UPPER RESPIRATORY

TRACT INFECTIONS
 Pharyngitis
◦ Acute pharyngitis is described as a triad of a sore throat, fever, and pharyngeal
inflammation.
◦ Acute pharyngitis can be a primary disorder, but it can also be the manifestation of a
noninfectious disorder (e.g., postnasal drip, thyroiditis, allergies).
◦ Most cases are due to a virus and are self-limited.
◦ Viruses (eg, rhinovirus, coronavirus, and adenovirus) cause most of the cases of acute
pharyngitis.
◦ A bacterial etiology for acute pharyngitis is far less likely. Of all of the bacterial causes,
GABHS is the most common (10%–30% of cases in pediatric patients and 5%–15% in
adults).
CLINICAL PRESENTATION
◦ The most common symptom of pharyngitis is sore throat of sudden onset that is mostly
self-limited.
◦ Fever and constitutional symptoms resolve in about 3–5 days.
◦ Signs and symptoms of GABHS pharyngitis include sore throat; pain on swallowing;
fever; headache; nausea; vomiting; and abdominal pain (especially in children);
erythema/inflammation of the tonsils and pharynx with or without patchy exudates;
enlarged; tender lymph nodes; red swollen uvula; petechiae on the soft palate; and a
scarlatiniform rash.
◦ Signs suggestive of viral origin for pharyngitis include conjunctivitis, coryza, and cough.
◦ Diagnosis can be confirmed by throat swab and culture and a rapid antigen-detection
test (RADT).
TREATMENT
◦ Goals of Treatment: Improve clinical signs and symptoms, minimize adverse drug
reactions, prevent transmission to close contacts, and prevent acute rheumatic fever
and suppurative complications such as peritonsillar abscess, cervical lymphadenitis,
and mastoiditis.
◦ Antimicrobial therapy should be limited to those who have clinical and epidemiologic
features of GABHS pharyngitis, preferably with a positive laboratory test.
◦ Because pain is often the primary reason for visiting a physician, emphasis on
analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)
to aid in pain relief is strongly recommended.
◦ Penicillin and amoxicillin are the treatments of choice. Antimicrobial treatment should
be limited to those who have clinical and epidemiologic features of GABHS pharyngitis
with a positive laboratory test (Table 45-2). Table 45-3 presents antibiotics and doses for
eradication of GABHS in chronic carriers.
◦ The duration of therapy for GABHS pharyngitis is 10 days, except for benzathine penicillin
and azithromycin, to maximize bacterial eradication. However, 3–6 days of oral antibiotics
has comparable efficacy to oral penicillin for 10 days.
◦ • Amoxicillin–clavulanate, clindamycin, penicillin/rifampin combination, and benzathine
penicillin G/rifampin combination may be considered for recurrent episodes of pharyngitis
to maximize bacterial eradication in potential carriers and to counter co-pathogens that
produce β-lactamases.
◦ Most cases of pharyngitis are self-limited; however, antimicrobial therapy will hasten
resolution when given early to proven cases of GABHS. Symptoms generally resolve by 3 or 4
days even without antibiotics; however, symptoms will improve 0.5–2.5 days earlier with
antibiotic therapy.
◦ Follow-up testing is generally not necessary for index cases or in asymptomatic contacts of
the index patient; however, throat cultures 2–7 days after completion of antibiotics are
warranted for patients who remain symptomatic or when symptoms recur despite
completion of treatment.
Diphtheria
◦ An acute bacterial toxin-mediated infectious disease caused by Corynebacterium species
that presents with either upper respiratory tract pseudomembrane formation or cutaneous
ulcerative disease.
◦ Nonimmune individuals are at risk for severe respiratory disease and toxin-mediated
complications.
◦ The classic presentation affects the upper respiratory system, leading to clinical
manifestations such as a sore throat, low grade fever, and an adherent grayish
pseudomembrane of the tonsils and pharynx.
◦ Diagnosis is confirmed with isolation of toxin-producing Corynebacterium diphtheriae.
◦ Treatment includes respiratory isolation, antitoxin administration in consultation with the CDC,
antibiotic treatment, and monitoring for complications.
◦ Systemic complications include myocarditis and delayed peripheral nerve conduction.
◦ In addition, the pseudomembrane can become dislodged and lead to acute airway
obstruction.
Streptococcal Scarlet Fever

◦ Streptococcus pyogenes causes scarlet fever or scarlatina.

◦ Pharyngitis and scarlet fever tend to peak in the winter and early spring.
◦ This type of syndrome is caused by the streptococcal erythrogenic toxin.
◦ Classically, the presentation involves the sudden onset of fever, chills, malaise, sore throat
before an exanthem appears 12–48 hours later that begins on the trunk and spreads
peripherally.
◦ The remaining skin becomes diffusely erythematous leading to the sunburn appearance of
erythroderma (texture is of a sandpaper quality and erythema blanches with pressure)
◦ Petechiae can appear 1–3 days after the appearance of the rash in a linear distribution
along the creases forming Pastia lines.
◦ Papillae on the tongue become erythematous leading to the “strawberry tongue”
appearance.
◦ Treatment with a 10-day course of penicillin or clindamycin (penicillin-allergic patient) is
recommended for reduction in transmission and prevention of complications.
