This report was reviewed for medical and scientific accuracy by Catherine A. Monteleone, MD, Associate Professor of Medicine, Division of Allergy, Immunology and Infectious Diseases, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Expert Commentary

Michael S. Benninger, MD, Chair, Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, Michigan; Steering Committee of the Sinus and Allergy Health Partnership.

Appropriate antibiotic utilization is a common goal of clinicians everywhere, and is dependent on accurate diagnosis and thoughtful selection of antimicrobial therapy. Diagnostic guidelines developed by the Rhinosinusitis Task Force of the American Academy of Otolaryngology-Head and Neck Surgery are a useful clinical tool that can aid the differentiation of nonbacterial and bacterial rhinosinusitis and acute and chronic forms of the disease.¹ These guidelines identify major and minor factors associated with the disease and direct clinicians to consider symptom duration when evaluating patients with symptoms suggestive of the disease.

Treatment guidelines for bacterial rhinosinusitis continue to evolve as bacterial resistance patterns change and new antimicrobial therapies become available. The recently updated Sinus and Allergy Health Partnership (SAHP) guidelines for the treatment of acute bacterial rhinosinusitis provide clinicians with a simple algorithm that takes into consideration illness severity and recent history of antibiotic use to aid therapeutic decision making.² An improved mathematical model (the Poole Therapeutic Outcome Model) was used to predict efficacy of available antimicrobials and develop recommendations. This model considered multiple disease (pathogens and susceptibilities) and drug (pharmacokinetic and pharmacodynamic properties) factors that can influence outcomes. However, the model does not account for all factors that can influence choice of therapy. Other factors that clinicians must consider when choosing appropriate antibiotic therapy include those that influence compliance (eg, formulation, dosing frequency, taste, side effects, cost, and formulary availability). It is hoped that the availability of comprehensive guidelines such as these will improve antibiotic utilization and curb the further development of antibiotic resistance.

Introduction

In the age of increasing bacterial resistance, the importance of appro-priate antibiotic utilization is at the forefront of clinicians' minds. Streptococcus pneumoniae (S. pneumoniae), the most common cause of acute bacterial rhinosinusitis in adults and children, is increasingly resistant to commonly prescribed antibiotics, including penicillin, trimethoprim/sulfamethoxazole and doxycycline.² This increasing resistance is likely a result of a variety of factors, including the inappropriate use of antibiotics and noncompliance with prescribed antibiotic therapy.

The SAHP, a group of expert otolaryngologists representing the American Academy of Otolaryngic Allergy, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Rhinologic Society, recently updated comprehensive antibiotic treatment guidelines for acute bacterial rhinosinusitis.² These guidelines, published in the January 2004 issue of Otolaryngology-Head and Neck Surgery, highlight important patient, disease, and drug characteristics that clinicians should evaluate when prescribing antibiotics for the treatment of acute bacterial rhinosinusitis. Michael S. Benninger, MD, Chair, Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, Michigan presented highlights from these guidelines at the recent American Rhinologic Society Scientific Meeting held in September 2003 in Orlando, Florida.³ In his presentation, Dr. Benninger emphasized the importance of synthesizing patient and drug characteristics in the decision-making treatment process. By doing this, clinicians can increase the likelihood of clinical and bacteriologic success in treating acute bacterial rhinosinusitis.

Rhinosinusitis: The Primary Care Perspective

Respiratory tract infections, including acute and chronic rhinosinusitis, are a leading cause of office visits and antibiotic prescriptions in the United States. Nearly 30% of patients who visit their physician have a primary diagnosis of acute respiratory tract infection and approximately 18% have chronic sinusitis.⁴ Primary care physicians diagnose and treat a large proportion of these infections, and can therefore have a substantial impact on appropriate antibiotic utilization for this condition.

Rhinosinusitis comprises a spectrum of diseases characterized by inflammation and frequently infection of the nose and paranasal sinuses.⁵ Symptoms may result from noninfectious, infectious, or allergic processes and vary from patient to patient, thus complicating diagnosis. The original Rhinosinusitis Task Force developed a list of symptoms associated with bacterial rhinosinusitis (Table 1) and recommended that a diagnosis of acute bacterial rhinosinusitis may be made in adults or children with a viral upper respiratory tract infection who showed no improvement after 10 days or worsened after 5 to 7 days and was accompanied by some or all of these symptoms.¹ Patients with a longer history of symptoms (≥12 weeks) should be considered for a diagnosis of chronic rhinosinusitis, particularly those who report the continuous presence of two or more symptoms for 12 weeks or more, and meet the recently defined clinical criteria for chronic rhinosinusitis.⁵

Differentiation of nonbacterial and bacterial rhinosinusitis is an important first treatment step for clinicians and can prevent unnecessary antibiotic prescriptions. Symptoms present for less than 7 days are commonly associated with viral causes. However, bacterial superinfection is common after 10 days and should be considered in patients who experience symptom worsening after 5 to 7 days, or persisting for longer than 10 days. This is because most bacterial infections result from mucosal inflammation, which may develop in response to viral or allergic stimuli. In the mucosal inflammation cycle, swelling caused by upper respiratory infections, allergies, environmental factors, medications, or other triggers leads to ostial occlusion. This in turn leads to mucous stasis and subsequent bacterial infection and obstruction, which further contributes to mucosal swelling.

