Acute Respiratory Tract Infection

Most acute respiratory infections encountered in adult patients in ambulatory practice (e.g., cough, sore throat, nasal congestion) are caused by viruses rather than bacteria. Although some patients expect antibiotic prescriptions even if their diagnosis is viral, clinicians may overestimate patients’ expectations for antibiotics. It’s important to understand how to evaluate upper respiratory symptoms, know when antibiotics are indicated and when they are not, and be able to identify appropriate alternatives for symptomatic treatment. For information on Covid-19, please see the NEJM Coronavirus (Covid-19) topic page. In this section, we will cover the following:

• ACP/CDC Guidelines for Initiating Antibiotics

• Streptococcal Pharyngitis

• Acute Bronchitis

• Acute Rhinosinusitis

ACP/CDC Guidelines for Initiating Antibiotics

The 2016 American College of Physicians and the Centers for Disease Control and Prevention provide four evidence-based recommendations for initiating antibiotics for upper respiratory infections:

High-Value Care Advice 1:

Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected.

High-Value Care Advice 2:

Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis.

High-Value Care Advice 3:

Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39°C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening).

High-Value Care Advice 4:

Clinicians should not prescribe antibiotics for patients with the common cold.

Streptococcal Pharyngitis

Group A streptococcus (Streptococcus pyogenes) is one of the few causes of pharyngitis for which antibiotic therapy is warranted. By some estimates, group A streptococcus accounts for about 10% of bacterial pharyngitis cases in adults, but this figure is likely an overestimate, because some adults with viral pharyngitis are also strep carriers. Although streptococcal pharyngitis is generally a self-limited infection, antibiotics reduce the duration of symptoms and the risk of suppurative complications (e.g., acute otitis media, peritonsillar abscess) and acute rheumatic fever, although antibiotics have not been shown to prevent poststreptococcal glomerulonephritis.

Although most nonstreptococcal cases of pharyngitis are viral, clinicians should keep in mind less common bacterial causes that require identification and treatment (e.g., gonorrhea) and have increased suspicion for both opportunistic infections and common bacterial infections in immunocompromised patients. Recognize difficulty swallowing or tolerating secretions and neck tenderness as symptoms and signs of rarer throat infections (e.g., peritonsillar abscess, epiglottitis, or Lemierre syndrome). Among viral causes, it is worthwhile to identify infectious mononucleosis (caused by Epstein-Barr virus) because of the systemic implications of this infection; tests for heterophile antibodies (e.g., the Monospot test) can confirm this diagnosis.

Diagnosis

Diagnosis of streptococcal pharyngitis is guided by clinical evidence and the rapid antigen detection test (RADT). Validated clinical scoring tools such as the modified Centor score and the McIsaac score (reproduced below) can help clinicians to estimate pretest probability of streptococcal infection. Of note, the Infectious Diseases Society of America (IDSA) guidelines do not formally recommend using these risk scores but do reinforce that certain clinical features (e.g., rhinorrhea, cough, oral ulcers, and hoarseness) are more suggestive of viral infection. The IDSA guideline does not recommend checking antistreptococcal antibody titers for routine diagnosis. Additionally, empiric treatment of asymptomatic household contacts is not recommended.

Treatment

The following table summarizes recommended treatment regimens and special considerations for treatment of Group A streptococcal pharyngitis:

(Source: Streptococcal Pharyngitis. N Engl J Med 2011.)

Acute Bronchitis

Acute bronchitis is a self-limited inflammation of the large airways of the lungs characterized by cough without pneumonia. However, cough in patients with upper respiratory infection (URI) isn’t always bronchitis — it can also be a manifestation of postnasal drainage.

Bronchitis is usually viral in nature. Common implicated viruses include influenza, parainfluenza, respiratory syncytial virus, coronavirus, adenovirus, rhinovirus, and human metapneumovirus. Except for influenza virus, diagnosis of a specific pathogen is rarely pursued in the ambulatory setting. Less often, bronchitis is caused by atypical bacteria such as Bordetella pertussis, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), and Mycoplasma pneumoniae. Identification of these pathogens is typically pursued in the context of an outbreak in a community or in a residential facility such as a nursing home or dormitory.

