Internal Medicine: Pulmonology

PNEUMONIA


1Infection of the pulmonary parenchyma - Neutrophil influx

2Alower respiratory tract infection acquired in the
community within 24 hours to less than 2 weeks
2Presents with an acute cough, abnormal vital
signs of tachypnea, tachycardia, and fever with at
least one abnormal chest finding of diminished
breath sounds, rhonchi, crackles, or wheeze
PATHOPHYSIOLOGY
Results from the proliferation of microbial
pathogens at the alveolar level and the host's
response to those pathogens
- Microaspiration from the oropharynx- S.
pneumoniae, H. influenzae
- Gross aspiration- anaerobic, Gm (-) bacilli
- Inhalation of contaminated droplets- M. Tb,
legionella, Blastomyces sp.,Histoplasma
capsulatum, Coxiella burnetti, respiratory
viruses esp Influenza viruses A and B
- Hematogenous spread- endocarditis, IV
catheter infections (staph aureus including
MRSA), UTI (E. coli)
Host Defense
i. Hairs and turbinates of the nares
ii. Branching architecture of the tracheobronchial
tree
iii. Gag reflex and cough mechanism
iv. Normal flora
v. Resident alveolar macrophages (surfactants
proteins A and D)
- Bacteria are seen in collected specimen
3. Gray hepatization
- Neutrophilic predominance
- Fibrin deposition
- Disappearance of bacteria
4. Resolution
- Macrophages are the predominant cell type
- Debris of neutrophils, fibrin, and bacteria has
been cleared
COMMUNITY AQCUIRED PNEUMONIA
Most commonly caused by Streptococcus
pneumoniae
Consider the patient’s risk factors and severity of
illness
~10–15% of CAP cases are polymicrobial
A virus may be responsible for up to 18% of
cases of CAP that require admission to the
hospital
Atypical pathogens
- Intrinsically resistant to all B-lactam agents
and must be treated with a macrolide, a
fluoroquinolone, or a tetracycline

The host inflammatory response, rather than the

proliferation of microorganisms, triggers the
clinical syndrome of pneumonia
- Interleukin (IL)-1 and tumor necrosis factor ETIOLOGY
(TNF)
- Chemokines, such as IL-8 and granulocyte Anaerobes Staphylococcus aureus
colony-stimulating factor
- Other inflammatory mediators causing • Aspiration • MRSA
increased capillary leakage • Combination of an • Spread of MRSA from
- Increased respiratory drive in the systemic unprotected airway the hospital setting to
inflammatory response syndrome and significant the community
gingivitis constitutes • Emergence of
PATHOLOGY the major risk factor genetically distinct
1. Congestion - vascular congestion & alveolar • Complicated by strains of MRSA in
edema abscess formation the community
- Proteinaceous exudates in the alveoli, i.e. and significant
bacteria empyemas or
parapneumonic
- Rarely evident
effusions
2. Red hepatization
- Presence of erythrocytes

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 EPIDEMIOLOGY
CLINICAL MANIFESTATIONS
Results in more than 600,000 hospitalizations, 64
million days of restricted activity, and 45,000 Vary from indolent to fulminant in presentation
deaths annually and from mild to fatal in severity

Incidence rates are highest at the extremes of - Fever with tachycardia or may have a history
age of chills and/or sweats
- Children <4 years of age and persons >60 - Cough may be either nonproductive or
years of age productive of mucoid, purulent, or blood-
tinged sputum
Risk Factors - Pleuritic chest pain

CAP Pneumococcal Pneumonia - 20% of patients may have gastrointestinal

symptoms such as nausea, vomiting, and/or
1. Alcoholism 1. Dementia diarrhea
2. ▪
Asthma 2. Seizure disorders - Fatigue, headache, myalgias, and arthralgias
3. Immunosuppression 3. Heart Failure
4. Cerebrovascular disease
4. Institutionalization PHYSICAL FINDINGS
5. Alcoholism
5. Age of 70 years versus 6. Tobacco Smoking Increased respiratory rate and use of accessory
60–69 years 7. COPD muscles of respiration
8. HIV infection
Palpation may reveal increased or decreased
tactile fremitus
Entertobacteriaceae Percussion note can vary from dull to flat,
Tend to infect patients who have recently been hospitalized and/or reflecting underlying consolidated lung and
received antibiotic therapy or who have comorbidities such as pleural fluid, respectively
alcoholism, heart failure, or renal failure Crackles, bronchial breath sounds and, possibly a
pleural friction rub may be heard on auscultation
Pseudomonas aeruginosa
Septic shock and organ failure
Severe structural lung disease, such as bronchiectasis, cystic fibrosis,
or severe COPD
CLINICAL DIAGNOSIS
Legionella Sensitivity and specificity of the findings on
physical examination are less than ideal,
Diabetes, hematologic, malignancy, cancer, severe renal disease, HIV averaging 58% and 67%, respectively
infection, smoking, male gender, and a recent hotel stay or ship cruise
Chest radiography is often necessary to
Among the three most common causes of severe pneumonia and is differentiate CAP from other conditions
isolated in 1-40% of cases of hospital-acquired pneumonia
CT is rarely necessary but may be of value in a
Unexplained confusion, lethargy, loose stools or watery diarrhea, patient with suspected post obstructive
abdominal pain, relative bradycardia, and lack of response to B- pneumonia caused by a tumor or foreign body
lactams

