Clinical Guidelines
19 January 2016

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 PreventionFREE

Publication: Annals of Internal Medicine
Volume 164, Number 6

Abstract

Background:

Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI.

Methods:

A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: “acute bronchitis,” “respiratory tract infection,” “pharyngitis,” “rhinosinusitis,” and “the common cold.”

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.
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 23 000 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, Stevens–Johnson 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 500 000 infections and 29 300 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 (9–19) 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
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.
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 >38 °C), 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, amoxicillin–clavulanic 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 β-agonists (albuterol), although data to support specific therapies are limited. β-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, Epstein–Barr virus, cytomegalovirus, and influenza (35). Patients with a sore throat and associated symptoms, including cough, nasal congestion, conjunctivitis, hoarseness, diarrhea, or oropharyngeal lesions (ulcers or vesicles), are more likely to have a viral illness and should not have further testing. Providers must rule out group A Streptococcus, the predominant bacterial pathogen, and exclude more serious infections (13). Patients with symptoms suggesting a bacterial cause should be tested for group A Streptococcus with a rapid antigen detection test, throat culture, or both. Suspicious symptoms include persistent fever, rigors, night sweats, tender lymph nodes, tonsillopharyngeal exudates, scarlatiniform rash, palatal petechiae, and swollen tonsils.
Clinical scoring criteria have been developed to help determine the likelihood of a bacterial cause. The most widely used are the modified Centor criteria, which include fever by history, tonsillar exudates, tender anterior cervical adenopathy, and absence of cough (36). Because the Centor criteria have a low positive predictive value for determining the presence of group A streptococcal infection, the IDSA suggests that they can be used to identify patients who have a low probability of group A streptococcal pharyngitis and do not warrant further testing (13). Patients who meet fewer than 3 Centor criteria do not need to be tested. Those who present with unusually severe signs and symptoms, such as difficulty swallowing, drooling, neck tenderness, or swelling, should be evaluated for rare throat infections (such as peritonsillar abscess, parapharyngeal abscess, epiglottitis, or Lemierre syndrome). Recent data suggest that Fusobacterium necrophorum is implicated in approximately 10% to 20% of endemic pharyngitis cases in adolescents (37, 38). It has also been implicated as a cause of Lemierre syndrome (39), which is a rare and life-threatening condition. The role of F necrophorum in pharyngitis and subsequent development of Lemierre syndrome warrant further study. Routine testing for F necrophorum is not recommended, but clinicians should remain vigilant and suspect Lemierre syndrome in adolescent and young adult patients with severe pharyngitis. Urgent diagnosis and treatment of Lemierre syndrome is necessary to preclude complications and death. Other rare bacterial causes are listed in the Table. No rapid diagnostic tests for other bacterial causes of pharyngitis exist, and the risks and benefits associated with antibiotic treatment are unclear.

Appropriate Management Strategies

The 2012 IDSA clinical guidelines recommend antibiotic therapy only for patients with a positive streptococcal test result (13). Patients with confirmed acute group A streptococcal pharyngitis should be treated for a duration likely to eradicate group A Streptococcus from the pharynx (usually 10 days) with an appropriate narrow-spectrum antibiotic. Specific regimens are listed in the Table.
Even though most pharyngitis cases are caused by viruses, more than 60% of adults presenting with a sore throat receive an antibiotic prescription (34). For patients diagnosed with group A streptococcal infection, antibiotics shorten the duration of sore throat by 1 to 2 days, but the benefit is modest and the number needed to treat to reduce symptoms is 6 after 3 days of treatment and 21 after 1 week of treatment (40). Evidence suggests that antibiotics may prevent complications from group A streptococcal infection, including acute rheumatic fever (which is more common in children and adolescents than adults), peritonsillar abscess, and further spread of group A Streptococcus in outbreaks (40). However, little evidence supports the prevention of acute glomerulonephritis (40). Antibiotics are not recommended for chronic group A Streptococcus carriers because they are unlikely to spread infection to close contacts and are at little or no risk for complications. Tonsillectomy solely to reduce the frequency of group A streptococcal pharyngitis in adults is not recommended (13).
Adult patients with sore throat should be offered analgesic therapy, such as aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, and throat lozenges, which can help reduce pain. Salt water, viscous lidocaine, and other mixtures are often used in clinical practice for topical pain relief, but there are few data examining these approaches. Patients can be assured that the typical course of a sore throat is less than 1 week and that antibiotics are usually not needed because they do little to alleviate symptoms and may have adverse effects (12, 13, 40).

