Transcript Treatment

82 title slides
246 total slides
Lecture 47-49 – not included
We are nearly finished with our first year!
Congratulations everyone!
1
1.
2.
3.
4.
Define asthma
Workup for possible asthma
Associations and triggers for asthma
Treatment categories of asthma
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EXAM … Kudlak’s said “know these”

Symptoms/definition of asthma
 Variable obstruction

Testing
 CXR, PFT (spirometry), methacholine challenge

Presentation
 FamHx, allergies, eczema

2 tables
 Intermittent
 Mild

Treatment algorithm
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1. Define asthma
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Asthma
VARIABLE Airflow Obstruction - Disease of the
airways
 Reversibility
 Inflammation

 Infiltration of inflammatory cells and mediators
 Mucous gland hyperplasia and production

Remodeling … if untreated
 Basement membrane thickening, smooth muscle
hyperplasia and transition to squamous epithelium
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Symptoms and Complaints
Dyspnea at rest or exertion
 Cough
 Wheezing

 What is a wheeze?
 Symptom, non specific
 Wheezing vs stridor
○ Wheeze – expiratory
Stridor – inspiratory (e.g. vocal cord dysfunction, granulation
[d/t poor previous ET intubation])
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2. Workup for possible asthma
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Ancillary Studies
CXR - PA & lateral
 Spirometry – pre & post bronchodilator
 Methacholine Challenge
 HRCT
 Cardiopulmonary Exercise Testing
 IgE & RAST
 Exhaled NO - eNO

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CXR & HRCT

CXR
 May be normal
 Abnormal findings:
○ Hyperexpansion
○ Mucous plugging and atelectasis

HRCT may reveal:
 Air Trapping
 Mucous plugging and atelectasis
 Remodeling
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Spirometry (PFT)

FEV-1/FVC – is obstruction present or not?
 FEV-1 / FVC < 70% = obstruction present

FEV-1 – severity of obstruction
 70% = mild
 50% = severe
 30% = very severe

FEF 25-75 – thought by some to reflect the small
airways.
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Methacholine Challenge

Bronchoprovacation – methacholine, mannitol, histamine
 i.e. provoking an asthma attack
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Serial measurement of FEV-1 at increasing
concentrations of methacholine
Provocative Concentration of methacholine to produce a
20% decrease in FEV-1
PC02- at 8 mg/ml
Can demonstrate hyperresponsiveness and reversibility
Discontinuation of medications prior to testing.
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3. Associations and triggers for asthma
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Common Link/Associations
Triggers
Family History
 Allergy – Atopy (IgE)
 Eczema
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AR = allergic rhinitis
PND = paroxysmal nocturnal dyspnea
GERD … MedHx of every single S.P. this block

Seasonal allergies – AR,
PND
GERD
Changes in temperature and
or humidity
Cats
Dust Mites
Mold
Upper respiratory infections
First and second hand
smoking
Fragrances
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4. Treatment categories of asthma
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Treatment Goals
Reduce symptoms and limitations
 Identify triggers
 Prevent remodeling
 Objectively measure control of disease
 Education:

 Maintenance - long term care (change the car’s oil)
 Rescue – short term fix
○ Intermittent, mild asthma (albuterol, 2 days in spring and 2 days in fall)
 Use of MDI
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Categories of asthma:
Intermittent vs. mild/persistent

Intermittent
 i.e. high school football player wheezes 2x/year (fall and spring)
 Nocturnal awakenings (< 2 times / month)
 # uses of rescue inhaler (< 2 days / week)

Mild (persistent)
 Nocturnal awakenings (> 3 times / month)
 # uses of rescue inhaler (> 2 days / week)

Severe
 Symptoms all day long
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Treating asthma:
Intermittment vs. mild/persistent
Refer to figure on previous slide, steps 1-3
(SABA  ICS  ICS + LABA)
 Intermittent asthma
 SABA PRN (albuterol)

Mild, persistent asthma
 Low dose ICS (fluticasone)

Persistent asthma (using ICS and SABA 4x/day)
 ICS + LABA (Advair, Symbicort, Breeu)
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Abbreviations/Tx options
SABA
 LABA
 ICS

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SABA … Short Acting Beta Agonist
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Quick acting, short lasting
Rescue therapy for symptom relief
Increased use usually indicates a need for step up in
therapy
Relaxes bronchial smooth muscles
They do not control the underlying inflammation
Beta – 2 agonists
Most common are albuterol and levalbuterol
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LABA … Long Acting Beta Agonist
i.e. symbicort, advair
 All have a black box warning
 Smart Trial lessons learned
 Never use LABA to Tx asthma without an inhaled
corticosteroid

 Patients die if you change from SABA  LABA (without adding ICS)
 Proper changes: SABA  ICS  ICS + LABA
Can decrease need for repetitive SABA use
 Effective in decreasing night time symptoms
 Can be given by MDI or Nebulized

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ICS (Inhaled Corticosteroids)
i.e. fluticasone
 Treat the underlying inflammation
 The most effective maintenance medication
 Reduce the number and activity of inflammatory cells
in the airways
 Minimal absorption into the systemic circulation
 Excellent deposition in target tissue
 Can be given by MDI or Nebulized

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1.
2.
3.
4.
5.
Micro of acute bronchitis
URI viruses
Treatment for acute exacerbations
Workup and treatment
Flu treatments
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1. Micro of acute bronchitis
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Acute Bronchitis
Generally cause by a virus
 Influenza A and B
 Para influenza
 Coronavirus
 Rhinovirus
 RSV (Respiratory syncytial virus)
 Human metapneumovirus
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Acute Bronchitis
Other Pathogens:
 Mycoplasma pneumoniae - pharyngitis, constitutional
symptoms and cough. (Common case)
 Chamydophilia pneumoniae - pharyngitis, laryngitis
and bronchitis, hoarseness and low grade fever.( 5%
of cases)
 Pertussis - 1% of cases in US
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2. URI viruses
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URI Epidemiology
Seasonal Patterns:
 Rhinoviruses and Para
influenza
 Fall and late spring

Non-seasonal Patterns:
 Adenoviruses
 Military facilities, daycare
centers and hospital wards
RSV and coronaviruses
 Winter and spring

Enteroviruses
 Summer
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URI Virology
Over 200 subtypes of viruses
 Rhinovirus which includes more than 100 serotypes
is the most common (30-50%)
 Coronaviruses responsible for 10-15%
 Influenza virus responsible for 5-15%
 Respiratory syncytial virus (RSV) responsible for 5%
 Most are capable of reinfection

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3. Treatment for acute COPD exacerbations
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COPD treatment

Oxygen

 How much?
 IV solumedrol (60-125mg) vs PO
prednisone (30-60mg)
○ 2 Liters
○ IV – if pt cannot breathe well or swallow
 Is hypercapnia a problem?
○ PO – at home therapy
○ Yes, watch out for acidosis and
low mental status
○ Non-rebreather can worsen
hypercapnia

Bronchodilators
 beta adrenergic agents -
albuterol
 anticholinergic agents ipratropium
Steroids – reduce inflammation

Antibiotics?
 YES

BiPAP vs. intubation?
 If looking crappy but can follow
commands, consider BiPAP
 If unable to follow commands, ET
intubation
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4. Workup and treatment
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4a. Workup
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A 56 year old male with a PMHx of COPD presents with a c/c
of increasing cough and sputum production.

What questions should you ask?
 Fever? Constitutional? Eating? Sleeping? Able to get out of bed?

