Community-Acquired Pneumonia

Shireesha Dhanireddy, MD

Division of Allergy & Infectious Diseases

University of Washington

12 September 2014

Objectives

Diagnosis and management of CAP

Differentiate between healthcare-associated pneumonia (HCAP) and CAP

Identify risk factors for resistant organisms and less common causes of pneumonia

CAP - Epidemiology

Very common 5 million cases/year in North America At least 1 million hospitalizations/year

9th leading cause of infectious death in US 30 day morality for hospitalized patients is up

to 23% $17 billion/year in healthcare costs in US

www.cdc.gov/flu

Which of these patients have community-acquired pneumonia (CAP)?

34 yo hospital employee, previously healthy, admitted for acute pneumonia.

56 yo man admitted with CHF, noted to have pneumonia the day after admission.

76 yo bedridden man transferred from a nursing home for acute confusion, noted to have a new infiltrate on CXR.

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Alphabet Soup of Terms

CAP: Community-acquired pneumonia Outside of hospital or extended-care facility

HCAP: Healthcare-associated pneumonia Long-term or extended care facility, hemodialysis,

outpatient chemo, wound care, etc. HAP: Hospital-acquired pneumonia

≥ 48 h from admission

VAP: Ventilator-associated pneumonia ≥ 48 h from endotracheal intubation

Pneumonia - Definitions

Kollef MH et al. CID 2008:46 (suppl 4)

Case 1

70 yo man presents to ED with acute onset of cough productive of yellow sputum, R-sided pleuritic CP and dizziness. Hx diabetes and HTN. Meds include: HCTZ, lisinopril, glyburide and metformin.

PEx: T 35° C, BP 110/70 HR 120 RR 36

GEN: Appears in acute respiratory distress. PULM: Dullness to percussion, increased fremitus, crackles at R base. NEURO: Oriented only to self.

LABS: WBC 23 (40% bands), Hct 42%, Plts 150. BUN 46, Cr 1.4.

ABG: 7.48 /30 /50 on RA. CXR shows RLL infiltrate.

Which of following is the most appropriate management?

1.Admit to general medical floor.2.Admit to intensive care unit.3.Observe in the ED for 12 hours.4.Treat as outpatient.

Clinical Presentation

Acute cough (>90%)Fevers/chills (80%)Sputum production (66%)Dyspnea (66%)Pleuritic chest pain (50%)

Tachypnea (RR > 24)

Egophony

Bronchial breath sounds

Percussion dullness

Diminished breath sounds

Clinical Presentation

Acute cough (>90%)Fevers/chills (80%)Sputum production (66%)Dyspnea (66%)Pleuritic chest pain (50%)

Tachypnea (RR > 24)

Egophony

Bronchial breath sounds

Percussion dullness

Diminished breath sounds

Lung physical examSensitivity 47-69% ; Specificity 58-75%

CXR

To Admit or Not?Pneumonia Severity & Deciding Site of Care

Objective criteria to risk stratify & assist in decision re outpatient vs inpatient management

Pneumonia Severity Index (PSI) CURB-65 Caveats

Other reasons to admit apart from risk of death Not validated for ward vs ICU Not validated in some populations (i.e. HIV+)

70

20

15

20

10

Total 135

Criteria for Severe CAP(Admit to ICU)

Minor criteriaRespiratory rate ≥30 breaths/minPaO2/FiO2 ratio ≥ 250Multilobar infiltratesConfusion/disorientationUremia (BUN ≥20 mg/dL)Leukopenia (WBC <4000 cells/mm3)Thrombocytopenia (platelets <100,000 cells/mm3)Hypothermia (core T <36C)Hypotension requiring aggressive fluid resuscitation

Major criteriaInvasive mechanical ventilationSeptic shock with the need for vasopressors

2007 IDSA/ATS Guidelines for CAP in Adults.

Microbiology

TYPICAL– Streptococcus pneumoniae– Haemophilus influenzae – Moraxella catarrhalis– Klebsiella pneumoniae