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.

Acute Rhinosinusitis

Acute rhinosinusitis is usually a self-limited illness resulting from a viral infection, allergy, or irritant that causes inflammation of the mucosal tissue in the nasal and paranasal sinus cavity. Clinical symptoms include nasal congestion and obstruction, purulent nasal discharge, maxillary tooth pain, facial pain or pressure, fever, fatigue, cough, hyposmia or anosmia, ear pressure or fullness, headache, and halitosis. Symptom duration ranges from 1 to 33 days, with most episodes resolving within a week (41). More than 4.3 million adults are diagnosed with sinusitis annually, and more than 80% of ambulatory care visits result in an antibiotic prescription, most commonly a macrolide (42). Most antibiotic prescriptions for this condition are unnecessary (43).

Determining the Likelihood of a Bacterial Infection

Acute rhinosinusitis is usually caused by a viral pathogen. Acute bacterial rhinosinusitis (ABRS) is considered to be a secondary infection resulting from obstruction of the sinus ostia that leads to impaired mucosal clearance as a result of a viral upper respiratory tract infection (URI). Fewer than 2% of viral URIs Althoughare complicated by ABRS (14). The gold standard for diagnosis of bacterial sinusitis is sinus puncture with aspiration of purulent secretions, although it is rarely performed. Common bacteria isolated from sinus puncture are listed in the Table. Radiographic imaging has no role in ascertaining a bacterial cause (14, 44). radiologic findings, such as mucous membrane thickening or sinus fluid or opacity, have a sensitivity of 90% in detecting a bacterial cause, the specificity is only 61% (44). Imaging is not helpful in guiding treatment because viral and bacterial causes have similar radiologic features, and it would increase costs by at least 4-fold (44).
Because ABRS lacks a simple and accurate diagnostic test, clinical guidelines recommend using clinical signs and symptoms to differentiate bacterial from viral causes (15). A bacterial cause is more likely when symptoms persist for more than 10 days without clinical improvement, symptoms are severe (fever >39 °C, purulent nasal discharge, or facial pain lasting for >3 consecutive days), or symptoms worsen after an initial period of improvement (double sickening) for more than 3 days. In addition, a patient with new-onset fever, headache, or increased nasal discharge after a typical viral URI that was initially improving is suspicious for a bacterial cause.

Appropriate Management Strategies

The 2012 IDSA clinical practice guidelines recommend empirical antibiotics as soon as a clinical diagnosis of ABRS is established on the basis of clinical criteria (15). Amoxicillin–clavulanate is the preferred agent, and doxycycline or a respiratory fluoroquinolone may be used as an alternative in patients with ABRS. The American Academy of Otolaryngology–Head and Neck Surgery emphasizes watchful waiting (without antibiotic therapy) as initial management for all patients with uncomplicated ABRS, regardless of severity (16). Some professional societies, including the American Academy of Allergy, Asthma & Immunology and the American Academy of Family Physicians, recommend amoxicillin as the preferred agent (17, 18). Although the IDSA recommendation is based on concern for antibiotic resistance, specifically ampicillin-resistant Haemophilus influenzae and Moraxella catarrhalis, no direct evidence suggests that amoxicillin–clavulanate is superior. Adjunctive therapy, such as intranasal saline irrigation or intranasal corticosteroids, has been shown to alleviate symptoms and potentially decrease antibiotic use (15). Patients who are seriously ill, who deteriorate clinically despite antibiotic therapy, or who have recurrent episodes should be referred to a specialist (for example, an otolaryngologist, infectious disease specialist, or allergist) (15).
Acute uncomplicated rhinosinusitis is a self-limited infection that usually resolves without antibiotics, even in patients with a bacterial cause. Most patients diagnosed with acute rhinosinusitis have more adverse effects than benefits from antibiotics (45). A meta-analysis of adults with acute rhinosinusitis showed that the number needed to treat was 18 for 1 patient to be cured rapidly, but the number needed to harm from adverse effects from antibiotics was 8 (45).
Most patients with acute rhinosinusitis should be managed with supportive care (16); analgesics may be offered for pain, and antipyretics may be offered for fever. Additional therapies that may provide symptomatic relief include systemic or topical decongestants, saline nasal irrigation, mucolytics, intranasal corticosteroids, and antihistamines tailored to the patient's symptoms.

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).

