Merle A. Sande

Principles of Appropriate Antibiotic Use for Acute Pharyngitis in Adults: Background

1.0 Background Sore throat is one of the most common chief complaints of adults treated in an outpatient setting. Although its differential diagnosis is large and includes many other causes that are important to recognize (Table), the vast majority of immunocompetent adults presenting with sore throat have acute infectious pharyngitis. Most of the widespread antibiotic use in such patients is based on an effort to treat bacterial (particularly streptococcal) pharyngitis. Recognition and specific treatment of some of these other sore throat entities are important but are beyond the scope of this paper, which addresses the treatment of nongonococcal, nondiphtherial acute pharyngitis in healthy adults. Table. Differential Diagnosis of Sore Throat in the Immunocompetent Adult 1.1 Acute pharyngitis accounts for 1% to 2% of all visits to outpatient departments, physician offices, and emergency departments (1). A wide range of infectious agents, most commonly viruses, cause acute pharyngitis. Approximately 5% to 15% of cases in adults are caused by group A -hemolytic streptococcus (GABHS) (2-7). In some patients, it can be important to identify an infectious cause other than GABHS (for example, gonococcal pharyngitis, EpsteinBarr virus, and acute HIV infection), but in the vast majority of cases, acute pharyngitis in an otherwise healthy adult is self-limited and rarely produces significant sequelae. 1.2 Antibiotics are prescribed to a substantial majority (approximately 75%) of adult patients with acute pharyngitis (8). Physicians report that they prescribe unwarranted antibiotics because they believe that patients expect them, that patients will reconsult if antibiotics are not prescribed, that patients will be unsatisfied without a prescription, and that it is quicker to write a prescription than to explain why a prescription is not indicated (9-11). However, physicians are not very good at predicting which patients expect antibiotics (11, 12), and patient satisfaction depends less on whether an antibiotic is prescribed, or even whether preconsultation expectations are met, than on whether the physician shows concern and provides reassurance (9, 11-15). Delaying antibiotic prescriptions does not increase the chance that patients will return in the next few days for reconsultation. Prescribing antibiotics medicalizes the illness, and one study found increased likelihood that patients would return for the next similar illness (13, 15, 16). The inappropriate use of antibiotics can have significant negative consequences both to individual patients and to public health. Goals This paper examines the available evidence regarding the diagnosis and treatment of acute GABHS pharyngitis in adult patients. It makes recommendations that balance concerns about the potential consequences of untreated GABHS and the goal of decreasing inappropriate antibiotic prescriptions. It discusses pharyngitis in adults (patients 18 years of age), a population in which GABHS accounts for only approximately 5% to 15% of cases (2-7) and in which such complications as acute rheumatic fever are much less common. These guidelines do not apply to patients with a history of rheumatic fever, valvular heart disease, immunosuppression, or recurrent or chronic pharyngitis (symptoms > 7 days), or to patients whose sore throats have a cause other than acute infectious pharyngitis. They are not intended to apply during a known epidemic of acute rheumatic fever or streptococcal pharyngitis or in nonindustrialized countries in which the endemic rate of acute rheumatic fever is much higher than in the United States. Clinicians should always consider the epidemiologic circumstances when applying these recommendations in practice. Furthermore, these principles are not intended to comment on or contradict previous practice guidelines from other organizations (17, 18), which are primarily directed at sore throat evaluation in children. 2.0 Methods We conducted a systematic review of the literature from 1950 to 2000 for these evidence-based management principles. We identified all randomized, controlled trials or meta-analyses of randomized, controlled trials that contained clear definitions of criteria for inclusion, diagnosis, and outcomes, as well as studies evaluating diagnostic strategies for GABHS pharyngitis. We searched MEDLINE and the Cochrane Library, and we also searched the references of the inception articles to identify other studies. Our search strategy sought English-language articles and used the keywords sore throat, group A streptococcus, pharyngitis, tonsillitis, streptococcal pharyngitis, throat culture, and strep. Many of the identified articles had easily recognizable methodologic flaws (for example, use of convenience samples, exclusion of patients without a throat culture or those without a positive throat culture, and lack of an appropriate or clearly identified criterion standard), and we considered these limitations when evaluating the evidence and making our recommendations. Furthermore, the efficacy reported in the clinical trials may have been affected in part by repeated clinic visits, repeated cultures, and checks of patient adherence to pill ingestion, all of which would result in overestimation of the effect size of treatment. We did not mathematically summarize the various trials because of the variable quality of the cited evidence. 