Primary-care medicine is as much art as it is science, but clinicians sometimes rely too heavily on the former when it comes to prescribing antibiotics. Nowhere is this truer than in the treatment of respiratory tract infections (RTIs).
Most cases of bronchitis are caused by viruses, but many clinicians prescribe antibiotics at their patients' insistence. Patients may explain that they are going on a long-planned vacation and just can't afford to be sick, or they are getting married that weekend and desperately need to get over an annoying cold. After a while, the clinician caves in, prescribes something, and vows this exception will be the last one.
For the first time, there are now data to back up the assertion that when it comes to treating ambulatory viral infections, antibiotics do more harm than good—and that these infections do get better on their own and without specific therapy.
One of the most surprising findings shows that while there is a 1-in-4,000 chance that an antibiotic will help an acute RTI, there's a 1-in-1,000 chance that the same prescription will send the patient to the emergency department (ED) with a rash, allergic reaction, or diarrhea. In fact, antibiotics are three times more risky than aspirin, glyburide, or anticonvulsants and cause one fifth of all ED visits for adverse drug events (142,000 visits a year).1
When are antibiotics truly indicated, and when do other treatments suffice? The following discussions—organized by diagnosis—are intended to provide assistance to the busy practitioner who is sorting out the options.
Otitis media
Though not technically part of the respiratory system, the middle ear is infected by the same spectrum of pathogens seen in the upper respiratory tract.
Ear infections are common but rarely serious. Recent years have seen a shift away from automatic prescription of antibiotics to cautious observation in many cases. Current recommendations for treating acute otitis media (OM) include the option to observe a child (without prescribing any antibiotic at all) as long as the ear is not draining, the child is older than age 2 years and otherwise healthy, and he or she has not had OM in the previous three months.
If an antibiotic is used, the drug of choice is still amoxicillin for five to seven days (or 10 days if the patient is younger than two years or if the infection is complicated or recurrent). The correct dose of amoxicillin is 80-90 mg/kg/day.2,3
Secondary choices include a macrolide (erythromycin-sulfisoxazole [Pediazole], azithromycin [Zithromax], or clarithromycin [Biaxin]) or a cephalosporin (cefdinir [Omnicef], cefpodoxime [Vantin], or cefuroxime [Ceftin]). Trimethoprim/sulfamethoxazole (TMP/SMX) is no longer useful in areas with a high percentage of resistant pneumococci.
Antibiotics should not be used to treat middle-ear effusions, however, which tend to resolve spontaneously or are treated by surgical drainage and ventilation.
Pharyngitis
When faced with a sore throat, the clinician's main task is to identify and treat cases of group A beta-hemolytic streptococcal (GABHS) pharyngitis (Figure 1). All other pathogens can be grouped together because they do not require specific antibiotic treatment. It's important to remember that the only reason we treat strep throat is to prevent acute rheumatic fever and peritonsillar abscess. Antibiotics remain the standard of care despite evidence showing that both complications (at least in adults who live in developed countries) are exceedingly rare.4
The classic presentation of strep throat infection includes fever, sore throat, headache, abdominal pain, exudative pharyngitis, and cervical adenopathy—without cough, rhinorrhea, or diarrhea, all three of which point toward a viral etiology. However, diagnosis should be based on objective laboratory data from a rapid antigen test or culture. Neither the patient history nor the clinical examination is reliably sensitive or specific.
If GABHS is identified, the treatment of choice remains penicillin. Amoxicillin has an unnecessarily broad spectrum and should be avoided. Use of the macrolides, while effective, has been associated with emerging bacterial resistance. In practice, however, such first-generation cephalosporins as cephalexin (Keflex) are often used. This is because cephalexin has repeatedly led to higher cure rates and lower recurrence rates (perhaps because it has a greater bactericidal effect against intracellular streptococci than penicillin).5 Cephalexin has not, however, translated into lower rates of local suppurative complications or rheumatic fever.
