Pneumonia Symposia - The CRUDEM Foundation
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Pneumonia Symposia presented at Hôpital Sacré Coeur in Milot, Haiti, 2011. CRUDEM’s Education Committee (a subcommittee of the Board of Directors) sponsors one-week medical symposia on specific medical topics, i.e. diabetes, infectious disease. The classes are held at Hôpital Sacré Coeur and doctors and nurses come from all over Haiti to attend.
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Pneumonia Symposia - The CRUDEM Foundation
- 1. Pneumonia Greg Schumaker, MD Assistant Professor Pulmonary, Cri;cal Care & Sleep Medicine Tu@s Medical Center
- 2. Overview • Diagnosis • Epidemiology /Microbiology • Triage/Severity Scoring • Treatment • Special Popula;ons/Bugs • Summary of ATS/IDSA Guidelines • Nosocomial pneumonias
- 3. Types of Pneumonia • Community-‐acquired -‐ Present on admit or within 1st 48 hours -‐ No risk for nosocomial pathogens • Healthcare-‐associated (HCAP) -‐ pa;ents with extensive exposure to healthcare system prior to admit • Hospital-‐acquired (HAP) -‐ develops ≥ 48 hours post admit • Ven;lator-‐associated (VAP) -‐ Develops ≥ 48 hours post intuba;on
- 4. Epidemiology • 450 million cases worldwide • 4 million deaths per year • Highest risk in children < 5 and adults over 75 • 1.4 million children under 5 died in 2010 -‐ 18% of deaths -‐ More than TB, HIV & malaria combined -‐ Most of those deaths in developing countries -‐ Major risks are malnutri;on and poverty WHO and Ruuskanen, O, et al. Lancet, 2011.
- 5. Preven;on • Vaccina;on -‐ Hib, pertussis, measles, pneumococcus -‐ up to 30% reduc;on in incidence • Nutri;on • Breas^eeding 1st six months -‐ up to 15% reduc;on in incidence • Prompt access to treatment • Reduce indoor air pollu;on WHO, 2011.
- 6. Epidemiology • Common cause of sepsis • 7th leading cause of death • 5-‐6 million pa;ents/year • Mortality not significantly improved for years • ~ $10B per year spent • Over 1 million cases per year
- 7. Microbiology • S. pneumo remains most common bacteria • Influenza most common virus -‐ RSV, metapneumo, parainfluenza, adeno • Mycobacteria • Fungi
- 8. Microbiology -‐ Bacteria • Typical -‐ S. pneumo -‐ H. influenza -‐ Moraxella -‐ Staph a. -‐ Aerobic gram nega;ve
- 9. Microbiology -‐ Bacteria • Atypical Bacteria -‐ Legionella -‐ Mycoplasma -‐ Chlamydia
- 10. • Table 6. Most common e0ologies of community-‐acquired pneumonia. Pa;ent type E;ology Outpa;ent Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory viruses Inpa;ent (non-‐ICU) S. pneumoniae Respiratory viruses M. pneumoniae C. pneumoniae H. influenzae Legionella species Aspira;on
- 11. Table 6. Most common e0ologies of community-‐ acquired pneumonia. Pa;ent type E;ology Inpa;ent (ICU) S. pneumoniae Staphylococcus aureus Gram-‐nega;ve bacilli H. influenzae
- 12. Specific Bugs • S. pneumo -‐ Lobar consolida;on -‐ Rust colored sputum • H. flu -‐ elderly or underlying lung disease
- 13. Specific Bugs • Legionella -‐ < 10% of CAP, higher mortality, epidemics • Mycoplasma -‐ Children, young adults & elderly • Chlamydia -‐ Older adults • Influenza
- 14. Specific Bugs • Staph aureus -‐ Elderly -‐ Post-‐influenza • CA-‐MRSA -‐ Necro;zing pna in healthy young pt -‐ Shock -‐ Neutropenia -‐ Panton-‐Valen;ne Leukocidin -‐ Usually suscep;ble to Bactrim, Clinda, Rifampin
- 15. Exposures and Bugs • Bats – Histoplasma capsulatum • Birds – C. psijaci, Cryptococcus, Histoplasma • Farm animals – Coxiella burne; (Q fever) Niederman, Ther Adv Respir Dis, 2011.
