Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold—typically a mild, self-limited, catarrhal syndrome of the nasopharynx—to life-threatening illnesses such as epiglottitis (see the image below).
View Image | Lateral neck radiograph demonstrates epiglottitis. Courtesy of Marilyn Goske, MD, Cleveland Clinic Foundation. |
Details of the patient's history aid in differentiating a common cold from conditions that require targeted therapy, such as group A streptococcal pharyngitis, bacterial sinusitis, and lower respiratory tract infections. Clinical manifestations of these conditions, as well as allergy, show significant overlap.
Viral nasopharyngitis
Patients with the common cold may have a paucity of clinical findings despite notable subjective discomfort. Findings may include the following:
Group A streptococcal pharyngitis The following physical findings suggest a high risk for group A streptococcal disease[1] :
Acute bacterial rhinosinusitis In children, acute bacterial sinusitis is defined as a URI with any of the following[3] :
In older children and adults, symptoms (eg, pain, pressure) tend to localize to the affected sinus.
Epiglottitis
This condition is more often found in children aged 1-5 years, who present with a sudden onset of the following symptoms:
Laryngotracheitis and laryngotracheobronchitis
Features of whooping cough (pertussis) are as follows:
The 3 classic phases of whooping cough are as follows:
See Clinical Presentation for more detail.
Tests of nasopharyngeal specimens for specific pathogens are helpful when targeted therapy depends on the results (eg, group A streptococcal infection, gonococcus, pertussis). Specific bacterial or viral testing is also warranted in other selected situations, such as when patients are immunocompromised, during certain outbreaks, or to provide specific therapy to contacts.
Diagnosis of specific disorders is based on the following:
Blood cultures are typically appropriate only in hospitalized patients with suspected systemic illness. Imaging studies are warranted in patients with suspected mass lesions (eg, peritonsillar abscess, intracranial suppurative lesions).
See Workup for more detail.
Symptom-basedtherapy represents the mainstay of URI treatment in immunocompetent adults. Antimicrobial or antiviral therapy is appropriate in selected patients.
Epiglottitis
Laryngotracheitis
Rhinosinusitis
Group A streptococcal disease
See Treatment and Medication for more detail.
Upper respiratory tract infection (URI) represents the most common acute illness evaluated in the outpatient setting. URIs range from the common cold—typically a mild, self-limited, catarrhal syndrome of the nasopharynx—to life-threatening illnesses such as epiglottitis.
Viruses account for most URIs (see Etiology). Appropriate management in these cases may consist of reassurance, education, and instructions for symptomatic home treatment. Diagnostic tests for specific agents are helpful when targeted URI therapy depends on the results (see Workup). Bacterial primary infection or superinfection may require targeted therapy (see Treatment).
The upper respiratory tract includes the sinuses, nasal passages, pharynx, and larynx, which serve as gateways to the trachea, bronchi, and pulmonary alveolar spaces. Rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis, and tracheitis are specific manifestations of URIs. Further information can be found in the Medscape Reference articles Acute Laryngitis, Acute Sinusitis, Allergic Rhinitis, Bacterial Tracheitis, Croup, Epiglottitis, Pharyngitis, and Viral Pharyngitis.
Common URI terms are defined as follows:
URIs involve direct invasion of the mucosa lining the upper airway. Inoculation of bacteria or viruses occurs when a person’s hand comes in contact with pathogens and the person then touches the nose or mouth or when a person directly inhales respiratory droplets from an infected person who is coughing or sneezing.
After inoculation, viruses and bacteria encounter several barriers, including physical, mechanical, humoral, and cellular immune defenses. Physical and mechanical barriers include the following:
Adenoids and tonsils contain immune cells that respond to pathogens. Humoral immunity (immunoglobulin A) and cellular immunity act to reduce infections throughout the entire respiratory tract. Resident and recruited macrophages, monocytes, neutrophils, and eosinophils coordinate to engulf and destroy invaders.
A host of inflammatory cytokines mediates the immune response to invading pathogens. Normal nasopharyngeal flora, including various staphylococcal and streptococcal species, help to defend against potential pathogens. Patients with suboptimal humoral and phagocytic immune function are at increased risk for contracting a URI, and they are at increased risk for a severe or prolonged course of disease.
Inflammation (chronic or acute) from allergy predisposes to URI. Children with allergy are particularly subject to frequent URIs.
Infection
Person-to-person spread of viruses accounts for most URIs. Household and child care settings can serve as reservoirs for infection. Bacterial infections may develop de novo or as a superinfection of a viral URI.
Viral agents occurring in URIs include a vast number of serotypes, which undergo frequent changes in antigenicity, posing challenges to immune defense. Pathogens resist destruction by a variety of mechanisms, including the production of toxins, proteases, and bacterial adherence factors, as well as the formation of capsules that resist phagocytosis.
Incubation times before the appearance of symptoms vary among pathogens. Rhinoviruses and group A streptococci may incubate for 1-5 days, influenza and parainfluenza may incubate for 1-4 days, and respiratory syncytial virus (RSV) may incubate for a week. Pertussis typically incubates for 7-10 days, or even as long as 21 days, before causing symptoms. Diphtheria incubates for 1-10 days. The incubation period of Epstein-Barr virus (EBV) is 4-6 weeks.
Most symptoms of URIs—including local swelling, erythema, edema, secretions, and fever—result from the inflammatory response of the immune system to invading pathogens and from toxins produced by pathogens.
An initial nasopharyngeal infection may spread to adjacent structures, resulting in the following:
Inflammatory narrowing at the level of the epiglottis and larynx may result in a dangerous compromise of airflow, especially in children, in whom a small reduction in the luminal diameter of the subglottic larynx and trachea may be critical. Beyond childhood, laryngotracheal inflammation may also pose serious threats to individuals with congenital or acquired subglottic stenosis.
Susceptibility
Genetic susceptibility is involved in determining which patients have more severe disease courses than others. There are some recognized candidate gene polymorphisms with known functional changes in genes that may lead to immunosuppression.[8] It has also been shown that host immunogenetic variation plays a role in the immune response to H1N1 and H5N1 viruses, thereby influencing disease severity and outcome in influenza caused by these viruses.[9, 10]
Most URIs are viral in origin. Typical viral agents that cause URIs include the following:
For the most part, similar agents cause URI in adults and children; however, Moraxella catarrhalis and bocavirus cause URIs more commonly in children than in adults.
Of the more than 200 viruses known to cause the symptoms of the common cold, the principal ones are as follows:
Other viruses that account for many URIs include the following:
Unidentified, but presumably viral, pathogens account for more than 30% of common colds in adults. In addition, varicella, rubella, and rubeola infections may manifest as nasopharyngitis before other classic signs and symptoms develop.
This is most often viral in origin. Recognition of group A streptococcal pharyngitis is vital because serious complications may follow untreated disease.
Viral causes of pharyngitis include the following:
Bacterial causes of pharyngitis include the following:
Rhinosinusitis in an immunocompetent person is typically related to an uncomplicated viral URI. Viral causes are similar to those of viral nasopharyngitis and include the following:
Bacterial causes are similar to those seen in otitis media. Bacterial pathogens isolated from maxillary sinus aspirates of patients with acute bacterial rhinosinusitis include the following[7] :
Other pathogens include group A streptococci and other streptococcal species. Uncommon causes include C pneumoniae, Neisseria species, anaerobes, and gram-negative rods.
Nosocomial sinusitis often involves pathogens that colonize the upper respiratory tract and migrate into the sinuses. Prolonged endotracheal intubation places patients at increased risk for nosocomial sinusitis. Methicillin-resistant S aureus (MRSA) is less common than sensitive staphylococci.[7] Gram-negative bacilli (eg, Escherichia coli,Pseudomonas aeruginosa) are other causes.
Aspergillus species are the leading causes of noninvasive fungal sinusitis. Although fungi are part of the normal flora of the upper airways, they may cause acute sinusitis in patients with immunocompromise or diabetes mellitus.
This is a bacterial infection. In the vast majority of children, H influenzae type b (Hib) is isolated from blood or epiglottal cultures. Since the routine use of the Hib conjugate vaccine began in 1990, case rates in children younger than 5 years have declined by more than 95%. The prevalence of invasive Hib disease is approximately 1.3 cases per 100,000 children.[12] Rates in adults have remained low and stable; Alaskan Natives have the highest rates of disease.
Other bacteria, found more commonly in adults than in children, include group A streptococci, S pneumoniae, and M catarrhalis. In adults, cultures are most likely to be negative.
Croup, or laryngotracheobronchitis, is typically caused by PIV type 1, 2, or 3. PIVs account for up to 80% of croup cases. PIV type 1 is the leading cause of croup in children.[13] Other viruses include influenza viruses and RSV. Uncommon causes include hMPV, adenovirus, rhinovirus, enterovirus (including coxsackievirus and enteric cytopathic human orphan [ECHO] viruses), and measles virus.
Approximately 95% of all cases of whooping cough are caused by the gram-negative rod Bordetella pertussis. The remaining cases result from B parapertussis.
Other forms of laryngitis and laryngotracheitis are typically caused by viruses similar to those that cause nasopharyngitis, including rhinovirus, coronavirus, adenovirus, influenza virus, parainfluenza virus, and RSV. Candida species may cause laryngitis in immunocompromised hosts.
Bacterial laryngitis is far less common than viral laryngitis.[14] Bacterial causes include the following:Group A streptococci
Risk factors for contracting a URI include the following:
URIs are the most common infectious illness in the general population and are the leading cause of missed days at work or school. They represent the most frequent acute diagnosis in the office setting.[15]
The incidence of the common cold varies by age. Rates are highest in children younger than 5 years. Children who attend school or day care are a large reservoir for URIs, and they transfer infection to the adults who care for them. In the first year after starting at a new school or day care, children experience more infections, as do their family members. Children have about 3-8 viral respiratory illnesses per year, adolescents and adults have approximately 2-4 colds annually, and people older than 60 years have fewer than 1 cold per year.
Acute pharyngitis accounts for 1% of all ambulatory office visits.[15] The incidence of viral and bacterial pharyngitis peaks in children aged 4-7 years.
Sinusitis is common in persons with viral URIs. Transient changes in the paranasal sinuses are noted on computed tomography (CT) scans in more than 80% of patients with uncomplicated viral URIs.[16] However, bacterial rhinosinusitis occurs as a complication in only about 2% of persons with viral URIs.[17]
The occurrence of epiglottitis has decreased dramatically in the United States and other developed nations since the introduction of Hib vaccine. A Swedish study documented that the Hib vaccination program was associated with a decrease in the overall annual incidence of acute epiglottitis from 4.5 cases to 0.98 cases per 100,000 population; the incidence decreased in children and adults. However, the annual incidence of pneumococcal epiglottitis in adults increased from 0.1 to 0.28 cases per 100,000 population over the same period.[18]
Croup, or laryngotracheobronchitis, may affect people of any age but usually occurs in children aged 6 months to 6 years. The peak incidence is in the second year of life. Thereafter, the enlarging caliber of the airway reduces the severity of the manifestations of subglottic inflammation.
Vaccination has dramatically reduced rates of pertussis. However, the incidence of whooping cough in the United States has increased steadily since 2007, reaching approximately 9 cases per 100,000 population in 2010. Rates of pertussis are highest in infants below age 1 year; adolescents and adults accounted for approximately 44% of the 27,550 cases of pertussis reported in the United States in 2010.[19]
Worldwide, pertussis has an estimated incidence of 48.5 million cases and causes nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%.[20]
Although pertussis is a nationally notifiable disease in the United States, many cases likely go undiagnosed and unreported. On the other hand, challenges in laboratory diagnosis and overreliance on polymerase chain reaction (PCR) assays have resulted in reports of respiratory illness outbreaks mistakenly attributed to pertussis.[21]
Group A streptococcal bacteria cause approximately 5-15% of all pharyngitis infections,[2] accounting for several million cases of streptococcal pharyngitis each year. This infection is rarely diagnosed in children younger than 2 years.
Influenza affects approximately 5-20% of the US population during each flu season.[22] Early presentations include symptoms of URI.
EBV infection affects as many as 95% of American adults by age 35-40 years. Childhood EBV infection is indistinguishable from other transient childhood infections. Approximately 35-50% of adolescents and young adults who contract EBV infection have mononucleosis.[23]
Diphtheria rates fell dramatically in the United States after the advent of diphtheria vaccine. Since 1980, the prevalence of diphtheria has been approximately 0.001 case per 100,000 population. A confirmed case of the disease has not been reported in the United States since 2003.[24] However, diphtheria remains endemic in developing countries.
Although URIs may occur year round, in the United States most colds occur during fall and winter. Beginning in late August or early September, rates of colds increase over several weeks and remain elevated until March or April.[25] Epidemics and mini-epidemics are most common during cold months, with a peak incidence from late winter to early spring.
Cold weather results in more time spent indoors (eg, at work, home, school) and close exposure to others who may be infected. Humidity may also affect the prevalence of colds, because most viral URI agents thrive in the low humidity that is characteristic of winter months. Low indoor air moisture may increase friability of the nasal mucosa, increasing a person's susceptibility to infection.