ATYPICAL– Mycoplasma pneumoniae– Chlamydophila pneumoniae– Legionella pneumophila

Microbiology of CAP among hospitalized patientsOutpatient Streptococcus pneumoniae

Mycoplasma pneumoniae

Haemophilus influenzae

Chlamydophila pneumoniae

Respiratory viruses

Inpatient (Ward) S. pneumoniae

M. pneumoniae

H. influenzae

C. Pneumoniae

Legionella species

Respiratory viruses

Aspiration

Inpatient (ICU) S. pneumoniae

Legionella spp.

Staphylococcus aureus

Gram-negative bacilli

Age-specific Rates of Hospital Admission by Pathogen

Marsten. Community-based pneumonia incidence study group.Arch Intern Med 1997;157:1709-18

Comorbidities & Associated PathogensAlcoholism

COPD and/or Tobacco

Strep pneumoniae Oral anaerobes Klebsiella pneumoniae Acinetobacter spp M. tuberculosis

Haemophilus influenzae Pseudomonas aeruginosa Legionella spp S. pneumoniae Moraxella catarrhalis Chlamydophila pneumoniae

Aspiration

Lung Abscess

Structural lung disease (e.g. bronchiectasis)

Advanced HIV

Gram-negative enteric pathogens Oral anaerobes CA-MRSA Oral anaerobes, microaerophilic

streptococci, Actinomyces, Nocardia spp Endemic fungi M. tuberculosis, atypical mycobacteria

P. aeruginosa Burkholderia cepacia S. aureus

Pneumocystis jirovecii Cryptococcus Histoplasma Tuberculosis Aspergillus P. aeruginosa

MRSAModern-day CAP pathogen

51 Staphylococcus aureus CAP cases in 19 states reported 2006-2007

79% MRSA Median age 16 yrs (range <1 to 81) 47% antecedent viral illness 11 of 33 (33%) tested had lab-confirmed influenza 51% died a median of 4 days from symptom onset

Lesson: Must consider MRSA, MSSA coverage in severe CAP, esp during flu season!

Kallen, Ann Emerg Med. 2009 Mar;53(3):358-65.

MRSA CAPClinical Features

Cavitary infiltrate or necrosis Rapidly increasing pleural effusion Gross hemoptysis (not just blood-streaked) Concurrent influenza Neutropenia Erythematous rash Skin pustules Young, previously healthy patient Severe pneumonia during summer months

Wunderink, N Engl J Med. 2014;370:543-51.

Is sputum culture helpful?

Sputum Gram stain and culture Low sensitivity (25-40%) Considered optional for

outpatients Blood culture

Positive < 10% May help guide

antibiotic therapytextbookofbacteriology.net

Diagnosis: Cultures Pre-abx Blood Cultures

Yield 5-15% Stronger indication for severe CAP Host factors: cirrhosis, asplenia, complement

deficiencies, leukopenia Pre-abx expectorated sputum Gs & Cx

Yield can be variable Depends on multiple factors: specimen collection,

transport, speed of processing, use of cytologic criteria Adequate sample w/ predominant morphotype seen in

only 14% of 1669 hospitalized CAP pts (Garcia-Vasquez, Arch Intern Med 2004)

Pre-abx endotracheal aspirate Gs & Cx Pleural effusions >5 cm on lateral upright CXR

Diagnosis: Other testing Urinary antigen tests

S. pneumoniae

L. pneumophila serogroup 1

60-80% sensitive, >90% specific in adults

Pros: rapid (15 min), simple, more sensitive than Cx, can detect Pneumococcus after abx started

Cons: no susceptibility data, not helpful in patients with recent CAP (prior 3 months)

Diagnosis: Other testing Acute-phase serologies

C. pneumoniae, Mycoplasma, Legionella spp Not practical given slow turnaround & single acute-phase

result unreliable Influenza testing

Hospitalized patients: Severe respiratory illness (T> 37.8°C with SOB, hypoxia, or radiographic evidence of pneumonia) without other explanation and suggestive of infectious etiology should get screened during season