Sinusitis
When does a common cold become a sinus infection? This question is usually answered by the patient, who comes into the office seeking treatment for a nagging cold that is getting worse or has not gone away after many days or even weeks. Nevertheless, the evidence shows that the vast majority of sinus infections resolve spontaneously and without specific treatment.6
Consensus guidelines recommend an antibiotic only if the patient fails to improve after 10 days or gets worse after five to seven days. Admittedly, the signs and symptoms that suggest the diagnosis are nonspecific; they include purulent nasal discharge, facial and dental pain, fever, cough, fatigue, anosmia, and ear pressure or fullness. The recommendations are based on the usually self-limited nature of the disease in primary care, difficulties with clinical diagnosis, and the resultant overuse of antibiotics in primary-care settings (as well as the rare incidence of complications).7
If antibiotics are used, most experts still favor amoxicillin, with TMP/SMX as an alternative for patients allergic to penicillin. Such macrolides as azithromycin and clarithromycin are often used but should be avoided because of concerns about rising bacterial resistance. For patients with severe symptoms or a history of antibiotic use in the past three months, consider amoxicillin clavulanate (Augmentin), cefpodoxime, cefuroxime, cefdinir, levofloxacin (Levaquin), or moxifloxacin (Avelox).8
Acute bronchitis
When an otherwise healthy adult develops acute bronchitis, the rule is still to withhold antibiotics since more than 90% of cases are viral.9 Exceptions include infection with Chlamydia, Mycoplasma, and Bordetella pertussis (these organisms cause fewer than 10% of acute bronchitis cases).6 When these atypical agents are suspected, therapy with a macrolide or doxycycline is not inappropriate. (Such laboratory investigations as polymerase chain reaction or culture for B. pertussis and serology for Mycoplasma may be prudent in the setting of an outbreak but are impractical and unhelpful in individual cases.)
For the other 90% of acute bronchitis cases, the patient should be advised that the infection is likely to be self-limited. Treatment is supportive and includes rest, fluids, and time. A bronchodilator can help with wheezing (even if the patient is not known to have asthma).10 Obviously, it is important to rule out pneumonia first. The presence of fever, tachypnea, tachycardia, consolidation, or rales should trigger further evaluation with chest radiography. Rapid antigen tests for influenza are also helpful when this diagnosis is suspected and can further reduce inappropriate antibiotic use.
One question that frequently arises in clinical practice is whether treating bronchitis with an antibiotic will prevent pneumonia. For a number of years, the prevailing wisdom was that it did not. Data now both support and qualify this. In fact, in a British study that looked at the use of antibiotics to prevent pneumonia in patients with acute chest infections, the number needed to treat was 39 above age 65 but closer to 100 for younger age groups.11 In the 30 days following diagnosis, pneumonia developed in 4% of those not treated with antibiotics but in only 1.5% of those who received them. Surprisingly, smokers did not appear to have different outcomes than nonsmokers.
Of course, common sense and clinical judgment support the early use of antibiotics in patients whose pulmonary function is otherwise limited (e.g., patients who are immunocompromised in any way or have such chronic diseases as cystic fibrosis).
Chronic obstructive pulmonary disease
Acute exacerbations of chronic obstructive pulmonary disease should be treated with oral steroids and broad-spectrum antibiotics, according to published guidelines.12 The fluoroquinolones levofloxacin and moxifloxacin are superior to such first-line drugs as amoxicillin, doxycycline, and TMP/SMX.13
Pneumonia
Any one of the following oral regimens is recommended for uncomplicated pneumonia (Figure 2) in patients who do not require hospitalization, have no significant comorbidities, and/or have not used antibiotics within the past three months, and in locations where there is not a high prevalence of macrolide-resistant bacterial strains: azithromycin (500 mg on day 1 followed by four days of 250 mg a day, three days of 500 mg a day, or a single 2-g dose), clarithromycin XL (two 500-mg tablets daily for five days or until afebrile for 48-72 hours), or doxycycline (100 mg twice a day for 7-10 days).14 Erythromycin, though effective and inexpensive, is not well tolerated, requires multiple daily doses, and may cause fatal arrhythmias (especially when used with other drugs).
The use of fluoroquinolones in ambulatory community-acquired pneumonia without comorbid conditions or recent antimicrobial use is discouraged unless there is a high prevalence of strongly macrolide-resistant Staphylococcus pneumoniae in the local community. If a respiratory fluoroquinolone is used, experts advise gemifloxacin (Factive) 320 mg daily, levofloxacin 750 mg daily, or moxifloxacin 400 mg daily for a minimum of five days.
These agents are expensive, however, and combination therapy with a beta-lactam effective against S. pneumoniae and a macrolide or doxycycline is an acceptable alternative (e.g., high-dose amoxicillin 1 g three times daily or amoxicillin-clavulanate 2 g twice daily or cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily PLUS either a macrolide [azithromycin 500 mg on day 1 followed by four days of 250 mg a day or clarithromycin 250 mg twice daily or clarithromycin XL 1,000 mg once daily] or doxycycline 100 mg twice daily). Treatment should continue for a minimum of five days.
Preventing antibiotic resistance
The problem of evolving antibiotic resistance can be addressed from three different angles: (1) avoiding antibiotics altogether when they are not clearly indicated; (2) using the right antibiotic; and (3) using the antibiotic for an appropriate length of time.