Common Cold (Nonspecific Upper Respiratory Infection)

The common cold, a benign, self-limited illness, is the most common acute illness in the United States (19). It is a mild upper respiratory viral illness that may include some or all of the following symptoms: sneezing, rhinorrhea, sore throat, cough, low-grade fever, headache, and malaise. The symptoms are dependent on the host's inflammatory response to the particular viral infection (23). Complications of the common cold include acute bacterial sinusitis, asthma exacerbation, and otitis media; antibiotics play no role in preventing these complications (19, 46). There are about 37 million (3%) ambulatory care visits each year for the common cold, and roughly 30% result in an antibiotic prescription (47).

Causes

Multiple viruses have been associated with the common cold (Table). These viruses demonstrate seasonality and are spread through various routes of transmission: direct hand contact, contact with a contaminated environmental surface, or airborne droplets after an infected person sneezes or coughs (48). The most efficient means of transmission is direct hand contact; thus, the best method to reduce spread is appropriate handwashing.

Appropriate Management Strategies

Clinical guidelines state that symptomatic therapy is the appropriate management strategy for the common cold and that antibiotics should not be prescribed because they are not effective and lead to significantly increased risk for adverse effects (9, 19, 49). Patients seeking medical advice for the common cold should be advised that symptoms can last up to 2 weeks and should be advised to follow up with the clinician if symptoms worsen or exceed the expected time of recovery (9, 19, 49). They should also be apprised of the risks and benefits of symptomatic therapy and should be assured that antibiotics are not needed and may have adverse effects.
Symptomatic therapy is recommended for management of common cold symptoms. Although antihistamines have more adverse effects than benefits when used alone, 1 out of 4 patients treated with combination antihistamine–analgesic–decongestant products has significant symptom relief (50). Other symptomatic treatments that may offer relief include inhaled ipratropium bromide, inhaled cromolyn sodium, antitussives, and analgesics. Zinc supplements have been shown to reduce the duration of common cold symptoms in healthy persons if administered less than 24 hours after symptom onset; however, their potential benefits should be weighed against adverse reactions, such as nausea and bad taste (51, 52). No evidence supports the use of vitamins and herbal remedies, such as vitamin C or echinacea (53, 54).

High-Value Care Advice 4

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

Does Practice Follow the Evidence?

Antibiotic prescribing for ARTI has decreased since the 1990s according to the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, but the greatest reductions have been seen for ambulatory care visits for children (8, 55). This may be a result of the Centers for Disease Control and Prevention's “Get Smart: Know When Antibiotics Work” campaign and program, as well as efforts by state and local health departments to promote appropriate antibiotic use, especially among parents and providers who care for children (56–58). Furthermore, introduction of the pneumococcal conjugate vaccine for children has led to decreases in pneumococcal disease burden in both children and adults (59). Despite improvements, antibiotics are often prescribed for adults when they are not indicated, and broad-spectrum agents are prescribed at 61% of visits that lead to an antibiotic prescription even though a narrow-spectrum agent is usually preferred (1).

How Can Clinicians Promote Appropriate Antibiotic Prescription?

Over the past 2 decades, many interventions have been shown to decrease inappropriate antibiotic use by targeting physicians, patients, or both, including education, physician audit and feedback, delayed prescribing strategies, financial incentives, and health information technologies. Concern over patient satisfaction scores may limit the success of these interventions given that patient pressure plays a role in antibiotic overprescribing (60). However, patient satisfaction depends more on the patient-centered quality of the encounter, such as the provider spending enough time with the patient to explain the patient's illness, than on the receipt of an antibiotic prescription (61).
To increase patient satisfaction and decrease antibiotic prescriptions for ARTI, we offer the following evidence-based strategies. Clinicians can promote appropriate antibiotic use by labeling acute bronchitis as a “chest cold” or “viral upper respiratory infection” (62) and providing patient information sheets about appropriate antibiotic use and alternatives to antibiotics for managing symptoms (www.cdc.gov/getsmart) (63). A recent study showed an 85% decrease in antibiotic prescribing for ARTI and increased satisfaction ratings when providers gave advice on symptomatic therapy and explained why antibiotics were not needed for ARTI (64). A symptomatic prescription pad can be used to provide recommendations for management of symptoms, allowing patients to walk away with a plan of action (Supplement). When it is unclear whether an antibiotic is needed, delayed or postdated antibiotic prescriptions (also known as the wait-and-see approach) offer the possibility of future antibiotic treatment if the condition does not improve. This approach has also been shown to increase patient satisfaction and decrease antibiotic use (65).
Reducing antibiotic prescriptions on a large scale will require a multidimensional approach. A community-level, randomized trial in Massachusetts showed that implementing a multichannel intervention that includes targeting physician behavior, small-group education, disseminating educational materials to the community, and providing provider prescribing feedback in various settings further decreases antibiotic prescription rates (66). A systematic review of 39 studies showed that multifaceted interventions that combine physician, patient, and public education in various settings are most effective (67). In addition to education, examples of provider-level interventions that have been shown to be effective include audit and feedback and clinical decision support (68, 69). Although it is everyone's responsibility to use antibiotics appropriately, providers have the power to control prescriptions. Reducing inappropriate antibiotic prescribing will improve quality of care, decrease health care costs, and preserve the effectiveness of antibiotics.

