Definition and Causes

Upper respiratory tract infection (URI) is a nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, larynx, trachea, and bronchi. The prototype is the illness known as the common cold, which is discussed here, in addition to pharyngitis, sinusitis, and tracheobronchitis. Influenza is a systemic illness that involves the upper respiratory tract and should be differentiated from other URIs.

Viruses cause most URIs, with rhinovirus, parainfluenza virus, coronavirus, adenovirus, respiratory syncytial virus, Coxsackie virus, human metapneumovirus, and influenza virus accounting for most cases.¹ Group A beta-hemolytic streptococci (GABHS) cause 5% to 10% of cases of pharyngitis in adults.² Other less common causes of bacterial pharyngitis include group C beta-hemolytic streptococci, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Arcanobacterium haemolyticum, Chlamydophila (formerly Chlamydia) pneumoniae, Mycoplasma pneumoniae, and herpes simplex virus. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common organisms that cause the bacterial superinfection of viral acute rhinosinusitis.³ Less than 10% of cases of acute tracheobronchitis are caused by Bordetella pertussis, B. parapertussis, M. pneumoniae, or C. pneumoniae.⁴

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Prevalence and Risk Factors

Most URIs occur more frequently during the cold winter months, because of overcrowding. Adults develop an average of 2 to 4 colds annually. Antigenic variation of hundreds of respiratory viruses result in repeated circulation in the community. A coryza syndrome is by far the most common cause of physician visits in the United States.⁵ Acute pharyngitis accounts for 1% to 2% of all visits to outpatient and emergency departments, resulting in 7 million annual visits by adults alone.² Acute bacterial sinusitis develops in 0.5% to 2% of cases of viral URIs.³ Approximately 20 million cases of acute sinusitis occur annually in the United States. About 12 million cases of acute tracheobronchitis are diagnosed annually, accounting for one third of patients presenting with acute cough.⁴ The estimated economic impact of non–influenza-related URIs is $40 billion annually.⁵

Influenza epidemics occur every year between November and March in the Northern Hemisphere. Approximately two thirds of those infected with influenza virus exhibit clinical illness, 25 million seek health care, 100,000 to 200,000 require hospitalization, and 40,000 to 60,000 die each year as a result of related complications.⁶ The average cost of each influenza epidemic is $12 million, including the direct cost of medical care and indirect cost resulting from lost work days. Pandemics in the 20th century claimed the lives of more than 21 million people. The 2009 influenza A H1N1 pandemic infected more children than adults,⁷ but children were less likely to progress to severe disease than were adults; particularly those who were obese, pregnant, or had underlying medical conditions. A widespread H5N1 pandemic in birds is ongoing, with continued threats of a human pandemic.

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Pathophysiology and Natural History

Transmission of organisms causing URIs occurs by aerosol, droplet, or direct hand-to-hand contact with infected secretions, with subsequent passage to the nares or eyes.⁸ Thus, transmission occurs more commonly in crowded conditions. Direct invasion of the respiratory epithelium results in symptoms corresponding to the area(s) involved.

Sinusitis and acute bronchitis are frequently preceded by a common cold. Sinonasal allergies, anatomic abnormalities such as a deviated nasal septum, sinus ostial blockade caused by mucosal edema, immunodeficiency disorders such as hypogammaglobulinemia and human immunodeficiency virus infection, and abuse of nasally inhaled cocaine predispose to the development of acute sinusitis.³

Most influenza epidemics in the 20th century were caused by the influenza A virus, but a few were caused by the influenza B virus. Most epidemics are believed to spread from schoolchildren to their families. Annual influenza epidemics result from the transmission of a mutated influenza virus for which most humans do not have immunity (antigenic drift). Pandemics, on the other hand, occur when a totally new influenza virus is transmitted to humans from other species, most commonly swine and birds (antigenic shift). People older than 65 years and those with comorbidities are at higher risk than healthy people for hospitalization and death because of exacerbation of their underlying medical conditions as a result of influenza.