S. pneumoniae and Haemophilus influenzae (H. influenzae) are the most common pathologic organisms (20% to 43%, 15% to 35%, respectively) identified in adults and children with acute bacterial rhinosinusitis.² These organisms are becoming increasingly resistant to commonly prescribed antibiotics. Data from the 1998 Alexander Project (a community-based surveillance study), demonstrated that 28.6% of S. pneumoniae isolates were resistant to penicillin, 32.5% to macrolides, 43.2% to trimethoprim/sulfamethoxazole, and 21.7% to doxycycline.⁶ Further-more, cross-resistance among agents is common.⁷

Considerations for Choosing Appropriate Antibiotic Therapy for Acute Bacterial Rhinosinusitis

Clinicians must choose from a wide array of antibiotic therapies that are potentially useful for patients with acute bacterial rhinosinusitis, including beta-lactams (eg, penicillins, cephalosporins), macrolides/azalides, tetracyclines, trimethoprim/sulfamethoxazole, clindamycin, and fluoroquinolones. Recent Food and Drug Administration (FDA) approvals of new antibiotic formulations (eg, high-dose amoxicillin/ clavulanate; Augmentin XR, Augmentin ES) and agents (eg, cefdinir; Omnicef) further expand the treatment options. Clinical considerations should include the pharmacokinetic and pharmacodynamic properties of the antibiotic agents, their activity against likely pathogens, ease of dosing, adverse events, resistance patterns, cost, and medication allergies.⁸

Pharmacokinetic/pharmacodynamic therapeutic goals vary among the antimicrobials. Those that exhibit concentration-dependent killing (eg, fluoroquinolones, macrolides) are best evaluated through examination of area under the plasma drug concentration versus time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC/MIC). The pharmacokinetic/pharmacodynamic goal for S. pneumoniae is a 24-hour AUC/MIC ratio of 25 to 30.⁹ Antimicrobials that exhibit time-dependent killing (eg, beta-lactams and clindamycin) are better evaluated using percentage of dosing interval above MIC. Optimal outcomes are associated with regimens that result in drug levels that are above the MIC for greater than 40% to 50% of the dosing interval. Both efficacy and the development of resistance are influenced by drug levels; therefore, factors that affect compliance (and subsequently, drug levels) should not be overlooked. These factors include dosing frequency, length of therapy, formulation, taste, and adverse events.

Because no statistically useful comparative studies of available antibiotic therapies for acute bacterial rhinosinusitis had been conducted at the time of the original treatment guidelines, the SAHP used a mathematical model (Poole Therapeutic Outcome Model1) to predict efficacy of various antimicrobial regimens in acute bacterial rhinosinusitis. This model was developed to take into account the multiple factors that can influence outcomes, including the proportion of patients with a clinical diagnosis of acute bacterial rhinosinusitis who are likely to have a positive sinus aspirate (typically 60% of patients in primary care practices); the expected rate of clinical resolution of disease in culture-negative patients (typically 40% of patients, with complete resolution of disease occurring in 88% of this group [or 35% of the total patient group]); the expected distribution of pathogens found in a culture-positive group; the estimated spontaneous resolution rate of each pathogen; and the in vitro susceptibility of the major sinusitis pathogens to antibiotic agents at their pharmacokinetic/pharmacodynamic breakpoints. The predicted clinical efficacy of antibiotics using this model has been incorporated into the updated recommended therapies for acute bacterial rhinosinusitis as illustrated in Tables 2 and 3.

SAHP Recommendations for Acute Bacterial Rhinosinusitis Therapy

The new SAHP guidelines contain a simple algorithm to guide clinicians through the primary considerations that should be used to choose appropriate antimicrobial therapy for acute bacterial rhinosinusitis.² Basic information gathered from each patient's history and physical examination (age, disease severity, recent antibiotic history) and knowledge of predicted efficacy of antimicrobial therapies are all used in the guidelines to allow for a practical application of clinical criteria along with bacteriologic efficacy in order to guide clinical care decision making in acute bacterial rhinosinusitis. With changes in antimicrobial resistance patterns or alterations in antimicrobial effectiveness, the guidelines can be adapted to stay contemporary in the management decision making.