CXR?
 Yes, especially if (1) COPDers are looking worse than normal, OR (2) O2
sat is unresponsive to O2 therapy

Labs? ABG?
 Determine pt baseline (PaO2 and PaCO2)
 Is patient part of 50/50 club? PaO2 = 50, PaCO2 = 50

Antibiotics?
 Yes, especially for COPDers getting worse
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Admission?
 If they look bad (SEE NEXT SLIDE)
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COPD admission … these make sense
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Inadequate response to treatment – no change
Marked increase in dyspnea – more dyspnea
Inability to eat or sleep due to symptoms – anorexia, insomnia
Worsening hypoxemia (drop from PaO290 82)
Worsening hypercapnia – PaCO2 (50-70)
Changes in mental status
Inability to care for oneself
High risk comorbidities including pneumonia, cardiac
arrhythmia, CHF, DM, renal failure or liver failure
Uncertain diagnosis
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4b. Treatment
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COPD treatment … same as slide 32

Oxygen

 How much?
 IV solumedrol (60-125mg) vs PO
prednisone (30-60mg)
○ 2 Liters
○ IV – if pt cannot breathe well or swallow
 Is hypercapnia a problem?
○ PO – at home therapy
○ Yes, watch out for acidosis and
low mental status
○ Non-rebreather can worsen
hypercapnia

Bronchodilators
 beta adrenergic agents -
albuterol
 anticholinergic agents ipratropium
Steroids – reduce inflammation

Antibiotics?
 YES

BiPAP vs. intubation?
 If looking crappy but can follow
commands, consider BiPAP
 If unable to follow commands, ET
intubation
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5. Flu treatments
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Acute Bronchitis

Mycoplasma pneumoniae or Chlamydophila
pneumoniae
 Suspect with prolonged cough and URI symptoms
 Treatment: tetracyclines, macrolides and fluoroquinolones

Pertussis
 Treatment: erythromycin or clarithromycin

Influenza
 Consider treatment of neuraminidase inhibitors if symptoms
onset within 48 hours (oseltamivir, zanamavir)
 Supportive therapy (hydration)
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1.
2.
3.
4.
Define emphysema, chronic bronchitis
PFT in COPD
Classes of drugs with mechanisms
Adult bronchiectasis causes
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1. Define emphysema, chronic bronchitis
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1a. Define emphysema
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Emphysema - Clinical definition
Emphysema
 Chronic progressive dyspnea with little sputum
production, hypoxemia, decreased expiratory flow
and end stage cachexia.
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Emphysema - Anatomical definitions
Permanent enlargement of the air spaces (acini) distal
to the terminal bronchioles.
 Centrilobular or Centriacinar emphysema.

 Disease of respiratory bronchioles (primarily)
 This is a common finding in smokers.

Panacinar or Panlobular emphysema
 Disease of entire air space, acini, distal to the terminal bronchiole
 This is more common in Alpha-1 anti-trypsin deficiency.

Possible for combinations of disease entities
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1b. Define chronic bronchitis
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Clinical Definition
Chronic Bronchitis
 Persistent cough resulting in sputum production for
more than 3 months in each of the past 2 years .
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2. PFT in COPD
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Lung Function; Normal and abnormal
1. Most adult nonsmoking men show a decline in their forced expiratory
volume in 1 second (FEV1) of 35-40ml/year
2. Smokers show a decrease in the FEV1 of 45-60ml/yr.
3. Those who smoke and develop COPD show loses of FEV1 of 70-120ml/yr.!!!50
Normal Pulmonary Function Test:
VOLUMES:
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TV = Tidal Volume
IRV= Inspiratory Reserve Volume
ERV = Expiratory Reserve Volume
RV= Residual Volume
FEV1 = Forced Expiratory Volume in the
first second
CAPACITIES:
TLC = Total Lung Capacity
IC = Inspiratory Capacity = TV + IRV
FRC = Functional Residual Capacity,
ERV + RV
 VC or FVC= Vital Capacity or Forced
Vital Capacity = IRV + TV + ERV.



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3. Classes of drugs with mechanisms
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Therapy and Prevention:
 Bronchodilators (SABA, LABA)
 Beta 2 agonists - open airways

Anticholinergic
 Block secretions

Steroids (PO vs. IV vs. ICS)
 Reduce inflammation

Oxygen (acute vs. chronic AND
QHS vs. continuous)
 Increase O2 sat

Antibiotics (for acute exacerbations)
 Limit infections

Holistic and Surgical:
 Smoking cessation
 Avoid airway irritants
 Diet
 Exercise
 Chest Physical Therapy
 OMT
 Chronic Pulmonary
Rehabilitation

Lung Resection, Bullectomy
Mucolytic agents
 Thin mucus secretions

Vaccinations (Pneumococcal and
influenza vaccines)
 Prevention
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Inhaled bronchodilators
Relaxation airway
smooth muscle
 Decreases mast cell
mediator release
 Increases mucociliary
clearance
 Increases mucus
secretion (thinned)

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4. Adult bronchiectasis causes
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Causes/Etiology of Bronchiectasis
1/3 of cases – unknown etiology (unknown cause)
 1/3 of case - infections

 Pertussis in children
 MAI (mycobacterium avium) in adults

Remaining 1/3 (other):
 Genetic - Cystic Fibrosis, Primary ciliary dyskinesia, and
alpha1-antitrypsin deficiency
 Anatomic - dysphagia and esophageal dysfunction
 Immune and autoimmune - Primary
Hypogammaglobulinemia, HIV, RA and Sjogren’s
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Bronchiectasis - definition

Abnormal and
permanent dilation
of the bronchi caused
by repeated cycles of
infection and
inflammation
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1.
2.
3.
4.
5.
Incidence of lung cancer
6.
Pancoast definition / associations
7.
Horners syndrome
8.
CA with keratinization
Treatment of squamous CA early
Small cell systemic complications,
histologic cells
Treatment of Small cell early
Stage IV treatment
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1. Incidence of lung cancer
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Incidence = # new cases / unit time

Lung cancer is the most common cancer worldwide,
 Estimated 1,600,000 new cases and 1,380,000 deaths in 2008.
 In the United States, there will be an estimated 226,000 new cases of lung cancer and
160,000 deaths in 2012.
Around 1953, lung cancer became the most common cause of cancer deaths
in men, and in 1985, it became the leading cause of cancer deaths in women.
Lung cancer deaths have begun to decline in men, reflecting a decrease in
smoking. The rise in the death rate in women appears to have reached a plateau,
although almost one-half of all lung cancer deaths now occur in women.
 The term lung cancer, or bronchogenic carcinoma, refers to malignancies that
originate in the airways or pulmonary parenchyma. Approximately 95 percent of
all lung cancers are classified as either small cell lung cancer (SCLC) or nonsmall cell lung cancer (NSCLC). This distinction is essential for staging,
treatment, and prognosis. Other cell types comprise about 5 percent of
malignancies arising in the lung (mesothelioma d/t asbestos exposure)s

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2. Pancoast definition / associations
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Pancoast's syndrome

Lung cancers arising in the superior sulcus cause a
characteristic Pancoast's syndrome manifested by:
 Pain (usually in the shoulder, and less commonly in the forearm,
scapula, and fingers),
 Horner's (ptosis, miosis, and anhidrosis),
 Bony destruction, and
 Atrophy of hand muscles.
 Pancoast's syndrome is most commonly
caused by NSCLC (typically squamous cell)
and only rarely by SCLC .
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3. Horners syndrome
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Horner's syndrome (ipsilateral ptosis, anhidrosis, and miosis) may be due
to invasion of the last cervical or first thoracic segment of the sympathetic
trunk (T4 disease).
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Horner’s Syndrome

