Issues in the pharmacotherapy of bacterial sinusitis

November 2001

New guidelines have recently been published for the treatment of sinusitis. Because of the commonality of sinusitis in children and the concern of increasing bacterial resistance to antibiotics, guidelines written by national experts are welcome.

As all clinicians working with children are aware, numerous antibiotics are available to treat sinusitis and other common infectious diseases. Certainly, these antibiotics differ in their spectrum of activity toward the most common bacterial pathogens in pediatric sinusitis: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. They also differ in their activity toward drug-resistant S. pneumoniae, which is becoming increasingly important as a pathogen for pediatric upper respiratory infections (URI). Choosing an antibiotic that is most likely to be effective for a specific patient can be difficult, and guidelines can be helpful in explaining the rationale when making these choices. Other guidelines have also been published; the Sinus and Allergy Health Partnership published “Antimicrobial Treatment Guidelines for Acute Bacterial Rhinosinusitis” in 2000.

Clinical practice guidelines

Clinical practice guidelines (Pediatrics, September 2001) were prepared by the Subcommittee on Management of Sinusitis and the Committee on Quality Improvement of the American Academy of Pediatrics (AAP). While these guidelines are not intended as a protocol for all patients with sinusitis, they are intended as an “analytic framework” for evaluation and treatment. Patients aged 1-21 years with uncomplicated acute, subacute and recurrent acute bacterial sinusitis are the focus for the recommendations. The two subcommittees were comprised of pediatricians with expertise in infectious disease, allergy and epidemiology, as well as an otolaryngologist and radiologist. Other professional organizations were allowed to review and critique the guidelines. Specific issues addressed were evidence for the efficacy of various antibiotics; evidence for the efficacy of various ancillary, non antibiotic regimens; the diagnostic accuracy and concordance of clinical symptoms, radiography and sinus aspiration.

The AAP subcommittees prepared these guidelines with the Agency for Healthcare Research and Quality along with centers that focus on conducting systematic reviews of the literature. The literature was searched through March 1999. Only 5 controlled, randomized trials and 8 case series of antimicrobial therapy in children were located. A total of only 255 children were included in these randomized trials. Considering how common sinusitis is diagnosed and how often antibiotics are used in children for this condition, this relative lack of data from well-done studies is surprising. As well, there is relatively little data on accurately diagnosing sinusitis, and no consensus appears to exist on which signs and symptoms should be used for diagnosis, or on the role of other diagnostic methods, such as radiography. Taken together, these concerns suggest that little evidence (based upon well-done clinical studies) exist supporting the use of newer broad-spectrum antibiotics over amoxicillin.

--- Although several adjuvant therapies have been recommended for treatment of sinusitis, the panel gave no specific recommendations on these therapies, due to lacking data on efficacy.

The first recommendation on diagnosis was a “strong recommendation, based on limited scientific evidence and strong consensus of the panel.” The panel stated that the diagnosis of acute bacterial sinusitis is based on clinical criteria in children with persistent or severe upper respiratory symptoms. Persistent symptoms are defined as those lasting longer than 10-14 days (and <30 days); namely nasal or postnasal discharge (of any quality), daytime cough or both. Severe symptoms are defined as a temperature of >102° F (39° C) and purulent nasal discharge present concurrently for >3-4 days in a child who appears ill. Recommendations 2a and 2b detail the role of imaging studies, stating that imaging studies are not necessary to confirm a diagnosis of clinical sinusitis in children <6 years of age.

Recommendation 3 describes the role of antibiotics, which are recommended to achieve a more rapid clinical cure (“strong recommendation based on good evidence and strong consensus panel”). The panel emphasizes how important it is to adhere to the described diagnostic criteria in hopes of avoiding antibiotic use for viral URIs (ie, not using antibiotics for symptoms lasting <10 days, a presumed viral infection). Specific antibiotics recommended in the guideline’s algorithm are based upon several criteria: severity of symptoms (mild/moderate or severe), attendance at day care or recent (<90 days) antibiotic use. Attendance at day care or recent antibiotic use have been shown in published studies to be significant risk factors for acquisition of drug-resistant S. pneumoniae (DRSP).

A child diagnosed with sinusitis of mild/moderate severity who does not attend day care or has not recently been prescribed antibiotics, should receive usual or high-dose amoxicillin (45 mg/kg/day to 90 mg/kg/day divided twice daily). Children who attend day care, have been prescribed a recent course of antibiotics, or who present with severe symptoms should receive high-dose amoxicillin-clavulanate (Augmentin, GlaxoSmithKline), cefuroxime (Zinacef, GlaxoSmithKline), cefpodoxime (Vantin, Pharmacia), or cefdinir (Omnicef, Abbott) (see table for doses).

