Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention

Acute respiratory tract infection (ARTI), which includes acute uncomplicated bronchitis, pharyngitis, rhinosinusitis, and the common cold, is the most common reason for acute outpatient physician office visits and antibiotic prescription in adults. Antibiotics are prescribed at more than 100 million adult ambulatory care visits annually, and 41% of these prescriptions are for respiratory conditions (1). Inappropriate antibiotic use for ARTI is an important contributor to antibiotic resistance, an urgent public health threat (2). In the United States, at least 2 million antibiotic-resistant illnesses and 23000 deaths occur each year, at a cost to the U.S. economy of at least $30 billion (2). Increased community use of antibiotics is highly correlated with emerging antibiotic-resistant infections. In places with greater prescribing of broad-spectrum antibiotics, specifically extended-spectrum cephalosporins and macrolides, rates of multidrug-resistant pneumococcal disease are higher (3). Antibiotics are also responsible for the largest number of medication-related adverse events, implicated in 1 of every 5 visits to emergency departments for adverse drug reactions (4). Adverse events range in severity from mild (for example, diarrhea and rash) to life-threatening (for example, StevensJohnson syndrome, anaphylaxis, or sudden cardiac death). Although data on adverse events after inappropriate antibiotic use are not available, an estimated 5% to 25% of patients who use antibiotics have adverse events, and about 1 in 1000 has a serious adverse event (2). Clostridium difficile diarrhea, which can be life-threatening and is usually a result of antibiotic treatment, causes nearly 500000 infections and 29300 deaths in the United States each year, leading to an estimated $1 billion in extra medical costs (5). In 2009, direct antibiotic prescription costs totaled $10.7 billion; 62% of these costs ($6.5 billion) were attributed to antibiotic prescribing in the community setting, followed by $3.6 billion in hospitals and $527 million in nursing homes and long-term care facilities (6). An estimated 50% of antibiotic prescriptions may be unnecessary or inappropriate in the outpatient setting (7) (Unpublished data. Centers for Disease Control and Prevention), which equates to more than $3 billion in excess costs. Over the past decade, antibiotic prescriptions have decreased by 18% among persons aged 5 years or older in the United States; however, prescriptions for broad-spectrum antibiotics (fluoroquinolones and macrolides) have increased by at least 4-fold (8). Reducing inappropriate antibiotic prescribing in the ambulatory setting is a public health priority. This article by the American College of Physicians (ACP) and the Centers for Disease Control and Prevention presents available evidence on the appropriate prescribing of antibiotics for adult patients with ARTI. The high-value care advice is intended to amplify rather than replace messages from recent clinical guidelines on appropriate antibiotic prescribing (919) and serves as an update of the 2001 Principles of Appropriate Antibiotic Use for Treatment of Acute Respiratory Tract Infections in Adults (9) and a complement to the pediatric principles published in 2013 (20). The target audience for this article is all clinicians providing care to adults seeking ambulatory care for ARTI. Methods We conducted a narrative review of evidence about appropriate antibiotic use for treatment of patients with ARTI syndromes, including acute uncomplicated bronchitis, pharyngitis, rhinosinusitis, and the common cold. We included current clinical guidelines from leading professional societies, such as the Infectious Diseases Society of America (IDSA). Clinical guideline recommendations were augmented with evidence-based meta-analyses, systematic reviews, and randomized clinical trials. To identify these evidence-based articles, we conducted literature searches in the Cochrane Library, PubMed, MEDLINE, and EMBASE through September 2015. We included only English-language articles and used the following Medical Subject Headings terms: acute bronchitis, respiratory tract infection, pharyngitis, rhinosinusitis, and the common cold. The focus of the article was limited to healthy adults without chronic lung disease (such as cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease) or immunocompromising conditions (congenital or acquired immunodeficiencies, HIV infection, chronic renal failure, nephrotic syndrome, leukemia, lymphoma, Hodgkin disease, generalized cancer, multiple myeloma, iatrogenic immunosuppression, or a history of solid organ transplantation). We present our findings for 4 ARTI syndromes and present a framework for antibiotic prescribing strategies for each (Table). Table. Antibiotic Prescribing Strategies for Adult Patients With Acute Respiratory Tract Infection This article was reviewed and