Download PowerPoint Presentation - Infectious Diseases of the Respiratory

Upper and Lower
Respiratory Tract Infections
Meral SÖNMEZOĞLU, MD
Yeditepe University Hospital
Associate Professor of
Department of Infectious Diseases and
Microbiology
Infections of the Respiratory tract
• Most common entry point for
infections
• Upper respiratory tract
–nose, nasal cavity, sinuses,
mouth, throat
• Lower respiratory tract
–Trachea, bronchi, bronchioles,
and alveoli in the lungs
Fig. 21.1a
Upper Respiratory Infections
•
•
•
•
•
•
Common Cold/ Influenza
Pharyngitis, tonsillitis
Acute sinusitis
Acute laryngitis
Acute laryngotracheobronchitis (Croup)
Otitis media, otitis externa, mastoitidis
5
Bacterial causes of URIs
• Streptococcus pyogenes (group A
ßhemolytic)
• Group C streptococci
• Haemophylus influenza
• Moraxella catarrhalis
• Staphylococcus aureus
• Klebsiella pneumoniae
• Haemophylus parainfluenzae
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
Viral causes of URIs
•
•
•
•
•
•
•
•
•
•
Rhinovirus (100 types and 1 subtype)
Coronavirus (>3 types)
Parainfluenza virus
Respiratory syncytial virus
İnfluenza virus
Adenovirus (type 3,4,7,14,21)
Coxsackievirus A (type 2,4-6,8,10)
Epstein Barr virus
Cytomegalovirus
HIV-1
Clinical characteristics of
“common cold”
• Incubation period 12-72 hrs
• Cardinal symptoms:
– Nasal discharges
– Nasal obstuctions
– Sneezing
– Sore and scratchy throat
– Cough
• Slight fever
• Duration 1 week, self limited
Diagnosis
• Typical and easy
• Differential diagnosis;
• -hay fever
• -vasomotor rhinitis
• Major challenge is to distinguish the
uncomplicated cold from secondary
bacterial sinusitis and otitismedia
Treatment
• First generation antihistaminics
• Nonsteroidal anti-inflammatory
drugs
• Sore throat reliefs with warm saline
gargles and topical anesthetics
• Oseltamivir?
Prevention
• Isolation of the patients for first
days
• Influenza vaccines
Respiratory Syncytial Virus
• Enveloped (membrane) RNA virus
• Spread by respiratory droplets
• Community outbreaks in late fall to
spring
• Upper respiratory tract infection –
epithelial cells
• May be fatal in infants
Influenza Virus
An enveloped RNA virus
Structure
Influenza Virus
New human strains every year
• Mutations
Pandemic strains

Genetic Recombinant Viruses
•1957 Asian Flu
H2N2
•1968 Hong Kong Flu H3N2
•1977 Russian Flu
H1N1
Bird Flu
Directly from birds
•??
H5N1
‘H’ and ‘N’ Flu Glycoproteins
H – Hemagglutinin

• Specific parts bind to host
cells of the respiratory mucosa
• Different parts are
recognized by the host antibodies
• Subject to changes
N - Neuraminidase
• Breaks down protective
mucous coating
• Assist in viral release
Influenza
• Epidemics and pandemics, mostly in
winter
• Upper respiratory tract infection –
epithelial cells
• Multivalent killed virus vaccine with
strains from the previous year (Grown in
embryonated eggs)
• Bird flu (H5N1) pandemic in birds
Pathogenesis of Influenza
• Influenza can be transmitted through small or large particle
• aerosols or through contact with contaminated surfaces
• If not neutralized by mucosal antibodies, virus attacks
respiratory tract epithelium
• Infection of respiratory epithelial cells leads to cellular
dysfunction, viral replication, and release of viral progeny
• Release of inflammatory mediators contributes to
systemic manifestations of disease
Bridges CB et al. Clin Infect Dis. 2003;37:1094-101. Heikkinen T et al. Lancet. 2003;361:51-9.
Clinical Features of Influenza
• Sudden onset of symptoms, persist for
7+ days
• Incubation period: 1-4 days, average 2
days
• Infectious period of wild type virus:
– Adults shed virus typically from 1 day before
through 5 days after onset of symptoms
– Children shed higher titers for a longer
duration than adults
ACIP. MMWR. 2004,53(RR06)1-40. Kavet J. Am J Public Health. 1977;67:1063-70. Frank AL et al. J Infect Dis.
