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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 64: Acute Bronchitis and Upper Respiratory Tract Infections Cedric W. Lefebvre

FIGURE 64–1.

INTRODUCTION AND EPIDEMIOLOGY

Bacterial and viral infections of the respiratory tract can result in a wide range of clinical syndromes includingacute bronchitis, the common cold, influenza, and respiratory distress syndromes. Uniform definitions forthe most common of these clinical syndromes are lacking because the symptoms associated with upperrespiratory tract infections (URIs) frequently overlap and their causative pathogens are similar. The broaddefinition of acute bronchitis is as follows: a self-limited inflammation of the large airways characterized bycough without evidence of pneumonia, without an alternative medical disorder to explain the symptoms, or

without a history of chronic lung disease.1

The common cold is a viral infection of the upper respiratory tract, primarily a�ecting the nasal mucosa,causing congestion, rhinorrhea, and sneezing. Influenza, or the "flu," is a respiratory illness caused byinfluenza viruses. Symptoms of influenza infection range from mild to severe and include fever, chills,myalgias, headache, malaise, cough, and fatigue. Severe acute respiratory syndrome is a unique respiratoryillness that has clinical characteristics similar to other URIs but confers a high rate of mortality. Reported in2012, Middle East respiratory syndrome coronavirus is novel viral respiratory infection that became a concernto the World Health Organization due to its fatality rate. Infections of the upper respiratory tract also causespecific clinical conditions like otitis media, pharyngitis, epiglottitis, bronchiolitis, laryngitis, tracheitis, andsinusitis (see corresponding chapters that discuss these diseases).

EPIDEMIOLOGY

In ambulatory care settings nationwide, URIs are the third most common diagnosis.2 Annually, the estimateddirect costs of noninfluenza viral URI in the United States is $17 billion, with indirect costs exceeding $22

billion.3 Acute bronchitis is among the most commonly diagnosed outpatient illnesses in the United States

every year, with an annual incidence of about 5%,4 predominantly during fall and winter.1 The disorderaccounts for approximately 10 million o�ice visits per year, or 10 ambulatory visits per 1000 people per year.Symptom relief is the primary reason for o�ice visits among adults within the first 2 weeks of illness, and

many of these visits result in the unnecessary prescription of antibiotics by clinicians.5 The common cold

a�licts adults two or three times every year, whereas children su�er up to eight colds annually.6,7,8 The

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incidence of colds caused by rhinovirus peaks during autumn months.9 Responsible for 22 million missed

school days and 23 million lost work days, the common cold generates an enormous economic burden.4

Influenza a�ects millions of people worldwide every year during seasonal outbreaks (typically Novemberthrough March in the northern hemisphere). An annual average of 41,000 Americans died from influenza

infection from 1979 to 2001.10 The Centers for Disease Control and Prevention reported influenza-associatedannual death rates between 1976 and 2007 that ranged from 1.4 to 16.7 deaths per 100,000 persons. Deathsassociated with influenza have increased in recent decades in the United States. With 90% of influenza-associated deaths occurring among people 65 years or older, influenza poses a particular threat to the

elderly.11,12 In 2009, an outbreak of swine-origin influenza A (H1N1) virus, known as "swine flu," occurred in

Mexico and the United States.13,14

Influenza viruses are classified into three genera: A, B, and C. Of these, influenza A has the greatest impact onhuman populations and has the greatest potential to cause pandemics. Influenza A has many serotypes,including H1N1 and H3N2, both of which are currently active among humans. Influenza viruses are uniquepathogens because their evolution involves a complex process of antigenic shi�s and sporadic cross-speciestransmissions between humans, swine, and birds. The intensity of seasonal influenza varies from one year to

the next, and localized influenza outbreaks can occur during interpandemic years.15 Furthermore, seasonalinfluenza outbreaks tend to occur simultaneously in countries on similar latitudes. Population immunityagainst influenza can be achieved by natural infection or vaccination; however, antigenic shi�s allowinfluenza viruses to survive from year to year and preserve their capacity to cause global pandemics.

