Lecture: Respiratory Infection – An ABC Guide

respiratory infection - AN ‘ABC’ GUIDE (FOR STUDENTS*) Dr Devesh J Dhasmana Consultant Respiratory Physician, NHS Fife Clinical Teacher, St Andrews djd5@ Declaration of interests None related to this talk Learning outcomes Recognise the normal host defence mechanisms of the respiratory tract and...

respiratory infection - AN ‘ABC’ GUIDE (FOR STUDENTS*) Dr Devesh J Dhasmana Consultant Respiratory Physician, NHS Fife Clinical Teacher, St Andrews djd5@ Declaration of interests None related to this talk Learning outcomes Recognise the normal host defence mechanisms of the respiratory tract and how these influence infection Detail the infective agents which cause respiratory tract infections Recognise and describe the clinical features of respiratory tract infections Identify the main treatment modalities for respiratory tract infections Understand the key areas in the diagnosis and management of pneumonia Appreciate some future directions of care, including use of rapid diagnostics, sequencing, and health economics Respiratory infection 1 Nose to alveolus ◦ ‘Devesh, the respiratory tree starts at the nose, always scope through the nose’, (Dent 2007) Pathogen ◦ Virus ◦ Bacteria (typical’ vs ‘atypical’) ◦ Other – other bacteria, Mycobacteria (TB, MOTT/NTM), Actinomyces, fungus (mould, yeasts), parasite Differential – ‘interstitial pneumonia’ (‘-ia’), inhalation, allergy Respiratory infection 2 URTI – rhinitis, sinusitis, pharyngitis, tonsillitis (Quinsy), laryngitis LRTI – laryngo-tracheo-bronchitis (LTB), bronchiolitis, pneumonitis Pneumonia/Bronchopneumonia Empyema (not emphysema….and not “emphysemia”) Bronchiectasis (not bronchitis; could be ‘bronchiolectasis’) Lung abscess: cavitating pneumonia, mycosis (Aspergillosis) also, ‘Exacerbation of…’ ..COPD, Asthma ..Bronchiectasis ..Fibrotic lung disease Infection vs ‘non-infective’ exacerbations Infections provoke inflammatory response Inflammatory response may be damaging Tools required/needed to differentiate infection from inflammation Principles of treatment Source control (not source code) Consider the pathogen Consider the host (immune system) Consider the severity Infection Outcome = pathogen x host Basic practice 1 Basic microbiology Respiratory microbiology ◦ Commensal organisms vs. respiratory pathogens ◦ the lung microbiome ◦ Why do we get pneumonia? “Every pneumonia is an immune system failure …” (Kelleher, 2007) “I feel like a failure” (Professor, StA) BTS, 2009 Gadsby et al., CID 2016 Gadsby et al., CID 2016 Medical Microbiology Gillespie, Bamford 2012 Basic practice 2 Basic antibiotic biology Respiratory antibiotics ◦ Consider spectrum, route of administration, bioavailability, duration ◦ Consider goal of treatment – cure, control, maintenance - ‘immune-modulation’ Basic practice 3 Basic immunology Bannister, Gillespie, Jones, Infection Sepsis “A life-threatening organ dysfunction caused by a dysregulated host response to infection” Septic shock is a subset of patients with profound circulatory, cellular and metabolic abnormalities MAP <65 mmHg, lactate >2 mmol/l hypotension despite fluid resuscitation, requiring vasopressors Consider sepsis alongside consideration of pneumonia & antibiotics 3rd International Consensus Definition Statement, JAMA 2016 Standards of care - updates BTS guidelines of practice; BTS Audit NICE Pneumonia Guidelines, 2014 British Infection Association (BIA) guidelines – see BTS/NICE International guidelines ◦ European Respiratory Society – ERM (Monograph) on CAP, 2014 ◦ ATS/IDSA Guidelines, 2019 treatments Treatments for respiratory infection 1. URTI Supportive, Not antibiotics (probably) Special diagnoses – stridor, croup, quinsy Consider underlying diagnosis – allergy, polyps, immunity Consider ENT review and direct nasendoscopy Treatments for respiratory infection 2. LRTI (Supportive) Maybe antibiotics Consider related morbidity – URT, LRT, asthma, chronic cough Make a back-up plan – consider CXR, antibiotics, referral Treatments for respiratory infection 3. PNEUMONIA (consolidation on chest imaging) (Supportive) Yes, antibiotics. Difficult not to, even if likely virus. Decisions on antibiotic choice (spectrum), duration (5-7-10 days) Consider underlying diagnoses – allergy, polyps, immunity, co-morbidities, bronchiectasis, COPD Consider admission