UPPER RESPIRATORY INFECTIONS (URIs)

EPIDEMIOLOGY

URIs are the most common infectious illness in the general population and are the leading cause of missed days at work or school. They represent the most frequent acute diagnosis in the office setting.⁽¹⁾

PATHOPHYSIOLOGY⁽²⁾:

URIs involve direct invasion of the mucosa lining the upper airway. Inoculation of bacteria or viruses occurs when a person’s hand comes in contact with pathogens and the person then touches the nose or mouth or when a person directly inhales respiratory droplets from an infected person who is coughing or sneezing.

After inoculation, viruses and bacteria encounter several barriers, including physical, mechanical, humoral, and cellular immune defenses. Physical and mechanical barriers include the following:

• Hair lining the nose filters and traps some pathogens
• Mucus coats much of the upper respiratory tract, trapping potential invaders
• The angle resulting from the junction of the posterior nose to the pharynx causes large particles to impinge on the back of the throat
• Ciliated cells lower in the respiratory tract trap and transport pathogens up to the pharynx; from there they are swallowed into the stomach

Adenoids and tonsils contain immune cells that respond to pathogens. Humoral immunity (immunoglobulin A) and cellular immunity act to reduce infections throughout the entire respiratory tract. Resident and recruited macrophages, monocytes, neutrophils, and eosinophils coordinate to engulf and destroy invaders.

A host of inflammatory cytokines mediates the immune response to invading pathogens. Normal nasopharyngeal flora, including various staphylococcal and streptococcal species, help to defend against potential pathogens. Patients with suboptimal humoral and phagocytic immune function are at increased risk for contracting a URI, and they are at increased risk for a severe or prolonged course of disease.

Inflammation (chronic or acute) from allergy predisposes to URI. Children with allergy are particularly subject to frequent URIs.

INFECTION: Person-to-person spread of viruses accounts for most URIs. Household and child care settings can serve as reservoirs for infection. Bacterial infections may develop de novo or as a superinfection of a viral URI.

Viral agents occurring in URIs include a vast number of serotypes, which undergo frequent changes in antigenicity, posing challenges to immune defense. Pathogens resist destruction by a variety of mechanisms, including the production of toxins, proteases, and bacterial adherence factors, as well as the formation of capsules that resist phagocytosis.

Incubation times before the appearance of symptoms vary among pathogens. Rhinoviruses and group A streptococci may incubate for 1-5 days, influenza and parainfluenza may incubate for 1-4 days, and respiratory syncytial virus (RSV) may incubate for a week. Pertussis typically incubates for 7-10 days, or even as long as 21 days, before causing symptoms. Diphtheria incubates for 1-10 days. The incubation period of Epstein-Barr virus (EBV) is 4-6 weeks.

Most symptoms of URIs—including local swelling, erythema, edema, secretions, and fever, result from the inflammatory response of the immune system to invading pathogens and from toxins produced by pathogens.

An initial nasopharyngeal infection may spread to adjacent structures, resulting in the following:

• Sinusitis
• Otitis media
• Epiglottitis
• Laryngitis
• Tracheobronchitis
• Pneumonia

Inflammatory narrowing at the level of the epiglottis and larynx may result in a dangerous compromise of airflow, especially in children, in whom a small reduction in the luminal diameter of the subglottic larynx and trachea may be critical. Beyond childhood, laryngotracheal inflammation may also pose serious threats to individuals with congenital or acquired subglottic stenosis.

SUSCEPTIBILITY: Genetic susceptibility is involved in determining which patients have more severe disease courses than others. There are some recognized candidate gene polymorphisms with known functional changes in genes that may lead to immunosuppression.⁽³⁾ It has also been shown that host immunogenetic variation plays a role in the immune response to H1N1 and H5N1 viruses, thereby influencing disease severity and outcome in influenza caused by these viruses.^(4,5)

SIGN AND SYMPTOMS:

Symptoms of the common cold usually begin 2-3 days after inoculation. Viral URIs typically last 6.6 days in children aged 1-2 years in home care and 8.9 days for children older than 1 year in daycare. Cold symptoms in adults can last from 3-14 days, but most people recover or have symptomatic improvement within a week. If symptoms last longer than 2 weeks, consider alternative diagnoses, such as allergy, sinusitis, mononucleosis, tuberculosis, or pneumonia.