Acute Epiglottitis
◦ Acute epiglottitis is an invasive cellulitis of the epiglottis and its surrounding structures.
◦ Has the potential to cause abrupt airway obstruction.
◦ Prior to routine Haemophilus influenzae type b conjugate vaccination, the majority of
cases occurred in children aged 1 to 4 years old.
◦ The incidence of epiglottitis has remained stable in the adult population with no
identification of a pathogen in the majority of cases.
◦ The classic clinical presentation is a child who develops fever, irritability, and
experiences rapidly progressive respiratory distress with stridor.
◦ Children affected are classically described as experiencing hoarseness with a muffled
voice.
◦ Lateral neck radiographs demonstrate an enlarged epiglottis (thumbprint sign) with
ballooning of the hypopharynx and prevertebral soft tissue swelling.
◦ Diagnosis: established by visualization of an edematous, cherry-red epiglottis.
◦ Croup can present in a similar fashion but children tend to be less toxic, experience
more frequent episodes of coughing, and have a lack of drooling compared to
epiglottitis.
◦ Therapy/Management
◦ Management of the airway is most important consideration.
◦ Antibiotic management normally directed at Streptococcus pneumoniae,
Haemophilus influenzae, and occasionally Staphylococcus aureus.
Chronic Epiglottitis
◦ Described as a presentation consisting of mild dysphagia, dysphonia, and/or sore
throat.
◦ Often treated as an outpatient initially with antibiotics.
◦ Viral etiologies have also been described.
◦ Diagnosis ultimately relies on direct laryngoscopy and biopsy.
◦ Treatment is directed at the causative agent or condition.
Acute Bacterial Rhinosinusitis
◦ Sinusitis is an inflammation and/or infection of the paranasal sinuses, or membranelined
air spaces, around the nose. The term rhinosinusitis is now preferred, because sinusitis
typically also involves the nasal mucosa. The majority of these infections are viral in
origin. It is important to differentiate between viral and bacterial sinusitis to aid in
optimizing treatment decisions.
◦ Acute bacterial sinusitis is most often caused by the same bacteria implicated in acute
otitis media: S. pneumoniae and H. influenzae. These organisms are responsible for
~50%–70% of bacterial causes of acute sinusitis in both adults and children.
CLINICAL PRESENTATION
◦ There are three clinical presentations that are most consistent with acute bacterial vs viral
rhinosinusitis:
◦ 1) Onset with persistent signs or symptoms compatible with acute rhinosinusitis, lasting for ≥10
days without any evidence of clinical improvement;
◦ 2) Onset with severe signs or symptoms of high fever (≥39°C [102.2°F]) and purulent nasal
discharge or facial pain lasting for at least 3–4 consecutive days at the beginning of illness;
◦ 3) Onset with worsening signs or symptoms characterized by new-onset fever, headache, or
increase in nasal discharge following a typical viral URI that lasted 5–6 days and were initially
improving (“double sickening (worsening symptoms after a period of improvement). ”).
◦ Signs and symptoms of bacterial rhinosinusitis include purulent anterior nasal discharge,
purulent or discolored posterior nasal discharge, nasal congestion or obstruction, facial
congestion or fullness, facial pain or pressure, fever, headache, ear pain/ pressure/fullness,
halitosis, dental pain, cough, and fatigue.
TREATMENT
◦ Goals of Treatment:
◦ Reducing signs and symptoms, achieving and maintaining patency of the ostia, limiting
antimicrobial treatment to those who may benefit,
◦ eradicating bacterial infection with appropriate antimicrobial therapy, minimizing the
duration of illness,
◦ preventing complications, and preventing progression from acute disease to chronic
disease.
◦ Nasal decongestant sprays such as phenylephrine and oxymetazoline that reduce
inflammation by vasoconstriction are often used in nonbacterial rhinosinusitis.
◦ Use should be limited to the recommended duration of the product (no more than 3
days) to prevent development of tolerance and/or rebound congestion.
◦ Oral decongestants may also aid in nasal or sinus patency.
◦ Irrigation of the nasal cavity with saline and steam inhalation may be used to increase
mucosal moisture, and mucolytics (eg, guaifenesin) may be used to decrease the
viscosity of nasal secretions.
◦ Antihistamines and oral decongestants should not be used for acute bacterial sinusitis
in view of their anticholinergic effects that can dry mucosa and disturb clearance of
mucosal secretions.
◦ Amoxicillin–clavulanate is first-line treatment for acute bacterial rhinosinusitis. The
approach to treating acute bacterial rhinosinusitis in children and adults is given in
Tables 45-4 and 45-5.
◦ High-dose amoxicillin–clavulanate is preferred in the following situations:
◦ (a) geographic regions with high endemic rates (10% or greater) of invasive penicillin
nonsusceptible S. pneumoniae,
◦ (b) severe infection,
◦ (c) attendance at daycare,
◦ (d) age less than 2 or greater than 65 years,
◦ (e) recent hospitalization,
◦ (f) antibiotic use within the last month,
◦ (g) immunocompromised persons.
◦ Doxycycline is also second line for adults but should be avoided in children.
◦ The duration of antimicrobial therapy for acute bacterial rhinosinusitis is not well established.
Most trials have used 10- to 14-day antibiotic courses for uncomplicated rhinosinusitis.
