Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 2 of 38http://www.aacijournal.com/content/7/1/2and productivity. It is estimated that approximately and neck surgery, allergy and immunology, or infectious6 billion dollars is spent in the United States annually disease who dispense first-line care or teach colleagueson therapy for rhinosinusitis . A recent study in on the subject. This document is specifically adapted forCanada described the impact of chronic rhinosinusitis the needs of the Canadian practice environment and(CRS) on patients and healthcare utilization . Patients makes recommendations that take into account factorswith CRS had a health status similar to patients with such as wait times for computed tomography scans orarthritis, cancer, asthma, and inflammatory bowel dis- specialist referral. These guidelines are intended to pro-ease. Compared with people without CRS, those with vide useful information for CRS by addressing this areaCRS reported more days spent bedridden and more vis- where controversy is unresolved and evidence is typi-its to family physicians, alternative healthcare providers, cally Grade D - requiring incorporation of expert opi-and mental health experts. These findings underscore nion based on pathophysiology and current treatmentthe significant impact of this disease on patient quality regimens. Thus, the main thrust is to provide a compre-of life, as well as costs of care to patients and society. hensive guide to CRS and to address changes in the In Canada, 2.89 million prescriptions were dispensed management of ABRS.for acute rhinosinusitis (ARS) or CRS in 2006, withapproximately 2/3 for ARS and 1/3 for CRS . Despite Guideline Preparation Processwell-established differences between these 2 diseases in An increased emphasis on evidence-based recommenda-pathophysiology, bacteriology, and standard specialist tions over the past decade has significantly improvedtreatment strategies, an assessment of therapies pre- the overall quality of most published guidelines, but pre-scribed in Canada for CRS has shown that medications sent significant difficulties in developing guidelinesprescribed for CRS exactly paralleled those prescribed where the evidence base for long-standing, traditionalfor ARS . remedies is often weak or anecdotal, or in emerging The incidence of bacterial rhinosinusitis is difficult to entities such as chronic rhinosinusitis (CRS) where con-obtain precisely given that not all patients will seek medi- troversy remains and evidence is sparse. In developingcal help. In the United States in 2007, ARS affected 26 these guidelines, standard evidence-based developmentmillion individuals and was responsible for 12.9 million techniques have been combined with the Delphi votingoffice visits . Although no specific Canadian data is process in order to offer the reader the opinion of aavailable, extrapolation from US data suggests an occur- multidisciplinary expert group in areas where evidencerence of 2.6 million cases in Canada annually. This is in is weak.line with prescription data from 2004. This high inci- Funding was obtained via an unrestricted grantdence is not unexpected given that acute bacterial rhino- obtained from 5 pharmaceutical manufacturers, withsinusitis (ABRS) usually develops as a complication in each contributing equally to this project. In order to0.5%-2% of upper respiratory tract infections (URTIs) . minimize any appearance of conflict of interest, all A survey of Canadian households reported the preva- funds were administered via a trust account held at thelence of CRS to be 5% . The prevalence was higher in Canadian Society of Otolaryngology-Head and Neckwomen compared with men (5.7% vs 3.4% for subjects Surgery (CSO-HNS). No contact with industry wasaged ≥12 years) and increased with age. CRS was asso- made during the guidelines development or reviewciated with smoking, lower income, history of allergy, process.asthma, or chronic obstructive pulmonary disease An English-language Medline® search was conducted(COPD), and was slightly higher for those living in the using the terms acute bacterial rhinosinusitis (ABRS),eastern region or among native Canadians. chronic rhinosinusitis (CRS), and nasal polyposis (lim- Guidelines for ARS have been developed over the past ited to the adult population, human, clinical trials, items5 years by both a European group (E3POS) and the with abstracts) and further refined based on the indivi-American Academy of Otolaryngology-Head and Neck dual topics. This is a multi-disciplined condition andSurgery (AAO-HNS). Both guidelines have limitations therefore input from all appropriate associations wasthat we believe are improved upon by the current docu- required. Inclusion criteria: most current evidence-basedment. This current document provides healthcare prac- data, relevance, subject specifics, caliber of the abstract,titioners with a brief, easy-to-read review of information Canadian data preferred but not exclusive. Exclusionregarding the management of ARS and CRS. These criteria: newer abstract of the same subject available,guidelines are meant to have a practical focus, directed non-human, not relevant.at first-line practitioners with an emphasis on patient- The quality of retrieved articles was assessed bycentric issues. The readership is considered to be family Society Team Leaders along with the principal authorphysicians, emergency physicians, or other point-of-care based on area of expertise. Where necessary, the princi-providers, as well as specialists in otolaryngology-head pal author invited input from the External Content
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 3 of 38http://www.aacijournal.com/content/7/1/2Experts. Articles were graded for strength of evidence by In situations where high-quality evidence is impossible todrawing upon strategies adapted from the American obtain and anticipated benefits strongly outweigh the harm,Academy of Pediatrics Steering Committee on Quality the recommendation may be based on lesser evidence .Improvement and Management (AAP SCQIM) guide- Thus, policy recommendations were formulated basedlines , the Grades of Recommendation, Assessment, on evidence quality and the balance of potential benefitsDevelopment and Evaluation (GRADE) grading system and harm. As many therapies have not been subjected, and the AAO-HNS guidelines in sinusitis , all of to safety evaluation in a clinical trial setting, the poten-which use similar strategies by classifying strength of tial for harm was assessed for each therapy and weighsevidence recommendations according to the balance of in the recommendation. The guidelines presented usedthe benefits and downsides after considering the quality these approaches to formulate strength of evidenceof the evidence. Accordingly, grades of evidence were recommendations, with options to recommend denoteddefined as: as: Grade A. Well-designed, randomized, controlled stu- • Strong dies or diagnostic studies on relevant populations • Moderate Grade B. Randomized controlled trials or diagnostic • Weak studies with minor limitations; overwhelmingly con- • An option for therapy, or sistent evidence from observational studies • Not recommended as either clinical trial data of a Grade C. Observational studies (case control or given therapy did not support its use or a concern cohort design) for toxicity was noted. Grade D. Expert opinion, case reports, reasoning from first principles Grade X. Exceptional situations where validating stu- Strength of Recommendation dies cannot be done and there is a clear predomi- Recommendations were assessed according to a Delphi nance of benefit or harm . voting process, whereby voting options included to accept completely, to accept with some reservation, toStrength of Evidence accept with major reservation, to reject with reservation,Definitions for the strength of evidence recommenda- or to reject completely [7,10]. Only statements that weretions combine the balance of benefit versus harm of accepted by over 50% of the group were retained.treatment with the grade of the evidence, as follows: Strength of the recommendation by the multidisciplin- ary group of experts was denoted as: Strong Recommendation: Benefits of treatment clearly exceed harm; quality of evidence is excellent • Strong (for accept completely) (Grade A or B). A strong recommendation should • Moderate (for accept with some reservation), or be followed unless there is a clear and compelling • Weak (for accept with major reservation). reason for a different approach. Recommendation: Benefits exceeded harm, but qual- Thus, strength of recommendation is a measure of ity of evidence is not as strong (Grade B or C). A endorsement by the group of experts. recommendation should generally be followed, but These guidelines have been developed from the outset clinicians should remain alert to new information to meet the AGREE criteria  to ensure maximum and consider patient preferences. impact. Option: Quality of evidence is suspect (Grade D) or DISCLAIMER: These guidelines are designed to offer well-done studies (Grade A, B or C) show little clear evidence-based strategies in the management of acute advantage. An option reflects flexibility in decision- and chronic rhinosinusitis. They are, however, not making regarding appropriate practice, but clinicians intended to replace clinical judgment or establish a pro- may set limits on alternatives. The preference of the tocol for all individuals with suspected rhinosinusitis. Dif- patient should influence the decision. ferent presentations, associated comorbidities, or No Recommendation: A lack of relevant evidence availability of resources may require adaptation of these (Grade D) and an unclear balance between benefits guidelines, thus there may be other appropriate and harm. No recommendation reflects no limita- approaches to diagnosing and managing these conditions. tions on decision-making and clinicians should be vigilant regarding new information on the balance of Summary of Guideline Statements and Strengths benefit versus harm. The preference of the patient Statements and their ratings for strength of evidence should influence the decision. and recommendation are summarized in Table 1.