3.0 Evidence for Antibiotic Treatment of Pharyngitis Caused by GABHS Pharyngitis caused by GABHS is predominantly a disease of children 5 to 15 years of age. It has a prevalence of approximately 30% in pediatric pharyngitis but only 5% to 15% in adult pharyngitis in nonepidemic conditions (2-7, 19, 20). Physicians may consider prescribing antibiotics for streptococcal pharyngitis to prevent rheumatic fever, prevent acute glomerulonephritis, prevent suppurative complications, decrease contagion, and relieve symptoms. 3.1 Acute Rheumatic Fever Early randomized trials demonstrated that penicillin treatment of streptococcal pharyngitis is effective in preventing acute rheumatic fever (21-23) (relative risk, 0.28 [24]). This translated into a number needed to treat for benefit (NNTB) of approximately 63 to prevent one case of acute rheumatic fever in the samples studied. These early trials were usually performed in populations with a much higher incidence of acute rheumatic fever in both the treated and control groups than is present today. The reported incidence per population was approximately 60 times greater in 1965 than in 1994 (the last year for which the Centers for Disease Control and Prevention reported statistics); therefore, the NNTB today is undoubtedly much higher, in the range of approximately 3000 to 4000 (25-27). Carditis is the most serious complication associated with acute rheumatic fever. In recent outbreaks of acute rheumatic fever, carditis was seen in 50% to 91% of pediatric cases (28-31). These data probably reflect diagnosis of subclinical cases by echocardiography. Carditis occurred in approximately one third of adult cases of acute rheumatic fever (32, 33). The most important consequence of carditis, permanent valvular dysfunction, is most common after clinically severe carditis (28). Given that acute rheumatic fever is rare in adults, that carditis is not a common feature of adult cases of acute rheumatic fever, and that most cases of carditis in adults are mild or asymptomatic, the likelihood of permanent cardiac dysfunction seems to be very small. Thus, the NNTB to prevent a single case of clinically significant carditis is substantially greater than the NNTB to prevent a single case of acute rheumatic fever. During the 1980s, several outbreaks of acute rheumatic fever occurred, causing concern about reemergence of the disease (29-32, 34, 35). It is important to consider local epidemics. Physicians should be prepared to revise their treatment approaches if evidence suggests an outbreak. 3.2 Acute Glomerulonephritis Although poststreptococcal acute glomerulonephritis occurs, it is extremely rare, even in the absence of antibiotic treatment (36-41). Furthermore, no evidence shows that antibiotic therapy for pharyngitis decreases the incidence of this complication (36-41). 3.3 Peritonsillar Abscess The incidence of suppurative complications, regardless of treatment with antibiotics, is also low (42-45). A review of randomized trials from the 1950s and 1960s indicates that antibiotics decrease the incidence of peritonsillar abscess (quinsy) complicating streptococcal pharyngitis (24), with a best estimate for NNTB of 27. Modern clinical trials (44, 45) provide some evidence that targeting antibiotics to a subset of patients with higher clinical likelihood of GABHS may prevent peritonsillar abscess. However, in another recent review of GABHS pharyngitis in practice, Little and Williamson (46) reported that the risk for peritonsillar abscess was not reduced because many patients did not present for care until after the complication had developed (46). A recent retrospective study of more than 30 000 patients confirms these findings (47). Among patients who developed suppurative complications, 31 of 71 (44%) had them at first presentation (47). Of the other 56% who presented with pharyngitis before subsequent development of peritonsillar abscess, only approximately 25% showed GABHS on culture or rapid antigen test, and most (67%) had been treated with antibiotics that effectively eradicated GABHS. 3.4 Prevention of Spread of Disease Streptococcal infection often occurs in epidemics, and contagion is a problem in areas of overcrowding or close contact. Although treatment must continue for 10 days, 24 hours of antibiotic therapy greatly reduces the recovery of GABHS from pharyngeal cultures (41, 48-50). While antibiotics are recommended as a means of reducing spread in schools and other closed settings (20), the impact of treatment on disease spread in noninstitutionalized adult po

