Year 2004 ATBS (Antibiotic Therapy for Bacterial Sinusitis) Clinical Consensus Panel Report® and Treatment Recommendations, Part II
Author: Gideon Bosker, MD, Assistant Clinical Professor, Section of Emergency Services, Yale University School of Medicine; Editor-in-Chief, Clinical Consensus Reports®, writing on behalf of the ATBS Clinical Consensus Panel.
Peer Reviewers: Theodore C. Chan, MD, FACEP, FAAEM, Associate Professor of Clinical Medicine, University of California, San Diego; Stephen A. Crabtree, DO, Assistant Professor, Department of Emergency Medicine, Medical College of Georgia, Augusta.
In part II of this two-part series, the Antibiotic Therapy in Bacterial Sinusitis (ATBS) Clinical Consensus Panel outlines risk-directed strategies for management of patients with acute bacterial rhinosinusitis. Outlining specific symptomatic, historical, and host criteria that prompt empiric antibiotic therapy, and a sequencing strategy for antimicrobial drug selection, this review provides practical, evidence-based strategies for patient management.
Tables are provided that will assist emergency physicians in identifying triggers for referral to otolaryngologists, while other resources in this report outline a comprehensive strategy for management of acute bacterial rhinosinusitis, including inhaled corticosteroids, antihistamines, and other agents when indicated.—The Editor
Approach to Antibiotic Therapy: Comparative and Non-comparative Clinical Trials in Acute Sinusitis
Short-Course Therapy. The majority of approved courses of antibiotic therapy for acute bacterial sinusitis recommend 10-14 days of therapy, although recent approval of azithromycin for a three-day course has prompted interest in evaluating the safety and efficacy—as well as possible other advantages—of shorter treatment duration in this condition.1,2 The approval of a three-day treatment regimen for acute sinusitis represents an important advance in the management of this common condition, and more data on abbreviated therapeutic courses for acute bacterial rhinosinusitis (ABRS) and other common infections will help clarify the role of such approaches. The use of short-course antimicrobial therapy, in general, has potential economic benefits, including reduced cost, improved adherence (compliance), reduced adverse events, reduced office visits, and increased patient compliance. However, a potential disadvantage includes lower efficacy compared with longer treatments (including the attendant costs of failure, relapse, recurrence, and disease complications).1
Unfortunately, many design flaws have been identified that apply to studies evaluating antimicrobial therapy for acute sinusitis. In this regard, diagnostic sensitivity and specificity of clinical examination vs. radiography vs. computerized tomography (CT) are controversial; equally difficult is differentiation between viral upper respiratory tract infections and acute bacterial sinusitis on the basis of clinical features. In addition, most antimicrobial studies in sinusitis have involved acute maxillary disease, and whether these results can be generalized to frontal, ethmoidal, and sphenoidal sinusitis is unknown.3-6 Few published data are available regarding the efficacy of short-course antimicrobial therapy for acute sinusitis.1,7-15
Potential clinical advantages of short-course antimicrobial therapy include reduced drug acquisition costs, fewer adverse events, better adherence, and reduced impact on resident flora. Of interest, three cephalosporins, three fluoroquinolones, and two macrolides have been approved for short-course therapy (i.e., < 5 days of therapy) for bacterial infections (acute bacterial exacerbation of chronic bronchitis, acute otitis media, community-acquired pneumonia [CAP]) of the respiratory tract, including one agent, azithromycin, which, in January 2004, received approval as a three-day treatment course for acute bacterial sinusitis.2,16
In a broad range of studies, short-course therapy has been shown to reduce adverse event incidence,1,6-12,17-23 a factor that may reduce the costs of additional office visits, drugs, and monitoring often necessitated by their occurrence. In addition, short-course therapy should be more acceptable to the patient and has the potential to enhance medication compliance, although this has not yet been proven in clinical trials evaluating short-course therapy in sinusitis. At least theoretically, short-course therapy has the potential for reducing the impact on resident (commensal) flora. This may, in turn, reduce the potential for development of drug resistance and suppression of protective native bacterial flora (the latter providing so-called colonization resistance against overgrowth of pathogenic microorganisms).1
Direct costs of treatment may be reduced by short-course treatment, unless more expensive agents are substituted to achieve the same degree of clinical efficacy in a shorter treatment period. In this case, more detailed evaluation is required to assess all treatment costs, i.e., acquisition costs, costs of telephone contacts and office visits, treatment failures (including office visits and drugs to manage the adverse events), enhanced bacterial resistance, and time off work or school as a result of treatment failures or adverse events. A more expensive agent from the sole perspective of acquisition cost may prove to be more cost effective than a less expensive agent when all of these factors are taken into account.1
Azithromycin. The shortest treatment course currently approved by the Food and Drug Administration (FDA) for acute bacterial sinusitis is for azithromycin.16 In a randomized, double-blind, controlled clinical trial of acute bacterial sinusitis, azithro-mycin (500 mg once daily for 3 days) was compared with amoxicillin/clavulanate (500/125 mg TID for 10 days). Clinical response assessments were made at day 10 and day 28. The primary end point of this trial was prospectively defined as the clinical cure rate at day 28. For the 594 patients analyzed in the modified intent-to-treat analysis at the day 10 visit, the clinical cure rate for three days of azithromycin was 88% (268/303) compared to 85% (248/291) for 10 days of amoxicillin/clavulanate. For the 586 patients analyzed in the modified intent-to-treat analysis at the day 28 visit, the clinical cure rate for three days of azithro-mycin was 71.5% (213/298) compared to 71.5% (206/288), with a 97.5% confidence interval of -8.4 to 8.3, for 10 days of amoxicillin/clavulanate.2,16