ACUTE BRONCHITIS

PATHOPHYSIOLOGY

Etiologic studies of acute bronchitis are di�icult to interpret because the disease lacks a precise definition

and the cause is undetermined in 31% to 84% of cases vigorously tested.16,17,18,19,20,21,22,23 Respiratoryviruses are the most common causative agents, with confirmed cases in 9% to 63% of patients studied,

depending on the criteria used to make the diagnosis and the population.16,17,18,19,20,21,22,23 Influenza A and

B viruses are the most common cause, accounting for 6% to 35% of cases.16,17,18,19,20,21,22,23 Parainfluenzavirus, respiratory syncytial virus, coronavirus, adenovirus, rhinovirus, and human metapneumovirus

combined account for another third of cases.16,17,18,19,20,21,22,23 Bacterial causes of acute bronchitis range

from less than 10%16 to as much as 44% of cases in studies of older populations with comorbidities and

severe symptoms.21 Streptococcus pneumoniae (0% to 30% of cases), Haemophilus influenzae (0% to 9% ofcases), and Moraxella catarrhalis (0% to 2% of cases) have been isolated in patients with acute

bronchitis.16,17,18,19,20,21,22,23 Atypical bacterial species such as Bordetella pertussis (0% to 1%),24

Chlamydia pneumoniae (0% to 17%), and Mycoplasma pneumoniae (1% to 10%) also cause acute

bronchitis.16,17,18,19,20,21,22,23

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There are two overlapping sequential phases in the pathophysiology of acute bronchitis.25 The first phaseresults from the direct inoculation of the tracheobronchial epithelium, yielding variable constitutionalsymptoms of fever, myalgias, malaise, and organism-specific upper respiratory symptoms, lasting 1 to 5days, the severity of which depends on the infectious agent. The second phase is characterized byhypersensitivity of the tracheobronchial epithelium and airway receptors resulting in persistent, productivecough and lasting 1 to 3 weeks, peaking at 7 to 14 days. It is this second phase that best characterizes theillness. Sloughed epithelial cells and increased mucus produce sputum in most patients; sputum is not an

indication of ongoing bacterial infection as frequently suspected by clinicians.25 Inflammation andthickening of the bronchial and tracheal mucosa (Figure 64–1) result in airflow obstruction and decreasedforced expiratory volume in 1 second, manifesting as wheezing and dyspnea in many patients.

FIGURE 64–1.

The respiratory epithelial infection of acute bronchitis leads to inflammation, thickening, and increasedmucus production in the airways.

CLINICAL FEATURES

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The clinical manifestations of acute bronchitis depend on the infectious agent, especially in the first phase ofthe illness. Therefore, the initial symptoms are variable and may include fever, dyspnea, myalgias, malaise,sore throat, nasal congestion, and cough. The hallmark of acute bronchitis is cough (with or without phlegmproduction) persisting into the second phase of the illness lasing more than 5 days and up to 3 or 4

weeks.1,25 The mean duration of cough is 18 days.26 During this phase, the patient may or may not havedyspnea and/or chest discomfort. Physical exam may be completely normal, or the patient may havetachypnea, tachycardia, fever, wheezing, rhonchi, or rales. One important etiology of acute bronchitis to

identify is Bordetella pertussis, because antibiotic treatment is recommended (see later discussion).25,27

Suspect pertussis in patients with posttussive emesis or inspiratory whoop27; consider pertussis in anypatient with cough lasting greater than 2 weeks if exposed to a known case or presenting during an

epidemic.1,25

DIAGNOSIS

The diagnosis of acute bronchitis is made using clinical findings and historical information: when acutecough (dry or productive) is present for more than 5 days and when evidence of pneumonia, acute asthma,or an alternative explanation for the symptoms is are absent. Patients with chronic obstructive pulmonarydisease are excluded from the diagnosis (see chapter 70, Chronic Obstructive Pulmonary Disease).

The primary objective in patient evaluation is carefully excluding pneumonia, either clinically orradiographically. Physicians are poor at di�erentiating patients with pneumonia from patients with

bronchitis based on history and physical exam.28,29,30,31 The addition of C-reactive protein testing does not

improve diagnostic accuracy.29,32 Identification of patients at low risk for pneumonia may be accomplished

based on the absence of vital sign abnormalities and physical exam findings.30,31,33 See Table 64–1 forcriteria suggesting pneumonia; patients meeting none of these criteria have a probability of pneumonia of5% or less, and further testing is not required provided the patient has follow-up in the next 3 days and is

able to return to the ED if symptoms worsen.30,31,33 Patients with hypoxia or unstable vital signs (in thesetting of respiratory symptoms) are at high risk for pneumonia and require further testing and treatment(see chapter 65, Pneumonia and Pulmonary Infiltrates). Obtain a chest radiograph in patients at intermediaterisk for pneumonia. Although chest radiography remains the most common confirmatory test for