Nasal symptoms of rhinorrhea, congestion or obstruction of nasal breathing, and sneezing are common early in the course. Clinically significant rhinorrhea is more characteristic of a viral infection rather than a bacterial infection. In viral URI, secretions often evolve from clear to opaque white to green to yellow within 2-3 days of symptom onset.⁽⁶⁾ Thus, color and opacity do not reliably distinguish viral from bacterial illness.

On the other hand, the existence of persistent, purulent nasal discharge, especially if accompanied by crusts or sores in the nares, may indicate bacterial infection, particularly with S aureus. Other indicators of bacterial infection are skin pustules or impetigo and the presence of purulent signs in other family or household members.

Pharyngeal symptoms include sore or scratchy throat, odynophagia, or dysphagia. Sore throat is typically present at the onset of illness, although it lasts only a few days. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable sensation of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in a dry mouth, especially after sleep.

Cough may represent laryngeal involvement, or it may result from upper airway cough syndrome related to nasal secretions (postnasal drip). Cough typically develops on the fourth or fifth day, subsequent to nasal and pharyngeal symptoms.

Other manifestations are as follows:

• Foul breath: Occurs as resident flora processes the products of the inflammatory process; foul breath may also occurs with allergic rhinitis
• Hyposmia: Also termed anosmia, it is secondary to nasal inflammation
• Headache: Common with many types of URI
• Sinus symptoms: May include congestion or pressure and are common with viral URIs
• Photophobia or conjunctivitis: May be seen with adenoviral and other viral infections; influenza may evoke pain behind the eyes, pain with eye movement, or conjunctivitis; itchy, watery eyes are common in patients with allergic conditions
• Fever: Usually slight or absent in adults, but temperatures can reach 102°F in infants and young children;⁽⁷⁾ if present, fever typically lasts for only a few days; influenza can cause fevers as high as 40°C (104°F)
• Gastrointestinal symptoms: Nausea, vomiting, and diarrhea may occur in persons with influenza, especially in children; nausea and abdominal pain may be present in individuals with strep throat and various viral syndromes⁽⁷⁾
• Severe myalgia: Typical of influenza infection, especially in the setting of sudden-onset sore throat, fever, chills, nonproductive cough, and headache
• Fatigue or malaise: Any type of URI can produce these symptoms; extreme exhaustion is typical of influenza.

PHARYNGITIS FROM GROUP A STREPTOCOCCI:

The history alone is rarely a reliable differentiator between viral and bacterial pharyngitis. However, persistence of symptoms beyond 10 days or progressive worsening after the first 5-7 days suggests a bacterial illness. Assessment for group A streptococci warrants special attention.

The health status of contacts and local epidemiologic trends are important factors to consider. A personal history of rheumatic fever (especially carditis or valvular disease) or a household contact with a history of rheumatic fever increases a person's risk. Other factors include occurrence from November through May and patient age of 5-15 years.

Pharyngeal symptoms of sore or scratchy throat, odynophagia, or dysphagia are common. If the uvula or posterior pharynx is inflamed, the patient may have an uncomfortable feeling of a lump when swallowing. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Group A streptococcal infections often produce a sudden sore throat.

Fever increases the suspicion that infection with group A streptococci is present, as does the absence of cough, rhinorrhea, and conjunctivitis, because these are common in viral syndrome; however, symptoms overlap between streptococcal and viral illness.

Other manifestations are as follows:

• Secretions: May be thick or yellow; however, these features do not differentiate a bacterial infection from a viral one
• Cough: May be due to laryngeal involvement or upper airway cough syndrome related to nasal secretions (postnasal drip)
• Foul breath: May occur because resident flora processes the products of the inflammatory process; foul breath may also occur with allergic rhinitis and viral infections
• Headache: While common with group A streptococci and mycoplasma infections, it also may reflect URI from other causes
• Fatigue or malaise: These may occur with any URI; extreme exhaustion is typical of influenza
• Fever: While usually slight or absent in adults, temperatures may reach 102°F in infants and young children
• Rash: A rash may be seen with group A streptococcal infections, particularly in children and in adolescents younger than 18 years
• Abdominal pain: This symptom may occur in streptococcal disease, most commonly in young children, but also in influenza and other viral conditions.