In the safety analysis for this study, the overall incidence of treatment-related adverse events, primarily gastrointestinal, was lower in the azithromycin treatment arm (31%) than in the amoxicillin/clavulanate arm (51%). The most common side effects were diarrhea (17% in the azithromycin arm vs 32% in the amoxicillin/clavulanate arm) and nausea (7% in the azithromycin arm vs 12% in the amoxicillin/clavulanate arm). In trials in which adults have been dosed 500 mg/d for three days to manage bacterial respiratory tract infections, the discontinuation rate due to treatment-related side effects has been about 0.6%.2,16
In an open-label, non-comparative study requiring baseline sinus punctures, clinical success outcomes were assessed at day 7 and day 28 for the modified intent-to-treat patients administered 500 mg of azithromycin once daily for three days. For Streptococcus pneumoniae isolates, days 7 and 28 clinical success rates were 88% (23/26) and 84% (21/25), respectively; for Haemophilus influenzae isolates, days 7 and 28 clinical success rates were 87% (28/32) and 75% (24/32), respectively; and for Moraxella catarrhalis isolates, days 7 and 28 clinical success rates were 93% (14/15) and 87% (13/15), respectively. The overall incidence of treatment-related adverse events in the non-comparative study was 21% in modified intent-to-treat patients treated with azithromycin at 500 mg once daily for three days with the most common side effects being diarrhea (9%), abdominal pain (4%), and nausea (3%).16
Amoxicillin/Clavulanate. Amoxicillin/clavulanate is active against bacterial pathogens commonly encountered in acute bacterial rhinosinusitis, including S. pneumoniae, H. influenzae, and M. catarrhalis. It widely is recommended as an initial treatment for this condition, and the ATBS Consensus Panel concurs it has an important role in managing this common infection. Studies supporting the safety and efficacy of both amoxicillin/clavulanate and amoxicillin/clavulanate extended release are available.24 Adults with a diagnosis of acute bacterial sinusitis were evaluated in three clinical studies. In one study, 363 patients were randomized to receive either amoxicillin/clavulanate extended release tablets 2000 mg/125 mg orally every 12 hours or levofloxacin 500 mg orally for 10 days in a double-blind, multicenter, prospective trial.24 These patients were evaluated clinically and radiologically at the test-of-cure visit (day 17-28). The combined clinical and radiological responses were 83.7% for amoxicillin/clavulanate extended release and 84.3% for levofloxacin at the test-of-cure visit in clinically evaluable patients (95% CI for treatment difference = -9.4, 8.3). The clinical response rates at the test-of-cure visit were 87% and 88.6%, respectively.24
Two other non-comparative, multicenter center studies were designed to assess the bacteriological and clinical efficacy of amoxicillin/clavulanate extended release 2000 mg/125 mg orally every 12 hours for 10 days in 1554 patients with acute bacterial sinusitis. Evaluation time points were the same as in the prior study. Patients underwent maxillary sinus puncture for culture prior to receiving the medication. At the test-of-cure visit, the clinical success rates were 87.5% and 87.1% (intention-to-treat) and 92.5% and 94% (per protocol populations).
Patients with acute bacterial sinusitis due to S. pneumoniae with reduced susceptibility to penicillin were accrued through enrollment in these two open-label, non-comparative clinical studies. Microbiological eradication rates for the three principal isolates were as follows: 1) all S. pneumoniae isolates (92.5% [222/240] for intent-to-treat, and 97.7% [210/215] for clinically evaluable patients); 2) H. influenzae (87.2% [177/203] for intent-to-treat, and 94.1% [167/170] for clinically evaluable patients); and 3) M. catarrhalis (90.5% [67/74] for intent-to-treat, and 98.4% [61/62] for clinically evaluable patients).24
The incidence of diarrhea and other side effects associated with amoxicillin/clavulanate extended release tablets administered for seven days has been evaluated and reported in patients with CAP.25 In this study, amoxicillin/clavulanate extended release 2000 mg/125 mg orally every 12 hours (n = 255) was compared to amoxicillin/clavulanate 875 mg/125 mg orally every 12 hours (n = 259). Treatment-related adverse events were reported in 25.1% of patients who received the extended-release formulation vs. 24.7% in the comparator group. In each group, the most frequently reported adverse events were diarrhea (18% vs 14.3%, p = 0.28), nausea (4.3% vs 5.4%), and headache (4.3% vs 5.0%).38
Amoxicillin also may be useful for treatment of ABRS. According to the American Academy of Otolaryngology and Head and Neck Surgery (AAOHNS) rhinosinusitis guidelines, amoxicillin requires 2-3 times higher-than-typical daily doses to eradicate S. pneumoniae isolates (even high doses may be insufficient vs the most resistant strains). Moreover, this higher dose is not FDA approved and has not undergone any systematic or safety evaluation.3,4
Extended Spectrum Fluoroquinolones: Intensification of Coverage and Patient Selection in Acute Bacterial Rhinosinusitis (ABRS)
The extended spectrum quinolones moxifloxacin, levofloxacin, and gatifloxacin are indicated for treatment of acute bacterial sinusitis. Because of concerns about overuse and inducing drug resistance, these agents generally are recommended in patients who have failed treatment with or who are allergic to advanced generation macrolides or amoxicillin/clavulanate, and in patients with more serious infections involving drug-resistant S. pneumoniae (DRSP) or gram-negative pathogens.