- 16. HIV Pa;ents • TB • P. jiroveci • Cryptococcus • CMV • ‘Usual’ typical and atypical agents
- 17. Aspira;on • CVA • Esophageal disorders • Swallowing problems • Neuromuscular disease • Drug/alcohol abuse • Anaerobes/Gram Nega;ve Rods
- 18. CA-‐MRSA Risk Factors • Contact sports • IVDA • Prisoners • Living in crowded condi;ons • MSM
- 19. Diagnosis – Signs/Sx’s • Fever • Cough • CXR Infiltrate • Rales, rhonchi, bronchial BS, egophony • Altered MS • GI sx’s • Leukocytosis • ↑ HR and RR • Chest retrac;on in kids
- 20. Diagnosis • No set of clinical criteria have great sensi;vity • Must have infiltrate on CXR • Sputum and CXR pajerns not consistent
- 21. Diagnosis -‐ CXR • Lobar infiltrate – typical bacteria • Inters;;al – viral or PCP • Nodular – fungal, mycobacteria, nocardia, ac;no
- 22. • Table 4. Criteria for severe community-‐acquired pneumonia. • Minor criteriaa Respiratory rateb >=30 breaths/min Pa02/Fi02 ra;ob <=250 Mul;lobar infiltrates Confusion/disorienta;on Uremia (BUN level, >=20 mg/dL) Leukopeniac (WBC count, <4000 cells/mm3) Thrombocytopenia (platelet count, <100,000 cells/mm3) Hypothermia (core temperature, <36°C) Hypotension requiring aggressive fluid resuscita;on • Major criteria Invasive mechanical ven;la;on Sep;c shock with the need for vasopressors
- 23. Micro Tes;ng • Up to 70% of cases never have iden;fied bug • Out-‐pa;ents – no specific tes;ng needed • Floor Pa;ents – targeted tes;ng • ICU Pa;ents: -‐ Blood Cultures -‐ Sputum Cultures -‐ Urine an;gen tes;ng (Legionella, Pneumo) -‐ Tes;ng may improve mortality in this group
- 24. Blood Cultures • Only + in ~ 15% of pneumonia pa;ents • Majority of + cultures are strep pneumo • ATS/IDSA recommend cultures in: -‐ ICU pa;ents -‐ Cavity on CXR -‐ Leukopenia -‐ Chronic liver disease or EtOH abuse -‐ Asplenia -‐ Pleural Effusion
- 25. Sputum Cultures • Rate of + cultures highly variable (10-‐80%) • ATS/IDSA guidelines: -‐ ICU Pa;ents -‐ Failure of empiric therapy -‐ Cavity on CXR -‐ Alcohol abuse or immunocompromise -‐ Severe lung disease -‐ Pleural effusion
- 26. Urinary An;gen Tes;ng • Bejer accuracy vs. sputum & blood tes;ng • Easier to obtain vs. sputum • Fast turn around • Not affected by abx treatment up to 3 days • Cannot do sensi;vity tes;ng • Legionella test only for Group 1 (~ 80% of dz) • ? Lower accuracy in absence of bacteremia
- 27. Severity Assessment -‐ PSI • Derived from 14K pa;ents with CAP • Validated in 40K pa;ents with CAP • Designed to predict mortality • Excluded immunosuppression • 20 variables • 2 step process • Complexity limits use Fine, MJ, et al. NEJM, 1997.
- 28. PSI • Demographics -‐ Age (years) -‐ Gender (-‐10 for women) -‐ Nursing home (10) • Co-‐morbidi;es -‐ Malignancy (30) -‐ Neuro (10) -‐ CHF (10) -‐ CKD (10) -‐ ESLD (20)
- 29. PSI • Exam -‐ Altered MS (20) -‐ RR > 30 (20) -‐ HR > 125 (10) -‐ SBP <90 (20) -‐ Temp < 35⁰ or > 40⁰ (15)
- 30. PSI • Labs/CXR -‐ pH < 7.35 (30) -‐ Sodium < 130 (20) -‐ Hct < 30 (10) -‐ BUN > 30 (20) -‐ PaO2 < 60 (10) -‐ Glucose > 250 (10) -‐ Pleural Effusion (10)
- 31. PSI -‐ Mortality • Class I – 0.1-‐0.4% (no predictors) • Class II – 0.6-‐0.7% (< 70 points) • Class III – 0.9-‐2.8% (70-‐90) • Class IV – 4-‐10% (90-‐130) • Class V – 27% (>130)
- 32. PSI -‐ U;lity • Performs well at mortality predic;on • Unable to consistently predict need for ICU • Mixed success at guiding out-‐pt vs. in-‐pa;ent -‐ Class I-‐III poten;al out-‐pa;ent therapy shown in some ED studies -‐ In studies using PSI, up to 30-‐60% of low risk pts were s;ll admijed Singanayagam, A ,et al. Q J Med, 2009. Niederman, M, Respirology, 2009.