◦ For adults, the recommended duration is 5–7 days.
◦ If symptoms persist or worsen after 48–72 hours of appropriate antibiotic therapy, then the
patient should be reevaluated and alternative antibiotics should be considered.
Chronic Sinusitis
◦ Defined as signs and symptoms that persist for at least 12 weeks.
◦ Similar factors as acute sinusitis play a role in the pathogenesis (e.g., obstruction of
sinus ostia, mucociliary impairment, and thickening of secretions).
◦ Bacteria profile may involve other pathogens, such as gram-negative bacilli, MRSA,
and anaerobes.
Pertussis
◦ Pertussis, which is also known as “whooping cough,” is a highly contagious respiratory illness
caused by the gram-negative coccobacillus Bordetella pertussis.
◦ The organism is fastidious and requires special media for culture.
◦ The incubation period is 1–3 weeks but typically is 7–10 days.
◦ Pertussis is spread by respiratory droplets.
◦ In the prevaccine era, it was common in children, but now it is more common in adolescents
and adults.
◦ The classic symptoms are paroxysmal cough, inspiratory whoop, and post-tussive emesis.
◦ Antibiotic treatment given during the early (catarrhal) phase may decrease the duration
and severity of cough.
◦ Specifically, macrolides are effective at eradicating B. pertussis from the nasopharynx.
◦ In addition, antibiotic therapy can decrease the spread of the organism to uninfected
individuals.
◦ Childhood vaccination has been highly effective at preventing infection with this
organism.
◦ Routine vaccination with DTaP vaccine is performed in the United States.
◦ Adults aged 19–64 years old should receive a booster administration with the DTaP
vaccine.
◦ For pregnant women, administration of DTaP to all women between 27–36 weeks
gestation is recommended.
◦ Postexposure prophylaxis should be administered to individuals with close contact to a
person with pertussis (face-to-face contact within 3 feet of an infected individual).
◦ The same regimens recommended for treatment should be given for postexposure
prophylaxis.
Acute Otitis Media
◦ Otitis media is an inflammation of the middle ear that is most common in infants and
children.
◦ There are three subtypes of otitis media: acute otitis media, otitis media with effusion,
and chronic otitis media.
◦ The three are differentiated by (a) acute signs of infection, (b) evidence of middle ear
inflammation, and (c) presence of fluid in the middle ear.
PATHOPHYSIOLOGY
◦ Bacteria have been found in more than 90% of cases of otitis media.
◦ Common bacterial pathogens include Streptococcus pneumoniae, nontypeable
Haemophilus influenzae, and Moraxella catarrhalis.
◦ Acute otitis media usually follows a viral upper respiratory tract infection that impairs
the mucociliary apparatus and causes eustachian tube dysfunction in the middle ear.
◦ Many S. pneumoniae isolates in the United States are penicillin nonsusceptible, and
most nonsusceptible strains have high-level penicillin resistance.
◦ Many H. influenzae isolates and nearly all M. catarrhalis isolates, from the upper
respiratory tract, produce β-lactamases.
CLINICAL PRESENTATION
◦ Acute otitis media is characterized as acute onset of otalgia (ear pain). Irritability and
tugging on the ear are often the first clues that a child has acute otitis media.
◦ Children should be diagnosed with acute otitis media if they have middle ear effusion
and either (1) moderate-to-severe bulging of the tympanic membrane or new onset
otorrhea not due to acute otitis externa or (2) mild bulging of the tympanic membrane
and onset of ear pain within the last 48 hours or intense erythema of the tympanic
membrane.
◦ Nonverbal children with ear pain might hold, rub, or tug their ear. Very young children
might cry, be irritable, and have difficulty sleeping. Signs and symptoms include bulging
of the tympanic membrane, otorrhea, otalgia (considered to be moderate or severe if
pain lasts at least 48 hours), and fever (considered to be severe if temperature is 39°C
or higher).
Sequelae of Otitis Media
◦ Hearing loss.
◦ Cholesteatoma.
◦ Chronic perforation of tympanic membrane.
TREATMENT
◦ Goals of Treatment:
◦ Pain management, prudent antibiotic use, and secondary disease prevention.
◦ Acute otitis media should first be differentiated from otitis media with effusion or chronic
otitis media.
◦ Primary prevention of acute otitis media with pneumococcal conjugate vaccine and
annual influenza vaccine are recommended for all children.
◦ Pain of otitis media should be addressed with oral analgesics. Acetaminophen or a
nonsteroidal anti-inflammatory agent, such as ibuprofen, should be offered early to
relieve pain of acute otitis media.
◦ Children 6 months–12 years of age, with moderate-to-severe ear pain or temperature
of 39°C (102.2°F) or higher should receive antibiotics.
◦ Children 6–23 months of age, with non-severe bilateral acute otitis media should also
receive antibiotics.
◦ Children 6–23 months, with non-severe unilateral acute otitis media
◦ Children 24 months–12 years of age, with non-severe acute otitis media, may receive
initial antibiotics or initial observation without antibiotics.
◦ The central principle is to administer antibiotics quickly when the diagnosis is certain,
but to withhold antibiotics, at least initially, when the diagnosis is uncertain.
◦ High-dose amoxicillin (80–90 mg/kg/day) is recommended for most children.
