Prevention and Management of Antimicrobial
Resistance in the Community: Do No Harm

Introduction:
The development of antimicrobials is undeniably one of the greatest advances of modern medicine. Unfortunately, widespread use and misuse of antibiotics has contributed to a dramatic worldwide increase in the incidence of antimicrobial resistance. Changing patterns of resistance have made organisms less susceptible to easily available and less expensive medications and have necessitated the empiric use of antimicrobials which provide broader coverage. Thus, a vicious cycle begins.

In Canada, the last decade has seen alarming increases in the rates of resistance to first-line antibiotics among pathogens responsible for common infections (Table 1). Clearly, unless the problem of antimicrobial resistance is acknowledged and aggressive action taken to control and prevent it, we may soon face an era in which previously treatable infections have become untreatable. It is well established that increasing antibiotic use leads to increased drug resistance.^1-4 The single most important risk factor for colonization or infection with an antimicrobial-resistant organism is prior exposure to antibiotics.^3,4,5,6

Rational Antimicrobial Use for Upper Respiratory Tract Infection: Targeting the Big Five

Although education of the public is a critical element of the fight to reduce inappropriate antibiotic use in the community, perhaps more important is the education of physicians about the rational use of antibiotics in the management of upper respiratory tract infections (URI). It is critical that physicians managing patients with URI understand the role of antimicrobials in this setting so that, when indicated, the proper antibiotic, dose and duration are selected and more importantly, so that antimicrobials are withheld in patients for whom they are not indicated.

Upper Respiratory Tract Infection (URI):
The term "upper respiratory tract infection" is a non-specific one which encompasses a wide variety of clinical syndromes and is typically reserved for those patients in whom a predominant symptom is not present. When symptoms are severe, particularly if they include myalgias and fatigue, influenza and parainfluenza virus infections predominate. When symptoms are mild, rhinoviruses predominate; adenovirus and respiratory syncytial virus are also important causes of URI. Antibiotic therapy of URI does not reduce the duration of symptoms or prevent complications. Despite this, 50-60% of patients presenting with symptoms of non-specific URI or a "cold", receive antibiotics.^7,8

Acute Bronchitis:
Acute bronchitis, defined as acute upper respiratory illness of ≤3 weeks duration characterized by predominant cough and sputum production, typically occurs in otherwise healthy children and adults and is caused by viruses in ≥90% of cases.⁹ Because the etiology and management of coughs of >3 weeks duration or those occurring in patients who have underlying lung or heart disease or who are immunosuppressed differs from that of acute bronchitis, cough in these settings will not be discussed.

In patients presenting with an acute cough illness and a presumptive diagnosis of acute, uncomplicated bronchitis, the most important priority of the initial evaluation is the exclusion of pneumonia. Further investigations are not warranted in patients who present with heart rate <100 beats/minute, temperature <38°C, respiratory rate <24 breaths/minute, and a normal chest examination as the likelihood of pneumonia in this setting is very low.¹⁰ Purulence of sputum reflects mucosal inflammation and sloughing and can result from either bacterial or viral infections and is therefore not useful in differentiating viral from bacterial infection. Likewise, bacterial cultures from the sputum are not helpful in the setting of acute bronchitis without pneumonia as pathogenic respiratory flora may be isolated but colonization cannot be differentiated from infection.

Routine use of antimicrobial therapy is not currently recommended for the management of acute, uncomplicated bronchitis in adults or children.^11-13 Alternatives to antibiotic therapy have been evaluated. Bronchial hyperresponsiveness plays a role in 30-65% of cases and inhaled albuterol has been shown to shorten the duration of cough.¹⁴

Although ≥90% of episodes of acute bronchitis are caused by viruses, Bordetella pertussis, Mycoplasma pneumoniae and Chlamydia pneumoniae are associated with 5% to 10% of episodes in adults.^15,16 Treatment of suspected pertussis is the most compelling reason for initiation of antibiotic therapy in patients with acute bronchitis and prolonged duration of cough. Although antibiotic therapy in adults with pertussis does not impact illness duration, it is important to reduce community spread of this organism and selection of a macrolide (erythromycin, clarithromycin or azithromycin) is most appropriate in this setting (Table 2).

Acute Sinusitis:
Acute sinusitis, or inflammation of the mucosa of the paranasal sinuses, can result from infection, allergy, and local irritants. Only 0.2% to 2% of URIs in adults are complicated by bacterial sinusitis and abnormalities on sinus x-ray and CT are present in up to 87% of adults with uncomplicated URI making these investigations of limited value in determining the etiology.^17,18 Review of studies of acute bacterial sinusitis suggests that the most reliable clues to a bacterial etiology are (1) mucopurulent discharge, (2) unilateral maxillary sinus pain, (3) maxillary tooth tenderness (4) worsening symptoms following initial improvement and (5) failure to improve or resolve on decongestants.^19,20

In general, antibiotic therapy should be reserved for patients with severe symptoms or patients with moderate symptoms who meet the clinical case definition for acute bacterial sinusitis: symptoms lasting >7 days which include maxillary pain in the face or teeth and purulent nasal secretions.¹⁹ In patients in whom antibiotic treatment for sinusitis is deemed necessary, a ten day course of therapy should be prescribed (Table 2).