A history of recent orogenital contact suggests possible gonococcal rather than streptococcal pharyngitis. However, most gonococcal infections of the pharynx are asymptomatic.⁽⁸⁾

ACUTE VIRAL OR BACTERIAL RHINOSINUSITIS:

The presentation of rhinosinusitis is often similar to that of nasopharyngitis, because many viral URIs directly involve the paranasal sinuses. Symptoms may have a biphasic pattern, wherein cold like symptoms initially improve but then worsen. Acute bacterial rhinosinusitis is not common in patients whose symptoms have lasted fewer than 7 days. Unilateral and localizing symptoms raise the suspicion for sinus involvement.

In children with bacterial sinusitis, the most common signs are cough (80%), nasal discharge (76%), and fever (63%). In adults, the classic triad of facial pain, headache, and fever is not common.⁽⁶⁾

The 2013 American Academy of Pediatrics (AAP) guidelines define acute bacterial sinusitis in children as a URI with any of the following:⁽⁹⁾

• Persistent nasal discharge (any type) or cough lasting 10 days or more without improvement
• Worsening course (new or worse nasal discharge, cough, fever) after initial improvement
• Severe onset (fever of 102°F or greater with nasal discharge) for at least 3 consecutive days.

NASAL DISCHARGE:

Nasal discharge may be persistent and purulent, and sneezing may occur. Mucopurulent secretions are seen with viral and bacterial infections. Secretions may be yellow or green; however, the color does not differentiate a bacterial sinus infection from a viral one, because thick, opaque, yellow secretions may be seen with uncomplicated viral nasopharyngitis.⁽⁶⁾

Compared with allergy or viral infection, rhinorrhea may be less predominant, and not respond to decongestants or antihistamines. Congestion and nasal stuffiness predominate in some individuals.

FACIAL AND DENTAL PAIN:

Facial or dental pressure or pain may be present. In older children and adults, symptoms tend to localize to the affected sinus. Frontal, facial, or retro-orbital pain or pressure is common. Maxillary sinus inflammation may manifest as pain in the upper teeth on the affected side. Pain radiating to the ear may represent otitis media, local adenopathy, or a peritonsillar abscess.

SORE THROAT AND DRY MOUTH:

Sore throat may result from irritation from nasal secretions dripping down the posterior pharynx. Nasal obstruction may cause mouth breathing, which may result in dry mouth, especially in the morning. Mouth breathing may especially be noted in children. Dry mouth may be prominent, especially after sleep. Foul breath may be noted, because resident flora processes the products of the inflammatory process; this symptom may also occur with allergic rhinitis.

COUGH:

Frequent throat clearing or cough may develop as a result of nasal secretions (postnasal drip). Rhinosinusitis-related cough is usually present throughout the day. The cough may also be most prominent on awakening, because of secretions that have gathered in the posterior pharynx overnight.

Daytime cough that lasts more than 10-14 days suggests sinus disease, asthma, or other conditions. Nighttime-only cough is common in numerous disorders, in part because of reduced throat clearing and airway mechanics; many forms of cough are most noticeable at night.

Upper airway cough syndrome related to nasal secretions occasionally precipitates post-tussive emesis; this may also occur with asthma. Clinically significant amounts of purulent sputum may suggest bronchitis or pneumonia.

OTHER:

Hyposmia or anosmia may result from nasal inflammation. Fatigue or malaise may be seen with any URI.

EPIGLOTTITIS:

This condition is more often found in children aged 1-5 years, who present with a sudden onset of the following symptoms:

• Sore throat
• Drooling, odynophagia or dysphagia, difficulty or pain during swallowing, globus sensation of a lump in the throat
• Muffled dysphonia or loss of voice
• Dry cough or no cough, dyspnea
• Fever, fatigue or malaise (may be seen with any URI)
• Tripod or sniffing posture

LARYNGOTRACHEITIS AND LARYNGOTRACHEOBRONCHITIS:

Nasopharyngitis often precedes laryngitis and tracheitis by several days. Swallowing may be difficult or painful, and patients may experience a globus sensation of a lump in the throat. Hoarseness or loss of voice is a key manifestation of laryngeal involvement.