Supplemental Material

Supplement. Symptomatic Relief for Viral Illnesses Prescription Pad

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Jan Matthys, MD. 26 January 2016
Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: different advices for pharyngitis.
Dear editor,
The advice that ‘clinicians should test patients with symptoms suggestive of group A streptococcal (GAS) pharyngitis by rapid antigen detection test (RAT) and/or culture for group A Streptococcus’ (1) is not in agreement with different European guidelines. (2)
The problem with GAS is that there is no sufficient reliability of clinical findings and tests, even in combination. According to the guidelines from the UK National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network (NICE/SIGN) (3), neither RAT nor throat swab culture can differentiate between the streptococcal carrier state and invasive infection.
Reflexive culture with throat swab has a poor sensitivity (73%–80%); results take up to 48 hours to be reported which is too late to significantly influence the clinical course (3); there is an asymptomatic carriage range from 6% to 40%: Streptococcus can live in our noses, mouths, and throats and not make us sick, which means that having a positive RAT or culture does not necessarily mean there is an infection. Swabs may be useful in high-risk groups, to guide the choice of treatment if treatment failure occurs. (3)
Increasingly more and European guidelines consider acute sore throat a self-limiting disease (2). Antibiotics are prescribed immediately only when the patient has risk factors, decreased immunocompetence, or extreme illness (approximately 5% of cases). (2)
Antibiotics should not be used to secure symptomatic relief in sore throat. (3) One or 2 days of extra acetaminophen/paracetamol (or nonsteroidal anti-inflammatory drugs) every 4 hours can replace unnecessary antibiotic use in most cases and might reduce the problem of antibiotic resistance.When the patient does not improve within 2 or 3 days, the physical examination must be repeated to exclude peritonsillar abscess and even the Lemierre syndrome.(4)
The conclusion is that in patients with respiratory infections where clinicians feel it is safe not to prescribe antibiotics immediately, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use, while maintaining similar patient satisfaction. (5)

We applaud that the guideline does not recommend tonsillectomy solely to reduce the frequency of group A streptococcal pharyngitis in adults. (1)

1. Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. 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. Ann Intern Med. 2016 Jan 19. doi: 10.7326/M15-1840
2. Matthys J, De Meyere M, van Driel ML, De Sutter A. Differences among international pharyngitis guidelines: not just academic. Ann Fam Med. 2007; 5:436-43.
3. National Institute of Clinical Excellence. Clinical knowledge summaries. 2012. Great Britain. SIGN. Scottish Intercollegiate Guidelines Network. Available at: http://cks.nice.org.uk/sore-throat-acute, http://www.sign.ac.uk/. Accessed 2010.
4. Matthys J, De Meyere M, De Sutter A. Fusobacterium-Positive and Streptococcal-Positive Pharyngitis. Ann Intern Med. 2015 Jun 16;162:876. doi: 10.7326/L15-5099.
5. Spurling GK, Del Mar CB, Dooley L, Foxlee R, Farley R Delayed antibiotics for respiratory infections. Cochrane Database Syst Rev 2013;4:CD004417.