pneumonia,34,35 the sensitivity of a standard two-view chest film ranges from 69% in symptomatic patients

suspected of pneumonia in the community,36 to as low as 43.5% in patients being evaluated for pulmonary

embolism in the ED37 (both studies using high-resolution CT scan as the criterion reference). Therefore, ifpneumonia is suspected on clinical grounds, treat accordingly regardless of a negative chest radiograph (seechapter 65) especially in the elderly, among whom distinctive signs and symptoms of pneumonia may be

lacking.1 Laboratory tests should be obtained if treatment for B. pertussis is being planned; tests include aculture, using a Dacron swab specimen, collected from the posterior nasopharynx; performing directfluorescent antibody staining; collecting a polymerase chain reaction test; or testing for serum antibodies by

enzyme-linked immunosorbent assays or Western blot.27 Otherwise, further testing for acute bronchitis is

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All five criteria must be absent in an individual patient to lower the probability of pneumonia to 5% or less.

not necessary unless alternative diagnoses require investigation. The di�erential diagnosis of cough is broad;see Table 64-5, Di�erential of Consequence: Cough, in chapter 62, Respiratory Distress.

Table 64–1

Clinical Criteria Suggesting Possible Pneumonia

Criteria Clinical Finding

1 Heart rate >100 beats/min

2 Respiratory rate >24 breaths/min

3 Temperature of >38°C (100.4°F)

4 Chest examination findings of focal consolidation, egophony (increased resonance of voice sounds

heard when auscultating the lungs), or fremitus (tactile vibrations felt over the chest when the

patient repeats "boy oh boy")

5 Age > 64 y old

TREATMENT

Case definitions of acute bronchitis that specify constitutional or respiratory symptoms includingcharacteristics of sputum are used by research investigators and can define the spectrum of microbiologiccauses but have not identified a patient subset that clearly benefits from antibiotics (see Acute Bronchitis,Treatment, later in this chapter).

Despite the fact that some patients with acute bronchitis have evidence of a bacterial infection in

epidemiologic studies, antibiotics are not beneficial and are not indicated except in isolated cases.1,5,38,39 ACochrane analysis reviewed 15 randomized controlled trials, involving 2618 patients, including smokers andnonsmokers, comparing any antibiotic versus placebo or no treatment for acute bronchitis. At follow-up,patients receiving antibiotics were less likely to have cough (relative risk 0.64; 95% confidence interval 0.49 to0.85), were less likely to have abnormal lung exam findings (relative risk 0.54; 95% confidence interval 0.41 to0.70), experienced fewer days of feeling ill (mean di�erence –0.64; 95% confidence interval –1.16 to –0.13),

and had fewer days with limited activity (mean di�erence –0.49; 95% CI –0.94 to –0.04).39 Although thedi�erences between these outcome measures reached statistical significance, the benefits demonstratedwere modest (less than 1-day benefit in an illness lasting 10 to 21 days). Consider potential medication sidee�ects, cost, and the potential for microbial resistance when using antibiotics to achieve these modest

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benefits for an otherwise self-limiting illness. Despite the lack of evidence supporting their use, the majority

of acute bronchitis patients receive antibiotics, especially elderly patients and smokers.1,5,38,40,41,42

To counter public perception and patients' prior experiences with antibiotics, o�er patient education.43 Bothprinted and computer-assisted patient educational intervention reduce antibiotic prescriptions in the

primary care setting.44 For confirmed or presumed B. pertussis infection give azithromycin (500 milligrams

on day 1, 250 milligrams on days 2 to 5) to prevent transmission to contacts.1,5,27 For influenza, if the patientpresents very early in the course and influenza is suspected as the cause, consider influenza-specific antiviraltherapy (see later section, Influenza).

There is little evidence to support the routine use of β2-agonists for acute bronchitis in the absence of

wheezing on physical exam.1,5,39 A Cochrane Review reported no significant di�erences in daily cough scoresor in duration of cough among adults with acute bronchitis who received β2-agonists versus placebo or no

treatment. Adults treated with β2-agonists were more likely to report adverse e�ects such as tremor,

shakiness, and nervousness (relative risk 7.94; 95% confidence interval 1.17 to 53.94).45 However, amongpatients with evidence of airflow obstruction, β2-agonists result in lower symptom scores and faster cough

resolution.45 Therefore, consider bronchodilators in acute bronchitis patients with wheezing.46