1981;144:433-441. Hayden FG et al. JAMA. 1999;282:1240-6.
Influenza Manifestations &
Complications
Frequent
Rare
Exacerbations
of underlying
disease
Children
Adults
Sinusitis, bronchitis,
bronchiolitis, pneumonia,
croup, acute otitis media
Encephalopathy, myositis,
rhabdomyolysis, myocarditis,
pericarditis, Reye syndrome,
sepsis-like syndrome
Cardiovascular, diabetes,
asthma, cystic fibrosis
Primary viral pneumonia,
secondary bacterial pneumonia,
sinusitis, bronchitis
Myositis, rhabdomyolysis,
myocarditis, pericarditis
Cardiovascular, diabetes,
asthma, COPD
Loughlin J et al. Pharmocoeconomics. 2003;21:273-283. Treanor JJ. Influenza virus. In: Mandell GL, Bennett
JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed.
Philadelphia, PA: Churchill Livingstone; 2000:1823-1849. ACIP. MMWR 2004;53 (RR06):1-40.
Patient Groups at Risk for
Complications
• Increased risk of influenza complications
among:
– Children <2 years
– Children and adolescents receiving long-term
aspirin therapy
– Children and adults with chronic conditions
• Chronic pulmonary, metabolic, or CV disorders
• Renal dysfunction
• Hemoglobinopathies
• Immunosuppression, including HIV infection
– Pregnant women
– Residents of chronic care facilities
– Persons 65 years old
ACIP. MMWR. 2004;53(RR06):1-40.
Complications
Pulmonary:
Non-Pulmonary:
 Primary influenza viral
pneumonia
 Secondary bacterial
pneumonia
 Croup
 Asthma, COPD,*
bronchitis, cystic fibrosis
exacerbation
 Increased severity of
influenza in HIV patients







* Chronic obstructive pulmonary disease
Myositis
Cardiac complications
Toxic shock syndrome
Guillain-Barré syndrome
Transverse myelitis
Encephalitis
Reye syndrome
Influenza Diagnostic Testing
• Rapid Antigen (EIA)
– NP aspirates and swabs only
– Detects Influenza A/B nucleoproteins
– 1 hour TAT, batched on the hour
– Upper and lower respiratory specimens
– Detects Influenza A/B, Parainfluenza 1/2/3,
Adenovirus and RSV
– 24-72 hour TAT
• Real-time RT-PCR
–
–
–
–
Upper and lower respiratory specimens
Detects Influenza A matrix gene
Influenza B validation in progress
24 hour TAT
Increase in Sensitivity
• Viral Culture (Shell Vial)
Treatment
• Rest, liquids, anti-febrile agents (no
aspirin for ages 6mths-18yrs)
• Be aware of complications and
treat appropriately
• Oseltamivir for patients at risk
Sinusitis — facts and figures
Definition:
– infection of frontal, ethmoidal or maxillary
sinuses
Symptoms:
– facial pain, headache, nasal discharge, fever
Prevalence:
– 31.2 million cases per year in the USA
– 16 million outpatient visits
Complications:
– permanent mucosal damage and chronic
sinusitis
– rarely, optic neuritis, subdural abscess and
meningitis
Schwartz. Nurse Pract 1994;19:58–63
Etiology of acute sinusitis
Streptococci
S. aureus
8%
Staphylococci
6%
M. catarrhalis
7%
1%
Anaerobes
7%
S. pneumoniae
34%
Other bacteria
5%
H. influenzae
35%
Total percentages greater than 100% because of multiple organisms
Willett et al. J Gen Intern Med 1994;9:38–45
Sinusitis
• Acute sinusitis ;
– into three main syndromes:
