Randomized, Placebo-Controlled Trials of Antimicrobial Treatment of Acute Sinusitis in Children

VariableWald et al7Garbutt et al8Kristo et al9Wald et al6
Inclusion criteriaNasal discharge of any quality“Persistent upper respiratory symptoms”Acute respiratory symptoms suggestive of sinusitis that were “not improving”Persistent: nasal discharge of any quality and/or daytime cough persisting for >10 d without improvement
and/orNasal discharge and obstruction, sneezing, coughWorsening: worsening on or after day 6 with fever or increase in symptoms
CoughSevere: temperature ≥102°F with purulent nasal discharge for at least 3 consecutive days
Symptoms present for 10–30 dSymptoms present for 10–28 dSymptoms present <3 wk, no lower boundSymptoms present <30 d, lower bound per definitions above
Age: 2–16 yAge: 1–18 yAge: 4–10 yAge: 1–10 y
Abnormal radiograph resultsNAAbnormal USNA
Exclusion criteriaPenicillin allergyAllergyAllergyAllergy
Previous Rx within 3 dPrevious Rx within 2 wkPrevious Rx within 4 wkPrevious Rx within 15 d
Underlying conditions (asthma, allergic rhinitis, CF, sickle cell anemia, congenital heart disease, immunodeficiency)CF onlyPrevious sinus surgeryUnderlying conditions (immunodeficiency or anatomic abnormality of upper respiratory tract)
Otitis media, pneumonia, GAS pharyngitis (throat/NP culture performed at study enrollment)“Fulminant sinusitis”Current antimicrobial RxConcurrent bacterial infection
Severe headache or periorbital swelling(fever >39°C, facial swelling, facial pain)“Complications of sinus disease”Complication of sinusitis requiring hospitalization, IV antibiotics, or subspecialty evaluation.
Normal radiograph of paranasal sinusesNANANA
Source of patientsPrimary or secondary care patients at an academic children’s hospital3 suburban primary care practices1 private health care center2 private practices, 1 hospital-based clinic
RandomizationBlock randomizationAssigned to persistent or nonpersistent group then
Stratified by age: (<6 and ≥6 y)Stratified by age: (<7 and ≥7 y)Stratified by age: (<6 and ≥6 y)
And clinical severityAnd clinical severityAnd clinical severity
Then randomizedThen randomizedThen randomized
Metric for severityClinical severity score: <8 is mild and ≥8 is severeClinical severity score using S5 score8 acute symptoms, rated 0–4Same as Wald et al7
Telephone follow-up1, 2, 3, 5, and 7 d3, 7, 10, 14, 21, 28, and 60 dNA1, 2, 3, 5, 7, 10, 20, and 30 d
Clinical visitDay 10Day 14Day 14Day 14
Primary outcomeClinical outcome at 3 and 10 dChange in sinus symptoms at day 14% complete cure at 2 wkCure at day 14
Secondary outcomesNot specifiedAdverse eventsAdverse effectsAdverse events
RelapseImprovement without complicationsProportion with treatment failure
Change in functional status
Parental satisfaction with treatmentDays when analgesics, nasal decongestants or cough mixtures were given
N placebo35554128
N treatment group30 amoxicillin (40 mg/kg per day) divided 3 times/d for 10 d58 amoxicillin (40 mg/kg per day) divided 3 times/d for 14 d41 cefuroxime 125 mg 2 times/d for 10 d28 amoxicillin/clavulanate (90 mg/kg amoxicillin + 6.4 mg clavulanate) divided 2 times/d for 14 days
28 amoxicillin/clavulanate48 amoxicillin/clavulanate (45 mg/kg per day amoxicillin) divided 2 times/d for 14 d
Adjuvant therapyNone were prescribed. Not formally studiedPrescription or over-the-counter symptomatic treatments allowed. Use recordedAnalgesics, nose drops, and cough mixtures allowed. Use recorded in diaryUse “discouraged”—not formally studied
ComplianceHistory and remaining medications at follow-up visitSelf-report at day 14Residual drugs collected at day 14History and remaining medications at follow-up visit
Adverse eventsChildren who developed rash and diarrhea were excluded from analysisAssessed at day 14Assessed at day 14Assessed at day 14
Loss to follow-up15 children excluded because of adverse events (8) and noncompliance (7)None (typographic error in original manuscript)3 children (2 placebo, 1 treatment) lost to follow-up6 lost to follow-up in treatment group
Primary outcomeCure at 10 d:Improvement at 14 d:Cure at 14 d:Cure at 14 d:
Amoxicillin: 20/30 (67%); Amoxicillin/clavulanate: 18/28 (64%); Placebo: 15/35 (43%)Amoxicillin: 79% (46/58); Amoxicillin/clavulanate: 81% (39/48); Placebo: 79% (43/55)22/35 in experimental group vs 21/37 in placebo (63% vs 57%; P = .64)14/28 in experimental group vs 4/28 in placebo (50% vs 14%’ P = .01)
Total: Antibiotic: 38/58; Placebo: 15/35 (66% vs 43%; P < .05)Failure at 14 d: 4/28 in experimental group vs 19/28 in placebo (14% vs 68%; P < .001)
Failure at 10 d: Amoxicillin: 5/30; Amoxicillin/clavulanate: 7/28; Placebo: 14/35If all subjects lost to follow-up were considered failures, therapy is still effective (35% vs 68%; P = .032)
Total: Antibiotic: 12/58; Placebo: 15/35 (21% vs 43%; P < .05)
Jadad score3544
  • CF, cystic fibrosis; GAS, group A streptococcal; IV, intravenous; NA, not applicable; NP, nasopharyngeal; Rx, prescription; US, ultrasonography.