Antihistamines do not reduce mean cough scores in acute bronchitis. Limited data are available on thee�icacy of antitussives for acute bronchitis, and no data exist on the value of oral corticosteroids in

nonasthmatics with acute bronchitis.47 Dextromethorphan and codeine preparations may be no more

e�ective than placebo in improving symptoms or reducing cough severity in acute bronchitis.38 If used, limitantitussive therapy to those patients with a cough causing discomfort where inhibition of airway secretion

clearance will not compromise breathing.46

COMMON COLD

PATHOPHYSIOLOGY

The pathogens responsible for causing the common cold include rhinovirus, adenovirus, parainfluenza virus,respiratory syncytial virus, enterovirus, and coronavirus. The rhinovirus, a species of the Enterovirus genus ofthe Picornaviridae family, is the most common cause of the common cold and causes up to 80% of all

respiratory infections during peak seasons.8,9,48 Dozens of rhinovirus serotypes and frequent antigenicchanges among them make identification, characterization, and eradication exceedingly complex. A�erdeposition in the anterior nasal mucosa, rhinovirus replication and infection are thought to begin uponmucocilliary transport to the posterior nasopharynx and adenoids. As soon as 10 to 12 hours a�erinoculation, symptoms may begin. The mean duration of symptoms is 7 to 10 days, but symptoms can persist

for as long as 3 weeks.9 Nasal mucosal infection and the host's subsequent inflammatory response cause

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vasodilation and increased vascular permeability. These events result in nasal obstruction and rhinorrhea,whereas cholinergic stimulation prompts mucus production and sneezing.

CLINICAL FEATURES

Patients a�licted with the common cold can experience nasal congestion, rhinorrhea, sneezing, sore throat,

cough, and malaise.6 Clinical signs of rhinovirus infection include nasal discharge and hoarse voice. Theconsistency and purulence of nasal discharge in patients with the common cold do not necessarily indicate abacterial infection. The high incidence of sinus abnormalities in patients with uncomplicated colds makesthe identification of true bacterial sinusitis challenging. Sinusitis is estimated to complicate rhinovirus illnessin 0.5% to 2% of cases (see chapter 244, Nose and Sinuses). Although fever is a common finding in childrenwith rhinovirus infection, fever is uncommon in adults. Middle ear e�usions may be noted, particularly

among children, in whom acute otitis media occurs in up to 20% of viral URIs.9

DIAGNOSIS

The presence of classical features for rhinovirus infection, coupled with the absence of signs of bacterialinfection or serious respiratory illness, is su�icient to make the diagnosis of the common cold. The commoncold is a clinical diagnosis, and diagnostic testing is not necessary.

TREATMENT

The goal of treatment for the common cold is symptom relief. Decongestants and combinationantihistamine/decongestant preparations can decrease cough, congestion, and other symptoms in

adults.43,49 Avoid cough preparations in children.50,51 H1-receptor antagonists may o�er a modest reduction

of rhinorrhea and sneezing during the first 2 days of a cold in adults.6 First-generation antihistamines aresedating, so advise the patient about caution during their use. Topical and oral nasal decongestants (i.e.,topical oxymetazoline, oral pseudoephedrine) have moderate benefit in adults and adolescents in reducing

nasal airway resistance.6,51 Evidence-based data do not support the use of antibiotics in the treatment of the

common cold because they do not improve symptoms or shorten the course of illness.6,51,52 There is also alack of compelling evidence supporting the use of dextromethorphan for acute cough.

According to a Cochrane Review,53 vitamin C used as daily prophylaxis at doses of ≥0.2 grams or more had a"modest but consistent e�ect" on the duration and severity of common cold symptoms (8% and 13%decreases in duration for adults and children, respectively). When taken therapeutically a�er the onset of

symptoms, however, high-dose vitamin C has not shown clear benefit in trials.53 Echinacea is an herbalremedy commonly used for treating the common cold; at this time, there is no clear evidence that echinaceais e�ective. Zinc has also been proposed for the treatment of common cold symptoms, and a meta-analysisfound that oral zinc lozenges may shorten the course of symptoms in adults (no benefit in children), but

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nausea and altered taste were common, and the authors cautioned against a generalized

recommendation.54

INFLUENZA

PATHOPHYSIOLOGY

The incubation period for influenza is 1 to 4 days, and the time interval between symptom onset amongrelated household cases is estimated to be 3 to 4 days. Viral shedding can occur 1 day before the onset ofsymptoms. Shedding generally decreases by 3 to 5 days a�er illness in adults but can continue for more than