In adolescents and adults, laryngotracheal infection may manifest as severe dry cough following a typical URI prodrome. Mild hemoptysis may be present; however, hemoptysis may also be seen with tuberculosis and other conditions. Children with laryngotracheitis or laryngotracheobronchitis (croup) may have the characteristic brassy, seal-like barking cough. Symptoms may be worse at night. Diphtheria also produces a barking cough.

Myalgias are characteristic in influenza, especially in the setting of hoarseness with sudden sore throat, fever, chills, nonproductive cough, and headache. Fever may be present, but it is not typical in persons with croup. Fatigue or malaise may occur with any URI.

WHOOPING COUGH:

In whooping cough, the classic whoop sound⁽¹⁰⁾ is an inspiratory gasping squeak that rises in pitch, typically interspersed between hacking coughs. The whoop is more common in children. Coughing often comes in paroxysms of a dozen coughs or more at a time and is often worst at night.

Whooping cough has 3 classic phases, as follows:

• Catarrhal (7-10 days): With predominantly URI symptoms
• Paroxysmal (1-6 weeks): With episodic cough
• Convalescent (7-10 days): Gradual recovery⁽¹¹⁾

Post-tussive symptoms include gagging or emesis after paroxysms of whooping cough. Subconjunctival hemorrhage may result from severe cough. Rib pain with pinpoint tenderness worsening with respiration may reflect rib fracture associated with severe cough.

Dyspnea and increased work of breathing may be worse at night in patients with whooping cough, because of changes in airway mechanics while the patient is recumbent. Apnea may be a chief feature in infants with pertussis. Apnea may also result from upper airway obstruction due to other causes.

DIAGNOSTIC TESTS:

NASOPHARYNGEAL SAMPLING:

Culturing of throat swabs, nasal swabs or washes, or nasal aspirates remains the standard for confirming bacterial URI pathogens. Samples should be taken from the posterior pharynx or tonsils, not from the oral cavity. In typical circumstances, rapid antigen detection tests for group A strep need not be routinely backed up by cultures in adults.⁽¹²⁾

For pharyngitis, a throat swab may be performed by vigorously rubbing a dry swab over the posterior pharynx and both tonsils to obtain a sample of exudates, if any exist. Avoid touching other surfaces of the oropharynx. Samples should be transported dry.

To perform a nasal wash, fill a small syringe (3-5 mL) with sodium chloride solution and attach a short length of flexible tubing. With the patient's head tilted back, instill the solution rapidly into the nostril, then immediately aspirate secretions back into the syringe and transfer the aspirate to laboratory specimen containers.

Nasopharyngeal specimens are indicated for suspected pertussis; the sample can be used for culture and for polymerase chain reaction (PCR) assay.⁽¹³⁾ Special selective growth media are required for Corynebacterium diphtheriae. This organism must be distinguished from the diphtheroids that commonly inhabit the nasopharynx. Neisseria gonorrhoeae also requires special culture media.

For confirming viral nasopharyngeal infection, viral cultures remain the standard. Throat swabs, nasal swabs or washes, or sputum may be cultured on special viral media to detect influenza virus, parainfluenza virus (PIV), adenovirus, respiratory syncytial virus (RSV), and other viruses. Culturing may require days to weeks.

Rapid tests for viruses include various antigen, immunofluorescence, and PCR assays. Rapid tests for influenza can be conducted on specimens from nasopharyngeal swabs, washes, or aspirates, yielding results within 30 minutes. Swabs should be taken from the posterior pharynx or tonsils, not from the oropharynx.

Enzyme immunoassays are available to detect PIV in respiratory secretions. Reverse transcriptase PCR assay may detect various viruses in nasopharyngeal samples. PCR assay detection of various viruses from blood samples is emerging as a way to track certain viral infections.

Antibody titers compared between paired specimens obtained weeks apart may help in retrospectively identifying a particular pathogen in immunocompetent patients. The first sample should be obtained during the first week of illness, and the second should be obtained 2-4 weeks later.

BLOOD COUNT AND CULTURES:

On complete blood count (CBC) with differential, patients with URIs may have an increased white blood cell (WBC) count with a left shift. Atypical lymphocytes, lymphocytosis, or lymphopenia may be seen in some viral infections; lymphocytosis may also be seen in pertussis.

However, a CBC is not likely to be helpful in differentiating the infectious agent or in directing therapy in uncomplicated URIs in the outpatient setting. Blood cultures are typically appropriate only in hospitalized patients with suspected systemic illness.