Principles of Appropriate Antibiotic Use for Treatment of acute respiratory Tract Infections in adults: Background, specific aims, and methods

Background The Need To Improve Antibiotic Prescription for Acute Respiratory Infections 1. The epidemic increase in antibiotic-resistant Streptococcus pneumoniae is an ambulatory care problem. Excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community (1-4). Penicillin resistance in S. pneumoniae has increased in an epidemic manner in the past 10 years (5, 6). Resistance to macrolides, doxycycline, trimethoprimsulfamethoxazole, and second- and third-generation cephalosporins has also increased. Special attention to antibiotic-resistance profiles of S. pneumoniae is warranted, since this pathogen is the leading cause of community-acquired bacterial pneumonia, bacterial meningitis, bacterial sinusitis, and otitis media in the United States (7). 2. Previous antibiotic use is an important risk factor for carriage of and infection with antibiotic-resistant Streptococcus pneumoniae. The major risk factors for carriage of and infection with antibiotic-resistant S. pneumoniae are geographic location, recent exposure to antibiotics, and exposure to young children. Carriage of S. pneumoniae (and antibiotic-resistant S. pneumoniae) primarily occurs in the nasopharynx and oropharynx of susceptible hosts (8, 9). Factors contributing to the spread of S. pneumoniae (such as close contact and viral respiratory infections) are also associated with the spread of antibiotic-resistant S. pneumoniae (10-12). For example, carriage and transmission of antibiotic-resistant S. pneumoniae are greatest during winter months and in environments that facilitate the transmission of respiratory secretions (8). The prevalence of carriage of S. pneumoniae and antibiotic-resistant S. pneumoniae appears to be greatest in young children; up to one third of children who visit health clinics are reported to be nasopharyngeal carriers of antibiotic-resistant S. pneumoniae (13-15). The prevalence of S. pneumoniae colonization in the upper airways in adults is about 5%; this value increases if children are present in the household (10). Although the risks for transmission of antibiotic-resistant S. pneumoniae mirror those for S. pneumoniae, numerous retrospective and prospective carriage studies have also identified previous antibiotic use, especially for a prolonged period (for example, as prophylaxis against recurrent acute otitis media), to be the most significant risk factor for carriage and subsequent spread of antibiotic-resistant S. pneumoniae (14-18). The risk for carriage of antibiotic-resistant S. pneumoniae is two to nine times greater in persons who have recently used antibiotics. A precipitously rapid increase in antibiotic resistance has also been observed for strains of S. pneumoniae in blood, cerebrospinal fluid, and joint fluid in the United States since 1986, when invasive antibiotic-resistant S. pneumoniae isolates were rare or absent (5). Like carriage of antibiotic-resistant S. pneumoniae, invasive infection with antibiotic-resistant S. pneumoniae is associated with previous antibiotic use (6, 19-22). When invasive infection with antibiotic-resistant S. pneumoniae occurs, antibiotics with poor central nervous system penetration and bacteriostatic (instead of bactericidal) properties must sometimes be used. Treatment failures have been reported in patients with pneumococcal meningitis after therapy with penicillin, chloramphenicol, clarithromycin, ceftriaxone, and cefotaxime (12, 23-26). The management of outpatient bacterial infections, such as acute otitis media, becomes substantially more difficult because of high rates of antibiotic-resistant S. pneumoniae in children with such infections (27, 28). However, few studies have quantified the clinical impact of antibiotic-resistant S. pneumoniae on morbidity, mortality, and health care costs in children or adults. In a study of hospitalized patients with severe pneumococcal pneumonia in Spain, where a high prevalence of antibiotic-resistant S. pneumoniae preceded the current increase in the United States, no association was seen between antibiotic resistance and mortality (29). However, most patients had intermediate-level penicillin resistance; in such patients, serum and lung interstitium concentrations of antibiotic are sufficiently high to overcome resistance. A recent study of U.S. adults hospitalized with community-acquired pneumonia due to S. pneumoniae found that mortality was significantly associated with high-level antibiotic-resistant S. pneumoniae (minimum inhibitory concentration 4 g/mL), after exclusion of deaths that occurred within the first 2 to 4 days of hospitalization (30). Exclusion of early deaths is justified, since antibiotic therapy has not been shown to affect early mortality in adults with antibiotic-susceptible pneumococcal disease (31). Because of the current increase in antibiotic resistance in community bacterial pathogens, many experts are predicting an impending postantibiotic era (2-4). 