SINUSITIS






















ADULTS (2012 IDSA)
Standard
High-dose therapy
  • High-dose therapy is recommended if one of the following is present:
    • Geographic regions with high endemic rates (≥10%) of invasive penicillin-resistant S. pneumoniae
    • Those with severe infection (e.g. fever ≥ 39°C [102°F], and threat of suppurative complications
    • Age > 65 years
    • recent hospitalization
    • Antibiotic use within the past month
    • Immunocompromised [3]
ADULTS (PENICILLIN ALLERGIC)

  • ✝ Risk of penicillin cross-sensitivity is very low with these cephalosporins [4]
  • AAP - American Academy of Pediatrics
CHILDREN (2014 AAP)
Standard
  • Amoxicillin 45 mg/kg/day in 2 divided doses for a minimum of 10 days
High-dose therapy - recommended in communities with a high prevalence of nonsusceptible S. pneumoniae (>10%, including intermediate- and high-level resistance)
  • Amoxicillin 80 - 90 mg/kg/day in 2 divided doses (maximum of 2 g per dose) for a minimum of 10 days
Moderate-to-severe illness - defined as the presence of one of the following: < 2 years old; attending child care; recently been treated with an antimicrobial
  • Amoxicillin-clavulanate (Augmentin®) 80 – 90 mg/kg/day of the amoxicillin component with 6.4 mg/kg per day of clavulanate in 2 divided doses with a maximum of 2 g per dose for a minimum of 10 days [4]
CHILDREN (PENICILLIN ALLERGIC)
  • Cefdinir✝ 7 mg/kg every 12 hours or 14 mg/kg once daily for a minimum of 10 days
  • Cefpodoxime (Vantin®)✝ 5 mg/kg every 12 hours (Max 200 mg/dose) for a minimum of 10 days
  • Cefuroxime (Ceftin®)✝ 30 mg/kg/day divided twice a day (Max 1,000 mg/day) for a minimum of 10 days [4,5]
Young children (< 2 years old)








Amoxicillin vs Placebo for Acute Sinusitis, JAMA (2012) [PubMed abstract]
  • A study published in the JAMA enrolled 166 patients with acute sinusitis
Main inclusion criteria
  • All of the following must be present: history of maxillary pain or tenderness in the face or teeth, purulent nasal secretions, rhinosinusitis symptoms for ≥ 7 days that were not improving or rhinosinusitis symptoms for < 7 days that had worsened after initial improvement
Main exclusion criteria
  • Antibiotic treatment within 4 weeks
  • Patients who rated symptoms as very mild or mild
Baseline characteristics
  • Median age 32 years
  • History of sinus disease - 73%
  • Using daily intranasal steroid - 6%
  • Average number of days with symptoms - 11
  • Baseline SNOT-16 score - 1.71
Randomized treatment groups
  • Group 1 (85 patients) - Amoxicillin 500 mg 3 times a day for 10 days
  • Group 2 (81 patients) - Placebo for 10 days
  • All patients also received guaifenesin, dextromethorphan, pseudoephedrine, and saline nasal spray
Primary outcome: Change in disease-specific quality of life after 3 to 4 days of treatment assessed with the Sinonasal Outcome Test-16 (SNOT-16) (average of 16 sinus-related symptoms rated from 0 - 3 where 0=no problem and 3=severe problem)
Results

Duration: 10 days
Outcome Amoxicillin Placebo Comparisons
Primary outcome (Day 3) 0.59 0.54 p=0.69
Primary outcome (Day 7) 1.06 0.86 p=0.02
Primary outcome (Day 10) 1.23 1.20 p=0.85
  • There was no significant difference in adverse events

Findings: Among patients with acute rhinosinusitis, a 10-day course of amoxicillin compared with placebo did not reduce symptoms at day 3 of treatment
Amoxicillin ± Nasal Steroid vs Placebo for Acute Sinusitis, JAMA (2007) [PubMed abstract]
  • A study published in the JAMA enrolled 240 patients with acute sinusitis
Main inclusion criteria
  • Two or more of the following: purulent nasal discharge predominantly on one side, sinus pain predominantly on one side, purulent nasal discharge on both sides and pus on inspection inside the nose
Main exclusion criteria
  • History of recurrent sinusitis (≥ 2 attacks in previous 12 months)
  • History of allergies
Baseline characteristics
  • Average age 42 years
  • History of previous sinusitis - 80%
  • Median length of symptoms - 7 days
Randomized treatment groups
  • Group 1 (53 patients) - Amoxicillin 500 mg 3 times a day for 7 days and nasal steroid for 10 days
  • Group 2 (60 patients) - Amoxicillin 500 mg 3 times a day for 7 days and placebo spray
  • Group 3 (64 patients) - Placebo and nasal steroid for 10 days
  • Group 4 (63 patients) - Double placebo
Primary outcome: Proportion clinically cured at day 10 using patient symptom diaries and the duration and severity of symptoms. Patient diaries included 11 symptom variables assessed on 7-point Likert scales.
Results