◦ Children who have received amoxicillin in the last 30 days, have concurrent purulent
conjunctivitis, or have a history of recurrent infection unresponsive to amoxicillin should
receive high-dose amoxicillin–clavulanate (90 mg/kg/day of amoxicillin, with 6.4
mg/kg/day of clavulanate, in two divided doses) instead of amoxicillin.
◦ Antibiotic treatment recommendations for acute otitis media are given in Table 45-1.
◦ If treatment failure occurs with amoxicillin, an agent should be chosen with activity
against β-lactamase-producing H. influenzae and M. catarrhalis, as well as drug
resistant S. pneumoniae, such as high-dose amoxicillin–clavulanate (recommended) or
cefuroxime, cefdinir, cefpodoxime, or intramuscular or intravenous ceftriaxone.
◦ Traditional recommendations call for 10 days of antibiotic therapy. In children at least 6
years old who have mild-to-moderate acute otitis media, a 5- to 7-day course of
antibiotics may be used.
◦ Short-course treatment is not recommended in children younger than 2 years of age.
◦ Surgical insertion of tympanostomy tubes (T tubes) is an effective method for
preventing recurrent otitis media. Patients with acute otitis media should be reassessed
after 48–72 hours, with most children being asymptomatic at 7 days.
TREATMENT SUMMARY

◦ Agent chosen should provide coverage against Streptococcus pneumoniae,

Haemophilus influenzae, and Moraxella catarrhalis (e.g., amoxicillin).
◦ Agents active against gram-negative bacilli and MRSA should be considered for the
newborn infant, patients with a depressed immune system, and the patient with
suppurative complications of chronic otitis media.
◦ Surgical management is a potential therapeutic option for recurrent episodes of AOM
(e.g., myringotomy, adenoidectomy, and placement of tympanostomy tubes).
RESPIRATORY TRACT
INFECTIONS
COMMUNITY RESPIRATORY VIRUSES
COMMUNITY RESPIRATORY VIRUSES
◦ Include many common DNA and RNA viruses that cause respiratory infections.
◦ In healthy individuals, these viruses usually result in mild to moderate disease but can
cause more serious disease in the very young, elderly, and immunocompromised.
Influenza

◦ Influenza has been causing recurrent epidemics every 1–3 years for the past 400 years.
◦ A unique feature of influenza is its ability to alter the antigenic properties of the envelope
glycoproteins, the hemagglutinin (HA), and neuraminidase (NA).
◦ Antigenic drift refers to minor modifications (point mutations) within HA, NA, or both leading
to localized outbreaks.
◦ Antigenic shift refers to more radical changes in the antigenicity of HA, NA, or both
(segment reassortment) leading to widespread disease or pandemics.
◦ The greatest pandemic was in 1918–1919, when 21 million deaths were recorded worldwide.
◦ In 2009 the H1N1 influenza pandemic demonstrated the risk of severe influenza associated
with pregnancy.
In general, excess mortality has been associated with influenza
A/H3N2 and to a lesser extent with influenza A/H1N1.
• Influenza should be suspected in any patient who presents with acute onset of fever,
cough, and systemic symptoms, such as myalgias, between fall and spring.
• Fever and cough during a local epidemic are the most predictive findings of influenza
infection.
◦ Influenza is a viral illness associated with high mortality and high hospitalization rates.
The highest rates of severe illness, hospitalization, and death occur among those older
than age 65 years, young children (younger than 2 years old), and those who have
underlying medical conditions, including pregnancy and cardiopulmonary disorders.
◦ The route of influenza transmission is person-to-person via inhalation of respiratory
droplets, which can occur when an infected person coughs or sneezes. The incubation
period for influenza ranges between 1 and 7 days, with an average incubation of 2
days.
◦ Adults are considered infectious from the day before their symptoms begin through 7
days after the onset of illness, whereas children can be infectious for longer than 10
days after the onset of illness. Viral shedding can persist for weeks to months in severely
immunocompromised people.
CLINICAL PRESENTATION
◦ The presentation of influenza is similar to a number of other respiratory illnesses.
◦ The clinical course and outcome are affected by age, immunocompetence, viral
characteristics, smoking, comorbidities, pregnancy, and the degree of preexisting
immunity.
◦ Complications of influenza may include exacerbation of underlying comorbidities,
primary viral pneumonia, secondary bacterial pneumonia or other respiratory illnesses
(eg, sinusitis, bronchitis, and otitis), encephalopathy, transverse myelitis, myositis,
myocarditis, pericarditis, and Reye’s syndrome.
SIGNS AND SYMPTOMS
◦ Classic signs and symptoms of influenza include rapid onset of fever, myalgia,
headache, malaise, nonproductive cough, sore throat, and rhinitis.
◦ Nausea, vomiting, and otitis media are also commonly reported in children.
◦ Signs and symptoms typically resolve in 3–7 days, although cough and malaise may
persist for more than 2 weeks.
LABORATORY TESTS
◦ The gold standard for diagnosis of influenza is reverse-transcription polymerase chain
reaction (RT-PCR) or viral culture.
◦ Rapid influenza diagnostic tests (RIDTs), also known as point-of-care (POC) tests, direct
(DFA) or indirect (IFA) fluorescence antibody tests, and the RT-PCR assay may be used
for rapid detection of virus.