Laryngotracheobronchitis, or croup, occurs in fall and winter. Seasonality does not affect rates of epiglottitis.
The figure below illustrates the peak incidences of various agents by season. Rhinoviruses, which account for a substantial percentage of URIs, are most active in spring, summer, and early autumn. Coronaviral URIs manifest primarily in the winter and early spring. Enteroviral URIs are most noticeable in summer and early fall, when other URI pathogens are at a nadir. Adenoviral respiratory infections can occur throughout the year but are most common in the late winter, spring, and early summer.
View Image | Seasonal variation of selected upper respiratory tract infection pathogens. PIV is parainfluenza virus, RSV is respiratory syncytial virus, MPV is met.... |
Seasonal influenza typically lasts from November until March. Some PIVs have a biennial pattern. The patterns for human PIV types 1-3 are as follows:
Human metapneumovirus (hMPV) infection may also occur year round, although the infection rates peak between December and February.
No notable racial difference is observed with URIs. However, Alaskan Natives have rates of Hib disease higher than those of other groups.[12]
Sexual disparities among URIs are as follows:
The incidence of the common cold varies by age. Rates are highest in children younger than 5 years. Children have approximately 3-8 viral respiratory illnesses per year, while adolescents and adults have approximately 2-4 colds a year, and people older than 60 years have fewer than 1 cold per year.
The age-related occurrence of other infections is as follows:
URIs cause people to spend time away from their usual daily activities, but alone, these infections rarely cause permanent sequelae or death. URIs may, however, serve as a gateway to infection of adjacent structures, resulting in the following infections (and others, as well):
Serious complications may result in clinically significant morbidity and rare deaths.
A common cold may last up to 14 days, with symptoms averaging 7-11 days in duration.[17]
Fever, sneezing, and sore throat typically resolve early, whereas cough and nasal discharge are among the symptoms that last longest.
Attendance at day care may affect the duration of symptoms in young children. In one study, the duration of viral URIs ranged from 6.6 days for children aged 1-2 years in home care to 8.9 days for children younger than 1 year who were in day care. Young children in day care were also more likely to have protracted respiratory symptoms lasting more than 15 days.[26]
Most patients with influenza recover within a week, although cough, fatigue, and malaise may persist for up to 2 weeks. For newborns, elderly persons, and patients with chronic medical conditions, the flu may be life threatening. More than 200,000 people per year are hospitalized because of complications of the flu, with 0.36 deaths per 100,000 patients occurring annually.[27] Influenza may be followed by bacterial superinfection.
Viral pharyngitis typically resolves in 1-2 weeks, but immunocompromised persons may have a more severe course.
Untreated group A streptococcal pharyngitis can result in the following:
Mortality from group A streptococcal pharyngitis is rare, but serious morbidity or death may result from one of its complications.
Streptococcal pharyngitis without complications rarely poses significant risk for morbidity. However, retropharyngeal, intraorbital, or intracranial abscesses may cause serious sequelae. The risk of mortality is significant in patients who progress to streptococcal toxic shock syndrome, which is characterized by multiorgan failure and hypotension.
In patients with penicillin-sensitive streptococcal pharyngitis, symptomatic improvement is expected within 24-72 hours if antibiotic treatment is started in the first 24 hours after onset. Treatment failures are common and are mainly attributed to poor adherence, antibiotic resistance, and untreated close contacts, usually within the household or family.
A chronic carrier state may develop with group A streptococcal infection. Eradicating the pathogen is difficult in these cases; however, carriers without active symptoms are unlikely to spread group A streptococci, and they are at low risk for developing rheumatic fever.
Mononucleosis
With infectious mononucleosis from EBV, complete resolution of symptoms may take up to 2 months. Acute symptoms rarely last more than 4 months. EBV typically remains dormant throughout the patient's life. Reactivation of the virus is not usually symptomatic.
The prognosis is generally favorable for acute rhinosinusitis, and many cases appear to resolve even without antibiotic therapy. As many as 70% of immunocompetent adults with rhinosinusitis begin to improve within 2 weeks of presentation without antibiotics. With antibiotics, up to 85% have improvement at 2 weeks. Complete resolution may take weeks to months.
Sinusitis itself is rarely life threatening, but it can lead to serious complications if the infection extends into surrounding deep tissue, including the following:
Epiglottitis poses a risk of death due to sudden airway obstruction and other complications, including septic arthritis, meningitis, empyema, and mediastinitis. In adults, epiglottitis has a fatality rate of approximately 1%.
The prognosis is favorable with appropriate airway management, and most patients noticeably improve within 24-48 hours after antibiotics are started. Rarely, cases of epiglottitis may recur. Recurrent symptoms raise concern about potential underlying disorders, such as rheumatic conditions, sarcoidosis, and occult malignancy.
With croup, laryngotracheobronchitis typically begins to improve within 3-4 days. Recovery is usually complete. However, patients may have a recurrence, including during the same season.
Pertussis (whooping cough) leads to hospitalization in more than half of infants younger than 12 months and particularly in infants younger than 6 months. Infants and young children are most susceptible to severe courses that include respiratory compromise.
Of infants who are hospitalized with pertussis, approximately 50% have apnea, 20% develop pneumonia, 1% have seizures, 1% die, and 0.3% have encephalopathy.[28] Recovery from whooping cough is typically complete. However, paroxysms of coughing may last for several weeks.
Most URIs are self-limited and resolve completely. However, a variety of conditions may complicate a URI. Fluid loss may occur in patients unable to tolerate adequate oral intake because of upper airway inflammation or may result from fever. Otitis media may complicate 5% of colds in children and up to 2% of colds in adults[29]
Airway hyperreactivity may increase after a URI, resulting in new or exacerbated asthma. Cough asthma, wherein a cough is the predominant manifestation of reactive airways disease, may mimic ongoing infection. This may be diagnosed with pulmonary function testing.
A postinfectious cough is defined as coughing that persists 3-8 weeks after the onset of a URI in the absence of other clearly defined causes. Exacerbations of chronic obstructive pulmonary disease, including emphysema and chronic bronchitis, may occur during and after a URI. Upper airways cough syndrome (post-nasal drip) may result from upper airway secretions dripping onto the pharynx. Epistaxis may also occur.
Lower respiratory tract disease and sepsis represent serious complications, especially in patients with immunocompromise. Lower respiratory tract disease should be considered when symptoms such as fever, cough, sputum, and malaise worsen progressively or after initial transient improvement. Tachypnea and dyspnea are also signs of lower respiratory involvement.
Viral infection and resulting inflammation may make an individual susceptible to concomitant or sequential infection with a bacterial agent. Streptococcus pneumoniae, Staphylococcus aureus, H influenzae, and Streptococcus pyogenes are common superinfecting agents. Meningococci may cause superinfection with influenzal infections.
Inflammation of the larynx and trachea area may lead to airway compromise, especially in children and in patients with narrowed airways due to congenital or acquired subglottic stenosis. The work of breathing during epiglottitis or laryngotracheitis may lead to respiratory failure. Sleep apnea may occur from hypertrophied tonsils.
Deep tissue infection may occur by extension of the infection into the orbit, middle ear, cranium, or other areas. Peritonsillar abscess (quinsy) may complicate bacterial pharyngitis, leading to difficulty swallowing and pain radiating to the ear. Retropharyngeal abscess may also complicate pharyngitis. Lemierre syndrome is an extension of pharyngitis that leads to a suppurative thrombophlebitis of the internal jugular vein; septic thromboemboli may then spread throughout the body.
Complications of sinusitis include the following:
Suspect a deep tissue infection when a patient has orbital or periorbital swelling, proptosis, impaired extraocular movements, or impaired vision. Signs of increased intracranial pressure (eg, papilledema, altered mental status, neurologic findings) may suggest intracranial involvement.
Encephalitis, meningitis, or subarachnoid hemorrhage may follow a URI. Osteomyelitis may complicate persistent or recurrent sinusitis. Osteomyelitis may affect the orbital plate, frontal bone, or sphenoid bone. Mucoceles are expanding cystic defects of the paranasal sinuses that may result from prolonged sinusitis. Epiglottic abscess may result from epiglottitis.
Lymphadenitis may follow or accompany URI. Guillain-Barré syndrome may manifest as an ascending polyneuropathy a few days or weeks after a URI. In children or adolescents, the use of aspirin during a viral infection may rarely cause Reye syndrome. Aspirin is contraindicated for the management of fevers in children or adolescents.
URI, especially with fever, may increase the work of the heart, adding strain to persons with suboptimal cardiovascular status, and can lead to cardiovascular decompensation. Myositis or pericarditis may result from viral infection.
Hyperglycemia may occur during a URI in patients with diabetes. Rib fracture may be seen following an episode of severe coughing, such as that associated with whooping cough. Hernia may develop following an episode of severe coughing.
Cutaneous complications such as rash, cellulitis, and toxic shock syndrome may occur with group A streptococcus. This pathogen can also be associated with glomerulonephritis, acute rheumatic fever, and PANDAS syndrome (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections).
Hemoptysis suggests the possibility of tuberculosis. A tuberculin skin test, chest radiography, or both are appropriate in these patients.
Complications of group A streptococcal disease
Group A streptococcal pharyngitis is of special concern because its complications include streptococcal toxic shock syndrome, acute rheumatic fever (ARF), acute glomerulonephritis, and scarlet fever, as well as cutaneous infections. In addition, this pathogen is readily transmissible, especially in households, families, and other intimate groups.
ARF affects approximately 3% of patients with strep throat, primarily occurring in persons aged 6-20 years. The condition develops approximately 2-4 weeks after streptococcal pharyngitis occurs, and it may last several months. Signs of rheumatic fever include arthritis, fever, and valvular disease. Uncommon features include an expanding truncal exanthem (erythema marginata), subcutaneous nodules, and chorea.
Poststreptococcal glomerulonephritis can affect persons of any age group, but it is most common in children aged 3-7 years. Boys are affected slightly more often than girls. Patients with glomerulonephritis may have loss of appetite, lethargy, dull back pain, and dark urine. Blood pressure may be elevated, and edema may occur.
Scarlet fever is a self-limited exanthem that spreads from the chest and abdomen to the entire body. Tiny red papules create a rough skin texture similar to that of sandpaper. The rash is typically blanching. Although it commonly affects the face, circumoral pallor is present. During recovery, the skin on the fingers and toes peels. Streptococcal toxic shock syndrome may also occur, affecting skin and mucosa.
PANDAS is a rare syndrome in children and adolescents, who experience sudden onset or worsening of obsessive-compulsive disorder following streptococcal infection. Associated manifestations include tics and a variety of neuropsychiatric symptoms.[30]
Complications of mononucleosis
Complications can include the following:
Complications of diphtheria
Complications may include airway obstruction, myocarditis, polyneuritis, thrombocytopenia, and proteinuria. Among patients who survive diphtheria, as many as 20% have permanent hearing loss or other long-term sequelae.[13]
Complications from pertussis
More than half of infants younger than 12 months who contract pertussis require hospitalization, especially those who are younger than 6 months. Complications of pertussis in hospitalized infants include the following[28] :
In addition, severe cough may result in rib fractures, hernia, incontinence, or subconjunctival hemorrhages.
Complications of influenza
These include the following:
As with any systemic infection, the flu poses a risk of worsening underlying medical conditions, such as heart failure, asthma, or diabetes. After influenzal infection, children may experience sinus problems or otitis media.
Address the patient's expectations about antibiotic therapy. Validate the patient's symptoms and their severity, listen to the concerns expressed, and educate the patient about possible consequences of inappropriate antibiotic use, including consequences affecting him/her and the community.
Many people hold misperceptions about the duration and intensity of symptoms associated with URI and about the benefits and risks of antibiotic therapy. Some are unaware that cold symptoms may last as long as 14 days. Some believe that antibiotics will help them to avoid serious disease and recover more quickly than without treatment.
Patients may expect to receive antibiotics solely based on the severity of their symptoms, and they may not appreciate the negative consequences of using antibiotics in viral disease. Negative results on a rapid strep test may provide reassurance about the appropriateness of supportive care.
Actively promote self-care, and outline a realistic time course for the resolution of symptoms. Reassure the patient about access to clinical care and follow-up in the event that symptoms progress. Briefly explore factors that may have contributed to the current infection, and address prevention for the future.
Patient satisfaction is less linked to antibiotic prescriptions and more linked to the quality of the physician-patient interaction. Reflecting understanding of the details of the patient's situation, expressing concern for the patient's well-being, explaining how recommendations are appropriately tailored to the individual's current condition, and providing reassurance are important to patient satisfaction.
Patients should be counseled on handwashing and proper methods of covering coughs and sneezes. Patients who smoke should receive smoking cessation encouragement and materials. When antibiotics are prescribed, patients should be instructed to complete the full course of antibiotic therapy.