- 33. CURB-‐65 (BTS) • Confusion • Uremia (BUN > 20) • RR ≥ 30 • BP – SBP < 90 or DBP < 60 • 65 or older • CRB-‐65 excludes BUN Lim, WS, et al. Thorax, 2003.
- 34. CURB-‐65 • Get 1 point for each of 5 items • 0 – 0.7% mortality • 1 – 1.7% mortality • 2 – 8.3% mortality • 3 – 17% mortality • 4 – 41% mortality • 5 – 57% mortality
- 35. CURB-‐65 • 0-‐1 – treat as out-‐pa;ent • 2 – brief observa;on admit • 3 or more – admit, assess for ICU
- 36. ATS/IDSA • Table 4. Criteria for severe community-‐acquired pneumonia. • Minor criteria Respiratory rate >=30 breaths/min Pa02/Fi02 ra;o <=250 Mul;lobar infiltrates Confusion/disorienta;on Uremia (BUN level, >=20 mg/dL) Leukopeniac (WBC count, <4000 cells/mm3) Thrombocytopenia (platelet count, <100,000 cells/mm3) Hypothermia (core temperature, <36°C) Hypotension requiring aggressive fluid resuscita;on • Major criteria Invasive mechanical ven;la;on Sep;c shock with the need for vasopressors
- 37. SMART-‐COP • Tool to predict need for vasopressors/MV • Based on study of 882 pa;ents • SBP < 90 • Mul;lobar infiltrates • Albumin <3.5 • RR > 25 or 30 (depending upon age) • Tachycardia > 125 • Confusion • Oxygen reduced • pH < 7.35 Charles, PC, et al., Clin Infect Dis, 2008.
- 38. SMART-‐COP • Hypotension, hypoxia & low pH each 2 points • All others 1 point each • 92 % of pa;ents requiring ICU care had ≥ 3 points • Less accurate in pa;ents < 50
- 39. Biomarkers – Procalcitonin (PCT) • Levels rise during infec;on -‐ ? More specific to bacterial infec;on -‐ ? More specific to infec;on that CRP • Low PCT high NPPV (98.9%) for mortality from CAP -‐ even in pa;ents with high CRB-‐65 • High PCT, and failure to drop, a/w ↑ mortality • High PCT a/w blood culture + Kruger, S, et al., Eur Resp J, 2008.
- 40. PCT Guided Abx Therapy • 302 CAP pa;ents, randomized, open trial • Control pa;ents – usual prac;ce • PCT group – abx use encouraged if PCT high, discouraged if PCT low -‐ PCT done Day 1, 4, 6 and 8 • PCT group had much less abx use -‐ mostly via shorter courses of abx in PCT pts • Similar need for ICU, mortality, etc Christ-‐Crain, M, et al. AJRCCM, 2006.
