Infectious Diseases of the Respiratory System PDF

Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM1011 Yr. 2024-2025 Infections by : LECTURE 3 COR...

Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM1011 Yr. 2024-2025 Infections by : LECTURE 3 CORE Dr. GARCIA-LARA SLIDES Bitesize 1 Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 1  Dr Jorge Garcia-Lara And when it comes down to the whole body, you know the drill, rules of thumb … OUTSIDE tooth - INSIDE foreign brushing endocarditis body transient constant skin endocarditis Local Bacteraemia Systemic GI infection Viremia / Fungemia infection osteomyelitis UTI pneumonia RT meningitis trauma Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 2  Dr Jorge Garcia-Lara Respiratory tract infections Sinusitis Nasopharyngitis (common cold) Otitis (media and externa) Tonsillitis UPPER Pharyngitis Epiglottis Laryngitis Tracheitis Bronchiolitis LOWER Bronchitis bronchus Pulmonary tuberculosis bronchiole Pneumonia Empyema alveoli Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 3  Dr Jorge Garcia-Lara Some Statistics (no, you do not need to memorize these numbers) we breathe 12 times/minute 0.5 liters of air each time 860,000 bacteria/per day inhaled 200-300 different species from at least 7 different phyla Bowers et al. 2011. Sources of bacteria in outdoor air across cities in the Midwestern 4 United States. Applied Environmental Microbiology. 77 (18), 6350-6356. 4  Dr Jorge Garcia-Lara Infectious disease, the science of likelihood & intent 5  Dr Jorge Garcia-Lara A "multiphase turbulent buoyant cloud " (no need to learn the term) Borouiba, Bush & Dehandschoewercker. The physics of sneeze: 6 2014. Journal of Fluid Mechanics. https://www.youtube.com/watch?v=bFxgVkslD-k Away yet close: 30 meters away Fungi remain in suspension 7  Dr Jorge Garcia-Lara Defense mechanisms (RT): Cell types along the tract conducting respiratory only 616 mill. GAS pharyngitis / yr primarily (not exclusively) affects 5-15 yr old gram +ve ovococci bacterium nose / throat microflora contact with infected individuals Groups A Streptococci (GAS) i.e., S. pyogenes – b-haemolytic Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 27  Dr Jorge Garcia-Lara Activity Lecture : Respiratory Tract Infections Who are the Group A streptococci ? A. Streptococcus pyogenes B. Streptococcus agalactiae C. Staphylococcus aureus D. Streptococcus pneumoniae E. Klebsiella pneumoniae Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 28  Dr Jorge Garcia-Lara Bacterial – Pharyngitis/Tonsilitis (Strep throat) generic features (GF) malaise fever (pyrexia) throat soreness headache patchy exudates cervical lymphadenopathy chills orally: mucositis & gingivitis erythema & discomfort petechiae on soft palate 29 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM1011 Yr. 2024-2025 influenza by : LECTURE 3 CORE Dr. GARCIA-LARA SLIDES Bitesize 4 Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 30  Dr Jorge Garcia-Lara Classification of viruses; typically to know Family and Species suffices rotavirus papilloma hepatitis B adenoviruses smallpox herpes simplex influenza rabies varicella-zoster cytomegalovirus Epstein-Barr Japanese encephalitis human herpes Ebola RSV yellow fever mumps hepatitis C measles dengue MERS West Nile HIV SARS polio hepatitis A rubella rhinovirus 31  Dr Jorge Garcia-Lara Influenza (Orthomyxovirus) clinical diagnosis aerosol inhalation community- & health-care infection complications children and elderly highly infectious 20,000 deaths/year US whole respiratory tract sore throat influenza pandemic – life- nasal congestion threatening headaches pneumonia tiredness bronchitis dry cough otitis myalgia sinusitis typically self-limiting 3 different strains, A, B and C (based on different molecular patterns and clinical properties) 32  Dr Jorge Garcia-Lara Influenza virus binds sialic acid epithelial cells nystatin destroys sialic acid Influenza strains nomenclature, e.g., H1N1 33  Of course, we always have ”the flu” Symptom Cold Flu Development A few days Very quickly Fever Rare High Headaches Rare Prominent Chills Rare Probable General aches Mild Severe Fatigue Mild Can last for 2-3 weeks Extreme exhaustion Absent Early and prominent Coughing Hacking (with mucus) Coughing (little mucus) Chest discomfort Mild Present Blocked nose Common Sometimes Sneezing Usual Sometimes Sore throat Common Sometimes 34  Dr Jorge Garcia-Lara MICROBIOLOGY Unit: ISCM Module: UM1011 Yr. 2024-2025 pneumonia by : LECTURE 3 CORE Dr. GARCIA-LARA SLIDES Bitesize 5 Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 35  Dr Jorge Garcia-Lara Pneumonia aerosol inhalation; microbiota aspiration; blood common cause of infection-related death agents: commonly professional virus – children commonly - bacteria – adults 480,000 cases of adult pneumonia (UK) risk factors: age influenza primary infection leading to secondary bacterial pneumonia pneumonia, as a COMPLICATION pandemic Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 36  Dr Jorge Garcia-Lara Pneumonia Which one of the following microorganisms does not typically cause pneumonia ? Mycoplasma pneumoniae Klebsiella pneumoniae Chlamydophilia pneumoniae Parainfluenza virus Streptococcus pneumoniae Coxiella burnetii Moraxella catharralis Influenza virus Legionella pneumophila 37  Dr Jorge Garcia-Lara John Doe’s symptoms Typically rapid progression 24-48h ( … to days) difficulty/ rapid shortness chest heartbeat fever cough congestion pain of breath pain >30 breathing brths/min sweating/ chills dry sputum common rare Low BP headaches haemoptysis 65 38  Dr Jorge Garcia-Lara Assessment of pneumonia severity CRB65 score = or >2 Confusion CRB65 = 1 Respiration rate CRB65 = 1 Blood pressure CRB65 = 1 age CRB65 = 1 hospitalization 39  Dr Jorge Garcia-Lara John Doe’s symptoms Typically rapid progression 24-48h ( … to days) difficulty/ rapid shortness chest heartbeat fever cough congestion pain of breath pain >30 breathing brths/min sweating/ chills dry sputum common CRB65 = 1 rare Low BP headaches haemoptysis 65 40  Dr Jorge Garcia-Lara VIRAL BACTERIAL RSV, Influenza, VZV, Common : Measles, CMV Streptococcus pneumoniae Haemophilus influenza FUNGAL Candida, Histoplasma, More atypical: Coccidium, Pneumocystis Mycoplasma pneumoniae Toxoplasma Legionella pneumophila S. aureus (after Influenza) – “pandemic terror” Even more atypical: Clamydophilia pneumoniae Coxiella burnetii Moraxella catharralis (opportunistic) Mycobacterium tuberculosis Klebsiella pneumoniae Streptococcus pneumoniae 41 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara Pneumonia Haemophilus influenzae Moraxella catharralis Streptococcus pneumoniae Klebsiella pneumoniae Moraxella catharralis 42 Bachelor of Medicine and Bachelor of Surgery MBBS Pneumonia Chlamydophilia pneumoniae ” The intracellular ” Mycoplasma pneumoniae Coxiella burnetii Legionella pneumophila 43 Types of pneumonia Moraxella catharralis Have you been to the hospital No Yes developed within Community 48/72 hours upon Acquired admission ? Pneumonia Yes Hospital Acquired Pneumonia (nosocomial) 44  Dr Jorge Garcia-Lara Pneumonia - "CSI Preston" Diagnosis (Clinical) Moraxella catharralis clinical diagnosis – easy DDx – difficult : o acute bronchitis, tuberculosis, Pneumocystis pneumonia, … o pneumonia severity (clinical skill) Particularly in Hospital-Acquired: o sputum contains bacteria which may not be linked to pneumonia o atypical serology (acute pneumonia): o Respiratory rate >30 o Bacteraemia o Urea > 7mmol/l o Albumin < 35g/dl o Low blood pressure 60/90 mmHg 45 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara Diagnosis (Laboratory) o C-Reactive Protein (CRP) (normal 38.3oC (101oF) for more than 3 wks body temperature 38oC 38oC body site 37.5oC (101oF) person healthy (99.5oF) rectal age individual 37oC temperature activity variation (98.6oF) oral time of day temperature 36oC 54  Dr Jorge Garcia-Lara Fevers of Unknown Origin (FUO) Classic definition (1961) 1 2 abnormal increase in body temperature > 38.3oC (101oF), > 3 wks diagnosis uncertain (after 3 days) despite appropriate investigations Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 55  Dr Jorge Garcia-Lara Fever pattern provide clues to specific infectious culprits 2 main types FUO continuous / several FUO occasions intermitent / recurrent swings less than 1oC swings more than 1oC Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 56  Dr Jorge Garcia-Lara Revised groups since 1991 (with the advances on technological advances) Nosocomial