pneumonia symposia - the crudem foundation
DESCRIPTION
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.TRANSCRIPT
Pneumonia
Greg Schumaker, MD Assistant Professor
Pulmonary, Cri;cal Care & Sleep Medicine Tu@s Medical Center
Overview
• Diagnosis • Epidemiology /Microbiology
• Triage/Severity Scoring • Treatment
• Special Popula;ons/Bugs • Summary of ATS/IDSA Guidelines
• Nosocomial pneumonias
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
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.
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.
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
Microbiology
• S. pneumo remains most common bacteria • Influenza most common virus
-‐ RSV, metapneumo, parainfluenza, adeno
• Mycobacteria
• Fungi
Microbiology -‐ Bacteria
• Typical -‐ S. pneumo
-‐ H. influenza
-‐ Moraxella
-‐ Staph a.
-‐ Aerobic gram nega;ve
Microbiology -‐ Bacteria
• Atypical Bacteria -‐ Legionella
-‐ Mycoplasma
-‐ Chlamydia
• 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
Table 6. Most common e0ologies of community-‐acquired pneumonia.
Pa;ent type E;ology
Inpa;ent (ICU) S. pneumoniae Staphylococcus aureus Legionella species Gram-‐nega;ve bacilli H. influenzae
Specific Bugs
• S. pneumo -‐ Lobar consolida;on
-‐ Rust colored sputum
• H. flu -‐ elderly or underlying lung disease
Specific Bugs
• Legionella -‐ < 10% of CAP, higher mortality, epidemics • Mycoplasma -‐ Children, young adults & elderly • Chlamydia -‐ Older adults • Influenza
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
Exposures and Bugs
• Bats – Histoplasma capsulatum • Birds – C. psijaci, Cryptococcus, Histoplasma
• Farm animals – Coxiella burne; (Q fever)
Niederman, Ther Adv Respir Dis, 2011.
HIV Pa;ents
• TB • P. jiroveci • Cryptococcus • CMV
• ‘Usual’ typical and atypical agents
Aspira;on
• CVA • Esophageal disorders • Swallowing problems
• Neuromuscular disease
• Drug/alcohol abuse • Anaerobes/Gram Nega;ve Rods
CA-‐MRSA Risk Factors
• Contact sports • IVDA • Prisoners • Living in crowded condi;ons • MSM
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
Diagnosis
• No set of clinical criteria have great sensi;vity • Must have infiltrate on CXR
• Sputum and CXR pajerns not consistent
Diagnosis -‐ CXR
• Lobar infiltrate – typical bacteria • Inters;;al – viral or PCP • Nodular – fungal, mycobacteria, nocardia, ac;no
• 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
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
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
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
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
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.
PSI
• Demographics -‐ Age (years) -‐ Gender (-‐10 for women) -‐ Nursing home (10) • Co-‐morbidi;es -‐ Malignancy (30) -‐ Neuro (10) -‐ CHF (10) -‐ CKD (10) -‐ ESLD (20)
PSI
• Exam -‐ Altered MS (20)
-‐ RR > 30 (20)
-‐ HR > 125 (10)
-‐ SBP <90 (20)
-‐ Temp < 35⁰ or > 40⁰ (15)
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)
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)
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.
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.
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
CURB-‐65
• 0-‐1 – treat as out-‐pa;ent • 2 – brief observa;on admit
• 3 or more – admit, assess for ICU
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
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.
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
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.
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.
Other Biomarkers of Interest
• CRP -‐ ? Par;cular sugges;ve of pneumococcus
• Pro-‐atrial natriure;c pep;de • Pro-‐vasopressin
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
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
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
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
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
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
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
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
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
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
Risk Factors for Lack of Response
• Mul;-‐lobar pneumonia • High PSI • Cavity or effusion • Leukopenia • Liver disease
Evalua;on of Non-‐responders
• Repeat cultures • Chest CT • Invasive tes;ng -‐ Bronch
-‐ Thoracentesis
-‐ Lung biopsy
• Reassess pre-‐hospital exposure risks
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
CAP Mortality
• > in resistant GNR and Staph • Intermediate in Strep, influenza
• Lowest in mycoplasma
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.
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.
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.
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
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.
Viral Pneumonia -‐ Diagnosis
• Nasal swabs, aspirates, washes • Throat swab • Expectorated or induced sputum
• BAL • PCR techniques have increased yield
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
Viruses
• RSV • Influenza • Parainfluenza • Human metapneumo virus • Coronavirus (SARS) • Avian influenza A (H5N1) -‐ 60% fatality rate • Pandemic influenza A (H1N1)
An;-‐virals
• Neurominidase inhibitors – Influenza viruses -‐ Oseltamivir, peramivir, zanamivir, amantadine and rimantadine
• Ribavirin – RSV, human metapneumo, para
Health Care-‐Associated Pneumonia (HCAP)
• Nursing home residents • Recent hospitaliza;on • Chronic dialysis • Home infusion therapy
• Home wound care therapy
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
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
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
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)
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.
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.
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.
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.