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 4 of 38http://www.aacijournal.com/content/7/1/2Table 1 Guideline Statements and Strengths for Acute Bacterial Rhinosinusitis and Chronic RhinosinusitisStatement Strength of Strength of Evidence* Recommendation†Acute Bacterial Rhinosinusitis1: ABRS may be diagnosed on clinical grounds using symptoms and signs of more than 7 days Moderate Strongduration.2. Determination of symptom severity is useful for the management of acute sinusitis, and can be Option Strongbased upon the intensity and duration and impact on patient’s quality of life.3: Radiological imaging is not required for the diagnosis of uncomplicated ABRS. When performed, Moderate Strongradiological imaging must always be interpreted in light of clinical findings as radiographic imagescannot differentiate other infections from bacterial infection and changes in radiographic images canoccur in viral URTIs.Criteria for diagnosis of ABRS are presence of an air/fluid level or complete opacification. Mucosalthickening alone is not considered diagnostic. Three-view plain sinus X-rays remain the standard.Computed tomography (CT) scanning is mainly used to assess potential complications or where regularsinus X-rays are no longer available.Radiology should be considered to confirm a diagnosis of ARBS in patients with multiple recurrentepisodes, or to eliminate other causes.4: Urgent consultation should be obtained for acute sinusitis with unusually severe symptoms or Option Strongsystemic toxicity or where orbital or intracranial involvement is suspected.5: Routine nasal culture is not recommended for the diagnosis of ABRS. When culture is required for Moderate Strongunusual evolution, or when complication requires it, sampling must be performed either by maxillary tapor endoscopically-guided culture.6: The 2 main causative infectious bacteria implicated in ABRS are Streptococcus pneumoniae and Strong StrongHaemophilus influenzae.7: Antibiotics may be prescribed for ABRS to improve rates of resolution at 14 days and should be Moderate Moderateconsidered where either quality of life or productivity present as issues, or in individuals with severesinusitis or comorbidities. In individuals with mild or moderate symptoms of ABRS, if quality of life is notan issue and neither severity criterion nor comorbidities exist, antibiotic therapy can be withheld.8: When antibiotic therapy is selected, amoxicillin is the first-line recommendation in treatment of Option StrongABRS. In beta-lactam allergic patients, trimethoprim-sulfamethoxazole (TMP/SMX) combinations or amacrolide antibiotic may be substituted.9: Second-line therapy using amoxicillin/clavulanic acid combinations or quinolones with enhanced Option Stronggram positive activity should be used in patients where risk of bacterial resistance is high, or whereconsequences of failure of therapy are greatest, as well as in those not responding to first-line therapy. Acareful history to assess likelihood of resistance should be obtained, and should include exposure toantibiotics in the prior 3 months, exposure to daycare, and chronic symptoms.10: Bacterial resistance should be considered when selecting therapy. Strong Strong11: When antibiotics are prescribed, duration of treatment should be 5 to 10 days as recommended by Strong Moderateproduct monographs. Ultra-short treatment durations are not currently recommended by this group.12: Topical intranasal corticosteroids (INCS) can be useful as sole therapy of mild-to-moderate ARS. Moderate Strong13: Treatment failure should be considered when patients fail to respond to initial therapy within 72 Option Stronghours of administration. If failure occurs following use of INCS as monotherapy, antibacterial therapyshould be administered. If failure occurs following antibiotic administration, it may be due to lack ofsensitivity to, or bacterial resistance to, the antibiotic, and the antibiotic class should be changed.14: Adjunct therapy should be prescribed in individuals with ABRS. Option Strong15. Topical INCS may help improve resolution rates and improve symptoms when prescribed with an Moderate Strongantibiotic.16. Analgesics (acetaminophen or non-steriodal anti-inflammatory agents) may provide symptom relief. Moderate Strong17. Oral decongestants may provide symptom relief. Option Moderate18. Topical decongestants may provide symptom relief. Option Moderate19. Saline irrigation may provide symptom relief. Option Strong20. For those not responding to a second course of therapy, chronicity should be considered and the Option Moderatepatient referred to a specialist. If waiting time for specialty referral or CT exceeds 6 weeks, CT should beordered and empiric therapy for CRS administered. Repeated bouts of acute uncomplicated sinusitisclearing between episodes require only investigation and referral, with a possible trial of INCS. Persistentsymptoms of greater than mild-to-moderate symptom severity should prompt urgent referral.21: By reducing transmission of respiratory viruses, hand washing can reduce the incidence of viral and Moderate Strongbacterial sinusitis. Vaccines and prophylactic antibiotic therapy are of no benefit.
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 5 of 38http://www.aacijournal.com/content/7/1/2Table 1 Guideline Statements and Strengths for Acute Bacterial Rhinosinusitis and Chronic Rhinosinusitis (Continued)22: Allergy testing or in-depth assessment of immune function is not required for isolated episodes but Moderate Strongmay be of benefit in identifying contributing factors in individuals with recurrent episodes or chronicsymptoms of rhinosinusitis.Chronic Rhinosinusitis23: CRS is diagnosed on clinical grounds but must be confirmed with at least 1 objective finding on Weak Strongendoscopy or computed tomography (CT) scan.24: Visual rhinoscopy assessments are useful in discerning clinical signs and symptoms of CRS. Moderate Moderate25: In the few situations when deemed necessary, bacterial cultures in CRS should be performed either Option Strongvia endoscopic culture of the middle meatus or maxillary tap but not by simple nasal swab.26: The preferred means of radiological imaging of the sinuses in CRS is the CT scan, preferably in the Moderate Strongcoronal view. Imaging should always be interpreted in the context of clinical symptomatology becausethere is a high false-positive rate.27: CRS is an inflammatory disease of unclear origin where bacterial colonization may contribute to Weak Moderatepathogenesis. The relative roles of initiating events, environmental factors, and host susceptibility factorsare all currently unknown.28: Bacteriology of CRS is different from that of ABRS. Moderate Strong29: Environmental and physiologic factors can predispose to development or recurrence of chronic Moderate Strongsinus disease. Gastroesophageal reflux disease (GERD) has not been shown to play a role in adults.30: When diagnosis of CRS is suggested by history and objective findings, oral or topical steroids with Moderate Moderateor without antibiotics should be used for management.31: Many adjunct therapies commonly used in CRS have limited evidence to support their use. Saline Moderate Moderateirrigation is an approach that has consistent evidence of benefiting symptoms of CRS.32. Use of mucolytics is an approach that may benefit symptoms of CRS. Option Moderate33. Use of antihistamines is an approach that may benefit symptoms of CRS. Option Weak34. Use of decongestants is an approach that may benefit symptoms of CRS. Option Weak35. Use of leukotriene modifiers is an approach that may benefit symptoms of CRS. Weak Weak36: Failure of response should lead to consideration of other possible contributing diagnoses such as Option Moderatemigraine or temporomandibular joint dysfunction (TMD).37: Surgery is beneficial and indicated for individuals failing medical treatment. Weak Moderate38: Continued use of medical therapy post-surgery is key to success and is required for all patients. Moderate ModerateEvidence remains limited.39 Part A: Patients should be referred by their primary care physician when failing 1 or more courses of Weak Moderatemaximal medical therapy or for more than 3 sinus infections per year.39 Part B: Urgent consultation with the otolaryngologist should be obtained for individuals with Weak Strongsevere symptoms of pain or swelling of the sinus areas or in immunosuppressed patients.40: Allergy testing is recommended for individuals with CRS as potential allergens may be in their Option Moderateenvironment.41: Assessment of immune function is not required in uncomplicated cases. Weak Strong42: Prevention measures should be discussed with patients. Weak Strong*Strength of evidence integrates the grade of evidence with the potential for benefit and harm.† Strength of recommendation indicates the level of endorsement of the statement by the panel of experts.Acute Bacterial Rhinosinusitis (ABRS) DefinitionDefinition and Diagnosis The common cold is caused by a rhinovirus, and in mostStatement 1: ABRS may be diagnosed on clinical grounds cases peak symptom severity is reached by 3 days .using symptoms and signs of more than 7 days duration. However, the same virus can activate an inflammatory Strength of evidence: Moderate process that can lead to bronchitis, pharyngitis, and rhino- Strength of recommendation: Strong sinusitis . Thus, the term rhinosinusitis has been used Rationale: ABRS is a clinical diagnosis that must be to distinguish this more severe phenotypic entity from thedifferentiated from uncomplicated viral infections of the common cold, which is associated with sinusitis .upper respiratory passages. Although no single symptom Despite the frequency of the common cold, 0.5% to 2% ofaccurately predicts the presence or absence of bacterial individuals with the common cold will develop ABRS .infection, the presence of several signs and symptoms ABRS is defined as a bacterial infection of the parana-increases the predictive value. sal sinuses, described as a sudden onset of symptomatic