Each of these agents is available as an oral and intravenous preparation. Quinolones have been associated with cartilage damage in animal studies; therefore, they are not recommended for use in children, adolescents, and pregnant and nursing women. Upon review of multiple studies, resistance data, and pharmacodynamic data, the ATBS Consensus Panel has concluded that all advanced generation fluoroquinolones do not possess the same properties or susceptibility/resistance profiles, and that prudent, resistance-sensitive choices require differentiation among the available agents.
Among the new fluoroquinolones, moxifloxacin has the lowest minimum inhibitory concentrations (MICs) against S. pneumoniae and more specific gram-positive coverage; therefore, it is recommended by the ATBS Consensus Panel as the fluoroquinolone of choice—when a fluoroquinolone is indicated—for managing patients with acute bacterial rhinosinusitis. Moxifloxacin generally is well tolerated. In clinical trials, the most common adverse events were nausea (8%), diarrhea (6%), dizziness (3%), headache (2%), abdominal pain (2%), and vomiting (2%).26,27 The agent is contraindicated in patients with a history of hypersensitivity to moxifloxacin or any quinolone antibiotic. The safety and effectiveness of moxifloxacin in pediatric patients, pregnant women, and lactating women have not been established.
Levofloxacin. Levofloxacin, the S-enantiomer of ofloxacin, is a fluoroquinolone antibiotic which, when compared to older agents in this class, has improved activity against gram-positive organisms, including S. pneumoniae. This has important drug selection implications for the management of patients with acute bacterial sinusitis. Levofloxacin is well-tolerated, with the most common side effects including nausea, diarrhea, headache, and constipation. Food does not affect the absorption of the drug, but it should be taken at least two hours before or two hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc. Dosage adjustment for levofloxacin is recommended in patients with impaired renal function (clearance < 50 mL/min). In general, levofloxacin has greater activity against gram-positive organisms than ofloxacin and is slightly less active than ciprofloxacin against gram-negative organisms. Levofloxacin generally is well tolerated (incidence of adverse reactions, < 7%). The recommended dose for acute bacterial sinusitis is 500 mg orally QD for 10-14 days.28
In patients with acute sinusitis, 10 to 14 days treatment with oral levofloxacin 500 mg once daily was as effective as oral amoxicillin/clavulanic acid (500/125 mg three times daily) or clarithromycin (500 mg twice daily) in three randomized trials.29 Overall, clinical response rates ranged from 88% to 96% with levofloxacin, and from 87% to 94% with comparators 2-5 days after completion of therapy. Follow-up at one month in patients who were evaluable at clinical end point indicated long-term success rates of 79-85% with levofloxacin and 76-83% with amoxicillin/ clavulanic acid or clarithromycin.30-32 In addition, one study found that resolution or improvement was demonstrated in 215 of the 262 (82%) levofloxacin recipients who had abnormal x-ray findings at admission and underwent post-therapy radiographs, and in 215 of 262 (82%) amoxicillin/clavulanic acid recipients.30 Bacteriological efficacy was not assessed in any of these studies.
Moxifloxacin. Among the new fluoroquinolones, moxifloxacin has the lowest MICs against S. pneumoniae33 and more specific gram-positive coverage; therefore, it is recommended by the ATBS Consensus Panel as the oral fluoroquinolone of choice—when a fluoroquinolone is indicated—for managing patients with comorbid conditions who have acute bacterial rhinosinusitis.34-36 Moxifloxacin reaches higher sinus cavity concentrations compared to levofloxacin; this is important because quinolones demonstrate concentration-dependent killing.36,37
Its safety and efficacy in acute bacterial sinusitis have been established. In one prospective, multicenter, randomized, non-blinded phase III clinical trial, 475 adult patients with acute sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or amoxicillin/clavulanate (875 mg twice daily).26 The primary measure of efficacy was clinical resolution. Secondary outcome measures included clinical relapse at follow-up and evaluation of patient-reported outcomes.