Treatments for respiratory infection 4. EMPYEMA Definitely antibiotics! Definitely drain! (French saying, Hopkins, 2007) Supportive – comorbidities, psycho-social, pain (drain), oxygen Consider underlying diagnosis – pathogen, immunity SURGERY? THORACOSCOPY? ‘Medical treatment’ second choice – 6 weeks+ abx Treatments for respiratory infection 5. BRONCHIECTASIS Treatments for respiratory infection 5. BRONCHIECTASIS AIRWAY CLEARANCE! then Antibiotics Long-term chronic lung disease, ‘management plan’, specialist nurses, interested GPs, motivated patient, preventative therapies, rescue therapies Consider exacerbation of BE vs pneumonia vs progression Treatments for respiratory infection 6. LUNG ABSCESS, CAVITATION Definitely antibiotics! Treatment defined by cause Identify the pathogen SURGERY? Antibiotics. Inhaled/intravenous/oral ‘Medical treatment’ first choice – 6 weeks+ abx Clinical presentation Decision to admit H@H MILD ILLNESS Consider: Discharge Advice Support at home Household contacts Clinical Research Trials Treatment (eg.RECOVERY) Observational (e.g.ISARIC, GenOMICC) Palliation/(H)ACP End of life care Involvement family COVID19 - suspected or confirmed ARDS PNEUMONIA Severity scores SOFA/qSOFA/lac >2 CURB65 SEPSIS severe sepsis/septic shock Establish ceiling of care and HACP MILD SEVERE Consider the following: Severity of disease Admission vs discharge O2 – low flow, high flow (VM) Antibiotics Plan ward Consider discussion with ICU ARDS: criteria, severity, alternative diagnoses Severe sepsis, septic shock O2 – mod-high flow (VM); sats >94%, then >90% Ventilation – CPAP, (BiPAP), Mechanical Plan ward – O2, AGPs, NIV, (HDU) ≧2 organ failure AGPs: Aerosol Generating Procedures; ARDS: Acute Respiratory Distress Syndrome; CPAP: Continuous Positive Airway Pressure; CURB65: Confusion, Urea>7, RR>30, BP <90/60, Age>65; HACP: Hospital Anticipatory Care Plan; NIV: non-invasive ventilation; (q)SOFA: (quick) Sequential Organ Failure Assessment; VM: Venturi Mask Dexamethasone et al. Hydroxychloroquine not effective, may be harmful Dexamethasone is effective, and not harmful Lopinavir/ritonavir is not effective Remdesivir MAY be effective (given early, immune-suppressed) Azithromycin is not effective Convalescent plasma is not effective Tocilizumab is effective (where significant inflammatory response) Aspirin is not effective Colchicine is not effective REGN-COV2 monoclonal antibodies were effective – NOT TODAY! CPAP (Continuous Positive Airway Pressure) best in respiratory failure Baricitinib is effective (in addition to steroids/tocilizumab) Current drugs under investigation include: High dose dexamethasone, empagliflozin, molnupiravir, Paxlovid, Sotrovimab Dexamethasone cases CASE 1 URTI CASE 2 LRTI CASE 3 LRTI Mucus plugging (pneumonia) CASE 4 Right basal pneumonia (probably) “Devesh, ask the patient – they’ll tell you what’s wrong” (Davidson, 2008) CASE 5 Pneumonia - May 2017 - Left lower lobe Pneumonia - June 2017 - improving June 2017 May 2017 May 2017 May 2017 May 2017 May 2017 May 2017 May 2017 May 2017 Oct 2018 Oct 2018 Dec 2018 Jan 2019 Jan 2019 Feb 2019 CASE 5 Aspergillosis ‘Pneumonia’ (Emphysema, Bronchiectasis) Total IgE 1451 iu/l Aspergillus-IgE 9.4 Aspergillus-IgG >200mgA/l Chronic Pulmonary Aspergillosis Chronic Cavitatory Pulmonary Aspergillosis (CCPA) CASE 6 CASE 6 Total IgE 143 iu/l Aspergillus-IgE Aspergillus-IgG >200mgA/l Voriconazole 3 months later But still fever CRP> 150 Malaise, weakness ANCA+ PR3+ Granulomatous polyangiitis (GPA) (not Wegener’s) Prednisolone Rituximab Pneumonia – Community Acquired Definition - clinical features + radiology Incidence - 1% adults; 5-10% of GP-presentation with ‘LRTI’ Aetiology – virus, bacteria (Strep, H.inf), co-infection Sex – same in incidence; possibly slightly worse outcomes F>M Geography – relevant in aetiology & outcomes (socio-economics) Pathology (MM) – consolidation, pus/necrosis, nph/lph/eos Symptoms and Signs – cough + phlegm, SOB, fever Prognosis – consider CURB65: <1%  50%; consider CAP/HAP BTS Guidelines for CAP 2009, 2015 ‘CURBing’ our enthusiasm CURB65 30d mortality 0 0.7% 1 2.1% 2 2-9% 3 17% 4 (40) 5 (45-60) CRB65 – no blood test required Similar spread of severity: 1.2% - 5% – 12% - >33% PSI – Pneumonia Severity Index Comparable scores More comprehensive, more time-consuming Antibiotics – which ones? ‘CURBing’ our