NP swab or nasal wash/aspirate Rapid flu test (15 min) - Distinguishes A vs B

Sensitivity 50-70%; specificity >90% Respiratory virus DFA & culture - reflex subtyping for A Respiratory viral PCR panel - reflex subtyping for A Epidemic Influenza PCR panel – screens for A & B with

reflex subtyping for A

Case29 yo previously healthy but morbidly obese woman admitted in March with 5 days of progressive SOB, intubated in field after being found home unresponsive, hypoxic with Sat 80%. Initial BP 100/80, HR 120. PaO2 60 on 80% FiO2.

CXR reveals diffuse patchy infiltrates with some lower lobar consolidation R>L.

Sputum could not be obtained but endotracheal aspirate shows 3+ polys and 3+GPC in clusters. Which of the following abx would you start empirically?

1.Ceftriaxone + azithromycin

2.Zanamavir + vancomycin + azithromycin

3.Oseltamavir + vancomycin + azithromycin

4.Oseltamavir + vancomycin + piperacillin-tazobactam

5.Oseltamavir + daptomycin + azithromycin

Outpatient Empiric CAP Abx

Healthy; no abx x past 3 months Macrolide: azithromycin 2nd choice: doxycycline

Comorbidities; abx x past 3 mon Respiratory fluoroquinolone: Moxifloxacin, levofloxacin

750 mg, gemifloxacin Beta-lactam (preferred: amoxicillin 1 g3 or amox/clav 2 g2;

alternative: ceftriaxone, cefuroxime 500 mg2), + macrolide

Regions with >25% high-level macrolide-resistant S. pneumo (MIC ≥16), consider alternative agents

2007 IDSA/ATS Guidelines for CAP in Adults.

Inpatient Empiric CAP Abx1

Inpatients in ward Respiratory fluoroquinolone ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) +

macrolide

Inpatients in ICU ß-lactam + macrolide Respiratory fluoroquinolone for PCN-allergic pts

Pseudomonas (if concerns exists) Anti-pneumococcal & anti-pseudomonal ß-lactam +

azithromycin + cipro/levofloxacin (750 mg) Can substitute quinolone with aminoglycoside PCN-allergic: can substitute aztreonam

CA-MRSA: Add vanco or linezolid* (or ceftaroline2) CA-MSSA: Nafcillin or cefazolin or ceftriaxone

1 2007 IDSA/ATS Guidelines for CAP in Adults.2 File, et. al. CID 2010. 51(12): 1395-1405.

Risk Factors for Multidrug Resistance (MDR)

Kollef MH et al. CID 2008:46 (suppl 4)

Antibiotics in the past 90 daysHigh frequency of antibiotic resistance in communityImmunosuppressive disease or medicationsHCAP Risk Factors:• Hospitalization for at least 2 days in the past 90 days• Residence in a SNF• Home infusion therapy• Dialysis within 30 days• Family member with MDR infection

Kollef MH et al. CID 2008:46 (suppl 4)

Influenza pneumoniaTreatment

First-line Tx is neuroaminidase inhibitors for both influenza A and B: Oseltamavir 75-150* mg PO BID x 5+ days Zanamavir 10 mg INH BID x 5+ days

NOTE: influenza A resistant to adamantanes (amantadine, rimantadine)

* There is limited data in support of double dosing. But we do it anyway.

Antiviral Therapy for Influenza

CDC Guidelines for Influenza 2012-2013

Should be started ASAP in:

Anyone hospitalized with suspected or confirmed

influenza

Anyone with severe, complicated or progressive

respiratory illness

Anyone at higher risk of complications from influenza

Individuals at Higher Risk for Influenza Complications

CDC Guidelines for Influenza 2012-2013

Extremes of age: children <2, adults ≥65 years Comorbid conditions:

Chronic pulmonary Cardiovascular (except HTN alone) Renal, hepatic, hematologic, metabolic (DM) Neurologic, neuromuscular (cerebral palsy, epilepsy, CVA, SCI)

Immunosuppression (caused by meds, HIV infection) Pregnant or post-partum (<2 wks) women Persons <19 years on long-term aspirin American Indians & Alaskan Natives Morbidly obese (BMI ≥40) Residents in NH or chronic-care facilities

Influenza pneumoniaWhat about the 48-hr rule?

