Overview of Pediatric Sinusitis

					Overview of Pediatric Sinusitis

          Ellen R. Wald M.D.
      Professor and Chair of Pediatrics
  University of Wisconsin School of Medicine
               and Public Health
Sinusitis in Children 2009
Si   iti i Child

• Anatomy and physiology
• Clinical presentations
• Need for imaging procedures
• Microbiology
• Need for antibiotic treatment
Anatomy Of The Paranasal Sinuses
       Normal Physiology of
        Paranasal Sinuses
        P       l Si




Patency of   Intact Ciliary
                              Secretions
                              S    ti
  Ostia       Apparatus
Narrow Caliber of the Sinus Ostia



  Maxillary sinus = 2 5 mm
• M ill      i      2.5

• Ethmoid sinus = 1.0 to 2.0 mm
    Common Clinical Presentations
    for Acute Bacterial Sinusitis


                       Severe

Persistent Symptoms

                       Worsening
Acute Sinusitis “Persistent Symptoms”


• 10 - 30 days (no improvement)
• Nasal discharge (any quality)
• Daytime cough (worse at night)
• Fever - variable
• Headache and facial pain - variable
       Acute Sinusitis “Severe Symptoms”

• High fever (T ≥ 39o C) and
  Purulent
• P l t nasal di h                     tl
                  l discharge concurrently
  for at least 3-4 days
• Need to distinguish from uncomplicated
  viral infections with moderate illness
• May have intense headache
    Worsening Symptoms

• Typical viral URI symptoms
• Nasal d/c or cough or both for 5-6 days
                                 56
  which is improving
• Sudden onset of worsening manifest as
  - Onset of new fever
   Increase nasal d/ or cough or b th
  -I            l d/c       h both
  - Severe headache
        Images

Question:

Are imaging studies necessary
to confirm a diagnosis of acute
bacterial sinusitis in children?
Plain Radiographs


• Anteroposterior
• Lateral
• Occipitomental (Water’s)
Radiographic Abnormalities


• Diffuse opacification
• Mucosal swelling ≥ 4 mm
• Air-fluid level
Images


Question:

         g g
Are imaging studies necessary    y
to confirm a diagnosis of acute
bacterial sinusitis in children?
  Acute Maxillary Sinusitis
               NEJM, 1981


• Purpose: correlate the clinical,
  radiographic & bacteriologic findings
  Age: 2 16 years
• A     2-16
• Presentation: “persistent” or “severe”
  Radiographs performed:
• R di        h    f     d
    - anteroposterior
    - lateral
    - occipitomental
    Acute Maxillary Sinusitis
                 NEJM, 1981


• Abnormal xrays:
   - opacification
   - mucosal swelling ≥ 4mm
     air-fluid
   - air fluid level
• Maxillary sinus aspirate performed
• Bacteria in high density ≥ 104
  cfu/ml in 75% of children
  Comparative effectiveness of two antibiotics
    in    t            l i   i f ti     i
    i acute paranasal sinus infections in
                   children
                     Pediatrics, 1986

• History of persistent symptoms predicted
  significantly abnormal radiographs
• For children ≤ 6 yrs history predicted
  abnormal radiographs in 88% children
• For children > 6 yrs history predicted
  abnormal radiographs in 70% children
• Peak age for bacterial sinusitis < 6 yrs
  Images

• For children ≤ 6 yrs, history predicts
  abnormal radiographs ~90% of time

• History plus abnormal radiographs results
       p                p
  in a positive sinus aspirate in 75%

• Radiographs can be omitted and a
  diagnosis of acute bacterial sinusitis can
  be made on clinical grounds alone for
  children ≤ 6 yrs
Images

         for
• Need f any image in children > 6 yrs
  with persistent symptoms and for all
  children with severe or worsening
  symptoms is controversial
• When abnormalities of the mucosa
  are found on images they indicate the
  presence of inflammation but do not
  tell us the cause, ie, viruses, bacteria,
  allergy or chemical mucositis.
        Microbiology of Acute
        Bacterial Sinusitis

• Streptococcus pneumoniae   30-40%
• Haemophilus influenzae        20
• Moraxella catarrhalis         20
• Streptococcus pyogenes        4
• Sterile                       25
      Microbiology of Acute
      Bacterial Sinusitis

      p         pneumoniae
• Streptococcus p            25%
• Haemophilus influenzae     25%
• Moraxella catarrhalis      20%
• Streptococcus pyogenes     4%
• Sterile                    25%
   Microbiology of A t B t i l Si
   Mi bi l                              iti
                 f Acute Bacterial Sinusitis



                   β lactamase( )
• 35% H influenzae β-lactamase(+)
• 100% M catarrhalis β-lactamase(+)
• 25-50% S pneumoniae penicillin R
  (one half
  (one-half are highly resistant)
Are antibiotics necessary for children
    with acute bacterial sinusitis?

