Evidence based management of community acquired Pneumonias | Jindal Chest Clinic

Presentation on "Evidence based management of community acquired Pneumonias"

1. Dr. S.K JINdal www.jindalchest.com E vidence based management of community acquired Pneumonias

2. What is Pneumonia? Pneumonia – Alveolar infection resulting from the invasion and overgrowth of microorganisms in lung parenchyma . Anatomical Lobar / segmental Bronchopneumonia Microbiological Empirical Community acquired Hospital acquired Aspiration Immuno compromised host Behavioural / therapeutic Easy / difficult Recurrent / complicated Persistent / resistant

3. CLASSIFICATION OF PNEUMONIAS Community-acquired pneumonia - infection in a non-hospitalized population. Health-Care associated pneumonia (HCAP) is type of CAP. Pneumonia in the Immunosuppressed individuals . Hospital-acquired pneumonia - pneumonia 48 hours or more after admission, and was not incubating at the time of admission Ventilator-associated pneumonia - pneumonia that arises more than 48-72 hours after endotracheal intubation

4. Homeostasis - unbalanced in CAP The germ is NOTHING… the soil is EVERYTHING… Louis Pasteur 189 5 Host defenses Pathogens

5. Management Issues Presence of any Risk Factors? What other organs are involved? Which organism is likely ? Is it drug-sensitive? Multiple organisms? Antibiotic choice? How long to continue? Supportive therapy? Future course- Resolution/ Complications/ Failure/ Mortality? What is the evidence for each decision?

6. Risk Factors Increased incidence: COPD, DM, CHF, CAD, malignancies, ch. neurol or liver disease, CRF Increased mortality: DM, CAD, CHF , neurologic dis Immunosuppression,., active malignancies, increasing age, bacteraemia, leukopenia , hypotension, hypoxemia , altered mental status, tachypnea , aspiration pn ., Gram – ve inf. Modifying factors: Risk of inf. with drug resistance and unusual pathogens Age > 65 yrs, Alcoholism  Lactam therapy within past 3 months Immunosuppression, Multiple comorbidities Exposure/s to child in a day care centre

7. Risk for enteric gram – ve inf Recent antibiotic therapy Underlying cardiopulm dis Residence in a nursing home Multiple medical co-morbidities Risk for P. aeruginosa Structural lung dis BSA therapy for > 7 days in the past month Corticosteroids (at least 10 mg predn /day) Malnutrition

8. Grading ( Modified GRADE System) Strength of recommendation A or B Quality of evidence, supporting the recommendation 1, 2 or 3 Usual Practice Point (UPP) if evidence is inadequate or not documented Grade A: Strong recommendation to do (or not,do ): where the benefits clearly outweigh the risk (or vice versa) for most , if not all patients Grade B: Weaker recommendation where benefits and risk are more closely balanced or are more uncertain

9. Level of Evidence Level I: High quality – consistent results from well performed RCTs, or overwhelming evidence from well-executed observational studies with strong effects Level 2: Moderate quality evidence from randomized trials (that suffer from flaws in conduct , inconsistency, indirectness, imprecise estimates, reporting bias, or other limitations) Physiologic studies Level 3: Low-quality evidence from observational evidence or from controlled trials with several serious limitations

10. Diagnostic algorithm Clinical features CXR (If available) Yes No Radiol . Features Present CRB-65 Score Absent < 1 >1 Oximetry Consider alternate Dx Yes SaO2 < 92% (Age < 50) or < 90% (age > 50) No Admit Manage as OPD pt. CXR, Blood tests Bl. Gases, sputum Ist dose of antibiotic Decide or ICU/Non ICU adm . (ATS criteria)

11. Role of diagnostic tests CXR, if feasible (1A) CT chest only in those with non-resolution or for assessment of complication (2A) Bl. Culture in hospitalized patients (2A) Sputum/BAL smear and culture for hospitalized patients (2A) Sputum for AFB (UPP)

12. Chest radiographs False-negative False-positive Early in course Interstitial lung dis PCP pneumonia Vasculitis Miliary TB Atelectasis Dehydration CHF Neutropenia Pulmonary infarcts Malignancies Miscellaneous