• acute,
• subacute
• chronic
– In young adults, acute sinusitis is
responsible for 4.6% of physician
consultations
RV in Acute Sinusitis
• Sinusitis is an extremely common part
of the common cold syndrome
• RV has been detected in 50% of adult
patients with sinusitis by RT-PCR of
maxillary sinus brushings or nasal
swabs1
• Frequency of association of RV infection
with sinusitis suggests the common cold
could be considered a rhinosinusitis2
1. Pitkäranta A et al. J Clin Microbial. 1997;35:1791.
2. Gwaltney JM Jr. Clin Infect Dis. 1996;23:1209.
Acute pharyngitis/tonsillitis —
facts and figures
Definition:
– inflammation of the pharynx or tonsils
Symptoms:
– pharyngeal pain, dysphagia and fever
Epidemiology: – 1% physician visits/year
– most common childhood bacterial
infectiona
Complications: – acute rheumatic fever and
glomerulonephritisa
aStreptococcal
pharyngitis
Gwaltney. In: Principles and Practices
of Infectious Disease 1990;43:493–8
Acute streptococcal pharyngitis
/tonsillitis
Etiology of pharyngitis
Coronavirus
(5%)
Adenovirus
(5%)
Rhinovirus
(20%)
Other bacteria/viruses
(7%)
S. pyogenes
(15–30%)
Unknown
(40%)
Gwaltney. In: Principles and Practices of Infectious Disease 1990;43:493–8
Acute otitis media — facts and
figures
Definition:
– infection of the middle ear leading to
accumulation of fluid and inflammation of the
tympanic membrane
Symptoms:
– cough, fever, irritability, earache
Epidemiology:
– 24.5 million physician visits per year
– majority of cases occur in children <2 years
– most frequent indication for antimicrobial
treatment in children in the USA
Complications:
– loss of hearing
Garau et al. Clin Microbiol Infect 1998;4:51–8
Klein. Clin Infect Dis 1994;19:823–33
Infected
Middle
Ear
(otitis
media)
Acute otitis media — etiology
M. catarrhalis
14%
H. influenzae
23%
S. pneumoniae
35%
Unknown
16%
Others
32%
S. pyogenes
3%
S. aureus
1%
2807 effusions from patients in the USA 1980–1989
Total percentages greater than 100% because of multiple organisms
Bluestone et al. Paediatr Infect Dis J 1992;11:7–11
Acute Bronchitis
Inflammation of the bronchial
respiratory mucosa leading to
productive cough.
Acute Bronchitis
• Etiology: A)Viral
B) Bacterial (Bordetella pertussis,
Mycoplasma pneumoniae, and
Chlamydia pneumoniae)
• Diagnosis: Clinical
• S/S: Productive cough, rarely fever or
tachypnea.
Treatment
A) Symptomatic
B) If cough persists for more than
10 days:
Azithro x 5 days OR
Clarithro x 7 days
PNÖMONİ
Pneumonia
Bacterial, viral or fungal infection can cause
Inflammation of the lung with fluid filled alveoli
Aetiology
Frequency of causative organisms of community-acquired pneumonia
(CAP) in Europe.
Welte T et al. Thorax 2012;67:71-79
Treatment setting
Frequency of Isolation of Causative
Organisms of CAP in Europe by Country
Percentage Means of Frequency of Isolation in Each Country
Franc
e
Italy
Spain
Turkey
UK
German
y
S pneumoniae
37.2
11.9
33.7
25.5
42.1
40
Haemophilus influenzae
10.3
5.1
5.3
44.9
12.3
8
Legionella spp.
2.0
4.9
12.9
0
9.1
3.1
Staphylococcus spp.
11.7
6.5
3.2
1.0
2.6
5
Moraxella catarrhalis
3.3
1.0
2.7
12.2
0.8
0
Gram-negative bacilli
16.8
24.3
7.9
4.1
2.6
7
Mycoplasma pneumoniae
0.7
7.0
8.4
0
5.3
5.6
1
2.4
7.2
0
5.9
1.3
Coxiella burnetii
0.2
0.4
6.2
0
0.3
0
Viruses
1.7
11.6
5.9
0
18.6
9
No pathogen identified
35.6
67.3
56.8
40.6
38.4
NR
Chlamydophila spp.
Protective Mechanisms
Normal flora: Commensal organisms
• Limited to the upper tract
• Mostly Gram positive or anaeorbic
• Microbial antagonist (competition)
Defense Mechanisms
• 80% of cells lining central airways are
ciliated, pseudostratified,
columnar epithelial cells
• Each ciliated cell contains
about 200 cilia that beat in
coordinated waves about
1000x/minute
• So the lower respiratory tract
is normally sterile
Protective Mechanisms
Clearance of particles
and organisms from the respiratory tract
Cilia and microvilli move
particles up to the throat 
where they are swallowed.