10 days a�er illness onset in children.55 Understanding the routes of influenza transmission is critical to thedevelopment of e�ective infection control guidelines and for the planning of global, regional, and localpandemic responses. A debate exists over the route(s) of influenza virus transmission in mammals. It isbelieved that influenza can be transferred among humans by direct contact, indirect contact, droplets, oraerosolization. Short distances (<1 m) are generally required for contact and droplet transmission to occurbetween the source person and the susceptible individual. Airborne transmission may occur over longerdistances (>1 m). Experimental and observational studies support the possibility of influenza transmission byall of these routes. However, most evidence-based data suggest that direct contact and droplet transfer are

the predominant modes of transmission for influenza.56

CLINICAL FEATURES

Influenza infection is characterized by abrupt onset of fever, headache, dry cough, sore throat, myalgias, andrhinitis. Oropharyngeal irritation and mild cervical lymphadenopathy may be present. Although the presenceof fever can help distinguish influenza from the common cold, up to one third of H1N1 influenza cases in 2009

demonstrated flu symptoms without fever.55 Hence, influenza can be di�icult to distinguish from other viralURIs. Fever and intense myalgias are generally more prevalent in influenza infection than other viral URIs.Healthy individuals with uncomplicated influenza illness will generally experience resolution of symptoms in3 to 7 days, although cough and malaise may persist beyond 2 weeks (see earlier section, Acute Bronchitis).

DIAGNOSIS

During seasonal influenza outbreaks, most cases of influenza can be diagnosed on clinical grounds alone. Aretrospective analysis of 3744 subjects showed that the development of cough and fever are the best

multivariate predictors of influenza infection with a positive predictive value of 79% (P <0.001).57 Duringinterpandemic periods, clinical signs and symptoms may be less predictive of sporadic influenza infection,and management decisions may be aided by diagnostic testing.

If the diagnostic test result for influenza will influence management decisions, certain patients shouldundergo testing. When signs of influenza infection are present during an influenza outbreak, perform testingon hospitalized patients, patients with high-risk conditions, and patients for whom a positive result would

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impact clinical care decisions. When a patient presents with signs of influenza infection at any time of year,consider testing for (1) healthcare personnel or visitors linked to an influenza outbreak presenting within 5days of illness and (2) patients who are epidemiologically linked to an influenza outbreak presenting within 5

days of symptom onset.58

When testing for influenza, obtain specimens as close to symptom onset as possible. Nasal aspirates andswabs are the best specimens to obtain when testing infants and young children. For older children andadults, swabs and aspirates from the nasopharynx are preferred. Additional specimens from endotrachealaspirates and/or bronchoalveolar lavage fluid should be obtained from ventilated patients to allow testing of

the lower respiratory tract.58 Several influenza tests are available for clinical use (Table 64–2). Given theirability to provide results rapidly (<30 minutes), commercially available rapid influenza diagnostic tests aremost practical in the ED. However, with reported sensitivities of these kits ranging from 10% to 80%

(specificity 85% to 100%), negative rapid influenza tests do not completely exclude infection.58,59

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Abbreviations: EIA, enzyme immunoassay, RT-PCR, reverse transcription polymerase chain reaction.

Adapted with permission from Harper S, Bradley J, Englund J, et al: Seasonal influenza in adults and children—

diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the

Infectious Diseases Society of America. Clin Infect Dis 48: 1003, 2009. Copyright Oxford University Press.

Table 64–2

Influenza Testing Modalities

Test

Time

to

Results

Comments

Rapid influenza test–

antigen detection (EIA)

10–20

min

70%–90% sensitivity in children, <40%–60% sensitivity in adults, follow-

up testing with RT-PCR should be considered to confirm negative result

Rapid influenza test–

neuraminidase

detection assay

20–30

min

Detects but does not distinguish between influenza A and B

RT-PCR 2 h High sensitivity and specificity, highly recommended test for influenza

Immunofluorescence 2–4 h Direct and indirect immunofluorescent antibody staining detects and

distinguishes between influenza A/B and other viruses

Viral culture–shell vial

Viral culture–cell

culture isolation

48–72

h

3–10 d

Viral isolation/cultures are not screening tests; highest specificity,

moderately high sensitivity; useful for confirming screening tests and

surveillance purposes

TREATMENT

Early antiviral treatment for influenza infection shortens the duration of influenza symptoms, decreases the

length of hospital stays, and reduces the risk of complications.60 Recommendations for the treatment ofinfluenza are updated frequently by the Centers for Disease Control and Prevention based on epidemiologicdata and antiviral resistance patterns. The treatment of influenza infection is recommended as early aspossible for any patient with confirmed or suspected influenza who (1) is at high risk for influenza

complications (Table 64–3), (2) has severe, complicated or progressive illness, or (3) is hospitalized.55,60