◦ Chest radiograph should be obtained if pneumonia is suspected.
PREVENTION
◦ The best means to decrease the morbidity and mortality associated with influenza is to
prevent infection through vaccination.
◦ Appropriate infection control measures, such as hand hygiene, basic respiratory
etiquette (cover your cough and throw tissues away), and contact avoidance, are
also important in preventing the spread of influenza.
◦ Additionally, chemoprophylaxis is useful in certain situations.
◦ Annual vaccination is recommended for all persons age 6 months or older and
caregivers (eg, parents, teachers, babysitters, nannies) of children less than 6 months of
age.
◦ Vaccination is also recommended for those who live with and/or care for people who
are at high risk, including household contacts and healthcare workers.
Homework
◦ List the main recommendations of The Advisory Committee on Immunization Practices
(ACIP)regarding Influenza vaccination.
POSTEXPOSURE PROPHYLAXIS
◦ Antiviral drugs available for prophylaxis of influenza should be considered adjuncts but
are not replacements for annual vaccination.
◦ Amantadine and rimantadine are currently not recommended for prophylaxis or
treatment in the United States because of the rapid emergence of resistance.
◦ The neuraminidase inhibitors oseltamivir and zanamivir are effective prophylactic
agents against influenza in terms of preventing laboratory-confirmed influenza when
used for seasonal prophylaxis and preventing influenza illness among persons exposed
to a household contact who were diagnosed with influenza.
◦ Peramivir is not approved for chemoprophylaxis.
◦ In those patients who did not receive the influenza vaccination and are receiving an
antiviral drug for prevention of disease during the influenza season, the medication
should optimally be taken for the entire duration of influenza activity in the community
◦ Prophylaxis should be considered during influenza season for the following groups of
patients:
◦ ✓Persons at high risk of serious illness and/or complications who cannot be vaccinated.
◦ ✓Persons at high risk of serious illness and/or complications who are vaccinated after
influenza activity has begun in their community because the development of sufficient
antibody titers after vaccination takes ~2 weeks.
◦ ✓Persons with severe immune deficiency or who may have an inadequate response to
vaccination (eg, advanced human immunodeficiency virus [HIV] disease, persons
receiving immunosuppressive medications), after exposure to an infectious person.
◦ ✓Long-term care facility residents, regardless of vaccination status, when an outbreak
has occurred in the institution
◦ LAIV should not be administered until 48 hours after influenza antiviral therapy has
stopped, and influenza antiviral drugs should not be administered for 2 weeks after the
administration of LAIV because the antiviral drugs inhibit influenza virus replication.
◦ Pregnant women, regardless of trimester, should receive annual influenza vaccination
with IIV but not with LAIV.
◦ The adamantanes and neuraminidase inhibitors are not recommended during
pregnancy because of concerns regarding the effects of the drugs on the fetus.
◦ Immunocompromised hosts should receive annual influenza vaccination with IIV but
not LAIV.
TREATMENT
◦ Goals of Therapy: To shorten the duration of illness and provide symptom control.
◦ Antiviral drugs are most effective if started within 48 hours of the onset of illness.
◦ Adjunct agents, such as acetaminophen for fever or an antihistamine for rhinitis, may
be used concomitantly with the antiviral drugs.
◦ Patients suffering from influenza should get adequate sleep and maintain a low level of
activity.
◦ They should stay home from work and/or school in order to rest and prevent the spread
of infection.
◦ Appropriate fluid intake should be maintained.
◦ Cough/throat lozenges, warm tea, or soup may help with symptom control (cough and
sore throat).
PHARMACOLOGIC THERAPY
◦ The neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir) are the only
antiviral drugs available for treatment and prophylaxis of influenza.
◦ Peramivir is the only intravenous formulation commercially available.
◦ The adamantanes (amantadine and rimantadine) are no longer recommended due to
high resistance among influenza viruses.
◦ Oseltamivir, zanamivir, and peramivir have activity against both influenza A and
influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir
and zanamivir may reduce the duration of illness by ~1 day versus placebo.
◦ Benefits are highly dependent on the timing of initiation of treatment, ideally being
within 12 hours of illness onset, up to 48 hours after onset of illness.
◦ Oseltamivir is approved for treatment in those older than 14 days, zanamivir is
approved for treatment in those older than 7 years, and peramivir for those 18 years
and older.
◦ The recommended duration of treatment for both agents is 5 days for oseltamivir and
◦ zanamivir and one dose for 1 day for peramivir.
◦ Neuropsychiatric complications consisting of delirium, seizures, hallucinations, and self-
injury in pediatric patients have been reported following treatment with oseltamivir and
peramivir.
◦ Oseltamivir and zanamivir have been used in pregnancy, but solid clinical safety data
are lacking.
◦ Oseltamivir is preferred for the treatment of pregnant women because of its systemic
activity; however, the drug of choice for chemoprophylaxis is not yet defined.
◦ Both the adamantanes and the neuraminidase inhibitors are excreted in breast milk
and should be avoided by mothers who are breast-feeding their infants.
Respiratory Syncytial Virus (RSV)
◦ RSV is a well-recognized cause of morbidity and mortality in immunocompromised
individuals.