Carl Llor, Ana Moragas 2 February 2016
Guidelines on appropriate antibiotic use for acute respiratory tract infections
The four high-value care recommendations described in the recently published guidelines on appropriate antibiotic use for acute respiratory tract infections (RTI) in adults are very clear, thereby assisting clinicians in providing the best care for patients as well as reducing variations and arbitrariness in practice (1). Notwithstanding, clinical guidelines are particularly challenging to apply to some groups in which the evidence is not sufficiently solid, such as in very severe infections and elderly patients with multiple comorbidities. Clinical trials comparing antibiotic and placebo very often do not include this kind of patients, the so-called ‘special’ cases. The key question is how applicable clinical guidelines are to these patients. In addition, a fear of complications as well as complacency and the existence of different guidelines across countries, i.e. acute pharyngitis, may explain the greater prescription of antibiotics for processes for which they are not indicated (2). This is why clinical practice guidelines have been criticized as being disease-driven rather than patient-driven (3).
The new Spanish guidelines on RTIs in primary care clearly state that antibiotics are never required for the common cold and influenza. However, there are some situations of otitis media, rhinosinusitis, pharyngitis, acute bronchitis and exacerbations of chronic obstructive pulmonary disease for which antibiotics are warranted. Moreover, in an attempt to consider this grey area these guidelines also define categories of patients for whom clinicians might consider prescribing an antibiotic, recommending in these cases, for instance, delayed prescribing of antibiotics, which has recently been shown to be an effective way of reducing antibiotic consumption in Spain (4).
With the aim of evaluating the percentage of cases for which antibiotics may be prescribed, we carried out an audit-based study from January to March 2015, in which a total of 248 general practitioners throughout Spain registered all cases with RTIs over a 3-week period, including a total of 11,137 patients. The overall antibiotic prescribing rate was 27.2% whereas they should have only been definitely prescribed in 7.5% of the cases and might have been prescribed in another 6.4% according to these guidelines. Doctors know that unnecessary antibiotics expose patients to adverse drug reactions and increase the prevalence of antibiotic-resistant bacteria but uncertainty in some cases makes the therapeutic decision of antibiotic prescription difficult in practice and guidelines should also endorse these situations. However, even with the use of conservative guidelines, current antibiotic prescription clearly surpasses the recommended rate.

References
1. Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. 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. Ann Intern Med 2016 Jan 19. doi: 10.7326/M15-1840.
2. González-González C, López-Vázquez P, Vázquez-Lago JM, Piñeiro-Lamas M, Herdeiro MT, Chávarri Arzamendi P, Figueiras A, and GREPHEPI Group. Effect of physicians' attitudes and knowledge on the quality of antibiotic prescription: A cohort study. PLoS One. 2015;10:e0141820.
3. Tinetti ME, Bogardus ST, Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multiple conditions. N Engl J Med. 2004;351:2870–4.
4. de la Poza Abad M, Mas Dalmau G, Moreno Bakedano M, González González AI, Canellas Criado Y, Hernández Anadón S, et al; Delayed Antibiotic Prescription (DAP) Group. Prescription strategies in acute uncomplicated respiratory infections: A randomized clinical trial. JAMA Intern Med 2016;176:21–9.

Disclosures: CL reports a grant from the Jordi Gol i Gurina Foundation for a research stage at the University of Cardiff in 2013, as well as research grants from the European Commission (Sixth and Seventh Programme Frameworks, and Horizon 2020), Catalan Society of Family Medicine, and Instituto de Salud Carlos III.

Aaron M. Harris, MD, Lauri A. Hicks, DO, Amir Qaseem, MD, PhD 13 May 2016
Author's Response
We appreciate Dr. Matthys’s comments (1) and acknowledge that even when patients with pharyngitis meet recommended criteria for group A streptococcal (GAS) testing, as many as 20% of children and fewer adults will have a positive result from colonization rather than true disease (2). This leads to overuse of antibiotics for pharyngitis.
In a recent study examining outpatient antibiotic prescribing, pharyngitis was one of the conditions for which antibiotics were most commonly prescribed; 56% and 72% of pediatric and adult pharyngitis cases, respectively, resulted in an antibiotic prescription far exceeding estimates of the true prevalence of GAS infection and colonization (37% for children and 18% for adults) (3). This suggests that in many cases providers are either not testing for GAS or are prescribing antibiotics despite a negative test result. The 2012 Infectious Diseases Society of America (IDSA) clinical guideline for diagnosis and management of GAS pharyngitis recommends testing for GAS in patients with clinical symptoms suggestive of GAS pharyngitis and prescribing antibiotics for patients with a positive GAS test result (4). An important first step in reducing unnecessary antibiotic use in the United States would be to follow the IDSA recommendation to only treat patients with positive GAS test results. We agree with Dr. Matthys that providers should offer recommendations for symptomatic relief. The Centers for Disease Control and Prevention has developed a symptomatic prescription pad that providers can use to guide symptom management in their patients (http://www.cdc.gov/getsmart/community/materials-references/print-materials/hcp/viral-rx-pad-color.pdf).
While acute pharyngitis in adults is usually self-limited, antibiotic treatment in patients with confirmed GAS pharyngitis has been shown to provide modest benefit (4,5). The goals of treatment in patients with GAS pharyngitis are to prevent nonsuppurative complications, reduce the duration of symptoms, and reduce transmission of GAS to close contacts (4,5). The magnitude of the benefit depends on the epidemiology of GAS infections in the region and the risk of post-streptococcal complications. In light of the growing threat of antibiotic resistance and increasing recognition of adverse events associated with antibiotic use, including community-associated Clostridium difficile infection, studies that carefully weigh the benefits and risks of antibiotic treatment for GAS pharyngitis are needed.