Amoxicillin, amoxicillin/clavulanate, cefpodoxime, cefdinir and cefuroxime continue to be recommended for the initial treatment of adults with mild disease (Table 2). Respiratory fluoroquinolones, high-dose amoxicillin/clavulanate, ceftriaxone or combination therapies should be considered as first-line therapies for adults with mild disease who have a recent history of antibiotic use, or for adults who have moderate disease.

Similarly, amoxicillin, amoxicillin/clavulanate, cefpodoxime, cefdinir and cefuroxime are recommended for the initial treatment of children with mild disease (Table 3). High-dose amoxicillin/clavulanate, ceftriaxone or combination therapies should be considered as first-line therapies for children with mild disease who have a recent history of antibiotic use, or those with moderate disease.

Second-line or "switch" recommendations are also provided in the new SAHP guidelines. These recommendations are for patients who fail to respond to initially recommended therapies (no improvement or symptom worsening after 72 hours of therapy) (Tables 2 and 3). When a change in antibiotic therapy is made, the physician should consider the limitations in coverage of the initial agent. Patients who have received effective antibiotic therapy and remain symptomatic should be further evaluated.

The SAHP guidelines provide a basis for antibiotic selection for physicians to use in clinical practice. Clinicians may also factor in considerations not addressed in this algorithm, such as factors that may affect compliance with therapy. Formulations that are easy to use (eg, once- or twice-daily dosing) and acceptable to patients (eg, easy-to-swallow, good-tasting) may result in improved compliance and, therefore, influence clinical and microbiologic outcomes.

Conclusion

Appropriate antibiotic use in the treatment of acute bacterial rhinosinusitis can help curb the development of antibiotic resistance without compromising patient outcomes. Clinicians must consider both patient and drug characteristics when individualizing drug therapy. Important considerations include patient age, severity of disease, recent antibiotic history, and predicted efficacy of various antimicrobial agents. Additional considerations that can be used to individualize drug therapy include product characteristics that can influence compliance, such as dosing frequency, taste, and side-effect profile.

References

1. Report of the Rhinosinusitis Task Force Committee Meeting, Alexandria, VA, August 17, 1996. Otolaryngol Head Neck Surg. 1997;117:S1-S68.
2. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:S5-S45.
3. Benninger MS. Antimicrobial Update in Rhinology: Perspectives from the Sinus & Allergy Health Partnership. Symposium held during the 2003 American Rhinologic Society Scientific Meeting, September 20, 2003, Orlando, Florida.
4. National Disease and Therapeutic Index, IMS Health Incorporated, 1999.
5. Benninger MS, Ferguson BJ, Hadley JA, et al. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. 2003;129(3 Suppl):S1-S32.
6. Jacobs M, Bajaksouzian S, Lin G, et al. Susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis to oral agents: results of a 1998 US outpatient surveillance study. Presented at the 39th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 26-29, 1999, San Francisco, California. Abstract C-61.
7. Hoban DJ, Doern GV, Fluit AC, Roussel-Delvallez M, Jones RN. Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Inf Dis. 2001;32(Suppl 2):S81-S93.
8. Gwaltney JM Jr, Jones JG, Kennedy DW. Medical management of sinusitis: educational goals and management guidelines. The International Conference on Sinus Disease. Ann Oto Rhinol Laryngol Suppl. 1995;167:22-30.
9. Vesga O, Craig WA. Activity of levofloxacin against penicillin-resistant Streptococcus pneumoniae in normal and neutropenic mice. Presented at the 36th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 15-18, 1996, New Orleans, Louisiana.

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Disclosure

Catherine A. Monteleone, MD
No significant relationships to disclose.

Michael S. Benninger, MD
Grant/Research Support-Aventis, Novartis; Consultant-Abbott Laboratories, Aventis, Bayer AG, GlaxoSmithKline; Speakers Bureau-Aventis, GlaxoSmithKline, Ortho-McNeil

This report contains no information on commercial products that are unlabeled for use or investigational uses of products not yet approved.

This report is supported by an educational grant from Abbott Laboratories.

The opinions expressed in this publication are those of the participating faculty and do not necessarily reflect the opinions or the recommendations of their affiliated institutions: University of Medicine & Dentistry of New Jersey; MMC, Inc.; or any other persons. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this publication should not be used by clinicians without evaluation of their patients' conditions, assessment of possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with the recommendation of other authorities. This Sinusitis Newsletter does not include discussion of treatment and indications outside of current approved labeling. This Sinusitis Newsletter was made possible through an educational grant from Abbott Laboratories.

©2004 Millennium Medical Communications, Inc. and UMDNJ-Center for Continuing and Outreach Education