3. Most antibiotic prescriptions in the ambulatory setting are for acute respiratory infections. Intervention strategies aimed at reducing community use of antibiotics must address the management of acute respiratory infections. These illnesses are the most frequent reasons for seeking medical attention in the United States, and they are associated with up to 75% of total antibiotic prescriptions each year (32). Transmission of S. pneumoniae is enhanced during viral acute respiratory infection through increased respiratory and nasal secretions (10). As a result, antibiotic treatment of viral acute respiratory infections is particularly problematic, since it may selectively promote the acquisition and spread of antibiotic-resistant bacteria by patients. Specific acute respiratory infections that must be targeted for reducing unnecessary antibiotic use in adults are uncomplicated acute bronchitis (not including acute exacerbations of chronic bronchitis), acute sinusitis, pharyngitis, and nonspecific upper respiratory tract infection (including the common cold). These diagnoses are usually made in the presence of a clinical syndrome with a predominant clinical feature, so that prominent acute cough is taken to mean acute bronchitis, prominent nasal and sinus symptoms are thought to signify sinusitis, and prominent acute sore throat is considered pharyngitis. Acute respiratory symptoms in the absence of a predominant symptom are typically diagnosed as upper respiratory tract infection. Each of these syndromes can be caused by a multitude of different viruses and, on occasion, bacteria. The degree of excess prescription of antibiotics varies for each diagnosis. Antibiotic treatment of a cold, an upper respiratory tract infection, or acute bronchitis is almost always inappropriate because the vast majority of these syndromes have a nonbacterial cause. Antibiotic treatment of sinusitis and pharyngitis is sometimes justified but should be limited to appropriate subsets of patients. Potential Benefit and Harm of Adherence to Principles of Appropriate Antibiotic Prescription Potential Benefits of Indiscriminant Antibiotic Prescription Some clinicians may prescribe antibiotics because they believe that a very small fraction of patients might benefit or they hope to prevent the remote case of a bad outcome (and a potential lawsuit). A theoretical clinical benefit of treating viral respiratory tract infections with antibiotics cannot be excluded. A truism for all clinical trials performed in medicine is that a benefit of treatment cannot be excluded for outcomes that occur less frequently than the sample size can detect (that is, there will always be specific outcomes that were not or cannot be measured). For example, invasive bacterial disease, such as sepsis or bacterial meningitis, is too rare an event to be evaluated in a randomized, controlled trial with enough power to exclude a potential benefit of antibiotic treatment. The incidence of bacterial meningitis in the United States is about 3 per 100 000 persons in the general population (1995) (33) or about 9 per 100 000 persons with an office visit for an acute respiratory illness (unpublished data based on the National Ambulatory Medical Care Survey, 1997). Indiscriminant use of antibiotics may also in theory prevent complications of other undiagnosed bacterial infections, such as acute rheumatic fever. While these hypothetical benefits are possible, no evidence supports their existence. Potential Harms of Indiscriminant Antibiotic Prescription In contrast to the theoretical clinical benefit of indiscriminant prescription of antibiotics, the potential harm of this practice is well established at the level of the patient and society. At the patient level, risks include allergic reactions (such as urticaria, rash, and anaphylaxis), adverse reactions (such as gastrointestinal discomfort or yeast infections), and drugdrug interactions (such as QT interval prolongation caused by warfarin and oral contraceptives), as well as the increased likelihood that a pneumococcal infection in the ensuing months will be due to an antibiotic-resistant strain. At the societal level, the adverse effects of indiscriminant antibiotic use on rates of antibiotic resistance are well established, and the effects on health care costs (for antibiotics and office visits) are straightforward. Finally, indiscriminant antibiotic use could serve to inappropriately medicalize viral illnesses. This tendency not only usurps the ability of individual persons to care for self-limited illnesses but also carries large associated costs in terms of unnecessary office visits and prescriptions. Potential Benefits of Limiting Indiscriminant Antibiotic Prescription Besides decreasing the risk for the harms noted above, the intended result of efforts to decrease indiscriminant antibiotic use in the ambulatory setting is to reduce (and preferably reverse) the increase in antibiotic-re