Of 471 adults comprising the intent-to-treat population (234 moxifloxacin, 237 amoxicillin/clavulanate), moxifloxacin treatment was statistically equivalent to amoxicillin/clavulanate at the test-of-cure visit (85% vs 82%; 95% CI -6%, 13%). Analysis of the efficacy evaluable population confirmed statistical equivalence (86% vs 84%; 95% CI -7%, 13%). Of note, by day three of treatment, significantly more moxifloxacin-treated patients (n = 47; 24%) than amoxicillin/clavulanate-treated patients (n = 28; 14%) reported feeling better (p < 0.02). Frequency of drug-related adverse events was similar between groups: nausea (11% in the moxifloxacin cohort, and 5% in amoxicillin/clavulanate group) and diarrhea (3% in moxifloxacin, 10% in amoxicillin/clavulanate). The investigators concluded that once-daily moxifloxacin is as effective and safe as twice-daily amoxicillin/clavulanate in the treatment of acute sinusitis, and that moxifloxacin was associated with more rapid symptomatic relief.26
Cefuroxime. Recent, comparative randomized trials evaluating the therapeutic efficacy of oral cefuroxime axetil in patients with acute sinusitis show safety and efficacy in cases caused by such commonly isolated pathogens as H. influenzae, S. pneumoniae, M. catarrhalis, and S. aureus.38 In most trials, patient criteria included clinical signs and symptoms of acute sinusitis, generally of fewer than four weeks duration,71-76 with the diagnosis confirmed using a sinus radiograph or ultrasound. In one nonblind, general practice study, cefuroxime axetil provided similar efficacy to cefprozil in 381 adolescent and adult patients with acute sinusitis.39 In clinically evaluable patients, satisfactory clinical responses (cure or improvement) reported at the end-of-treatment visit (80 vs 88% of patients) were maintained at 18-22 days follow-up in 88% and 89% of cefuroxime axetil (250 mg twice daily for 10 days) and cefprozil (500 mg twice daily for 10 days) recipients, respectively.39 No bacteriological efficacy data were reported.39
Generally, cefuroxime axetil (250 mg twice daily for 8-10 days) provided comparable clinical and bacteriological efficacy to that of 7-10 days treatment with a quinolone agent, including moxifloxacin (400 mg once daily),34 gemifloxacin (320 mg once daily),40 or ciprofloxacin (500 mg twice daily).41,42 In clinically evaluable patients, clinical responses (cure or improvement) occurred in 83-90% of patients receiving cefuroxime axetil vs. 83-97% of recipients treated with a quinolone comparator agent. Clinical response rates were similar, although slightly lower, in intent-to-treat populations.34,40 Overall bacteriological eradication rates paralleled satisfactory clinical responses, with eradication occurring in 89-95% of microbiologically evaluable cefuroxime axetil recipients vs. 94-97% of those treated with a quinolone agent.
Nevertheless, in a double-blind trial, fewer cefuroxime axetil (250 mg twice daily for 10 days) recipients experienced clinical cure than moxifloxacin-treated (400 mg once daily for 7 days) patients in clinically evaluable patients (91% vs 97% of patients; 95% CI, 1.5%, 10.6%; p-value not reported).35 Respective clinical cure rates in the intent-to-treat population showed cefuroxime axetil was as effective as moxifloxacin (87% and 89% of patients; 95% CI, -3.7%, 7.8%).35 Sustained (27-31 days post-therapy) clinical response rates were comparable in the two treatment groups, occurring in 89% of cefuroxime axetil-treated patients and 91% of moxifloxacin recipients (95% CI, -4.3%, 5.4%).35 Presumed or documented bacteriological eradication occurred in fewer microbiologically evaluable patients receiving cefuroxime axetil than moxifloxacin recipients (84% vs 95% of patients; 95% CI, 3.6%, 19.7%; p-value not reported).35
Cefuroxime axetil (250 or 500 mg twice daily) also provided comparable clinical efficacy to that of clarithromycin43,44 (250 or 500 mg twice daily) or amoxicillin/clavulanic acid45,46 (500/125 mg three times daily or 875/125 mg twice daily). Of note, in one study, although cefuroxime axetil provided similar efficacy to that of clarithromycin, patients received cefuroxime axetil for five days vs. clarithromycin for 10 days.44 Overall clinical responses (cure or improvement) occurred in 85-96% of groups receiving cefuroxime axetil or a comparator agent.43-46 At follow-up (4-5 weeks post-therapy), satisfactory clinical responses persisted in 81% and 83% of cefuroxime axetil and clarithromycin recipients, respectively.43 However, in a nonblind study, satisfactory clinical responses were maintained (2-4 weeks post-therapy) in significantly fewer cefuroxime axetil-treated patients than amoxicillin/clavulanic acid recipients (78% [91/116] vs 90% [104/115] of patients; p = 0.009).46 Only one of these studies reported bacteriological efficacy, with bacteriological success (eradication or presumed eradication) occurring in 68% and 65% of cefuroxime axetil and amoxicillin/clavulanic acid recipients, respectively.46
The Challenge of Patient Evaluation: Methods, Modality, and Clinical Strategies in Acute Bacterial Rhinosinusitis (ABRS)
Accurate diagnosis of acute sinusitis will depend both on the history and clinical examination of the patient. While the clinical signs and symptoms of acute sinusitis often are difficult to distinguish from viral upper respiratory infection,47,48 such an assessment remains the best approach to diagnosing acute sinusitis. As a general rule, there is no role for routine imaging or radiography in the diagnosis of acute sinusitis. For patients who have persistent symptoms despite adequate medical therapy, evidence of serious complications, or those in whom surgery is being considered, coronal CT scan of the paranasal sinuses may be considered.49
Three recent, evidence-based guidelines50-52 suggest that children and adults with acute bacterial sinusitis may benefit from treatment with antibiotics more than those with rhinitis. However, to ensure that antibiotics are being used for patients with bona fide bacterial infections, clinicians must develop assessment strategies that permit them to distinguish uncomplicated, self-limited rhinitis from bacterial rhinosinusitis. In the absence of a clear diagnosis of acute bacterial sinusitis, antibiotics are unlikely to improve symptoms or clinical outcomes and symptomatic measures may be appropriate. (See Table 1.)