Pancoast's syndrome — Lung cancers arising in the superior
sulcus cause a characteristic Pancoast's syndrome manifested
by
 Pain (usually in the shoulder, and less commonly in the forearm,
scapula, and fingers),
 Horner's = ipsilateral ptosis, miosis, and anhidrosis
○ Usually due to pancoast tumor invasion of superior
cervical ganglion
 Bony destruction, and
 Atrophy of hand muscles. Pancoast's syndrome is most commonly
caused by NSCLC (typically squamous cell) and only rarely by SCLC .
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4. CA with keratinization
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EXAM!!!
SQUAMOUS CELL CARCINOMA (NSCLC) …
KERATINIZATION
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CLINICAL MANIFESTATIONS
•
Paraneoplastic phenomena (COMLEX) — Paraneoplastic effects of tumor
are remote effects that are not related to the direct invasion, obstruction, or
metastasis.
•
Hypercalcemia — Hypercalcemia in patients with lung cancer may arise
from a bony metastasis or less commonly tumor secretion of a parathyroid
hormone-related protein (PTHrP), calcitriol or other cytokines, including
osteoclast activating factors. Cases with hypercalcemia are divided as such:
squamous cell carcinoma (51%), adenocarcinoma (22%), and SCLC
(15%). Most patients with hypercalcemia have advanced disease (stage III or
IV) and a median survival of a few months .
• Symptoms of hypercalcemia include anorexia, nausea, vomiting,
constipation, lethargy, polyuria, polydipsia, and dehydration. Confusion and
coma are late manifestations, as are renal failure and nephrocalcinosis.
Symptomatic patients who have serum calcium of 12 or higher require
treatment that includes hydration and bisphosphonate.
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5. Treatment of squamous CA (NSCLC) early
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NSCLC (Squamous) Treatment
•
•
•
Surgical resection offers the best opportunity for longterm survival and cure in patients with resectable NSCLC. The
appropriateness of surgical resection of candidates with known or
suspected NSCLC includes preoperative staging and an assessment
of performance status with concurrent comorbidities and pulmonary
function to allow prediction of postoperative function.
A patient with lung cancer may be "resectable" by virtue of
having a surgically removable NSCLC, but may not be
"operable" due to poor pulmonary function or comorbidities.
Patients with stage I or II NSCLC should be treated with
complete surgical resection whenever possible.
• Postoperative adjuvant chemotherapy has been shown to improve survival in
patients with pathologic stage II disease and may have a role for patients with
stage IB NSCLC.
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6. Small cell systemic complications,
histologic cells
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6a. Small cell (SCLC) systemic
complications
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CLINICAL MANIFESTATIONS

SIADH secretion — The syndrome of inappropriate antidiuretic
hormone secretion (SIADH) is frequently caused by SCLC and
results in hyponatremia.
 Symptoms include anorexia, nausea, and vomiting.
 Cerebral edema can occur with the onset of hyponatremia is rapid. Symptoms caused
by cerebral edema may include irritability, restlessness, personality changes,
confusion, coma, seizures, and respiratory arrest.
 Treatment of SIADH focuses on treating the malignancy. In the majority of patients with
SCLC, the hyponatremia will resolve within weeks of starting chemotherapy.

Neurologic — Lung cancer is the most common cancer associated with
paraneoplastic neurologic syndromes; typically these are associated with
SCLC. Paraneoplastic neurologic syndromes are thought to be immunemediated, and autoantibodies have been identified in a number of
instances.
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CLINICAL MANIFESTATIONS

These diverse neurologic manifestations include, but are not limited to,
Lambert-Eaton myasthenic syndrome (LEMS),
cerebellar ataxia, sensory neuropathy, limbic encephalitis,
encephalomyelitis, autonomic neuropathy, retinopathy, and
opsomyoclonus .


The most common of these is LEMS, which may be seen in
approximately 3 percent of patients with SCLC. The neurologic
symptoms of LEMS precede the diagnosis of SCLC in more than 80
percent of cases, often by months to years.
Paraneoplastic neurologic syndromes generally do not improve with
immunosuppressive treatment. However, symptoms may stabilize with
response of the underlying neoplasm to treatment.
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CLINICAL MANIFESTATIONS
•
•
•
Hypertrophic osteoarthropathy — Hypertrophic pulmonary osteoarthropathy (HPO) is
defined by the presence of clubbing and periosteal proliferation of the tubular bones
associated with lung cancer or other lung disease. Clinically, HPO is characterized by a
symmetrical, painful arthropathy that usually involves the ankles, knees, wrists, and
elbows. The metacarpal, metatarsal, and phalangeal bones may also be involved.
Dermatomyositis and polymyositis — Dermatomyositis and polymyositis are two
distinct forms of inflammatory myopathy, both of which are manifested clinically by muscle
weakness. These inflammatory myopathies can be the presenting symptom in patients
with lung cancer or can develop later in the course of disease.
Cushing's syndrome — Ectopic production of adrenal corticotropin (ACTH) can
cause Cushing's syndrome. Patients typically present with muscle weakness, weight
loss, hypertension, hirsutism, and osteoporosis. Hypokalemic alkalosis and
hyperglycemia are usually present. Cushing's syndrome is relatively common in
patients with SCLC and with carcinoid tumors of the lung. Patients with Cushing's
syndrome and SCLC appear to have a worse prognosis than patients with SCLC without
Cushing's syndrome.
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6b. Small cell histologic cells
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EXAM!!!
SCLC … small blue cells
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7. Treatment of Small cell (SCLC) early
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SCLC Treatment
Patients with limited stage SCLC
•
Primary Tx = combination of chemotherapy and radiation
therapy,
• Addition of radiation therapy has been shown to prolong survival compared to
chemotherapy therapy alone.
•
Surgery is palliative…is not used except in the rare patient who presents with
a solitary pulmonary nodule without metastases or regional lymph node
involvement. SCLC HAPPENS SO FAST THAT THERE IS USUALLY NO
TIME FOR SURGICAL RESECTION.
For patients with extensive stage SCLC,
• Chemotherapy alone is used as the initial therapy.
• Prophylactic radiation has been shown to decrease the incidence of brain
metastases and prolong survival in patients with both limited and extensive
stage SCLC who respond to their initial treatment.
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8. Stage IV treatment
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Treatment (NSCLC)
Patients with stage IV disease
•
Systemic therapy OR
• Symptom-based palliative approach.
• In appropriately selected patients, chemotherapy and/or molecularly
targeted therapy may prolong survival without sacrificing quality of
life.
• Radiation therapy and surgery may also be useful for symptom
palliation in some patients.
Patients with stage IV disease based upon the presence of an
isolated metastasis (brain, adrenal)
• May benefit from resection of the metastasis as well as aggressive
treatment of the primary tumor… palliative, NOT curative
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1.
2.
3.
4.
5.
ABG interpretation
Define ARDS
Inhalation toxins & treatment
Sleep apneas (central v. sleep)
Treat lung symptoms anaphylaxis
84
1. ABG interpretation
Refer back to Dr. J’s CM
Lecture 34 (block 4) if
this doesn’t make sense
85
ABG
Normal Measures:
 PaO2 (>80 mmHg)
 PaCO2 (35-45 mmHg)
 pH (7.35-7.45)
 SaO2 (>95%)
 HCO3 (21-27 mEq/L)
86
ABG
pH 7.25
 PaO2 92
 PaCO2 82
 Sat 90%
 HCO3 30