IMAGING STUDIES:

Imaging studies are not indicated for the common cold. On the other hand, suspected mass lesions, such as a peritonsillar abscess or intracranial suppurative lesions, warrant imaging. If the patient's history and physical findings suggest lower respiratory tract disease, chest imaging may be useful. Similarly, routine acute rhinosinusitis (i.e. during the first weeks of symptoms) does not require imaging unless suppurative complications or structural anomalies are suspected. In laryngitis, radiographs are of little use except to exclude foreign-body aspiration.

Laryngotracheitis in a patient with typical symptoms that respond appropriately to treatment does not require imaging. Laryngoscopy may be considered, however, if the patient is not in extremis. Hemoptysis or the presence of risk factors for tuberculosis should prompt consideration for tuberculin testing and chest radiography.

In laryngotracheobronchitis (croup), soft-tissue neck images may reveal the classic steeple sign, which represents subglottic narrowing. However, this sign is not always present and is not specific for croup.

SUSPECTED GROUP A STREPTOCOCCAL INFECTIONS:

The diagnosis should be pursued on the basis of clinical findings or a history of exposure to a case, supported by results of rapid-detection assays and cultures. Patients with a personal history of rheumatic fever or a household contact with a history of rheumatic fever are at high risk for group A streptococcal infection. In addition, the following features may raise suspicion for group A streptococcal disease:⁽¹⁴⁾

• Erythema, swelling, or exudates of tonsils or pharynx
• Fever with a temperature of at least 38.3°C (100.9°F) in the preceding 24 hours
• Tender anterior cervical lymph nodes (1 cm or larger)
• Absence of cough, rhinorrhea, and conjunctivitis (these are common in viral illness)
• Patient aged 5-15 years
• Occurrence in the season with highest prevalence (i.e. November to May)
• Local case trends

The 2012 Infectious Diseases Society of America (IDSA) guidelines recommend that swabbing the throat and testing for group A streptococcal pharyngitis by rapid antigen detection testing, culture, or both should be performed to diagnose group A streptococcal pharyngitis.⁽¹²⁾ The rationale is that clinical features alone do not reliably discriminate between streptococcal and viral pharyngitis, except when overt viral features (e.g. rhinorrhea, cough, oral ulcers, and / or hoarseness) are present.

The IDSA guidelines also suggest that diagnostic studies for group A streptococcal pharyngitis are not indicated in children under age 3 years, as acute rheumatic fever and a classic presentation of strep throat are uncommon in this age group. However, selected children under age 3 years who have other risk factors (e.g. an older sibling with known infection) may be considered for testing.⁽¹²⁾

Positive rapid antigen detection tests are highly specific and therefore do not necessitate a backup culture. Negative tests should be backed up by a throat culture in children and adolescents. Routine backup throat culture for adults with a negative rapid strep test is not typically necessary, due to the low incidence of streptococcal pharyngitis in adults and the low risk of subsequent acute rheumatic fever. Testing of asymptomatic household contacts of patients with acute streptococcal pharyngitis is not routinely recommended.

Cultures may be falsely negative for group A streptococci, because of inadequate specimen collection, covert use of antibiotics, or suboptimal laboratory practices. In addition, prolonged illness may reduce the sensitivity of culture. Specimens are optimally obtained in the first 4 days of illness. Some patients may be chronically colonized with group A streptococcus.

The level of streptococcal antibodies (antistreptolysin O) does not peak until 4-5 weeks after the onset of pharyngitis. Therefore, testing for these antibodies has no role in the diagnosis of acute pharyngitis.

SUSPECTED ACUTE BACTERIA RHINOSINUSITIS:

Laboratory studies are generally not indicated in cases of suspected acute bacterial rhinosinusitis, because the causative agents in immunocompetent individuals are well characterized.  

IMAGING STUDIES:

COMPUTED TOMOGRAPHY SCANNING: Imaging studies are not indicated for routine acute rhinosinusitis (i.e. during the first 4 weeks of symptoms). A negative study may be helpful in ruling out rhinosinusitis, but imaging studies do not help in distinguishing bacterial from viral disease, because no diagnostic signs are unique to bacterial sinus infection. Moreover, although sinus CT scanning is highly sensitive, its specificity for demonstrating acute sinusitis is low; 40% of asymptomatic patients and 87% of those with common colds have sinus abnormalities.⁽¹⁵⁾

In children, the lack of fully developed sinuses poses challenges in image interpretation. The frontal sinuses do not typically appear until age 5-8 years, and they may not develop fully in all individuals.