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 6 of 38http://www.aacijournal.com/content/7/1/2sinus infection. Each episode usually lasts less than Williams et al identified 5 independent predictors of4 weeks. Within this 4-week period, symptoms resolve sinusitis that were consistent with radiographic findingseither spontaneously or with appropriate treatment (Table 5) .[15,16]. There may be up to 3 episodes per year and full Prediction rules can be used to aid in diagnosis. Usingrecovery in between episodes. ABRS commonly occurs either the Berg or Williams prediction rules, the prob-as a complication of a viral upper respiratory tract infec- ability of ABRS increases with cumulative symptomstion (URTI) [16,17] and is therefore difficult to differ- [24,25]. Although none of these symptoms are individu-entiate from a viral infection. Recurrent ABRS is defined ally sensitive or specific for diagnosis, the reported num-as 4 or more episodes of ABRS per year. Symptoms of ber of diagnostic factors is felt to correlate well with theABRS have been classified as major and minor (Table 2) likelihood of bacterial infection .. Although minor symptoms may be clinically help- A Canadian Medical Association evidence-basedful, they are not used for the diagnosis of ABRS. review recommended a score based on Williams’ 5 inde-Diagnosis pendent predictor symptoms . Fewer than 2 symp-Although sinus aspirates are considered to be the gold toms ruled out ABRS (positive predictive value [PPV], <standard for diagnosis, this invasive procedure is not 40%), 4 or more symptoms ruled in ABRS (PPV, 81%),recommended in a primary care setting . Clinicians and 2 or 3 symptoms (PPV, 40%-63%) suggested thatthus must rely on history and physical examination for radiography might be beneficial to clarify the diagnosis.the initial evaluation of ABRS. ABRS can be diagnosed More recent studies have emphasized limitations of clin-based on the presence of persistent or worsening symp- ical findings alone and have either introduced new diag-toms (Table 3) [9,19-21]. An algorithm for the diagnosis nostic elements or else assessed the accuracy of existingand treatment of ABRS is presented in Figure 1. symptoms. In a study of 50 patients with upper respiratory In sinus aspirate studies, symptoms lasting longer than tract symptoms of at least 1 week and self-suspected acute10 days were more likely due to ABRS . The 7-to- maxillary sinusitis, no distinct clinical signs or symptoms10-day specification is based on the natural history of were identified that increased diagnostic accuracy .rhinovirus infections . The presence of several signs The sensitivity and specificity of the usual clinical signsand symptoms increases the predictive value. and symptoms ranged from 0.04 to 0.74 in a small pro- Several consensus-based diagnostic criterion have been spective study that defined acute sinusitis (not necessarilydeveloped to aid clinicians in the diagnosis. The Centers bacterial) as 1 or more sinuses with an air fluid level orfor Disease Control and Prevention recommends reser- complete opacification . A history of facial pain andving the diagnosis of ABRS for patients with: sinus tenderness on percussion were inversely associated with sinusitis (likelihood ratio [LR] < 1.0). Positive LRs • Symptoms lasting at least 7 days and were 1.89 (95% confidence interval [CI], 1.06 to 3.39) for • Purulent nasal secretions and symptom duration longer than 10 days, 1.47 (CI, 0.93 to • 1 of the following: 2.32) for purulent nasal secretions on history, 2.11 (CI, ○ Maxillary pain 1.23 to 3.63) for oropharyngeal red streak in the lateral ○ Tenderness in the face (especially unilateral) pharyngeal recess, 1.89 (CI, 1.08 to 3.32) for transillumina- ○ Tenderness of the teeth (especially unilateral) tion, and 1.22 (CI, 0.08 to 18.64) for otitis media. . Although transillumination is not considered accurate in the diagnosis of acute rhinosinusitis (ARS), visualiza- Two studies of patients presenting with symptoms of tion of purulent secretions from the middle meatus usingsinusitis have led to the development of predictionrules. In 1 study, Berg et al reported that 2 or morepositive findings provided 95% sensitivity and 77% speci- Table 3 ABRS Diagnosis Requires the Presence of at Leastficity for sinusitis (Table 4) . In the second study, 2 Major Symptoms* Major Symptom P Facial Pain/pressure/fullnessTable 2 Symptoms of ABRS O Nasal ObstructionMajor Minor D Nasal purulence/discolored postnasal DischargeFacial pain/pressure/fullness Headache S Hyposmia/anosmia (Smell)Nasal obstruction HalitosisNasal purulence/discolored postnasal discharge Fatigue *At least 1 symptom must be nasal obstruction or nasal purulence/discolored postnasal discharge. Thus, a diagnosis requires at least 2 PODS, one of whichHyposmia/anosmia Dental pain must be O or D. Cough Consider ABRS when viral URTI persists beyond 10 days or worsens after 5 to Ear pain/pressure 7 days with similar symptoms . Bacterial etiology should be suspected if sinus symptoms persist for more than 7 days without improvement .
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 7 of 38http://www.aacijournal.com/content/7/1/2 Figure 1 Algorithm for the Diagnosis and Treatment of ABRS.a short wide speculum has been reported to be highly pre- Taken together, these results emphasize the diffi-dictive of ARS . Young et al suggested that purulent culty of making an accurate diagnosis of sinusitis butnasal discharge, signs of pus in the nasal cavity, or sore support existing consensus that symptoms with dura-throat are better criteria than radiography for selecting tion-based criteria are the best currently availablepatients who would benefit from antibiotic therapy . tool.
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 8 of 38http://www.aacijournal.com/content/7/1/2Table 4 Berg Prediction Rule Based on Signs and Symptoms of ABRS Sign or Symptom Positive Predictive Value (PPV), %Purulent rhinorrhea with unilateral predominance 50Local pain with unilateral predominance 41Pus in nasal cavity 17Bilateral purulent rhinorrhea 15Presence of ≥3 symptoms has a positive likelihood ratio (LR) of 6.75.Symptom Severity Criteria for diagnosis of ABRS are presence of an air/Statement 2: Determination of symptom severity is use- fluid level or complete opacification. Mucosal thickeningful for the management of acute sinusitis, and can be alone is not considered diagnostic. Three-view plainbased upon the intensity and duration and impact on sinus X-rays remain the standard. Computed tomogra-patient’s quality of life. phy (CT) scanning is mainly used to assess potential Strength of evidence: Option complications or where regular sinus X-rays are no Strength of recommendation: Strong longer available. Rationale: Although most of the emphasis of diagno- Radiology should be considered to confirm a diagnosissis has been placed upon differentiating between viral of ARBS in patients with multiple recurrent episodes, orand bacterial causes of sinusitis, or when bacterial sinu- to eliminate other causes.sitis is diagnosed, little attention has been devoted to Strength of evidence: Moderatedetermining the severity of symptomatology as mea- Strength of recommendation: Strongsured by its impact on the patient’s quality of life. While Rationale: Studies demonstrate that abnormalguidelines for determining severity of sinusitis have not images of the sinuses cannot stand alone as diagnosticbeen extensively studied , it is clear that a need for evidence of bacterial rhinosinusitis. Radiologic changesthis exists. These guidelines recommend determining such as simple mucosal thickening are present in mostthe severity of sinusitis, whether viral or bacterial, based cases of acute viral infections of the upper respiratoryupon the intensity and duration of symptoms and their tract when sensitive detection methods such as CTimpact on the patient’s quality of life. scan are used. Incidental findings of mucosal thicken- Symptom severity can be generally categorized as: ing can also be seen in a high percentage of asympto- matic individuals. • Mild: occasional limited episode In 1994, Gwaltney et al found that abnormalities of • Moderate: steady symptoms but easily tolerated the paranasal sinuses on CT scan are extremely com- • Severe: hard to tolerate and may interfere with mon in young adults with acute uncomplicated viral activity or sleep. URTIs . Another study reported that abnormalitiesRadiological Imaging on CT scans were common even among the generalStatement 3: Radiological imaging is not required for the population . Furthermore, radiographic findings ofdiagnosis of uncomplicated ABRS. When performed, inflammation demonstrating chronic rhinosinusitisradiological imaging must always be interpreted in light (CRS) are found in 27% to 42% of asymptomatic indivi-of clinical findings, as radiographic images cannot differ- duals [32,33]. Taken together, these studies highlight theentiate other infections from bacterial infection and need to correlate clinical presentation with radiographicchanges in radiographic images can occur in viral URTIs. results when imaging is used to diagnose ABRS. Statement 4: Urgent consultation should be obtainedTable 5 Williams Prediction Rule Based on Signs and for acute sinusitis with unusually severe symptoms orSymptoms of ABRS  systemic toxicity or where orbital or intracranial involve-Sign or Symptom Likelihood Ratio (LR) ment is suspected. (present) Strength of evidence: OptionMaxillary toothache 2.5 Strength of recommendation: StrongPoor response to antihistamines/ 2.1 Rationale: Extension of disease beyond the confines ofdecongestants the sinuses is a medical emergency and requires aggres-Purulent nasal secretions 2.1 sive assessment, medical therapy, and potential surgicalAbnormal transillumination 1.6 drainage. Individuals with suspected complicationsColored nasal discharge 1.5 should be urgently referred to a setting with appropriatePresence of ≥4 symptoms has a positive LR of 6.4. imaging facilities and qualified specialty care.
