Pediatric Sinusitis

From the Katz-Wilfert Update in Pediatric Infectious Diseases, presented by Duke University School of Medicine, Durham, NC

Ellen R. Wald, MD, Professor and Chair, Department of Pediatrics, University of Wisconsin,
School of Medicine and Public Health, Madison

Educational Objectives

The goal of this program is to improve the management of acute bacterial sinusitis in children. After hearing and as­similating this program, the clinician will be better able to:

1.   Detail the pathophysiology of acute bacterial sinusitis in children.

2.   Distinguish between uncomplicated viral upper respiratory infections and secondary bacterial sinusitis in chil­dren.

3.   Discuss the role of plain radiographs in the diagnosis of acute bacterial sinusitis in children.

4.   Summarize the results of key clinical studies of the efficacy of antibiotics for treating children with acute bac­terial sinusitis, and discuss the factors that may have contributed to conflicting data.

5.   Describe the advantages and disadvantages associated with antibiotic treatment in these patients.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Wald and the plan­ning committee reported nothing to disclose.

Acknowledgments

Dr. Wald was recorded at Katz-Wilfert Update in Pediatric Infectious Diseases, presented by Duke University School of Medicine, and held April 25, 2009, in Durham, NC. The Audio-Digest Foundation thanks Dr. Wald and the Duke University School of Medicine for their cooperation in the production of this program.

Introduction: important to distinguish between simple viral upper respiratory infection (URI) and secondary bacte­rial infection of paranasal sinuses; continuous membranes line nose and sinus cavities, so even uncomplicated URIs may have element of sinusitis; antimicrobial therapy not required for children or adults with uncomplicated URIs

Anatomy of paranasal sinuses: maxillary  —  outflow tract positioned high on medial wall; intact mucociliary appa­ratus required to move mucus and debris from sinus into nose; maxillary sinusitis (as complication of URI) occurs with moderate frequency; ethmoid  —  3 to 15 air cells (on left and right sides), separated by thin bony partitions; each air cell drains by tiny ostium into middle meatus; ostium easily obstructed during URI; frontal  —develops from anterior ethmoid cell; achieves supraorbital position by »6 yr of age; uncommon site of infection, but poten­tial conduit of infection to central nervous system (CNS) or orbit; sphenoid  —  located behind posterior ethmoids and anterior to pituitary fossa; uncommon source of infection but potential conduit of infection to CNS; factors that affect function  —  patency of ostia; function of ciliary apparatus; quality and quantity of secretions; sinus ostia  —  drainage routes for paranasal sinuses; because of small diameter (1.0-2.5 mm), easily occluded by mucosal inflam­mation

Pathogenesis of sinusitis: inflammatory process (caused by, eg, viral URI, allergic response) results in mucositis of upper respiratory tract (nose and paranasal sinuses); spontaneous resolution typical; if mechanical or functional ob­struction of outflow tract occurs, pressure within paranasal sinuses initially increases, then decreases (caused by rapid absorption of oxygen by sinus mucosa); pressure gradient favors aspiration of bacteria-laden mucus from nose into maxillary sinus; obstruction sequesters bacteria and allows proliferation and development of secondary infection

Uncomplicated viral URIs: symptoms typically last 5 to 10 days, peaking between days 3 and 6; fever uncommon (when present, accompanied by other constitutional symptoms, and typically resolves within first 24-48 hr); symptoms  —  nasal discharge, congestion, and/or cough or scratchy throat; initially, nasal discharge clear and wa­tery, then becomes mucoid or purulent (thick, colored, opaque); as URI resolves, discharge may become clear and thin again before drying

Acute bacterial sinusitis: 3 clinical presentations commonly associated with secondary bacterial infection; persis­tent symptoms  —  last >10 days but <30 days without improvement; symptoms must include nasal discharge (any quality) and daytime cough (may worsen at night) and may include fever, headache, or facial pain; severe symptoms  —  fever ³39°C and purulent nasal discharge lasting 3 days; persistent fever helps distinguish from mod­erate to severe uncomplicated URI; severe headache (often reported behind or above eye) may occur; worsening symptoms  —  typical URI symptoms for »6 days, followed by sudden onset of worsening symptoms, which may in­clude fever, increased nasal discharge and/or cough, and severe headache

Imaging: radiographic views  —  anteroposterior (ethmoid sinuses); lateral (frontal and sphenoid sinuses); occipito­mental (maxillary sinus); radiographic findings suggestive of acute sinusitis  —  diffuse opacification (most com­mon finding in children with acute bacterial sinusitis); mucosal swelling ³4 mm; presence of air-fluid level (may not occur in children)

Study (Wald et al, 1981): participants  —  children, 2 to 16 yr of age, with persistent or severe symptoms; diagnostic studies  —  anteroposterior, lateral, and occipitomental radiographs; maxillary sinus aspiration; results  —  aspirate recovered bacteria at density ³10⁴ CFU/mL from 75% of children with abnormal radiographic findings

Study (Wald et al, 1986): history of persistent upper respiratory symptoms predicted abnormal findings on radio­graphs in 88% of children £6 yr of age and in 70% of children >6 yr of age; frequency of bacterial sinusitis peaks by 6 yr of age