If rhinosinusitis symptoms persist despite therapy or if complications (e.g. extension of disease into surrounding tissue) are suspected, sinus imaging may be appropriate to evaluate the anatomy. Signs or symptoms consistent with intracranial extension of infection warrant CT scanning to evaluate the possibility of an intracranial abscess or other suppurative complication. Such symptoms may include the following:

• Proptosis
• Impaired intraocular movements
• Decreased vision
• Papilledema
• Changes in mental status
• Other neurologic findings

CT scanning yields more detailed information than plain radiography, especially regarding the ostiomeatal complex. Such information may be relevant to surgical planning. Common CT scan findings include mucosal thickening, air-fluid levels, and obstruction of the ostiomeatal complex. Not all patients with acute rhinosinusitis have air-fluid levels.

SINUS PUNCTURE AND ASPIRATION:

The sinus puncture and aspiration procedure has no role in the routine assessment of acute rhinosinusitis. However, maxillary sinus puncture and aspiration performed by an otolaryngologist may be indicated in patients with any of the following:

• Complex and persistent disease
• Suppurative extensions of disease
• Serious immunocompromise
• Nosocomial sinus infection

Rigid nasal endoscopy is a less robust option than sinus puncture because of specimen contamination by nasal flora. Respiratory flora also commonly contaminates nasal swabs and washes.

SUSPECTED INFLUENZA:

In cases of suspected influenza, confirmation of a serotype-specific diagnosis may direct options for antiviral therapy. Testing may also assist the clinician in avoiding unnecessary prescriptions for antibacterials. Most rapid tests to detect influenza that are performed in a physician's office have a sensitivity of approximately greater than 70% and a specificity of approximately greater than 90%. Therefore, viral culture may yield a positive result in up to 30% of cases with negative rapid influenza test results.⁽¹⁶⁾

TREATMENT OPTIONS:

PHARMACOLOGICAL OPTIONS:

Therapy addressing specific symptoms is the mainstay for most upper respiratory infections (URIs). Most URIs are self-limited viral infections that resolve without prescription drugs.

Recognizing viral and bacterial diseases for which specific therapy is available is important. Awareness of local trends in prevalent organisms and local resistance patterns is key. Antibacterial therapy is appropriate for patients with any of the following:

• Group A streptococcal pharyngitis
• Bacterial sinusitis
• Epiglottitis
• Pertussis
• Diphtheria

PENICILLINE V: Penicillin is the antimicrobial agent of choice for treatment of group A streptococcal pharyngitis. It is indicated for the treatment of infections caused by susceptible organisms involving the respiratory tract.

PENICILLIN G: Penicillin is the antimicrobial agent of choice for treatment of group A streptococcal pharyngitis. It is indicated for the prophylaxis or treatment of mild to moderately severe upper respiratory tract infections caused by organisms susceptible to low concentrations of penicillin G.

AMPICILLIN: Ampicillin is a second-generation penicillin that is active against many strains of Escherichia coli, Proteus mirabilis, Salmonella, Shigella, and Haemophilus influenzae. It is available in oral and injection forms.

AMOXICILLIN: Amoxicillin is the equivalent of penicillin for bacteriologic eradication of group A streptococcal infection from the tonsillopharynx. It is also appropriate for uncomplicated bacterial rhinosinusitis. It is further indicated for the treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the upper and lower respiratory tract.

AMOXICILLIN / CLAVULANATE: Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase producing bacteria. This combination is a good alternative for patients allergic to or intolerant of macrolide antibiotics. It is usually well tolerated and provides good coverage of most infectious agents, but it is not effective against Mycoplasma and Legionella species.

The half-life of oral amoxicillin / clavulanate is 1-1.3 hours. Amoxicillin has good tissue penetration but does not enter the cerebrospinal fluid.

For children over 3 months, base dosing on the amoxicillin content. Due to different amoxicillin / clavulanic acid ratios in 250-mg tablets (250 / 125) vs. 250-mg chewable tablets (250 / 62.5), do not use the 250-mg tablet until the child weighs over 40 kg.