- 41. Other Biomarkers of Interest • CRP -‐ ? Par;cular sugges;ve of pneumococcus • Pro-‐atrial natriure;c pep;de • Pro-‐vasopressin
- 42. ATS/IDSA Summary Site of Care • Consider CURB-‐65 or PSI to guide tx loca;on -‐ CURB-‐65 ≥ 2, in-‐pa;ent • ICU if ≥ 3 minor criteria of ATS criteria Diagnos;c Tes;ng • Must have infiltrate on CXR • Diagnos;c tes;ng op;onal for outpa;ents
- 43. ATS/IDSA Summary – Outpt Treatment • No significant co-‐morbidi;es -‐ Macrolide (Level 1) -‐ Doxycycline (Level 3) • Major co-‐morbidi;es -‐ Respiratory quinolone (Level 1) -‐ β-‐lactam + macrolide • Cochrane Review (2009) – current evidence insufficient for abx choice in out-‐pt CAP
- 44. ATS/IDSA Summary – Inpt Treatment • Non-‐ ICU -‐ Respiratory quinolone -‐ β-‐lactam + macrolide • ICU -‐ β-‐lactam + either an IV macrolide or respiratory quinolone -‐ Assess for Pseudomonas & CA MRSA
- 45. ATS/IDSA Summary – Abx Issues • Time to 1st Dose -‐ Did not specify exact ;me, but -‐ 1st dose should be given in ED • Switch IV to Oral -‐ Hemodynamically stable -‐ Clinically improving -‐ Able to take PO with normal GI func;on
- 46. ATS/IDSA Summary – Abx Dura;on • At least 5 days of effec;ve therapy • Afebrile for at least 48 hours • At most fail 1 criteria of clinical stability • Longer dura;on if: -‐ Ini;al abx not effec;ve against pathogen -‐ Resistant organism -‐ Extrapulmonary infec;on -‐ Immunosuppressed host
- 47. Table 10. Criteria for clinical stability • Temperature <=37.8°C • Heart rate <=100 beats/min • Respiratory rate <=24 breaths/min • Systolic blood pressure >=90 mm Hg • Arterial oxygen satura;on >=90% or pO2 >=60 mm Hg on room air • Ability to maintain oral intakea • Normal mental statusa
- 48. Clinical Stability • Hospitalized pa;ents take 2-‐4 days to achieve stability • May be longer with lobar or necro;zing pna • Can take up to 1 month for all symptoms to resolve • Can take up to 3 months for CXR to clear
- 49. Treatment Failure • Lack of improvement or clinical deteriora;on • Occurs in up to 15% of cases • Early – worsening in first 72 hours • Late -‐ ≥ 72 hours of therapy
- 50. PaAerns and e0ologies of types of failure to respond Deteriora;on or progression Early (<72 h of treatment) Severity of illness at presenta;on Resistant microorganism Uncovered pathogen Inappropriate by sensi;vity Metasta;c infec;on Empyema/parapneumonic Endocardi;s, meningi;s, arthri;s Inaccurate diagnosis PE, aspira;on, ARDS, Vasculi;s (e.g., SLE) Delayed Nosocomial superinfec;on Nosocomial pneumonia Extrapulmonary Exacerba;on of comorbid illness Intercurrent noninfec;ous disease PE Myocardial infarc;on Renal failure
- 51. PaAerns and e0ologies of types of failure to respond. • Failure to improve -‐ Early (<72 h of treatment) Normal response -‐ Delayed Resistant microorganism Uncovered pathogen Inappropriate by sensi;vity Parapneumonic effusion/empyema Nosocomial superinfec;on Nosocomial pneumonia Extrapulmonary Noninfec;ous Complica;on of pneumonia (e.g., BOOP) Misdiagnosis: PE. CHF, vasculi;s Drug fever
- 52. Risk Factors for Lack of Response • Mul;-‐lobar pneumonia • High PSI • Cavity or effusion • Leukopenia • Liver disease
- 53. Evalua;on of Non-‐responders • Repeat cultures • Chest CT • Invasive tes;ng -‐ Bronch -‐ Thoracentesis -‐ Lung biopsy • Reassess pre-‐hospital exposure risks
- 54. CAP Mortality in US • ~ 1% in out-‐pa;ents • ~ 5-‐10% in ward pa;ents • Up to 1/3 of ICU pa;ents • Higher mortality in non-‐responders • Higher mortality in pa;ents with concomitant acute cardiac event
- 55. CAP Mortality • > in resistant GNR and Staph • Intermediate in Strep, influenza • Lowest in mycoplasma
- 56. CAP Outcomes • 1,555 pa;ents in study of pna outcomes • Both in-‐pa;ents and out-‐pa;ents included • 8.7% died within 90 days • 29% died within 1st year, 19% died in 2nd year 16% died in year 3 • Outcome compared to age matched controls • Mortality higher in pna pts across all age groups Mortensen, EM, et al., Clin Inf Dis, 2003.
- 57. CAP Outcomes • 170 Pa;ents with pneumococcal pneumonia • Assessed incidence of -‐ Acute MI -‐ Afib or VT -‐ New or worsening CHF • 33 (19%) had ≥ 1 cardiac event -‐ 12 MI -‐ 13 CHF -‐ 8 arrhythmia Musher, DM, et al., Clin Inf Dis, 2007.
- 58. CAP & Steroids • 46 pa;ent RCT in severe CAP • Hydrocor;sone 200 mg bolus then 10mg/hr for 7 days • 1⁰ end-‐point: improvement in P/F, MODS and development of sep;c shock by Day 8 • 2⁰ end-‐point: dura;on MV, LOS, mortality • All 1⁰ end-‐points bejer in tx group • 2⁰ end-‐points also bejer Confalonieri, M, et al. AJRCCM, 2005.