One group46 studied 150 patients with a clinical diagnosis of sinusitis and found that 85% had positive sinus puncture. In another review of 11 studies that met evidence-based inclusion criteria, the authors concluded that clinical evaluation has a sensitivity of about 75%, whereas radiographic methodologies have sensitivities slightly greater than 80%.53 In a prospective trial and subsequent reviews of the literature,54-56 a number of authors suggest a constellation of key clinical signs and symptoms that provide a level of sensitivity that approaches that of CT or MRI, while enhancing specificity.
Among criteria proposed for helping distinguish between viral and bacterial rhinosinusitis are the following: 1) Mild-to-moderate symptoms lasting for at least seven days; 2) severe symptoms and associated findings, even if present for fewer than seven days; 3) purulent secretion reported as a symptom or found in the nasal cavity by the doctor; 4) pain in the teeth; 5) pain on bending forward (inconsistent findings between studies); 6) two phases (bimodal course) in the illness history; or 7) elevated erythrocyte sedimentation rate or increased C-reactive protein.
The clinical value of imaging techniques for initial assessment of uncomplicated bacterial rhinosinusitis has been reviewed by a number of investigators52,57 who recommend reserving these techniques for high-risk and atypical patient subgroups. Investigators57 reviewed 14 studies that compared various imaging studies with clinical evaluation or sinus puncture and aspiration with culture or both. A positive aspirate for bacterial pathogens was defined as the clinical standard for diagnosis of sinusitis. When comparing standard sinus x-rays to sinus puncture, depending on the criteria used to define a diagnosis of sinusitis on plain radiograph, estimates of sensitivity in these studies ranged from 0.41 to 0.90, and specificity estimates ranged from 0.61 to 0.85. Imaging studies that included "mucous membrane thickening" as a criterion for sinusitis were more sensitive but less specific than studies defining positive radiographs as "opacification of sinus."
While a CT scan is more sensitive than plain x-ray film,25 and MRI is more sensitive than a CT scan,58,59 the specificity of these studies is unclear. For example, in children and adults without symptoms of sinusitis, the prevalence of sinusitis signs on CT and MRI is 45% and 42%, respectively.53,54,60 In light of such findings, these imaging methodologies are better reserved for patients in whom surgery is being contemplated, who have signs of neurological compromise, risk of invasive infection, or for whom chronic sinusitis is a concern. In the 1980s and 1990s, ultrasound was studied enthusiastically. Variability in test performance is great.53 Since the cost of this procedure is similar to that of a sinus CT, ultrasound is not indicated in the diagnostic evaluation of the sinuses. Though the sensitivity and specificity of a clinical evaluation possibly could be enhanced with the use of imaging studies, diagnostic accuracy of acute disease is not sufficiently improved to justify the cost or inconvenience of such interventions.
Most national panels concur with this approach. In guidelines on appropriate antibiotic use in sinusitis,4,51,54,55,57 endorsed by the Centers for Disease Control and Prevention, the American Academy of Family Physicians, the American College of Physicians-American Society of Internal Medicine, and the Infectious Diseases Society of America (IDSA), radiography uniformly is not recommended for confirming the diagnosis of acute sinusitis. Rather, the guidelines recommend that clinicians rely on duration of illness (i.e., at least 7 days) and severity of symptoms to arrive at a diagnosis. This approach has gained wide acceptance among different organizations that have evaluated the appropriateness of immediate radiographic assessment in patients suspected of having bacterial sinusitis.
The Institute for Clinical Systems Improvement recommends that radiology be used only if initial maximal medical (i.e., antimicrobial) therapy has failed, and notes that a primary goal of its guideline was to reduce the number of x-rays that physicians order for this diagnosis.61 In addition, the American College of Radiology’s criteria for sinusitis in the pediatric population ranked several radiographic studies based on their appropriateness for given clinical conditions. This review62 suggests imaging is not appropriate if symptoms have persisted fewer than 10 days. For patients with symptoms lasting more than 10 days and with persistent fever, CT scan is recommended.49,62
Summary of ATBS Consensus Panel Guidelines and Recommendations
Most cases of acute rhinosinusitis diagnosed in ambulatory care are caused by uncomplicated viral upper respiratory tract infections. Bacterial and viral rhinosinusitis are difficult to differentiate on clinical grounds. Because ABRS resolves without antibiotic treatment in most cases, the ATBS Consensus Panel recommends specific treatment triggers for initiating antibiotic therapy. The clinical diagnosis of ABRS and antibiotic treatment, in general, should be reserved for patients with mild-to-moderate rhinosinusitis symptoms lasting seven days or more or for patients with severe symptoms lasting for fewer than seven days. (See Table 2.)