CEFADROXIL: Cefadroxil is indicated for the treatment of susceptible bacterial infections, including those caused by group A beta-hemolytic Streptococcus.

CEFACLOR: Cefaclor is a second-generation cephalosporin that binds to 1 or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity. It has the gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, Klebsiella pneumoniae, and Moraxella catarrhalis.

This agent is indicated for management of infections caused by susceptible mixed aerobic-anaerobic microorganisms. Determine the proper dosage and route based on the condition of the patient, the severity of the infection, and the susceptibility of the causative organism.

CEFUROXIME: Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis.

This agent binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in bacterial cell wall death. The condition of the patient, the severity of the infection, and the susceptibility of the microorganism determine the proper dose and route of administration. Cefuroxime resists degradation by beta lactamase.

CEFOTAXIME: Cefotaxime is a third-generation cephalosporin with a broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. It arrests bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins, which, in turn, inhibits bacterial growth. Its safety profile is more favorable than that of aminoglycosides.

ERYTHROMYCIN: Erythromycin covers most potential etiologic agents in rhinosinusitis, including Mycoplasma species; however, it is less active against H influenzae. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for treatment of staphylococcal and streptococcal infections. This agent has the added advantage of being a good anti-inflammatory agent by inhibiting migration of polymorphonuclear leukocytes.

In children, the patient's age and weight and the severity of the infection determine proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose. The recommended dosing schedule of erythromycin may result in gastrointestinal upset. Patients may require an alternative macrolide or a change to 3-times-daily dosing. Although the standard course of treatment seems to be 10 days, treating until the patient has been afebrile for 3-5 days seems more rational.

AZITHROMYCIN: Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

This agent concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that the concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Azithromycin is used for the treatment of mild to moderate microbial infections, including group A streptococcal infection and pertussis. Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. It has a long tissue half-life.

CLARITHROMYCIN: Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

ACETAMINOPHEN: Acetaminophen is the drug of choice for pain relief in patients with documented hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), who have upper gastrointestinal disease, or who are taking oral anticoagulants. It reduces fever by directly acting on hypothalamic heat-regulating centers, increasing dissipation of body heat by means of vasodilation and sweating.

NAPROXEN: Naproxen is indicated for mild to moderate pain. Other indications include ankylosing spondylitis, osteoarthritis, and rheumatoid disorders. Onset of action for relieving pain is typically 1 hour.

IBUPROFEN: Ibuprofen is indicated for mild to moderate pain. Other indications include inflammatory diseases and rheumatoid disorders. It is available in oral forms, as well as in an injection form. Onset of action for relieving pain is typically 30 to 60 minutes.

IPRATROPIUM: Ipratropium, which is chemically related to atropine, has antisecretory properties. When applied locally, it inhibits secretions from serous and seromucous glands lining the nasal mucosa.

DIPHENHYDRAMINE: Diphenhydramine is a first-generation antihistamine with anticholinergic effects.

CHLORPHENIRAMINE: Chlorpheniramine is a first-generation agent that competes with histamine or H1-receptor sites on effector cells in blood vessels and the respiratory tract. It is one of the safest antihistamines to use during pregnancy.

BROMPHENIRAMINE: This oral H1 blocker is used for allergic conjunctivitis and rhinitis, angioedema, pruritus, and urticaria. It does not tend to cause drowsiness and is suitable to use on a day-to-day basis.

GUAIFENESIN AND DEXTROMETHORPHAN: This compound treats minor cough resulting from bronchial and throat irritation.

CODEINE: Codeine is a centrally acting antitussive that also helps to manage the pain of intercostal muscle strain associated with cough.

EPINEPHRINE: Epinephrine is used for severe bronchoconstriction, especially with underlying reactive airway disease. Its alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropy.

DEXAMETHASONE: Dexamethasone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Prednisone in equivalent doses may be substituted if administered over the course of 5 days.

PSEUDOEPHEDRINE: This agent causes vasoconstriction by directly stimulating alpha-adrenergic receptors in the respiratory mucosa. It is used for symptomatic relief of nasal congestion due to common cold, upper respiratory tract allergies, and sinusitis. It promotes nasal or sinus drainage.

PHENYLEPHRINE NASAL: This agent is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body.

