Data from the National Center for Health Statistics indicate that, in recent years, approximately 75 percent of all outpatient prescriptions for antimicrobial medications have been issued for these five conditions: otitis media, sinusitis, bronchitis, pharyngitis or nonspecific upper respiratory tract infection.¹ Rates of antimicrobial drug use are highest in children¹; therefore, the pediatric age group is the appropriate initial focus for these guidelines. The principles presented here focus on areas in which antimicrobial therapy could be curtailed without compromising patient care.

The first part of this two-part article reviews the appropriate use of antimicrobial therapy in the treatment of otitis media and sinusitis; the second part reviews appropriate therapy for bronchitis, pharyngitis and nonspecific upper respiratory tract infections (common colds). The complete set of principles with supporting evidence and references has been published separately.^2–7

Physicians report receiving heavy pressure to prescribe unnecessary antimicrobial therapy, most often the expectation of patients or parents that they will receive antimicrobial prescriptions.⁸ Most parents do not acknowledge that they pressure their physician for antimicrobial agents.⁹ Recently, however, patient satisfaction with an office visit for a respiratory infection has been shown to correlate with the quality of the patient-physician interaction rather than with the prescription of an antimicrobial agent.¹⁰ A national campaign to improve parental and physician awareness of antimicrobial resistance and unnecessary antimicrobial use is under way.¹¹ An improved understanding on the part of the general public as well as the realization by physicians that patient satisfaction does not depend on prescribing an antimicrobial agent should help conscientious physicians in their efforts to restrict overuse of antimicrobial agents.

With the accumulation of evidence that antimicrobial treatment increases the patient's risk for both colonization and invasive disease with nonsusceptible Streptococcus pneumoniae,¹² observation without antimicrobial therapy now appears to be the preferable treatment option. Physicians and public health professionals have long shared concerns about the effect of antimicrobial use on the increasing prevalence of resistant organisms in the community. Occasionally, a practicing physician who sees a well-appearing child with middle ear effusion may consider the risks and benefits to that specific child to be of more immediate concern. However, individual children also may be placed at risk by the prescription of unnecessary antimicrobial agents. Recent studies show that children treated with a course of antimicrobial medications have a greater risk of becoming carriers of nonsusceptible pneumococci as a result of that treatment¹³ and that carriers of nonsusceptible strains are more likely to fail antimicrobial therapy.¹⁴

Reducing the spread of resistant bacterial pathogens through judicious antimicrobial use is feasible and good for both individual patients and the community. The following principles are the first steps in accomplishing this objective.

Otitis Media

Principles of Antimicrobial Therapy

1. Episodes of otitis media should be classified as acute otitis media or otitis media with effusion.

2. Antimicrobial agents are indicated in the treatment of acute otitis media; however, diagnosis requires documented middle ear effusion and signs or symptoms of acute local or systemic illness.

3. In certain patients, uncomplicated cases of acute otitis media may be treated with a five- to seven-day course of antimicrobial agents.

4. Antimicrobial agents are not indicated in the initial treatment of otitis media with effusion, although treatment may be indicated if effusions persist for three months or longer.

5. Persistent middle ear effusion (otitis media with effusion) after therapy for acute otitis media is expected and does not warrant repeated treatment.

6. Antimicrobial prophylaxis should be reserved for control of recurrent acute otitis media, defined by three or more distinct and well-documented episodes every six months or four or more episodes every 12 months.

Rationale

Distinguishing each episode of otitis media as acute otitis media or otitis media with effusion leads to a management strategy that provides antimicrobial therapy for children who will benefit from it but avoids antimicrobial exposure for those who will not.

Acute otitis media is defined as the presence of fluid in the middle ear in association with signs or symptoms of acute local or systemic illness. Middle ear effusion should be documented by using pneumatic otoscopy; techniques such as tympanometry or acoustic reflectometry may be useful adjuncts. Accompanying signs and symptoms that meet the criteria for acute otitis media include otalgia, fever, otorrhea or a bulging yellow or red tympanic membrane. Antimicrobial agents are indicated for use in this condition.

The cumulative evidence from randomized controlled trials in which antimicrobial therapy has been compared with no therapy for acute otitis media is persuasive in favoring antimicrobial therapy, although the treatment effect is small.^15–17 Approximately 80 percent of untreated children have clinical resolution by seven to 14 days, compared with approximately 95 percent of those treated with antimicrobial medications.¹⁵

In treating acute otitis media, a shorter course of antimicrobial therapy (five to seven days) may be appropriate in children two years of age or older with uncomplicated presentations¹⁸ (Table 1). A short course of therapy is not currently recommended for use in children with complications such as perforation of the tympanic membrane, chronic or recurrent acute otitis media, craniofacial abnormalities or immunocompromise.

Otitis media with effusion is defined as the presence of fluid in the middle ear in the absence of signs or symptoms of acute infection. Antimicrobial therapy may appropriately be deferred in this group of children, as recommended in the clinical guideline published by the U.S. Agency for Health Care Policy and Research.¹⁹ Recent comprehensive reviews of the literature indicate that antimicrobial therapy can be safely deferred in most cases while otitis media with effusion resolves spontaneously.