Guidelines: diagnosis of acute bacterial sinusitis does not require radiographic imaging in children £6 yr of age with persistent upper respiratory symptoms; diagnosis based on clinical findings only; no consensus about need for imaging for children >6 yr of age with persistent symptoms and for all children with severe or worsening symptoms; note  —   abnormalities on imaging indicate inflammation but do not identify source (eg, viral or bacte­rial infection, allergy, or chemical irritation)

Pathogens: identified using aspiration of maxillary sinus (1981 study); Streptococcus pneumoniae, 30% to 40%; Haemophilus influenzae, 20%; Moraxella catarrhalis, 20%; Streptococcus pyogenes (group A streptococci), 4%; no bacteria recovered from 25% of samples; widespread use of pneumococcal vaccine has likely resulted in changes in prevalence; recent data from tympanocentesis studies of children with acute otitis media show decreased rate of infection with S pneumoniae and increased rate of infection with H influenzae; resistance  —  35% of isolates of H influenzae and 100% of isolates of M catarrhalis resistant to b-lactam antibiotics; 25% to 50% of isolates of S pneumoniae resistant to penicillin (half are highly resistant)

Rationale for antibiotic therapy: to justify use, must achieve faster clinical cure or prevent complications or trans­mission; for acute bacterial sinusitis, speed of clinical cure most important

Conflicting data: Wald et al, 1986  —  children, 2 to 16 yr of age, with persistent upper respiratory symptoms and ab­normal radiographic findings, randomized to amoxicillin, amoxicillin-clavulanate, or placebo for 10 days; 45% of children in active treatment groups and 11% of those in placebo group cured on day 3; on day 10, 79% of children receiving antibiotics cured or improved, compared to »60% of those receiving placebo; Garbutt et al, 2001  —  children 1 to 18 yr of age (mean, 8 yr of age), with persistent upper respiratory symptoms; those with fever >39°C or facial pain excluded; participants stratified by age and clinical severity, then randomized to receive 40 or 45 mg/kg per day amoxicillin, amoxicillin-clavulanate, or placebo; no differences observed in overall cure rates or time to clinical cure; factors that may contribute to discordant results  —  different age ranges; Garbutt study in­cluded many older children (may have different presentation and response to antibiotic therapy, compared to younger children); earlier data show 30% of children >6 yr of age who have symptoms do not have sinusitis, but Garbutt study did not use radiographs to identify older children who did not have acute sinusitis; Garbutt study ex­cluded sickest children, potentially leading to bias against active treatment; relatively low dose of antibiotics used may have prevented effective treatment in children with infections caused by resistant S pneumoniae; conclusion  —  moderate differences between groups possibly obscured by differences in cohorts and/or by insufficient dose of an­tibiotic

New data: study by Wald et al (publication expected in summer, 2009) sought to address issues that may have led to conflicting results; children, 1 to 10 yr of age, with clinical presentation compatible with diagnosis of acute bac­terial sinusitis, stratified by age and clinical severity; randomized to receive 90 mg/kg per day (2 divided doses), amoxicillin-clavulanate, or placebo; clinical severity score  —  for initial stratification; based on presence of nasal or postnasal discharge, nasal congestion, cough, malodorous breath, facial tenderness, erythematous nasal mu­cosa, fever, and headache or irritability; exclusion criteria  —  receipt of antibiotics within 15 days of new symp­toms; symptoms lasting >30 days; concurrent bacterial infection (eg, otitis media); allergy to penicillin; severity or complication requiring intravenous antibiotics; immunodeficiency or anatomic problems that might alter re­sponse to antibiotics; symptom score  —days 0, 1, 2, 3, 5, 7, 10, 20, and 30; 2 points for each symptom (fever; na­sal discharge; nasal congestion; cough; headache or irritability; facial pain; facial swelling; altered activity level; sleep disturbance; impaired appetite) present at baseline; on subsequent evaluation, 1 point added to score for each symptom that worsened, and 1 point subtracted for each symptom that improved; end points  —  cure defined as symptom score <2; clinical improvement defined as symptom score decreased by ³50%; treatment failure de­fined as symptom score worsened by ³4 points at any time, failure of symptom score to improve by ³2 points by 48 hr, failure of symptom score to improve by ³50% by 72 hr, or symptom score of >5 at day 14; when criteria for treatment failure met, child switched to cefpodoxime (without unblinding); adverse effects also recorded; out­come measures  —  proportion of children cured on day 14; proportion who failed therapy; proportion who devel­oped adverse reactions

Patient selection: 2135 children screened for eligibility; 139 patients eligible for study; 58 children enrolled, but 2 withdrew before treatment began; remaining children stratified by age (<6 yr vs ³6 yr) and symptom severity (<8 points vs ³8 points); 22 children received antibiotics and 28 received placebo; analysis showed groups to be com­parable in age, sex, ethnicity, type of presentation, and severity of symptoms