◦ Disease can range from a bronchiolitis or mild URI to a more fulminant lower respiratory tract
infection (LRTI).
◦ RSV is a leading cause of viral LRTI in immunocompromised children and adults.
◦ RSV usually begins with signs and symptoms of a URI, which can progress to bronchiolitis,
pneumonitis, and pneumonia.
◦ Both standard and contact precautions are needed for hospitalized patients with RSV.
◦ Treatment of RSV must take into consideration the patient’s risk of developing more serious
disease.
◦ Ribavirin is a potential treatment option with limited efficacy data.
◦ Palivizumab is another option on the market that is a humanized monoclonal antibody
designed to reduce RSV infections.
Parainfluenza Virus (PIV)
◦ PIV are the major causes of croup or laryngotracheobronchitis in young children.
◦ PIV has also been identified as causing disease in adult immunocompromised patients.
◦ There is no proven treatment for PIV infection.
◦ PIV infection has been demonstrated to be a risk factor for airflow decline and a cause
of long-term pulmonary complications in hematopoietic stem cell transplant (HSCT)
recipients.
Adenovirus (AdV)
◦ Adenoviruses are DNA viruses that usually cause self-limited disease in normal hosts.
◦ AdV has been described with respiratory, gastrointestinal, and conjunctival infections.
◦ AdV can cause end-organ disease and disseminated infections in patients who are
recipients of stem cell and solid organ transplants.
◦ In HSCT recipients, AdV infections have been specifically associated with the following:
• T-cell depleted graft recipients.
• Acute graft versus host disease.
◦ Real-time PCR has been useful for monitoring patients with disseminated AdV infection.
◦ Cidofovir has been shown to be active against all strains of AdV during in vitro testing
and has been used to treat AdV infections.
Coronavirus
◦ Coronaviruses normally cause mild respiratory infections in humans but can occasionally
lead to more severe infections.
◦ Coronaviruses also infect many animals and have crossed over to humans (e.g., severe
acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]).
◦ SARS was originally identified in Guangdong Province of the People’s Republic of China,
spread to Hong Kong, and then to the rest of the world.
◦ A rapid public health effort was coordinated by the WHO and transmission ceased
throughout the world.
◦ Infection control work dedicated to contact and droplet spread was used successfully to
control the outbreak.
◦ MERS coronavirus was discovered when a man was admitted in 2012 to a hospital in Saudi
Arabia with the presentation of acute pneumonia and renal failure.
◦ More cases were subsequently discovered in individuals living in or traveling in the Middle
East.
RESPIRATORY TRACT
INFECTIONS
Acute Bronchitis
◦ Bronchitis is frequently classified as either acute or chronic.
◦ Acute bronchitis is characterized by inflammation of the epithelium of the large
airways resulting from infection or exposure to irritating environmental triggers (eg, air
pollution and cigarette smoke).
◦ Acute bronchitis occurs year-round, but more commonly during the winter months.
◦ Viral infections, cold, damp climates, and/or the presence of high concentrations of
irritating environmental triggers such as air pollution or cigarette smoke may precipitate
attacks.
◦ Respiratory viruses are the predominant infectious agents associated with acute
bronchitis. The most common infecting agents include influenza A and B, respiratory
syncytial virus (RSV), and parainfluenza virus.
◦ Bacterial pathogens are involved in a minority of cases and involve pathogens often
associated with community-acquired pneumonia (CAP).
◦ Infection of the trachea and bronchi causes hyperemic and edematous mucous
membranes and an increase in bronchial secretions.
◦ Destruction of respiratory epithelium can range from mild to extensive and may affect
bronchial mucociliary function. In addition, the increase in desquamated epithelial
cells and bronchial secretions, which can become thick and tenacious, further impairs
mucociliary activity.
◦ Recurrent acute respiratory infections may be associated with increased airway
hyperreactivity and possibly the pathogenesis of asthma and chronic obstructive lung
disease.
CLINICAL PRESENTATION
◦ Acute bronchitis usually begins as an upper respiratory infection with nonspecific
complaints.
◦ Cough is the hallmark of acute bronchitis and occurs early. The onset of cough may be
insidious or abrupt, and the symptoms persist despite resolution of nasal or
nasopharyngeal complaints; cough may persist for up to 3 or more weeks.
◦ Frequently, the cough initially is nonproductive, but then progresses, yielding
mucopurulent sputum.
◦ Fever, when present, rarely exceeds 39°C and appears most commonly with
adenovirus, influenza virus, and Mycoplasma pneumoniae infections.
◦ Bacterial cultures of expectorated sputum are generally of limited utility because of the
inability to avoid normal nasopharyngeal flora by the sampling technique. For the vast
majority of affected patients, an etiologic diagnosis is unnecessary and will not change
the prescribing of routine supportive care for the management of these patients.
TREATMENT
◦ Goals of Treatment: The goal is to provide comfort to the patient and, in the unusually
severe case, to treat associated dehydration and respiratory compromise.
◦ The treatment of acute bronchitis is symptomatic and supportive. Reassurance and
antipyretics alone are often sufficient.
◦ Bedrest for comfort may be instituted as desired.
◦ Patients should be encouraged to drink fluids to prevent dehydration and possibly to
decrease the viscosity of respiratory secretions.
◦ • Aspirin or Acetaminophen or ibuprofen can be administered.