REFERENCES:
1. Matthys J, De Meyere M, van Driel ML, De Sutter A. Differences among international pharyngitis guidelines: not just academic. Ann Fam Med. 2007; 5:436-43.
2. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th Edition Edited by John E. Bennett MD MACP, Raphael Dolin MD, Martin J. Blaser MD. Saunders, 2014.
3. Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, Lynfield R, Margolis DJ, May LS, Merenstein D, Metlay JP, Newland JG, Piccirillo JF, Roberts RM, Sanchez G, Suda KJ, Thomas A, Woo TM, Zetts RM, Hicks LA. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016 May 3;315(17):1864-73.
4. 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 Disease Society of America. Clin Infect Dis. 2012; 55:1279-82.
5. Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2013; 11:CD000023.

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 164Number 615 March 2016
Pages: 425 - 434

History

Published online: 19 January 2016
Published in issue: 15 March 2016

Keywords

Authors

Affiliations

Aaron M. Harris, MD, MPH
From the Centers for Disease Control and Prevention, Atlanta, Georgia, and the American College of Physicians, Philadelphia, Pennsylvania.
Lauri A. Hicks, DO
From the Centers for Disease Control and Prevention, Atlanta, Georgia, and the American College of Physicians, Philadelphia, Pennsylvania.
Amir Qaseem, MD, PhD, MHA
From the Centers for Disease Control and Prevention, Atlanta, Georgia, and the American College of Physicians, Philadelphia, Pennsylvania.
for the High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention
Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank Dr. Adam Hersh from the University of Utah for his thoughtful review and feedback in the development of this manuscript.
Financial Support: Financial support for the development of this guideline comes exclusively from the operating budgets of ACP and the Centers for Disease Control and Prevention.
Disclosures: Dr. Moyer reports that she is Chair of the Board of Governors of the American College of Physicians. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1840. Any financial and nonfinancial conflicts of interest of the group members were declared, discussed, and resolved. A record of disclosures of interest is kept for each High Value Care Task Force meeting and conference call and can be viewed at http://hvc.acponline.org/clinrec.html.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, [email protected].
Current Author Addresses: Dr. Harris: Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA 30329.
Dr. Hicks: Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop A-07, Atlanta, GA 30329.
Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Author Contributions: Conception and design: A.M. Harris, L.A. Hicks, A. Qaseem.
Analysis and interpretation of the data: A.M. Harris, L.A. Hicks, A. Qaseem.
Drafting of the article: A.M. Harris, L.A. Hicks, A. Qaseem.
Critical revision of the article for important intellectual content: A.M. Harris, L.A. Hicks, A. Qaseem.
Final approval of the article: A.M. Harris, L.A. Hicks, A. Qaseem.
Statistical expertise: A. Qaseem.
Obtaining of funding: A. Qaseem.
Administrative, technical, or logistic support: A.M. Harris, L.A. Hicks, A. Qaseem.
Collection and assembly of data: A.M. Harris.
* This paper, written by Aaron M. Harris, MD, MPH; Lauri A. Hicks, DO; and Amir Qaseem, MD, PhD, MHA, was developed for the High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. Individuals who served on the High Value Care Task Force from initiation of the project until its approval were Amir Qaseem, MD, PhD, MHA (Chair); John Biebelhausen, MD, MBA; Sanjay Desai, MD; Lawrence Feinberg, MD; Carrie A. Horwitch, MD, MPH; Linda L. Humphrey, MD, MPH; Robert M. McLean, MD; Tanveer P. Mir, MD; Darilyn V. Moyer, MD; Kelley M. Skeff, MD, PhD; Thomas G. Tape, MD; and Jeffrey Wiese, MD. Approved by the ACP Board of Regents on 19 October 2015.
This article was published at www.annals.org on 19 January 2016.

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Aaron M. Harris, Lauri A. Hicks, Amir Qaseem, et al; for the High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention . 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. Ann Intern Med.2016;164:425-434. [Epub 19 January 2016]. doi:10.7326/M15-1840

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