Results: antibiotic group  —  50% cured, 14% improved, 64% cured or improved, 14% failed therapy, and 6 children withdrew; placebo group  —  14% cured; 18% improved; 32% cured or improved; 68% failed therapy; none with­drew; summary of clinical outcomes  —significantly more children in antibiotic group considered cured or im­proved, and significantly fewer children in antibiotic group failed therapy, compared to placebo group;  6 children in antibiotic group lost to follow-up; of these, 2 had excellent early response; even if these 2 children were considered to have failed therapy, difference between active treatment and placebo remains significant; compliance high in both groups; failure rate  —  83% of children on placebo met criteria for therapeutic failure; most of these occurred within 72 hr; failure occurred in 14% of children on active therapy (3 had sluggish re­sponse; 1 responded well initially, then had new symptoms on day 11); symptom recurrences occurred in 4 chil­dren on active therapy and 3 children on placebo (all recurrences deemed viral URIs and not treated); adverse events  —experienced by 44% of children on active therapy and 14% of children on placebo; mild diarrhea most common adverse event (generally did not interfere with continuation of therapy)

Conclusions: stringent eligibility criteria likely excluded children with uncomplicated viral URIs; other factors in­clude narrower age range, inclusion of patients with more severe disease, and strict definitions for clinical cure, improvement, and failure

Recommendations: for children with uncomplicated mild to moderate acute bacterial sinusitis without risk factors (age <2 yr; recent use of antibiotics; attendance at daycare), give amoxicillin or amoxicillin-clavulanate, 45 to 90 mg/kg per day (in 2 divided doses); dose based, in part, on likelihood of exposure to resistant organisms (eg, early or late in season); penicillin allergy  —  cefdinir, cefuroxime, or cefpodoxime for children with mild allergy; clar­ithromycin or azithromycin for children with type-1 hypersensitivity (but these have low activity against Haemoph­ilus); salvage treatment  —  reconsider diagnosis or choice of antibiotic for patients who fail to improve within 72 hr; consider increasing dose of amoxicillin-clavulanate to 80 to 90 mg/kg per day (2 divided doses) for patients who do not improve within 72 hr, those who have recently received antibiotics, and those with moderate to severe disease; higher dose achieves concentration sufficient to eradicate intermediately-susceptible and most highly-resistant S pneumoniae; treatment duration  —  optimal duration unknown; speaker recommends treating for 7 days after symp­toms resolve (mandates 10-day course, but precludes use of antibiotics in child who has long been well and there­fore unlikely to be compliant)

Summary: acute bacterial sinusitis common complication of URI in children; clinical diagnosis sufficient in child with persistent symptoms (at least in younger patients); treatment with amoxicillin-clavulanate associated with sig­nificantly higher cure rate and lower failure rate (based on resolution of symptoms), compared to placebo

Questions and answers: role of corticosteroids  —  some studies show modest benefit of intranasal corticosteroids; speaker avoids use in order to minimize medications (speaker also avoids antihistamines and decongestants for same reason); other adjuvant therapies  —  patients respond quickly (generally £72 hr) to antibiotic therapy; adding medications to facilitate nasal drainage unlikely to result in additional clinically significant benefit; intranasal de­congestants (eg, oxymetazoline) or saline irrigation may be useful, but insufficient data in setting of acute sinusitis

Suggested Reading

Brook I: Current issues in the management of acute bacterial sinusitis in children. Int J Pediatr Otorhinolaryngol 71:1653, 2007; Cox ED, Saluja S: Criteria-based diagnosis and antibiotic overuse for upper respiratory infections. Ambul Pediatr 8:250, 2008; Edmonson NE, Parikh SR: Complications of acute bacterial sinusitis in children. Pediatr Ann 37:680, 2008; Esposito S et al: From clinical practice to guidelines: how to recognize rhinosinusitis in children. Pediatr Allergy Immunol 18(Suppl):53, 2007; Falgas ME et al: Comparison of antibiotics with placebo for treatment of acute sinusitis: a meta-anal­ysis of randomised controlled trials. Lancet Infect Dis 8:543, 2008; Garbutt JM et al: A randomized, placebo-controlled trial of antimicrobial treatment for children with clinically diagnosed acute sinusitis. Pediatrics 107:619, 2001; Konno M et al: Study of nasopharyngeal bacterial flora. Variations in nasopharyngeal bacterial flora in schoolchildren and adults when administered antimicrobial agents. J Infect Chemother 13:235, 2007; Marchisio P et al: Paranasal sinuses and mid­dle ear infections: what do they have in common? Pediatr Allergy Immunol 18 (Suppl):31, 2007; Payne SC, Benninger MS: Staphylococcus aureus is a major pathogen in acute bacterial rhinosinusitis: a meta-analysis. Clin Infect Dis 45:e121, 2007; Wald ER et al: Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal sinus infections in children: a double-blind, placebo-controlled trial. Pediatrics, 77:795, 1986; Wald ER et al: Acute max­illary sinusitis in children. N Engl J Med 304:749, 1981; Yamanaka N et al: Clinical bacteriology and immunology in acute otitis media in children. J Infect Chemother 14:180, 2008.