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 CHEST RADIOGRAPH
Essential in the diagnosis of CAP, assessing
severity, differentiating pneumonia from other
conditions, and in prognostication (Grade A)
A new parenchymal infiltrate in the chest
radiograph remains the reference diagnostic
standard for pneumonia
A chest x-ray should be done in patients
suspected to have CAP to confirm the diagnosis
A chest x-ray may not be routinely done in patients
strongly suspected to have CAP with the following
conditions:
1. Healthy individuals or those with stable co-
morbid conditions, and
2. Normal vital signs and physical examination
findings, and
3. Reliable follow-up can be ensured
A radiographic reading of “pneumonitis” should
always be correlated clinically. (Grade C)
- Non-infectious causes of pneumonitis may
include fibrosis (immunologic, occupational
lung disease)
- If pneumonitis is infectious in nature, it could
relate to the first stage in the process of
pneumonia.
▪ Congestive phase
‣ Infection is contained within the
interstitial compartment or
peribronchial region before it extends
to involve the alveoli (consolidation)
- Neutropenia secondary to pneumonia,
asplenia, or complement deficiencies; chronic
liver disease; or severe CAP
3. Antigen Tests
- Legionella antigens in urine
‣ Test for L. pneumophila detects only
serogroup 1, but this serogroup accounts
for most community-acquired cases of
Legionnaires' disease
‣ 90% sensitive and 99% specific
- Pneumococcus
- Influenza
- RSV
4. PCR
- Generally limited to research studies
- In patients with pneumococcal pneumonia, an
increased bacterial load documented by PCR
is associated with an increased risk of septic
shock, need for mechanical ventilation, and
death
5. Serology
- A fourfold rise in specific IgM antibody titer
between acute- and convalescent-phase
serum samples is generally considered
diagnostic of infection with the pathogen in
question

An initial “normal” chest x-ray may connote a

radiographic lag phase
- May repeat imaging 24-48 hours if the
initial CXR is normal
- Repeat radiograph is recommended
during a follow-up office visit,
approximately 4 to 6 weeks after hospital
discharge

ETIOLOGIC DIAGNOSIS
1. Gram’s Stain and Culture of Sputum
- Main purpose of the sputum Gram's stain is to
ensure that a sample is suitable for culture
- Adequate for culture, a sputum sample must
have >25 neutrophils and <10 squamous
epithelial cells per low-power field
- Inability to produce sputum can be a
consequence of dehydration
- Even in cases of proven bacteremic
pneumococcal pneumonia, the yield of
positive cultures from sputum samples is 50%
2. Blood Cultures
- Only ~5–14% of cultures of blood from
patients hospitalized with CAP are positive,
and the most frequently isolated pathogen is
S. Pneumoniae

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 Co-morbid conditions
- Diabetes Mellitus
- Neoplastic diseases
- Congestive Heart Failure
- Coronary Artery Disease
- Renal Insufficiency
- COPD
- Bronchial Asthma
- Chronic Liver Disease
- Chronic Alcohol Abuse
2 sets of criteria used for assessing management
and prognostication
1. Pneumonia Severity Index
- prognostic model used to identify patients
at low risk of dying
2. CURB-65
- severity-of-illness score

PNEUMONIA SEVERITY INDEX (PSI)