FUO: Classic FUO: hospital-acquired infection (see above) patient w/o a fever upon admission (fever 72 hours after) Neutropenic FUO: HIV-associated FUO: (hours to days) lasting >4wks (as outpatient); low neutrophil count >3 days as hospital inpatient If NO FEVER or CELLULAR MATERIALS in laboratory samples – more likely a toxin-based or virus infection 57  Dr Jorge Garcia-Lara A few facts Fever – a recognized characteristic of infection 25-50% FUO are due to infections 5-15% go undiagnosed rest, non-infectious agents Key, history taking, e.g, parasitic causes of FUO more common in: immunocompromised patients patients with a travelling history Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 58  Dr Jorge Garcia-Lara FUO due to CVS Infections of the infections bloodstream of the heart (systemic) sepsis endocarditis myocarditis (septicaemia) Yr.2 pericarditis Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 59  Dr Jorge Garcia-Lara Matters of the heart prevention cardiac overload muscle blood vessels nerves * (Pericardial Sac/Fluid) * endothelium epithelium 60 *connective tissue  Dr Jorge Garcia-Lara The microbial way to your breach intact epithelium – broken epithelium heart: something similar 2 happens in the respiratory tract remotely-produced damage 1a toxin-mediated inflammatory response-mediated 4 1b cyto/chemokines upon invasion Systemic/remote indirect autoimmunity inflammation or autoimmune rxn 3 system infections to the blood and then to.. any organ Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 61  Dr Jorge Garcia-Lara Toxins affecting the heart SEC, Staphylococcal Enterotoxin C Staphylococcus aureus a-toxin Streptococcal Pneumolysin (mop it up, with liposomes) Streptococcal Streptolysin O Clostridium perfringens enterotoxin & alpha toxin Escherichia coli ST toxin Clostridium difficile toxin A & B Diphteria toxin (Dtx) If NO FEVER or CELLULAR MATERIALS in laboratory samples – it is more likely a toxin-based infection … or it can be a virus 62  Dr Jorge Garcia-Lara CVS – Infective endocarditis (IE) aortic mitral valve valve 63  Dr Jorge Garcia-Lara Any irregularity, an opportunity to crash >20% of S. aureus bacteraemias lead to endocarditis Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 64  Dr Jorge Garcia-Lara Endocardium, maybe similar structure but different flow 65 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara CVS – Endocarditis or Infective endocarditis (IE) inflammation of the inner lining of heart chambers and valves mainly affecting people with (risk factors): o damaged or artificial heart valves o congenital/structural heart defects o implanted medical devices (heart or blood vessels) o IVD abusers o bloodstream infections approx. 4000 cases / yr UK uncommon in patients with healthy hearts ?!?!?!? 66  Dr Jorge Garcia-Lara reported incidence of IE is increasing in England and Wales. trend may be due to: 1. an ageing population with relatively greater prevalence of: degenerative valve disease prosthetic valves intracardiac devices 2. more patients are receiving haemodialysis 3. periodontal disease remains common. Watkin & Sandoe. 2012. British Society of Antimicrobial Chemotherapy (BSAC) guidelines for the diagnosis and treatment of endocarditis: what the cardiologist needs to know. 98(10):757-759. 67 Categories of infective endocarditis (IE) Native valve endocarditis (NVE) immunology not involved colonize surface acute – normal valves (typically) symptoms develop over days rapidly getting worse immunology involved subacute – abnormal valves (typically) colonize on & below the surface symptoms develop slowly (wks/mo), slow valve destruction Prosthetic valve endocarditis (PVE) 20% of all endocarditis cases early 5% of replaced valves late become infected Intravenous drug abuse (IVDA) endocarditis 68  Dr Jorge Garcia-Lara Not all organisms destroy equally 1 2 3 4 tissue valve tissue valve mechanical valve tissue destruction & aortic root abscess (less aggressive) (aggressive) Enterococcus Staphylococcus aureus faecium small vegetations, extensive tissue with recurrent destruction within weeks 69 episodes of sepsis https://consultqd.clevelandclinic.org/images-of-note-in-infective-endocarditis-not-all-organisms-destroy-equally/  Dr Jorge Garcia-Lara CVS – Infective endocarditis (acute) often non-specific symptoms commonly FUO (>38 °C) chills/night sweats up to 50% or patients require heart murmurs vascular surgery headaches shortness of breath if untreated vegetations can tiredness lead to: muscle & joint pain o Rheumatic fever persistent cough o Heart failure swelling of feet, legs or o Stroke abdomen paleness Splinter haemorrhages Osler’s nodes Janeway lesions Roth’s spots Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) Physician Associate Studies (MPAS) 70  Dr Jorge Garcia-Lara IE: the signs Clinical assessment, unreliable common in S. aureus endocarditis microabscesses and septic emboli (vasculitis ?!?) Janeway’s lesions Roth spots vasculitis, e.g., immune complex deposition, clots, … Splinter hemorrhages Osler nodes 71  Dr Jorge Garcia-Lara IE – the causative agents most commonly caused by any organism entering the bloodstream (infectious); typically bacteria role of viruses unclear important in dentistry (teeth cleaning/procedures) aetiology varies w/: native valves prosthetic valves IntraVenous Drug abusers (IVD) Acute – highly virulent organisms (e.g., Streptococcus agalactiae ) Subacute – low virulence / community organisms (e.g., viridans streptococcis, i.e., Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans, Enterococcus faecalis ) 72  Dr Jorge Garcia-Lara If you let them, they will do it ! native valves prosthetic valves IVD oral microflora surgery accidental injection sepss into bloodstream (haematogenous spread) oral streptococci & CoNS staphylococci Staphylococcus aureus enterococci Staphylococcus aureus oral streptococci & Staphylococcus aureus Gram –ve (enteric) enterococci CoNS staphylococci bacilli Gram –ve (enteric) Gram –ve (enteric) oral streptococci & bacilli bacilli enterococci Fungi (mainly Fungi (mainly Fungi (mainly Candida) – Candida) – Candida) – uncommon uncommon uncommon Medicinae Baccalaureus Baccalaureaus Chirurgiae (MBBS) CoNS staphylococci Physician Associate Studies (MPAS) 73  Dr Jorge Garcia-Lara Intracellular pathogens Mycoplasma pneumonia Legionella pneumophila Chlamydia pneumophila Coxiella burnetii 74 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara IE - Diagnosis blood culture - single more endocardial echocardiogram important laboratory diagnosis test – incubation up MAJOR CRITERIA (GOLD to 5 to 10 days STANDARDS) serology – fastidious slow growers microorganisms (e.g., Coxiella require very rich media burnetti & Bartonella henselae); need unique growth maybe, Mycoplasma conditions pneumoniae, Legionella and recalcitrant to growth Brucella abortus) 16S RNA PCR – not routine or infalible 75 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara antibiotic When in Rome as the Romans ! susceptibility determined before antimicrobial therapy is started synergistic antibiotics 4-6 wks, e.g.,: (really ?!?) o NVE severe: gentamycin + vancomycin o NVE Indolent: amoxycillin + gentamycin o PVE: gentamycin + vancomycin + rifampicin for some intracellular pathogens it can go on for years antibiotic prescribing guidelines recommendations vary once you know the microorganism: guidelines for treatment, e.g.,: local practice 76 expert opinion informed by microbiologist  Dr Jorge Garcia-Lara o Gentamycin, for G- o Vancomycin, for G+ o Rifampicin, penetrates the biofilm of S. aureus & CONS in subacute endocarditis treatment may be safely delayed until culture & sensitivity results are available 77  Dr Jorge Garcia-Lara The not so good old culture False negatives in blood cultures: previous antibiotic treatment fastidious organisms (either because they are or because bacterial subpopulation selection after antibiotic treatment) size decrease of a positive vegetation (e.g., after antibiotic treatment) >85% false negatives (-) ~30% false positives (+) 78  Dr Jorge Garcia-Lara Learning outcomes M1.I.CVS.MIC1 - Recognise different bacterial, viral, fungal and parasitic infections of the cardiovascular system M1.I.RES.MIC1 - Demonstrate an understanding of lower respiratory tract infections and name the common pathogens 79 Bachelor of Medicine and Bachelor of Surgery MBBS  Dr Jorge Garcia-Lara Questions? [email protected] @GarciaLaraClan #UCLanMicrobiology 80 Bachelor of Medicine and Bachelor of Surgery MBBS