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Signs and Symptoms

Significant overlap exists in the clinical manifestations of the different forms of URIs. Onset of symptoms occurs 1 to 3 days after exposure to the infectious agent. Nasal congestion, sneezing, and sore throat are the hallmarks of the common cold. A predictive index score for the diagnosis of picornavirus infections has been developed, but is not of practical use.⁹ Conjunctivitis is characteristically seen with adenovirus infections. Sudden onset of sore throat, fever, absence of cough, and exposure to a person with known streptococcal pharyngitis in the preceding 2 weeks suggest the diagnosis of GABHS-related pharyngitis.^2,10 Patients with acute bacterial rhinosinusitis experience symptoms for more than 1 to 2 weeks after a common cold, including unilateral facial pain, maxillary toothache, headache, and excessive purulent nasal discharge.^3,11 Acute tracheobronchitis is an illness characterized by cough, with or without sputum production, or wheezing, lasting 1 to 3 weeks.⁴ Pertussis in adults occurring with waning immunity from previous childhood pertussis illness or immunization may not manifest with the typical whooping cough seen in children with primary infection. Influenza is a sudden illness characterized by high fever, severe headache, myalgia, and dry cough, followed by significant fatigue and malaise.¹² The constellation of these symptoms during influenza epidemics is 70% to 80% predictive of the diagnosis. Older patients with influenza may also present with confusion and somnolence. The presence of sneezing among adults older than 60 years reduces the likelihood of influenza.¹²

On physical examination, patients with common colds may have a low-grade fever, nasal vocal tone, macerated skin over the nostrils, and inflamed nasal mucosa.⁹Patients with GABHS-related pharyngitis may have pharyngeal erythema and exudate, palatal petechiae (doughnut lesions), tender anterior cervical lymphadenopathy, and occasionally a scarlatiniform rash.^2,10 Pharyngeal or palatal vesicles and ulcers (herpangina) suggest enteroviral or herpetic pharyngitis. Pharyngeal exudates occur most commonly with GABHS-related pharyngitis, but can also be seen with infectious mononucleosis caused by Epstein-Barr virus, acute retroviral syndrome, candidal infections, and diphtheria. Swelling, redness, and tenderness overlying the affected sinuses and abnormal transillumination are specific for, but not commonly seen, in patients with acute sinusitis.^3,11 Generalized lymphadenopathy associated with sore throat, fever, and rash should raise the possibility of a systemic viral infection, such as Epstein-Barr virus, cytomegalovirus, or human immunodeficiency virus. Patients with acute tracheobronchitis may also have audible respiratory wheezes. Patients with influenza appear toxic and may have pulmonary rhonchi and diffuse muscle tenderness.

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Diagnosis

Laboratory Tests

Because viruses cause most URIs, the diagnostic role of laboratory investigations and radiologic studies is limited. Viral culture, rapid antigen detection, or polymerase chain reaction (PCR) assay of influenza virus on a nasopharyngeal swab is indicated in patients for whom specific antiviral therapy is recommended. Similar tests are also available for adenovirus, respiratory syncytial virus, human metapneumovirus and parainfluenza virus. Experience with the use of reverse-transcriptase PCR for the diagnosis of enterovirus and rhinovirus infections is growing, but it is not currently available for daily clinical care.¹³ Serologic tests for viruses that can cause a mononucleosis-type illness should be considered in the appropriate clinical setting. Influenza serologies have epidemiologic value only and should not be used for clinical care. A pharyngeal swab for rapid antigen detection of GABHS is 90% sensitive and 95% specific in adults.^14,15 Increased antistreptolysin O titer is not helpful during the acute illness, and is usually detected several days later. Cultures obtained by paranasal sinus puncture or sinus endoscopy should be reserved only for severely ill patients with acute sinusitis and intracranial or orbital complications. In patients with acute bronchitis, a normal C-reactive protein level can reasonably exclude pneumonia, but may be elevated with several other infectious and noninfectious conditions. Procalcitonin is another biomarker that has been used successfully to guide antibiotic use for acute respiratory tract infections in primary care.¹⁶