13. General Laboratory Tests Leucocytosis (polymorphonuclear) Raised ESR Arterial blood gases S. electrolytes; liver & renal function tests Blood sugar H.I.V. serology Blood cultures Others

14. Microbiological tests NOT INDICATED in OUT-PATIENTS BUT ONLY in IN-PATIENTS Blood culture - Positive in around 25%; indicator of severity Sputum smear and culture - Rapid, inexpensive, variable sensitivity & specificity Serology - Initial testing only if onset > 7 days, or severe or unresponsive to -l actams Legionella urine antigen - Highly specific & sensitive; intubated patients with severe disease

15. “Pulmonary Samples” for Diagnosis Sputum / induced sputum Bronchoscopic - Washings - Bronchial / bronchoalveolar lavage - Biopsy (bronchial / TBLB) - Needle aspiration Transthoracic needle biopsy Transtracheal aspiration Pleural aspirate / biopsy Thoracoscopic specimens

16. Assessment of Severity Routine C linical Assessment Host factors General indicators: Fever, Leucocytosis, blood cultures, C Reactive Protein Clinical Scoring System Micro organism pattern Biomarkers

17. Markers of Severity Age over 65 yr Presence of coexisting illnesses such as COPD, bronchiectasis, malignancy, diabetes mellitus, CRF, CHF, chronic liver disease, alcoholism, malnutrition, cerebrovascular disease, postsplenectomy and history of hospitalization within the past year RR > 30 bpm, DBP < 60 mm Hg, SBP < 90 mm Hg, HR > 125 bpm, fever < 35 o > 40 o C, altered mental status and evidence of extrapulmonary sites of infection

18. Clinical Assessment Scores CURB – 65, CRB Pneumonia Severity Index (PSI) Apache scoring system (APACHE II) PIRO score SMART COP and SMRT-CO A-DROP Others : Multivariate prediction model

19. Criteria for risk stratification in CAP CURB-65 CRB-65 ATS-IDSA criteria Confusion Urea > mmol /L Respiratory rate > 30/min Blood pressure (diastolic blood pressure < 60mmHg or systolic blood pressure < 90mmHg) Age > 65 years Confusion Respiratory rate > 30 min Low blood pressure (diastolic blood pressure < 60mmHg or systolic blood pressure < 90mmHg) Age > 65 years Major criteria Invasive mechanical ventilation Septic shock with the need for vasopressors Minor criteria Respiratory rate > 30 PaO2/FiO2 ratio < 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN level > 20 mg/ dL ) Thrombocytopenia (platelet count < 100,000 cells/mm 3 ) Hypothermia (core temperature < 36 o C)

20. Biochemical markers of Diagnosis/ Severity/Prognosis To aid diagnosis Procalcitonin C Reactive protein Leukocytosis Pro-inflammatory cytokines- Il 2, IL 6, TNF a Indicators of prognosis PCT , Markers of coagulation As a guide to antibiotic therapy: PCT Others : Plasma cystatin CPlasma Cathepsin B Natriuretic peptides (NT-pro BNP, MR-pro ANP, BNP) Variant promoter of IL-6 (IL-6 – 174 GG genotype )

21. Procalcitonin (PCT) Inflammatory biomarker Acute phase reactant primarily produced by liver in bacterial infections Inhibited by viral related cytokines Increased PCT: help to identify patients who – Benefit from antibiotics Increased risk of death PCT-guided group had significantly less antibiotic use and duration of therapy (Christ-Crain et al 2006).

22. How do the cytokine activation patterns and biomarkers help? Influenced by micro-organisms (Facilitate only a broader understanding of host inflammatory response to micro-organism) Provide important information on diagnosis, severity and prognosis. Not predictive of either classification or failure. Not possible to score and classify severity on basis of biomarkers.