When are antibiotics not indicated? As noted earlier, the etiology of most cases of bronchitis is viral. Numerous studies over the past 30 years have shown that these infections are for the most part self-limited and improve over time or with a bronchodilator. Bronchodilators are underused and should be prescribed for any patient with bronchitis (not just those with known asthma).
Patients with asthma do not need an antibiotic. These patients need oral or inhaled steroids and bronchodilation. Patients with a short-lived cold need a decongestant, lozenge, or analgesic and not an antibiotic (the color of their nasal discharge notwithstanding).
Despite all these caveats, it is important to remember that for the individual patient, the infection is not just a cold or viral illness. Recognize that the infection must have interfered enough with work, sleep, or leisure to drive the patient to your office or ED.
Writing instructions on a prescription pad seems to validate many patients' concerns and serves to fulfill the unspoken wish for a prescription. For example, write out a detailed “viral” prescription of rest, fluids, OTC analgesics, and albuterol. At the same time, write out a backup plan informing patients that if their condition does not improve by a specific date, they should call the office and you will prescribe an antibiotic. Even if the prescription is never filled, patients will leave the office happier and more satisfied.
Backup prescriptions intended to be filled only under certain conditions (e.g., the patient is no better after 48 hours, temperature goes over 100°F, etc.) demonstrate that the clinician cares and seem to reassure patients, especially those who are anxious about work or travel. One study showed that more than half of such backup prescriptions were never filled,15 while another suggested that they could significantly reduce the rate of inappropriate antibiotic use.16
What antibiotics are best avoided and when? Azithromycin is popular because it is easy to prescribe and use, but its prolonged half-life, which results in slowly falling serum levels over many days, is the perfect setup for the emergence of resistant strains. Doxycycline and TMP/SMX may be much better choices for acute bronchitis. Amoxicillin is far preferable for ear infections or sinusitis. For streptococcal pharyngitis, penicillin and cephalexin are still the drugs of choice.
How long should common RTIs be treated? Shorter courses of antibiotics are becoming increasingly popular and have not been associated with higher failure rates. These treatments are less expensive, equally effective, and associated with a lower resistance rate than traditional longer courses of treatment.17,18 There are exceptions, however. Streptococcal pharyngitis should be treated for a full 10 days,19 and sinus infections may require several weeks to clear. On the other hand, a five-day course for a middle-ear infection is acceptable and has the advantage of increased patient compliance.
Alternative therapies
Many patients ask about alternative therapies, and my answer often surprises them. I don't believe in alternative medicine. I believe only in medicine that works. When there are no numbers or studies to guide me, I steer away from potentially harmful treatments (i.e., products whose purity and consistency cannot be confirmed), but when there are controlled studies to support their use, natural remedies can be enthusiastically applied. One of my favorites is elderberry, which has been proven to reduce the duration of flulike illnesses by up to four days (for more information, see Elderberry).20 In comparison, oseltamivir (Tamiflu) and zanamivir (Relenza) reduce the duration of symptoms by only one day. Honey, which was recently shown to be as effective as dextromethorphan for treating cough in children,21 is another example (for more information, see Honey found more effective than dextromethorphan in children with nocturnal cough). Others abound, and as long as the treatment is safe and inexpensive, I try to be open-minded to patients' ideas.
Mr. Zimmerman is in family practice with Esopus Medical, PC, in Rifton, N.Y.
References
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2. American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113:1451-1465.
3. Glasziou PP, Del Mar CB, Sanders SL, Havem M. Cochrane Database Syst Rev. 2004;(1):CD000219.
4. Bartlett JG. Approach to acute pharyngitis in adults. In: Rose BD, ed. UpToDate. Wellesley, Mass.: UpToDate;2008.
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8. Prescriber's Letter. February 2004, Volume 11.
9. Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):95S-103S.
10. Prescriber's Letter. January 2007, Volume 14.
11. Petersen I, Johnson AM, Islam A, et al. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ. 2007;335:982.
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14. File TM. Treatment of community-acquired pneumonia in adults in the outpatient setting. In: Rose BD, ed. UpToDate. Wellesley, Mass.: UpToDate;2008.
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16. Martin CL, Njike VY, Katz DL. Back-up antibiotic prescriptions could reduce unnecessary antibiotic use in rhinosinusitis. J Clin Epidemiol. 2004;4:429-434.
17. El Moussaoui R, Roede BM, Speelman P, et al. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax. 2008;63:415-422.
18. Haider BA, Saeed MA, Bhutta ZA. Short-course versus long-course antibiotic therapy for non-severe community-acquired pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2008;(2): CD005976.
19. Pichichero ME. Cephalosporins are superior to penicillin for treatment of tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis J. 1993;12:268-274.
20. Zakay Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res. 2004;32:132-140.
21. Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med. 2007;161:1140-1146.
All electronic documents accessed January 12, 2009.