Imaging Studies

A lateral neck radiograph should be taken in a patient with stridor to assess the airways. However, this should not deviate attention from close monitoring for patency of the airways if epiglottitis is clinically suspected. Chest radiography should be reserved for patients with acute tracheobronchitis who have other comorbid conditions, those with abnormal vital signs or signs of consolidation on chest examination, or those with persistent symptoms for longer than 3 weeks. Plain radiography has been largely replaced by computed tomography (CT) in the evaluation of sinusitis, particularly in preparation for corrective surgery.¹⁷ Complete opacification and air-fluid level are the most specific findings for acute sinusitis. However, a large proportion of patients with the common cold have radiologic abnormalities on CT. Imaging should be considered for patients who do not respond to treatment with antibiotics, but is not advised for the diagnosis of uncomplicated sinusitis. Mastoiditis and other intracranial complications of URIs should be evaluated by CT or magnetic resonance imaging.

Procedural Considerations

Only those experienced in endotracheal intubation should perform laryngoscopic examination of patients with suspected epiglottitis. Paranasal sinus endoscopy is not indicated for patients with uncomplicated acute sinusitis, and endoscopic cultures obtained from the middle meatus should be interpreted with caution because of potential contamination with nasal secretions.

Differential Diagnosis

Prodromal symptoms of viruses that cause systemic syndromes, such as measles and chickenpox, can mimic the common cold. Allergic rhinitis is characterized by itchy eyes and excessive lacrimation; it is often seasonally exacerbated or related to certain allergen exposure, which differentiates it from URIs. Sore throat could be a presenting symptom of acute thyroiditis, Ludwig’s angina, and gastroesophageal reflux disease, all of which should be differentiated from pharyngitis. Drug-induced mucositis can cause a noninfectious form of pharyngitis. Wegener’s granulomatosis should be considered when sinusitis does not respond to usual therapy. The most important step in the evaluation of someone with acute tracheobronchitis is to exclude pneumonia. If a cough lasts more than 3 weeks, postnasal drip, asthma, and gastroesophageal reflux disease are the most likely considerations.

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Treatment

Lifestyle Modifications

Rest is generally recommended for patients with URIs, mainly to allow patients to cope with their illness. There is no evidence that complete bed rest shortens the duration of illness. Voice rest is important for patients with hoarseness. The cardiovascular benefits of exercise are well established, but exercise may also reduce the incidence of colds; particularly among postmenopausal women.¹⁸ Chronic exercise has also been shown to reduce illness severity, viral load, and inflammatory markers during influenza infection.¹⁹

Medical Options

Symptomatic treatment for URIs should be directed to maximize relief of the most prominent symptom(s). Increased fluid intake is generally recommended in an attempt to thin respiratory secretions; however, caution about the development of hyponatremia should be considered in certain patients. Hundreds of over-the-counter (OTC) medications are available in various combinations, but none of these agents has proved to be a magic bullet.²⁰ Americans spend more than $2 billion on OTC medications each year.

A meta-analysis of the literature²¹ has shown that nasal symptoms improve after treatment with α-adrenergic agonists such as oxymetazoline HCl, anticholinergic (parasympatholytic) agents such as ipratropium bromide, and first-generation antihistamines such as chlorpheniramine maleate. Only the first dose of decongestants has been proved to be effective, and repeated use may result in a rebound phenomenon-rhinitis medicamentosa-after discontinuation. The sedating effect of first-generation antihistamines can be hazardous in people driving cars or operating heavy machinery, but the effect may be desirable in patients who have difficulty falling asleep at night as a result of their symptoms.

The role of antitussives and expectorants in the treatment of URIs remains controversial.²² Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for relieving fever, headache, and malaise, but these agents may be associated with gastrointestinal irritation. Warm saline gargles and steam inhalation are inexpensive and relatively safe measures that provide temporary relief of throat symptoms. Camphor and menthol also have been used in various concentrations for temporary relief of various URI symptoms. Mast cell stabilizers such as cromolyn sodium are widely used in preventing asthma attacks, but their role in treating URIs remains unknown. Topical intranasal steroids such as fluticasone propionate and mometasone furoate offer a small therapeutic benefit in acute sinusitis; particularly when given in high doses for 21 days.²³ Systemic steroids should not be used for the treatment of URIs.