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 9 of 38http://www.aacijournal.com/content/7/1/2 Red flags for urgent referral include: (but not limited to) ophthalmology, neurosurgery, and infectious diseases. • Systemic toxicity Microbiology of ABRS • Altered mental status Statement 5: Routine nasal culture is not recommended • Severe headache for the diagnosis of ABRS. When culture is required for • Swelling of the orbit or change in visual acuity. unusual evolution, or when complication requires it, sampling must be performed either by maxillary tap or Orbital and intracranial complications are the most endoscopically-guided culture.feared complications of both acute and chronic rhinosi- Strength of evidence: Moderatenusitis. In the pre-antibiotic era, 20% of patients with Strength of recommendation: Strongorbital cellulitis went blind and 17% of patients died Rationale: Sinus puncture and aspiration remain the goldfrom intracranial sepsis . Even in the current era, standard for determining the etiology of ABRS. Howevercomplications can result in permanent blindness or because of the invasive nature of sinus puncture requireddeath if not treated appropriately and aggressively. for bacterial studies, this procedure is rarely performed.Visual loss from sinusitis was reported at a rate of up to The bacterial etiology of ABRS has been well defined10% in a 1991 study . by numerous studies dating back almost 50 years. Typi- Periorbital or orbital cellulitis is the most common cally, the findings between investigators have been con-complication of ABRS and most often caused by acute cordant [5,43-46]:ethmoid and/or frontal disease [36,37]. Infection spreadsfrom the sinuses to the orbit with relative ease [38,39]. • Sinus puncture and aspiration remain the goldPeriorbital cellulitis is seen on CT as soft tissue swelling standard for determining the etiology of ABRS, butand manifests as orbital pain, edema, and high fever. If are rarely performed due to the invasive nature ofnot aggressively treated, it may spread beyond the orbi- sinus puncturetal septum. Postseptal inflammation involves structures • Cultures obtained from the nasal passages do notof the orbit with the development of proptosis, limita- provide any diagnostic valuetion of ocular motion, pain and tenderness, and con- • ABRS can be differentiated from viral etiology by ajunctival chemosis. A subperiosteal or orbital abscess sinus aspirate that shows the presence of >104 col-may result in ophthalmoplegia (globe becomes fixed as a ony forming units of bacteria/mL or if polymorphresult of extra-ocular muscle paralysis) and diminished nuclear cells in sinus fluid exceeds 5000 cells/mLvisual acuity. A CT scan showing evidence of an abscess, • Lower quantities of bacteria may represent earlyor lack of clinical improvement after 24 to 48 hrs of stages of infection.intravenous antibiotics are indications for surgicalexploration and drainage. Blindness may result from Comparisons of endoscopically-directed middle meatuscentral retinal artery occlusion, optic neuritis, corneal cultures (EDMM), a less invasive approach to bacterialulceration, or pan-ophthalmitis. sampling, with maxillary sinus aspirate (MSA; the gold Altered mental status and non-specific signs charac- standard) have reported similar results [47-49]. A meta-terized by high fever, frontal or retro-orbital migraine, analysis comparing the sensitivity and specificity ofand the presence of generic signs of meningeal irritation EDMM with MSA for ABRS reported that EDMM had awarrant immediate consultation with an Ear Nose sensitivity of 81%, specificity of 91%, and overall accuracyThroat (ENT) specialist and CT scanning (with con- of 87% compared with MSA . Study authors con-trast). Infection can spread from the sinuses to the cluded that EDMM was a reliable alterative to MSA forintracranial structures . Intracranial complications obtaining cultures from patients with suspected ABRS.can include osteomyelitis of the frontal bone (Pott’s Take Home Pointspuffy tumor), meningitis, subdural empyema, epidural ABRS is a bacterial infection of the paranasal sinusesabscess, brain abscess, and cavernous sinus thrombosis. characterized by:The mortality rate for intracranial complications ranges • Sudden onset of symptomatic sinusfrom 20% to 60% . High-dose, long-term intravenous infectionantibiotic therapy followed by endoscopic drainage or • Symptom duration > 7 dayscraniotomy and surgical drainage are usually required • Length of episode < 4 weeks.for successful treatment . Major symptoms (PODS): Because of the serious nature of complications, • Facial Pain/pressure/fullnesspatients with suspected complications of ABRS should • Nasal Obstructionbe immediately referred to an otolaryngologist with • Nasal purulence/discolored postnasalappropriate consultation from other services, including Discharge
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 10 of 38http://www.aacijournal.com/content/7/1/2 • Hyposmia/anosmia (Smell). found together or in combination with other organisms Diagnosis requires the presence of ≥ 2 PODS, one of [45,46,52,54]. H influenzae strains isolated from sinus which must be O or D, and symptom duration of > puncture are almost exclusively unencapsulated (non- 7 days without improvement. typeable). Diagnosis is based on history and physical Other Pathogens examination: M catarrhalis is infrequently isolated from the adult • Sinus aspirates or routine nasal culture are population, but is more common in children where it not recommended accounts for approximately 25% of bacteria . Other • Radiological imaging is not required for organisms commonly isolated include S pyogenes, S aur- uncomplicated ABRS. eus, gram-negative bacilli, and the oral anaerobes The severity of sinusitis, whether viral or bacterial, [5,51,52]. should be based upon the intensity and duration of An exception appears to be acute sinusitis of odonto- symptoms and their impact on the patient’s quality genic origin, where anaerobic organisms appear to pre- of life. dominate. In 1 study, anaerobes were recovered in 50% Because complications of ABRS can elicit a medical of patients, and predominately consisted of Peptostrepto- emergency, individuals with suspected complications coccus spp, Fusobacterium spp, and Prevotella spp . should be urgently referred for specialist care. Mixed anaerobic and facultative anaerobic bacteria were Red flags for urgent referral include: recovered in an additional 40% of patients, including the • Systemic toxicity alpha-haemolytic Streptococci, microaerophilic Strepto- • Altered mental status cocci, and S aureus. Only 5% of odontogenic specimens • Severe headache grew either S pneumoniae or H influenzae. Beta-lacta- • Swelling of the orbit or change in visual mase producing bacteria were isolated from 10 of 20 acuity. specimens. Severity of Disease Linked to PathogenBacteriology Several recent studies have increased our understandingStatement 6: The 2 main causative infectious bacteria of the bacterial etiology associated with ABRS. At leastimplicated in ABRS are Streptococcus pneumoniae and 1 study has demonstrated that severity of disease isHaemophilus influenzae. dependent on the infecting pathogen . Compared Strength of evidence: Strong with patients infected with H influenzae, patients Strength of recommendation: Strong infected with S pneumoniae showed a significantly Rationale: The bacteriology of ABRS in adults has higher incidence of severe disease (39.2% vs 23.6%, P =been well documented in multiple clinical trials and .0097) and complete sinus opacification (46.2% vs 29.2%,mainly involves S pneumoniae and H influenzae, with a P = .0085). Another study has suggested that although Ssmall percentage of other agents such as Moraxella cat- pneumoniae and H influenzae remain the predominantarhallis and Staphylococcus aureus. The causative role pathogens, the relative frequency between them mayof these less common pathogens has not been well have been altered in adults by the use of the 7-valentestablished. pneumococcal vaccine in children . In the 4 yearsStreptococcus pneumoniae and Haemophilus influenzae prior to the introduction of the vaccine, isolatesIn virtually every study, S pneumoniae and H influenzae obtained from the maxillary sinus of 156 adults predo-remain the 2 most predominant pathogens cultured minately grew S pneumoniae (46%), followed by H influ-from the maxillary sinus, typically accounting for more enzae (36%). After introduction of the vaccine, the mostthan 50% of cases [5,43-46]. Between 1975 and 1989, predominant organisms recovered from 229 adults wereGwaltney et al demonstrated that the most common H influenzae (43%) and then S pneumoniae (35%). Thepathogens in patients with ABRS were S pneumoniae difference noted in the rate of recovery of H influenzae(41%) and H influenzae (35%) . Several years later, and S pneumoniae between the 2 time frames was statis-the same author compiled data from 8 additional studies tically significant (P < .05).and again S pneumoniae and H influenzae remained the The Rise of Resistant Bacteriamost frequent pathogens isolated from diseased maxil- Recent reviews of antimicrobial resistance trends high-lary sinuses . More recent data has borne out the light the increasing rates of penicillin, macrolide, andresults of historical studies [51,52]. Although limited multi-drug resistant S pneumoniae in community-data exist, cultures obtained from other sinus cavities acquired respiratory tract infections. Ongoing cross-appear to correlate with findings obtained from the Canada surveillance has reported increased non-suscept-maxillary sinus . H influenzae and S pneumoniae are ibility and resistance since 1988 (Figure 2) [58,59]. Inmost often isolated in pure culture but are occasionally 2007, the prevalence of penicillin non-susceptibility in
