TITLE: UPPER RESPIRATORY TRACT INFECTIONS
AUTHOR: SHERIF B. MOSSAD -- Department of Infectious Disease
REVISED: JULY 29, 2005
DEFINITION

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 will be 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 causes of URI. Acute laryngotracheobronchitis (croup), epiglottitis, and otitis media are infections that occur primarily in the pediatric population and will not be discussed in this chapter.
PREVALENCE
Most URIs occur more frequently during the cold winter months. Adults develop an average of two to four colds per year. Antigenic variation of hundreds of respiratory viruses result in repeated circulation in the community. A coryzal syndrome is by far the most common cause of physician visits in the United States. Colds and influenza-like illnesses also have a significant impact on the health and academic performance of university students.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.2 It is estimated that 31 million to 35 million US citizens have sinus disease.3 About 12 million individuals are diagnosed with acute tracheobronchitis annually, accounting for one third of patients presenting with acute cough.4 The estimated economic impact of non-influenza-related URI 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 up to 64,000 die each year as a result of related complications.6 Pandemics in the 20th century have claimed the lives of more than 21 million people. The average cost of each influenza epidemic is $12 million, including the direct costs of medical care and indirect costs resulting from lost work days. It is projected that the next pandemic will cost the United States $70 billion to $160 billion.7
PATHOPHYSIOLOGY
Viruses cause most URIs, with rhinovirus, parainfluenza virus, coronavirus, adenovirus, respiratory syncytial virus, coxsackievirus, and influenza virus accounting for most cases. Group A beta hemolytic streptococci (GABHS) cause 5% to 10% of cases of pharyngitis in adults. 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 bacterial superinfection of viral acute sinusitis. Less than 10% of cases of acute tracheobronchitis are caused by Bordetella pertussis, B. parapertussis, M. pneumoniae, or C. pneumoniae (TWAR). Direct invasion of respiratory epithelium results in symptoms respective to the area or areas involved.

Almost all influenza epidemics in the 20th century were caused by influenza A, but a few were due to influenza B. Most epidemics are thought to spread from school children to their families. Annual influenza epidemics result from transmission of a mutated influenza virus to 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).

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. Sinusitis and otitis media are frequently preceded by a common cold. Sinonasal allergies, anatomic abnormalities such as deviated nasal septum, sinus ostial blockade due to mucosal edema, immunodeficiency disorders such as hypogammaglobulinemia and human immunodeficiency virus infection, and cocaine abuse predispose to development of acute sinusitis.
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 diagnosis of picornavirus infections has been developed, but is not very practical.9 Conjunctivitis is characteristically seen with adenovirus infections. A sudden onset of sore throat associated with pain on swallowing, fever, absence of cough, and exposure to a person with known streptococcal pharyngitis in the previous 2 weeks support the diagnosis of GABHS-related pharyngitis.10 Patients with acute sinusitis experience symptoms for more than 1 week, including facial pain (more specific if unilateral), maxillary toothache, headache, and excessive purulent nasal discharge.11-13 Presence of hoarseness should suggest development of laryngitis. Patients with eustachian tube dysfunction will also complain of blocked ears. Difficulty in swallowing oral secretions and stridor should raise the suspicion for epiglottitis or pharyngeal abscess. Acute tracheobronchitis is an illness characterized by cough, with or without sputum production, or wheezing, lasting 1-3 weeks.4,14 Pertussis in adults with immunity due to previous illness or immunization may not present 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.15 The constellation of these symptoms during influenza epidemics is 80% sensitive in making the diagnosis. Elderly patients with influenza may also present with confusion and somnolence. The presence of sneezing among adults > 60 years reduces the likelihood of influenza.

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. Patients with GABHS-related pharyngitis may have pharyngeal erythema and exudate, palatal petechiae (doughnut lesions), tender anterior cervical lymphadenopathy, and occasionally a scarlatiniform rash.10 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 due to 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.11-13 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.14 Patients with influenza appear toxic and may have pulmonary rhonchi and diffuse muscle tenderness.
DIAGNOSIS
Because viruses cause most URIs, the diagnostic role of laboratory investigations and radiologic studies is limited. Viral culture or rapid antigen detection of influenza virus on a nasopharyngeal swab is indicated in cases where specific antiviral therapy is recommended.15 Similar tests are also available for adenovirus, respiratory syncytial virus, and parainfluenza virus. Experience with the use of reverse-transcriptase polymerase chain reaction for the diagnosis of enterovirus and rhinovirus infections is growing, but not available for daily clinical care.16 Serologic tests for viruses that can cause a mononucleosis-type illness should be done in the correct clinical setting. Influenza serologies only have epidemiologic value and should not be used for clinical care. Pharyngeal swab for rapid antigen detection of GABHS is 80% to 90% sensitive in adults and should be considered in all patients in whom GABHS-related pharyngitis is highly suspected. However, pharyngeal culture remains the gold standard for diagnosis in children and adolescents in whom GABHS-related pharyngitis is highly likely on clinical grounds, but in which the rapid antigen detection test is negative.17 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 for only severely ill patients with acute sinusitis and intracranial or orbital complications. Blood cultures should be done in severely ill patients or in those with epiglottitis or pharyngeal abscess. In patients with acute bronchitis, a normal C-reactive protein can reasonably exclude pneumonia, but may be elevated with several other infectious and noninfectious conditions.

