1. Community acquired pneumonia A/Prof Peter Wark Department of Respiratory and Sleep Medicine John Hunter Hospital

2. Ms AN, 37 year old Previously well 3 day history –Sore throat –Dry cough Today –Left sided sharp chest pain –Felt hot and unwell, rigors

3. Differential diagnosis Pneumonia Bronchitis Asthma Pulmonary embolus

5. Epidemiology In US pneumonia –6 th leading cause of death –Leading cause of death from an infectious disease Mortality –1-5% –Up to 40%

6. Identifying a pathogen

7. In clinical practice an organism is found in only 50% No single test is available that can identify all organisms History, clinical findings and X-ray changes are not diagnostic of a particular organism ? Mixed infection, especially viral and bacterial

8. CAP, no history of significant chronic disease 20-60%, Strep Pneumoniae 3-37%, Mycoplasma Pneumoniae and Chlamydia Pneumoniae 10% cases –Viral (exceptions influenza, adenovirus) –Staph Aureus (MSSA and MRSA) –Gram neg organisms –Legionella pneumophilia (3-10%)

9. CAP and co-morbid diseases Risk is increased –Nursing home resident –Cardiorespiratory disease (COPD, CCF) –Immunosuppression –Alcoholism –Recent antibiotic use –Age > 65 years Cause –more gram negative organisms or resistant pathogens –Viral (CMV, VSZ, respiratory viruses –PCP –Fungal

10. Severe CAP 20-50%, Strep Pneumoniae 10-30% E.Coli, K Pneumoniae, Enterobacter 3-10% Legionella pneumophilia (adm ICU) Staph Aureus – MSSA –MRSA Viral Pseudomonas Aerugniosa ?

11. Viral pneumonia PCR improves detection Some series, accounts for up to 24% Not predicted by CXR or CRP Pathogens –Influenza –SARS –RSV –Rhinovirus (co-pathogen 35% severe CAP) –Adenovirus

12. How to identify the pathogen?

13. Sputum Sensitivity 10-54% “good sample” and cultured quickly Gram stain positive (esp Pneumococcus) Culture best with heavy growth and correlation with gram stain Special culture medium for Legionella, sensitivity 10- 80% (better with BAL), specificity 80% High false positive, especially Staph Aureus & GNB

14. Blood cultures Sensitivity 7-16%, specificity 90% (depends on organism) Strep Pneumoniae, –accounts for 2/3 positive blood cultures –Pneumococcal bacteraemia, 1%, mortality 19% vs 4% hospitalised with pneumococcal pneumonia

15. Urinary antigens Detection of Strep Pneumoniae & Legionella Advantages –Easily available –Valid after antibiotics initiated Pneumococcus –Sensitivity 82%, specificity 97% (bacteraemic) Legionella –Sensitivity 70-80%, specificity 97% –Only L. Pneumophilia

16. Severity scoring CURB-65 –Confusion (1 point) –Urea >7mmols (1) –Respiratory rate >30 (1) –BP, systolic <90 or diastolic < 60 (1) –Age >65yrs ScoreImplication 0-1Risk death <3%, OP 2-3 3-5 Risk death 9% hospitalise Mortality 15-40% consider ICU

17. PSI in adults Sex M (0 points) F (-10 points) Demographic factors Age (1 point for each year) Nursing home resident (10 points) Comorbid illnesses Neoplastic disease (30 points) Liver disease (20 points) Congestive heart failure (10 points) Cerebrovascular disease (10 points) Renal disease (10 points) Physical examination findings Altered mental status (20 points) Respiratory rate >= 30/minute (20 points) Systolic blood pressure < 90 mmHg (20 points) Temperature = 40 degrees C (15 points) Pulse >= 125/minute (10 points)

18. PSI in adults Laboratory and radiographic findings Arterial pH < 7.35 (30 points) Blood urea nitrogen >= 30 mg/dL (11 mmol/L) (20 points) Sodium < 130 mEq/L (20 points) Glucose 14 mmol/L) (10 points) Hematocrit < 30 percent (10 points) Partial pressure of arterial oxygen < 60 mmHg or oxygen saturation < 90% (10 points) Pleural effusion (10 points) 0-50 Points:Class I 0.1% Mortality 51-70 Points:Class II 0.6% Mortality 71-90 Points:Class III 0.9% Mortality 91-130 Points:Class IV 9.3% Mortality 131-395 Points:Class V 27.0% Mortality