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 11 of 38http://www.aacijournal.com/content/7/1/2Canada was approximately 17% . However, amoxicil-lin remains active against S pneumoniae, with the rateof resistance remaining under 2% [57,61]. Also, despitethe increasing use of levofloxacin, moxifloxacin and gati-floxacin, resistance to ciprofloxacin has remained stable. It should be noted that resistance to erythromycinimplies cross-resistance to the newer macrolides, clari-thromycin and azithromycin. Resistance to the newerfluoroquinolones (levofloxacin and moxifloxacin)remains very low (< 2%) . Higher levels of beta-lactamase production in H influ-enzae and M catarrhalis have been reported . Also,since the introduction of the 7-valent pneumococcalvaccine in children, there has been a shift in the causa-tive agent of adult community acute maxillary sinusitis.Specifically, there is a trend of decreased recovery of S Figure 2 Trends in Antimicrobial Resistance in Canada [58,59].pneumoniae resistant to penicillin from 41% to 29% andan increase in beta-lactamase producing H influenzaefrom 33% to 39% . considered where either quality of life or productivity The primary concern for H influenzae is ampicillin present as issues, or in individuals with severe sinusitisresistance, mediated by the production of a beta-lacta- or comorbidities. In individuals with mild or moderatemase. Approximately 19% of H influenzae produce a symptoms of ABRS, if quality of life is not an issue andbeta-lactamase . H influenzae remains predictably neither severity criterion nor comorbidities exist, anti-susceptible to amoxicillin-clavulanate, the cephalospor- biotic therapy can be withheld.ins, and the fluoroquinolones . Trimethoprim-sulfa- Strength of evidence: Moderatemethoxazole (TMP/SMX) and clarithromycin resistance Strength of recommendation: Moderatereported from Canadian laboratories are approximately Rationale: Antibiotics may speed time to resolution of14% and 2%, respectively. Higher levels of beta-lacta- symptoms in individuals with ABRS. However, overallmase production in H influenzae and M catarrhalis response rates evaluated at 14 days are similar for bothhave been reported . antibiotic-treated and untreated patients. Incidence of Almost 95% of M catarrhalis produce a beta-lacta- side effects, mainly digestive, increases with antibioticmase resulting in penicillin resistance. Aside from the administration.amino-penicillins, M catarrhalis remains predictably The goals of treatment for ABRS are to relieve symp-susceptible to virtually all other antibiotics. toms by controlling infection, decreasing tissue edema, Methicillin-resistant Staphylococcus aureus (MRSA) is and reversing sinus ostial obstruction to allow drainagetypically considered a multi-drug resistant pathogen. of pus . Treatment approaches are shown in Figure 1.MRSA had a 2.7% incidence in a study from Taiwan, There is no evidence to support prophylactic antibioticwith nasal surgery being the most important risk factor therapy.in adults and prior antibiotic use as the major risk factor Many studies support the efficacy of antibiotics forin children . Community acquired MRSA (CA- acute sinusitis. Results from a meta-analysis of 6 rando-MRSA) strains are resistant to all beta-lactam agents, mized, placebo-controlled trials of amoxicillin or folatebut typically remain susceptible to TMP/SMX, doxycy- inhibitors for acute sinusitis or acute exacerbation ofcline, and clindamycin . At least 1 study has demon- chronic sinusitis reported that antibiotics decreased riskstrated that 4% of ABRS infections were associated with of clinical failure by half (risk ratio [RR] = 0.54; 95% CI,CA-MRSA in the United States . 0.37-0.79) compared with placebo treatment . A Clinicians should be cognizant of their local patterns 2009 meta-analysis of 6 placebo-controlled studiesof resistance, as regional variations exist and some pro- reported a RR of 0.66 (95% CI, 0.44 to 0.98) for antibio-vinces report significantly higher rates of resistance than tic use versus placebo, but noted questionable clinicalothers. significance of the results as both groups had high cure rates (80% placebo vs 90% antibiotics) . Their con-Treatment of ABRS clusions agreed with the previous meta-analysis in thatRole of Antibiotics clinical failure was significantly less frequent with anti-Statement 7: Antibiotics may be prescribed for ABRS to biotics compared with placebo at 7 to 15 days of followimprove rates of resolution at 14 days and should be up (RR, 0.74; CI, 0.65 to 0.84). In a third meta-analysis,
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 12 of 38http://www.aacijournal.com/content/7/1/216 randomized, placebo-controlled studies of antibiotics absolute utility of antibiotic treatment compared withfor the treatment of presumed ABRS were included placebo.. This study used a random effect model odds ratio Combined, the various studies and meta-analyses do(OR) and reported a higher proportion of improvement suggest that antibiotic use, in the setting of ABRS, mayor cure (OR = 1.60, 95% CI, 1.31 to 1.96), but also a speed time to symptom resolution, but that little effecthigher rate of adverse events (OR = 1.94, 95% CI, 1.29- is noted upon ultimate outcome, with similar rates of2.92) for the antibiotic group versus the placebo group. resolution. Although antimicrobial therapy is recommended for Take Home Pointsthe management of ABRS, this recommendation is not Microbiology of ABRS:without controversy [15,16,69-71]. In a meta-analysis of • Main causative bacteria are S pneumoniae andstudies enrolling patients with suspected ABRS not con- H influenzaefirmed by imaging, laboratory testing, or cultures, analy- • Minor causative bacteria are Moraxella catar-sis of individual patient data resulted in an OR of 1.37 hallis and S aureus(95% CI, 1.13 to 1.66) for antibiotic use versus placebo ○ M catarrhalis is infrequent in the adult. The calculated number needed to treat was 15. population, but accounts for about 25% ofStudy authors concluded that clear justification for anti- bacteria in childrenbiotic treatment was lacking when ABRS was based on • Anaerobic organisms appear to predominate inclinical signs and symptoms. However, because the ana- acute sinusitis of odontogenic origin.lysis included studies of patients who had not had Role of antibiotic therapy in individuals with ABRS:X-rays of the sinuses, and studies enrolled patients with • Goals of treatment are to relieve symptoms by:obvious viral infection, the meta-analysis missed an ○ Controlling infectionopportunity to assess antibiotic efficacy in patients who ○ Decreasing tissue edemawere clearly likely to benefit from treatment . In ○ Reversing sinus ostial obstruction to allowanother meta-analysis of patients with symptoms of drainage of pusacute sinusitis or rhinitis (10 studies) or acute rhinor- • Antibiotics may be prescribed to improve ratesrhea (3 studies), symptom duration averaged 8.1 days of symptom resolution(studies ranged from a median of 4.5 days to a mean of ○ Overall response rates are similar for anti-15.4 days), and diagnosis was made from signs and biotic-treated and untreated individuals.symptoms in over half of the studies. Although cure or • Antibiotics should be considered forimprovement rates were significantly better for the anti- individuals:biotic group at 7 to 12 days, there was no difference ○ With severe sinusitis or comorbiditiesbetween treatment groups at 15 days, suggesting that ○ Where quality of life or productivity arethere was no difference between