After several decades of debate and numerous studies, the role of vitamin C for the treatment of URIs remains controversial. It appears that large doses of vitamin C are necessary to achieve its beneficial effect as an antioxidant in activated leukocytes. However, doses in excess of 4 g/day have been associated with diarrhea. The average benefit in studies using 2 to 4 g/day of vitamin C has been a decrement of about half a day (15%) in the duration of illness.²⁴

Similarly, the role of zinc salts remains controversial, and the specific mechanism of action is unknown. Duration of illness was reduced by about 1 day in studies that showed benefit.²⁵ The ionic bioavailability of zinc salts is an important factor in producing a beneficial effect.²⁶ Bad taste occurs in up to 80% of patients receiving zinc lozenges, and nausea in about 20%. The long-term effects of cumulative doses of zinc are unknown, and altered lipid metabolism and copper deficiency are potential concerns. An intranasal formulation of zinc gel appears to have the same beneficial effect as oral zinc lozenges, with significantly fewer systemic side effects, but concerns about permanent anosmia have been raised.²⁷ If considered, zinc lozenges or intranasal zinc gel should be started within 24 to 48 hours of the onset of cold symptoms.

The therapeutic effectiveness of echinacea in the treatment of URIs has not been established because of the heterogeneous nature of the preparations evaluated in published studies.²⁸ Other traditional medicines, such as troxerutin,²⁹ Andrographis paniculata,³⁰ and elderberry syrup³¹ have been shown in small studies to shorten the duration and decrease the severity of URIs. Because herbal agents are neither patentable nor regulated by the U.S. Food and Drug Administration (FDA), dosages and formulations are not standardized.

Although viruses cause most URIs, antibiotics continue to be inappropriately widely prescribed for these illnesses.³² Data have clearly shown that individuals prescribed antibiotics for respiratory tract infections become at least twice as likely to harbor organisms that are resistant to antimicrobial agents for the ensuing 12 months, compared to those who are not prescribed antibiotics.³³ Unnecessary adverse effects of antibiotics and the development of antimicrobial resistance can be reduced by judicious use of these drugs. Healthcare providers should educate their patients about the self-limited nature of most URIs and the hazards of inappropriate use of antibiotics for the individual and the community.

Antibiotics are currently prescribed to 41% of patients with suspected viral pharyngitis; ranking third among activities thought to be in common practice, but of little benefit, with additional annual cost of $116.3 million.³⁴ Although office visits for URI in people > 5 years did not decrease from 1995 to 2006, antibiotic prescriptions decreased by 18%.32 Prescriptions for penicillins, cephalosporins, trimethoprim-sulfamethoxazole, and tetracyclines have decreased, but those for macrolides and fluoroquinolones have increased.³² Antibiotics account for 20% of all drug-related emergency department visits in the US; 80% of which are for allergic reactions. Antibiotics are the second most common cause of adverse drug events in the elderly, with a risk comparable to insulin, warfarin, and digoxin.³² Moreover, concurrent use of warfarin and any antibiotic is associated with an increased risk of bleeding.³⁵

Studies have shown that sputum color reported by patients is not a reliable marker of the presence of bacteria.³⁶ Moreover, several symptoms predictive of physicians’ behavior to prescribe antibiotics for URIs actually have poor predictive value with respect to the efficacy of antibiotics. These include cough productive of yellow sputum, sore throat, fever, and colored nasal discharge. Patient satisfaction with an office visit is independent of a patient’s initial belief about antibiotics and whether antibiotics were prescribed. A study conducted in Japan showed that adhering to a guideline proposed by the American College of Physicians limited antibiotic use to only 5% to 7% of non-influenza URI; mainly acute pharyngitis, with 90% of patients feeling better and expressing satisfaction within 7 days of treatment.³⁷ Thus, satisfaction is more closely related to whether health care providers addressed patients’ concerns than to whether the provider administered antibiotics. Providing patients with written information, in addition to verbal advice about the lack of evidence to support the use of antibiotics, has been found to be valuable.³⁸ Another approach might involve giving the patient a prescription for an antibiotic, with instructions to fill it only after 3 days if symptoms fail to improve.³⁹

Patients with clinical and epidemiologic features consistent with GABHS-related pharyngitis should be started on antimicrobial therapy pending microbiologic confirmation.^2,10 Oral penicillin or erythromycin (in penicillin-allergic persons), given for 10 days, remains the preferred agent. Fortunately, no resistance to penicillin has been reported so far in GABHS-related pharyngitis patients.