19. PSI and assessment

20. Assessment; co-morbidities Age >65yrs Chronic disease –COPD –CCF –Diabetes –Liver disease –Chronic renal failure –Neoplasia Alcoholism Immunosuppression

21. Assessment examination Altered mental state Tachypnoea (RR>30) Hypotension (systolic <90mmHg) Temperature 40 o C Tachycardia (125bpm)

22. Assessment, investigations Electrolytes –Na <130mmol –Glucose >14mmol Renal impairment (Urea >11mmol/L) Gas exchange and acid base –pH <7.35 –PaO 2 <60mmHg CXR –Extent consolidation –Presence of an effusion

23. Ms AN ClinicalInvestigations Age 39 years No co-morbidities Altered mental state BP 100/50 Temp, 39.5 RR, 32bpm HR 125 pH 7.38 pO2 68mmHg Na 135mmols HCT 32% Urea 8mmols BGL 8mmols No effusion Score 104 Class 4 mortality 9.3%

24. Management

26. Empirical antibiotics Moderate –Penicillin 1.2g 4hrly IV + –Doxycycline or clarithromycin or azithromycin orally –If gram negative, add gentamicin for 2-3 doses (7mg/kg/d) Severe –Penicillin 1.2g IV 6hrly + –Gentamicin IV 2-3 doses + –Azithromycin 500mg IV Alternate –Ceftriaxone 1g/d or –Tazocin 4.5gm QID –Moxifloxacin 400mg IV/PO daily

27. Outcomes with empirical antibiotics (Asadi et al Resp Med 2012 2973 patients mild pneumonia Those who received guideline based treatment, less likely to die, 6% v 1% (OR 0.23, 0.09 to 0.59) Those who received macrolides (as opposed to fluroquinolones) were less likely to die.

28. Watching the clinical response

29. The usual response 24-72 hrs, see stability Day 3, –improvements in symptoms –Defervescence by day 4 (most rapid Strep Pneumoniae) –Fall in WCC & CRP or 50% reduction PCT CXR –Slow to resolve (60% some abnormality at 4 weeks)

30. Responders 48 to 72hrs Switch to PO therapy –Improvement in cough and dyspnoea –Afebrile –WCC & CRP improving Discharge No need to repeat CXR now, but 4-6 weeks post discharge

31. Procalcitonin in CAP PCT >0.25 mcg/L and decision to use antibiotics reduces unnecessary antibiotic use in 2 RCTs –Improves diagnosis in those with heart failure –Cost effective in ICU Higher PCT predicts the presence of bacteraemia Increase in PCT in first 72hrs was associated with reduced survival Fall in PCT by 50% indicates an ability to switch to PO antibiotics

32. PCT and CURB-65

33. Progress 24-72hrs clinical response Early clinical response Switch to oral & discharge Lack of clinical response Deteriorating Revaluate Host Pathogen Complications

34. Failure to respond

35. Lack of response or deterioration Host factors –Elderly –Immunosuppressed –Bacteraemia –Chronic illness –Diabetes –Alcoholism –Second nosocomial pneumonia Misdiagnosis –Pulmonary embolus –CCF –Pulmonary haemorrhage –Pulmonary vasculitis –BOOP –Acute interstitial pneumonitis –Eosinophilic pneumonia –Hypersensitivity pneumonitis Local factors –Effusion/empyema –Abscess

36. Called to Ms AN Agitated and very breathless P 140, BP 90/50, RR 38, T 39 0 C ABGs (FiO 2 0.5) –pH 7.32 –PaO 2 55mmHg –PaCO 2 30mmHg –HCO 3 16mmols

37. Called to see Ms AN Agitated and very breathless P 140, BP 90/50, RR 38, T 39 0 C ABGs (FiO 2 0.5) –pH 7.32 –PaO 2 55mmHg –PaCO 2 30mmHg –HCO 3 16mmols

38. The cause? Progression of pneumonia ARDS Bacteraemia Shock

39. Empyema Suspect –Persistent fever –Pleuritic chest pain –Organisms (pneumococcous, Strep Milleri, Staph Aureus) Clinical examination Image again

40. Empyema

41. Lung abscess/necrotising pneumonia

42. Conclusions 1.Clinical assessment –Diagnosis with CXR –Risk factors for poor outcomes –Severity assessment 2.Follow guidelines for empirical antibiotics 3.Assess response 4.Reassess if response is not typical