Alveolar macrophages
migrate and engulf particles
and bacteria in the alveoli
deep in the lungs.
Other Protective Mechanisms
•
•
•
•
•
Nasal hair, nasal turbinates
Mucus
Involuntary responses (coughing)
Secretory IgA
Immune cells
First cause of death in the United
States from infectious disease is:
A. Meningitis
B. Pneumonia
C. Gastroenteritis
D. Urinary Tract Infections
E. Toe fungus
First cause of death in the United
States from infectious disease is:
A. Meningitis
B. Pneumonia
C. Gastroenteritis
D. Urinary Tract Infections
E. Toe fungus
Mortality due to infections
DM Morens et al. Nature 463, 122-122 (2010)
doi:10.1038/nature08554
Pneumonia
• Most deadly infectious disease in the
U.S.
• 6th leading cause of death
• Average mortality 14%
• $20 billion/year in U.S.1
• Community acquired pneumonia affects
~4 million patients and results in 10
million physician visits,
• 1 million hospitalizations, and >50,000
deaths annually
File Chest 2004; 125:1888-1901
Pneumonia Pathophysiology
• Microbial pathogens enter the lung by:
• Aspiration of organisms from oropharynx
– More common in patients with impaired level of consciousness:
alcoholics, IVDA, seizures, stroke, anesthesia, swallowing disorders,
NG tubes, ETT
– Gram positive and anaerobes: Strep pneumo, H flu, Mycoplasma,
Moraxella, Actinomyces
– Gram negatives:
• more likely with hospitalization, debility, alcoholism, DM, and advanced age
• Source may be stomach which can become colonized with these organisms
with use of H2blockers
• Inhalation of Infectious Aerosols
– Influenza, Legionella, Psittacosis, Histoplasmosis, TB
• Hematogenous Dissemination
– Staph aureus
– Fusobacterium infections of the retropharyngeal tissues: Lemierre’s
syndrome
• Direct inoculation and Contiguous Spread
– Tracheal intubation, stab wounds
At the left the alveoli are filled with a neutrophilic exudate that corresponds to
the areas of consolidation seen grossly with the bronchopneumonia. This
contrasts with the aerated lung on the right of this photomicrograph.
Clinical presentation
• Pneumonia should be considered in any patient
who has newly acquired respiratory symptoms:
cough, sputum production, dyspnea, especially if
accompanied by fever and abnormal breath
sounds and crackles
• In elderly or immunocompromised, pneumonia
may present with confusion, failure to thrive,
worsening of underlying chronic illness, falling
Pneumonia Symptoms
• “Typical” pneumonia: sudden onset of
fever, cough productive of purulent
sputum, pleuritic chest pain
• “Atypical”: gradual onset, dry cough,
prominence of extrapulmonary
symptoms: headache, myalgias,
fatigue, sore throat, nausea, vomiting
• Includes diverse entities and has limited
clinical value
Pneumonia Diagnosis
• Radiography: CXR
– confirm the presence and location of the
pulmonary infiltrate
– assess the extent of the infection
– detect pleural involvement, pulmonary cavitation,
or lymphadenopathy
• May be normal when the patient is unable to
mount an inflammatory response
(immunocompromised) or
• is in the early stage of an infiltrative process
(hematogenous S. aureus pneumonia)
Pneumonia Diagnosis
• Sputum gram stain and culture:
• Controversial: no rapid, easily done, accurate,
cost-effective method to allow immediate results
• Expectorated sputum is frequently contaminated
by oropharyngeal flora
– Low power magnification to assess squamous
epithelial cells
– Culture and sensitivity are only accurate if there are
<10 epi’s per low power field
– Best results if the specimen contains >25 WBCs per
LPF
• If patient has a productive cough, send sputum
for gram stain and culture: could be of use in
directing treatment if patient fails to respond to
empiric therapy
Pneumonia Diagnosis
• Blood cultures are positive in 11% of patients
with CAP, more commonly in patients with
severe illness
• Urine antigen assays for L pneumophila
serogroup 1 can be done easily and rapidly.