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*Includes persons with chronic pulmonary (including asthma, cystic fibrosis), cardiovascular (except hypertension

alone), renal, hematologic (including sickle cell disease), and hepatic diseases; metabolic disorders (including diabetes

mellitus); cancers; or neurologic and neurodevelopment conditions including disorders of the brain, spinal cord,

peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability (mental

retardation), moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.

Table 64–3

Persons at Higher Risk for Complications of Influenza Infection34

Children <5 y (especially <2 y)

Adults ≥65 y

Persons with chronic illnesses and/or conditions*

Persons with immunosuppression, including secondary to human immunodeficiency virus infection or

medications

Women who are pregnant or postpartum (within 2 weeks of delivery)

Persons <18 y receiving long-term aspirin therapy

Residents of nursing homes and other chronic care facilities

Persons who are morbidly obese (body mass index ≥40)

American Indians/Alaska Natives

A patient who does not meet the above criteria may still require treatment depending on clinicalcircumstances and clinician concern. Give antiviral therapy for influenza within 48 hours of symptom onset(or earlier), and do not delay treatment for laboratory confirmation if a rapid test is not available. Antiviral

treatment can provide benefit even a�er 48 hours in pregnant and other high-risk patients.61,62 Therefore,

consider antiviral treatment even 3 or 4 days a�er onset of illness in certain high-risk populations.60

For the 2012 to 2013 influenza season, the neuraminidase inhibitors zanamivir and oseltamivir wererecommended by the Centers for Disease Control and Prevention for the prevention and treatment of

influenza infection55,60 (see Table 64–4 for dosing recommendations). The recent development of resistanceamong several influenza strains to the neuraminidase inhibitors emphasizes the importance of followingupdated epidemiologic reports and recommendations by the Centers for Disease Control and Prevention andother health agencies.

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*Longer courses can be considered for patients who remain severely ill a�er 5 days of treatment.

†For controlling outbreaks in long-term care facilities, the Centers for Disease Control and Prevention recommend a

minimum of 2 weeks of chemoprophylaxis and up to 1 week a�er the last identified case, and 7 days a�er most recent

known exposure in other cases.

Table 64–4

Neuraminidase Inhibitor Dosing Recommendations60

Oseltamivir (Tamiflu®)

Treatment Chemoprophylaxis

Adults 75 milligrams twice daily × 5 d* 75 milligrams once daily × 7 d†

Children‡

<15 kg 30 milligrams twice daily × 5 d* 30 milligrams once daily × 7 d

15–23 kg 45 milligrams twice daily × 5 d* 45 milligrams once daily × 7 d

24–40 kg 60 milligrams twice daily × 5 d* 60 milligrams once daily × 7 d

>40 kg 75 milligrams twice daily × 5 d* 75 milligrams once daily × 7 d

Zanamivir (Relenza®)

Treatment Chemoprophylaxis

Adults 10 milligrams (2 inhalations) twice daily × 5 d* 10 milligrams (2 inhalations) once daily × 7 d†

Children‡

≥5 y old# N/A 10 milligrams (2 inhalations) once daily

≥7 y old 10 milligrams (2 inhalations) twice daily × 5 d* 10 milligrams (2 inhalations) once daily × 7 d†

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‡Antiviral medications are not Food and Drug Administration approved for treatment or prophylaxis of influenza in

children age <12 months. Limited data are available in this age group. Oseltamivir was used in infants during the 2009

influenza A (H1N1) pandemic under Emergency Use Authorization (expired June 2010).

#Zanamivir is approved for treatment of influenza in children age ≥7 years and for influenza chemoprophylaxis in

children age ≥5 years.

