Upper Respiratory Tract Infection Workup

In upper respiratory tract infections (URIs), tests for specific pathogens are helpful when targeted therapy depends on the results (eg, group A streptococcal infection, gonococcus, pertussis). Specific bacterial or viral testing is also warranted in other selected situations, such as when patients are immunocompromised, during certain outbreaks, or to provide specific therapy to contacts. There is insufficient evidence that testing for atypical bacteria (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae) would improve clinical outcomes in pharyngitis. ^[33]

Targeted therapy is not available for most viruses that cause URI. Therefore, viral testing is rarely indicated for uncomplicated viral URIs in the outpatient setting. However, confirmation of a viral condition such as influenza may reduce inappropriate use of antibiotics. In addition, URI suspected to be due to herpes simplex virus (HSV) warrants diagnosis because specific therapy is available for this infection.

Testing may be required if progressive URI symptoms last longer than 14 days and have no other identifiable cause, such as asthma or allergic rhinitis. Testing is also indicated if the clinical assessment suggests sexually transmitted disease–related oropharyngeal disease; specific therapy exists for pathogens such as Neisseria gonorrhoeae.

With immunocompromised patients, specific information about infection may help to tailor antimicrobial choices, herald potential complications, and aid in determining whether hospitalization would be appropriate. Viral testing may be used for making the diagnosis, monitoring the patient, or predicting the prognosis.

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. ^[2]

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

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

Nasopharyngeal specimens are indicated for suspected pertussis; the sample can be used for culture and for polymerase chain reaction (PCR) assay. ^[37] 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 (ie, during the first weeks of symptoms) does not require imaging unless suppurative complications or structural anomalies are suspected. In laryngitis, radiographs are of little use except to exclude foreign-body aspiration.

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

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

Suspected Group A Streptococcal Infection

The diagnosis should be pursued on the basis of clinical findings or a history of exposure to a case, supported by results of rapid-detection assays and cultures. Patients with a personal history of rheumatic fever or a household contact with a history of rheumatic fever are at high risk for group A streptococcal infection. In addition, the following features may raise suspicion for group A streptococcal disease ^[1] :

• 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 (ie, 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. ^[2] The rationale is that clinical features alone do not reliably discriminate between streptococcal and viral pharyngitis, except when overt viral features (eg, rhinorrhea, cough, oral ulcers, and/or hoarseness) are present.

The IDSA guidelines also suggest that diagnostic studies for group A streptococcal pharyngitis are not indicated in children under age 3 years, as acute rheumatic fever and a classic presentation of strep throat are uncommon in this age group. However, selected children under age 3 years who have other risk factors (eg, an older sibling with known infection) may be considered for testing. ^[2]

Positive rapid antigen detection tests are highly specific and therefore do not necessitate a backup culture. Negative tests should be backed up by a throat culture in children and adolescents. Routine backup throat culture for adults with a negative rapid strep test is not typically necessary, due to the low incidence of streptococcal pharyngitis in adults and the low risk of subsequent acute rheumatic fever. Testing of asymptomatic household contacts of patients with acute streptococcal pharyngitis is not routinely recommended. ^[2]

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

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

Laboratory studies are generally not indicated in cases of suspected acute bacterial rhinosinusitis, because the causative agents in immunocompetent individuals are well characterized. ^[7] (See Acute Sinusitis.)

Imaging studies

Computed tomography scanning

Imaging studies are not indicated for routine acute rhinosinusitis (ie, during the first 4 weeks of symptoms). A negative study may be helpful in ruling out rhinosinusitis, but imaging studies do not help in distinguishing bacterial from viral disease, because no diagnostic signs are unique to bacterial sinus infection. Moreover, although sinus CT scanning is highly sensitive, its specificity for demonstrating acute sinusitis is low; 40% of asymptomatic patients and 87% of those with common colds have sinus abnormalities. ^[16]

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

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

• 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. The image below reveals sinusitis on a CT scan.

Other imaging studies

If a patient cannot tolerate CT scanning, a plain radiographic Waters view of the frontal and maxillary sinuses may be considered. Most cases of rhinosinusitis involve the maxillary and frontal sinuses, so views that include these sinuses are important. Common radiographic findings include air-fluid levels and mucosal thickening, although not all sinusitis patients have air-fluid levels.