enthusiasm CRB65 – no blood test required CURB65 30d mortality 0 0.7% 1 2.1% 2 2.9% 3 17% 4 (40) 5 (45-60) Similar spread of severity: 1.2% - 5% – 12% - >33% CURB initially meant to offer prognostic information But more severe ≠ atypical & ≠ response to macrolide Why do we separate macrolide use in national policies? Singanayagam et al., ERJ 2017 Antibiotics – how long? Not known. It depends. Depends on pathogen – consider sensitive Streptococcus pneumoniae pneumonia vs Staphylococcus aureus pneumonia Depends on disease – consider pneumonia + cavity + bacteraemia + signal change in bone Depends on host response ◦ TCS: ‘Time-to-Clinical Stability’ Infection Outcome = pathogen x host Antibiotics – no really, how long? Pneumonia - 5-7 days; 3 days may be sufficient (pneumococcus) Deep seated infection – 14 days Empyema – 4-6 weeks Cavitation – pyogenic >6 weeks, TB 6 months, NTM 18 months Requires confidence in diagnosis, in pathogen, with monitoring Hospital acquired pneumonia HAP, HealthCare Associated Infection (HCAI), HAI Healthcare facilities – nursing home, residential home Includes >48h after admission – or within 10-30 days of discharge Radiographic change – pneumonia, effusion, empyema Altered microbiological context – gram-negative, anaerobes; MRSA, (C.difficile) Worse outcomes – 25-50% mortality Other things on pneumonia Drug resistance Antibiotic stewardship Health economics – OP vs IP treatment, high cost orals (100% bioavailability), ‘OPAT’, ‘Hospital@Home’ TCS – time to clinical stability ?>CRP ?>7days ?=stratified medicine Current concepts Consider microbiome, metabolome, rapid diagnostics What is the context – how much money do you have? What is the end-goal – pathogen, severity, host Vaccination! Follow-up What’s the goal? Consider exclusion of other diagnoses, exclusion of residual infection, complications of infection Consider pneumonia vs bronchiectasis vs pleural infection control The post-pneumonia CXR ◦ Cancer, residual infection or complication, ◦ To be sure to be sure? No! ◦ High risk patients – includes ever-smokers, age >50, recent history of cancer CASE 7 Pneumonia - July 2017 - Right lower lobe Pneumonia - Sept 2017 - improved Pneumonia? - Jan 2019 Pneumonia - nope Differential diagnoses - Organising pneumonia - Bronchoalveolar carcinoma (BAC) - Vasculitis Bronchoscopy 13th Feb 2019 ? Future directions Rapid diagnostics Rapid drug sensitivities Improved community support (‘Hospital@Home’) Immunomodulatory therapy Biomarkers to assess response (‘7 day course’) PAYG vs subscriptions – health-economics, QALY 2.0 ◦ 5d amox; 1 bed-day; 2 weeks Caspofungin; 1x WGS Summary Consider the severity of the infection, the cause of the infection and then the best treatment strategy for that person Use resources wisely – blood tests, sputum, review in hospital, CXR….sputum, CT PET, sequencing Consider a range of alternative explanations in pneumonia – the ‘differential diagnosis’. Work with colleagues for both the individual and the wider community Learning outcomes Recognise the normal host defence mechanisms of the respiratory tract and how these influence infection Detail the infective agents which cause respiratory tract infections Recognise and describe the clinical features of respiratory tract infections Identify the main treatment modalities for respiratory tract infections Understand the key areas in the diagnosis and management of pneumonia Appreciate some future directions of care, including use of rapid diagnostics, sequencing, and health economics References BTS CAP Guidelines 2009 https://www.brit-thoracic.org.uk/document-library/clinical-information/pneumonia/adultpneumonia/bts-guidelines-for-the-management-of-community-acquired-pneumonia-in-adults-2009update/ BTS CAP Summary Recommendations https://www.brit-thoracic.org.uk/document-library/clinical-information/pneumonia/adultpneumonia/annotated-bts-cap-guideline-summary-of-recommendations/ NICE Pneumonia Guidelines, 2014 https://www.nice.org.uk/guidance/cg191/resources/pneumonia-in-adults-diagnosis-andmanagement-pdf-35109868127173 End [email protected] Acknowledgements NHS Fife R&D NRS Fellowship/CSO School of Medicine for interest… Sequencing Whole Genome Sequencing Cost, speed, logistics Bioinformatics Clinical utility Rapid diagnostics – in action https://nanoporetech.com/applications/dna-nanoporesequencing