Debate continues over whether to observe or administer any form of treatment to patients with mild-to moderate-sinusitis, which are mostly viral.⁴⁰ Both topical and oral decongestants are likely to alleviate symptoms.¹¹ Topical nasal corticosteroids decrease inflammation of the nasal mucosa, thus may also have some efficacy.²³Antihistamines may have a minor role in treating allergic acute rhinosinusitis, but are not indicated in nonatopic patients.¹¹ Buffered isotonic saline nasal irrigation is reasonable for patients seeking to supplement pharmacotherapy with a self-care option.¹¹ Randomized controlled trials showed that antibiotics should not be prescribed for mild-to-moderate sinusitis within the first week of the illness, because improvement or rates of cure 1 to 2 weeks after beginning treatment were 64% to 80% in the placebo groups compared to 71% to 90% in the antibiotic groups; representing a small difference of only 7%-14%, with no difference in the rate of complications or recurrence, but with an 80% increased incidence of adverse events; particularly diarrhea.⁴¹ Patients with symptoms of acute rhinosinusitis persisting for ≥10 days without improvement, or those with severe symptoms, such as fever ≥39 C, purulent nasal discharge, or facial pain lasting 3-4 consecutive days, and those with a “double sickening” illness characterized by initial improvement of a typical viral URI that lasted 5-6 days, followed by worsening of symptoms, identify patients likely to have acute bacterial – rather than viral – rhinosinusitis.^11,42,43 Empiric antimicrobial therapy should be initiated for suspected moderate or severe acute bacterial rhinosinusitis based on the aforementioned criteria. Current guidelines for treatment of acute bacterial rhinosinusitis⁴² recommend amoxicillin-clavulanate be used as first-line empiric therapy ─ rather than amoxicillin alone, which was recommended by the older version of these guidelines ─ due to the high rates of penicillin-resistant Streptococcus pneumoniae, and Haemophilus influenzae. Moreover, in order to overcome such resistance, high-dose (2 grams orally twice daily for adults) amoxicillin-clavulanate is recommended for patients ≥65 years, those from geographic regions with high endemic rates (≥10%) of invasive penicillin-nonsusceptible Streptococcus pneumoniae, those with severe infection, attendance at daycare, hospitalization within the preceding 5 days, antibiotic use within the preceding month, or who are immunocompromised.

Doxycycline may be used as an alternative first-line agent, but macrolides, trimethoprim-sulfamethoxazole, and second-generation cephalosporins are no longer recommended for empiric therapy of suspected acute bacterial rhinosinusitis due to high rates of resistance among Streptococcus pneumoniae, and Haemophilus influenzae. Respiratory fluoroquinolones (moxifloxacin and levofloxacin), or a combination of an oral third-generation cephalosporins (cefixime or cefpodoxime) plus clindamycin are appropriate second-line agents. Patients who improve after 3-5 days of initiating a first-line agent should complete 5-7 days of antimicrobial therapy. Patients who do not improve after 3-5 days of initiating a first-line agent should be switched to a second-line agent. Patients who improve after 3-5 days of either initiating a second-line agent from the outset, or after switching from a first-line to a second-line agent should be treated for 7-10 days. Although 10% of patients who undergo sinus cultures grow Staphylococcus aureus,⁴⁴ empiric antimicrobial therapy for suspected acute bacterial rhinosinusitis should not include routine coverage for this organism.

Treating acute tracheobronchitis with antibiotics is not recommended, because most cases are viral and thus resolve spontaneously.⁴ There is considerable variation in the rate of antibiotic prescribing for patients with acute cough, with no effect on the rate of recovery.⁴⁵ In adults with persistent cough who report exposure to a patient with confirmed or suspected pertussis, erythromycin or trimethoprim-sulfamethoxazole should be administered for 14 days. This decreases contagion from bacterial shedding, but it is not expected to improve resolution of symptoms, unless started within 10 days of the onset of illness. Selective beta-agonist bronchodilators offer symptomatic relief for cough in patients with acute tracheobronchitis.