Patients should be instructed to follow up when indicated or if symptoms worsen. Finally, patients with infectious mononucleosis should be instructed to avoid contact sports for 6 weeks because of the possibility of splenic rupture.
For patient education information, see the Headache and Migraine Center, as well as Sinus Infection and Sore Throat.
Details of the patient's history aid in differentiating a common cold from conditions that require targeted therapy, such as group A streptococcal pharyngitis, bacterial sinusitis, and lower respiratory tract infections. The table below contrasts symptoms of upper respiratory tract infection (URI) with symptoms of allergy and seasonal influenza (adapted from the National Institute of Allergy and Infectious Diseases).[22, 25]
Table. Symptoms of Allergies, URIs, and Influenza
View Table | See Table |
Symptoms of the common cold usually begin 2-3 days after inoculation. Viral URIs typically last 6.6 days in children aged 1-2 years in home care and 8.9 days for children older than 1 year in daycare. Cold symptoms in adults can last from 3-14 days, but most people recover or have symptomatic improvement within a week. If symptoms last longer than 2 weeks, consider alternative diagnoses, such as allergy, sinusitis, mononucleosis, tuberculosis, or pneumonia.
Nasal symptoms of rhinorrhea, congestion or obstruction of nasal breathing, and sneezing are common early in the course. Clinically significant rhinorrhea is more characteristic of a viral infection rather than a bacterial infection. In viral URI, secretions often evolve from clear to opaque white to green to yellow within 2-3 days of symptom onset.[7] Thus, color and opacity do not reliably distinguish viral from bacterial illness.
On the other hand, the existence of persistent, purulent nasal discharge, especially if accompanied by crusts or sores in the nares, may indicate bacterial infection, particularly with S aureus. Other indicators of bacterial infection are skin pustules or impetigo and the presence of purulent signs in other family or household members.
Pharyngeal symptoms include sore or scratchy throat, odynophagia, or dysphagia. Sore throat is typically present at the onset of illness, although it lasts only a few days. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable sensation of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in a dry mouth, especially after sleep.
Cough may represent laryngeal involvement, or it may result from upper airway cough syndrome related to nasal secretions (postnasal drip). Cough typically develops on the fourth or fifth day, subsequent to nasal and pharyngeal symptoms.
Other manifestations are as follows:
The history alone is rarely a reliable differentiator between viral and bacterial pharyngitis. However, persistence of symptoms beyond 10 days or progressive worsening after the first 5-7 days suggests a bacterial illness. Assessment for group A streptococci warrants special attention.
The health status of contacts and local epidemiologic trends are important factors to consider. A personal history of rheumatic fever (especially carditis or valvular disease) or a household contact with a history of rheumatic fever increases a person's risk. Other factors include occurrence from November through May and patient age of 5-15 years.
Pharyngeal symptoms of sore or scratchy throat, odynophagia, or dysphagia are common. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable feeling of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Group A streptococcal infections often produce a sudden sore throat.
Fever increases the suspicion that infection with group A streptococci is present, as does the absence of cough, rhinorrhea, and conjunctivitis, because these are common in viral syndrome; however, symptoms overlap between streptococcal and viral illness.
Other manifestations are as follows:
A history of recent orogenital contact suggests possible gonococcal rather than streptococcal pharyngitis. However, most gonococcal infections of the pharynx are asymptomatic.[32]
The presentation of rhinosinusitis is often similar to that of nasopharyngitis, because many viral URIs directly involve the paranasal sinuses. Symptoms may have a biphasic pattern, wherein coldlike symptoms initially improve but then worsen. Acute bacterial rhinosinusitis is not common in patients whose symptoms have lasted fewer than 7 days. Unilateral and localizing symptoms raise the suspicion for sinus involvement.
In children with bacterial sinusitis, the most common signs are cough (80%), nasal discharge (76%), and fever (63%). In adults, the classic triad of facial pain, headache, and fever is not common.[7]
The 2013 American Academy of Pediatrics (AAP) guidelines define acute bacterial sinusitis in children as a URI with any of the following[3] :
Nasal discharge
Nasal discharge may be persistent and purulent, and sneezing may occur. Mucopurulent secretions are seen with viral and bacterial infections. Secretions may be yellow or green; however, the color does not differentiate a bacterial sinus infection from a viral one, because thick, opaque, yellow secretions may be seen with uncomplicated viral nasopharyngitis.[7]
Compared with allergy or viral infection, rhinorrhea may be less predominant, and not respond to decongestants or antihistamines. Congestion and nasal stuffiness predominate in some individuals.
Facial and dental pain
Facial or dental pressure or pain may be present. In older children and adults, symptoms tend to localize to the affected sinus. Frontal, facial, or retro-orbital pain or pressure is common. Maxillary sinus inflammation may manifest as pain in the upper teeth on the affected side. Pain radiating to the ear may represent otitis media, local adenopathy, or a peritonsillar abscess.
Sore throat and dry mouth
Sore throat may result from irritation from nasal secretions dripping down the posterior pharynx. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Mouth breathing may especially be noted in children. Dry mouth may be prominent, especially after sleep. Foul breath may be noted, because resident flora processes the products of the inflammatory process; this symptom may also occur with allergic rhinitis.
Cough
Frequent throat clearing or cough may develop as a result of nasal secretions (postnasal drip). Rhinosinusitis-related cough is usually present throughout the day. The cough may also be most prominent on awakening, because of secretions that have gathered in the posterior pharynx overnight.
Daytime cough that lasts more than 10-14 days suggests sinus disease, asthma, or other conditions. Nighttime-only cough is common in numerous disorders, in part because of reduced throat clearing and airway mechanics; many forms of cough are most noticeable at night.
Upper airway cough syndrome related to nasal secretions occasionally precipitates posttussive emesis; this may also occur with asthma. Clinically significant amounts of purulent sputum may suggest bronchitis or pneumonia.
Other
Hyposmia or anosmia may result from nasal inflammation. Fatigue or malaise may be seen with any URI.
This condition is more often found in children aged 1-5 years, who present with a sudden onset of the following symptoms:
Nasopharyngitis often precedes laryngitis and tracheitis by several days. Swallowing may be difficult or painful, and patients may experience a globus sensation of a lump in the throat. Hoarseness or loss of voice is a key manifestation of laryngeal involvement.
In adolescents and adults, laryngotracheal infection may manifest as severe dry cough following a typical URI prodrome. Mild hemoptysis may be present; however, hemoptysis may also be seen with tuberculosis and other conditions. Children with laryngotracheitis or laryngotracheobronchitis (croup) may have the characteristic brassy, seal-like barking cough. Symptoms may be worse at night. Diphtheria also produces a barking cough.
Myalgias are characteristic in influenza, especially in the setting of hoarseness with sudden sore throat, fever, chills, nonproductive cough, and headache. Fever may be present, but it is not typical in persons with croup. Fatigue or malaise may occur with any URI.
Whooping cough
In whooping cough, the classic whoop sound[4] is an inspiratory gasping squeak that rises in pitch, typically interspersed between hacking coughs. The whoop is more common in children. Coughing often comes in paroxysms of a dozen coughs or more at a time and is often worst at night.
Whooping cough has 3 classic phases, as follows:
Posttussive symptoms include gagging or emesis after paroxysms of whooping cough. Subconjunctival hemorrhage may result from severe cough. Rib pain with pinpoint tenderness worsening with respiration may reflect rib fracture associated with severe cough.
Dyspnea and increased work of breathing may be worse at night in patients with whooping cough, because of changes in airway mechanics while the patient is recumbent. Apnea may be a chief feature in infants with pertussis. Apnea may also result from upper airway obstruction due to other causes.
Patients with the common cold may have a paucity of clinical findings despite notable subjective discomfort. Findings may include the following:
Pharyngeal erythema is typically marked in adenoviral infection. In contrast, rhinoviral and coronaviral infections are not likely to manifest as severe erythema.
Exudates may occur in half the patients with adenovirus infections. Exudative pharyngitis and tonsillitis may be seen with mononucleosis caused by Epstein-Barr virus (EBV), while exudates are uncommon in rhinoviral, coxsackievirus, and herpes simplex virus (HSV) pharyngitis. Yellow or green secretions do not differentiate a bacterial pharyngitis from a viral one. Thick, yellow secretions are commonly seen with uncomplicated viral nasopharyngeal infections.
The presence of palatal vesicles or shallow ulcers is characteristic of primary infection with herpes simplex virus. Ulcerative stomatitis may also occur in coxsackievirus or other enteroviral infections, and mucosal erosions may also be seen in primary HIV infection. Small vesicles on the soft palate, uvula, and anterior tonsillar pillars suggest herpangina, which is caused by coxsackieviral infection.
Profuse nasal discharge is more characteristic of viral infections than bacterial infections. Initially clear secretions typically become cloudy white, yellow, or green over several days, even in viral infections. Halitosis may be noted, because resident flora processes the products of the inflammatory process.
Anterior cervical lymphadenopathy is seen with viral and bacterial infections. Approximately half of EBV mononucleosis cases involve generalized adenopathy or splenomegaly. An enlarged liver may also be palpable. Primary HIV infection can be another cause of lymphadenopathy.
Conjunctivitis may be seen with adenoviral pharyngoconjunctival fever and is present in one half to one third of all adenoviral URIs. Watery, injected conjunctiva may also be seen with allergic conditions.
Other signs that may accompany viral pharyngitis include the following:
This may be difficult to distinguish from viral pharyngitis. Assessment for group A streptococcal infection warrants special attention. The following physical findings suggest a high risk for group A streptococcal disease[1] :
Less common findings in streptococcal pharyngitis are petechiae of the palate and a scarlatiniform rash. These are not uniquely specific to this disorder.
Exudates manifest as white or yellow patches. A whitish coating may appear on the tongue, causing the normal bumps to appear more prominent. Yellow or green coloration does not differentiate bacterial pharyngitis from a viral disease, because thick, yellow secretions may be seen with uncomplicated viral nasopharyngitis. Foul breath may be noted because resident flora processes the products of the inflammatory process.
A whitish adherent membrane forming on the nasal septum, along with a mucopurulent blood-tinged discharge, should prompt consideration of diphtheria. Pharyngeal and tonsillar diphtheria may manifest as an adherent blue-white or gray-green membrane over the tonsils or soft palate; if bleeding has occurred, the membrane may appear blackish.
A peritonsillar abscess may manifest as unilateral palatal and tonsillar pillar swelling, with downward and medial tonsil displacement; the uvula may tilt to the opposite side. Bulging of the posterior pharyngeal wall may signal a retropharyngeal abscess.
Tender anterior cervical adenopathy may be part of the presentation in patients with streptococcal or viral infections. In persons with diphtheria, submandibular and anterior cervical edema may be present along with adenopathy.
Fever is more likely to occur in group A streptococcal infections than in other URIs, although it may be absent. Temperatures around 38.3°C (101°F) may occur in group A streptococcal infection.
Rash may be seen with group A streptococcal infections, particularly in patients younger than 18 years. The scarlet fever rash appears as tiny papules over the chest and abdomen, creating roughness similar to sandpaper and producing a sunburned appearance. The rash spreads, causing erythema in the groin and armpits. The face may be flushed, with pallor around the lips. Approximately 2-5 days later, the rash begins to resolve. Peeling is often noted on the tips of toes and fingers.
Cutaneous diphtheria may appear as a scaling rash or as well-demarcated ulcers with membranes. Neisseria gonorrhoeae infection may also cause a rash.
Uncommon findings in bacterial pharyngitis include the following:
In the setting of acute pharyngitis, the presence or absence of preexisting cardiac murmurs should be documented for comparative purposes in case rheumatic fever later develops.
This is most often viral; however, differentiating common viral illnesses from uncommon bacterial cases on clinical grounds alone can be challenging. Suspicion is raised for acute bacterial rhinosinusitis when symptoms last more than 7 days and when the patient has maxillary pain or tenderness in the face or teeth (especially unilateral), headache, and purulent nasal secretions. Occasionally, patients with acute bacterial sinusitis present with severe symptoms, especially unilateral facial pain, even when symptoms have not lasted at least 7 days.
However, the classic triad of fever, headache, and facial pain occurs uncommonly in adults with bacterial sinusitis; in children with bacterial sinusitis, nasal discharge is present in 76% of patients and fever is found in 63%.[7] Foul breath may be noted, because resident flora processes the products of the inflammatory process.
The paranasal sinuses develop and enlarge after birth; ethmoid and sphenoid sinuses may not be of significant size until age 3-7 years. The frontal sinuses are the last to develop and may not be of significant size until adolescence.
Exudates
Mucopurulent secretions may be present in the nares with either viral or bacterial sinusitis. A lighted nasal speculum directed posteriorly allows the clinician to view secretions emanating from the area of the middle meatus. Secretions may be thick and yellow; however, color does not differentiate a bacterial sinus infection from a viral one. Thick, yellow secretions may be seen several days into the course of uncomplicated viral nasopharyngitis.