approved by the Centers for Disease Control and Prevention and by the ACP High Value Care Task Force, whose members are physicians trained in internal medicine and its subspecialties and which includes experts in evidence synthesis. The Task Force developed the high-value care advice statements, which are summarized in the Figure, based on the narrative review of the literature. At each conference call, all members of the High Value Care Task Force declared all financial and nonfinancial interests. Figure. Summary of the American College of Physicians and Centers for Disease and Control and Prevention advice for high-value care on appropriate antibiotic use for acute respiratory tract infection in adults. Acute Uncomplicated Bronchitis Acute uncomplicated bronchitis is defined as a self-limited inflammation of the large airways (bronchi) with a cough lasting up to 6 weeks. The cough may or may not be productive (24) and is often accompanied by mild constitutional symptoms. Acute bronchitis is among the most common adult outpatient diagnoses, with about 100 million (10%) ambulatory care visits in the United States per year (8), more than 70% of which result in a prescription for antibiotics (25, 26). Acute bronchitis leads to more inappropriate antibiotic prescribing than any other ARTI syndrome in adults (8). Determining the Likelihood of a Bacterial Infection More than 90% of otherwise healthy patients presenting to their outpatient providers with an acute cough have a syndrome caused by a virus (Table) (10, 21, 22). Nonviral pathogens, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, are occasionally identified in patients with acute bronchitis (10), and Bordetella pertussis may be considered in situations where transmission in the community has been reported. However, determining whether a patient has a viral or nonviral cause can be difficult. The presence of purulent sputum or a change in its color (for example, green or yellow) does not signify bacterial infection; purulence is due to the presence of inflammatory cells or sloughed mucosal epithelial cells. Acute bronchitis must be distinguished from pneumonia. For healthy immunocompetent adults younger than 70 years, pneumonia is unlikely in the absence of all of the following clinical criteria: tachycardia (heart rate >100 beats/min), tachypnea (respiratory rate >24 breaths/min), fever (oral temperature >38C), and abnormal findings on a chest examination (rales, egophony, or tactile fremitus) (10, 27). Appropriate Management Strategies The most recent clinical guidelines for management of acute uncomplicated bronchitis recommended against routine antibiotic treatment in the absence of pneumonia (11). A systematic review of 15 randomized, controlled trials found limited evidence to support the use of antibiotics for acute bronchitis and a trend toward increased adverse events in patients treated with antibiotics (28). A randomized, placebo-controlled trial (not included in the Cochrane review) comparing ibuprofen, amoxicillinclavulanic acid, and placebo showed no significant differences in the number of days to cough resolution (24). Although macrolides (azithromycin) are frequently prescribed for patients with a cough, one study showed that patients with acute bronchitis treated with a macrolide had significantly more adverse events than those receiving placebo (29). Patients may benefit from symptomatic relief with cough suppressants (dextromethorphan or codeine), expectorants (guaifenesin), first-generation antihistamines (diphenhydramine), decongestants (phenylephrine), and -agonists (albuterol), although data to support specific therapies are limited. -Agonists have not been shown to benefit patients without asthma or chronic obstructive lung disease (30), and symptomatic therapy has not been shown to shorten the duration of illness (30, 31). Over-the-counter symptomatic relief has a low incidence of minor adverse effects, including nausea, vomiting, headache, and drowsiness (32). Providers and patients must weigh the benefits and potential for adverse effects when considering symptomatic therapy. High-Value Care Advice 1 Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected. Pharyngitis Pharyngitis is usually a benign, self-limited illness characterized by a sore throat that is worse with swallowing, with or without associated constitutional symptoms. It is a common outpatient condition, with about 12 million visits representing 1% to 2% of all ambulatory care visits in the United States annually (33). Although antibiotics are usually unnecessary, they are prescribed at most visits for pharyngitis (34). Determining the Likelihood of a Bacterial Infection Most pharyngitis cases have a viral origin; common causes include rhinovirus, coronavirus, adenovirus, herpes simplex virus, parainfluenza, enterovirus, EpsteinBarr virus, cytomegalovirus, and influenza (35). Patients with a sore throat and associated symptoms, including