Vaccination is the most e�ective method of preventing influenza illness. Antiviral chemoprophylaxis is alsohelpful in preventing influenza (70% to 90% e�ective) and should be considered as an adjunct to vaccinationin certain scenarios or when vaccination is unavailable or not possible. Generally, antiviral chemoprophylaxisis used during periods of influenza activity for (1) high-risk persons who cannot receive vaccination (due tocontraindications) or in whom recent vaccination does not, or is not expected to, a�ord a su�icient immuneresponse; (2) controlling outbreaks among high-risk persons in institutional settings; and (3) high-risk

persons with influenza exposures.58,60 For more information about the indications for antiviralchemoprophylaxis, consult the Centers for Disease Control and Prevention website (http://www.cdc.gov/flu).Widespread and routine use of chemoprophylaxis is discouraged due to the possibility of promotingresistance and depleting supplies for high-risk or critically ill patients during influenza outbreaks.

DISEASE COMPLICATIONS

Complications of influenza infection include primary influenza viral pneumonia; secondary bacterialpneumonia; sinusitis; otitis media; coinfection with bacterial agents; and exacerbation of preexisting medicalconditions, particularly asthma and chronic obstructive pulmonary disease. Pneumonia is one of the mostcommon complications of influenza illness in children and contributes significantly to morbidity andmortality. Children who develop pneumonia in association with influenza are more likely to developrespiratory failure (11% vs. 3%), require intensive care unit admission (21% vs. 11%), and die (0.9% vs.

0.3%).63

SEVERE ACUTE RESPIRATORY SYNDROME (SARS)

Severe acute respiratory syndrome is a rapidly progressive illness caused by a coronavirus, the severe acuterespiratory syndrome coronavirus. Emerging in China in November 2002, severe acute respiratory syndromequickly became a global health concern by early 2003. The World Health Organization reported 8096probable severe acute respiratory syndrome cases worldwide through April 21, 2004. Deaths attributed to

severe acute respiratory syndrome totaled 774 during that time period (9.6% case fatality rate).64 Isolationprocedures for suspected severe acute respiratory syndrome patients include airborne, droplet, and contactisolation. Healthcare providers should wear an N95 or higher respiratory facemask when caring for patientswith severe acute respiratory syndrome, in addition to glove, gown, and eye protection.

Although severe acute respiratory syndrome shares many clinical features with viral URIs, its clinicalcharacteristics are ill-defined, and case definitions were updated frequently during its emergence. The

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clinical features of coronavirus infection include fever (99% frequency), nonproductive cough, dyspnea,myalgias, headache, and diarrhea. Many cases progress to a moderate-severe condition characterized byhypoxia and dyspnea at rest. Respiratory failure requiring mechanical ventilation occurs in 10% to 20% ofhospitalized patients with severe acute respiratory syndrome. Risk factors for death in coronavirus infection

include age >60 years, diabetes mellitus, and hepatitis B infection.65

Consider the diagnosis of severe acute respiratory syndrome on clinical grounds when the patient has beenexposed to known cases or has traveled to regions with severe acute respiratory syndrome activity. Chestradiographs may show subtle peripheral pulmonary infiltrates. Chest CT demonstrates ground-glassconsolidation during early phases of illness. Lymphopenia, thrombocytopenia, elevated lacticdehydrogenase, liver enzymes, and creatine phosphokinase levels have been reported but are not

pathognomonic for severe acute respiratory syndrome.66 When severe acute respiratory syndrome issuspected, collect two specimens (from di�erent locations) for polymerase chain reaction testing and obtainserum for serologic testing. To date, several diagnostic tests are available to detect coronavirus, but each hassubstantial limitations in sensitivity, specificity, or clinical practicality. Treatment for severe acute respiratorysyndrome is largely supportive. When lopinavir-ritonavir was added to standard therapy (ribavirin andcorticosteroids) for severe acute respiratory syndrome during a nonrandomized, open-label study in HongKong, a significant reduction in death rate was noted. Limitations in this study, however, make it di�icult to

derive definitive conclusions about its e�icacy.65

MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS (MERS)

In the summer of 2012, in Jeddah, Saudi Arabia, a novel coronavirus was isolated from the sputum of a

patient with pneumonia and renal failure.67 Since that time, the virus has been named the Middle Eastrespiratory syndrome coronavirus. As of August 30, 2013, there have been 108 reported cases (several still

hospitalized at that time) and 50 deaths.68 All cases have been directly or indirectly linked to one of fourcountries: Saudi Arabia, Qatar, Jordan, and the United Arab Emirates, with the largest number from Saudi