Rhinitis
When rhinitis is present, nasal mucosa may be inflamed. Typical findings include swelling and redness of the turbinates. In many cases of sinusitis, the nares serve only as a conduit for purulent secretions, and the nasal mucosa may not be inflamed. Pallor and edema may be associated with underlying allergic rhinitis. The presence of unilateral signs suggests sinus involvement rather than uncomplicated rhinitis.
Preexisting obstructions
Nasal obstruction due to preexisting polyps or septal deviation may contribute to sinusitis. It is best appreciated upon direct inspection with nasal endoscopy.
Facial tenderness
Facial tenderness to palpation or percussion may be present and most easily appreciated over the frontal or maxillary sinuses. Percuss and apply digital pressure to the forehead above the brow to evaluate frontal sinus area tenderness. The floor of the frontal sinuses may be approached by pressing upward on the supraorbital area of the skull beneath the eyebrows.
Maxillary sinuses are posterior to the cheekbones; use digital pressure and percussion on the cheeks to elicit tenderness. Tapping on the upper teeth with a tongue depressor may evoke pain in the corresponding maxillary sinus. The floor of the maxillary sinuses may be approached by pressing upward on the palate.
Ethmoid sinuses are between the eyes and behind the nasal bridge. Palpate the area around the middle canthus to assess the ethmoids. The sphenoid sinuses are deep to the ethmoids and behind the eyes. Evaluating the ethmoid and sphenoid sinuses during routine physical examination is challenging. Periorbital swelling may be present in ethmoid sinusitis.
Sinus opacity
Sinus cavity opacity on transillumination suggests sinusitis. Opacity is best appreciated in a completely darkened room. Place the illuminator directly on the skin at the level of the infraorbital rim to evaluate the maxillary sinuses and at the medial aspect of the supraorbital rim to evaluate the frontal sinuses. The maxillary sinuses may also be transilluminated by placing a light beam inside the patient's mouth against the palate directed upward.
Bright transmission of light suggests a normal air-filled sinus; absent light transmission suggests the presence of fluid. This approach depends on the examiner's skill and experience, and results are best interpreted along with other findings. Transillumination findings may be unreliable in children. The frontal sinuses may not begin to develop until age 5-8 years.
Intracranial suppurative complications
Suspect an intracranial suppurative complication (eg, abscess) when the examination reveals signs such as the following:
Direct visualization is the best way to confirm the diagnosis of epiglottitis. However, such examination may compromise the airway. Therefore, in suspected epiglottitis, limit the examination to observation and an assessment of the vital signs. Oropharyngeal examination performed by using a tongue depressor or speculum can provoke laryngospasm. Direct visualization of the upper airway should be performed only when emergency endotracheal intubation or cricothyroidotomy can be safely performed if necessary.
Physical findings associated with epiglottitis include the following:
Respiratory distress in patients with epiglottitis may manifest as tachypnea, tachycardia, and the use of accessory muscles of respiration. Observe the patient for rib retractions, use of strap muscles, and perioral cyanosis. In response to respiratory distress, patients with epiglottitis may assume the classic tripod position: sitting upright, supported by the hands, with the tongue out and head forward.
Many patients with croup or laryngotracheitis are less ill than they sound. In severe cases, however, children may have respiratory fatigue that leads to respiratory failure.
Hoarseness is a hallmark of laryngeal involvement. Lowered vocal pitch and loss of voice may occur.
Dry cough may be present with laryngeal involvement. Children with laryngotracheitis or croup may have the characteristic brassy, seal-like barking cough. A barking cough may also be present in diphtheria laryngitis. In whooping cough, the classic whoop sound[4] is an inspiratory gasping squeak that rises in pitch, typically interspersed between hacking coughs. The whoop is more common in children than in adults.
Inspiratory stridor may be audible with croup or whooping cough. It typically can be heard without a stethoscope, but it is especially obvious with the stethoscope placed on the anterior aspect of the trachea during inspiration.
Mild hemoptysis may be present; however, hemoptysis made also be seen with tuberculosis and other conditions. Clinically significant amounts of purulent sputum may suggest bronchitis or pneumonia.
Respiratory compromise manifests as tachypnea, tachycardia, and the use of accessory muscles of respiration. Diminished breath sounds in association with pallor and cyanosis may indicate impending respiratory failure.
Paroxysms of coughing may produce conjunctival hemorrhages. Petechial hemorrhages may be noted in the upper body, resulting from severe paroxysms of coughing, such as those associated with whooping cough. Rib fracture, with pinpoint tenderness worsening with respiration, may result from severe coughing, such as that seen in whooping cough.
Lymphadenopathy may be present in the anterior cervical nodes. Fever may be present, but it is not typical in persons with croup. Fever may be seen with influenza laryngitis.
In upper respiratory tract infections (URIs), tests for specific pathogens are helpful when targeted therapy depends on the results (eg, group A streptococcal infection, gonococcus, pertussis). Specific bacterial or viral testing is also warranted in other selected situations, such as when patients are immunocompromised, during certain outbreaks, or to provide specific therapy to contacts. There is insufficient evidence that testing for atypical bacteria (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae) would improve clinical outcomes in pharyngitis.[33]
Targeted therapy is not available for most viruses that cause URI. Therefore, viral testing is rarely indicated for uncomplicated viral URIs in the outpatient setting. However, confirmation of a viral condition such as influenza may reduce inappropriate use of antibiotics. In addition, URI suspected to be due to herpes simplex virus (HSV) warrants diagnosis because specific therapy is available for this infection.
Testing may be required if progressive URI symptoms last longer than 14 days and have no other identifiable cause, such as asthma or allergic rhinitis. Testing is also indicated if the clinical assessment suggests sexually transmitted disease–related oropharyngeal disease; specific therapy exists for pathogens such as Neisseria gonorrhoeae.
With immunocompromised patients, specific information about infection may help to tailor antimicrobial choices, herald potential complications, and aid in determining whether hospitalization would be appropriate. Viral testing may be used for making the diagnosis, monitoring the patient, or predicting the prognosis.
Culturing of throat swabs, nasal swabs or washes, or nasal aspirates remains the standard for confirming bacterial URI pathogens. Samples should be taken from the posterior pharynx or tonsils, not from the oral cavity. In typical circumstances, rapid antigen detection tests for group A strep need not be routinely backed up by cultures in adults.[2]
For pharyngitis, a throat swab may be performed by vigorously rubbing a dry swab over the posterior pharynx and both tonsils to obtain a sample of exudates, if any exist. Avoid touching other surfaces of the oropharynx. Samples should be transported dry.
To perform a nasal wash, fill a small syringe (3-5 mL) with sodium chloride solution and attach a short length of flexible tubing. With the patient's head tilted back, instill the solution rapidly into the nostril, then immediately aspirate secretions back into the syringe and transfer the aspirate to laboratory specimen containers.
Nasopharyngeal specimens are indicated for suspected pertussis; the sample can be used for culture and for polymerase chain reaction (PCR) assay.[34] Special selective growth media are required for Corynebacterium diphtheriae. This organism must be distinguished from the diphtheroids that commonly inhabit the nasopharynx. Neisseria gonorrhoeae also requires special culture media.
For confirming viral nasopharyngeal infection, viral cultures remain the standard. Throat swabs, nasal swabs or washes, or sputum may be cultured on special viral media to detect influenza virus, parainfluenza virus (PIV), adenovirus, respiratory syncytial virus (RSV), and other viruses. Culturing may require days to weeks.
Rapid tests for viruses include various antigen, immunofluorescence, and PCR assays. Rapid tests for influenza can be conducted on specimens from nasopharyngeal swabs, washes, or aspirates, yielding results within 30 minutes. Swabs should be taken from the posterior pharynx or tonsils, not from the oropharynx.
Enzyme immunoassays are available to detect PIV in respiratory secretions. Reverse transcriptase PCR assay may detect various viruses in nasopharyngeal samples. PCR assay detection of various viruses from blood samples is emerging as a way to track certain viral infections.
Antibody titers compared between paired specimens obtained weeks apart may help in retrospectively identifying a particular pathogen in immunocompetent patients. The first sample should be obtained during the first week of illness, and the second should be obtained 2-4 weeks later.
On complete blood count (CBC) with differential, patients with URIs may have an increased white blood cell (WBC) count with a left shift. Atypical lymphocytes, lymphocytosis, or lymphopenia may be seen in some viral infections; lymphocytosis may also be seen in pertussis.
However, a CBC is not likely to be helpful in differentiating the infectious agent or in directing therapy in uncomplicated URIs in the outpatient setting. Blood cultures are typically appropriate only in hospitalized patients with suspected systemic illness.
Imaging studies are not indicated for the common cold. On the other hand, suspected mass lesions, such as a peritonsillar abscess or intracranial suppurative lesions, warrant imaging. If the patient's history and physical findings suggest lower respiratory tract disease, chest imaging may be useful. Similarly, routine acute rhinosinusitis (ie, during the first weeks of symptoms) does not require imaging unless suppurative complications or structural anomalies are suspected. In laryngitis, radiographs are of little use except to exclude foreign-body aspiration.
Laryngotracheitis in a patient with typical symptoms that respond appropriately to treatment does not require imaging. Laryngoscopy may be considered, however, if the patient is not in extremis. Hemoptysis or the presence of risk factors for tuberculosis should prompt consideration for tuberculin testing and chest radiography.
In laryngotracheobronchitis (croup), soft-tissue neck images may reveal the classic steeple sign, which represents subglottic narrowing. However, this sign is not always present and is not specific for croup.
The diagnosis should be pursued on the basis of clinical findings or a history of exposure to a case, supported by results of rapid-detection assays and cultures. Patients with a personal history of rheumatic fever or a household contact with a history of rheumatic fever are at high risk for group A streptococcal infection. In addition, the following features may raise suspicion for group A streptococcal disease[1] :
The 2012 Infectious Diseases Society of America (IDSA) guidelines recommend that swabbing the throat and testing for group A streptococcal pharyngitis by rapid antigen detection testing, culture, or both should be performed to diagnose group A streptococcal pharyngitis.[2] The rationale is that clinical features alone do not reliably discriminate between streptococcal and viral pharyngitis, except when overt viral features (eg, rhinorrhea, cough, oral ulcers, and/or hoarseness) are present.
The IDSA guidelines also suggest that diagnostic studies for group A streptococcal pharyngitis are not indicated in children under age 3 years, as acute rheumatic fever and a classic presentation of strep throat are uncommon in this age group. However, selected children under age 3 years who have other risk factors (eg, an older sibling with known infection) may be considered for testing.[2]
Positive rapid antigen detection tests are highly specific and therefore do not necessitate a backup culture. Negative tests should be backed up by a throat culture in children and adolescents. Routine backup throat culture for adults with a negative rapid strep test is not typically necessary, due to the low incidence of streptococcal pharyngitis in adults and the low risk of subsequent acute rheumatic fever. Testing of asymptomatic household contacts of patients with acute streptococcal pharyngitis is not routinely recommended.[2]
Cultures may be falsely negative for group A streptococci, because of inadequate specimen collection, covert use of antibiotics, or suboptimal laboratory practices. In addition, prolonged illness may reduce the sensitivity of culture. Specimens are optimally obtained in the first 4 days of illness. Some patients may be chronically colonized with group A streptococcus.
The level of streptococcal antibodies (antistreptolysin O) does not peak until 4-5 weeks after the onset of pharyngitis. Therefore, testing for these antibodies has no role in the diagnosis of acute pharyngitis.
Laboratory studies are generally not indicated in cases of suspected acute bacterial rhinosinusitis, because the causative agents in immunocompetent individuals are well characterized.[7] (See Acute Sinusitis.)
Computed tomography scanning
Imaging studies are not indicated for routine acute rhinosinusitis (ie, during the first 4 weeks of symptoms). A negative study may be helpful in ruling out rhinosinusitis, but imaging studies do not help in distinguishing bacterial from viral disease, because no diagnostic signs are unique to bacterial sinus infection. Moreover, although sinus CT scanning is highly sensitive, its specificity for demonstrating acute sinusitis is low; 40% of asymptomatic patients and 87% of those with common colds have sinus abnormalities.[16]
In children, the lack of fully developed sinuses poses challenges in image interpretation. The frontal sinuses do not typically appear until age 5-8 years, and they may not develop fully in all individuals.
If rhinosinusitis symptoms persist despite therapy or if complications (eg, extension of disease into surrounding tissue) are suspected, sinus imaging may be appropriate to evaluate the anatomy. Signs or symptoms consistent with intracranial extension of infection warrant CT scanning to evaluate the possibility of an intracranial abscess or other suppurative complication. Such symptoms may include the following:
CT scanning yields more detailed information than plain radiography, especially regarding the ostiomeatal complex. Such information may be relevant to surgical planning. Common CT scan findings include mucosal thickening, air-fluid levels, and obstruction of the ostiomeatal complex. Not all patients with acute rhinosinusitis have air-fluid levels. The image below reveals sinusitis on a CT scan.