Three meta-analyses^19–21 of published trials of antimicrobial therapy for otitis media with effusion have led to the conclusion that there is a small but statistically significant effect on short-term resolution. Most of these trials enrolled children with documented middle ear effusion but no recent history of acute otitis media. No beneficial effect of therapy was seen in studies that enrolled children with illnesses characterized by a high natural cure rate, such as those with effusion after a recent episode of acute otitis media.²⁰ Approximately 65 percent of all cases of otitis media with effusion resolve within three months without antimicrobial therapy,²² as do 90 percent of the subset of cases of otitis media with effusion that immediately follow a diagnosed episode of acute otitis media. Although the overall difference in the rate of short-term resolution between treated and untreated children in the meta-analyses was statistically significant, about seven children would have to be treated with antimicrobial agents for one child to benefit.²³ More importantly, there was no significant difference in the persistence of otitis media with effusion when assessed more than one month after treatment was completed, whether placebo or antimicrobial therapy was used.²¹ These findings have prompted many experts to recommend that middle ear effusion in the absence of acute otitis media should not be treated with antimicrobial therapy at all.²⁴

The natural history of appropriately treated acute otitis media includes persistence of middle ear effusion for weeks to months, a fact that may not be clearly recognized by physicians who reexamine patients' ears soon after therapy is completed. Approximately 70 percent of children have fluid in the middle ear at two weeks, 50 percent have fluid at one month, 20 percent have fluid at two months and 10 percent have fluid at three months after appropriate antimicrobial therapy.^24–26 Thus, when middle ear fluid is detected in asymptomatic children at follow-up visits for acute otitis media, administering additional courses of antimicrobial agents is generally unnecessary.²⁷ An important step in reducing the burden of unnecessary antimicrobial treatment for otitis media is the recognition that persistent effusions are part of the expected course of the condition and do not warrant therapy.

Acute Sinusitis

Principles of Antimicrobial Therapy

1. Clinical diagnosis of bacterial sinusitis requires the following: prolonged nonspecific upper respiratory signs and symptoms, such as rhinosinusitis and cough without improvement for 10 to 14 days or longer or more severe upper respiratory tract signs and symptoms, such as fever higher than 39.0°C (102.2°F), facial swelling and facial pain.

2. The common cold often includes radiologic evidence of sinus involvement, so radiographs should be used and interpreted with caution. They may be indicated under the following conditions: when episodes of sinusitis are recurrent, when complications are suspected and when the diagnosis is unclear.

3. The most narrow-spectrum agent that is active against the likely pathogens should be used for the initial antimicrobial treatment of acute sinusitis.

Rationale

Judicious antimicrobial therapy for bacterial sinusitis depends on limiting the use of these agents to children who will benefit from treatment. Therefore, the diagnosis of bacterial sinusitis should be limited to children with clinical signs and symptoms that are most likely to reflect bacterial disease. Acute sinusitis among older children and adults occasionally may be diagnosed by the presence of classic signs or symptoms such as sinus tenderness, tooth pain, headache and high fever.^28–30 However, in young children, these classic signs and symptoms are rarely present.

Uncomplicated upper respiratory tract infections and bacterial sinusitis may not be distinguished solely by clinical features. The duration of the signs and symptoms, rather than their mere presence, best distinguishes these two conditions. Therefore, it is important to understand the natural history of upper respiratory tract infections.

The natural history of uncomplicated viral upper respiratory tract infection has been well defined in studies of patients with documented community-acquired viruses, as well as in adult volunteers with experimentally induced rhinovirus upper respiratory tract infections.^31–33 Sore throat and sneezing commonly occur early in the course of illness and tend to resolve over three to six days. Fever, malaise and myalgia are reported by a smaller proportion of patients but also resolve by day 6 to day 8. Cough, nasal discharge and nasal obstruction are common and persistent; up to one quarter of patients still have these symptoms at 14 days.^31,33,34 Computed tomographic studies show that involvement of the paranasal sinuses, with thickened mucosa, infundibular occlusion and occasional air-fluid levels, is a consistent aspect of uncomplicated viral upper respiratory tract infection.³⁵

Although some clinicians have accepted the idea that mucopurulent rhinitis (thick, opaque or discolored nasal discharge) indicates the presence of bacterial sinusitis, this sign should be recognized as part of the natural course of a nonspecific, uncomplicated viral upper respiratory tract infection. Studies of experimental rhinovirus colds reveal that nasal discharge changes from clear to purulent during the first few days of illness.^33,36 Furthermore, the color and characteristics of the discharge do not predict the isolation of a bacterial pathogen.³⁶

Acute bacterial sinusitis can be diagnosed in children who have persistent symptoms without improvement by 10 to 14 days. However, children with rhinorrhea or cough on the 10th day of an illness that is improving are likely to have an uncomplicated viral upper respiratory tract infection and should not be treated with antibiotics.³⁴ Persistent clinical findings usually include nasal discharge and daytime cough. The nasal discharge may be of any color or quality (thick, thin, clear or purulent), so the character of the discharge is not helpful in distinguishing sinus fluid infected with a bacterial pathogen from uninfected fluid.^37,38 Persistent nocturnal cough is non-specific and may occur during uncomplicated viral upper respiratory tract infections. Daytime cough is less common and may indicate sinus drainage.³⁹

Final Comment

By using these principles along with those outlined in the second part of this article as a starting point for individualized patient treatment, concerned clinicians can reduce unnecessary use of antimicrobial agents and help to protect their patients from infections with resistant bacteria. Patient education is an essential part of any effort to promote judicious antimicrobial use. To assist clinicians in educating their patients, a variety of materials, such as pamphlets, posters and fact sheets, may be obtained free of charge from the Centers for Disease Control and Prevention (CDC). These materials may be ordered by calling 404-639-4702 to obtain a fax order sheet.

If these efforts to reduce unnecessary antimicrobial use are successful, the reduction in antimicrobial resistance in this country may be substantial. The CDC has estimated that following the principles outlined in this article would prevent approximately 50 million unnecessary antimicrobial prescriptions annually in the United States. This summary may help to reassure physicians and patients that these practices are in line with both scientific evidence and expert opinion.