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2. Define ARDS
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Acute Respiratory Distress Syndrome
(ARDS)

Acute, diffuse, inflammatory lung injury that leads to:
 Increased pulmonary vascular permeability (thick and soggy lungs)
 Increased lung weight
 Loss of aerated tissue
Hypoxemic respiratory failure
 Involves both lungs
 aka Shock lung

89
ARDS
Pathological Hallmark is diffuse alveolar damage
 Alveolar edema with or without focal hemorrhage
 Acute inflammation of the alveolar walls and hyaline
membranes

90
ARDS
Clinical features:
Rapid onset of 6-72 hours
 Worsens rapidly
 Dyspnea, cyanosis (hypoxemia), and diffuse crackles
 Tachypnea, tachycardia, diaphoresis and use of
accessory muscles
 May also have cough and chest pain

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ARDS - Testing
ABG:
 Hypoxemia
 Respiratory alkalosis
 Elevated alveolar-arterial
oxygen gradient (increased
A-a gradient)
CXR (Chest X-ray):

Bilateral alveolar infiltrates
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3. Inhalation toxins & treatment
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Inhalation Injuries
Simple asphyxiants:
Work related during the use of liquefied gas or airline
respirators or working in confined spaces
 Inert
 Produce toxicity by displacing oxygen and lowering FIO2

Treatment:
 Removal from exposure,
 Supplemental oxygen
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Inhalation injuries
Pulmonary irritants:
Chlorine, ammonia, sulfur dioxide, phosgene, etc.
 Dissolve in the respiratory tract mucous and alter the airlung interface by invoking an irritant or inflammatory
response.
 Produce and acid or alkaline product or direct cellular
toxicity

Treatment:
Bronchospasm-nebulizer,
 Consider early intubation

95
Inhalation injuries
Smoke inhalation – fires

Heat transfer causing damage and toxins produced by
the fire are adsorbed onto carbonaceous particles that
deposit in the airways
Treatment:
Rapid intubation, oxygen, nebulizers.
 Possible broncholavage to clear debris and toxins from
distal airways

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Inhalation injuries
Hydrogen sulfide
Petroleum refinery and sewage storage tank workers
 Rotten egg smell
 Pulmonary irritant and cellular poison

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Inhalation injuries
Cyanide





Many commercial uses
Bitter almonds
Rapidly absorbed, inhibition of oxidative metabolism
Tissue hypoxia in seconds to minutes
Coma, seizures, cardiovascular collapse
Antidote

Sodium thiosulfate
98
Inhalation injuries
Carbon monoxide
Most common cause of acute poisoning death
 Prevents binding of O2 to hemoglobin and shifts the
oxyhemoglobin dissociation curve to the left interfering
with the ability of normal hemoglobin to release its bound
O2 to the tissues
 Coma, seizures, cardiac arrest

Treatment

O2, hyperbaric
99
4. Sleep apneas (central v. obstructive)
100
4a. Sleep apneas (central)
101
Central sleep apnea (CSA)
Repetitive cessation or decrease of both airflow and
ventilatory effort during sleep
 Primary – just happens
 Secondary - include Cheyne-Stokes breathing, medical
condition, a drug/substance abuse
 Hyperventilation related CSA (brain causes tachypnea)

102
Central sleep apnea
Disrupted sleep with excessive daytime sleepiness
 Poor subjective sleep quality

 “I am not sleeping well”





Insomnia
Inattention
Poor concentration
Morning headaches
Nocturnal angina
103
Central sleep apnea
Diagnosis - in lab polysomnography
 3 findings

 > 5 central apneas per hour of sleep
 Excessive daytime sleepiness, awakening with SOB,
frequent arousals and awakening during sleep, or insomnia
 Not explained by another sleep disorder, medical disorder,
neurological disorder, medication use or substance abuse
104
4b. Sleep apneas (obstructive)
105
Obstructive sleep apnea (OSA)
Definition

Obstructive apneas and hypopneas caused by repetitive
collapse of the upper airway during sleep (think obesity)
106
Obstructive sleep apnea
Clinical presentation
Daytime sleepiness (“I am tired”)
 Loud snoring
 Gasping, snorting or interruptions in breathing while
sleeping

107
Obstructive sleep apnea
Diagnostic tests
Full-night in-laboratory polysomnography
 Diagnosis: 15 or more apneas per hour of sleep
OR
 Diagnosis: 5 or more obstructive apneas per hour of
sleep in a patient with signs and symptoms of disturbed
sleep

108
5. Treat lung symptoms anaphylaxis
109
Anaphylaxis
Treatment:

Assess for early intubation for airway issues
 i.e. large uvula
 Epinephrine!!!
 IM or IV
 2 large bore IV’s
 Oxygen
 Volume resuscitation with IV fluids
110
Anaphylaxis
Epinephrine doses:

IM 0.3 -0.5 mg (1 : 1,000)
 Infants and children IM 0.01 mg per kg (1 : 1,000)

IV infusion preferred over bolus dose 2-10 micrograms
per minute (1:10,000)
 ALWAYS do 1 : 10,000 first = proper dilution
 If you did 1 : 1,000 first, cause severe HTN  CVA and MI

No absolute contraindications to the use of epinephrine
111
Anaphylaxis
Adjunctive therapies: Always in addition to epinephrine
Antihistamines – H1 (Benadryl) or H2 (Zantac …if unresponsive)
 Bronchodilators - albuterol
 Glucocorticoids – prevents collapse after stable
 Other vasopressors 
112
There are some good CM Pearls floating around for these 3 lectures.
113
1.
2.
3.
4.
5.
Histology of acute TB lymph
PPD immune reaction
Isolation for TB
Immunocompromised workup for TB
Ranges for positive PPD
114
Lecture 50-51 Practice Questions
115
Question #1
80 year old nursing home resident presents to the ER with cough.
He has no other complaints. Nursing home care giver is present and states
four days ago he was well. ER work up is done including bacterial and acid
fast testing samples, CXR, and lab work is done. He is eventually diagnosed
with bronchitis and sent back to the NH on a Z-pack.
You as his primary care are notified the next day that his the acid fast stain is
positive.
What now?
A. Do nothing, await further testing from the laboratory
B. Isolate him, use airborne precautions, await further laboratory testing
C. Isolate him, order Chest CT scan, and more sputum cultures
D. Isolate him, order Chest CT scan, more sputum cultures, and start him on TB
treatment
116
Question
You are called by the director of your local hospital ER for the evaluation
of several people concerned that they may have TB. The people work on
different floors of an office building. Yesterday it was reported to them that
the night janitor had recently passed away from TB meningitis 3 weeks
ago. Several of the people remember passing him in the hallway.
The next step in the management of these patients is which of the
following?
A. Lumbar puncture and place a PPD
B. Place a PPD only, if positive in 48-72 hours then proceed to lumbar
puncture
C. Place a PPD, order a chest X-ray and if either are abnormal then proceed
to lumbar puncture
D. Give reassurance
117
1. Histology of acute TB lymph
118
Path
Necrotizing
granuloma or
caseating granuloma
is composed of
palisading of
epithelioid histiocytes
at the margin of the
necrosis; i.e., the
nuclei are lined up
perpendicular to the
necrotic center. On
AFB stains,
organisms are found
mainly in the zone of
necrosis.
119
“Red snappers”
“Serpentine cording”
120
Primary infection