antibiotics and placebo issueson patient outcomes. However, the meta-analysis • Incidence of side effects, mainly digestive,included studies of patients who likely had viral rhinosi- increases with antibiotic administration.nusits, in which antibiotics would be ineffective, thus Choosing an Antibioticreducing the ability to assess drug efficacy on patients Statement 8: When antibiotic therapy is selected, amox-most likely to benefit from treatment . A long-term icillin is the first-line recommendation in treatment ofobjection to interpretation of placebo versus antibiotic ABRS. In beta-lactam allergic patients, trimethoprim-studies of acute sinusitis has been that the presumed sulfamethoxazole (TMP/SMX) combinations or aeffectiveness of antibiotics in the management of bacter- macrolide antibiotic may be substituted.ial rhinosinusitis is diluted by the large number of indi- Strength of evidence: Optionviduals with viral disease participating in these trials. Strength of recommendation: StrongHowever, a recent study has suggested that even in Statement 9: Second-line therapy using amoxicillin/cases of bacterial rhinosinusitis confirmed by sinus aspi- clavulanic acid combinations or quinolones withrate obtained via puncture, antibiotics are no better enhanced gram positive activity should be used inthan placebo. In this study, patients with positive bacter- patients where risk of bacterial resistance is high, orial cultures for ABRS reported that while 5-day moxi- where consequences of failure of therapy are greatest, asfloxacin treatment led to numerically fewer clinical well as in those not responding to first-line therapy. Afailure rates versus placebo (19.2% vs 33.3%, respec- careful history to assess likelihood of resistance shouldtively), the difference was not statistically significant be obtained, and should include exposure to antibiotics(P = .122) . Although the findings suggested a trend in the prior 3 months, exposure to daycare, and chronicfor faster symptom resolution and lower failure rates for symptoms.antibiotic-treated individuals, they did not confirm the Strength of evidence: Option
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 13 of 38http://www.aacijournal.com/content/7/1/2 Strength of recommendation: Strong possibility of bacterial resistance should be suspected, Rationale: A comprehensive knowledge of the com- and therapy should be changed to a second-linemon etiologies associated with ABRS and the prevalence antibiotic.of antibiotic resistance among these pathogens is para- Second-line therapy using fluoroquinolones withmount to select appropriate treatment. Because antibio- enhanced gram-positive activity (ie, levofloxacin, moxi-tic selection will almost always be made in the absence floxacin) or amoxicillin-clavulanic acid inhibitors asof bacterial cultures to guide management, activity initial management may be needed when there are con-against the suspected pathogen should be considered. cerns of bacterial resistance or risk of complications in Some important considerations for choosing an anti- cases of failure due to underlying disease.biotic include: the suspected or confirmed etiology, Some populations have been found to be at greatermedical history, Canadian patterns of antimicrobial risk of harboring penicillin- and macrolide-resistantresistance, tolerability, convenience, and cost of treat- streptococci. Depending on geographic location andment. It should also be noted that an individual’s medi- environment, S pneumoniae may be resistant to macro-cal history is an important factor in treatment strategy. lides and TMP/SMX in nearly one third of cases .Patients who are at increased risk of bacterial resistance Compared with control subjects, those with exposure toand complications due to underlying disease (eg, dia- daycare settings had a 3.79 (CI, 0.85 to 7.77) higherbetes, chronic renal failure, immune deficiency) should odds of having penicillin-resistant infection . It hasnot be treated the same as otherwise healthy adults with been demonstrated that individuals with invasive strep-ABRS. Underlying systemic disorders place patients with tococcal infections and antibiotic use within the pastABRS at increased risk of recurrence, antibiotic resis- 3 months have a higher rate of antibiotic resistance, par-tance, and complications. ticularly in those treated with TMP-SMX (OR, 5.97) or Studies have reported that expensive antibiotics were the macrolide azithromycin (OR, 2.78) . Individualsno more effective than amoxicillin or folate inhibitors with antibiotic use within the past 3 months, chronicfor acute uncomplicated sinusitis in otherwise healthy symptoms greater than 4 weeks, or parents of childrenadults . A meta-analysis of 3338 patients from 16 in daycare have a higher risk of harboring penicillin-randomized comparative non-placebo studies concluded and macrolide-resistant bacteria and should be treatedthat differences between antimicrobial agents are small accordingly.in otherwise healthy adults and adolescents, and there- Second-line therapy used as initial management is alsofore an inexpensive antibiotic should initially be chosen needed in situations where a higher risk of complication. Current evidence based on randomized controlled is associated with treatment failure because of underly-trials suggest comparable efficacy amongst the antibio- ing systemic disease. Bacterial sinusitis of the frontaltics that have been approved for ABRS in Canada and sphenoid sinuses pose a higher risk of complication[15,16,76-85]. These include amoxicillin, amoxicillin/cla- than maxillary and ethmoid sinusitis and require morevulanate, cefuroxime axetil, clindamycin, TMP/SMX, aggressive management and surveillance, with first-lineclarithromycin, ciprofloxacin, levofloxacin, and moxi- therapy consisting of a second-line agent . Indivi-floxacin . duals with underlying immunosuppressive sites or medi- Selection between these different options may be diffi- cations, or with chronic medical conditions, are atcult. Current recommendations are made on the basis increased risk of complications if failure of therapyof presumed efficacy, risk of bacterial resistance, pre- occurs.sence of complications, or cost of therapy. Statement 10: Bacterial resistance should be consid- First-line therapy is amoxicillin. Surveillance studies ered when selecting therapy.demonstrate that resistance rates to amoxicillin by Strength of evidence: Strongstreptococci remain low and a consistent response Strength of recommendation: Strongremains predicted. Higher doses of amoxicillin are sug- Rationale: Bacterial resistance rates to penicillin andgested in suspected cases of penicillin-resistant S pneu- macrolide/streptogramin/licosamide families havemoniae . In patients with a questionable history of increased rapidly over the past decade to the extent thatbeta-lactam allergy, skin testing may be appropriate to penicillin and macrolide resistance is now common.confirm or deny sensitivity, as restricting use of penicil- Failure of therapy secondary to resistant organisms haslin and penicillin derivatives may result in disadvantages led to poor clinical outcomes in several well-documen-to the patient (ie, costs, side effects) . First-line use ted instances.of macrolides should probably be limited to patients There is increasing evidence for the associationallergic to penicillin. between antimicrobial resistance and adverse patient Individuals with no clinical response within 72 hours outcomes [91,92]. Clinicians should enquire aboutmay be presumed to be unresponsive to therapy. The recent antibiotic use and choose an alternate class of