Principles of appropriate antibiotic use for acute rhinosinusitis in adults: background.

1.0 The excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria (1-2, 4). Antibiotic treatment of common respiratory infections accounts for a large percentage of this excessive use. Rhinosinusitis is one of the 10 most common diagnoses in ambulatory practice and is the cause of an estimated 25 million U.S. physician office visits in 1995 (5). Fourteen percent of Americans claim to have had a previous diagnosis of sinusitis (6), but the term sinusitis typically has a different meaning for patients and for primary care physicians. When patients say I have sinus trouble, they usually describe acute or chronic symptoms, such as headache, facial pain, nasal congestion, or rhinorrhea, each of which may be due to a variety of causes. Primary care physicians tend to think of sinusitis as an acute bacterial infection, for which they prescribe an antibiotic in 85% to 98% of cases (7, 8). According to data from the National Ambulatory Medical Care Survey, sinusitis is the fifth most common diagnosis for which an antibiotic is prescribed (9). However, sinusitis is frequently caused by viral infection and will resolve in most patients without antibiotic treatment. These principles present an argument for a conservative approach to use of antibiotics in patients with sinusitis-like symptoms, consistent with efforts to reduce antibiotic use for respiratory infections in ambulatory patients. Background, rationale, and methods used for development of these principles have been published separately (10). 1.1 The term sinusitis refers to inflammation of the mucosa of the paranasal sinuses, regardless of cause. Because sinusitis is invariably accompanied by inflammation of the contiguous nasal mucosa, rhinosinusitis has become the preferred term. Most cases of rhinosinusitis involve more than one of the paranasal sinuses, most commonly the maxillary and ethmoid sinuses. Isolated infection of a frontal or sphenoid sinus is a rare and potentially dangerous condition, usually caused by bacteria, which presents very differently from the vast majority of cases of rhinosinusitis seen in primary care. Patients with this type of infection seem seriously ill and may show signs of cavernous sinus thrombosis or meningitis. Diagnosis and treatment of isolated frontal and sphenoid sinusitis are beyond the scope of this discussion. For purposes of diagnosis and treatment, rhinosinusitis is classified as acute (symptom duration < 4 weeks), subacute (symptom duration 4 to 12 weeks), and chronic (symptom duration > 12 weeks) (11). Patients may have recurrent acute attacks or acute exacerbations of chronic rhinosinusitis. Chronic and subacute bacterial sinus infections may require surgical consultation and management. Acute rhinosinusitis, however, makes up most cases in ambulatory care, and primary care clinicians treat most of these infections without consultation. These principles are limited to the diagnosis and treatment of acute maxillary and ethmoid rhinosinusitis in immunocompetent adults. 1.2 Acute bacterial rhinosinusitis is usually a secondary infection resulting from sinus ostia obstruction or impairment of mucus clearance mechanisms caused by an acute viral upper respiratory tract infection (12). Streptococcus pneumoniae and Haemophilus influenzae are the bacteria most commonly isolated from infected maxillary sinuses (13). Streptococcus pyogenes, Moraxella catarrhalis, and anaerobic bacteria each account for a small percentage of bacterial sinus infections. Current reviews providing more details of the pathogenesis of acute and chronic sinusitis have recently been published (11, 13). The gold standard for diagnosis of bacterial rhinosinusitis is sinus puncture with aspiration of purulent secretions that yield growth on culture of at least 105 organisms per milliliter of a likely respiratory pathogen (14). However, sinus puncture is an invasive procedure seldom performed in primary care and is usually indicated only in complicated cases, such as those resistant to treatment. Because no simple and accurate office-based tests for acute bacterial rhinosinusitis are available, clinicians rely on clinical findings to make the diagnosis. However, signs and symptoms of acute bacterial rhinosinusitis and of prolonged viral upper respiratory tract infections are extraordinarily similar, making the clinical diagnosis of acute bacterial rhinosinusitis difficult and resulting in frequent misclassification of viral cases. Antibiotics have potential value in treating acute rhinosinusitis only when true bacterial infection is present. Therefore, two issues must be addressed before use of antibiotics is considered for acute rhinosinusitis. First, can one reliably differentiate acute bacterial rhinosinusitis from acute viral rhinosinusitis and, if so, how? Second, are antibiotics effective in treatment of acute bacterial rhinosinusitis and, if so, how effective? Principles Principle 1. Most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections [A]. (Letters in square brackets are evidence ratings. See the background document in this issue [10] for explanation.) 