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 in patients with suspected epiglottitis. 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 more than 3 weeks. Plain radiography has been largely replaced by computerized tomography (CT) in the evaluation of sinusitis, particularly in preparation for corrective surgery.18 Complete opacification and air-fluid level are the most specific findings for acute sinusitis. However, a large proportion of patients with 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.3 Mastoiditis and other intracranial complications of URIs should be evaluated by CT or magnetic resonance imaging.18

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

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 is 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 or otitis media does not respond to usual therapy. The most important step in the evaluation of someone with acute tracheobronchitis is to exclude pneumonia. If cough lasts more than 3 weeks, postnasal drip, asthma, and gastroesophageal reflux disease are the most likely considerations.
THERAPY
Symptomatic treatment for URIs should be directed to maximize relief of the most prominent symptom or symptoms. Rest and increased fluid intake are nonspecific measures recommended for all URIs. Hundreds of over-the-counter (OTC) medications are available in a variety of combinations.19 None of these agents has proved to be a "magic bullet", however, Americans spend more than $2 billion on OTC medications each year.

A meta-analysis of the literature19 showed that nasal symptoms improved after treatment with alpha adrenergic agonists such as oxymetazoline HCl, anticholinergic (parasympatholytic) agents such as ipratropium bromide, and first-generation antihistamines such as chlorpheniramine maleate. The use of nasal decongestants should be limited to 3 to 5 days to avoid a rebound phenomenon (rhinitis medicamentosa) after discontinuation. The sedating effect of first-generation antihistamines can be hazardous in people driving cars or operating any form of heavy machinery, but the effect may be desirable in patients having difficulty falling asleep at night as a result of their symptoms.

The role of antitussives and expectorants in the treatment of URIs remains controversial, but may be useful in patients with acute tracheobronchitis. Nonsteroidal anti-inflammatory drugs (NSAIDS) are useful in relieving fever, headache, and malaise, but these agents may be associated with gastrointestinal irritation. In addition, two COX-2 selective NSAIDS, rofecoxib and valdecoxib have been withdrawn from the market due to increased cardiovascular risks. The Food and Drug Administration (FDA) has asked manufacturers of prescription and OTC NSAIDS to revise their labeling (package insert) to include specific information about the potential gastrointestinal and 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 a variety of URI symptoms. Voice rest is important in patients with hoarseness. Mast cell stabilizers such as cromolyn sodium are widely used in preventing asthma attacks, but their a potential 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 exacerbation of symptoms.20 Systemic steroids should not be used for treatment of URIs.

After several decades of debate and numerous studies, the role of vitamin C in 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 per day have been associated with diarrhea. The average benefit in studies using 2 g to 4 g of vitamin C per day has been a decrement of about one-half day (15%) in the duration of illness.

Similarly, the role of zinc salts remains controversial, and the specific mechanism of action is unknown.21 Ionic bioavailability of zinc salts is an important factor in producing a beneficial effect. Bad taste reactions occur in up to 80% of patients receiving zinc lozenges, and nausea occurs in about 20%. The long-term effects of cumulative doses of zinc are not known, but 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.22 If considered, zinc lozenges or intranasal zinc gel should be started within 24 hours of cold symptom onset.

Therapeutic effectiveness of Echinacea in the treatment of URIs has not been established.23,24 The rutosides are naturally occurring flavonoids, found in plants. Troxerutin, one of the rutosides, reduces capillary permeability and has been used to treat edema resulting from venous insufficiency. A recent study showed a 27% reduction in the severity of rhinorrhea associated with common cold.25 Andrographis paniculata has been used in traditional medicine in the Far East for treatment of sore throat. A recent systematic review suggested that it might be an appropriate alternative treatment of uncomplicated URI.26 Similarly, elderberry syrup has been shown in one small study to shorten the duration and decrease the severity of illness of influenza.27 Because herbal agents are neither patentable nor regulated by the FDA, dosages and formulations are not standardized. Reports of Echinacea-related anaphylaxis in patients with atopy raise the concern of using it in such a common illness.
Although viruses cause most URIs, antibiotics continue to be widely prescribed for these illnesses. Unnecessary adverse effects of antibiotics and development of antimicrobial resistance can be reduced by judicious use of these drugs. In patients with URIs in whom antimicrobial therapy is indicated (see below), it generally results in symptom relief, and resolution of illness 1 to 2 days sooner than when symptomatic measures alone are used. 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 patient and the community.