View Image | CT scan of the sinuses demonstrates maxillary sinusitis. The left maxillary sinus is completely opacified (asterisk), and the right has mucosal thicke.... |
Other imaging studies
If a patient cannot tolerate CT scanning, a plain radiographic Waters view of the frontal and maxillary sinuses may be considered. Most cases of rhinosinusitis involve the maxillary and frontal sinuses, so views that include these sinuses are important. Common radiographic findings include air-fluid levels and mucosal thickening, although not all sinusitis patients have air-fluid levels.
Sinus ultrasonography may be considered when pregnancy or radiation exposure is a concern. Ultrasonography may also be useful in the intensive care unit to evaluate nosocomial sinusitis.[35] Magnetic resonance imaging (MRI) may be optimal for evaluation of suspected fungal sinusitis or suspected tumor.
The sinus puncture and aspiration procedure has no role in the routine assessment of acute rhinosinusitis. However, maxillary sinus puncture and aspiration performed by an otolaryngologist may be indicated in patients with any of the following:
Rigid nasal endoscopy is a less robust option than sinus puncture because of specimen contamination by nasal flora. Respiratory flora also commonly contaminates nasal swabs and washes.
In cases of suspected influenza, confirmation of a serotype-specific diagnosis may direct options for antiviral therapy. Testing may also assist the clinician in avoiding unnecessary prescriptions for antibacterials. Most rapid tests to detect influenza that are performed in a physician's office have a sensitivity of approximately greater than 70% and a specificity of approximately greater than 90%. Therefore, viral culture may yield a positive result in up to 30% of cases with negative rapid influenza test results.[27]
For information on testing and case management of suspected influenza, see the Medscape Reference article Influenza.
In a person with sore throat, lymphadenopathy, and hepatosplenomegaly, testing may be required to confirm infectious mononucleosis. Confirmation may be helpful in guiding outpatient care and expectations. A positive result on a heterophile antibody test (eg, Monospot) is diagnostic.
Heterophile antibody levels are moderate to high in the first month of illness and decrease rapidly thereafter. Monospot results are positive in more than 85% of cases. False-positive results are seen in a few patients; false-negative results are seen in 10-15% of patients, primarily children younger than 10 years.[23]
In patients with mucocutaneous lesions suggestive of HSV infection, isolation of the virus in cell culture is the preferred virologic testing strategy. As lesions begin to heal, the sensitivity of culturing rapidly declines. Cytologic detection of cellular changes of HSV infection is insensitive and nonspecific and should not be relied on for diagnosis of HSV infection.[36] Testing with polymerase chain reaction (PCR) assay is available in some laboratories.
Pertussis is clinically diagnosed on the basis of symptoms of whooping cough. When bacteriologic confirmation is sought, the receiving laboratory should be contacted for special instructions on specimen collection. Culture of a nasopharyngeal aspirate is the criterion standard.[37] Nasopharyngeal aspirates are ideally collected 0-2 weeks after symptom onset but may provide accurate results for as long as 4 weeks in infants and unvaccinated patients.
Rapid direct fluorescent antibody testing is available to test for pertussis. Although PCR assay for pertussis is emerging as a sensitive detection tool, respiratory illness outbreaks mistakenly attributed to pertussis highlight the limitations of relying solely on PCR assays to confirm the disease. The positive predictive value is lower when PCR assay is used as a screening tool without culture confirmation during a suspected pertussis outbreak.[21]
Serologic testing is optimally performed 2-8 weeks after symptom onset, when antibody titers are highest. However, testing may be performed on specimens as long as 12 weeks after symptom onset.
In cases of suspected epiglottitis, aggressive instrumentation may precipitate spasm and airway compromise. If the diagnosis is suspected in patients not in extremis, an otorhinolaryngologist may perform direct visualization by laryngoscope to confirm the disease. Immediate access to intubation and cricothyroidotomy equipment is required. This diagnostic procedure is often performed in the operating room.
Laryngoscopy provides an opportunity for obtaining culture samples; however, contamination of the samples by upper airway flora is common. Direct visualization by laryngoscope is the standard for confirming epiglottitis.
During the procedure, a swab sample may be taken for culturing. However, because of contamination with upper airway flora, such cultures are not ideal unless an aspirate is taken from an epiglottic abscess. Therefore, blood cultures should also be ordered. Blood cultures for Haemophilus influenzae are positive in more than 80% of children and in approximately 25% of adults.[38]
Before ordering radiography, consider whether imaging may unnecessarily delay patient care. Note that patients with epiglottitis breathe most comfortably when they are upright; the supine position may precipitate respiratory compromise. For patients in whom the diagnosis of epiglottitis is uncertain, a lateral neck image obtained in the erect position with soft-tissue technique may be indicated.
In one small, retrospective study, lateral neck radiographs were 33% specific for epiglottitis, with a positive predictive value of only 50%; the negative predictive value was 100%.[39] Given the high false-positive rate, the authors concluded that the role of radiography was limited in epiglottitis. However, neck imaging may help to rule out the disease. Radiographic findings include a swollen epiglottis with a shape similar to the human thumb. The image below illustrates epiglottitis on a neck radiograph.
View Image | Lateral neck radiograph demonstrates epiglottitis. Courtesy of Marilyn Goske, MD, Cleveland Clinic Foundation. |
CT scanning may be superior to radiography in delineating the soft-tissue structures in the upper airway. However, CT scanning may unnecessarily delay therapy, and recumbent positioning may precipitate respiratory compromise.
Most upper respiratory tract infections (URIs) are self-diagnosed and self-treated at home. Patients who present with URIs often benefit from reassurance, education, and instructions for symptomatic home treatment.
Symptom-based therapy represents the mainstay of URI treatment in immunocompetent adults, although antimicrobial or antiviral therapy is appropriate in selected patients (see Medication). Several URIs warranting special attention are described in this section.
In November 2013, The American Academy of Pediatrics released a set of three basic principles for the effective use of antibiotics to treat pediatric URIs, including acute otitis media, acute bacterial sinusitis, and streptococcal pharyngitis.[40, 41] The principles are as follows:
These principles will help healthcare providers distinguish bacterial infections from viral infections.
Little et al evaluated the effectiveness of delayed antibiotic prescribing strategies for respiratory tract infections in 889 United Kingdom primary care patients (age ≥3 y) assessed as not requiring immediate antibiotics. They reported that using strategies of either no or delayed prescription resulted in fewer than 40% of the patients across 25 practices using antibiotics.[42] Delayed prescribing strategies consisted of recontact for a prescription, postdated prescription, collection of the prescription, and giving the prescription (patient led).
Moreover, no or delayed prescription strategies were associated with patients having less strong beliefs in the use of antibiotics, and symptomatic outcomes were similar to those observed in patients who received immediate prescription.[42]
The risk for airway compromise is notable, especially in children. Immediately admit the patient to the nearest hospital. Adults with epiglottitis typically have a relatively gradual course. However, some older children and adults may have respiratory compromise, especially those with congenital or acquired subglottic stenosis.
The treatment of epiglottitis in adults requires individual tailoring of therapy on the basis of the severity of the disease at presentation and the course of the disease as it unfolds under observation. An anesthesiologist or otorhinolaryngologist should be involved early on.
Avoid instrumentation in suspected epiglottitis. Limit the examination to observation and an assessment of the vital signs. Insertion of tongue depressors or other instruments may provoke airway spasm and precipitate respiratory compromise. Keep the patient comfortable, and avoid unnecessary examinations.
Patients must be monitored for respiratory fatigue, visually and with continuous pulse oximetry. Because immediate intubation is required in the event of respiratory failure, the availability of equipment and qualified personnel is critical. If endotracheal intubation is not possible, cricothyroidotomy may be required.
Oxygen is administered according to pulse oximetry results. Dry air may worsen inflammation, so the use of humidified oxygen or a room humidifier is recommended.
Presumptive intravenous antibiotics are indicated, tailored to results from blood cultures. Empiric coverage for Haemophilus influenzae is appropriate. Antibiotic therapy should begin after blood cultures (and epiglottic cultures, if laryngoscopy is performed) are taken. Common choices include ceftriaxone or other third-generation cephalosporins, cefuroxime, and cefamandole. After culture and sensitivity results are available, therapy may be further tailored. Close contacts should receive prophylactic oral therapy.
Either intravenous or inhaled glucocorticoids are sometimes given to reduce inflammation. However, controlled trials of the effectiveness of this approach in epiglottitis are limited. Correct volume deficits with intravenous fluids. Avoid sedatives that may suppress the respiratory drive.
Aerosolized racemic epinephrine is sometimes used to reduce mucosal edema in patients with croup, but its value in epiglottitis is not defined, and adverse events have been reported in patients with this disorder.[43] Beta2 -agonists are not typically used in patients who do not have asthma.
Hospitalization may be necessary in patients with laryngotracheitis, especially in infants and young children who have hypoxemia, volume depletion, a risk for airway compromise, or respiratory fatigue. Mild cases of croup (ie, laryngotracheobronchitis) may be managed at home with moist air inhalation. Patients with diphtheria may require isolation and hospitalization for airway management.
Hospitalized patients require monitoring for respiratory fatigue, visually and with continuous pulse oximetry. Clinicians with the expertise to perform immediate intubation and access to the necessary equipment are required if respiratory failure is a possibility. If endotracheal intubation is not possible, cricothyroidotomy is indicated for respiratory failure. Keep the patient comfortable, and avoid unnecessary procedures and examinations.
Administer humidified oxygen to all hypoxemic patients. In patients who do not require oxygen therapy, a cool-mist humidifier may be used, as dry air may worsen inflammation. Heliox, a mixture of helium and oxygen, compared favorably with inhaled racemic epinephrine in a small study of pediatric patients with moderate to severe croup.[44]
Intravenous or oral glucocorticoids are commonly used to reduce symptoms and shorten hospitalization in patients with moderate to severe croup. Inhaled steroids may be considered in cases that are not severe; however, evidence from large, controlled trials regarding the use of inhaled steroids in croup is lacking.
Inhaled racemic epinephrine may temporarily dilate the airways by relaxing bronchial smooth muscle and causing vasoconstriction that may reduce mucosal inflammation. Epinephrine may be considered in patients with persistent stridor. Because rebound edema may occur when inhaled epinephrine is stopped, monitoring and observation is required for several hours afterward.
In patients with croup, the use of steroids may reduce the need for epinephrine. In patients with whooping cough, evidence is insufficient to justify the use of long-acting beta agonists, antihistamines, or pertussis immunoglobulin.[45] Antibiotics are appropriate for whooping cough (pertussis); however, croup is typically a viral condition. Blood cultures should be ordered.
Correct volume deficits with intravenous fluids. Avoid sedatives that may suppress the patient's respiratory drive.
Acute maxillary-and-ethmoid bacterial rhinosinusitis in immunocompetent adults diagnosed in the outpatient setting is most often related to uncomplicated viral URIs. Most cases of acute rhinosinusitis, including mild and moderate cases of bacterial sinusitis, resolve without antibiotics.[6] Data from controlled trials indicated that more than half of adults and children improved within 3-10 days of treatment with placebo; however, the data also showed that at both time points, the use of amoxicillin increased the percentage of patients who improved.
The 2012 Infectious Disease Society of America (IDSA) guidelines on sinusitis recommend considering treatment if symptoms persist without improvement for 10 days or longer or if symptoms are severe or worsen during a period of 3-4 days or longer.[7] The 2013 American Academy of Pediatrics (AAP) guidelines recommend antibiotic treatment for children with severe onset or a worsening course; however, in children with persistent illness, clinicians should either treat the patient or observe him/her for an additional 3 days.[3]
First-line antibiotics for 5-7 days are appropriate in most adults; 2012 IDSA guidelines recommend 10-14 days of treatment in children. Patients at risk for antimicrobial resistance include the following:
For such patients, second-line antibiotics for 7-10 days is recommended. If symptoms do not improve in 3-5 days, broadening coverage to another antibiotic class may be considered.
Treatment should begin with an agent that most narrowly covers likely pathogens, including Streptococcus pneumoniae, nontypeable H influenzae, and Moraxella catarrhalis. Initial first-line options include amoxicillin/clavulanate.[7] High-dose therapy (2 g orally twice daily or 90 mg/kg/day orally twice daily) may be considered in geographic regions where invasive penicillin sensitivity is 10% or greater, as well as in patients with any of the following:
Per IDSA guidelines, in penicillin-allergic patients, doxycycline is an alternative, as are respiratory fluoroquinolones such as levofloxacin or moxifloxacin. Macrolides, trimethoprim-sulfamethoxazole, and second- or third-generation cephalosporins are not recommended for empirical therapy, due to high rates of S pneumoniae resistance.
In patients who worsen or do not improve after 3-5 days of empiric therapy, guidelines recommend exploration for resistant pathogens, structural abnormality, or noninfectious etiology. In such patients, cultures should be obtained by direct sinus puncture or middle meatus endoscopy rather than with nasopharyngeal swabs.[7]
Adjunctive therapy for adults includes nasal saline irrigation. Intranasal steroids may be considered, especially for those with a previous history of allergic rhinitis. Neither oral nor nasal antihistamines or decongestants are recommended for acute bacterial sinusitis.[7]
Beginning treatment of group A streptococcal disease before positive results are confirmed is not ideal, because therapy is often inadvertently continued even if the results are negative. Chronic carriage of group A streptococcus does not warrant antibiotic treatment.