Mild and nonfebrile influenza-like illness should not be treated with antiviral agents. The adamantanes, amantadine, and rimantadine, are M2 ion channel blockers that are only active against influenza A, and are associated with a high incidence of gastrointestinal and neuropsychiatric side effects, but are not currently recommended for clinical use due to wide-spread resistance of circulating influenza strains.⁴⁶ The neuraminidase inhibitors (NAIs), oseltamivir and zanamivir, are active against both influenza A and B and have fewer side effects and less propensity to induce viral resistance than the adamantanes, but are considerably more expensive. Treating healthy adults with anti-influenza drugs remains controversial,⁴⁷ but all patients hospitalized for management of influenza should receive such drugs. A recent meta-analysis showed that, in high-risk populations, NAI may reduce mortality, hospitalization, and duration of symptoms. When anti-influenza drugs are started within 1-2 days of onset of illness, most studies have shown a 1-2 days reduction in the duration of illness.⁴⁸

Several antiviral agents with activity against rhinovirus or other viruses that cause URIs have been studied. Interferon is a powerful antiviral drug approved for the treatment of hepatitis B and C virus infections. It has no role in the treatment of viral URIs at this time. Other investigational agents such as pleconaril, a viral capsid inhibitor,⁴⁹ and tremacamra, a soluble intercellular adhesion molecule,⁵⁰ have shown some promise, but are not available for clinical care.

Surgical Options

Patients with suppurative complications of URIs, such as peritonsillar abscess, or mastoiditis, and those with sinusitis refractory to medical treatment should be referred to an ear, nose, and throat surgeon.

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Treatment Outcomes

Most URIs resolve spontaneously in 3 to 10 days with symptomatic therapy alone. In patients with GABHS pharyngitis, moderate or severe suspected acute bacterial rhinosinusitis, and moderate or severe influenza, antimicrobial therapy generally results in symptom relief, and resolution of illness 1 to 2 days sooner than if symptomatic measures alone are used. In addition, prompt initiation of antibiotics in patients with GABHS pharyngitis decreases contagion and may prevent development of suppurative complications, such as peritonsillar abscess, as well as immunologic complications, such as rheumatic fever and glomerulonephritis. The benefits of anti-influenza drugs are more pronounced in patients presenting with more severe illness. Studies using NAIs have also shown a reduction in the incidence of complications from influenza in the frail older population and in patients with underlying medical conditions, such as chronic obstructive pulmonary disease or cardiomyopathy.⁴⁸

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Prevention and Screening

Frequent hand washing remains the most important preventive measure for most URIs, although a recent randomized trial showed that hand disinfection using 2% citric acid and 2% malic acid in 62% ethanol did not reduce rhinovirus-related common cold illnesses.⁵¹ Simple measures, such as covering the mouth and nose while sneezing or coughing with tissue napkin (not with one’s hand), or sneezing in one’s axillary or cubital fossa if a tissue napkin is not readily available, can decrease contagion. Aqueous iodine can prevent viral transmission when applied to the hands of patients with viral URIs, but it is cosmetically unacceptable and may be associated with systemic toxicity if ingested. The benefits of adequate duration and quality of sleep has been recently demonstrated in a rhinovirus challenge study,⁵²showing that those who slept ≤7 hours daily were about 3 times more likely to develop a cold than those who slept ≥8 hours, and those who spent <92% of time in bed actually sleeping were about 5 times more likely to develop a cold than those who spent ≥98% of time in bed actually sleeping.

Prophylactic antibiotics cannot prevent the development of bacterial superinfection of viral URIs and have no benefit in acute, clear or purulent rhinitis.⁵³ Antimicrobial treatment of the sexual partner can prevent reinfection in cases of gonococcal or herpetic pharyngitis.

Vitamin D plays a role in maintaining innate immunity. A recent study⁵⁴ showed that lower vitamin D levels correlated with higher risk of URIs; particularly in patients with asthma and chronic obstructive lung disease. However, it is not yet known whether vitamin D supplementation would decrease the frequency of URI.