Inhalation of airborne droplet nuclei size is important (1-5 microns in MTB)
First 3-4 weeks little immune response develops due to number of interacting
factors (low organism #, TB immune system inhibiting factors)
During this initial phase, the organism spreads (disseminated TB) via
macrophages into the surrounding lymphatic system and via blood to other
organs although primary infectious spread to other organs is very rare.
If conditions favor an early immune response then a Ghon complex will form
and be visible on CXR early on.
Later on as the immune system response increases caseating
granulomas will form with later granuloma formation in an attempt to either
eradicate the disease or reach a stalemate in the form of Latent TB
121
2. PPD immune reaction
122
PPD
 Mantoux
5 Tuburculin skin test (PPD)
 Due to a delayed hypersensitivity or type IV reaction
 Tuberculin skin test conversion … increase of >10mm
induration at 2 years
 Read PPD in 48-72 hours (most positive @ 48hrs)
 Boosting …. “2 step ppd” ( second step in 3-4 weeks),
not well supported, only used in cases of suspected
anergy or in patient that get tested frequently (i.e.)
medical student
123
PPD
Measure wheel from insideout (in mm)
Feels like a bumpy orange (raised and erythematous)
124
Neither are positive
125
3. Isolation for TB
To me, this could have two meanings:
1. We are supposed to isolate patients with TB
2. How do we isolate the TB pathogen?
126
Question #1
80 year old nursing home resident presents to the ER with cough.
He has no other complaints. Nursing home care giver is present and states
four days ago he was well. ER work up is done including bacterial and acid
fast testing samples, CXR, and lab work is done. He is eventually diagnosed
with bronchitis and sent back to the NH on a Z-pack.
You as his primary care are notified the next day that his the acid fast stain is
positive.
What now?
A. Do nothing, await further testing from the laboratory
B. Isolate him, use airborne precautions, await further laboratory testing
C. Isolate him, order Chest CT scan, and more sputum cultures
D. Isolate him, order Chest CT scan, more sputum cultures, and start him on TB
treatment
127
Culture




Remains gold standard for confirming diagnosis of
TB
Culture all specimens, even if smear or NAA negative
Results in 4–14 days when liquid medium systems
used
Culture monthly until conversion, i.e., 2 consecutive
negative cultures
128
Colonies of M. tuberculosis
Growing on Media
129
Direct Detection Using Nucleic Acid Amplification
(NAA)




NAA tests rapidly identify a specimen via DNA and RNA
amplification
Benefits may include
 Earlier lab confirmation of TB disease
 Earlier respiratory isolation and treatment initiation
 Improved patient outcomes; interruption of transmission
Perform at least 1 NAA test on each pulmonary TB suspect
A single negative NAA test does not exclude TB
130
Invasive testing
Bronchoscopy useful
Transbronchial biopsies increase diagnostic
yield
Gastric contents (am specimen) sometimes
in young children
Needle bx of pleura with pleural effusion
granulomas in up to 60% but culture of
pleural fluid on 25% cases positive
131
4. Immunocompromised workup for TB
132
Primary TB infection
Composes 2/3 of all MTB infections
 Immunocompetant host’s pulmonary infections develop primarily in the upper
lobes eventually leading to cavitary lesions rich in MTB (105-108 bact)
Older and severely immunocompromised hosts
 Middle to lower lobe disease with or without cavitations
 Both immunocompromised and immunocompetent * could stop at this stage
however, if not then hematogenous spread will occur
 Miliary TB, is a reference to chest x-rays that have a specific pattern.

 Observed only in disseminated TB
 More common to chronic forms of TB
133
“Millet seeds”
http://radiopaedia.org/cases/miliary-tuberculosis-2
134
Miliary TB
135
Suspected Co-infection of TB and HIV
2010 Co-infected study
NEJM 2010(362)707-16
136
5. Ranges for positive PPD
137
PPD cutoffs based risk stratification
- Immunosupressed
particularly defects in
cellular response
www.cdc.gov/ppd
138
Positive PPD/Latent TB
evaluation
STOP
139
PPD
Type of Reaction Possible Cause
 False-positive
 Nontuberculous
mycobacteria
 BCG vaccination***


False-negative
Anergy
Recent TB infection
Very young age (< 6
months old)
 Live-virus vaccination
 Overwhelming TB
disease


140
1.
2.
3.
4.
PPD testing
Treatment for different PPD results
Define MDRTB
Side effects of TB drug treatments
141
Other Exam Questions
142
Question
85 year old native SC male presents to your office from home due to a persistent
productive cough, low grade fever, and 10 lbs weight loss over the past 2 months.
Chest x-ray shows significant bilateral fibrosis with no mass or cavitations. No history
of tobacco usage. Further history reveals that he underwent treatment for TB at the
age of 6. He otherwise feels fine and would like to get back to sitting for his
grandchild.
Please choose one of the options below:
A.
B.
C.
D.
Place a PPD and if positive treat for active TB
Place a PPD, perform AFB sputum stain/culture x3 samples, treat if positive
Isolate patient, perform AFB sputum stain/culture x 3 samples, treat if positive
Isolate patient, perform a bronchoscope and collect samples for stain and culture
including AFB, treat if positive
143
Question

A.
B.
C.
D.
32 year old Hispanic female school teacher presents to your office for preemployment physical evaluation required by your local school district. Part
of the evaluation requires a PPD to be placed. Born in Brazil and left at
the age of 8 years old. She was told as a child that any PPD skin testing
would be positive as she received the BCG vaccination as a child. She
states no TB contacts as a child and has no complaints presently.
What is the next best step in the management of this patient?
Place the PPD anyway
Order a chest x-ray to rule out past or current TB disease
Order chest x-ray and three sputum samples at least 24 hours apart
You remembered Dr. Cook’s email and quickly send an E-consult
144
Question

55 year homeless female is involved in a hit and run. Past history is
significant for TB of which she is currently taking medication for. She is
admitted to the hospital and continued on her prior medications. Ten days
following ORIF of her left femur you are called to the bedside after she is
found to be hypotensive. Basic appropriate testing is done. Hct is 20 and
her PT/INR is prolonged.
Which of the following is the most likely cause of your patient’s condition?
A.
B.
C.
D.
Drug to drug interaction
Hemophilia
Surgical complication
Bacterial sepsis
145
Question
A ESRD patient is found to have a PPD of 12 mm on routine
screening. CXR shows no abnormalities.
What is the next best step in the management of this patient?
A. Place the patient on latent TB therapy
B. Place another PPD in 3-4 weeks, if positive treat for latent TB
C. Order a CT chest due to chance plain CXR is wrong, if abnormal
treat for latent TB
D. Order CT chest and 3 consecutive daily AFB sputum samples, if
abnormal treat for latent TB
146
1. PPD testing … repeat??
147
PPD
 Mantoux
5 Tuburculin skin test (PPD)
 Due to a delayed hypersensitivity or type IV reaction
 Tuberculin skin test conversion … increase of >10mm
induration at 2 years
 Read PPD in 48-72 hours (most positive @ 48hrs)
 Boosting …. “2 step ppd” ( second step in 3-4 weeks),
not well supported, only used in cases of suspected
anergy or in patient that get tested frequently (i.e.)
medical student
148
PPD cutoffs based risk stratification
- Immunosupressed
particularly defects in
cellular response
www.cdc.gov/ppd
149
Positive PPD/Latent TB
evaluation
STOP
150
PPD
Type of Reaction Possible Cause
 False-positive
 Nontuberculous
mycobacteria
 BCG vaccination***


False-negative
Anergy
Recent TB infection
Very young age (< 6
months old)
 Live-virus vaccination
 Overwhelming TB
disease