To justify treatment of any disorder
• Achieve a rapid clinical cure
  Prevent complications
• P     t     li ti
• Prevent transmission
 Co pa a e effectiveness of amoxicillin a d
 Comparative e ec e ess o a o c             and
  amoxicillin-clavulanate in acute paranasal
  sinus infections in children: a double-blind,
              l   b       t ll d trial
            placebo-controlled t i l

                y        p             p      y
• Children 2-16 yrs with persistent respiratory
  symptoms
                 y p
• Children with symptoms & abnormal xrays y
  randomized to amoxicillin, amox-clav or
  placebo for 10 days
• 3rd day Rx: 45% v 11% cured on antibiotics
  v placebo
  10th        9%
• 10 day Rx: 79% v 60 % better
               ,
A Randomized, Placebo-Controlled Trial of
 Antimicrobial Treatment for Children with
   Clinically Diagnosed Acute Sinusitis
                ed at cs, 00
               Pediatrics, 2001


• Goal: To establish if there is clinical
  benefit t antibiotic R of children with
  b     fit to tibi ti Rx f hild          ith
  a clinical dx of acute sinusitis
  Age 1-18     (mean age 8 0 yrs)
• A 1 18 years (         8.0    )
• Respiratory symptoms 10-28 days
• Excluded: T>39oC, facial pain
• Randomized: Amoxicillin, Amox/Clav
  or Placebo
Placebo-Controlled Trial

• No differences observed among
  treatment groups
Potential explanations:
• Age range too broad
   g     g
• Need for images in older children
• Exclusion of sickest children
• Ineffective antibiotic
Lessons from Contradictory Results

• Differences between treated
  and untreated patients ~ 20-
  30%
• Differences might be obscured
  by cohort of older children w/o
   i    iti
  sinusitis
• Differences might be obscured
  by ineffective antibiotic
• Important to do additional
  studies
                           Amoxicillin-Clavulanate
         Effectiveness of Amoxicillin Clavulanate
      Potassium in the Treatment of Acute Bacterial
      Sinusitis in Children: A Double-Blind, Placebo-
                   Trial.        al, Pediatrics,
       Controlled Trial Wald et al Pediatrics 2009

     g      y                y
• Eligibility: Children 1-10 yrs
• Clinical presentation compatible with ABS
• Stratified by age (<6 ≥ 6 yrs) and clinical
                    (<6,
  severity
• Randomized to either Amoxicillin
  (90mg/kg) with K clavulanate (6.4mg/kg) or
  p
  placebo
                  Score
Clinical Severity Score*
          Symptom or Sign               Points
Abnormal nasal or postnasal
discharge
di h
 Minimal                                  1
 Severe                                   2
Nasal Congestion                          1
Cough                                     2
Malodorous breath                         1
Facial tenderness                         3
Erythematous nasal mucosa                 1
Fever**
 e e
 <38.5°C                                  1
 ≥38.5°C                                  2
Headache (retro-orbital)/irritability
 Severe                                   3
 Mild                                     1
  Exclusion Criteria

• Receipt of antibiotics within 15 days of
  new symptoms
• Symptoms > 30 days
• Concurrent bacterial infection
• Allergy to penicillin
• Severity or complication requiring IV
  antibiotics
• Immunodeficiency or anatomic problem
    Treatment of ABS in Children

•   Symptom score= 0,1,2,3,5,7,10,20,30
•                         fever,
    Symptom score –fever, nasal discharge,
    nasal congestion, cough, headache or
    irritability, facial pain, facial swelling,
    activity sleep and impaired appetite
    activity,
•   If present score = 2; if absent = 0
•   Maximum score = 20 at entry
•   +1, -1, or 0 added to original score daily
     Treatment of ABS in Children

• Cure = total symptom score < 2 (0,1)
• Improved = symptoms score decreased by at
  least 50%
• Failed if
                            ( 4)
  a. worsened at any time (+4)
  b. score not reduced at 48 hrs (-2)
  c. not improved by 72 hrs
  d. score > 5 at 14 days
• Side effects: rash, diarrhea, vomiting, belly pain
Treatment of ABS in Children

• Pts examined on day 14
• Rated as cured, improved or failed
• If patient deemed a clinical failure, study
  drug d/c and cefpodoxime started
• All pts deemed failure or developing
  adverse reaction were seen by PCP
• PI available for consultation
              Outcome Measures