◦ In children under 19 years of age, aspirin should be avoided and acetaminophen used
as the preferred agent because of the possible association between aspirin use and
the development of Reye syndrome
◦ In otherwise healthy patients, no meaningful benefits have been described with the
use of oral or aerosolized β2-receptor agonists and/or oral or aerosolized
corticosteroids.
◦ Persistent, mild cough, which may be bothersome, may be treated with
dextromethorphan; more severe coughs may require intermittent codeine or other
similar agents. Codeine is no longer recommended for use in pediatric patients.
◦ Routine use of antibiotics in the treatment of acute bronchitis is strongly discouraged;
however, in patients who exhibit persistent fever or respiratory symptomatology for
more than 5–7 days, the possibility of a concurrent bacterial infection should be
suspected.
◦ When possible, antibiotic therapy is directed toward anticipated respiratory
pathogen(s) (ie, Streptococcus pneumoniae and Haemophilus influenzae).
◦ M. pneumoniae, if suspected by history or if confirmed by culture, serology, or PCR may
be treated with azithromycin. Also, a fluoroquinolone with activity against these
pathogens (levofloxacin or moxifloxacin) may be used empirically, but reserved for
patients not responding adequately to supportive care and deemed at risk of
associated complications.
Bronchiolitis
◦ Bronchiolitis is an acute viral infection of the lower respiratory tract of infants that
affects ~50% of children during the first year of life and 100% by 2 years.
◦ RSV is the most common cause of bronchiolitis, accounting for up to 75% of all cases.
◦ Other detectable viruses include parainfluenza, adenovirus, and influenza.
◦ Bacteria serve as secondary pathogens in a minority of cases.
CLINICAL PRESENTATION
◦ The most common clinical signs of bronchiolitis. A prodrome suggesting an upper
respiratory tract infection, usually lasting from 1–4 days, precedes the onset of clinical
symptoms. As a result of limited oral intake due to coughing combined with fever,
vomiting, and diarrhea, infants are frequently dehydrated.
◦ The diagnosis of bronchiolitis is based primarily on history and clinical findings.
◦ Identification of respiratory syncytial virus by PCR should be available routinely from
most clinical laboratories, but its relevance to the clinical management of bronchiolitis
remains obscure and routine testing is not recommended.
SIGNS AND SYMPTOMS
◦ Prodrome with irritability, restlessness, and mild fever.
◦ Cough and coryza.
◦ Vomiting, diarrhea, noisy breathing, and increased respiratory rate as symptoms
progress.
◦ Labored breathing with retractions of the chest wall, nasal flaring, and grunting
PHYSICAL EXAMINATION
◦ Tachycardia and respiratory rate of 40–80 per minute in hospitalized infants.
◦ Wheezing and inspiratory rales.
◦ Mild conjunctivitis in one-third of patients.
◦ Otitis media in 5%–10% of patients.
LABORATORY TESTS
◦ Peripheral white blood cell count normal or slightly elevated.
◦ Abnormal arterial blood gases (hypoxemia and, rarely, hypercarbia).
TREATMENT
◦ Bronchiolitis is a self-limiting illness and usually requires no therapy (other than reassurance,
antipyretics, and adequate fluid intake) unless the infant is hypoxic or dehydrated.
Otherwise healthy infants can be treated for fever, provided generous amounts of oral fluids,
and observed closely for evidence of respiratory deterioration.
◦ In severely affected children, the mainstays of therapy for bronchiolitis are oxygen therapy
and intravenous (IV) fluids.
◦ Aerosolized β-adrenergic therapy appears to offer little benefit for the majority of patients
but may be useful in the child with a predisposition toward bronchospasm.
◦ The routine use of systemically administered corticosteroids is not recommended.
◦ The American Academy of Pediatrics guidelines support the use of nebulized hypertonic
saline (eg, 3% saline) for the treatment of bronchiolitis in hospitalized infants and children.
◦ The American Academy of Pediatrics does not recommend the routine use of ribavirin in
children with bronchiolitis and most experts recommend reserving use of ribavirin for severely
ill patients. Use of ribavirin requires special equipment (small- particle aerosol generator) and
specifically trained personnel for administration via oxygen hood or mist tent.
Pneumonia
◦ Pneumonia remains one of the most common causes of severe sepsis and infectious
cause of death in children and adults in the United States, with a mortality rate as high
as 50%.
PATHOPHYSIOLOGY
◦ Respiratory pathogens enter the lower respiratory tract by one of three routes:
◦ (1) direct inhalation of infectious droplets; (2) aspiration of oropharyngeal contents; or
(3) hematogenous spread from another infection site.
◦ Pneumonia is caused by a variety of viral and bacterial pathogens.
◦ Pneumonia is categorized as either community-acquired or hospital-acquired.
◦ Pneumonia onset outside of the hospital or within 48 hours of hospital admission have
CAP.
◦ Pneumonia onset in the hospital after at least 48 hours of hospitalization have hospital-
acquired pneumonia (HAP).
◦ Pneumonia onset following 48 hours of endotracheal intubation have ventilator-
associated pneumonia (VAP).