23. Biomarkers: What one expects? Additional, actionable information to Assist a rapid and reliable diagnosis Indication of prognosis Select patients for specific interventions Reflect the efficacy (or its lack) of specific interventions Warns of progression Exhibit a large amplitude of variation Shows consistent response to infectious stimuli (Rapid, easy and inexpensive) Povoa , 2008

24. Management of CAP Anti-microbial therapy - Antibiotics Supportive & symptomatic therapy Fever, Dehydration, Systemic symptoms Stabilization of severity parameters De-oxygenation, Organ failure, Shock Treatment of complications Empyema , Cavitation, BP Fistulae Management of drug-toxicities Preventive strategies

25. Need for Pathogen detection “No difference in length of hospital stay and 30-day mortality between pathogen directed vs empirical broad spectrum antibiotic therapy” Van der Eerden et al, 2005 To confirm the diagnosis To guide antibiotic choice To define antibiotic sensitivities To reduce adverse events To reduce costs For epidemiological information about new emerging pathogens

26. Antibiotic Use Factors for Antibiotics use for empiric treatment The most likely pathogens Knowledge of local susceptibility patters Pharmacokinetics and pharmacodynamics of antibiotics Compliance, safety and cost of the drugs Recently administered drugs

27. Antibiotics for CAP As early as possible – more important in severe CAP (2A) In outpatient settings, tmt targeted to st . pneumoniae (1A) Stratification on basis of presence/absence of comorbidities Select antibiotics on basis of stratification (1A) Avoid fluoroquinolones (1A) Appropriate dose and duration (1A) Tetrocystine – insufficient evidence (3B)

28. Indications for empiric combination therapy in CAP Presence of comorbid medical conditions Chronic heart, lung, liver or renal disease Diabetes mellitus Alcoholism Malignancies Use of antimicrobials within the previous 3 months Severe CAP with or without comorbidities

29. Fluoroquinolones (FQs) in CAP Meta-analysis of nine trials. Mean duration of delayed diagnosis and treatment of pulmonary TB in FQ prescription group was 19.03 days, the odds ration of developing fluoroquinolone -resistant M. tuberculosis strain was 2.7 (95% CI, 1.3 – 5.6 ) Chan et al (2011) Case-control study> Multiple FQs imparted resistance to T.b . Long et al (2009) 3. Newer FQs appeared to mask active pulm TB Chang et al. (2010)

30. Doses of drugs used in CAP Drug Doses Amoxicillin 0.5-1 g thrice daily (PO or IV) Co- amoxiclav 625 mg thrice a day to 1 g twice daily (PO)/1.2 g thrice daily (IV) Azithromycin 500 mg daily (PO or IV) Cefriaxone 1-2 g twice daily (IV) Cefotaxime 1 g thrice daily (IV) Cefepime 1-2 g two or three times a day (IV) Ceftazidime 2 g thrice daily (IV) Piperacillin-tazobactam 4.5 g four times a day (IV) Imipenem 0.5-1 g three to four times a day (IV) Meropenem 1 g thrice daily (IV)

31. Rx of organism-documented CAP Pathogen Preferred Alternative Pneumococcus Amoxicillin or Penicillin G, ceftriaxone Macrolides, cefuroxime M. pneumoniae , C. pneumoniae , Legionella Macrolides, fluoroquinolones Tetracyclines H. influenzae Co- amoxiclav Cefotaxime, Ceftriaxone or fluoroquinolone Gram-negative enteric bacilli Cefuroxime , Cefotaxime , ceftriazone Fluoroquinolone or carbapenems Ps. aeruginosa Antipseudomonal β - lactam + aminoglycosides Antipseudomonal β - lactam + fluoroquinolones S. aureus Non-MRSA MRSA Cloxacillin Vancomycin Clindamycin Teicoplanin

32. Duration of therapy Duration of therapy Pneumococcus, Gram negative bacteria - 7 to 10 d M. pneumoniae & C. pneumoniae - 10 to 14 d Legionella, Pseudomonas, Staph. aureus – 14 to 21 d Switch to Oral Therapy Improvement in cough and dyspnea, afebrile (< 100 F) on two occasions 8 h apart, WBC count decreasing, functioning GIT with adequate oral intake