151
Other methods for detecting Mtb
IGRAs:
 QuantiFERON-TB Gold In-Tube (QFT-GIT)®, and
 T-Spot.TB®
 These tests do not exclude LTBI or TB disease
 Decisions about medical/public health
management should include other info/data, and
not rely only on TST/IGRA results
 Should be considered equivalent to PPD
152
2. Treatment for different PPD results
153
Treatment

Goal is to eliminate bacilli without resistance
 Multiple drugs to which organisms are sensitive
 Add at least 2 new drugs if failure suspected
 Safest / shortest effective therapy
 Ensure compliance
154
Latent TB Treatment
Below used in non-MDR suspected patients
 Regimens

 INH x 9 months (Why not 6 months or 12 months)
 INH +Rifapentine 12 weekly doses – $$$
 INH +RIF 3 months (not used)
 RIF +PZA x 2 mo ( now discouraged due to excessive
hepatotoxicity)
 RIF x 4 mo
155
Active Pulmonary Tb & HIV –

Previously untreated can generally be tx with
 6 or 9 month regimens

Initial 2 months
 RIPE = (RIF+INH+PZA+EMB)

Additional 4 month drop Strep and pyrazinamide (PZA) =
 IRE = (INH + RIF + EMB) – (PZA)

Pregnant women should not take pyrazinamide
156
Active Pulmonary Tb &
+
HIV
 Much
more complex.
 Basic approach similar but
 Longer duration of treatment
 Drug interactions with HIV meds
○ Rifamycins and protease inhibitors and non-nucleoside
reverse transcriptase inhibitors
 DOT (directly observed therapy) for all HIV
 Pyridoxine (vitamin B6) for all HIV
157
Second Line drugs for TB
Quinolones esp. moxifloxacin
 Cycloserine
 Ethionamide
 Capreomycin
 Other aminoglycosides ..amikacin, kanamycin

 Streptomycin – not used often today (nephrotoxic)

Para-aminosalicylic acid – not a good therapy (usually
3rd line drug)
158
3. Define MDRTB
159
Multidrug-Resistant (MDR) and Extensively DrugResistant (XDR) TB


MDR TB caused by bacteria resistant to best TB drugs,
isoniazid and rifampin
XDR TB caused by organisms resistant to isoniazid and
rifampin, plus fluoroquinolones and ≥1 of the 3 injectable
second-line drugs
All
TB
TB
with any
drug
resistance
MDR TB*
with drug resistance
to at least the firstline drugs isoniazid
and rifampin
XDR TB**
with drug resistance
to the first-line drugs
isoniazid and rifampin and
to specific second-line
drugs
*Often resistant to additional drugs
**Resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin
160
What five patient characteristics might make you suspect drugresistant TB even before you have drug susceptibility test results?
Mandell’s Textbook, 7th. Edition, Ch 250
Q1: Where can you get answers to these five questions?
Q2: If you either know, or even just suspect, that your patient has TB which is (i) DR, (ii)
MDR, (iii) MDR or (iv) TDR…. To whom would you look for advice regarding formulating a
regimen which might be able to cure the patient…. And render him non-infectious?
Remember that with TB you are NEVER ALONE. Behind you are DHEC and CDC…. And beyond them a
whole national network of resources (e.g. the RMTCCs and much more!)
161
How MDR comes about
Weak DOT programs
 Unreliable drug supply
 Uncontrolled usage of 2nd line drugs
 Inability of local laboratories to test for drug resistance

162
4. Side effects of TB drug treatments
163
Isoniazid (INH)BQ
Inhibits mycolic acid synthesis
 Main toxicities:

 Hepatitis
 Neuropathy (can avoid with vit B6)
○ Rare, occurs 4-5 months out
 Drug interaction
○ Dilantin metabolism
164
Rifampin (RIF)BQ




Inhibits DNA-dependant RNA polymerase
“-cidal”
Broad spectrum
Adverse effects
 Hepatitis
 Drug interactions
○ CYP450 inducer (i.e. coumadin / contraceptives)
 Rash – red man
 Changes body fluids color and stains everything including
contact lenses
 Flu like illness
165
Rifapentine (RIFP)
Highly protein bound rifamycin family drug
 Allows long half life compared to rifampin
 Now approved for usage in HIV (-), non-cavitary latent
MTB treatment in 12 week regiment with INH
 SE – same as rifampin

166
Pyrazinamide (PZA)
Bacteriostatic …. Inhibits fatty acid synthesis
Adverse effects

Hepatotoxicity (combined with INH therapy)
 Not used in combo therapy anymore in USA
Unusual arthralgias without arthritis
 Nausea / vomiting

167
Ethambutol (EMB)BQ

Bacteriostatic
 Inhibit proper attachment of mycolic acids to complex cell
wall sugars

Adverse effects
 Optic neuritis (red - green color testing)
 Hyperuricemia
 Peripheral neuropathy (rare)
Ishihara Test
What number is here?
168
Monitoring therapy
 LFTs (hepatotoxicity) for INH at initiation
 Visual acuity / red-green (optic neuritis) color
testing with EMB
 Audiometry (ototoxicity) if streptomycin (esp
prolonged)
 Monthly questioning rather than tests for liver
disease
 Sputum at 1 and 2 months ….if still + additional
testing for MDRTB and look for non-adherence
 MDRTB monthly during entire treatment course
169
1.
2.
3.
4.
5.
Micro of CAP
Viral agents in CAP
IV drug user pneumonias
Alcoholic pneumonias
Predictors of mortality and ICU admissions with CAP
170
Lecture 52-53: Ones I thought could be
exam questions
171
EXAM!!!
CAP- causative agents – bacterial most common
Streptococcus pneumonia
 Staphylococcus aureus
 Haemophilus influenzae
 Mixed anaerobes (aspiration)
 Enterbacteriaceae
 Pseudomonas aeruginosa
 Legionella spp.

172
EXAM!!!!
CAP - causative agents - viral - adults - common
Influenza A and B
 RSV
 Human metapneumovirus
 Adenovirus types 4 and 7 (in military recruits)

173
EXAM!!!
Pneumonia Syndromes










Acute CAP – most common
CAP in the older adult (>60yo)
Nursing home pneumonia
CAP in patients with HIV/AIDS
Severe CAP
Health Care-Associated Pneumonia (HCAP)
Atypical pneumonia syndrome
Aspiration pneumonia - alcoholics
Pulmonary infiltrates with eosinophilia
Nosocomial pneumonia and pneumonia in ICH
174
CAP-duration of therapy
The classic 10-14 days was unsupported by
evidence.
 Clinical stability occurs more quickly, therefore
antibiotic therapy can be discontinued earlier.
 Mild to moderate severity: 3-7 days
 Adjunct therapy: corticosteroids, macrolides, statins;
all due to antiinflammatory effects; study results have
been contradictory and no clear role has been defined

175
HAP/VAP pathogenesis

Outcome depends on:
 Number and types of colonizing pathogens that enter the LRT
 Host’s mechanical, cellular, and humoral defenses
 HAP-microaspiration
○ Sedation, vomiting, impaired swallowing, intubation during surgery
 VAP
○ Leakage around cuff
○ Inhalation of contaminated aerosols
○ Reflux of contaminated ventilator tubing condensate
○ Local trauma and inflammation from the endotracheal tube
○ Biofilm encased bacteria in the ETT lumen
176
Ventilator-associated events (VAE)
Based on objective, streamlined, and potentially
automatable criteria
 Three definition tiers

 Ventilator associated condition (VAC)
 Infection-related ventilator associated condition (IVAC)
 Possible and probable VAP
177
VAP-diagnosis

New VAE criteria focuses on:
 Indicators of worsening of oxygenation
 Fever OR leukocytosis/leukopenia AND
 A new antimicrobial agent(s) is started and continued for at
least 4 days
 Purulent respiratory secretions/positive cultures
178
HAP/VAP
Principles of Antibiotic Therapy
Assess risks for MDR pathogens
 Obtain blood and sputum for smear and culture
 Begin empirical early, appropriate, and adequate antibiotic
regimen
 Assess clinical response at 24-48 hours, review
microbiologic data, de-escalate initial antibiotics if possible
 Nonresponders vs. responders

179
HAP/VAP
Evaluation of clinical nonresponders
Wrong diagnosis?
 Wrong therapy?
 Wrong pathogen?
 Complication?
 Superinfection?