20 variables (age, coexisting illness, and
abnormal physical and laboratory findings)
❑ class 1 - 0.1% mortality
❑ class 2 - score of <70 (0.6% mortality)
❑ class 3 - score of 71-90 (2.8% mortality)
❑ class 4 - score of 91-130 (8.2% mortality)
❑ class 5 - score of >130 (29.2% mortality)
Lower admission rates for class 1 and class 2
patients
Patients in classes 4 and 5 should be admitted to
the hospital
Class 3 should ideally be admitted to an
observation unit until a further decision can be
made
CURB-65
confusion (C)
urea >7 mmol/L (U)
respiratory rate 30/min (R)
blood pressure, systolic 90 mmHg or diastolic 60
mmHg (B)
age 65 years (65)
- 0 - 1.5% mortality in 30 days, treated as
outpatient
ANTIBIOTIC RESISTANCE
S. pneumoniae
1. by direct DNA incorporation and remodeling
resulting from contact with closely related oral
commensal bacteria
2. by the process of natural transformation
3. by mutation of certain genes
- Pneumococcal resistance to B-lactam drugs
is due solely to low-affinity penicillin-binding
proteins
‣ Risk Factors: recent antimicrobial therapy,
an age of <2 years or >65 years,
attendance at day-care centers, recent
hospitalization, and HIV infection
- Macrolides
‣ Target-site modification is caused by
ribosomal methylation in 23S rRNA
encoded by the ermB gene
‣ Efflux mechanism encoded by the mef
gene (M phenotype) is usually associated
with low-level resistance

- 2 – 9.2% mortality rate, treated in the hospital

- Fluroquinolones
- 3 – 22% mortality rate, treated in ICU
‣ Mutations in the gyrA and parC genes
‣ Efflux pump

- Isolates resistant to drugs from three or more

antimicrobial classes with different
mechanisms of action are considered MDR
- The most important risk factor for antibiotic-
resistant pneumococcal infection is use of a
specific antibiotic within the previous 3 months

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 CA-MRSA
- Determined by the mecA gene, which
encodes for resistance to all B-lactam
drugs
- Five staphylococcal chromosomal cassette
mec (SCCmec) types have been
described
‣ Hospital-acquired strain usually has
type II or III, whereas CA-MRSA
has a type IV SCC mec element
- Often susceptible to trimethoprim-
sulfamethoxazole, clindamycin, and
tetracycline in addition to vancomycin and
linezolid
Gram Negative Bacilli
- Enterobacter spp. are typically resistant to
cephalosporins; the drugs of choice for use
against these bacteria are usually
fluoroquinolones or carbapenems

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TREATMENT
Therapy with a macrolide or a fluoroquinolone
within the previous 3 months is associated with
an increased likelihood of infection with a
resistant strain of S. pneumoniae
- A fluoroquinolone-based regimen should be
used for patients recently given a macrolide,
and vice versa
CAP admitted to ICU
- The risk of infection with P. aeruginosa or CA-
MRSA is increased, and coverage should be
considered when a patient has risk factors or
a Gram's stain suggestive of these pathogens
How long is the duration of treatment for CAP?
Duration of treatment is 5 to 7 days for low risk
uncomplicated bacterial pneumonia (Grade B).
For moderate-risk and high-risk CAP or for those
with suspected or confirmed Gram-negative, S.
aureus or P. aeruginosa pneumonia, treatment
should be prolonged to 14 - 21 days (Grade B)
A treatment regimen of 10-14 days is
recommended for Mycoplasma and
Chlamydophila pneumonia while Legionella
pneumonia is treated for 14-21 days (Grade B)
A 5-day course of oral or IV therapy for low-risk
CAP and a 10-day course for Legionella
pneumonia is possible with new agents such as
the azalides, which possess a long half-life and
achieve high tissue levels that prolong its duration
of effect (Grade B)
Patients should be afebrile for 48 to 72 hours with
no signs of clinical instability before
discontinuation of treatment (Grade B)
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Pseudomonas aeruginosa
Those with history of chronic or prolonged (>7
days within the past month) use of broad-
spectrum antibiotic therapy
Those with severe underlying
bronchopulmonary disease (COPD,
bronchiectasis)
Malnutrition
Chronic use of steroid therapy >7.5mg/day2.
Treatment
- CA-MRSA
‣ Either linezolid or vancomycin should
be added to the initial empirical
regimen
‣ Vancomycin does not reach significant
concentrations in epithelial lining fluid,
whereas concentrations of linezolid at
this site exceed the MIC for MRSA
during the entire dosing interval
- Fluoroquinolones and telithromycin
suggest that a 5-day course is sufficient for
otherwise uncomplicated CAP
‣ A longer course is required for patients
with bacteremia, metastatic infection,
or infection with a virulent pathogen
such as P. aeruginosa or CA-MRSA
“Although the newer antipneumococcal
quinolones such as levofloxacin or moxifloxacin are
also options for therapy, it is recommended that
they be reserved as potential second line agents
for the treatment of pulmonary tuberculosis,
particularly for multidrug-resistant tuberculosis.”
FAILURE TO IMPROVE
1. Noninfectious conditions (pulmonary edema,
pulmonary embolism, lung carcinoma, radiation
and hypersensitivity pneumonitis, and connective
tissue disease involving the lungs).
2. The pathogen may be resistant to the drug
selected, or a sequestered focus (e.g., a lung
abscess or empyema) may be blocking access of
the antibiotic(s) to the pathogen.
3. The patient may be getting either the wrong drug
or the correct drug at the wrong dose or
frequency of administration.
4. It is also possible that CAP is the correct
diagnosis but that an unsuspected pathogen
(e.g., CA-MRSA, M. tuberculosis, or a fungus) is
the cause.
5. Nosocomial superinfections—both pulmonary and
extrapulmonary
COMPLICATIONS
Respiratory failure
Shock and multiorgan failure
Coagulopathy
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 Exacerbation of co-morbid illnesses