Vitamin C is not recommended for prevention of URIs in the general community. However, in marathon runners, skiers, or soldiers, who are exposed to significant cold or physical stress, prophylactic vitamin C may reduce the incidence of colds by 50% and shorten the duration of colds by 8% in adults (approximately 0.6 day).²⁴

Multivitamin and mineral supplements, particularly vitamin E, have no effects on the incidence and severity of URIs in well-nourished noninstitutionalized older individuals,⁵⁴ but they may decrease the incidence of common colds in older nursing home residents,⁵⁵ as well as infectious illnesses and work-related absenteeism in diabetic community-dwelling adults.⁵⁶ These findings are ascribed to micronutrient deficiency.

The trivalent inactivated intramuscular influenza vaccine-the flu shot-is one of the few cost-saving interventions in medicine today. It results in a 30% to 50% reduction of respiratory illnesses, physician visits, and sick leave in vaccinated healthy adults, as well as reduction in hospitalization related to acute worsening of chronic obstructive pulmonary disease or congestive heart failure, and death from any cause among vaccinated older persons.⁵⁷ Despite numerous studies showing these benefits; the magnitude of vaccine effectiveness continues to be widely debated, and recent data suggest lesser benefits than previously demonstrated.⁵⁸ Influenza vaccination is currently recommended for all U.S. population age ≥6 months; regardless of underlying health status.⁵⁹ Influenza vaccine is provided from early fall through early spring. Local side effects, such as mild redness and soreness at the site of injection, occur in 10% to 40% of patients. Systemic reactions, such as fever, malaise, and myalgia, may develop in about 10% of patients, especially those without prior exposure to the influenza virus antigens in the vaccine.

Contrary to false belief among some patients, the inactivated influenza vaccine cannot cause influenza. This must be explained to skeptics, emphasizing that the gains of vaccination clearly outweigh its potential risks, and that respiratory illnesses caused by other infectious organisms are not prevented by the vaccine. The only absolute contraindication to the vaccine is prior severe allergic reaction to influenza vaccine, regardless of the component suspected to be responsible for the reaction. History of Guillain-Barré Syndrome that had developed within 6 weeks of receipt of previous influenza vaccine constitutes a relative contraindication; only in patients who are not at high risk for severe complications from influenza due to other reasons. Vaccination of persons with moderate to severe acute febrile illness should be postponed until symptoms resolve. Patients with mild URIs can still receive the vaccine.

Until 2010, influenza vaccination had been contraindicated in people with history of anaphylactic hypersensitivity to eggs. However, in 2011, these people were recommended to be referred to a physician with expertise in the management of allergic conditions for further risk assessment of vaccination.⁵⁹ Those who can eat lightly cooked eggs with no reaction may be vaccinated without additional precautions. Those with history of hives after eating eggs or egg-containing foods should be observed for 30 minutes after vaccination. Influenza vaccination rates have improved over the past several years; particularly following the 2009 influenza pandemic, but the rates are below target; especially in patients with underlying chronic underlying diseases. Automatic reminders and scheduling routine office visits for those at high risk for influenza-related complications during the early fall are some measures that can be used to increase the rate of vaccination. Inpatient computerized standing orders for vaccination, directed at nurses, are actually more effective than computerized reminders to physicians.⁶⁰ Novel methods, such text messaging have recently been shown to improve influenza vaccination rate in urban, low-income population.⁶¹ The live-attenuated, cold-adapted, intranasal influenza vaccine is as effective as the inactivated vaccine, and may be more appealing for those who would like to avoid an injection. However, it is only approved for healthy persons aged 2 to 49 years. In addition, because shedding of live-attenuated virus occurs for about 1 week after receiving this vaccine, health care providers and household contacts of severely immunocompromised patients should only receive the inactivated vaccine to avoid the theoretical risk of virus transmission causing disease.