Keep in mind that newer formulations of amoxicillin-clavulanate (eg, Augmentin suspension, 200/400 mg/5 ml, or Augmentin ES-600 suspension, 600 mg/5 ml) should be used when high-dose therapy is prescribed. These formulations have less clavulanate and, therefore, are less likely to result in diarrhea as an adverse effect. Ceftriaxone (Rocephin, Roche), 50 mg/kg, is recommended for children who are unable to tolerate oral therapy. Children with type 1 hypersensitivity (anaphylactic) reactions to penicillin or amoxicillin can receive clarithromycin (Biaxin, Abbott) or azithromycin (Zithromax, Pfizer). Children with other reactions to previous penicillin or amoxicillin therapy (eg, mild rash) can receive the cephalosporins listed above. The high-dose regimens of amoxicillin or amoxicillin-clavulanate will result in sinus concentrations above the minimum inhibitory concentration (MIC) for S. pneumoniae that have intermediate resistance to penicillin and above the MIC for many that are highly resistant. Amoxicillin-clavulanate in usual or high doses and the recommend cephalosporins all have good activity toward ß-lactamase producing H. influenzae and M. catarrhalis.

The optimal duration of antibiotic therapy has not been well studied, and definitive recommendations are not given. Empiric durations of 10-28 days are described. Another strategy suggests continuing therapy for 7 days beyond the resolution of symptoms.

The extent of resistance to penicillin by S. pneumoniae varies throughout the country, with an average rate of approximately 25% (50% intermediate resistance and 50% highly resistant). It is important for clinicians to familiarize themselves with resistant rates in their communities and to adjust these guidelines accordingly (ie, greater use of high-dose amoxicillin therapy with higher rates of resistance). Approximately 50% of H. influenzae and nearly 100% of M. catarrhalis organisms produce ß-lactamase enzymes, and thus are resistant to usual or high-dose amoxicillin.

Published clinical studies documenting the efficacy of one antibiotic over another are limited. Therefore, antibiotic recommendations are based mainly on antibacterial activity toward the major sinusitis pathogens, including activity to resistant pathogens. Several large surveillance studies have been published which document in vitro activity of numerous antibiotics to S. pneumoniae and H. influenzae from regions throughout the country. It is reasonable to conclude that an antibiotic with good activity (ie, low MIC values) to S. pneumoniae, H. influenzae and M. catarrhalis is more likely to be clinically effective. Antibiotics that are not recommended (eg, trimethoprim-sulfamethoxazole or loracarbef [Lorabid, Monarch]) have poorer activity toward S. pneumoniae and/or H. influenzae and M. catarrhalis and thus are not expected to be as clinically effective.

Although several adjuvant therapies have been recommended by some for sinusitis, the panel did not offer specific recommendations on these therapies, due to a lack of data on their efficacy. Such therapies include nasal irrigation, antihistamines, decongestants, mucolytic agents, or intranasal steroids. As well, the panel offered no recommendations on either the use of antibiotic prophylaxis or complementary/alternative medicine, due to a lack of sufficient data.

Other guidelines

The Sinus and Allergy Health Partnership (SAHP) published similar guidelines in 2000. “Antimicrobial Treatment Guidelines for Acute Bacterial Rhinosinusitis” were published with several organizations (American Academy of Otolaryngic Allergy, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Rhinologic Society). These guidelines apply to children and adults. Recommendations for antibiotics vary according to illness severity and a prior (<6 weeks) use of antibiotics. While the specific antibiotics recommended are generally similar to the AAP panel guidelines, some differences do exist. The AAP panel additionally recommends cefdinir as an alternative cephalosporin, and does not recommend erythromycin or trimethoprim-sulfamethoxazole (due to concerns of extensive bacterial resistance).

Conclusions

Despite the commonality of using antibiotics in the treatment of bacterial sinusitis in children, remarkably little published evidence exists supporting the use of one antibiotic over another. Despite this however, clinicians can still intelligently chose an antibiotic that would more likely be clinically effective for a specific patient. Using risk factors, such as day care attendance or recent prescription of an antibiotic, knowledge of in vitro activity of antibiotics towards major pathogens, and resistance patterns in the community, clinicians can make use of these guidelines to maximize the potential for therapeutic efficacy for their patients with sinusitis.

For more information:

• Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical practice guideline: management of sinusitis. Pediatrics. 2001;108:798-808.
• Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg. 2000;123(S1):S1-32.
• Doern GV, et al. Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999-2000, including a comparison of resistance rates since 1994-1995. Antimicrob Agents Chemother. 2001;45:1721-9.
• Thornsberry C, et al. Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective US study. Antimicrob Agents Chemother. 1999;43:2612-23.