FOLLOW-UP
Fever and leukocytosis usually resolve within 2–4
days in otherwise healthy patients with CAP, but
physical findings may persist longer
Chest radiographic abnormalities are slowest to
resolve and may require 4–12 weeks to clear
Follow-up radiograph can be done ~4–6 weeks
later
If relapse or recurrence is documented,
particularly in the same lung segment, the
possibility of an underlying neoplasm must be
considered

PROGNOSIS
Depends on the patient's age, co-morbidities, and
site of treatment (inpatient or outpatient)
Young patients without comorbidity do well and
usually recover fully after ~2 weeks.
The overall mortality rate for the outpatient group
is <1%.
Ventilator-Associated Pneumonia- development
For patients requiring hospitalization, the overall of new infiltrates on CXR, fever, purulent sputum
mortality rate is estimated at 10%, with ~50% of 48-72 hrs after endotracheal intubation
deaths directly attributable to pneumonia.
Non-MDR
PREVENTION - Nearly identical to the pathogens found in
severe CAP
The main preventive measure is vaccination
- Predominate if VAP develops in the first 5–7
Influenza outbreak days of the hospital stay
- unprotected patients at risk from MDR
complications should be vaccinated
immediately and given chemoprophylaxis with - If patients have other risk factors for HCAP
either oseltamivir or zanamivir for 2 weeks Virus
Fungi

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EPIDEMIOLOGY
On any given day in the ICU, an average of 10%
of patients will have pneumonia—VAP in the
overwhelming majority of cases
Highest hazard ratio in the first 5 days and a
plateau in additional cases (1% per day) after ~2
weeks
PATHOGENESIS
Colonization of the oropharynx with pathogenic
microorganisms
Aspiration of these organisms from the
oropharynx into the lower respiratory tract
Compromise of the normal host defense
mechanisms
TREATMENT
VENTILATOR-ASSOCIATED PNEUMONIA
The most obvious risk factor is the endotracheal
tube, which bypasses the normal mechanical
factors preventing aspiration
- Microaspiration
‣ Around one-third of colonized patients
develop VAP
- Pathogenic bacteria can form a glycocalyx
biofilm on the tube's surface that protects
them from both antibiotics and host defenses
- Overwhelming host defenses
‣ Hyperglycemia
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‣ Multiple
QUANTITATIVE-CULTURE APPROACH
Discriminate between colonization and true
infection by determining the bacterial burden
- The more distal in the respiratory tree the
diagnostic sampling, the more specific the
results and therefore the lower the threshold
of growth necessary to diagnose pneumonia
and exclude colonization
CLINICAL APPROACH
Clinical Pulmonary Infection Score (CPIS)
- allows the selection of low-risk patients who
may need only short-course antibiotic therapy
or no treatment at all
- The absence of bacteria in gram-stained
endotracheal aspirates makes pneumonia an
unlikely cause of fever or pulmonary infiltrates
- The absence of an MDR pathogen in tracheal
aspirate cultures eliminates the need for MDR
coverage when empirical antibiotic therapy is
narrowed
TREATMENT
The majority of patients without risk factors for
MDR infection can be treated with a single agent
The standard recommendation for patients
with risk factors for MDR infection is for three
antibiotics: two directed at P. aeruginosa and one
at MRSA
FAILURE TO IMPROVE
40% failure rate for MRSA infection treated with
vancomycin
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 VAP due to Pseudomonas has a 50% failure rate
A persistently elevated or rising CPIS value by
day 3 of therapy is likely to indicate failure

PROGNOSIS
Crude mortality rates of 50–70%
Patients who develop VAP are at least twice as
likely to die as those who do not

Health care associated Pneumonia

Diagnosis made after admission with any of the ff:
1. Hospitalized in an acute care hospital for >48
hrs w/in 90 days of the diagnosis
2. Resided in a nursing home or long term care
facility
R e c e i v e d r e c e n t I V a n t i b i o t i c t h e r a p y,
chemotherapy, or wound care w/in 30 days
preceding the current diagnosis
Attended a hospital or hemodialysis clinic

** Taken from the lecture ppt only, use at your own risk :) Goodluck

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