Oral penicillin or amoxicillin for 10 days is recommended for group A streptococcal pharyngitis in patients without an allergy to penicillin. No group A streptococci are resistant to penicillin, and this treatment is effective for treating pharyngitis and for preventing acute rheumatic fever.[2] If compliance with oral therapy is a concern, consider a single intramuscular injection of benzathine penicillin G.
A first-generation cephalosporin may be used in patients with non-anaphylactic penicillin allergy. Options for penicillin-allergic patients include clindamycin or clarithromycin for 10 days or azithromycin for 5 days.[2] For patients with recurrent or complicated group A streptococcal infections, cephalosporins may be appropriate.
In general, relapse of group A streptococcal disease may be treated with the same regimen as before or with a different one. In cases of relapse, determine whether adherence to previous therapy was sufficient. If adherence to oral therapy is a concern, consider a single injection of benzathine penicillin in patients not allergic to penicillin.
Patients who experience repeated bouts of acute pharyngitis with laboratory evidence of group A streptococcal infection may be experiencing actual streptococcal pharyngitis episodes. However, such patients may potentially be chronic pharyngeal streptococcal carriers who are experiencing repeated viral infections.
The 2012 IDSA guidelines suggest that efforts to identify group A Streptococcus carriers are not ordinarily justified, nor do carriers generally require antimicrobial therapy. Group A Streptococcus carriers are unlikely to spread streptococcal pharyngitis to close contacts, and they are at little or no risk for developing suppurative or nonsuppurative complications themselves.[2]
Adjunctive therapy for strep pharyngitis includes pain relievers; aspirin should be avoided in children due to risk of Reye syndrome. Corticosteroids are not recommended.[2]
Specific therapies are available for gonococcal and herpes simplex virus (HSV) pharyngitis. Gonococcal pharyngitis may be difficult to eradicate. Gonococcal therapy is typically a single intramuscular dose of ceftriaxone. Although coincident Chlamydia trachomatis pharyngitis is rare, Chlamydia coinfection in gonococcal urethritis, cervicitis, or proctitis sometimes occurs, so treatment for gonococcus and chlamydia are often combined.[32] HSV pharyngitis may be treated with antivirals. See Herpes Simplex for additional details.
Pertussis (whooping cough) infection warrants treatment with a macrolide antibiotic. Close contacts should receive prophylactic treatment.
Diphtheria warrants treatment with a macrolide or penicillin. Diphtheria antitoxin may neutralize circulating (unbound) toxin. Sensitivity testing is required before antitoxin is used. The US Centers for Disease Control and Prevention (CDC) provides guidance on the availability and use of this antitoxin.
For treatment options in seasonal influenza, see Influenza. The CDC tests circulating influenza viruses for resistance patterns to antiviral medications and issues treatment guideline updates each influenza season.[46]
Special attention is warranted in patients with suboptimal immune defenses, for reasons including the following:
Appropriate antimicrobial therapy and close follow-up may be appropriate, because a simple URI may quickly progress to a systemic illness in immunocompromised patients. Although the threshold for hospitalization is lowered for these patients, their risks of nosocomial infections must be weighed against the benefits of close monitoring in the inpatient setting.
Although antivirals do not generally play a role in most cases of upper respiratory tract disease, consider available treatment options for HSV pharyngitis, respiratory syncytial virus (RSV) infection, and cytomegalovirus (CMV) infection in immunocompromised patients.
HSV infection may be treated with acyclovir, famciclovir, or valacyclovir. For CMV infections, consider foscarnet or ganciclovir. RSV infections may respond to ribavirin. If lower respiratory tract disease is evident, these considerations become more compelling than for isolated URI.
Deep tissue infections of adjacent structures, such as a peritonsillar, oropharyngeal, intraorbital, or intracranial abscess, warrant hospitalization and immediate consultation with a surgeon. These infections may compromise the airway, vision, or neurologic function.
Repeated streptococcal infection may be an indication for surgical intervention. In patients with 4-5 confirmed group A streptococcal infections in a single year or in those with chronic sore throat with adenopathy that is not responsive to treatment over 6 months, tonsillectomy may be considered. For more information, see Tonsillectomy.
In a study from the Netherlands of children aged 1-6 years with recurrent URI, adenoidectomy did not reduce URI episodes compared with initial watchful waiting.[47] (Adenoidectomy rates in the Netherlands are several times that in the United States.)
Surgery is rarely warranted in acute rhinosinusitis but may be considered under the following circumstances:
If possible, the sinus mucosa should be left intact during sinus surgery. Functional endoscopic sinus surgery is designed to promote drainage of the sinuses by altering the ostiomeatal complex. For surgical management of chronic sinusitis, see Chronic Sinusitis.
The following home-care measures may help to provide relief of nasal and sinus symptoms:
Nasal and paranasal sinus mucosae may become more irritated with dry air. The following strategies may maintain the moisture of membranes and loosen nasal secretions:
If a vaporizer is used, the water must be changed daily to prevent microbial growth, especially with heated vaporizers. Heated systems may pose a risk for scalding injuries.
One way to provide moist, warm air is to pour boiled water into a shallow pan or bowl placed in a stable location (eg, middle of a kitchen counter) and have the patient drape a cloth over his/her head and lean over the bowl to inhale the steam. Exercise caution to avoid spilling boiling water, which may cause scalding injuries.
Sipping hot water or warm drinks may be more soothing to the nasal passages than ice cold drinks. Avoid extremely cool and dry air.
Nasal saline may provide temporary relief of congestion by removing nasal crusts and dried secretions. A systematic review of nasal saline irrigation as an adjunct in chronic rhinosinusitis symptom management concluded that the evidence shows symptom relief and that irrigation is well tolerated by most patients.[48] Patients with sinusitis experienced symptomatic benefit from use of a neti pot method of nasal irrigation.[49]
Saline drops or sprays are commercially available. A homemade normal saline solution can be prepared by placing a quarter of a teaspoon of table salt in 8 oz of water. A bulb syringe, dropper, clean pump spray bottle, or squeeze bottle can be used to instill the saline into each nostril while the person inhales and then expels the saline. Saline is safe to use as needed.
Drinking 8 or more 8-oz glasses of water, juice, or noncaffeinated beverages daily may help to thin mucous secretions and replace fluid losses. Patients with congestive heart failure or renal or liver disease may need to moderate their fluid intake to avoid volume excess.
Warm facial packs may provide comfort, relieve congestion, and promote drainage in cases of rhinosinusitis. A warm, folded washcloth or hot-water bottle (filled with hot water from a tap) may be applied directly to the face and cheek for 5-10 minutes. Facial packs may be repeated 3-4 times a day as needed.
For infants, a bulb syringe can be used to gently suction the nostrils before feeding to ease nasal breathing. Parents should clean the bulb after each use with hot soapy water followed by a rinse. Drain the bulb and allow it to dry before reuse.
Home-care measures to relieve throat symptoms include warm saline gargles, which may reduce associated edema; lozenges; popsicles; and cold and slushy beverages. Avoid choking hazards in small children.
Home-care measures to relieve cough include reducing irritating stimuli (eg, cold, dry air; indoor or outdoor air pollutants) that may provoke coughing. An upright or semiupright posture, such as sleeping with the head and shoulders raised, may decrease cough related to pharyngeal secretions. A 2007 study showed that honey was superior to dextromethorphan in reducing cough symptoms and improving sleep in children with URI.[50]
Home-care measures to improve sleep include sleeping with the head and shoulders slightly elevated, which may promote sinus and nasal drainage. Many symptoms worsen at night, because airway clearance mechanics are relatively ineffective in the prone position. In addition, distractions from the experience of symptoms are fewer than during the day.
Under normal circumstances, the 2 nares alternate between being open or closed throughout the day. Cycles last approximately 45-90 minutes per naris. When the person is lying recumbent on one side, the naris closest to the pillow or surface tends to become congested, while the higher nostril is decongested. During nasal congestion associated with URI, alternating positions or lying with the shoulders and head propped up may increase comfort.
Treatment of an uncomplicated URI is focused on specific measures to reduce symptoms, including use of the following:
Oral decongestants may provide symptom relief for patients with persistent rhinorrhea or sneezing associated with URI. However, despite common usage, evidence regarding the effectiveness of oral decongestants in acute sinusitis is scarce.
Adverse effects of oral decongestants include the following:
Exercise caution in patients with heart disease, hypertension, prostate enlargement, glaucoma, anxiety, hyperthyroidism, or other medical conditions and in pregnant or lactating women. Unlike topical nasal decongestants, oral decongestants do not appear to cause rebound phenomena after cessation of use.
The risk-to-benefit ratio for using cough and cold medicines in children younger than 2 years requires careful consideration because serious adverse events, including fatalities, have been reported with the use of over-the-counter preparations.[51] Numerous over-the-counter cough and cold preparations are labeled "do not use" in children younger than 4 years.[52]
Topical decongestants such as phenylephrine and oxymetazoline may provide rapid temporary relief of nasal obstruction. However, rebound congestion may occur after cessation of use. To avoid this rebound congestion, limit topical agents to 3-4 days of use. In addition, these decongestants may cause throat irritation in some individuals.
One study, in which oxymetazoline was administered to patients with a nasal bellows, suggested that oxymetazoline did not accelerate the rate of healing of acute maxillary sinusitis, as judged by sinus radiographs and subjective symptom scores. The researchers concluded that decongestion of the sinus ostia may not be of primary importance in the healing of acute sinusitis.[53]
This agent, which is an anticholinergic, has been evaluated in adults and young adults with rhinorrhea of moderate or greater severity. In one study, ipratropium reduced the severity of sneezing and rhinorrhea, but it did not appear to reduce nasal congestion. Rates of blood-tinged mucus and nasal dryness were higher in the treated group than in the control group.[54]
Histamines are not thought to play a role in generating URI symptoms; therefore, newer, nonsedating antihistamines are not useful in reducing URI symptoms. However, first-generation oral antihistamines (eg, diphenhydramine, chlorpheniramine, clemastine) have some anticholinergic effects, which, in theory, could reduce sneezing and rhinorrhea. (Such effects have been reported for clemastine fumarate in patients with the common cold.)[55]
These older antihistamines, however, are sedating. In nonallergic children with acute bacterial rhinosinusitis, data regarding the efficacy of H1 blockers as adjuvants to antibiotics are insufficient.[56] In theory, antihistamines may thicken secretions and thus reduce sinus drainage.
Topical and systemic steroids are often prescribed with the intention of reducing mucosal swelling in patients with acute viral or bacterial rhinosinusitis. However, little evidence supports their use for this indication.
In children who are taking antibiotics for acute bacterial rhinosinusitis, intranasal steroids do not appear to dramatically improve symptoms.[56] However, for adults with recurrent acute rhinosinusitis or acute rhinosinusitis superimposed on chronic rhinosinusitis, adjunctive use of high-dose nasal corticosteroids may decrease symptom duration and improve clinical success rates.[1, 57]
Saline nasal drops may provide relief from thick secretions and mobilize nasal crusting. Nasal saline irrigation is effective and well tolerated as an adjunct to persistent rhinosinusitis symptoms.[48]
The use of guaifenesin, a mucolytic, is commonly suggested with the intention of thinning secretions. However, data regarding its effectiveness in reducing secretions and promoting drainage in persons with nasopharyngitis or rhinosinusitis are limited.
Lozenges, gargles, or sprays that contain phenol may provide temporary relief of sore throat. In young children, however, lozenges may pose a choking hazard.
Gargles of viscous lidocaine may numb the throat, providing relief; however, swallowing may be impaired if sensation is reduced. Saline gargles may reduce swelling in individuals with pharyngitis.
Intranasal cromolyn sodium is typically used for relief of allergic rhinitis. Data are insufficient, however, to permit evidence-based recommendations regarding its use to treat URI-related nasal symptoms in nonallergic patients.
Cough suppression may increase comfort when cough is severe or when it prevents sleep.[45] As stated earlier, the risk-to-benefit ratio for using cough and cold medicines in children younger than 2 years requires careful consideration because serious adverse events, including fatalities, have been reported with the use of over-the-counter preparations in young children.[51] Since 2008, many nonprescription cough and cold product labels state "do not use" in children younger than 4 years.[52]
Cough associated with the common cold may be treated with a first-generation antihistamine combined with a decongestant (eg, brompheniramine with pseudoephedrine). Older-generation histamines have anticholinergic effects, which may account for cough reduction. Newer-generation (nonsedating) antihistamines are ineffective for cough.