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 14 of 38http://www.aacijournal.com/content/7/1/2antibiotic from that used in the past 3 months . For uncomplicated ABRS in otherwise healthySupporting this approach are new data that have shown adults, antibiotics show comparable efficacy.that therapy within the past 3 months is a risk factor forpneumococcal resistance. The Toronto Bacterial Net- Statement 11: When antibiotics are prescribed, dura-work evaluated data from patients in 3339 cases of inva- tion of treatment should be 5 to 10 days as recom-sive pneumococcal infection, of whom 563 had a history mended by product monographs. Ultra-short treatmentof antibiotic therapy in the preceding 3 months where durations are not currently recommended by this group.the identity of the therapy was known . In the study, Strength of evidence: Strongrecent therapy with penicillin, macrolides, trimetho- Strength of recommendation: Moderateprim-sulfa, and quinolones (but not cephalosporin) was Rationale: Some data support efficacy of shorter dura-associated with a higher frequency of resistance to that tions of therapy; however, none of these short durationssame agent. Other patient subgroups identified as at risk have been approved in Canada, and are thus not recom-for infection with resistant bacterial strains included the mended by this group.young (< 2 years of age), the elderly (> 65 years of age), Traditional approaches to antimicrobial managementand those with severe underlying disease. These findings of ABRS focus on courses of therapy of at least 10 daysemphasize the importance of taking a history of recent duration . The rationale for this length of therapyantibiotic use and choosing an agent that differs from originated from studies in tonsillopharyngitis. Potentialwhat the patient had recently received. benefits of short-course therapy include improved com-Take Home Points pliance, fewer adverse events, reduced risk of treatment There are increasing rates of antibiotic resistance: failure and bacterial resistance, and reduced cost. A • Penicillin-, macrolide-, and multi-drug resistant number of studies have investigated short-course ther- S pneumoniae in community-acquired respiratory apy with various antibiotics and have demonstrated tract infections similar benefit as comparators (Table 6). These studies • Be cognizant of local patterns of antibiotic have been performed using a variety of antibiotics, some resistance, as regional variations exist. recommended, some not presently recommended in Medical history influences treatment choice: these guidelines, and several either not or no longer • Identify patients at increased risk of bacterial marketed in Canada. Of note is that in the United resistance and complications States, a 1-day course of azithromycin reported compar- ○ Those with underlying disease (eg, diabetes, able efficacy to the comparator . Despite this result, chronic renal failure, immune deficiency) it is the opinion of the group that a recommendation ○ Those with underlying systemic disorders. for ultra-short courses of therapy be reserved until Considerations for choosing an antibiotic: further supporting trials are performed. • Suspected or confirmed etiology It is of the opinion of the group that 10 days of ther- • Medical history apy with an antibiotic is sufficient. Evolution of the dis- • Presence of complications ease and symptom response remains similar regardless • Canadian patterns of antimicrobial resistance of shorter or longer courses of antibiotics . Thus, • Risk of bacterial resistance absence of complete cure (improvement in symptoms • Tolerability without complete disappearance of symptoms) at the • Convenience end of therapy should be expected and should not cause • Cost of treatment. an immediate prescription of a second antibiotic. Antibiotic choice: Alternatives to Antibiotics: Intranasal Corticosteroids (INCS) • First-line: amoxicillin as Monotherapy ○ In beta-lactam allergy: TMP/SMX or Statement 12: Topical INCS can be useful as sole ther- macrolide apy of mild-to-moderate ARS. • Second-line: amoxicillin/clavulanic acid combina- Strength of evidence: Moderate tion, or quinolones with enhanced gram-positive Strength of recommendation: Strong activity (ie, levofloxacin, moxifloxacin) Rationale: Topical INCS offer an approach to hasten ○ For use where first-line therapy failed resolution of sinus episodes and clearance of infectious (defined as no clinical response within organisms by promoting drainage and reducing mucosal 72 hours), risk of bacterial resistance is high, swelling . They are also used to decrease the fre- or where consequences of therapy failure are quency and severity of recurrent episodes . Con- greatest (ie, because of underlying systemic cerns regarding safety of treatment with INCS have not disease). been borne out as their use has not been associated
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 15 of 38http://www.aacijournal.com/content/7/1/2Table 6 Studies Investigating Alternative Therapy Duration, Dose, or FormulationAgent Comparator Success Rate Side EffectsDurationAzithromycin  Amoxicillin/clavulanate 88.8% and 84.9%, vs Higher for amox/clav 84.9% group 500 mg/d 1500/375 mg/d 3 or 6 days 10 daysAzithromycin  Levofloxacin 92.5% vs 92.8% Comparablemicrospheres 2g 500 mg/d 1 day 10 daysAzithromycin  (meta- Amoxicillin, roxithromycin, cefaclor, erythromycin, amoxicillin/clavulanate, Comparable Comparableanalysis) clarithromycin, penicillin3 or 5 daysLevofloxacin  Levofloxacin >90% for both Comparable groups 750 mg/d 500 mg/d 5 days 10 daysGatifloxacin * Amoxicillin/clavulanate 74% and 80%, vs Comparable 72% 400 mg/d 1750/250 mg/d 5 or 10 days 10 daysGemifloxacin  Gemifloxacin 83.5% vs 84.2% Comparable 320 mg/d 320 mg/d 5 days 7 daysDosingAmoxicillin/clavulanate Amoxicillin/clavulanate 88% vs 93% Comparable 500/125 mg 875/125 mg Every 8 hours Every 12 hoursFormulationClarithromycin  ER Amoxicillin/clavulanate 98% vs 97% Comparable 1000 mg/d 1750/250 mg/d 14 days 14 days*The fluoroquinolone, gatifloxacin was removed from the market following a study demonstrating potentially life-threatening glycemic events .ER, extended release.with an increased incidence of complications as judged daily than with amoxicillin, the difference did not reachby adverse events or increased rates of infection . statistical significance. In a study assessing quality of life Two studies have identified a positive effect from the use with the SinoNasal Outcome Test (SNOT)-20 question-of an INCS as sole treatment modality on resolution of naire, 340 patients with acute uncomplicated RS were ran-ARS. A study of 981 patients with acute uncomplicated RS domized to mometasone furoate 200 mcg once daily orrandomized patients to receive mometasone furoate nasal twice daily, amoxicillin 500 mg 3 times daily, or placebospray 200 mcg once daily or twice daily for 15 days, amox- . After 15 days of treatment, the mometasone furoateicillin 500 mg 3 times daily for 10 days, or placebo . 200 mcg twice daily group had significantly improvedAt 14 days, mometasone furoate twice daily significantly scores on the SNOT-20 questionnaire compared with theimproved symptom scores compared with placebo (P < placebo group..001) and amoxicillin (P = .002). Symptom scores were sig- In another study, patients who presented with at leastnificantly improved beginning on day 2 with mometasone 2 of the Berg criteria were recruited from primary carefuroate twice daily compared with amoxicillin and placebo. practices and randomized to 1 of 4 treatment arms:Global response to treatment at day 15 was also signifi- antibiotic plus budesonide, antibiotic plus placebo bude-cantly improved with mometasone furoate twice daily sonide, placebo antibiotic plus budesonide, or placebocompared with amoxicillin and placebo. Although treat- antibiotic plus placebo budesonide . Interventionsment failure was lower with mometasone furoate twice were amoxicillin 500 mg thrice daily for 7 days and
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 16 of 38http://www.aacijournal.com/content/7/1/2200 mg of budesonide per nostril once daily for 10 days. Take Home PointsResults showed no significant difference between treat- Factors suggesting greater risk of penicillin- andment arms (OR = 0.99, 95% CI, 0.57 to 1.73 for antibio- macrolide-resistant streptococci:tic vs placebo; OR = 0.93, 95% CI, 0.54 to 1.62 for • Antibiotic use within the past 3 monthsbudesonide vs placebo). Authors concluded there was ○ Choose an alternate class of antibiotic fromno place for these agents in the treatment of ARS in pri- that used in the past 3 monthsmary care. However, because the median days of symp- • Chronic symptoms greater than 4 weekstom duration at presentation was shorter (7 days, with a • Parents of children in daycare.range of 4 to 14 days) than currently recommended, the When antibiotics are prescribed, treatment durationpatient population may have included a greater propor- should be 5 to 10 days as recommended by producttion than usual of viral rather than bacterial sinusitis monographs., thus limiting the ability to detect the benefit of • Improvement in symptoms without completetreatments on bacterial episodes. disappearance of symptoms at the end of therapy Although there is limited evidence for and against the should be expected and should not cause anuse of INCS as monotherapy in the treatment of ABRS, immediate prescription of a second antibiotic.it remains an interesting treatment approach. INCS cur- Topical INCS can be useful as sole therapy of mild-rently offers a novel option that may be explored based to-moderate ARS.on limited evidence suggesting benefit. In the context of Treatment of first-line therapy failure:conflicting results between