Community-acquired Pneumonia

H. Nina Kim, MD MSc

Harborview Medical Center

University of Washington

ID Fellows Orientation

July 5, 2011

Community-acquired Pneumonia

Epidemiology & Terminology

Site of care decision-making & Prognosis

Microbiology

Diagnosis

Treatment

Prevention

Alphabet Soup for Pneumonia

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

HCAP: Healthcare-associated pneumonia Long-term care facility (NH), hemodialysis, outpatient

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

≥ 48 h from admission

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

Which of these patients does NOT have CAP?

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

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

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

Epidemiology

Influenza & pneumonia = 8th leading cause of death in US in 20071

5 million cases per year in US – 20-25% require hospitalization Of those hospitalized: mortality 10% in 30 days, 40% in 1 year2

Almost 916,000 cases annually in pts >65 yo Case fatality rate has not changed substantially in recent years

1cdc.gov/nchs/data/hestat2Kaplan, et. al. Arch Intern Med. 2003;163:317-23.

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 Labs/vitals dynamic

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 Causative organism established in 60% CAP in

research setting, 20% in clinical setting

“Typical”: S. pneumoniae, Haemophilus influenzae,

Staphylococcus aureus, Group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria

“Atypical” - 20-28% CAP worldwide Legionella spp, Mycoplasma pneumoniae,

Chlamydophila (formerly Chlamydia) pneumoniae, and C. psittaci

Mainly distinguished from typical by not being detectable on Gram stain or cultivable on standard media

Microbiology of CAP among hospitalized patientsOutpatient Streptococcus pneumoniae

Mycoplasma pneumoniaeHaemophilus influenzaeChlamydophila pneumoniaeRespiratory viruses

Inpatient (Ward) S. pneumoniaeM. pneumoniaeH. influenzaeC. PneumoniaeLegionella speciesRespiratory virusesAspiration

Inpatient (ICU) S. pneumoniaeLegionella spp.Staphylococcus aureusGram-negative bacilli

Age-specific Rates of Hospital Admission by Pathogen

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

Typical vs Atypical CAP

Kauppinen et al. Arch Intern Med 1996; 156: 1851.

N=24 C. pneumoniae

N=13 Strep pneumoniae

N=8 Both CXR patterns

Bronchopneumonia:

88% C. pneumo vs 77% Pneumococcal, P=0.67

Lobar or air-space:

29% C. pneumo vs 54% Pneumococcal

Comorbidities & Associated PathogensAlcoholism Strep pneumoniae

Oral anaerobes Klebsiella pneumoniae Acinetobacter spp M. tuberculosis

COPD and/or Tobacco

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

Aspiration Gram-negative enteric pathogens Oral anaerobes

Lung Abscess CA-MRSA Oral anaerobes, microaerophilic

Actinomyces Endemic fungi M. tuberculosis, atypical mycobacteria

Structural lung disease (e.g. bronchiectasis)

P. aeruginosa Burkholderia cepacia S. aureus

Advanced HIV Pneumocystis jirovecii Cryptococcus Histoplasma Tuberculosis Aspergillus P. aeruginosa

Zoonotic Exposures & Associated Pathogens

Bat or bird droppings

Histoplasma capsulatum

Birds Chlamydophila psittaci Poultry: avian influenza

Rabbits Francisella tularensis

Farm animals or parturient cats

Coxiella burnetti (Q fever)

Exposures & Associated Pathogens

Hotel or cruise ship, built water sources

Legionella spp

Travel or residence in SW US Coccidioides spp Hantavirus pulmonary syndrome

(Sin Nombre virus)

Travel or residence in SE or E Asia

Burkolderia pseudomallei Staph aureus H.influenzae Avian influenza A (H5N1)

Influenza active in community Influenza S. pneumonae Staph aureus (MRSA) H. influenzae

Cough >2 wks with whoop or posttussive vomitting

Bordetella pertussis

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 coverage in severe CAP, esp during flu season!

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

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: Pop quiz Name 2 ways a gram stain of respiratory

specimen can be helpful in pt hospitalized with CAP.

True or False: Yield for culture is markedly affected by a single dose of abx for all CAP pathogens.

True or False: Failure to detect S. aureus or GNR in good-quality respiratory specimens (no abx exposure) is strong evidence against presence of these pathogens.