Inhaled ipratropium, an anticholinergic, may be useful in postinfectious cough (3-8 wk after the onset of the URI) in adults. Inhaled steroids may be considered in postinfectious cough (3-8 wk after URI onset) if ipratropium fails to control it. If postinfectious cough remains severe and if other causes (eg, rhinosinusitis, cough asthma, gastroesophageal reflux disease) have been excluded, a short, time-limited course of oral steroids may be considered.
Several agents (eg, codeine, guaifenesin, dextromethorphan) are intended for the symptomatic relief of cough. However, evidence is mixed regarding effectiveness of these agents. While codeine may inhibit cough under various circumstances, data are limited regarding its effectiveness in reducing acute cough from URI. As an expectorant, guaifenesin is intended to mobilize secretions. However, consistent data regarding its effectiveness in reducing discomfort from cough associated with URIs are scarce.
Dextromethorphan, a centrally acting cough suppressant, may be considered for the treatment of postinfectious cough in adults if other medications fail. However, this agent may have limited efficacy in treating cough related to acute URI. One study showed that honey was superior to dextromethorphan in reducing cough symptoms and improving sleep in children with URI.[50]
Over-the-counter cough suppressants may cause notable adverse effects in young children. Additional data are required to permit evidence-based recommendations for the use of central-acting antitussives in URI-related cough in children.[58]
Codeine is an effective, centrally acting cough suppressant in adults. As with other centrally acting antitussives, additional evidence is required to create evidence-based recommendations for the use of codeine in URI-related cough in children.[58] Clinically significant respiratory and nonrespiratory adverse events have been reported. Sedatives should be avoided in patients with chronic obstructive pulmonary disease and in others at risk of respiratory depression.
Beta agonists are not thought to be helpful in URI-related cough, including that due to pertussis. However, beta-agonists are recommended in the setting of asthma or chronic obstructive pulmonary disease exacerbated by URI.
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to reduce discomfort due to cough. Avoid aspirin in children with viral illness because aspirin is associated with Reye syndrome.
Inhaled cromolyn sodium is used for control of chronic asthma. Data are insufficient to permit evidence-based recommendations regarding the use of inhaled cromolyn sodium to treat URI-related cough in patients without asthma.
Fever may be physiologically helpful in eliminating pathogens from the body. In some individuals, however, fever poses a risk of provoking underlying illness. In a fragile cardiac patient, for example, increased metabolic demands associated with fever may increase the work of the heart. In children with a history of febrile seizures, avoiding high fevers may reduce the risk of seizure.
Acetaminophen, rather than aspirin, is recommended for the relief of fever, sore throat, myalgias, facial pain, and other uncomfortable sensations in pediatric patients because aspirin is associated with Reye syndrome. Avoid the use of respiratory depressants in patients with serious airway congestion or compromise.
Steroids should not be routinely used for pharyngitis pain relief. An analysis of steroids added to usual care for pharyngitis potentially caused by group A streptococcus noted a 4.5-hour reduction in time to pain relief and improved pain relief at 24 hours with oral or injected steroids.[59] However, significant heterogeneity was reported in the pooled results.
Alternative therapies and traditional folk remedies are widely used to treat URIs. While some may provide symptomatic relief, current studies are insufficient to permit evidence-based conclusions regarding effectiveness.
Zinc
Studies of oral zinc have yielded mixed results, and data on children are limited. Unpleasant taste and nausea have been reported. Zinc nasal gel has been studied for the common cold.[60] However, the US Food and Drug Administration (FDA) has issued a public health advisory against the use of intranasal zinc because of reports of long-lasting or permanent loss of smell associated with its use. In some cases, anosmia occurred with the first dose; in others, it occurred after multiple uses of intranasal zinc.[61]
Oral zinc has been studied as a supplement to prevent colds and as an acute remedy. A meta-analysis of randomized trials of oral zinc (lozenges, syrup, tablets) concluded that, statistically, healthy people who took oral zinc supplements for 5 months or more experienced fewer colds.[62]
The study also found that when oral zinc was taken as an acute remedy within 24 hours of symptom onset, it statistically improved symptom duration and severity. However, firm recommendations regarding routine use in healthy individuals are difficult to make, due to variability inherent in the course of URIs; the variability in dosing, timing, and formulations studied; and the balance required against side effects such as nausea.
Echinacea
Echinacea preparations are widely used for common colds. A meta-analysis noted that echinacea preparations tested in clinical trials differ greatly, but found some evidence that Echinacea purpura preparations may be effective in the early treatment of colds in adults.[63] In a randomized study of common cold symptom severity in older children and adults, standardized echinacea tablets started within the first 24 hours of symptoms were not superior to placebo.[64]
Vitamin C
High-dose oral vitamin C supplementation for the attenuation of URI symptoms has been studied. Results have been inconsistent.
Traditional folk remedies
Folk remedies include sipping hot water with a teaspoon of honey and fresh lime or lemon juice. However, the acids in fresh citrus may be irritating to sore throat. Honey has more demulcent qualities.
One study showed that honey was superior to dextromethorphan in reducing cough symptoms and improving sleep in children with URI.[50] Honey should not be given to infants, because of the rare possibility that it may contain Clostridium botulinum spores, which may germinate in the intestine and produce toxin that causes infant botulism.
Teas made from demulcent herbs are traditionally used to soothe sore throats. Such herbs include slippery elm bark (Ulmus rubra), marshmallow root (Althea officinalis), and licorice root (Glycyrrhiza glabra). A study of 60 adults revealed a temporary favorable trend toward improvement of pharyngitis symptoms when the patients drank a tea containing these herbs, compared with placebo.[65] Prolonged, excessive use of licorice may affect potassium levels and volume status.
Increased fluids are warranted to replace insensible losses and reduced oral intake. However, alcohol may cause swelling of the nasal and paranasal sinus mucosae.
Antibiotics alter the gastrointestinal flora, and some foods may not be as digestible for days or weeks after antibiotics are used. Consumption of yogurt containing active cultures has been advocated as an aid to restoring normal flora after antibiotic therapy. A meta-analysis suggests that probiotics may prevent antibiotic-associated diarrhea; Saccharomyces boulardii and lactobacilli may be particularly useful in this situation.[66]
Patients with the common cold may consider returning to their usual physical activity, including aerobic activity, if their symptoms are limited to the nose and throat. However, if cough, fever, or other systemic symptoms are present, rest is indicated to aid in recovery from the URI.
Patients with infectious mononucleosis should be instructed to avoid contact sports for 6 weeks because of the possibility of splenic rupture. Voice rest is indicated for patients with laryngitis or laryngotracheitis.
Patients may experience increased discomfort from upper airway infection during air travel. As atmospheric pressure drops during takeoff, expansion of soft tissues may block the eustachian tubes and increase pressure sensations in the sinuses.
Chlorine from pools may be irritating to inflamed nasal membranes. Diving, especially at depth, may cause uncomfortable pressure and impair drainage of the paranasal sinuses.
Several measures can reduce susceptibility to URIs. In newborns, the practice of breastfeeding transfers protective antibodies through the mother's milk, providing passive immunization against numerous pathogens.
In older children, adolescents, and adults, an adequate diet is necessary for overall health and optimal immune function. Eating 5 servings of fruits and vegetables each day is commonly recommended. Various vitamins and minerals are necessary for immunity. Obtaining these from food may have more nutritional benefit than taking individual supplements.
Lifestyle measures such as smoking cessation and reduction of exposure to secondhand smoke may reduce the incidence of URIs. Regular, moderate exercise may reduce susceptibility to URIs, whereas intensive training in high-performance endurance athletes may increase susceptibility.[67]
Stress has deleterious effects on the immune system. Measures to reduce stress may include changing schedules and responsibilities, increasing time spent doing relaxing activities, and increasing sleep time.
Hygiene
Handwashing is the mainstay for reducing the risk of contracting a URI. Wash the hands for 20 seconds with ordinary soap and water; include all surfaces of the hands, such as in between the fingers and around the nail bed where debris may accumulate. People should wash their hands before eating and preparing meals, after toileting, after changing diapers or handling other waste, and after coughing or sneezing. Especially during cold season, people should wash their hands frequently and avoid touching unwashed hands to their nose and mouth. Discourage sharing of items passed from hand to mouth.
Use of alcohol-based hand sanitizers is acceptable when soap and water are not available. Avoid contact with secretions of infected persons. Cover coughs and sneezes with a tissue or upper sleeve.
Rhinoviruses can survive for as long as 3 hours on skin and fomites, such as telephones, door handles, and stair railings. Regular cleaning of environmental surfaces with a disinfectant may reduce the spread of infection; however, optimal cleaning approaches have not been established.
Avoidance and treatment of the patient’s contacts
People with URI should reduce contact with others to avoid the spread of infection. Adults may be infectious from the day before symptoms begin through approximately 5 days after the onset of illness. Children may shed virus for several days before their illness begins, and they may remain infectious for up to 10 days after symptom onset.
Patients with pertussis may be contagious for weeks during the coughing phase. Severely immunocompromised persons may shed virus for weeks or even months. Patients with diphtheria should be isolated.
Patients with group A strep confirmed with culture or rapid antigen testing should not attend day care, school, or work for 24 hours after antibiotics are started. After 24 hours of antibiotic treatment, an infected person is not generally able to spread the bacteria.
Asymptomatic household contacts of patients with group A streptococcal pharyngitis do not generally require throat culture or rapid antigen testing.[2] However, in the setting of recurrent group A streptococcal disease, rheumatic fever, poststreptococcal glomerulonephritis, or outbreaks in semiclosed environments, testing and treating household contacts who are positive for group A streptococci may be advisable.[1]
Patients who are ill with influenza or similar infections should remain at home (except for receiving medical care and other necessities) until at least 24 hours have passed without a fever, without the use of fever-reducing medication.
To prevent the spread of epiglottitis, consider rifampin prophylaxis for close contacts of a patient with epiglottitis, especially when unvaccinated young children are among the contacts.
To prevent the spread of pertussis, patients should be isolated for 5 days. All close contacts should receive an antibiotic active against pertussis, such as azithromycin, erythromycin, or trimethoprim-sulfamethoxazole, regardless of their age or vaccination status. All close contacts younger than 7 years who have not received the complete 4-dose primary vaccination series should finish the series with minimal intervals between doses. Close contacts aged 4-6 years who have not yet received the second booster dose should be vaccinated.[68]
To prevent the spread of diphtheria, isolation is warranted until 48 hours after antibiotics are started, after which diphtheria is not usually contagious. Household or other close contacts should receive benzathine penicillin or a 7- to 10-day course of oral erythromycin and an age-appropriate diphtheria booster.[68]
Orogenitally transmitted infections (eg, HSV infection, gonorrhea) warrant evaluation of contacts to reduce the spread of infection. Partners who have had genital or orogenital contact with an N gonorrhoeae– infected patient should be evaluated and treated for N gonorrhoeae and Chlamydia trachomatis. This recommendation applies to partners whose last genital or orogenital contact was within 60 days before the patient's onset of symptoms or diagnosis.
Patients should avoid having intercourse until therapy is completed and until both patients and their partners no longer have symptoms.[69] Patients with HSV pharyngitis should be counseled about the spread of infection, and their contacts should be evaluated.
Vaccination against Haemophilus influenzae type b has dramatically reduced rates of epiglottitis. Immunization against diphtheria and pertussis is recommended for nonimmunized patients.
To address the increased rate of pertussis cases in adolescents whose immunity has waned, the American Academy of Pediatrics recommends that adolescents receive a single dose of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap).[70] Updated CDC recommendations are available, including guidance for children, pregnant patients, and adults (including those who may come into contact with young children).[71]
RSV passive immunoprophylaxis may be given as a monthly administration of anti-RSV immunoglobulin or monoclonal antibody to reduce the risk of lower respiratory tract disease and of hospitalization in infants and children at high risk for RSV disease. These high-risk patients include premature infants and children younger than 2 years with bronchopulmonary dysplasia. Prophylaxis is also considered for infants and young children with hemodynamically significant congenital heart disease.
For information on influenza vaccination, see the Medscape Reference article Influenza, as well as the CDC Web page What You Should Know for the 2013-2014 Influenza Season. Chemoprevention is available for influenza; however, it does not replace vaccination.
Complementary and alternative therapies and folk remedies are used by some to prevent URIs. Common choices include zinc, echinacea preparations, and vitamin C. However, conclusive evidence that these strategies reduce URI infection is inconsistent. Lactobacillus GG is being studied for a possible connection in reducing the incidence of respiratory infections.
Airway obstruction from epiglottitis, tonsillar hypertrophy, peritonsillar abscess, retropharyngeal abscess, or other causes of an obstructive mass requires emergency consultation with a surgeon. Sleep apnea associated with tonsillar hypertrophy may also prompt surgical consultation. Neurologic findings or mental status changes in the setting of suspected intracranial suppurative complications warrant emergency consultation with a neurosurgeon.