180
CMS “Never Events”





Unintended retention of foreign object (surgery)
Air embolism (product or device)
Death or serious disability due to hemolytic transfusion reaction or hypoglycemia, stage III
or IV pressure ulcers (Case Management)
Death or serious disability from a fall (Environmental)
Infection
 VAP - possible
 CLABSI - impossible
 CAUTI - impossible
 Clostridium difficile - impossible
 MRSA - impossible



SSI in CABG, Gastroenterotomy, certain ortho procedures, laparoscopic gastric restriction
surgery
Manifestations of poor glycemic control
Deep vein thrombosis/pulmonary embolism in TKA/THA
181
1. Micro of CAP
182
EXAM!!!
CAP- causative agents – bacterial most common
Streptococcus pneumonia
 Staphylococcus aureus
 Haemophilus influenzae
 Mixed anaerobes (aspiration)
 Enterbacteriaceae
 Pseudomonas aeruginosa
 Legionella spp.

183
2. Viral agents in CAP
184
EXAM!!!!
CAP - causative agents - viral - adults - common
Influenza A and B
 RSV
 Human metapneumovirus
 Adenovirus types 4 and 7 (in military recruits)

185
3. IV drug user pneumonias
186
CAP - Radiologic Exams

Chest x-ray/computed tomography (CT)/nuclear medicine
procedures demonstrate CAP:






Lobar
Nodular
Upper lobe vs. lower lobe
peribronchial
Diffuse bilateral interstitial (upper/lower)
Cavitary abscesses
 Septic emboli – IV drug users
 Pneumatoceles
 Pleural effusions (layered out or loculated)
187
4. Alcoholic pneumonias
188
EXAM!!!
Pneumonia Syndromes










Acute CAP – most common
CAP in the older adult (>60yo)
Nursing home pneumonia
CAP in patients with HIV/AIDS
Severe CAP
Health Care-Associated Pneumonia (HCAP)
Atypical pneumonia syndrome
Aspiration pneumonia – alcholics
Pulmonary infiltrates with eosinophilia
Nosocomial pneumonia and pneumonia in ICH
CAP - impairment of pulmonary defenses








Altered level of consciousness
Cigarette smoke
Alcohol
Infections may interfere with normal ciliary function,
chemotaxis, phagocytosis
Iatrogenic manipulations, medications
Older age
select immunodeficiency, immunosuppressive agents
Structural lung abnormalities, COPD, obstruction
190
5. Predictors of mortality and ICU
admissions with CAP
191
Severe CAP-Prediction Scores
Modified British Thoracic Society severity score
The pneumonia Patient Outcome Research Team
(PORT) score (aka pneumonia severity index – PSI)
 Confusion, Urea, Respiratory rate, low Blood pressure
(CURB) score (and CURB-65)








Confusion
Urea > 20
RR > 30
HoTN
Age > 65yo
Best predictors of mortality and need for ICU
192
1.
2.
3.
4.
Micro of VAP/HAP
Pathophysiology of HAP/VAP
Treatment plans for HAP/VAP (empiric)
Antibiotic coverage for VAP/HAP
193
Nosocomial Pneumonia
Nosokomos (Greek)- “one who tends the sick”….circa
1843: acquired or occurring in a hospital
 Hospital Acquired Pneumonia (HAP)

 Occurs in a patient who has been hospitalized more than 48
hours

Ventilator Associated Pneumonia (VAP)
 Occurs in an intensive care unit (ICU) patient more than 48 hours
after endotrachial intubation and mechanical ventilation.
194
1. Micro of VAP/HAP
195
HAP/VAP-etiologic agents









Streptococcus pneumonia inc. PRSP
Hemophilus influenzae
Anaerobes
Legionella pneumophila
Pseudomonas aeruginosa
Methicillin-Resistant Staphylococcus aureus
Acinetobacter, Stenotrophomonas, Burkholderia sps.
ESBL+ (extended-spectrum B-lactamase) Klebsiella
pneumonia/E. coli/Enterbacter sp./Serratia sp.
Fungal and viral pathogens-rare
196
HAP/VAP-etiologic agents
Early-onset HAP (first 5 days) more likely to be
caused by antibiotic-sensitive pathogens
 Predisposing factors for patient colonization and
infection with MDR pathogens include:

 Recent hospitalization
 Residence in a long-term care facility
 The presence of significant chronic disease
 Debility
 Recent antibiotic therapy
197
HAP/VAP-etiologic agents
Gram-negative organisms still most common, >60%,
including Pseudomonas, Klebsiella sp.,
Acinetobacter sp.
 Staphylococcus aureus now accounts for 20%-40%
of episodes, most of which are now MRSA
 HAP/VAP due to MRSA is increasing worldwide
 Community-acquired MRSA (CA-MRSA) is also now
a cause of HAP/VAP

198
2. Pathophysiology of HAP/VAP
199
HAP/VAP pathogenesis

Outcome depends on:
 Number and types of colonizing pathogens that enter the LRT
 Host’s mechanical, cellular, and humoral defenses
 HAP-microaspiration
○ Sedation, vomiting, impaired swallowing, intubation during surgery
 VAP
○ Leakage around cuff
○ Inhalation of contaminated aerosols
○ Reflux of contaminated ventilator tubing condensate
○ Local trauma and inflammation from the endotracheal tube
○ Biofilm encased bacteria in the ETT lumen
200
HAP/VAPpathogenesis
201
3. Treatment plans for HAP/VAP (empiric)
202
HAP/VAP - Initial Empiric Antibiotic Therapy

Assess risk factors for MDR + severity of illness

Consider known pathogens endemic in YOUR intensive care unit/hospital

Initiate antibiotic therapy:
 3rd/4th generation antipseudomonal cephalosporin
OR
 B-lactam/B-lactamase inhibitor
OR
• Cefepime plus Levofloxacin
• Piperacillin/tazobactam plus Tobramycin
• Meropenem plus Ciprofloxacin
 Carbepenem + aminoglycoside
OR
 Antipseudomonal fluoroquinolone

Consider extended-infusion vs. intermittent-infusion therapy
203
4. Antibiotic coverage for VAP/HAP
204
HAP/VAP
Principles of Antibiotic Therapy
Assess risks for MDR pathogens
 Obtain blood and sputum for smear and culture
 Begin empirical early, appropriate, and adequate antibiotic
regimen
 Assess clinical response at 24-48 hours, review
microbiologic data, de-escalate initial antibiotics if possible
 Nonresponders vs. responders

205
HAP/VAP-Treatment

Narrowing the spectrum
 At 24-48 hours
 Minimizes complications of broad-spectrum antibiotics
 Once pathogen known, dual therapy not usually necessary