Diagnosis: Other testing Urinary antigen tests

S. pneumoniae L. pneumophila

serogroup 1 50-80% sensitive,

>90% specific in adults Pros: rapid (15 min),

simple, can detect Pneumococcus after abx started

Cons: cost, 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 Influenza A PCR panel

How to obtain a nasopharyngeal swab

2010-2011 Influenza SurveillanceSeattle - King County

www.kingcounty.gov/healthservices/health/communicable/immunization/fluactivity.aspx

Outpatient Empiric CAP Abx

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

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

750 mg, gemifloxacin Beta-lactam + macrolide

Regions with >25% high-level macrolide-resistant S. pneumo, consider alternative agents

2007 IDSA/ATS Guidelines for CAP in Adults.

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

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 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

12007 IDSA/ATS Guidelines for CAP in Adults.2File, et. al. CID 2010. 51(12): 1395-1405.

Antiviral Therapy for Influenza 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

CDC Guidelines for Influenza 2010-2011

Influenza pneumoniaWhat about the 48-hr rule?

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

antibacterial use in outpatients Impact on hospitalized pts less clear

Possible exceptions to <48 h rule: Immunocompromised patients Severe, complicated or progressive illness To reduce viral shedding for infection control in

hospitalized patients

Influenza pneumoniaSome things to keep in mind… Influenza B

Oseltamavir 75 mg PO BID x 5 days Zanamavir 2 mg INH BID x 5 days

Influenza A* H3N2 (general seasonal), Novel H1N1 (Swine flu)

Sensitive to neuraminidase inhibitors Resistant to adamantane antivirals

H1N1 - general seasonal High rate of oseltamavir resistance in 2008-2009 Still susceptible to zanamavir Resistant to adamantanes

Drug-resistant Strep pneumoniaeß-lactam resistance

Risk factors Age >65 yrs ß-lactam x previous 3 mon Medical comorbidities Exposure to child in day care

Current levels of ß-lactam resistance do not generally result in treatment failure* with amoxicillin, ceftriaxone or cefotaxime As opposed to macrolide (& less so fluoroquinolone)

resistance

Long, Clin Infect Dis 2009. May 15; 48: 1355.

Case-control study from Canada - review of fluoroquinolone (FLQ) use among Cx-proven TB cases.

Of 148 isolates of M. TB, 3 were FLQ resistant. Patients who had received multiple FLQ prescriptions were more

likely than patients who had received a single FLQ prescription to be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%; odds ratio, 11.4; P<.04)

Case29 yo previously healthy but morbidly obese woman with severe CA pneumonia.

Nasopharyngeal swab (+)influenza A, novel H1N1. Sputum Cx (+) MRSA. Creatinine 3.2 and requiring HD.

On hospital day 14, still febrile – oxygenation requirements remain high – now on ARDS settings with high PEEP. Exam notable for persistent coarse BS throughout, deep sedation, very quiet abdomen – no bowel tones. No change in minimal respiratory secretions.

In addition to resending BCx & ET Cx, what would you do next?

1. Send stool for C. diff toxin A/B by PCR.

2. CT with contrast, PE protocol.

3. Stop oseltamavir.

4. Transition to oral antibiotics.

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

Inadequate Response to TherapyWhat to consider Consider S. aureus, virus, resistant organism, TB, endemic fungi,

Pneumocystis More unusual pathogens: atypical mycobacteria, higher bacteria

(Nocardia, actinomycetes), fungi Noninfectious illness:

Lung neoplasms with bronchial obstruction Lymphoma Systemic autoimmune disorders PE w/ infarct, pulm edema, ARDS

Consider other testing: Lower tract sampling (bronchoscopy) CT chest PE work-up? Serologic testing Open lung biopsy

VACCINE: Pneumococcal polysaccharide

Inactivated influenza Live attenuated influenza

Route & Type IMBacterial capsule

IMKilled virus

IntranasalLive virus

Recommended groups

All persons ≥65 High-risk (below) for

ages 2-64

All persons ≥50 High-risks for ages 2

to 49 yo Children 6-23 mon Healthcare providers Household contacts of

high-risk

Healthy persons aged 5-49 yrs

High-risk indications

Chronic CV, pulm, renal or liver dz

Diabetes CSF leaks Alcoholism Asplenia Immunocompromising

condition/meds Native American &

Alaskan natives Long-term care facility

residents

Chronic CV or pulm disease

Diabetes Renal dysfunction Hemoglobinopathy Immunocompromising

condition/meds Compromised resp fxn

or aspiration risk Pregnancy Long-term care

residents

AVOID in high-risk persons

Revaccinate 1 X after 5 yrs* Annual Annual

PreventionTried & true…

http://www2a.cdc.gov/eCards