Arabia.69 The original source is suspected to have come from bats.70 Median age of patients is 56 years (range2 to 94 years). All patients had respiratory symptoms, and some had GI symptoms including abdominal painand diarrhea. The majority of patients experience severe acute respiratory disease requiring hospitalization;the case fatality rate has been reported as 56%. In addition to respiratory failure, renal failure and septicshock are common causes of death. Several patients had significant preexisting comorbidities, includingimmunosuppression. Cases have included healthcare workers and family contacts. A documented patient-to-

patient nosocomial transmission has been reported in France.71 Treatment is supportive and frequentlyrequires mechanical ventilation, dialysis, and extracorporeal membrane oxygenation. Nonspecific antiviral

drugs have been used, such as ribavirin, lopinavir, and type I interferon, but their e�iciency is still unclear.72

Patients should be isolated in an airborne infection isolation room.73 Healthcare workers should wearpersonal protective equipment including gloves, gown, eye protection, and a fit-tested N95 respirator

facemask.73

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PERTUSSIS

Pertussis, or "whooping cough," is an acute respiratory infection in humans caused by the aerobic gram-negative rod, B. pertussis. Pertussis toxins cause respiratory epithelial and mucosal injury and interfere withimmune cell function. Pertussis pneumonia can occur in children, but in school-age children, adolescents,and adults, URIs are the rule.

IMMUNIZATION

Although pertussis is o�en considered a disease of infants (primarily in those <1 year old who have notcompleted three doses of vaccination) and a disease in developing countries where immunization is notuniversal, in North America, the disease is now more common in school-age children and adults. School-agechildren are the usual sources of infection, and adults may serve as carriers of disease. Cyclical outbreaksoccur every 3 to 5 years despite widespread immunization practices.

There are two types of vaccines, whole-cell and acellular. Whole-cell pertussis vaccination is e�ective forabout 10 years and is used in developing nations. The acellular diphtheria, tetanus, and pertussis vaccine(DTaP), developed to remove toxins from the cell membrane, does not protect as long as the whole-cell

vaccine and is typically used in the developed world.74 The typical immunization schedule is at 2, 4, 6, and 18months of age and a booster at age 5. Adolescents should receive a DTaP booster. Pregnant women shouldreceive a booster of DTaP to protect neonates and infants and to prevent infection in the mother. For the

unimmunized elderly (>65 years old), one dose of DTaP is recommended.75 Although the vaccine is

specifically not registered for the elderly,76 a study of nearly 120,000 individuals ≥65 years old did notdemonstrate any increase in inflammatory or allergic events in those receiving DTaP compared with those

receiving only the tetanus and diphtheria vaccine.77 There is no lifelong immunity a�er a clinical episode ofpertussis.

CLINICAL FEATURES

Clinical features in adults are those of the common cold, but a�er 1 week, prolonged, paroxysmal, and sleep-disturbing cough develops. Whooping is uncommon in adults. Consider pertussis in situations of chroniccough >2 weeks in duration. Cough may last for several months. Since pertussis is highly communicable, withan attack rate of about 20% even in the immunized, suspect pertussis if there is contact with otherindividuals with prolonged cough. Except in the elderly, pertussis in adults is not associated with pneumonia.Clinical or radiologic evidence of pneumonia in adults or the elderly suggests secondary bacterial infection.

DIAGNOSIS

Diagnosis is o�en clinical, especially during epidemics. Definitive diagnosis is usually by polymerase chainreaction of nasopharyngeal secretions or serologic detection of antibodies. Other causes of respiratoryillnesses with prolonged cough include Mycoplasma, Chlamydophila, influenza virus, and other respiratory

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viruses. In adults, chronic cough can be associated with angiotensin-converting enzyme inhibitors,gastroesophageal reflux, or asthma.

TREATMENT

Treatment of pertussis is azithromycin, 500 milligrams PO on day 1 and 250 milligrams PO on days 2 to 5.Trimethoprim-sulfamethoxazole, 160 milligrams/800 milligrams twice a day for 14 days (check renal dosing),is an alternative to those allergic to, or unable to tolerate, macrolides. Treatment is best if started early, in thefirst week. A�er that, antibiotic treatment does not alter the duration of cough. Chemoprophylaxis is typicallygiven for household contacts, although the evidence base for such treatment is weak.

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USEFUL WEB RESOURCES

Centers for Disease Control and Prevention: Current information regarding influenza—http://www.cdc.gov/flu, http://www.cdc.gov/flu/pdf/professionals/antivirals/antiviral-summary-clinicians.pdf

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World Health Organization: Information regarding severe acute respiratory syndrome—http://www.who.int/csr/sars/en/

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