2.0 Causes of acute sinus inflammation include infection, allergy, and local irritants. Cases due to allergy and irritants can usually be distinguished from infection on the basis of a careful history. Symptoms due to allergy and environmental irritants are usually more chronic or recurrent, are infrequently associated with purulent nasal discharge, frequently include itching and sneezing, and are often associated with specific exposures. Adult patients are often accurate in self-diagnosis of allergic rhinitis (15). Infectious causes of acute rhinosinusitis include respiratory viruses, fungi, and bacteria. Fungal infections are rare in immunocompetent hosts. Viruses cause most cases of acute sinus inflammation. Maxillary sinus radiographs of young adults with typical viral upper respiratory tract infections showed mucosal abnormalities in 39% of cases on the seventh day of illness (16), and computed tomographic scans were abnormal in 87% of similar cases (17). These studies show that some degree of sinus mucosa inflammation is very common in viral upper respiratory tract infections. On the basis of epidemiologic estimates, only 0.2% to 2% of viral upper respiratory tract infections in adults are complicated by bacterial rhinosinusitis (18, 19), and approximately 15% of people with symptoms of acute respiratory infection seek medical care (20). Presuming a 2% bacterial rhinosinusitis infection rate, if all patients with bacterial rhinosinusitis were among those seeking care, no more than approximately 13% (0.02/0.15) of patients who presented with symptoms of acute respiratory infection would have bacterial rhinosinusitis. Yet the ratio of cases in which primary care physicians diagnose upper respiratory tract infection and acute rhinosinusitis in adults is approximately 1:1 (7, 8), suggesting that clinicians frequently misclassify viral upper respiratory tract infections as acute bacterial rhinosinusitis. Principle 2. Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds [B]. The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for patients with rhinosinusitis symptoms lasting 7 days or more who have maxillary pain or tenderness in the face or teeth (especially when unilateral) and purulent nasal secretions. Patients who have rhinosinusitis symptoms for less than 7 days are unlikely to have bacterial infection. 3.0 Overdiagnosis of acute bacterial rhinosinusitis is not surprising, considering the lack of specific clinical features that distinguish it from nonbacterial upper respiratory tract infections. Relying on overall clinical impression, primary care physicians classifying patients as highly likely to have bacterial rhinosinusitis are correct in approximately 40% to 50% of cases (18-22). Often, patients and physicians believe that an upper respiratory tract infection has gone on for too long and that antibiotic treatment is therefore needed. Gwaltney and colleagues (21) studied the natural history of rhinovirus illness in young adults. Length of illness ranged from 1 to 33 days, and only one fourth of the patients had symptoms lasting longer than 14 days. Most were well or nearly well in 7 to 10 days. However, in clinical trials of diagnosis and treatment of rhinosinusitis, duration of illness alone does not reliably distinguish prolonged viral infection from bacterial rhinosinusitis (Williams J, Hansen JG, Lindbaek M. Personal communication). For example, Lindbaek found that, among patients with sinusitis-like symptoms referred from primary care physicians, 80% of those with computed tomography criteria for bacterial sinusitis (air-fluid level or total opacification) had had symptoms for longer than 7 days, while 70% of those without computed tomography criteria for bacterial rhinosinusitis also had symptoms for more than 7 days. Nonetheless, bacterial rhinosinusitis was seen in only 20% of patients whose symptoms lasted less than 7 days (Lindbaek M. Personal communication). Therefore, duration of symptoms of 7 days or greater is a moderately sensitive but nonspecific predictor of bacterial rhinosinusitis. 3.1 Aside from duration of illness, are any symptoms and signs helpful in distinguishing between bacterial and viral rhinosinusitis? Since 1976, seven investigators have published reports attempting to identify signs and symptoms specific to acute bacterial rhinosinusitis (22-28). All seven studies are limited by use of imperfect diagnostic standards. None used the best criterion for diagnosing bacterial rhinosinusitis, which is aspiration of purulent secretions on sinus puncture that grow at least 105 organisms per milliliter of a likely respiratory pathogen on culture. The findings of