The presence of immunosuppression, serious comorbidity, a history of recurrent infections, or other factors may prompt early antibiotic therapy in selected patients according to individual circumstances and clinical judgment. Sinus radiography is not recommended for diagnosis in routine cases. Referral to an otolaryngologist may be prompted by a number of factors, including neurological or ophthalmologic findings, suspicion of invasive infection, infection in a compromised host, and other clinical findings.
When patients do not meet criteria for antimicrobial treatment, symptomatic treatment and reassurance are the preferred initial management strategy for patients with mild symptoms. (See Table 1.) Agents directed toward symptomatic improvement in this subgroup have been described and indications for their use presented. As previously stressed, antibiotic therapy should be reserved for patients with severe symptoms who meet the criteria for the clinical diagnosis of ABRS regardless of duration of illness, or for those with mild-to-moderate symptoms not resolving after seven days. As a rule, patients who do not have persistent purulent nasal drainage, maxillary facial or tooth pain or tenderness, or both are unlikely to have bacterial rhinosinusitis, regardless of the duration of illness.
When antibiotic therapy is deemed to be appropriate, the ATBS Consensus Panel has issued recommendations and guidelines that account for the multiplicity of factors that go into the drug selection equation, including: resistance induction patterns among antimicrobial classes, susceptibility data, duration of therapy, cost of therapy, daily dose frequency, side effects, and patient convenience.
Based on this outcome-sensitive analysis, for first-line, initial and empiric therapy in otherwise healthy adult patients with acute bacterial rhinosinusitis, who do not have comorbid conditions, the ATBS Consensus Panel recommends azithromycin (3-day course), amoxicillin/clavulanate, or, when cost considerations predominate, high-dose amoxicillin therapy. (See Table 3.) As alternative first-line therapy, the panel recommends moxifloxacin (the preferred respiratory fluoroquinolone) or levofloxacin; other options include clarithromycin, gatifloxacin, or doxycycline.
In patients with ABRS who present with more severe disease or have comorbid conditions that necessitate more intensive antibiotic therapy (i.e, patients with comorbid conditions, immune system compromise, who are at risk for more invasive infection) the ATBS Consensus Panel recommends advanced generation fluoroquinolones such as moxifloxacin and levofloxacin as initial first-line therapy; amoxicillin/clavulanate and other beta-lactams also may be considered in this subgroup. (See Table 4.) In those selected cases in which a sinus puncture has yielded an infecting organism, antibiotic therapy should be pathogen-directed and based on culture sensitivities.
(Dr. Bosker served as moderator of the ATBS Consensus Panel. Panel members were Michael Armstrong, MD, Otolaryngologist, Private Practice, Richmond, VA; Elizabeth Blair, MD, Department of Otolaryngology, University of Chicago Hospitals and Medical Center, Chicago, IL; Charles Emerman, MD, FACEP, Professor and Chairman, Department of Emergency Medicine, Case Western Reserve University, Cleveland Clinic Foundation, Cleveland, OH; Daniel Kim, MD, FACS, Chief, Head and Neck Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Massachusetts, Worcester; Steven Mosher, MD, Infectious Diseases, Sharpe Clinic, San Diego, CA; Aphrodite Papadakis, MD, Department of Family Practice and Geriatrics, Metrohealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH; Isidro Pujol, DO, Department of Internal Medicine, Mt. Sinai Medical Center, Miami, FL; Paul Stander, MD, FACP, Medical Director, Banner Healthcare Systems, Department of Internal Medicine, Arizona Health Science University, Phoenix; and Gregory A. Volturo, MD, FACEP, Vice Chairman and Associate Professor, Department of Emergency Medicine, University of Massachusetts Medical School, Worcester.)
1. Guay DRP. Short-course antimicrobial therapy of respiratory tract infections. Drugs 2003;63:2169-2184.
2. Henry DC, Riffer E, Sokol WN, et al. Randomized double-blind study comparing 3- and 6-day regimens of azithromycin with a 10-day amoxicillin-clavulanate regimen for treatment of acute bacterial sinusitis. Antimicrob Agents Chemother 2003;47:2770-2774.
3. Young J, Bucher H, Tschudi P, et al. The clinical diagnosis of acute bacterial rhinosinusitis in general practice and its therapeutic consequences. J Clin Epidemiol 2003;56:377-384.
4. Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 2000;123(Suppl 1 Pt 2):S5-S31.
5. Karchmer AW. Antibacterial therapy. In: Goldman L, Bennett JC, eds. Cecil Textbook of Medicine, 21st ed. Philadelphia: WB Saunders Co; 2000:1591-1603.
6. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis medica, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J 1997;16:680-695.