Consider consulting an infectious disease specialist when patients have any of the following:
Patients with a chronic cough after a URI may benefit from a consultation with a pulmonologist or otorhinolaryngologist to evaluate persistent infection, asthma, gastroesophageal reflux disease, or other causes of chronic cough. Patients who have had 4-5 confirmed group A streptococcal infections in a single year or those with a chronic sore throat and adenopathy unresponsive to treatment over 6 months should be examined by an infectious disease specialist and/or surgeon.
Persistent hoarseness after 2 weeks warrants consultation with an otorhinolaryngologist. Patients with complex, persistent cases of rhinosinusitis should also be referred to an otorhinolaryngologist, for consideration of sinus puncture and aspiration.
In general, patients with URI should follow up with a physician if their symptoms do not improve, worsen within 72 hours, or recur. Patients with infectious mononucleosis should be instructed to follow up with their physician after a week. In patients with diphtheria, elimination of the organism should be documented with 2 consecutive negative culture results after the completion of therapy.[28]
Follow-up testing is not routinely necessary in cases of group A streptococcal pharyngitis that resolve. However, follow-up may be advisable in the setting of recurrent group A streptococcal disease, rheumatic fever, poststreptococcal glomerulonephritis, or outbreaks in semiclosed environments.[1]
Therapy addressing specific symptoms is the mainstay for most upper respiratory infections (URIs). Most URIs are self-limited viral infections that resolve without prescription drugs.
Recognizing viral and bacterial diseases for which specific therapy is available is important. Awareness of local trends in prevalent organisms and local resistance patterns is key. Antibacterial therapy is appropriate for patients with any of the following:
Antibiotics used in group A streptococcal infection are as follows:
Antibiotics used in epiglottitis are as follows:
Antibiotics used in pertussis are as follows:
Antibiotics used in acute bacterial rhinosinusitis are as follows:
The US Food and Drug Administration (FDA) has warned that azithromycin may lead to QT interval prolongation and torsades de pointes. The FDA notes that "health care professionals should consider the risk of fatal heart rhythms with azithromycin when considering treatment options for patients who are already at risk for cardiovascular events." These include patients with known QT interval prolongation, torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.[72]
Patients with herpes simplex virus (HSV) infection or gonococcal upper airway disease also benefit from specific treatment. In immunocompromised patients, treatment of respiratory syncytial virus (RSV) and cytomegalovirus infections may be appropriate, especially if lower airway disease is suspected.
In general, antivirals do not provide clinical benefits in persons with viral pharyngitis. However, in patients who are immunocompromised, antivirals have a role in treating illness that might progress. Acyclovir, famciclovir, and valacyclovir are recommended for patients with severe HSV pharyngitis and for immunocompromised patients. Foscarnet or ganciclovir are recommended for the treatment of cytomegalovirus infections (CMV) in immunocompromised patients.
Cough and cold medicines should be used with caution in children younger than 2 years because serious adverse reactions and fatalities have occurred with over-the-counter preparations.[51] In 2008, the Consumer Healthcare Products Association modified many over-the-counter cough and cold product labels to state "do not use" in children younger than 4 years.[52]
Clinical Context: Penicillin is the antimicrobial agent of choice for treatment of group A streptococcal pharyngitis. It is indicated for the treatment of infections caused by susceptible organisms involving the respiratory tract.
Clinical Context: Penicillin is the antimicrobial agent of choice for treatment of group A streptococcal pharyngitis. It is indicated for the prophylaxis or treatment of mild to moderately severe upper respiratory tract infections caused by organisms susceptible to low concentrations of penicillin G.
Penicillins are highly active against gram-positive organisms. Their bactericidal activity is the result of interfering with bacterial cell wall synthesis
Clinical Context: Ampicillin is a second-generation penicillin that is active against many strains of Escherichia coli, Proteus mirabilis, Salmonella, Shigella, and Haemophilus influenzae. It is available in oral and injection forms.
Clinical Context: Amoxicillin is the equivalent of penicillin for bacteriologic eradication of group A streptococcal infection from the tonsillopharynx. It is also appropriate for uncomplicated bacterial rhinosinusitis. It is further indicated for the treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the upper and lower respiratory tract.
Clinical Context: Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase producing bacteria. This combination is a good alternative for patients allergic to or intolerant of macrolide antibiotics. It is usually well tolerated and provides good coverage of most infectious agents, but it is not effective against Mycoplasma and Legionella species.
The half-life of oral amoxicillin/clavulanate is 1-1.3 hours. Amoxicillin has good tissue penetration but does not enter the cerebrospinal fluid.
For children over 3 months, base dosing on the amoxicillin content. Due to different amoxicillin/clavulanic acid ratios in 250-mg tablets (250/125) vs 250-mg chewable tablets (250/62.5), do not use the 250-mg tablet until the child weighs over 40 kg.
Penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins.
Clinical Context: Cefadroxil is indicated for the treatment of susceptible bacterial infections, including those caused by group A beta-hemolytic Streptococcus.
First-generation cephalosporins are active mainly against gram-positive bacteria. They inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins and eventually cause the bacteria to lyse.
Clinical Context: Cefaclor is a second-generation cephalosporin that binds to 1 or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity. It has the gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, Klebsiella pneumoniae, and Moraxella catarrhalis.
This agent is indicated for management of infections caused by susceptible mixed aerobic-anaerobic microorganisms. Determine the proper dosage and route based on the condition of the patient, the severity of the infection, and the susceptibility of the causative organism.
Clinical Context: Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis.
This agent binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in bacterial cell wall death. The condition of the patient, the severity of the infection, and the susceptibility of the microorganism determine the proper dose and route of administration. Cefuroxime resists degradation by beta lactamase.
The second-generation cephalosporins are less active against gram-positive bacteria than the first-generation agents are and are more active against certain gram-negative bacteria. Cephalosporins bind to penicillin-binding proteins and inhibit the final transpeptidation step of peptidoglycan synthesis, resulting in bacterial cell wall death.
Clinical Context: Cefotaxime is a third-generation cephalosporin with a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. It arrests bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins, which, in turn, inhibits bacterial growth. Its safety profile is more favorable than that of aminoglycosides.
Third-generation cephalosporins are less active against gram-positive organisms compared with first-generation cephalosporins. They are highly active against Enterobacteriaceae, Neisseria, and H influenzae.
Clinical Context: Erythromycin covers most potential etiologic agents in rhinosinusitis, including Mycoplasma species; however, it is less active against H influenzae. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for treatment of staphylococcal and streptococcal infections. This agent has the added advantage of being a good anti-inflammatory agent by inhibiting migration of polymorphonuclear leukocytes.
In children, the patient's age and weight and the severity of the infection determine proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose. The recommended dosing schedule of erythromycin may result in gastrointestinal upset. Patients may require an alternative macrolide or a change to 3-times-daily dosing. Although the standard course of treatment seems to be 10 days, treating until the patient has been afebrile for 3-5 days seems more rational.
Clinical Context: Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.
This agent concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that the concentration in phagocytes may contribute to drug distribution to inflamed tissues.
Azithromycin is used for the treatment of mild to moderate microbial infections, including group A streptococcal infection and pertussis. Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. It has a long tissue half-life.
The US Food and Drug Administration (FDA) has warned that azithromycin may lead to QT interval prolongation and torsades de pointes. The FDA notes that "health care professionals should consider the risk of fatal heart rhythms with azithromycin when considering treatment options for patients who are already at risk for cardiovascular events." These include patients with known QT interval prolongation, torsades de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
Clinical Context: Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.
Macrolides are appropriate for the treatment of group A streptococcal infection in patients with penicillin sensitivity. They are also used for some cases of rhinosinusitis, pertussis, and diphtheria. Macrolides block transpeptidation by binding to the 50S ribosome. They also inhibit RNA-dependent protein synthesis.
Clinical Context: Acetaminophen is the drug of choice for pain relief in patients with documented hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), who have upper gastrointestinal disease, or who are taking oral anticoagulants. It reduces fever by directly acting on hypothalamic heat-regulating centers, increasing dissipation of body heat by means of vasodilation and sweating.
Clinical Context: Naproxen is indicated for mild to moderate pain. Other indications include ankylosing spondylitis, osteoarthritis, and rheumatoid disorders. Onset of action for relieving pain is typically 1 hour.
Clinical Context: Ibuprofen is indicated for mild to moderate pain. Other indications include inflammatory diseases and rheumatoid disorders. It is available in oral forms, as well as in an injection form. Onset of action for relieving pain is typically 30 to 60 minutes.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are reversible inhibitors of cyclo-oxygenase–1 (COX-1) and COX-2 enzymes, which results in decreased formation of prostaglandin precursors. NSAIDs have antipyretic, analgesic, and anti-inflammatory properties.
NSAIDs typically contain a black-box warning about an increased risk of adverse cardiovascular thrombotic events, including myocardial infarction and stroke. Another black-box warning related to NSAIDs comments on the increased risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation with the use of these drugs.
Clinical Context: Ipratropium, which is chemically related to atropine, has antisecretory properties. When applied locally, it inhibits secretions from serous and seromucous glands lining the nasal mucosa.
Parasympatholytic inhalers inhibit vagally mediated reflexes by antagonizing the action of acetylcholine released by the vagus nerve. This action prevents the increase in intracellular concentration of cyclic guanosine monophosphate (cGMP) caused by the interaction of acetylcholine and muscarinic receptors on bronchial smooth muscle.
These agents help to reduce mucus in the lungs and relax the smooth muscles of large and medium bronchi. They may be used with short-acting beta2 -adrenergic bronchodilators.
Clinical Context: Diphenhydramine is a first-generation antihistamine with anticholinergic effects.
Clinical Context: Chlorpheniramine is a first-generation agent that competes with histamine or H1-receptor sites on effector cells in blood vessels and the respiratory tract. It is one of the safest antihistamines to use during pregnancy.
Clinical Context: This oral H1 blocker is used for allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria. It does not tend to cause drowsiness and is suitable to use on a day-to-day basis.
These agents act by competitively inhibiting histamine at the H1 receptor. This effect mediates bronchial constriction, mucus secretion, smooth muscle contraction, and edema.
Clinical Context: This compound treats minor cough resulting from bronchial and throat irritation.
Several agents (eg, codeine, guaifenesin, dextromethorphan) are intended for the symptomatic relief of cough. However, evidence is mixed regarding the effectiveness of these agents. Cough and cold medicines should be used with caution in children younger than 2 years because serious adverse reactions and fatalities have occurred with over-the-counter preparations. Many over-the-counter cough and cold preparation labels state that the product should not be used in children younger than 4 years.
Clinical Context: Codeine is a centrally acting antitussive that also helps to manage the pain of intercostal muscle strain associated with cough.
Opioid analgesics bind to opioid receptors in the central nervous system, thus inhibiting pain pathways. In addition, these agents cause cough suppression by direct central action in the medulla.
Clinical Context: Epinephrine is used for severe bronchoconstriction, especially with underlying reactive airway disease. Its alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropy.
Alpha stimulation causes mucosal vasoconstriction, decreasing edema of the subglottic region of the larynx. Although inhaled epinephrine is sometimes given in epiglottitis, its benefit is unproven.
Clinical Context: Dexamethasone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Prednisone in equivalent doses may be substituted if administered over the course of 5 days.
Steroids are used to decrease edema by suppressing local inflammation. They are frequently used to manage croup, and they may reduce the need for racemic epinephrine inhalation.
Clinical Context: This agent causes vasoconstriction by directly stimulating alpha-adrenergic receptors in the respiratory mucosa. It is used for symptomatic relief of nasal congestion due to common cold, upper respiratory tract allergies, and sinusitis. It promotes nasal or sinus drainage.
Clinical Context: Stimulates alpha-adrenergic receptors and causes vasoconstriction when applied directly to mucous membranes. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.
These drugs are typically used to relieve nasal symptoms. Decongestants and antihistamines should be used with caution in children younger than 2 years because serious adverse reactions and fatalities have occurred with over-the-counter cough and cold preparations. In 2008, the Consumer Healthcare Products Association modified many over-the-counter cough and cold product labels to state "do not use" in children younger than 4 years.
Clinical Context: This agent is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body.
Clinical Context: Oxymetazoline stimulates alpha-adrenergic receptors and causes vasoconstriction when applied directly to mucous membranes. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.
Symptom Allergy URI Influenza Itchy, watery eyes Common Rare; conjunctivitis may occur with adenovirus Soreness behind eyes, sometimes conjunctivitis Nasal discharge Common Common Common Nasal congestion Common Common Sometimes Sneezing Very common Very common Sometimes Sore throat Sometimes (postnasal drip); itchy throat Very common Sometimes Cough Sometimes Common, mild to moderate, hacking cough Common, dry cough, can be severe Headache Sometimes, facial pain Rare Common Fever Never Rare in adults, possible in children Very common, 100-102°F or higher (in young children), lasting 3-4 days; may have chills Malaise Sometimes Sometimes Very common Fatigue, weakness Sometimes Sometimes Very common, can last for weeks, extreme exhaustion early in course Myalgias Never Slight Very common, often severe Duration Weeks 3-14 days 7 days, followed by additional days of cough and fatigue