Uncomplicated Acute Bronchitis

The most frequent reason that persons in the U.S. visit ambulatory care physicians is cough, after general medical examination and progress visit. Bronchitis (acute or not otherwise specified) is the most frequent diagnosis given to these patients (1). In 1997, an estimated 30 million ambulatory visits for cough led to more than 12 million diagnoses of bronchitis. For most of these illnesses, acute bronchitis is the most accurate diagnosis. It applies to otherwise healthy adults with an acute respiratory illness lasting 1 to 3 weeks with cough as the prominent feature and in whom pneumonia has been excluded. Throughout the developed world, the diagnosis of acute bronchitis has become synonymous with antibiotic treatment. On average, 70% to 90% of office visits for acute bronchitis result in treatment with antibiotics. Yet, evidence-based reviews and meta-analyses of randomized, controlled trials conclude that routine antibiotic treatment does not provide major clinical benefit in adults with acute bronchitis. Lack of antibiotic treatment benefit should be expected because most cases of acute bronchitis have a viral cause. With the goal of improving the management of and curbing excess antibiotic use in adults with acute bronchitis, we describe recent developments in the pathophysiology, evaluation, and treatment of uncomplicated acute bronchitis and discuss the impact of efforts to reduce prescription of antibiotics for this illness. Methods A substantial portion of the literature review, analysis, and interpretation for this review was done during development of Principles of Appropriate Antibiotic Use for Adults with Acute Respiratory Tract Infections, a project supported in part by the Centers for Disease Control and Prevention. This paper provides a more expansive review of acute bronchitis in adults than do the Principles, which are intended primarily to be used as practice recommendations. The funding source had no role in collection, analysis, or interpretation of data or in the decision to submit this paper for publication. Studies of diagnosis, etiology, and treatment of acute bronchitis were retrieved from MEDLINE by using Medical Subject Heading and keyword searches for cough, bronchitis, and acute respiratory infection. Studies dated back to 1966 and were limited to those done in adult humans. Bibliographies from appropriate articles and textbook chapters on acute bronchitis were also searched for relevant studies. Studies identified from formal literature reviews in recently published meta-analyses of antibiotic treatment of acute bronchitis formed the basis for reviewing the efficacy of antibiotic treatment. Etiologic studies used to estimate incidence or prevalence of bacterial infections were excluded if they were conducted during known outbreaks or epidemics of that pathogen (for example, Chlamydia pneumoniae outbreaks in university settings) or in hospitalized persons, those referred to specialists for care, or those with chronic lung disease. Pathophysiology Definition The taxonomy currently used for diagnosis of acute respiratory infections is based primarily on the anatomic correlate of the predominant clinical feature of the illness (2). Hence, acute bronchitis is the acute or subacute onset of a cough illness lasting less than 2 to 3 weeks, with or without phlegm production, that is frequently accompanied by other upper respiratory tract and constitutional symptoms (2, 3). It has been proposed that cough persisting longer than 3 weeks be referred to as persistent or chronic cough but not chronic bronchitis, since this term has been defined by the American Thoracic Society to refer to patients with daily cough and sputum production for at least 3 months, for 2 consecutive years, and in the absence of any other disease that might account for daily productive cough (4). Diagnostic considerations in adults with persistent cough differ greatly from those in adults with a cough illness lasting less than 3 weeks. Postnasal drip, asthma, and gastroesophageal reflux disease account for more than 75% of cases in adults with cough lasting at least 3 weeks and a negative chest radiograph (5). This review focuses on uncomplicated acute bronchitis, as opposed to acute bronchitis in patients with underlying lung or heart disease, immunosuppression, or bacterial superinfection. Acute bronchitis in patients with documented emphysema or chronic bronchitis, for example, is usually considered a distinct clinical entity (acute exacerbation of chronic bronchitis) with unique etiologic and treatment issues. Because patients with heart disease (particularly congestive heart failure) or immunosuppression have been routinely excluded from pathophysiology and treatment studies of acute bronchitis, the generalizability of the findings to patients with these comorbid conditions is unknown. Bacterial superinfection after an acute viral respiratory infection (such as bacterial pneumonia or sepsis, particularly with influenza infection) should be considered when patients with acute bronchitis develop clinical signs of pneumonia. However, this complication is very uncommon in otherwise healthy adults. In a large study of pneumonia and influenza-associated deaths during influenza epidemics, 95% of deaths occurred in adults with a chronic medical condition (mostly chronic heart and lung disease), and 68% occurred in adults older than 65 years of age (6). Etiology Respiratory viruses, particularly influenza, appear to cause the large majority of cases of uncomplicated acute bronchitis in which an agent is identified by means of culture, antibody serology, or polymerase chain reaction (7-11). No isolated pathogen is also a frequent finding; it probably represents viral infections for which studies did not perform appropriate analyses. Under selected circumstances, noninfectious causes of uncomplicated acute bronchitis, such as cough-variant asthma or allergic or occupational exposures, should also be considered. The viruses most frequently associated with uncomplicated acute bronchitis are those that produce primarily lower respiratory tract disease (influenza B, influenza A, parainfluenza, and respiratory syncytial virus) and those that more commonly produce upper respiratory tract symptoms (coronavirus, adenovirus, and rhinoviruses). Increased attention has been given to respiratory syncytial virus as a cause of uncomplicated acute bronchitis in adults, particularly elderly persons. Infection with respiratory syncytial virus among exposed adults is common (with attack rates approaching 50%), particularly in households with children infected with respiratory syncytial virus and in institutional settings (12). Most young and middle-aged adults infected with respiratory syncytial virus develop asymptomatic or mildly symptomatic disease, including bronchitis, although respiratory syncytial virus can be associated with more severe clinical disease in otherwise healthy adults. In contrast to young adults, respiratory syncytial virus infection in elderly persons (age>60 years) more frequently leads to symptomatic lower respiratory tract disease. For example, a report of an outbreak of respiratory syncytial virus on a geriatrics ward found that 96% of persons reported intense coughing and fever, 64% developed a productive cough, and 40% had evidence of bronchopneumonia (13). Whether bronchopneumonia was actually due to respiratory syncytial virus or to bacterial superinfection was not examined. When microbiological studies are performed in unselected patients with uncomplicated acute bronchitis in nonoutbreak settings, fewer than 10% will have evidence of acute bacterial infection. To date, only Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydia pneumoniae have been clearly established as causes of acute bronchitis. There is no evidence that Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis cause acute bronchitis in adults without underlying lung disease; studies that found an association between these encapsulated bacteria and acute bronchitis failed to distinguish between colonization and acute infection (14). However, these bacteria are important causes of superinfections after acute viral respiratory illnesses (15). The discovery that C. pneumoniae infection can cause acute bronchitis is relatively new (16). This discovery rejuvenated speculation that a bacterial pathogen, and therefore antibiotic treatment, may in fact play a significant role in uncomplicated acute bronchitis. Several reports of outbreaks of C. pneumoniae cited attack rates exceeding 50% among families (17, 18) and 25% among students (19). However, surveillance studies have reported a much lower range of incidence rates, reflecting the seasonal, geographic, and epidemic nature of C. pneumoniae infection (20-25). Evidence that B. pertussis and B. parapertussis cause uncomplicated acute bronchitis in previously immunized adults is also fairly new. Although immunity after natural infection with pertussis appears to be lifelong (26), immunity conferred by childhood immunization begins to wane after as little as 3 years and is usually absent after 10 to 12 years. Attack rates as high as 100% have been reported among adult and adolescent household contacts of infected children (27). Infection in previously immunized adults appears to take a more benign course (28). Mechanism of Disease Manifestations Synthesis of the literature suggests that the clinical features of uncomplicated acute bronchitis develop in sequential phases. The acute phase of infection results from direct inoculation of the tracheobronchial epithelium by the infectious virus, leading to cytokine release and inflammatory cell activation. This phase is characterized by variable constitutional symptoms, such as fever, myalgias, and malaise, that last 1 to 5 days depending on the infectious agent. For example, uncomplicated acute bronchitis due to rhinovirus may pre

Principles of appropriate antibiotic use for acute pharyngitis in adults : Background