◦ The causative pathogen in CAP in adult patients is most commonly viral, with human
rhinovirus and influenza most common. The most prominent bacterial pathogen
causing CAP in otherwise healthy adults is S. pneumoniae accounting for up to 35%
(12%–68%) of all acute cases. Other common bacterial causes are H. influenzae, the
“atypical” pathogens including M. pneumoniae, Legionella species, C. pneumoniae.
◦ Viral pathogens (RSV and human rhinovirus) predominate in CAP among pediatric
patients with a prevalence of up to 80% in those less than 2 years of age.
◦ HAP is predominantly caused by gram-negative aerobic bacilli and S. aureus and is
much more likely to be caused by a multidrug-resistant isolate. P. aeruginosa and
Acinetobacter spp. are the most common cause of HAP (about 25%–45%) while K.
pneumoniae and E. coli are also common.
◦ Aspiration pneumonia has a bacteriology similar to CAP or HAP and anaerobic
pathogens are less common and typically seen in patients with specific risk factors such
as periodontal disease or alcoholism.
CLINICAL PRESENTATION
GRAM-POSITIVE AND GRAM-
NEGATIVE BACTERIAL PNEUMONIA
◦ Blood cultures and noninvasive sputum cultures (ie, expectorated sputum, sputum induction,
or nasotracheal suctioning) are recommended for all adult patients with suspected HAP or
VAP.
◦ The chest radiograph and sputum examination and culture are the most useful diagnostic
tests for gram-positive and gram-negative bacterial pneumonia. Typically, the chest
radiograph reveals a dense lobar or lobular consolidated infiltrates.
◦ Signs and symptoms: Abrupt onset of fever, chills, dyspnea, and productive cough; Rust-
colored sputum or hemoptysis; Pleuritic chest pain; and Dyspnea.
◦ Physical examination findings: Tachypnea and tachycardia; dullness to percussion;
increased tactile fremitus, whispered pectoriloquy, and egophony; Chest wall retractions
and grunting respirations; Diminished breath sounds over affected area; and Inspiratory
crackles during lung expansion.
◦ Chest radiograph findings: Dense lobar or segmental infiltrate.
◦ Laboratory tests: Leukocytosis with predominance of polymorphonuclear cells. Low oxygen
saturation on arterial blood gas or pulse oximetry.
ATYPICAL PNEUMONIA (M.
PNEUMONIAE AND C. PNEUMONIAE)
◦ Pneumonia caused by the atypical pathogens, such as M. pneumoniae and C.
pneumoniae, often has a more gradual onset and overall lower severity compared
with other bacterial causes. Patients with atypical pneumonia also commonly have
extrapulmonary, constitutional symptoms.
HOSPITAL-ACQUIRED PNEUMONIA
◦ The strongest predisposing factor for HAP is mechanical ventilation. Factors
predisposing patients to HAP include severe illness, long duration of hospitalization,
supine positioning, witnessed aspiration, coma, acute respiratory distress syndrome,
patient transport, and prior antibiotic exposure. HAP is exacerbated by the wide use of
acid-reducing drugs (eg, H2-receptor blocking agents and proton pump inhibitors)
which increases the pH of gastric secretions and may promote the proliferation of
microorganisms in the upper GI tract.
◦ The diagnosis of nosocomial pneumonia is usually established by the presence of a
new infiltrate on chest radiograph, fever, worsening respiratory status, and the
appearance of thick, neutrophil-laden respiratory secretions
TREATMENT
◦ Goal of Treatment:
◦ Eradication of the offending organism and complete clinical cure.
◦ Secondary goals include minimization of the unintended consequences of therapy,
including toxicities and selection for secondary infections such a Clostridioides difficile
or antibiotic-resistant pathogens, and minimizing costs through outpatient and oral
therapy when the patient’s severity of illness and clinical considerations permit.
◦ The supportive care of the patient with pneumonia includes the use of humidified oxygen for
hypoxemia, fluid resuscitation, administration of bronchodilators (albuterol) when
bronchospasm is present, and chest physiotherapy with postural drainage if there is
evidence of retained secretions.
◦ Important therapeutic adjuncts include adequate hydration (by IV route if necessary),
optimal nutritional support, and fever control.
◦ Severity scoring systems such as CURB-65 are used to guide treatment.
◦ For CURB- 65, patients receive 1 point for each criterion present:
◦ Confusion,
◦ Uremia (BUN >20 mg/dL [7.1 mmol/L]),
◦ Respiratory rate ≥30 breaths/min,
◦ Blood pressure (systolic <90 mm Hg, diastolic ≤60 mm Hg),
◦ age ≥65 years.
◦ Patients with CURB-65 score <2 are generally candidates for outpatient treatment.
◦ Patients with a score of 2 are typically admitted to the general ward of the hospital
◦ ICU admission considered for patients with scores ≥3.
◦ The treatment of bacterial pneumonia initially involves the empiric use of a relatively
◦ broad-spectrum antibiotic therapy effective against probable pathogens after
◦ appropriate cultures and specimens for laboratory evaluation have been obtained.
◦ Therapy should be narrowed to cover specific pathogens once the results of cultures
are known.
◦ The minimum duration of therapy for CAP is 5 days although CAP is commonly treated
for 7–10 days.
◦ The recommended duration of therapy for HAP/VAP is 7 days, as the clinical benefit of
longer durations of therapy (≥10 days) is not clear based on available clinical
evidence.