different trials, the use of • If symptoms do not at least partially attenuateINCS with established dosing requirements indicated for by 72 hours after INCS monotherapy:ABRS may be preferable. Additional clinical trials and ○ Administer antibiotic therapyfurther experience in coming years will better discern its • If symptoms do not at least partially attenuaterole in the management of ABRS. by 72 hours after antibiotic administration:Management of Failures of First-Line Therapy ○ Bacterial resistance should be considered,Statement 13: Treatment failure should be considered andwhen patients fail to respond to initial therapy within ○ Antibiotic class should be changed72 hours of administration. If failure occurs following ○ Switch to a second-line antibiotic, such asuse of INCS as monotherapy, antibacterial therapy ▪ Moxifloxacinshould be administered. If failure occurs following anti- ▪ Amoxicillin/clavulanic acid combinationbiotic administration, it may be due to lack of sensitivity ○ In the case of a second-line failure, switchto, or bacterial resistance to, the antibiotic, and the anti- to another antibiotic class.biotic class should be changed. Adjunct Therapy Strength of evidence: Option Statement 14: Adjunct therapy should be prescribed in Strength of recommendation: Strong individuals with ABRS. Rationale: In patients managed with a topical corti- Strength of evidence: Optioncosteroid as sole therapy, persistent bacterial infection Strength of recommendation: Strongmay be presumed and an antibiotic should be instituted, Statement 15. Topical intranasal corticosteroidsaccording to guidelines for selection of an antibiotic. (INCS) may help improve resolution rates and improveBacteriologic response to antibiotics should be expected symptoms when prescribed with an antibiotic.within 48 hours, thus symptoms should at least partially Strength of evidence: Moderateattenuate by 72 hours. If symptoms persist unchanged Strength of recommendation: Strongat this time, failure of response to antibiotic therapy Statement 16. Analgesics (acetaminophen or non-must be considered along with possible resistance . steriodal anti-inflammatory agents) may provide symp-Antibiotic therapy must be adjusted by switching to a tom relief.second-line antibiotic such as moxifloxacin or amoxicil- Strength of evidence: Moderatelin/clavulanic acid combination or, in the case of a sec- Strength of recommendation: Strongond-line failure, to another antibiotic class. Statement 17. Oral decongestants may provide symp- Studies using in-dwelling catheters for serial sampling tom relief.of sinus fluid have reported the time course of antibio- Strength of evidence: Optiontics to eradicate pathogens as ranging from 24 to 72 Strength of recommendation: Moderatehours [111-113]. In the absence of at least a partial clin- Statement 18. Topical decongestants may provideical response by 72 hours, bacterial resistance should be symptom relief.suspected as one of the causes of failure and appropriate Strength of evidence: Optionmeasures should be instituted. Strength of recommendation: Moderate
Desrosiers et al. Allergy, Asthma & Clinical Immunology 2011, 7:2 Page 17 of 38http://www.aacijournal.com/content/7/1/2 Statement 19. Saline irrigation may provide symptom There are no clinical studies supporting the use ofrelief. antihistamines in ABRS . Although 1 randomized Strength of evidence: Option controlled trial of human immunodeficiency virus- Strength of recommendation: Strong infected patients with acute or chronic sinusitis reported Rationale: Analgesics, oral and topical decongestants, benefit with the mucolytic agent guaifenesin , notopical INCS, and saline sprays or rinses can all help benefit was reported in a randomized controlled trial inrelieve symptoms of both viral and bacterial infections healthy subjects .of the upper respiratory passages and can all be sug- There is limited evidence suggesting benefit of salinegested for symptomatic relief. irrigation in patients with acute sinusitis. Many studiesAncillary and Alternative Therapies Recent reviews support the role of buffered hypertonic and bufferedsuggest that the evidence for use of ancillary therapies is normal nasal saline to promote mucociliary clearance.relatively weak, as few prospective randomized clinical In a study of patients with ABRS, thrice-daily irrigationtrials have been performed to assess their effectiveness. with 3% nasal saline improved mucociliary clearanceThis does not necessarily mean that the therapies are of beginning in week 1 . Moreover, subjects usingno benefit, as these have long been a part of clinical once daily hypertonic saline nasal irrigation reportedpractice and may offer benefits. However, the lack of significantly improved symptoms, quality of life, andgood quality trials supporting their use requires the decreased medication use compared with control sub-incorporation of weaker levels of evidence, thus recom- jects . However, the impact of saline sprays onmendations are derived from extension from first princi- nasal airway patency is less clear, with studies variouslyples and expert opinion. reporting no impact of saline sprays  and improved Based on its effects on inflammation, topical INCS in patency with buffered physiological saline spray .conjunction with antibiotic therapy have been assessed Their impact on symptom improvement is also uncer-for their effectiveness in improving resolution of signs tain, with a study of hypertonic saline spray reportingand symptoms of rhinosinusitis. In the Cochrane review no improvement in nasal symptoms or illness durationon this topic, 3 randomized, placebo-controlled studies . Saline therapy, either as a spray or high-volumeof the efficacy of 15- to 21-day courses of mometasone irrigation, has seen widespread use as adjunct treatmentfuroate, fluticasone propionate, or budesonide for nasal despite a limited evidence base. Although the utility ofendoscopy-confirmed ARS found limited but positive saline sprays remains unclear, the use of saline irrigationevidence for INCS as an adjuvant to antibiotics . as ancillary therapy is based on evidence of modestThe symptoms of cough and nasal discharge were signif- symptomatic benefit and good tolerability.icantly improved (P < .05) through the second week of Complementary and Alternative Medicine Recenttreatment for patients receiving budesonide (50 mcg) reviews have found limited evidence for alternative andplus amoxicillin-clavulanate potassium compared with complementary medicine for ABRS [71,123]. Some ofthose receiving placebo plus the antibiotic . In these therapies include home-based foods such as soups,patients receiving mometasone furoate (200 mcg or 400 fruit juices, teas, nutritional supplements, and herbalmcg twice daily) plus amoxicillin/clavulanate potassium, remedies. Alternative practices that have failed to showtotal symptom score days 1 to 15 averaged and over the efficacy under scientific trial conditions include acu-21-day study period were significantly improved (P ≤ puncture, chiropracty, naturopathy, aromatherapy, mas-.017) compared with patients receiving placebo plus sage, and therapeutic touch. Vitamin C preparations andantibiotic . In a third study, a 21-day course of flu- zinc lozenges are also felt to be controversial [71,123].ticasone propionate (200 mcg) plus cefuroxime Studies of zinc lozenges for the common cold have pro-improved the clinical success rate compared with pla- duced mixed results. A recent meta-analysis of Echina-cebo plus antibiotic (93.5% vs 73.9%, P = .009) as well cea preparations has shown some positive effects inas the speed of recovery (6 days vs 9.5 days, P = .01) reducing duration of respiratory tract symptoms .. No significant steroid-related adverse effects or A recent systematic review comparing placebo withrecurrence rates were reported. Topical INCS thus the herbal medications Sinupret or Bromelain as adjunctappear to be safe and to afford an additional benefit therapy reported limited evidence of improved symp-when antibiotics are used. toms. Further, single randomized controlled trials on Oral decongestants have been shown to improve nasal Esbetritox, Mytrol, Cineole, and Bi Yuan Shu showedcongestion and can be used until symptoms resolve, some initial positive evidence . A prospective ran-provided there are no contraindications to their use. domized controlled trial compared the homeopathicTopical decongestant use is felt to be controversial and medication Sinfrontal with placebo among 56 casesshould not be used for longer than 72 hours due to the and controls with radiograph-confirmed acute maxillarypotential for rebound congestion . sinusitis . Participants were allowed saline