33. What is Clinical Failure? Death Need for mechanical ventilation RR > 25 / min SaO 2 < 90%; PaO 2 < 55 mmHg Hemodynamic instability Less than 1 o C decline in admission temp. of > 38.5 o C Altered mental state

34. How to predict failure? Routine C linical Assessment Host factors General indicators: Fever, Leucocytosis, blood cultures, C Reactive Protein Clinical Scoring System Micro organism pattern Biomarkers

35. Causes of Clinical Failure Antimicrobial failure Patient noncompliance, improper dosing regimen, resistant pathogen, unusual or unsuspected pathogen Infectious complications Empyema, endocarditis, superinfection Incorrect diagnosis Malignancy, pulmonary embolism, other noninfectious etiologies

36. Approach to Treatment-Failure Persistent fever, worsening dyspnea, Un-resolving pneumonia symptoms, continued disability Chest X-Ray Chest CT Bronchoscopy Lab tests Lung biopsy Exclude Complications: Effusion, empyema, cavitation, bronchiectasis Comorbidities (Pulmonary / Non-pulmonary) Systemic complications – Sepsis, Infective endocarditis Non-infectious/Uncommon infectious etiologies Other infections: TB, Fungal, Zoonotic

37. Out-patients Recommendations No cardiopulmonary disease / No disease modifying factors β -lactam, macrolide, doxycycline Cardiopulmonary disease / disease modifying factors Beta lactam + macrolide (or doxy) Fluoroquinolones should be used ju diciously

38. Inpatient Recommendations Non-severe CAP β -lactam or macrolide Severe CAP/No risk factor for Pseudomonas IV Beta lactam + azithromycin Severe CAP/Risk factor for Pseudomonas IV anti-pseudomonal β -lactam + anti-pseudomonal fluoroquinolones IV antipseudomonal β -lactam + amino-glycoside + azithromycin Fluoroquinolones should be used judiciously

39. Recommendation for vaccination Pneumococcal vaccine: Routine use among healthy immun ocompetent adults for CAP prevention - not recommended (1A). May be considered in special populations at high risk for invasive pneumococcal disease (2A). 2 . Influenza vaccination: S hould be considered in adults for prevention of CAP (3A). Smoking cessation should be advised for all current smokers (1A).

40. High-risk groups for vaccination Pneumococcal disease Chronic cardiovascular, pulm , renal, or liver disease Diabetes mellitus, Cerebrospinal fluid leaks Alcoholism, Asplenia Immunocompromising conditions/medications Influenza Chronic cardiovascular or pulmonary disease Chronic metabolic disease (including diabetes mellitus) Renal dysfunction, Hemoglobinopathies Immunocompromising conditions/medications Compromised lung function or increased aspiration risk

41. Hippocrates…

42. Organisms Antibiotics Most aerobic and Penicillin G, β -lactam anaerobic cocci and β -lactamase inhibitors Gram + ve , E. coli, Ampi ., amoxicillin, β lactam Proteus & β -lactamase inhibitors Staph aureus - Cloxacillin Ps aeruginosa - Carbapenems , piperacillin- tazobactam , cefepime, ceftazidime , ciprofloxacin, aminoglycosides Anaerobes - Clindamycin , penicillin G + metronidazole , carbapenems, β -lacta and β lactamase inhibitors

43. Do Not Use a BOMB when a Bullet does the job The Bomb will certainly kill BUT the Bomb is….. Not cost-effective More destructive Responsible for extensive collateral damage Accompanied with long lasting effects, including rebound and chain reactions. It is much wiser to Choose the Bullet correctly

44. WHO mortality figures for lower respiratory tract infections in India Age group (years) No. of deaths per lakh population in 2008 15-59 6.2 > 60 622.2 Overall 35.1

45. SUMMARY Clinical diagnosis of pneumonia is important for early treatment decisions. Clinical scores constitute the most relevant criteria f or prediction of clinical failure and to decide the site of care. Biomarkers may aid in diagnosis, help to decide the antibiotic duration and the prognosis. An appropriate choice of antibiotic/s significantly improves the outcomes. Cause of failure should be identified and appropriate treated.

46. THANK YOU