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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



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.

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