Antibiotics have no role in the management of the common cold or any mild URI. However, almost 75% of adults with URIs are prescribed antibiotics by their physicians. This results in 41 million antibiotic prescriptions per year, 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.28 Unnecessary antibiotic prescriptions given for treatment of URIs cost approximately $700 million per year.29 Several symptoms predictive of physicians' behavior to prescribe antibiotics for URIs actually have poor predictive value with respect to the efficacy of antibiotics, according to the literature. 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 was independent of a patient's initial beliefs about antibiotics and whether antibiotics were prescribed.30 Satisfaction is more closely related to whether health care providers addressed patients' concerns.31 Providing patients with written information, in addition to verbal advice about the lack of evidence to support the use of antibiotics, has also been found to be valuable.32 Another approach could be giving the patient a prescription for an antibiotic with instructions to fill it only after 3 days if symptoms failed to improve.33

Patients with clinical and epidemiologic features consistent with GABHS-related pharyngitis should be started on antimicrobial therapy pending microbiologic confirmation.2 Duration of illness is shortened by 1 to 2 days when treatment is begun within 2 to 3 days of symptom onset. Prompt initiation of treatment will also decrease contagion. Oral penicillin or erythromycin (in penicillin-allergic individuals), given for 10 days, remain the preferred agents. Fortunately, no resistance to penicillin has been reported, so far, among 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 favored antibiotics for treatment of moderate to severe acute sinusitis.12,13,34 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 grams daily, or a combination of amoxicillin and clavulanate remain effective in most cases caused by resistant organisms. 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, broader-spectrum, and more expensive agents, including the newer macrolides clarithromycin and azithromycin, and the "respiratory" fluoroquinolones, levofloxacin, gatifloxacin, and moxifloxacin, are not more effective than amoxicillin.35 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 the ever-rising health care costs and, most importantly, curtail the emergence of drug-resistant organisms as a result of selection pressure. Referral to an ear, nose and throat specialist is recommended for patients who do not improve with antibiotic therapy.

Treating acute tracheobronchitis with antibiotics is not recommended, since most cases are viral, and thus resolve spontaneously.14,36 In adults who report exposure to a patient with confirmed or suspected pertussis, erythromycin or trimethoprim-sulfamethoxazole should be administered for 14 days. This will decrease contagion from bacterial shedding, but is not expected to improve resolution of symptoms, unless started within 10 days of the onset of illness. Selective beta agonist bronchodilators may offer symptomatic relief. Other measures to treat nonspecific URI, such as vaporizers, and acetaminophen may also be used.

Four agents are currently available for the treatment of influenza.37 Mild and nonfebrile influenza-like illness should not be treated with antiviral agents. Amantadine HCl and rimantadine are M2 ion channel blockers that have been available for influenza treatment for several years. They 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. Two newer agents, oseltamivir and zanamivir, are neuraminidase inhibitors (NAI), with activity against both influenza A and B. Clinical studies have shown that oseltamivir may be less effective as treatment for influenza B than for influenza A.38 NAI have significantly fewer side effects and less propensity to induce viral resistance than the adamantamines. However, they are considerably more expensive than the older agents and should be reserved for patients who do not respond to or are intolerant to these agents or for use during documented outbreaks due to influenza B virus. All influenza antiviral agents should be started within 1 to 2 days of onset of illness for maximum benefit. When used early in the course of influenza, studies have shown them to shorten the duration of illness by 1 to 2 days and to significantly reduce the severity of individual symptoms. These benefits are more pronounced in patients presenting with severe illness. Studies using neuraminidase inhibitors have also shown a reduction in the incidence of complications from influenza in the frail elderly 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.

Several antiviral agents with activity against rhinovirus or other viruses that cause URIs have been studied. Interferon is a powerful antiviral drug approved for treatment of hepatitis B and C. It has no role in the treatment of viral URIs at this time. Newer agents on the horizon, such as pleconaril,39 a viral capsid inhibitor, and tremacamra,40 a soluble intercellular adhesion molecule, show promise, but are not yet approved for the treatment of rhinovirus-related URIs.

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.41 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. A recent study showed that antibacterial home cleaning and handwashing products did not decrease the incidence of URIs.42 Treatment of the sexual partner can prevent reinfection in cases of gonococcal and herpetic pharyngitis.

