICAL DEVICE Biofilm formation. CoNS e.g. S. epidermidis and S. aureus (including MRSA!!) are extremely good at attaching to surfaces and producing biofilms PREVENTING STAPHYLOCOCCAL INFECTION • Protect the skin barrier Prevent transmission from patient-topatient: • Hand hygiene • Environmental and equipment hygiene • Transmissionbased precautions for MRSA: • Isolate/cohort • Contact precautions: gloves, apron/gown • Prevent pressure sores • Diabetic foot care • Care of wounds and surgical sites • Care of intravenous catheters • Don’t put them in unless needed • Review the ongoing need daily • Remove as soon as possible Gets in – • Look after them properly portal of entry Gets out & spreads further Causes damage to host cells Attaches to cells Defeats/evades the immune system Summary: Staphylococci Coagulase +ve (S. aureus) Coagulase –ve • 20-40% of population carry S. aureus without infection • But a common cause of infections: • Normal flora: coloniser of skin & mucosa • Rarely pathogenic in healthy individuals • S. epidermidis: • • – Skin + Soft tissue – Systemic – Toxin-mediated Virulence factors++ Treatment with flucloxacillin (MSSA) or vancomycin (MRSA) - infections associated with prosthetic devices - empiric treatment with vancomycin, as resistance is common - Source control (remove device – biofilm) • S. saprophyticus - UTI S. AUREUS TOXINS & VIRULENCE FACTORS Virulence factor Description Biological Role Coagulase Enzyme Converts fibrinogen into fibrin clot. Coats bacterial cells in self protein. Protein A Surface protein Binds IgG(heavy chain Fc region) hindering opsonisation and phagocytosis Alpha toxin Haemolysin Causes lysis of blood components, particularly monocytes and platelets Staphylokinase Enzyme Dissolves fibrin clots to facilitate spread Hyaluronidase Enzyme Breaks-down hyaluronic acid in connective tissue facilitating spread Toxic-shock syndrome toxin 1 Superantigen (Exotoxin) Stimulates T-cells to over produce IL-1, IL-2 and TNF-a Enterotoxin Six serotypes (A, B, C, D, E & G) Cause vomiting and diarrhoea when ingested Exfoliative toxins Esterase & (A&B) protease activity Target proteins that maintain epidermal integrity Panton-valentine Causes pores in leukocytes Cytotoxin 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. 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