Some Clinical Keys

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.
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,
Which of followingglyburide
is the mostand metformin.
appropriate management?
PEx: T 35
1.Admit C, BP medical
to general 110/70 floor.
HR 120 RR 36
2.Admit
GEN: to intensive
Appears care unit.
in acute respiratory distress. PULM:
3.Observetoinpercussion,
Dullness the ED for 12increased
hours. fremitus, crackles
4.Treat
at as outpatient.
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.
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
Lung(50%)
physical exam
Sensitivity 47-69% ; Specificity 58-75%
Tachypnea (RR > 24)
Egophony
Bronchial breath sounds
Percussion dullness
Diminished breath sounds
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 criteria
Respiratory rate 30 breaths/min
PaO2/FiO2 ratio 250
Multilobar infiltrates
Confusion/disorientation
Uremia (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 criteria
Invasive mechanical ventilation
Septic 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 patients
Outpatient 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
Marsten. Community-based pneumonia incidence study group.
Arch Intern Med 1997;157:1709-18
Comorbidities & Associated
Pathogens
Alcoholism Strep pneumoniae
Oral anaerobes
Klebsiella pneumoniae
Acinetobacter spp
M. tuberculosis
COPD and/or Haemophilus influenzae
Tobacco Pseudomonas aeruginosa
Legionella spp
S. pneumoniae
Moraxella catarrhalis
Chlamydophila pneumoniae
Aspiration Gram-negative enteric pathogens
Oral anaerobes
Lung Abscess CA-MRSA
Oral anaerobes, microaerophilic
streptococci, Actinomyces, Nocardia spp
Endemic fungi
M. tuberculosis, atypical mycobacteria

Structural lung P. aeruginosa

disease (e.g. Burkholderia cepacia
bronchiectasis) S. aureus
Advanced HIV Pneumocystis jirovecii
Cryptococcus
Histoplasma
Tuberculosis
Aspergillus
P. aeruginosa
MRSA - Modern-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 CAP - Clinical
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
therapy
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>
37.8C 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
Case
29 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
Abx 1
Inpatients in ward
Respiratory fluoroquinolone
-lactam (cefotaxime/ceftriaxone or
ampicillin/sulbactam) + macrolide
Inpatients in ICU
-lactam + macrolide
Respiratory fluoroquinolone for PCN-allergic pts

Pseudomonas (if concerns exists)

Anti-pneumococcal & anti-pseudomonal -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)
Antibiotics in the past 90 days
High frequency of antibiotic resistance in community
Immunosuppressive disease or medications

HCAP Risk Factors:

Hospitalization for at least 2 days in the past 90 day
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)

Kollef MH et al. CID 2008:46 (suppl 4)
Influenza pneumonia -
Treatment
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
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

CDC Guidelines for Influenza 2012-2013

Individuals at Higher Risk
for Influenza Complications
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

CDC Guidelines for Influenza 2012-2013

 Influenza pneumonia
What 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 Response
Expected 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. Cavitation
2. Pleural effusion
3. Multilobar involvement
4. Discordant antibiotic/etiology
5. Host factors
 May. Kennewick, WA.
A 58 y/o man with advanced liver disease, construction
worker in outdoor excavation
C/O acute fever, cough, pleuritic chest pain, WBC 23,000.
CXR and chest CT show RML nodule and effusion. No
response to Unasyn + Levo.
Concern for pneumococcal pneumonia. Thoracentesis and
BAL are performed.
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