OXYMETAZOLINE: Oxymetazoline stimulates alpha-adrenergic receptors and causes vasoconstriction when applied directly to mucous membranes. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.

GUIDELINES:

Treatment for URTI is based on guidelines from the prestigious societies such as NICE and American Family Physician (AFP).

To review the NICE guidelines, click on the below link:

https://www.nice.org.uk/guidance/cg69/chapter/Introduction

To review the AFP guidelines, click on the below link:

http://www.aafp.org/afp/topicModules/viewTopicModule.htm?topicModuleId=29

LONG TERM MONITORING:

In general, patients with URI should follow up with a physician if their symptoms do not improve, worsen within 72 hours, or recur. Patients with infectious mononucleosis should be instructed to follow up with their physician after a week. In patients with diphtheria, elimination of the organism should be documented with 2 consecutive negative culture results after the completion of therapy.⁽¹⁷⁾

Follow-up testing is not routinely necessary in cases of group A streptococcal pharyngitis that resolve. However, follow-up may be advisable in the setting of recurrent group A streptococcal disease, rheumatic fever, poststreptococcal glomerulonephritis, or outbreaks in semiclosed environments.

CONSULTATION AND COUNSELING:

Airway obstruction from epiglottitis, tonsillar hypertrophy, peritonsillar abscess, retropharyngeal abscess, or other causes of an obstructive mass requires emergency consultation with a surgeon. Sleep apnea associated with tonsillar hypertrophy may also prompt surgical consultation. Neurologic findings or mental status changes in the setting of suspected intracranial suppurative complications warrant emergency consultation with a neurosurgeon.

Consider consulting an infectious disease specialist when patients have any of the following:

• HIV infection
• Cancer-related or congenital immunodeficiency
• Other immunocompromise

Patients with a chronic cough after a URI may benefit from a consultation with a pulmonologist or otorhinolaryngologist to evaluate persistent infection, asthma, gastroesophageal reflux disease, or other causes of chronic cough. Patients who have had 4-5 confirmed groups A streptococcal infections in a single year or those with a chronic sore throat and adenopathy unresponsive to treatment over 6 months should be examined by an infectious disease specialist and / or surgeon.

Persistent hoarseness after 2 weeks warrants consultation with an otorhinolaryngologist. Patients with complex, persistent cases of rhinosinusitis should also be referred to an otorhinolaryngologist, for consideration of sinus puncture and aspiration.

PRECAUTIONS:

There are three categories of transmission-based precautions:

• Droplet precautions
• Contact (direct and indirect) precautions
• Airborne precautions

Interrupting transmission of a respiratory pathogen requires more than one category of respiratory precautions, including:

• The use of droplet and contact precautions at all times
• The addition of airborne precautions while undertaking an aerosol-generating procedure (AGP)

REFERENCES:

1. Cherry DK, Hing E, Woodwell DA, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2006 Summary. 2008. Available at http://www.cdc.gov/nchs/data/nhsr/nhsr003.pdf.
2. Anne Meneghetti,"Upper Respiratory Tract Infection":Pathophysiology, Emedicine.medscape.com,2017
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10. Utah Department of Health, Bureau of Epidemiology. Whooping Cough Sound Files. Utah Department of Health, Bureau of Epidemiology. Available at http://health.utah.gov/epi/diseases/pertussis/pertussis_sounds.htm. Accessed: November 29, 2012.
11. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Clinical Features. Available at http://www.cdc.gov/pertussis/clinical/features.html. Accessed: October 27, 2013.
12. [Guideline] Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.Clin Infect Dis. 2012 Nov 15. 55(10):1279-82.
13. Centers for Disease Control and Prevention. Pertussis (Whooping Cough): Specimen Collection. Full text: http://cid.oxfordjournals.org/content/early/2012/09/06/cid.cis629.full. Available at http://www.cdc.gov/pertussis/clinical/diagnostic-testing/specimen-collection.html. Accessed: October 17, 2013.
14. [Guideline] Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. Infectious Diseases Society of America.Clin Infect Dis. 1997 Sep. 25(3):574-83.
15. Fagnan LJ. Acute sinusitis: a cost-effective approach to diagnosis and treatment.Am Fam Physician. 1998 Nov 15. 58(8):1795-802, 805-6.
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