Fortunately, almost all URIs in children caused by H. influenzae type B have been eliminated by the widespread use of the H. influenzae type B vaccine, but cases of nontypable H. influenzae continue to occur in adults. The greatest impact of using the 23-valent pneumococcal polysaccharide vaccine has been on preventing bacteremic pneumonia and meningitis in older adults, and recent data showed that the 13-valent pneumococcal conjugate vaccine was more cost-effective than the polysaccharide vaccine among US adults.⁶² Several studies have also shown a reduction in invasive pneumococcal disease in adults since the introduction of the pediatric conjugated pneumococcal vaccine as a result of herd immunity.

An oral live attenuated adenovirus vaccine is available but is restricted for military use.

Chemoprophylaxis with anti-influenza drugs should be reserved for influenza outbreaks occurring before or despite influenza vaccination, or for immunocompromised individuals exposed to a patient with confirmed influenza. Chemoprophylaxis should not be considered as a substitute for vaccination. The costs of a 10-day course for postexposure prophylaxis or a 6-weeks course for seasonal prophylaxis are much more expensive than the vaccine.

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Considerations in Special Populations

Patients who are immunocompromised because of disease or medications are at higher risk for complications caused by URIs. Special attention should be paid to prevention of these infections, if possible, and to treat early to limit morbidity.

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Conclusions

Viruses cause most URIs. Penicillin is recommended for patients with GABHS pharyngitis, and amoxicillin-clavulanate for those with moderate or severe suspected acute bacterial rhinosinusitis. Patients with moderate or severe influenza, those with underlying medical conditions who develop influenza, and those hospitalized for management of influenza should be treated with a neuraminidase inhibitor.

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Summary

• Most URIs are viral in origin. Diagnosis is mainly based on clinical manifestations.
• Adults with clinical findings suggestive of GABHS pharyngitis should have a pharyngeal rapid streptococcal antigen detection test before considering antimicrobial therapy.
• Sinus puncture and sinus CT are not recommended for the diagnosis of uncomplicated sinusitis.
• If pneumonia is unlikely on clinical grounds, chest radiography is not recommended for patients with acute tracheobronchitis.
• A nasopharyngeal swab to confirm influenza by rapid antigen detection test or PCR is recommended before initiating antiviral treatment for patients with suspected influenza, or antiviral chemoprophylaxis for their household contacts.
• Symptomatic treatment is the mainstay of treatment for most URIs.
• Vitamin C and zinc remain controversial.
• Antibiotics should be avoided in patients with a common cold, mild acute rhinosinusitis, or acute bronchitis, but should be prescribed to patients with GABHS pharyngitis and to moderate or severe suspected acute bacterial rhinosinusitis.
• Penicillin is the recommended treatment for GABHS pharyngitis.
• Amoxicillin-clavulanate is the recommended first-line agent for treatment of suspected acute bacterial rhinosinusitis.
• Patients with moderate or severe influenza, those with underlying medical conditions who develop influenza, and those hospitalized for management of influenza should be treated with a NAI. If the rate of influenza resistance to adamantanes decreases in the future, this class of drugs may be reconsidered.

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Suggested Readings

• Institute for Clinical Systems Improvement: Health Care Guideline: Diagnosis and Treatment of Respiratory Illness in Children and Adults. https://www.icsi.org/_asset/1wp8x2/RespIllness.pdf. Accessed August 27, 2013.
• Musher DM: How contagious are common respiratory tract pathogens? N Engl J Med 2003;348:1256-1266.
• Smith MB, Feldman W: Over-the-counter cold medications. A critical review of clinical trials between 1950 and 1991. JAMA 1993;269:2258-2263.
• Chow AW, Benninger MS, Brook I, et al. IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults. Clin Infect Dis 2012; e1-e41 http://cid.oxfordjournals.org/content/early/2012/03/20/cid.cir1043.full.pdf+html. Accessed August 27, 2013.
• Bison AL, Gerber MA, Gwaltney JM Jr, et al: Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin Infect Dis2002;35:113-125.
• Wenzel RP, Fowler AA 3rd. Clinical practice. Acute bronchitis. N Engl J Med 2006;355(20):2125-2130.
• Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011 Aug 26;60(33):1128-32.
• Call SA, Vollenweider MA, Hornung CA, et al: Does this patient have influenza? JAMA 2005;293:987-997.
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