Infectious Disease

Upper Respiratory
Tract Infections

Sherif B. Mossad

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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, coxsackievirus, and influenza virus accounting for most cases.1 Human metapneumovirus is a newly discovered agent causing URIs. 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, 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 sinusitis.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 two to four 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.1 Acute pharyngitis accounts for 1% to 2% of all visits to outpatient and emergency departments, resulting in 7 million annual visits by adults alone.1 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.1

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.5 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. A widespread H5N1 pandemic in birds is ongoing, with threats of a human pandemic. It is projected that such a pandemic would cost the United States $70 to $160 billion.6

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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.7 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 cocaine abuse 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.8 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.9 Patients with acute sinusitis 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.10,11 Acute tracheobronchitis is an illness characterized by cough, with or without sputum production, or wheezing, lasting 1 to 3 weeks.4 Pertussis in adults with waning immunity caused by previous 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% sensitive for making 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.8 Patients with GABHS-related pharyngitis may have pharyngeal erythema and exudate, palatal petechiae (doughnut lesions), tender anterior cervical lymphadenopathy, and occasionally a scarlatiniform rash.9 Pharyngeal or palatal vesicles and ulcers (herpangina) should 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.10 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, 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 only have epidemiologic value 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 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.

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.16 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 is recommended for patients who do not respond to treatment with antibiotics and decongestants, 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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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 for influenza rapid antigen detection test or PCR is recommended before considering antiviral treatment for patients and antiviral chemoprophylaxis for their household contacts.

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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 bedrest shortens the duration of illness. Voice rest is important for patients with hoarseness.

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.17 Americans spend more than $2 billion on OTC medications each year.

A meta-analysis of the literature 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. Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for relieving fever, headache, and malaise, but these agents may be associated with gastrointestinal irritation. In addition, two cyclooxygenase 2 (COX-2) selective NSAIDS, rofecoxib and valdecoxib, have been withdrawn from the market because of increased cardiovascular risks. 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 nasal steroids such as fluticasone propionate improve the clinical success rates of patients with chronic or recurrent sinusitis who present with acute exacerbations.18 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.19

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.20,21 The ionic bioavailability of zinc salts is an important factor in producing a beneficial effect.22 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 side effects. 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.23-25 Reports of echinacea-related anaphylaxis in patients with atopy raise the concern of using it in such a common illness. Other traditional medicines, such as troxerutin,26 Androgrophis paniculata,27 and elderberry syrup28 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.29 Unnecessary adverse effects of antibiotics and the development of antimicrobial resistance can be reduced by judicious use of these drugs.30 Health care 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 have no role in the management of the common cold or any mild URI.31 However, almost 75% of adults with URIs are prescribed antibiotics by their physicians.32 This results in 41 million antibiotic prescriptions per year in the United States, accounting for more than 20% of all antibiotic prescriptions to adults. In addition, 68% of those receiving antibiotics are given nonrecommended, more expensive, broad-spectrum agents, a trend that has been increasing over time.29 Unnecessary antibiotic prescriptions for treatment of URIs cost approximately $700 million per year. 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. About 75% of patients with URIs who seek medical attention expect to receive antibiotics, particularly if they have sinus pain. However, studies have shown that patient satisfaction with an office visit is independent of a patient's initial belief about antibiotics and whether antibiotics were prescribed.33 Satisfaction is more closely related to whether health care providers addressed patients’ concerns. 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.34 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.35

Patients with clinical and epidemiologic features consistent with GABHS-related pharyngitis should be started on antimicrobial therapy pending microbiologic confirmation.2 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.