- 59. CAP & Steroids • 213 pa;ents hospitalized with CAP • Randomized to prednisone 40 for 7 d • 1⁰ outcome: cure at 7 d • 2⁰ outcome: cure at 30d, LOS, ;me to stability defervesence, CRP • Results – No difference, even in subset with severe pna -‐More late failure with prednisone
- 60. Viral Pneumonia • More common in children • Likely underdiagnosed historically • Diagnos;c op;ons are improving • O@en co-‐exists with bacterial pneumonia • Limited treatment op;ons • Seasonal pajerns • Can have epidemics Ruuskanen, O, et al. Lancet, 2011.
- 61. Viral Pneumonia -‐ Diagnosis • Nasal swabs, aspirates, washes • Throat swab • Expectorated or induced sputum • BAL • PCR techniques have increased yield
- 62. Viral Pneumonia -‐ Diagnosis • Signs & symptoms overlap with those of bacterial pneumonia • Viral may have more insidious onset or have prodrome • ? More likely to have wheeze • Consider if not responding to an;bio;cs
- 63. Viruses • RSV • Influenza • Parainfluenza • Human metapneumo virus • Coronavirus (SARS) • Avian influenza A (H5N1) -‐ 60% fatality rate • Pandemic influenza A (H1N1)
- 64. An;-‐virals • Neurominidase inhibitors – Influenza viruses -‐ Oseltamivir, peramivir, zanamivir, amantadine and rimantadine • Ribavirin – RSV, human metapneumo, para
- 65. Health Care-‐Associated Pneumonia (HCAP) • Nursing home residents • Recent hospitaliza;on • Chronic dialysis • Home infusion therapy • Home wound care therapy
- 66. Hospital-‐Acquired Pneumonia (HAP) • Develops ≥ 48 hours a@er admit • Highest risk of HAP is in intubated pa;ents • Es;mated incidence 4-‐7/1000 admits • Pa;ents with HAP have 20-‐50% mortality
- 67. Ven;lator-‐Associated Pneumonia (VAP) • Develops > 48 hours a@er intuba;on • Not present at ;me of intuba;on • 1-‐4% daily risk while intubated
- 68. MDR Organisms • Resistant to ≥ 2 an;bio;cs usually used to treat the organism • Risk Factors for MDR infec;on: -‐ Received an;bio;cs in last 90-‐180 days -‐ Hospitalized ≥ 2 days in last 90 days -‐ Current hospitaliza;on has been for ≥ 5 days -‐ High local incidence of MDR organisms -‐ Immunosuppressed pa;ent
- 69. Treatment • General Principles -‐ Start empiric an;bio;cs promptly based on local an;-‐biogram -‐ Blood & Sputum culture if possible -‐ Prompt ini;a;on of appropriate abx crucial -‐ Assess for risk for MDR organism -‐ Descalate as quickly as able (within 72 hours)
- 70. Importance of Timing of Abx • Observa;onal study of 107 consecu;ve VAP pa;ents in single ICU • Compared pt with > 24 hour delay in abx • Mortality in delay pa;ents 70% vs. 28% • Even adjusted for severity of illness, etc, delay abx s;ll led to increased mortality Iregui M, et al. Chest, 2002.
- 71. Importance of Appropriate Abx • Retrospec;ve study of 431 HCAP pa;ents • Single center • Mortality in pa;ents with appropriate regimen was 18% vs. 30% (p 0.013) Zilberberg, et al. Chest, 2008.
- 73. Treatment Guidelines • 303 pa;ents in 4 ICU’s • 129 had guideline recommended an;bio;cs • 174 pa;ents did not get recommended abx • 34% of adherent pa;ents died vs. 20% • Other studies have suggested opposite results • Emphasizes the importance of adjus;ng therapy to local pathogens Kett, DH, et al. Lancet Infect Dis, 2011.
- 74. Dura;on of An;bio;cs • Prospec;ve RCT of 401 pa;ent with VAP • Excluded immunosuppressed pa;ents • Compared 8 vs. 15 days of an;bio;cs • Outcomes: death, recurrence & abx free days • No difference in Mortality or ICU days • Overall recurrence rate not different • If GNR, 8d group had higher recurrence, but no mortality difference & less resistance Chastre, et al. JAMA, 2003.