Upper and Lower Respiratory Tract Infections

Meral SÖNMEZOĞLU, MDYeditepe University HospitalAssociate 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 FluDirectly 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

Bridges CB et al. Clin Infect Dis. 2003;37:1094-101. Heikkinen T et al. Lancet. 2003;361:51-9.

Pathogenesis of Influenza

• 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 tosystemic manifestations of disease

• Influenza can be transmitted through small or large particle

• aerosols or through contact with contaminated surfaces

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.

• 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

Clinical Features of Influenza

Influenza Manifestations & Complications

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.

Children AdultsFrequent Sinusitis, bronchitis,

bronchiolitis, pneumonia, croup, acute otitis media

Primary viral pneumonia, secondary bacterial pneumonia, sinusitis, bronchitis

Rare Encephalopathy, myositis, rhabdomyolysis, myocarditis, pericarditis, Reye syndrome, sepsis-like syndrome

Myositis, rhabdomyolysis, myocarditis, pericarditis

Exacerbations of underlying disease

Cardiovascular, diabetes, asthma, cystic fibrosis

Cardiovascular, diabetes, asthma, COPD

• 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

Patient Groups at Risk for Complications

ACIP. MMWR. 2004;53(RR06):1-40.

Complications

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

Non-Pulmonary: 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

• Viral Culture (Shell Vial)– 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

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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

Schwartz. Nurse Pract 1994;19:58–63

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

Etiology of acute sinusitis

Willett et al. J Gen Intern Med 1994;9:38–45

H. influenzae35%

S. pneumoniae34%

Other bacteria5%

Staphylococci7%

Streptococci8%S. aureus

6%M. catarrhalis

1% Anaerobes7%

Total percentages greater than 100% because of multiple organismsTotal percentages greater than 100% because of multiple organisms

Sinusitis

• Acute sinusitis ;– into three main syndromes:

• acute, • subacute

• chronic – In young adults, acute sinusitis is

responsible for 4.6% of physician consultations

• 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

RV in Acute Sinusitis

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

Gwaltney. In: Principles and Practicesof Infectious Disease 1990;43:493–8aStreptococcal pharyngitis

Acute streptococcal pharyngitis /tonsillitis

Etiology of pharyngitis

Gwaltney. In: Principles and Practices of Infectious Disease 1990;43:493–8

Other bacteria/viruses(7%)

Rhinovirus(20%)

Coronavirus(5%)

Adenovirus(5%)

S. pyogenes(15–30%)

Unknown(40%)

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;4:51–8Klein. Clin Infect Dis 1994;19:823–33

Infected Middle

Ear(otitis

media)

Acute otitis media — etiology

Unknown16%

H. influenzae23%

M. catarrhalisM. catarrhalis14%14%

M. catarrhalisM. catarrhalis14%14%

S. pneumoniae35%

Others32%

S. aureus1%

S. pyogenes3%

Bluestone et al. Paediatr Infect Dis J 1992;11:7–11

2807 effusions from patients in the USA 1980–1989Total percentages greater than 100% because of multiple organisms

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

PneumoniaBacterial, 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 CountryFranc

eItaly 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

Chlamydophila spp. 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

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

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.

Protective Mechanisms

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 factorsOrganism:

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: -lactam (oral

cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin/clavulanate or parenteral ceftriaxone

PLUS

• Macrolide or doxycyclineOR

• Antipneumococcal fluoroquinolone

Group III: Inpatients

• Organism

• Strep pneumonia

• Hemophilus influenzae

• Mycoplasma

• Chlamydia

• Mixed infection

• Enteric gram-negatives

• Aspiration

• Virus

• Miscellaneous

Therapy:

• 1. Intravenous -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 -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 -lactam (cefepime, imipenem, meropenem, piperacillin/tazobactam)

• PLUS iv antipseudomonal quinolone

• OR • 2. Selected iv

antipseudomonal -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 -lactam/-lactamase inhibitor

• PLUS• Antipseudomonal

fluoroquinolone OR aminoglycoside

• PLUSVancomycin 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 pneumoniaeB) Bordetella pertussisC) Mycoplasma pneumoniaeD) Legionella pneumophilaE) Haemophilus influenzae

TUS 2012

• Okul çağındaki çocuklarda trakeobronşite ve pnömoniye en sık neden olan mikroorganizma aşağıdakilerden hangisidir?

•A) Chlamydia pneumoniaeB) Bordetella pertussisC) Mycoplasma pneumoniaeD) Legionella pneumophilaE) 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