Diagnosis and Natural History

Diagnosis of acute bronchitis is usually clinical, based on the presence of cough with a normal lung examination and absence of dyspnea or tachypnea. However, up to 40% of patients with viral bronchitis experience bronchospasm with wheezing and dyspnea, and 50% of patients with acute bronchitis report purulent sputum production. Elderly patients can present with pneumonia with cough alone in the absence of other distinctive signs or symptoms. Purulent sputum in acute bronchitis is a result of sloughing of tracheobronchial inflammatory cells and epithelium and is unlikely to represent true alveolar disease. The cough and sputum production associated with acute bronchitis last ≥5 days and often persist for up to 3 weeks.

Treatment

Treatment of acute bronchitis is supportive and aimed at minimizing symptoms:

• If influenza is identified, treat with a neuraminidase inhibitor such as oseltamivir or zanamivir. The older adamantanes (e.g., amantadine) are no longer recommended for use in the United States.

• No specific antimicrobial therapeutic options are recommended for other viruses (e.g., adenovirus, parainfluenza virus, coronavirus other than SARS-CoV-2).

• Antiviral treatment is most effective if initiated ≤48 hours after symptom onset and can reduce duration of illness, nasal shedding of virus, and possibly rates of serious illness and death.

Cough: Although pharmacologic therapies are often prescribed to manage cough symptoms, the American College of Chest Physicians (ACCP) 2020 CHEST Expert Cough Panel does not recommend routine prescription of antibiotic therapy, antiviral therapy, antitussives, inhaled beta-agonists, inhaled anticholinergics, inhaled glucocorticoids, oral glucocorticoids, or oral nonsteroidal anti-inflammatory drugs (NSAIDs) for management of cough due to acute bronchitis. The panel found no difference in cough severity or cough duration between immunocompetent patients treated with an antibiotic or an oral NSAID, as compared with placebo. Clinical judgment is still advised for treatment of some patients (e.g., beta-agonist therapy for wheezing). If cough persists or worsens, consider reassessment, investigations, and therapy.

Bronchospasm: Note that acute viral bronchitis occasionally triggers substantial bronchospasm in patients with no previous history of asthma; such patients may require more-intensive bronchodilator therapy. When patients with chronic obstructive pulmonary disease (COPD) present with bronchitic exacerbations (e.g., increasing volume and purulence of sputum), antibiotic therapy is usually recommended. See COPD in the Pulmonology rotation guide for treatment of uncomplicated acute exacerbations.

Therapeutic options for the less common bacterial causes of acute bronchitis are summarized in the table below.

(Source: Acute Bronchitis. N Engl J Med 2006.)

Acute Rhinosinusitis

Rhinosinusitis is classified as follows:

• acute (≤4 weeks)

• subacute (4 to 12 weeks)

• recurrent acute (four or more episodes per year with complete resolution in between episodes)

  • chronic (≥12 weeks)

Rhinosinusitis can be caused by bacteria or viruses. Most cases are viral and associated with the common cold. The following factors can indicate that rhinosinusitis is bacterial, and antibiotics are required:

• no improvement or worsening of signs and symptoms after 7 days

• severe symptoms (e.g., severe pain or temperature ≥38.3°C)

• immunocompromised state

Diagnosis and Management

The following algorithm offers guidance for the diagnosis and management of acute sinusitis in adults. This algorithm allows for antibiotic therapy in patients with viral URI and persistent symptoms for more than 10 days, but some experts do not recommend antibiotic treatment in such patients. Oral or nasal decongestants, nasal glucocorticoids, or nasal saline irrigation may provide relief of symptoms, but compelling evidence for their effectiveness from randomized trials is lacking.

(Source: Acute Sinusitis in Adults. N Engl J Med 2016.)

Bacterial rhinosinusitis: If bacterial rhinosinusitis is strongly suspected, various guidelines recommend either amoxicillin or amoxicillin-clavulanate as the initial antibiotic choice.

• The Infectious Diseases Society of America recommends prescribing regular-strength amoxicillin-clavulanate (such as 875 mg by mouth twice daily for 5 to 7 days) as the initial choice for most patients and prescribing high-dose amoxicillin-clavulanate (2 g twice daily by mouth or 90 mg/kg/day twice daily by mouth) for patients with risk factors for resistance or severe infection (e.g., patients who have evidence of systemic toxicity with a fever of 39°C or higher, aged >65 years, recently hospitalized, taken antibiotics in the past month, immunocompromised, from regions with high endemic rates [≥10%] of invasive penicillin-resistant S. pneumoniae).

• Doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) can be used to treat patients with penicillin allergy, but the U.S. Food and Drug Administration recommends using fluoroquinolones only for patients without other treatment options.