Patients with only mild symptoms of acute sinusitis improve with topical nasal steroids and decongestants. Oral amoxicillin, trimethoprim-sulfamethoxazole, or doxycycline, given for 3 to 10 days, are the recommended first-line antibiotics for the treatment of moderate to severe acute sinusitis.2,36 The incidence of penicillin-resistant S. pneumoniae and beta-lactamase–producing organisms causing acute sinusitis has been steadily increasing in the community. However, larger doses of amoxicillin, up to 3 g daily, or a combination of amoxicillin and clavulanate remain effective in most cases caused by resistant organisms.3,10,11,36 Alternative agents include cefpodoxime, cefuroxime, and cefdinir. Factors predisposing patients to have antibiotic-resistant organisms include recent antibiotic use and exposure to children who attend daycare centers. Second-line, broad-spectrum, and more expensive agents, including the newer macrolides clarithromycin and azithromycin, and the “respiratory” fluoroquinolones—levofloxacin, gatifloxacin, and moxifloxacin—are no more effective than amoxicillin.37 These agents should be reserved for use in individuals who are allergic or intolerant to first-line agents, those who do not respond to first-line agents within 3 days, or for confirmed microbiologic resistance. This approach would help contain ever-increasing health care costs and, most importantly, curtail the emergence of drug-resistant organisms as a result of selection pressure.

Treating acute tracheobronchitis with antibiotics is not recommended, because most cases are viral and thus resolve spontaneously.4,38 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 β-agonist bronchodilators offer symptomatic relief for cough.

Four agents are currently available for the treatment of influenza. 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, as well as development of viral resistance. 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. In January 2006, a report of resistance to the adamantanes in 92% of circulating influenza isolates resulted in a national recommendation to use only NAI until this resistance pattern is reversed, hopefully in the coming years. Anti-influenza agents should be started within 1 to 2 days of onset of illness and continued for 5 days for maximum benefit.

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,39 and tremacamra, a soluble intercellular adhesion molecule,40 have shown some promise.

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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Summary

  • 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 or acute bronchitis, but should be prescribed to patients with GABHS pharyngitis and moderate or severe sinusitis. Narrow-spectrum agents such as amoxicillin should be the first-line agents.
  • Patients with moderate or severe influenza, and all patients with underlying medical conditions who develop influenza, should be treated with an NAI or an adamantane when the resistance pattern is reversed.

Treatment Outcomes

Most URIs resolve spontaneously in 3 to 10 days with symptomatic therapy alone. In patients with GABHS pharyngitis, moderate or severe sinusitis, 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. Concerns about preventing immunologic complications, such as rheumatic fever and glomerulonephritis, are more applicable to the developing world. 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. However, there are no data on their efficacy in treating influenza pneumonia or their use in severely immunocompromised patients, such as transplant recipients.

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Prevention and screening

Frequent hand washing remains the most important preventive measure for most URIs. Simple measures, such as covering the mouth and nose while sneezing, can decrease the risk of transmission of infectious agents. No study has ever shown that prophylactic antibiotics can prevent the development of bacterial superinfection of viral URIs. 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. One study has shown that antibacterial home cleaning and hand washing products do not decrease the incidence of URIs.41 Antimicrobial treatment of the sexual partner can prevent reinfection in cases of gonococcal and herpetic pharyngitis.

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).19

Multivitamin and mineral supplements, particularly vitamin E, have no effects on the incidence and severity of URIs in well-nourished noninstitutionalized older individuals,42,43 but they decrease the incidence of common colds in older nursing home residents,44 as well as infectious illnesses and work-related absenteeism in diabetic community-dwelling adults.45 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 a 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.46 Vaccination is recommended for almost 50% of the U.S. population, including children aged 6 to 23 months, adults 50 years and older, patients with chronic medical conditions that predispose for the development of influenza-related complications and their household members, residents of extended-care facilities, and health care providers. Influenza vaccine is provided from early fall through early spring and is well tolerated by patients. 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 widespread belief among 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 severe egg allergy. Patients with mild URIs can still receive the vaccine. Unfortunately, only about 65% of people in the United States who should be vaccinated are getting the vaccine, but the rate of vaccination has been steadily climbing over the past several years. Problems with shortage may hamper vaccination efforts. Automatic reminders and scheduling routine office visits for those at risk 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.47 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.48 However, it is only approved for healthy persons aged 5 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.49 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.50 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 patients exposed to a person with proven influenza. Chemoprophylaxis should not be considered as a substitute for vaccination. The cost of a 10-day course for postexposure prophylaxis or a 6-week course for seasonal outbreaks is 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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References