The following principles of appropriate antibiotic use for adults with acute pharyngitis apply to immunocompetent adults without complicated comorbid conditions, such as chronic lung or heart disease, and history of rheumatic fever. They do not apply during known outbreaks of group A streptococcus.1. Group A beta-hemolytic streptococcus (GABHS) is the causal agent in approximately 10% of adult cases of pharyngitis. The large majority of adults with acute pharyngitis have a self-limited illness, for which supportive care only is needed.2. Antibiotic treatment of adult pharyngitis benefits only those patients with GABHS infection. All patients with pharyngitis should be offered appropriate doses of analgesics and antipyretics, as well as other supportive care.3. Limit antibiotic prescriptions to patients who are most likely to have GABHS infection. Clinically screen all adult patients with pharyngitis for the presence of the four Centor criteria: history of fever, tonsillar exudates, no cough, and tender anterior cervical lymphadenopathy (lymphadenitis). Do not test or treat patients with none or only one of these criteria, since these patients are unlikely to have GABHS infection. For patients with two or more criteria the following strategies are appropriate: a) Test patients with two, three, or four criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results; b) test patients with two or three criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results or patients with four criteria; or c) do not use any diagnostic tests, and limit antibiotic therapy to patients with three or four criteria. 4. Throat cultures are not recommended for the routine primary evaluation of adults with pharyngitis or for confirmation of negative results on rapid antigen tests when the test sensitivity exceeds 80%. Throat cultures may be indicated as part of investigations of outbreaks of GABHS disease, for monitoring the development and spread of antibiotic resistance, or when such pathogens as gonococcus are being considered.5. The preferred antibiotic for treatment of acute GABHS pharyngitis is penicillin, or erythromycin in a penicillin-allergic patient.

Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: Background

Abstract The following principles of appropriate antibiotic use for adults with acute bronchitis apply to immunocompetent adults without complicating comorbid conditions, such as chronic lung or heart disease. 1. The evaluation of adults with an acute cough illness or a presumptive diagnosis of uncomplicated acute bronchitis should focus on ruling out serious illness, particularly pneumonia. In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and chest radiography is usually not indicated. In patients with cough lasting 3 weeks or longer, chest radiography may be warranted in the absence of other known causes. 2. Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough. If pertussis infection is suspected (an unusual circumstance), a diagnostic test should be performed and antimicrobial therapy initiated. 3. Patient satisfaction with care for acute bronchitis depends most on physician–patient communication rather than on antibiotic treatment. [Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann Emerg Med. June 2001;37:720-727.]

Principles of appropriate antibiotic use for acute rhinosinusitis in adults: Background

The following principles of appropriate antibiotic use for adults with acute rhinosinusitis apply to the diagnosis and treatment of acute maxillary and ethmoid rhinosinusitis in adults who are not immunocompromised. Most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections. Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds. The clinical diagnosis of acute bacterial rhinosinusitis should be reserved for patients with rhinosinusitis symptoms lasting 7 days or more who have maxillary pain or tenderness in the face or teeth (especially when unilateral) and purulent nasal secretions. Patients with rhinosinusitis symptoms that last less than 7 days are unlikely to have bacterial infection, although rarely some patients with acute bacterial rhinosinusitis present with dramatic symptoms of severe unilateral maxillary pain, swelling, and fever. Sinus radiography is not recommended for diagnosis in routine cases. Acute rhinosinusitis resolves without antibiotic treatment in most cases. Symptomatic treatment and reassurance is the preferred initial management strategy for patients with mild symptoms. Antibiotic therapy should be reserved for patients with moderately severe symptoms who meet the criteria for the clinical diagnosis of acute bacterial rhinosinusitis and for those with severe rhinosinusitis symptoms-especially those with unilateral facial pain-regardless of duration of illness. For initial treatment, the most narrow-spectrum agent active against the likely pathogens, Streptococcus pneumoniae and Haemophilus influenzae, should be used.

Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults: Background

The following principles of appropriate antibiotic use for adults with nonspecific upper respiratory tract infections apply to immunocompetent adults without complicating comorbid conditions, such as chronic lung or heart disease. 1. The diagnosis of nonspecific upper respiratory tract infection or acute rhinopharyngitis should be used to denote an acute infection that is typically viral in origin and in which sinus, pharyngeal, and lower airway symptoms, although frequently present, are not prominent. 2. Antibiotic treatment of adults with nonspecific upper respiratory tract infection does not enhance illness resolution and is not recommended. Studies specifically testing the impact of antibiotic treatment on complications of nonspecific upper respiratory tract infections have not been performed in adults. Life-threatening complications of upper respiratory tract infection are rare. 3. Purulent secretions from the nares or throat (commonly observed in patients with uncomplicated upper respiratory tract infection) predict neither bacterial infection nor benefit from antibiotic treatment.