• Proportion of children in each group who
  were cured on day 14
• Proportion of children who failed therapy
• Proportion of children with adverse rxns
• Number of children with recurrence
• Time to clinical improvement
Comparability of Baseline Characteristics of
Children Receiving Antimicrobial vs Placebo
              at Study Entry
                     Antibiotics    Placebo
                       (N=28)        (N=28)
    Age (months,
                     65 5 ± 26 6
                     65.5 26.6     66 5 ± 34 3
                                   66.5 34.3
    mean ± SD)

    Male              13 (46%)      17 (61%)
    African
    American           9 (32%)       6 (21%)
    Caucasian         18 (64%)      21 (75%)
    Other              1 (4%)        1 (4%)
    Persistent
                      25 (89%)      25 (89%)
    Non-persistent
                       3 (11%)       3 (11%)
    Mild
                      11 (39%)      13 (46%)
    Severe
                      17 (61%)      15 (54%)
Clinical Outcomes


Response    Antibiotic   Placebo
                                   P-value
              (N=28)      (N=28)

Cure        14(50%)      4(14%)     0.010

Improved      4(14%)      5(18%)    0 716
                                    0.716

Cure/Imp     18(64%)      9(32%)    0.032

Failed        4(14%)     19(68%)    0.001

Withdrawn     6(21%)      0(0%)     0.023
Outcomes of Subjects Lost to F/U
              Days of     Days to     Days to     Adverse
  P ti t
  Patient
                Rx       Improve       Cure       Events
     A           7           3           7           No

     B          10           2           5           No

     C           7           3           5          Yes

     D           1           2       Unknown        Yes*

     E           3           1       Unknown        Yes

     F       Unknown Unknown Unknown Unknown


       p                g
* This patient was having emesis before onset of treatment.
            Intent-to-Treat
            Intent to Treat Analysis

• If all 6 children are considered to have
  failed Rx
• P=0.032 for difference in proportion for
  children who failed for antibiotic v placebo
• If 4 children are considered to have failed
  Rx
• P=0.007
Outcome

• Rate of compliance = 85.7%
• 22/28 antibiotics
• 26/28 placebo
• Per Protocol Analysis (48
  children)
• 80% vs 31% cured or improved
  on antibiotic v placebo
                  p
    Outcome

•   19/23 (83%) children on placebo failed
•   17/19 (89.5%) failed in 72 hrs
•   2/19 (11%) failed on day 5
•   4/28 children (14%) on antibiotic failed
•   3 had sluggish response
•   1 responded promptly but new
    symptoms on day 11
Recurrent Symptoms & Adverse Events


• 4 children on antibiotic
• 3 children on placebo
• All deemed viral URIs

• Adverse events: 44% v 14%
  antibiotic v placebo (P = 0.014) =
  mild diarrhea
Explanation for Results


• Stringent entry criteria =
  fewer viral URIs
• Of 2135 screened only
      (6.5%) li ibl
  139 (6 5%) eligible
• Narrower age range
• Strict a priori definitions
               cure,
  for clinical cure
  improvement and failure
Recommendations

• For children with uncomplicated ABS (mild
  to moderate); no risk factors
  Amoxicillin 45 90 mg/kg/d i 2 d
• A     i illi 45-90     /k /d in doses or
• Amoxicillin/clavulanate at 45 - 90 mg/kg/day
  in 2 doses
• For penicillin allergy use cefdinir,
  cefuroxime, cefpodoxime
               ,    p
• For serious drug allergy use clarithromycin
  or azithromycin
 Recommendations

• Patients respond 48-72 hrs
• If fails to improve: either antibiotic
  ineffective or dx of sinusitis not correct
• If fails to improve or recently received
  antibiotics or moderate or more severe:
• Rx: high dose amoxicillin-clavulanate
  Amoxicillin 80-90 mg/kg/day
  Clavulanate 6.4 mg/kg/day in 2 doses
   Recommendations


• Alternative therapies: cefdinir, cefuroxime,
  cefpodoxime,
  cefpodoxime single dose ceftriaxone
• Optimal duration of treatment unknown
• Empiric suggestions:10,14, 21 or 28 d
• Alternative: Treat until symptom free plus
  additional 7 days
     Conclusions

• ABS is common complication (6.5%) of
  children with URI symptoms seen by PCP
• Sinusitis (persistent onset) can be
  diagnosed clinically without confirmatory
  radiographs
• Amoxicillin/K clavulanate results in
  significantly more cures and fewer failures
  than placebo according to parental report
  of time to resolution of clinical symptoms

				
DOCUMENT INFO