Antiviral treatment within 48 hrs Reduce likelihood of lower tract complications &

antibacterial use in outpatients Hospitalized patients likely benefit even if started up to 3-

5 days from illness onset 1,2,3

Additional exceptions to <48 h rule: Immunocompromised patients Severe, complicated or progressive illness

1 Siston, et. al. JAMA 2009.2 Yu, Clin Infect Dis 2011.3 Louie, Clin Infect Dis 2012.

Follow-up ResponseExpected improvement?

Clinical improvement w/ effective abx: 48-72 hrs Fever can last 2-5 days with Pneumococcus, longer

with other etiologies, esp Staph aureus CXR clearing

If healthy & <50 yo, 60% have clear CXR x 4 wks If older, COPD, bacteremic, alcoholic, etc. only 25% with

clear CXR x 4 wks

Switch from IV to PO Hemodynamically stable, improving clinically Able to ingest meds with working GI tract

Question…

What is far & away the most common reason for non-response to antibiotics in CAP?

1. Cavitation2. Pleural effusion3. Multilobar involvement4. Discordant antibiotic/etiology5. Host factors

• May. Kennewick, WA.May. Kennewick, WA.

• A 58 y/o man with advanced liver disease, A 58 y/o man with advanced liver disease, construction worker in outdoor excavationconstruction worker in outdoor excavation

• C/O acute fever, cough, pleuritic chest pain, C/O acute fever, cough, pleuritic chest pain, WBC 23,000.WBC 23,000.

• CXR and chest CT show RML nodule and CXR and chest CT show RML nodule and effusion. No response to Unasyn + Levo.effusion. No response to Unasyn + Levo.

• Concern for pneumococcal pneumonia. Concern for pneumococcal pneumonia. Thoracentesis and BAL are performed….Thoracentesis and BAL are performed….

Coccidioides immitisCoccidioides immitis

- Endemic to the desert southwest- Endemic to the desert southwest

- Dissemination more common in non-Caucasians, - Dissemination more common in non-Caucasians, pregnant, immunocompromisedpregnant, immunocompromised

- Acute & chronic pulmonary syndromes (“valley - Acute & chronic pulmonary syndromes (“valley fever”—fever, cough, arthralgias, Erythema fever”—fever, cough, arthralgias, Erythema nodosum)nodosum)

- Diagnosis based on serology, culture, or - Diagnosis based on serology, culture, or histopathologyhistopathology

NW Infections: NW Infections: CoccidioidesCoccidioides

Exposures & Associated Pathogens

Hotel or cruise ship, built water sources

Travel or residence in SW US

Travel or residence in SE or E Asia

Travel or residence in Arabian Peninsula

Influenza active in community

Cough >2 wks with whoop or posttussive vomitting

Legionella spp

Coccidioides spp Hantavirus pulmonary

syndrome (Sin Nombre virus) Burkolderia pseudomallei Avian influenza A (H7N9)

MERS-CoV

Bordetella pertussis

Influenza S. pneumoniae Staph aureus (MSSA, MRSA) H. influenzae

Zoonotic Exposures & Associated Pathogens

Bat or bird droppings

Histoplasma capsulatum

Birds Chlamydophila psittaci Avian influenza (H7N9)

Rabbits Francisella tularensis

Farm animals or parturient cats

Coxiella burnetti (Q fever)

Take Home Points

Ask patients about co-morbidities and travel/other potential exposures when they present with a respiratory illness

Evaluate patients for MDR risk factors when managing patients in the community with respiratory illness