7. Williams JW Jr, Holleman DR Jr, Samsa GP, et al. Randomized controlled trial of 3 vs 20 days of trimethoprim/sulfamethoxazole for acute maxillary sinusitis. JAMA 1995;273:1015-1021.
8. Casiano RR. Azithromycin and amoxicillin in the treatment of acute maxillary sinusitis. Am J Med 1991;91(Suppl 3A):27S-30S.
9. Khong TK. Shortened therapies in acute sinusitis. Hosp Pract 1996;31(Suppl 1):11-13.
10. Klapan I, Culig J, Oreskovic K, et al. Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis. Am J Otolaryngol 1999;20:7-11.
11. Gehanno P, Beauvillain C, Bobin S, et al. Short therapy with amoxicillin-clavulanate and corticosteroids in acute sinusitis. Scand J Infect Dis 2000;32:679-684.
12. Roos K, Brunswig-Pitschner C, Kostrica R, et al. Efficacy and tolerability of once-daily therapy with telithromycin for 5 or 10 days for the treatment of acute maxillary sinusitis. Chemotherapy 2002;48: 100-108.
13. Sher LD, McAdoo MA, Bettis RD, et al. A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/ clavulanate in patients with acute bacterial sinusitis. Clin Ther 2002;24:269-281.
14. Ferguson BJ, Anon J, Poole MD, et al. Short treatment durations for acute bacterial rhinosinusitis: Five days of gemifloxacin versus 7 days of gemifloxacin. Otolaryngol Head Neck Surg 2002;127:1-6.
15. Ng DK, Chow PY, Leung L, et al. A randomized controlled trial of azithromycin and amoxicillin/clavulanate in the management of subacute childhood rhinosinusitis. J Paediatr Child Health 2000; 36:378-381.
16. Zithromax package insert. Revised January 2004. Pfizer, Inc.
17. Hoberman A, Paradise JL, Burch DJ, et al. Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for the treatment of otitis media in children. Pediatr Infect Dis J 1997;16:463-470.
18. Gehanno P, Taillebe M, Denis P, et al. Short-course cefotaxime compared with five-day co-amoxyclav in acute otitis media in children. J Antimicrob Chemother 1990;26(Suppl A):29-36.
19. Cohen R, Navel M, Grunberg J, et al. One dose ceftriaxone vs ten days of amoxicillin/clavulanate therapy for acute otitis media. Pediatr Infect Dis J 1999;18:403-409.
20. Gooch WM 3rd, Blair E, Puopolo A, et al. Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media. Pediatr Infect Dis J 1996;15:157-164.
21. Roos K, Larsson P. Efficacy of ceftibuten in 5 vs 10 days treatment of recurrent otitis media in children. Int J Pediatr Otorhinolaryngol 2000;55:109-115.
22. Schaad U. Multicentre evaluation of azithromycin in comparison with co-amoxyclav for the treatment of acute otitis media in children. J Antimicrob Chemother 1993;31(Suppl E):81-88.
23. Khurana CM. A multicenter, randomized, open label comparison of azithromycin and amoxicillin/clavulanate in acute otitis media among children attending day care or school. Pediatr Infect Dis J 1996;15(9 Suppl):S24-S29.
24. Augmentin/Augmentin XR package insert. Revised January 2004. GlaxoSmithKline.
25. Cotter CS, Stringer S, Rust KR, et al. The role of computed tomography scans in evaluating sinus disease in pediatric patients. Int J Pediatr Otorhinolaryngol 1999;50:63-68.
26. Rakkar S, Roberts K, Towe BF, et al. Moxifloxacin versus amoxicillin clavulanate in the treatment of acute maxillary sinusitis: A primary care experience. Int J Clin Pract 2001;55:309-315.
27. Moxifloxacin (Avelox) package insert. October 2003. Bayer.
28. Levofloxacin (Levaquin) package insert. Ortho-McNeil.
29. Hurst M, Lamb HM, Scott LJ, et al. Levofloxacin: An updated review of its use in the treatment of bacterial infections. Drugs 2002;62:2127-2167.
30. Adelglass J, DeAbate CA, McElvaine P, et al. Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. Otolaryngol Head Neck Surg 1999;120:320-327.
31. Adelglass J, Jones TM, Ruoff G, et al. A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis. Pharmacotherapy 1998;18:1255-1263.
32. Lasko B, Lau CY, Saint-Pierre C, et al. Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: A multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group. J Int Med Res 1998;26: 281-291.
33. Scheld WM. Maintaining fluoroquinolone class efficacy: Review of influencing factors. Emerg Infect Dis 2003;9:1-5.
34. Burke T, Villanueva C, Mariano H Jr, et al. Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute maxillary sinusitis. Sinusitis Infection Study Group. Clin Ther 1999;21: 1664-1677.
35. Siegert R, Gehanno P, Nikolaidis P, et al. A comparison of the safety and efficacy of moxifloxacin (BAY 12-8039) and cefuroxime axetil in the treatment of acute bacterial sinusitis in adults. Sinusitis Study Group. Respir Med 2000;94:337-344.