The trivalent inactivated intramuscular influenza vaccine "the flu shot" is one of the few cost-saving interventions in medicine today. It results in a 30-50% reduction of respiratory illnesses, physician visits, and sick leave among 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.43 Vaccination is recommended for almost one half of the US population, including children aged 6-23 months, adults aged 50 years and older, patients with chronic medical conditions that predispose for development of influenza-related complications, their household members, 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 all patients, with emphasis that the gains of vaccination clearly outweigh its potential risks and that respiratory illnesses caused by other infectious organisms would not be 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 of the 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.44 In June 2003, the live-attenuated, cold-adapted, intranasal influenza vaccine became available in the United States.45 It 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 5-49 years. In addition, because shedding of live-attenuated virus occurs for about one week after receiving this vaccine, health care providers and household contacts of severely immunocompromised patients should 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 polyvalent pneumococcal polysaccharide vaccine has been on preventing bacteremic pneumonia in older adults.46 The conjugated pneumococcal vaccine is recommended as part of standard pediatric vaccinations. Studies are already showing a decrease in pediatric cases of acute otitis media and invasive pneumococcal disease.47 Similar reduction in adults has also been seen since the introduction of this vaccine.46 An oral live-attenuated adenovirus vaccine is available but is restricted for military use.

All four available anti-influenza drugs are also effective for prophylaxis against influenza. They should be reserved for influenza outbreaks occurring before or despite influenza vaccination, or for immunocompromised patients exposed to a person with proven influenza. Prophylaxis with any of the anti-influenza drugs should not be considered a substitute for vaccination, and fortunately they do not interfere with the antibody response to the influenza vaccine. To put things into perspective, inactivated influenza vaccine currently costs $8 and is covered by Medicare and most insurance plans, whereas a 5-days' course of rimantadine or oseltamivir costs $33 and $66, respectively. The cost of a 10-days' course for postexposure prophylaxis or a 6-weeks' course for seasonal outbreaks would be even more expensive.

Multivitamin and mineral supplements, particularly vitamin E, have no effect on the incidence and severity of URIs in well-nourished noninstitutionalized elderly individuals,48 but they decrease the incidence of common colds in elderly nursing home residents,49 as well as infectious illnesses and related work-absenteeism in diabetic community-dwelling adults.50 These findings are ascribed to micronutrient deficiency.
OUTCOMES
Most URIs resolve spontaneously in 3 to 10 days with symptomatic therapy alone. Acute bacterial sinusitis develops in 0.5% to 2% of cases of viral URI. Suppurative complications of acute pharyngitis, such as peritonsillar abscess (quinsy) or jugular venous thrombophlebitis, are uncommon. Nonsuppurative complications of pharyngitis due to GABHS, such as rheumatic fever or glomerulonephritis, are currently very rare in the United States, but they remain a major problem in developing countries. Nevertheless, long-term penicillin prophylaxis in patients with history of rheumatic fever carries a good prognosis. Patients with URI complicated by laryngitis or epiglottitis are at risk for upper airway obstruction. However, prompt attention to securing the airway, and initiation of antimicrobial therapy should result in complete recovery in these cases. Although intracranial complications of acute sinusitis, such as meningitis, brain abscess, and dural venous sinus thrombophlebitis are uncommon, they can be life threatening and may result in permanent disabilities. Mild cases of influenza in otherwise healthy individuals resolve spontaneously. People with underlying chronic medical conditions who develop influenza are at increased risk of hospitalization for treatment of exacerbation of their underlying illnesses. Influenza pneumonia is a rare complication that occurs shortly after the initial presentation of influenza. Most cases of pneumonia complicating influenza are caused by superinfection with Staphylococcus aureus or S. pneumoniae and occur several days or weeks later.
NATIONAL GUIDELINES
The general theme of these guidelines is that most URIs are viral in origin, thus would not require antimicrobial therapy. Symptomatic measures outlined above remain the mainstay of therapy. Only patients with probable or confirmed GABHS-related pharyngitis, moderately severe acute sinusitis, or moderately severe influenza should be considered for antimicrobial therapy. Influenza and pneumococcal vaccinations are recommended for people at risk for developing complications resulting from such infections.

Institution for Clinical Systems Improvement. Health Care Guideline: viral upper respiratory infection (VURI) in children and adults. Released 5/2004. Last updated 2/9//05. http://www.icsi.org. Accessed 5/21/05.

Institution for Clinical Systems Improvement. Health Care Guideline: acute pharyngitis. Released 5/2003. Last updated 2/9/05. http://www.icsi.org. Accessed 5/21/05.

Bison AL, Gerber MA, Gwaltney, Jr. JM, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Clin Infect Dis. 2002;35:113-25.

Institution for Clinical Systems Improvement. Health Care Guideline: acute sinusitis in adults. Released 5/2004. Last updated 2/9/05. http://www.icsi.org. Accessed 5/21/05.
Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2004;130:S1-S45.

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.

Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the advisory committee on immunization practices (ACIP). MMWR. 2004;53:1-40.
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