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  40. Arroll B, Kenealy T: Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database Syst Rev 2005;(3):CD000247.
  41. Larson EL, Lin SX, Gomez-Pichardo C, Della-Latta P. Effect of antibacterial home cleaning and handwashing products on infectious disease symptoms. Ann Intern Med. 2004, 140: 321-329.
  42. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons. A randomized controlled trial. JAMA. 2002, 288: 715-721.
  43. Avenell A, Campbell MK, Cook JA, et al: Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): Pragmatic, randomised, double-blind, placebo-controlled trial. BMJ. 2005, 331: 324-329.
  44. Meydani SN, Leka LS, Fine BC, et al: Vitamin E and respiratory tract infections in elderly nursing home residents. A randomized controlled trial. JAMA. 2004, 292: 828-836.
  45. Barringer TA, Kirk JK, Santaniello AC, et al: Effect of a multivitamin and mineral supplement on infection and quality of life. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003, 138: 365-371.
  46. Nichol KL, Nordin J, Mullooly J, et al: Influenza vaccination and reduction of hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003, 348: 1322-1332.
  47. Dexter PR, Perkins SM, Maharry KS, et al: Inpatient computer-based standing orders vs physician reminders to increase influenza and pneumococcal vaccination rates. A randomized trial. JAMA. 2004, 292: 2366-2371.
  48. Centers for Disease Control and Prevention. Using live, attenuated influenza vaccine for prevention and control of influenza. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mort Wkly Rep. 2003, 52: (RR-13): 1-8.
  49. Jackson LA, Neuzil KM, Yu O, et al: Vaccine Safety Datalink: Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med. 2003, 348: 1747-1755.
  50. Whitney CG, Farely MM, Hadler J, et al: Active Bacterial Core Surveillance of the Emerging Infections Program Network: Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003, 348: 1737-1746.

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Practice Guidelines

  • Anon JB, Jacobs MR, Poole MD, et al: Sinus and Allergy Health Partnership: Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004, 130: (Suppl 1): 1-45.
  • Bison AL, Gerber MA, Gwaltney JM Jr, et al: Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin Infect Dis. 2002, 35: 113-125.
  • Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the advisory committee on immunization practices (ACIP). MMWR Morb Mort Wkly Rep. 2007, 56: 1-54.
  • Gonzales R, Bartlett JG, Besser RE, et al: Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: Background. Ann Intern Med. 2001, 134: 521-529.
  • Institute for Clinical Systems Improvement. Health Care Guideline: Diagnosis and Treatment of Respiratory Illness in Children and Adults, 2008. Available at http://www.icsi.org/guidelines_and_more/gl_os_prot/respiratory/respiratory_illness_in_children_and_adults
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Suggested Readings

  • Aagaard E, Gonzales R. Management of acute bronchitis in healthy adults. Infect Dis Clin North Am. 2004, 18: 919-937.
  • Arroll B, Kenealy T: Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database Syst Rev 1998;(4):CD000247.
  • Avenell A, Campbell MK, Cook JA, et al: Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): Pragmatic, randomised, double blind, placebo controlled trial. BMJ. 2005, 331: 324-329.
  • Call SA, Vollenweider MA, Hornung CA, et al: Does this patient have influenza? JAMA. 2005, 293: 987-997.
  • Cooper RJ, Hoffman JR, Bartlett JG, et al: Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001, 134: 509-517.
  • Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect Dis. 2001, 33: 757-762.
  • Musher DM. How contagious are common respiratory tract pathogens? N Engl J Med. 2003, 348: 1256-1266.
  • Nichol KL, Nordin J, Mullooly J, et al: Influenza vaccination and reduction of hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003, 348: 1322-1332.
  • Poole MD, Portugal LG. Treatment of rhinosinusitis in the outpatient setting. Am J Med. 2005, 118: 45S-50S.
  • Smith MB, Feldman W. Over-the-counter cold medications. A critical review of clinical trials between 1950 and 1991. JAMA. 1993, 269: 2258-2263.