Sensitivity 70% Specificity >90%
• Assay for pneumococcal urinary antigen :
sensitivity 50-80% and specificity 90%
• Responsible pathogen is not defined in as
many as 50% of patients
Pneumonia Diagnosis
• Routine laboratory tests:
• (CBC, electrolytes, hepatic enzymes) are of
little value in determining the etiology of
pneumonia, but may have prognostic
significance and influence the decision to
hospitalization.
• Should be considered in patients who may
need hospitalization, >65 yr, or with
coexisting illness.
• All admitted patients should have oxygen
saturation assessed by oximetry
Pneumonia Diagnosis
• Invasive testing: percutaneous transthoracic
needle aspiration or bronchoscopy are not
routinely recommended.
– May be helpful in:
• immunocompromised hosts
• suspected tuberculosis in the absence of
productive cough
• non-resolving pneumonia
• pneumonia associated with suspected
neoplasm or foreign body
• suspected Pneumocystis jirovecii (carinii)
• Pneumonia
• Severity
• Index
Pneumonia
Severity
Index
PORT Score
•
•
•
•
•
•
Age 55-10=45
CHF
+10
RR
+20
HR 124
+10
BUN
+20
pO2
+10
115
Class IV Mortality 9%
Site of Treatment
• Class I or II: Outpatient treatment
• Class III: Potential outpatient or brief
inpatient observation
• Class IV and V: Inpatient
• Physician decision making: medical
and psychosocial comorbidities,
ability to take po, substance abuse,
ability to do ADLs
CURB 65
•
•
•
•
•
Confusion
Urea level (>19)
Respiratory rate (>30)
Blood Pressure SBP< 90 or DBP <60
Age
• Excellent indicator for mortality
ICU Admission
• Minor Criteria
–
–
–
–
–
RR>30/min
PaO2/FiO2 <250
Multilobar pneumonia
Systolic BP <90
Diastolic BP <60
• Major Criteria
– Need for mechanical ventilation
– Increase in the size of infiltrates by >50% within
48hrs
– Septic shock
– Acute renal failure (uop <80ml in 4 h or serum
Cr>2.0)
Modifying Factors that Increase the Risk of
infection with Specific Pathogens
• Penicillin-resistant pneumococci
–
–
–
–
–
Age >65
B-lactam therapy within the past 3 months
Alcoholism
Immune suppressive illness (including tx with corticosteroids)
Multiple medical comorbidities: DM, CRI, CHF, CAD, malignancy,
chronic liver disease
– Exposure to a child in a day care center
• Enteric gram negatives
–
–
–
–
Residence in a nursing home
Underlying cardiopulmonary disease
Multiple medical comorbidities
Recent antibiotic therapy
• Pseudomonas aeruginosa
–
–
–
–
Structural lung disease (bronchiectasis)
Corticosteroid therapy (>10mg prednisone/day)
Broad spectrum antibiotic therapy for > 7 days in past month
Malnutrition
Group I: Outpatients
No cardiopulmonary disease
No modifying factors
Organism:
Streptococcus pneumonia
Mycoplasma pneumonia
Chlamydia pneumonia
Hemophilus influenzae
Miscellaneous
Legionella
Mycobacterium
Fungi
Treatment:
Advanced generation
macrolide(azithromycin
or clarithromycin)
OR doxycycline
Group II: Outpatient, with
cardiopulmonary disease, and/or other
modifying factors
•
•
•
•
•
•
•
•
•
•
Organism:
Strep pneumonia
Mycoplasma
Chlamydia
Mixed infection
Hemophilus influenzae
Enteric gram-negatives
Viruses
Miscellaneous
Moraxella, Legionella,
anaerobes, TB, fungi
• Therapy:
 B -lactam (oral
cefpodoxime,
cefuroxime, high-dose
amoxicillin,