Pharyngitis:
The incidence of post-streptococcal glomerulonephritis is not altered by antibiotic treatment. In contrast, rheumatic fever risk is increased if GAS (group A streptococcus) is not treated; the actual risk is estimated to be 0.3-0.4% following an untreated GAS pharyngitis.

Differentiating bacterial pharyngitis from pharyngitis of viral etiology on clinical grounds alone is difficult. A scoring system which allows determination of the probability of streptococcal pharyngitis based upon clinical symptoms and signs has been developed (Table 3).²² Only patients with identified GAS or another bacterial pathogen known to cause pharyngitis should be treated. If antibiotics are started empirically, they should be discontinued if the culture is negative. Careful selection of patients for throat culture is essential and can be optimized using the sore throat score. Indiscriminate culturing in patients with a low pre-test probability of bacterial pharyngitis contributes to inappropriate antibiotic use because 5-15% of school age children are chronic carriers of GAS and do not require treatment. When treatment is deemed warranted, a 10 day course of therapy should be prescribed (Table 2). Group A Streptococci are universally susceptible to penicillin and the unnecessary use of broad spectrum antibiotics, observed in up to 68% of prescriptions for pharyngitis, should be avoided.²¹

Acute Otitis Media: The role of antimicrobial therapy in the treatment in acute otitis media remains controversial. It has been estimated that only 1 of 7 children treated with antibiotics will benefit and that 17 children must be treated to prevent pain in one child after 2-7 days of treatment.^23,24 Maximizing benefit of antibiotics in the management of children presenting with symptoms of acute otitis media relies on differentiating between serous otitis media of viral or post-infectious etiology and acute bacterial otitis media. Use of pneumatic otoscopy to assess position, color, translucency and mobility of the tympanic membrane is more useful in the diagnosis of bacterial otitis media than visual otoscopy alone.

Given the high rate of spontaneous resolution of symptoms, treatment is not necessary in all cases. It is wise however to treat those children with bilateral AOM, structural defects and those <2 yrs old as they may be more prone to complications. In those children in whom a decision has been made to start antibiotics, a 5-7 day course should be prescribed (Table 2). A 10 day course is recommended for children < 2yrs or with structural defects or recurrent AOM.²³

Conclusion:
Gone are the days when we can function on the premise that prescribing an antibiotic which won't help, can't hurt. While no guidelines can adequately encompass the variety and intricacies of every clinical situation, a thoughtful approach to the treatment of common infections can go a long way to avoiding inappropriate antibiotic use and stemming the tide of antimicrobial resistance. It is critical that we take the time to educate ourselves and our patients about the dangers of inappropriate antibiotic use and begin to consider the withholding of antibiotics when they're not indicated a marker of quality medical care.

- Ian Davis, MD, Kathryn Slayter, PharmD, Shelly McNeil, MD

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10. Metlay JP, Kapoor WN, Fine MJ. Does this patient have community acquired pneumonia? Diagnosing pneumonia by history and physical examination. JAMA 1997;278:1440-5.
     
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13. Bent S, Saint S, Vittinghoff E, et al. Antibiotics in acute bronchitis: a meta-analysis. Am J Med 1999;107:62-7.
     
14. Hallett J. Recurrent acute bronchitis: the association with undiagnosed bronchial asthma. Ann Allergy 1985;55:568-70.
     
15. Wright SW, Edwards KM, Decker MD, et al. Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough. Acad Emerg Med 1997;4:179-83.
     
16. Nenning ME, Shinefield HR, Edwards KM, et al. Prevalence and incidence of adult pertussis in an urban population. JAMA 1996;275:1672-4.
     
17. Berg O, Carenfelt C, Rystedt G, et al. Occurrence of asymptomatic sinusitis in common cold and other acute ENT infections. Rhinology 1986;24:223-5.
     
18. Gwaltney JM Jr., Phillips CD, Miller RD, et al. Computed tomographic study of the common cold. N Engl J Med 1994;330:25-30.
     
19. Hickner JM, Bartlett JG, Besser RE, et al. Principles of appropriate antibiotic use for acute rhinosinusitis in adults: Background. Ann Intern Med 2001;134:498-505.
     
20. Williams JW et al. Clinical evaluation for sinusitis: making the diagnosis by history and physical examination. Ann Intern Med 1992; 117: 705-710.
     
21. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians. JAMA 2001;286:1181-6.
     
22. McIsaac WJ, White D, Tannenbaum D, et al. A clinical score to reduce unnecessary antibiotic use in patients with sore throat. CMAJ 1998;158:75-83.
     
23. Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial drugs for acute otitis media: meta-analysis of 5400 children from thirty-three randomized trials. J Pediatr 1994;124:355-67.
     
24. Del Mar C, Glasgiou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ 1997;314:1526-29.

TABLE 1: Current rates of antimicrobial resistance among important respiratory pathogens in Canada and the Maritimes (Nova Scotia, New Brunswick, Prince Edward Island)

TABLE 2: Summary of treatment strategies for selected upper respiratory infections

TABLE 3: A clinical score developed to assist in the decision to initiate antibiotics in patients presenting with sore throats*

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