Duration: 10 days
  • The proportion of patients with symptoms lasting ≥ 10 days was 29% for amoxicillin vs 33.6% for no amoxicillin (odds ratio 0.99, 95%CI [0.57-1.73])
  • The proportion of patients with symptoms lasting ≥ 10 days was 31.4% for nasal steroid vs 31.4% for no steroid (odds ratio 0.93, 95%CI [0.54-1.62])
  • There were no significant interactions

Findings: Neither an antibiotic nor a topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.
Amoxicillin vs Placebo for Maxillary Sinusitis Confirmed with X-ray, Lancet (1997) [PubMed abstract]
  • A study published in the Lancet enrolled 214 patients with maxillary sinusitis confirmed on X-ray
Main inclusion criteria
  • Sinusitis symptoms (acute onset of a common cold with sickness, headache, nose obstruction, discharge, and tapping pain of the maxillary sinus) and a positive sinus X-ray that showed mucosal swelling of more than 5 mm, complete shadowing, or a fluid level
Main exclusion criteria
  • Current episode > 3 months
  • Antibiotics during previous month
Baseline characteristics
  • Average age 34 years
  • Average length of symptoms - 2.2 weeks
Randomized treatment groups
  • Group 1 (108 patients) - Amoxicillin 750 mg three times a day for 7 days
  • Group 2 (106 patients) - Placebo for 7 days
Primary outcome: Cure rate (defined as being symptom-free) after 2 weeks and symptom scores after 1 and 2 weeks
Results

Duration: 2 weeks
Outcome Amoxicillin Placebo Comparisons
Cure rate (2 weeks) 65% 52% p=0.06
Greatly decreased symptoms (2 weeks) 83% 77% p=0.20
Adverse events (mostly GI symptoms and rash) 28% 9% p<0.001
Relapse within 1 year 21% 17% p=0.42
  • Radiographs had no prognostic value, nor were they an effect modifier

Findings: Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice. For these patients, an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment. Whether antibiotics are necessary in more severe cases warrants further study.
Augmentin vs Placebo for Acute Sinusitis, Archives of IM (2003) [PubMed abstract]
  • A study published in the Archives of Internal Medicine enrolled 252 patients with acute sinusitis
Main inclusion criteria
  • All of the following: history of repeated purulent nasal discharge, unilateral or bilateral maxillary or frontal sinus pain for ≥ 48 hours, presence of pus under rhinoscopy
Main exclusion criteria
  • Symptoms > 1 month
  • Antibiotics during previous 4 weeks
  • Upper respiratory infection
Baseline characteristics
  • Average age 37 years
  • Median length of symptoms - 4.5 days
Randomized treatment groups
  • Group 1 (125 patients) - Augmentin 875/125 twice a day for 6 days
  • Group 2 (127 patients) - Placebo for 6 days
Primary outcome: Time to cure. Cure was defined as no activity restrictions due to symptoms at work or home. Patients were evaluated on days 7 and 14.
Results

Duration: 14 days
Outcome Augmentin Placebo Comparisons
Primary outcome (Day 7) 29.8% 30.7% p>0.05
Primary outcome (Day 14) 76.6% 74% p>0.05
  • Patients in the Augmentin group had significantly more diarrhea than patients in the placebo group (OR 3.89, 95%CI [2.09 - 7.25])
  • In a subgroup analysis that only included patients with pus on rhinoscopy, there was no significant difference between groups on days 7 and 14
  • 15% of the patients in the placebo group crossed over to antibiotics
  • 8.8% of the patients in the Augmentin group received open treatment

Findings: Adult patients in general practice with clinically diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with augmentin and are more likely to experience adverse effects


Prednisolone vs Placebo for Acute Sinusitis, CMAJ (2012) [PubMed abstract]
  • A study published in the CMAJ enrolled 185 patients with acute sinusitis
Main inclusion criteria
  • Symptoms for at least 5 days
  • At least 2 of the following: nasal discharge (posterior or anterior) or nasal congestion, facial pressure or pain, pain when chewing
Main exclusion criteria
  • Symptoms > 12 weeks
  • Recurrent sinusitis (≥ 2 episodes in previous year
  • Use of intranasal or oral corticosteroids in the previous 4 weeks
Baseline characteristics
  • Average age 43 years
  • Median length of symptoms - 13 days
  • History of allergic rhinitis - 19%
Randomized treatment groups
  • Group 1 (93 patients) - Prednisolone 30 mg/day for 7 days
  • Group 2 (92 patients) - Placebo for 7 days
  • Patients were allowed to use acetaminophen and xylometazoline 0.1% nasal spray
  • Family physicians were allowed to prescribe antibiotics or intranasal corticosteroid treatment but were advised to refrain from doing so as much as possible during the first week of study
Primary outcome: Resolution of facial pain or pressure on day 7 as recorded in a patient diary
Results

Duration: 7 days
Outcome Prednisolone Placebo Comparisons
Primary outcome 62.5% 55.8% Diff 6.7%, 95%CI [-7.9 to 21.2%]
  • There was no significant difference in adverse events between groups
  • Duration of symptoms did not differ significantly between groups
  • About 19% in each group received antibiotics
  • About 18% in each group received nasal steroids

Findings: Systemic corticosteroid monotherapy had no clinically relevant beneficial effects among patients with clinically diagnosed acute rhinosinusitis.