Sinus ultrasonography may be considered when pregnancy or radiation exposure is a concern. Ultrasonography may also be useful in the intensive care unit to evaluate nosocomial sinusitis. ^[35] Magnetic resonance imaging (MRI) may be optimal for evaluation of suspected fungal sinusitis or suspected tumor.

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.

For information on testing and case management of suspected influenza, see the Medscape Reference article Influenza.

 

Epstein-Barr virus (EBV) antibody tests are not usually needed to diagnose  infectious mononucleosis. However, specific antibody tests may be needed to for people who ^[23] :

• Do not have a typical case of infectious mononucleosis.
• Have other illnesses that can be caused by EBV infection.

Confirming the diagnosis may be helpful in guiding outpatient care and expectations. A positive result on a heterophile antibody test (eg, Monospot) is diagnostic but is not recommended by the CDC for general use because antibodies detected by Monospot can be caused by conditions other than infectious mononucleosis. ^[23]

 

In patients with mucocutaneous lesions suggestive of HSV infection, isolation of the virus in cell culture is the preferred virologic testing strategy. As lesions begin to heal, the sensitivity of culturing rapidly declines. Cytologic detection of cellular changes of HSV infection is insensitive and nonspecific and should not be relied on for diagnosis of HSV infection. ^[36] Testing with polymerase chain reaction (PCR) assay is available in some laboratories.

Pertussis is clinically diagnosed on the basis of symptoms of whooping cough. When bacteriologic confirmation is sought, the receiving laboratory should be contacted for special instructions on specimen collection. Culture of a nasopharyngeal aspirate is the criterion standard. ^[37] Nasopharyngeal aspirates are ideally collected 0-2 weeks after symptom onset but may provide accurate results for as long as 4 weeks in infants and unvaccinated patients.

Rapid direct fluorescent antibody testing is available to test for pertussis. Although PCR assay for pertussis is emerging as a sensitive detection tool, respiratory illness outbreaks mistakenly attributed to pertussis highlight the limitations of relying solely on PCR assays to confirm the disease. The positive predictive value is lower when PCR assay is used as a screening tool without culture confirmation during a suspected pertussis outbreak. ^[21]

Serologic testing is optimally performed 2-8 weeks after symptom onset, when antibody titers are highest. However, testing may be performed on specimens as long as 12 weeks after symptom onset.

In cases of suspected epiglottitis, aggressive instrumentation may precipitate spasm and airway compromise. If the diagnosis is suspected in patients not in extremis, an otorhinolaryngologist may perform direct visualization by laryngoscope to confirm the disease. Immediate access to intubation and cricothyroidotomy equipment is required. This diagnostic procedure is often performed in the operating room.

Laryngoscopy provides an opportunity for obtaining culture samples; however, contamination of the samples by upper airway flora is common. Direct visualization by laryngoscope is the standard for confirming epiglottitis.

During the procedure, a swab sample may be taken for culturing. However, because of contamination with upper airway flora, such cultures are not ideal unless an aspirate is taken from an epiglottic abscess. Therefore, blood cultures should also be ordered. Blood cultures for Haemophilus influenzae are positive in more than 80% of children and in approximately 25% of adults.

Before ordering radiography, consider whether imaging may unnecessarily delay patient care. Note that patients with epiglottitis breathe most comfortably when they are upright; the supine position may precipitate respiratory compromise. For patients in whom the diagnosis of epiglottitis is uncertain, a lateral neck image obtained in the erect position with soft-tissue technique may be indicated.

In one small, retrospective study, lateral neck radiographs were 33% specific for epiglottitis, with a positive predictive value of only 50%; the negative predictive value was 100%. ^[39] Given the high false-positive rate, the authors concluded that the role of radiography was limited in epiglottitis. However, neck imaging may help to rule out the disease. Radiographic findings include a swollen epiglottis with a shape similar to the human thumb. The image below illustrates epiglottitis on a neck radiograph.

CT scanning may be superior to radiography in delineating the soft-tissue structures in the upper airway. However, CT scanning may unnecessarily delay therapy, and recumbent positioning may precipitate respiratory compromise.