Limiting the duration of therapy
 7 days usually enough in responders who have no other
complication (empyema, bacteremia with MRSA)
206
1.
2.
3.
4.
Risks for non-TB mycobacteria
Indications for steroids in PCP
Micro involved compromised v. normal immune system
Treatment for histoplasmosis
207
1. Risks for non-TB mycobacteria
208
NONTUBERCULOUS MYCOBACTERIA IN HIVINFECTED PATIENTS
General categories
 Greatest




risk with CD4 count < 50cells/mm3
Diagnosis requires clinical assessment and culture
Sterile site
Non-sterile site
Infection vs Colonization
209
NONTUBERCULOUS MYCOBACTERIA IN HIVINFECTED PATIENTS

Mycobacterium kansasii
 Most frequent isolated NTM
 Person-to-person transmission DOES NOT occur
 Tap water is the most likely source
 Louisiana, Illinois, Texas and Florida
210
2. Indications for steroids in PCP
211
PCP
Prednisone indications
ABG showing PaO2 < 70 mmHg (hypoxia)
 A-a oxygen gradient > 35 mmHg
 Duration for 21 days.

212
3. Micro involved compromised v. normal
immune system
213
3a. Micro involved in compromised immune
system
214
Fungal Infections - Compromised hosts
Aspergillus sp.
 Zygomycetes
 Fusarium sp.
 Candida sp.
 Candida(Torulopsis) glabrata
 Curvularia lunata

215
Fungal Infections
Equally in normal and Compromised Hosts





Cryptococcus neoformans
Nocardia asteroides
Sporothrix schenckii
Penicillium marneffei
Geotrichum sp.
216
3b. Micro involved in normal immune
system
217
Fungal Infections - Mostly in normal hosts




Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Actinomyces sp.
218
Fungal Infections
Equally in normal and Compromised Hosts





Cryptococcus neoformans
Nocardia asteroides
Sporothrix schenckii
Penicillium marneffei
Geotrichum sp.
219
4. Treatment for histoplasmosis
220
Histoplasmosis
COMLEX!!!
Histoplasma capsulatum.
 Midwestern and central-eastern part of the USA.
 Worldwide distribution.
 Mostly rural areas and urban areas outbreaks with
exposure to droppings of urban-living birds.
 Spelunkers who explore caves laden with bat.

221
Histoplasmosis

Diagnosis
 Culture of expectorated sputum
 Culture of bronchoalveolar lavage

Treatment
 Amphotericin B
 Itraconazole
 Efficacy of treatment can be evaluated by monitoring blood
or urine Histoplasma antigen level
 Surgery for mediastinal fibrosis
222
1.
2.
3.
4.
5.
Prophylaxis
Compare RSV v. metapneumovirus
Flu vaccine recommendations
Treatments
Trivalent v. quadvalent vaccines
223
1. Prophylaxis (influenza)
224
Viral Pneumonia

Prevention
 Influenza vaccine. It is one of the greatest advances in public
health. It is also one of the greatest failures (only 1/5 of people
get it)
 Vaccine is trivalent. Two strains of type A and one of type B
chosen each year on basis of those strains that emerge as the
most prevalent at the end of the previous year.
 Given annually in fall.
225
Viral Pneumonia

Prevention
 Zanamivir 10mg once daily
 Oseltamivir 75 mg once daily
 Start within 48h of exposure
 Duration varies for 10 days after household exposure or 7 days
after exposure in other situations or 14 days in institutional
settings
226
2. Compare RSV v. metapneumovirus
227
2a. RSV
228
Viral Pneumonia

COMLEX!!!!
Epidemiology
 RSV common in infants less than 6 months old.
 RSV most common cause of pneumonia in infants.
 Late fall, peaks in winter.
 Adenovirus infections occurs in childhood.
 More than 50 serotypes. Types 1 to 7 cause most cases of
infection. 3,4,and 7 responsible for outbreaks.
 Tx is supportive care.
229
Viral Pneumonia

COMLEX!!!!
Clinical Manifestations
 Respiratory Syncytial Virus
○ Most common infection is URTI.
○ Most serious infection LRTI.
○ Causes bronchiolitis in children.
○ Adult infections are reinfections. URTI mostly.
○ Children at risk CF, congenital heart disease, malignant
neoplasms, combined immunodeficiencies. Mortality up to
80%.
230
2b. Metapneumovirus
231
Human metapneumovirus

Within Paramyxoviridae family 2 subfamilies
 Pneumovirinae and Paramyxovirinae

It is an RNA virus. Subgroups A and B. 2 Subgroups A1,
A2, B1, B2

Viral replication in the respiratory tract

Transmission direct or close contact with contaminated
secretion
232
Human metapneumovirus

Epidemiology
 Ubiquitous
 Cause upper and lower tract infection
 Young children and older adults
 Seasonal variation late winter early spring in the USA
 Most children are infected by age 5
233
Human metapneumovirus

Clinical Manifestations
 Incubation period is 5-6 days
 Children
○ Cough
○ Rhinitis
○ Fever
○ Wheezing
○ Range from bronchiolitis to ARDS
234
Human metapneumovirus

Clinical Manifestations
 Adults
○ Cough
○ Nasal congestion
○ Rhinorrhea
○ Dyspnea
○ Hoarseness
○ Wheezing
235
Human metapneumovirus

Diagnosis
 Reverse transcriptase-PCR
 Viral culture
 Serology with ELISA

Treatment
 Supportive
 No clinical data on susceptibility to antivirals
236
3. Flu vaccine recommendations
237
Viral Pneumonia

Prevention
 Influenza vaccine. It is one of
the greatest advances in
public health. It is also one of
the greatest failures (only 1/5
of people get it)
 Vaccine is trivalent. Two
strains of type A and one of
type B chosen each year on
basis of those strains that
emerge as the most prevalent
at the end of the previous year.
 Given annually in fall.

Prevention
 High risk population
○ Cardiopulmonary patients
○ Diabetes mellitus
○ Chronic renal failure
○ Nursing home residents
○ Health care workers
238
4. Treatments (influenza)
239
Viral Pneumonia
 Treatment
 Zanamivir 10mg twice daily for 5 days
 Oseltamivir 75 mg twice daily for 5 days
240
5. Trivalent v. quadvalent vaccines
241
Viral Pneumonia

Prevention
 Influenza vaccine. It is one of the greatest advances in public
health. It is also one of the greatest failures (only 1/5 of people
get it)
 Vaccine is trivalent.
○ Two strains of type A
+
○ One strain of type B
○ Chosen each year on basis of those strains that emerge as the most
prevalent at the end of the previous year.
 Given annually in fall.
242
5a. Trivalent vaccines
243
Viral Pneumonia

Prevention
 Influenza vaccine. It is one of the greatest advances in public
health. It is also one of the greatest failures (only 1/5 of people
get it)
 Vaccine is trivalent.
○ Two strains of type A
+
○ One strain of type B
○ Chosen each year on basis of those strains that emerge as the most
prevalent at the end of the previous year.
 Given annually in fall.
244
5b. Quadvalent vaccines
245
Quadrivalent flu vaccine … FDA approved
for 2013-2014
Fluzone Quadrivalent is the "first and only" 4-strain
influenza vaccine option for children as young as 6
months.
 Fluarix Quadrivalent (GlaxoSmithKline), approved for
adults and children aged 3 years or older
 FluMist (MedImmune), approved for adults and
children aged 2 years or older.

http://www.medscape.com/viewarticle/805587
246