36. Soman A, Honeybourne D, Andrews J, et al. Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1999;44:835-838.
37. Andrews JM, Honeybourne D, Jevons G, et al. Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1997;40:573-577.
38. Scott LJ, Ormrod D, Goa KL. Cefuroxime axetil: An updated review of its use in the management of bacterial infections. Drugs 2001;61: 1455-1500.
39. Brankston ER, et al. Cefprozil versus cefuroxime axetil in the treatment of acute sinusitis. Clin Drug Invest 1998;15:81-90.
40. Ferguson BJ, et al. Efficacy of once daily gemifloxacin for 7 days compared with cefuroxime twice daily for 10 days in the treatment of acute bacterial sinusitis [abstract]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Sept. 17, 2000; Toronto, Ontario. Abstract 475.
41. Johnson PA, Rodriguez HP, Wazen JJ, et al. Ciprofloxacin versus cefuroxime axetil in the treatment of acute bacterial sinusitis. Sinusitis Infection Study Group. J Otolaryngol 1999;28:3-12.
42. Weis M, Hendrick K, Tillotson G, et al. Multicenter comparative trial of ciprofloxacin versus cefuroxime axetil in the treatment of acute rhinosinusitis in a primary care setting. Rhinosinusitis Investigation Group. Clin Ther 1998;20:921-932.
43. Stefansson P, Jacovides A, Jablonicky P, et al. Cefuroxime axetil versus clarithromycin in the treatment of acute maxillary sinusitis. Rhinology 1998;36:173-178.
44. Elies W. Five days of treatment with cefuroxime axetil compared with 10 days of treatment with clarithromycin in acute sinusitis [abstract]. Clin Microbiol Infect 1999;(5 Suppl 3):277.
45. Henry DC, Sydnor A Jr, Settipaine GA, et al. Comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial sinusitis. Clin Ther 1999;21:1158-1170.
46. Namyslowski G, Misiolek M. Comparison of the efficacy and tolerability of amoxicillin/clavulanic acid, 875 mg bid, with cefuroxime, 500 mg bid, in the treatment of chronic sinusitis in adults [abstract]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. Sept. 26, 1999; San Francisco, Calif. Abstract 710.
47. Berg O, Carenfelt C. Analysis of symptoms and clinical signs in the maxillary sinus empyema. Acta Otolaryngol 1988;105:343-349.
48. Williams JW Jr., Simel DL, Roberts L, et al. Clinical evaluation for sinusitis. Making the diagnosis by history and physical examination. Ann Intern Med 1992;117:705-710.
49. Reider JM, Nashelsky J. Do imaging studies aid in diagnosis of acute sinusitis? J Fam Pract 2003;52:565-567; discussion 567.
50. American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement. Clinical Practice Guideline: Management of sinusitis. Pediatrics 2001;108: 798-808.
51. Snow V, Mottur-Pilson C, Hickner JM, et al. Principles of appropriate antibiotic use for acute sinusitis in adults. Ann Intern Med 2001; 134:495-497.
52. Lau J. Diagnosis and Treatment of Acute Bacterial Rhinosinusitis. Evidence Report/Technology Assessment No. 9. Rockville, Md: Agency for Health Care Policy and Research; 1999.
53. Varonen H, Makela M, Savolainen S, et al. Comparison of ultrasound, radiography, and clinical examination in the diagnosis of acute maxillary sinusitis: A systematic review. J Clin Epidemiol 2000;53:940-948.
54. Lindbaek M, Hjortdahl P, Johnsen UL. Use of symptoms, signs, and blood tests to diagnose acute sinus infections in primary care: Comparison with computed tomography. Fam Med 1996;28: 183-188.
55. Lindbaek M, Johnsen UL, Kaastad E, et al. CT findings in general practice patients with suspected acute sinusitis. Acta Radiol 1996; 37:708-713.
56. Lindbaek M, Hjortdahl P. The clinical diagnosis of acute purulent sinusitis in general practice: A review. Br J Gen Pract 2002;52: 491-495.
57. Benninger MS, Sedory Holzer SE, Lau J. Diagnosis and treatment of uncomplicated acute bacterial rhinosinusitis: Summary of the Agency for Health Care Policy and Research evidence-based report. Otolaryngol Head Neck Surg 2000;122:1-7.
58. Gordts F, Clement PA, Destryker A. et al. Prevalence of sinusitis signs on MRI in a non-ENT paediatric population. Rhinology 1997; 35:154-157.
59. Chong VF, Fan YF. Comparison of CT and MRI features in sinusitis. Eur J Radiol 1998;29:47-54.
60. Patel K, Chavda SV, Violaris N, et al. Incidental paranasal sinus inflammatory changes in a British population. J Laryngol Otol 1996;110:649-651.
61. Acute Sinusitis in Adults. Bloomington, Minn: Institute for Clinical Systems Improvement (ICSI), 2002. Available at: www.icsi.org. Accessed on June 17, 2003.
62. McAlister WH, Parker BR, Kushner DC, et al. Sinusitis in the pediatric population. American College of Radiology. ACR Appropriateness Criteria. Radiology 2000;215(Suppl): 811-818.