amoxicillin/clavulanate
or parenteral
ceftriaxone
PLUS
• Macrolide or
doxycycline
OR
• Antipneumococcal
fluoroquinolone
Group III: Inpatients
•
•
•
•
•
•
•
•
•
•
Organism
Strep pneumonia
Hemophilus influenzae
Mycoplasma
Chlamydia
Mixed infection
Enteric gram-negatives
Aspiration
Virus
Miscellaneous
•
•
•
•
•
Therapy:
1. Intravenous B lactam: cefotaxime,
ceftriaxone,
ampicillin/sulbactam,
high-dose amipicillin
PLUS
Intravenous or oral
macrolide or
doxycycline
OR
2. Antipneumococcal
fluoroquinolone
ICU Patients
•
•
•
•
•
•
•
•
•
Organisms:
Strep pneumonia
Legionella
Hemophilus influenzae
Enteric gram-negative
bacilli
Staphylococcus aureus
Mycoplasma
Respiratory Viruses
Miscellaneous
• Therapy:
• 1. Intravenous B lactam: cefotaxime,
ceftriaxone,
ampicillin/sulbactam,
high-dose amipicillin
• PLUS either
• Intravenous or oral
macrolide or
doxycycline
• or
• Antipneumococcal
fluoroquinolone
ICU Patients with Risks for
Pseudomonas aeruginosa
• 1. Selected iv
antipseudomonal B -lactam
(cefepime, imipenem,
meropenem,
piperacillin/tazobactam)
• PLUS iv antipseudomonal
quinolone
• OR
• 2. Selected iv
antipseudomonal B -lactam
PLUS iv aminoglycoside
PLUS either iv macrolide or
iv nonpseudomonal
fluoroquinolone
Hospital-Acquired Pneumonia
• Enteric aerobic gram
negative bacilli
• Pseudomonas
aeruginosa
• Staphylococcus aureus
• Oral anaerobes
• Antipseudomonal
cephalosporin (cefepime,
ceftazidime) OR
Antipseudomonal
carbepenem OR B lactam/B -lactamase
inhibitor
• PLUS
• Antipseudomonal
fluoroquinolone OR
aminoglycoside
• PLUS
Vancomycin or Linezolid
TUS 2012
• Üç hafta-4 yaş arasındaki çocuklarda, toplum
kaynaklı pnömoninin en sık bakteriyal etkeni
aşağıdakilerden hangisidir?
• A) Mycoplasma pneumoniae
• B) Haemophilus influenzae
• C) Staphylococcus aureus
• D) Streptococcus pneumoniae
• E) Chlamydia trachomatis
TUS 2012
• Üç hafta-4 yaş arasındaki çocuklarda, toplum
kaynaklı pnömoninin en sık bakteriyal etkeni
aşağıdakilerden hangisidir?
• A) Mycoplasma pneumoniae
• B) Haemophilus influenzae
• C) Staphylococcus aureus
• D) Streptococcus pneumoniae
• E) Chlamydia trachomatis
TUS 2012
• Okul çağındaki çocuklarda trakeobronşite
ve pnömoniye en sık neden olan
mikroorganizma aşağıdakilerden
hangisidir?
•
A) Chlamydia pneumoniae
B) Bordetella pertussis
C) Mycoplasma pneumoniae
D) Legionella pneumophila
E) Haemophilus influenzae
TUS 2012
• Okul çağındaki çocuklarda trakeobronşite
ve pnömoniye en sık neden olan
mikroorganizma aşağıdakilerden
hangisidir?
•
A) Chlamydia pneumoniae
B) Bordetella pertussis
C) Mycoplasma pneumoniae
D) Legionella pneumophila
E) Haemophilus influenzae
TUS 2010
• Aşağıdakilerden hangisi akut bronşiyolit
tedavisinin ilkelerinden biri değildir?
•
•
•
•
A) Bronşiyal obstrüksiyonun kaldırılması
B) Asiklovir tedavisi
C) Hipoksemi ve asidozun düzeltilmesi
D) Potansiyel kardiyak komplikasyonların
önlenmesi
• E) İkincil bakteriyal enfeksiyonların tedavisi
TUS 2010
• Aşağıdakilerden hangisi akut bronşiyolit
tedavisinin ilkelerinden biri değildir?
•
•
•
•
A) Bronşiyal obstrüksiyonun kaldırılması
B) Asiklovir tedavisi
C) Hipoksemi ve asidozun düzeltilmesi
D) Potansiyel kardiyak komplikasyonların
önlenmesi
• E) İkincil bakteriyal enfeksiyonların tedavisi
QUESTIONS