Slide job

1
Clinical Evaluation of ABS Diagnostic
Considerations Carl N. Kraus, M.D. Medical
Officer Division of Special Pathogen and
Immunologic Drug Product Office of Drug
Evaluation IV Center for Drug Evaluation and
Research U.S. Food and Drug Administration
2
Although common, it is difficult to differentiate
bacterial sinusitis from other causes of acute
sinusitis
3
Need for Population Definition
Which individuals have bacteria in their sinuses?
() Imaging
() Symptoms
() Culture
Enriched population with greatest potential to
benefit from antimicrobial therapy
4
What evidence is present in the literature
correlating specific diagnostic criteria for
individuals that have acute bacterial sinusitis
(ABS)?
5
Criteria Evaluated

1. Symptom Duration
2. Symptom Characteristics
3. Radiography
4. Endoscopy

6
Search Strategy

• Sought studies that specified inclusion criteria
  and had a sinus puncture with culture as part of
  the initial evaluation.
• Illness duration at time of inclusion
• Antimicrobial use prior to study inclusion
• Percent of patients that underwent sinus
  puncture
• Study population
• Use of a microbiologic cutoff
• Specified inclusion criteria (signs, symptoms,
  radiography)

7
General Search Methodology
MeSH Search 1966 to Present
Abstract Evaluation
Full Article Review
Keyword Search
Article References
8
Studies Identified

• Symptom duration 0 studies identified
• Symptom character 5 studies identified
• Radiography 12 studies identified
• Endoscopy 2 studies identified

9
Approaches to Population Enrichment
1. Symptom Duration 2. Symptom
Characteristics 3. Radiography 4. Endoscopy
10
1. Symptom Duration
No studies evaluating the timing of sinus taps
and microbiology identified in the literature.
Symptoms thought to be related to viral
rhinosinusitis typically have a median duration
of 1 week Gwaltney et.al., JAMA.
1967202(6)494-500. 90 of patient with the
common cold have () CT. Gwaltney
et. al., NEJM, 1994 33025-30 Bacterial
sinusitis is seen in only 20 of patients
with symptoms less than 7 days Comments in
Hickner JM et. al., Ann Intern Med.
2001134(6)498-505
11
Approaches to Population Enrichment
1. Symptom Duration 2. Symptom
Characteristics 3. Radiography 4. Endoscopy
12
Reporting Variations
Patient Based Reporting
Sinus Based Reporting
Aspirate Based Reporting
30 patients 15 with () cultures 50 () Culture
Rate
30 patients 80 sinus aspirates 60 ()
cultures 75 () Culture Rate
30 patients 60 sinus punctures 40 ()
cultures 67 () Culture Rate
13
Symptom Characteristics (2)
() Sinus Cultures
653
874
341
602
(N113)
(N81)
(N132)
Inclusion clinical symptoms and signs of
sinusitis indicating diagnostic and therapeutic
puncture and prevailing antral secretion at
aspiration
Headache
Nasal Symptoms
Purulence
Facial Pain
Post Nasal Drip
Upper Jaw Pain
Nasal Obstruction
Impaired Smell
1van Buchem L, Eur J Gen Pract, 1995. 1 155-60.
2Hamory, B.H., et al., J Infect Dis, 1979.
139(2) 197-202. 3Savolainen, S., et al., Acta
Otolaryngol Suppl, 1997. 529 p. 148-52. 4Berg O,
et. al., Scand J Infect Dis 20 511-516, 1988
14
Symptom Characteristics (4)
1 other study identified (24 adult pts, 17 with
acute symptoms) Specific signs/symptoms not
provided but quality, radiation, intensity of
facial pain, purulence of nasal discharge or
presence of fever did not accurately predict the
presence of infection as determined by aspiration
Evans FO et. al., NEJM 293 735-739, 1975
15
Symptom Characteristics (3)

• No maximum symptom duration cutoff
• No minimum duration of symptoms
• No exclusion secondary to antimicrobial use
• patient based reporting of data
• 4 patients enrolled but not punctured

Van Buchem N113

• --------------------------------------------------
  ---------------------------------------
• () maximum symptom duration cutoff
• No minimum duration of symptoms
• Sinus based reporting of data
• 4 patients enrolled but not punctured

Hamory N105 (81 subjects)

• --------------------------------------------------
  ---------------------------------------
• No maximum symptom duration cutoff
• No minimum duration of symptoms
• Patient based reporting of data
• 18 patients enrolled but not punctured

Savolainen N132
16
Approaches to Population Enrichment
1. Symptom Duration 2. Symptom
Characteristics 3. Radiography 4. Endoscopy
17
Radiography (1)

• The percentage of subject with sinus puncture
  cultures ranged from 30-77.
• Extreme heterogeneity of clinical inclusions
  criteria.

18
Radiography (2)
() Sinus Cultures 30-54
Inclusions
Reporting

• No antibiotic exclusion
• many patients with confounding illnesses
• No duration cutoff

• 4 studies (adult)
• 2 sinus based reporting
• 2 patient based reporting

Antila, J., J. Suonpaa, and O.P. Lehtonen,. Acta
Otolaryngol Suppl, 1997. 529162-4. Johnson,
P.A., et al., J Otolaryngol, 1999. 28(1) p.
3-12 Pahor, A.L, Ear Nose Throat J, 1978. 57(10)
p. 451-4. Talbot, G.H., et al., Clin Infect Dis,
2001. 33(10) p. 1668-75
19
Radiography (2)
() Sinus Cultures 60-66
Inclusions
Reporting

• Facial Pain
• () antibiotic exclusion
• () purulence
• No duration cutoff

• 3 studies (adult)
• 3 sinus based reporting
• 0 patient based reporting

Penttila, M., et al., Acta Otolaryngol Suppl,
1997. 529 p. 165-8. Camacho, A.E., et al., Am J
Med, 1992. 93(3) p. 271-6. Hamory, B.H., et al.,
J Infect Dis, 1979. 139(2) 197-202.
20
Radiography (2)
() Sinus Cultures 70-77
Inclusions
Reporting

• radiographic criteria
• () antibiotic exclusion
• () use of microbiologic cutoff
• duration cutoff in 1 subgroup

• 3 studies (2 pediatric)
• 2 patient based reporting
• 1 sinus based reporting

Wald, E.R., et al.,. N Engl J Med, 1981. 304(13)
p. 749-54. Wald, E.R., et al., J Pediatr, 1984.
104(2) p. 297-302 Rantanen, T, et al, Acta
Otolaryngol, 1973. 76(1) p. 58-62
21
Radiography (4)
34 culture positive sinuses 16/34 (47) Air
Fluid Level 10/34 (29) opacity 8/34
(24) mucosal thickening
Hamory, B.H., et al., J Infect Dis, 1979. 139(2)
p. 197-202.
22
Radiography (6)
Only 1 study identified with sinus puncture data
and CT
Requirments for study entry Clinical
Impression 174 subjects completed study 122 with
abnormal CTs 92 subjects met CT criteria for
Acute Sinusitis 61 found to have pathogenic
bacteria (61/92 66)
Hansen, J.G., et al., BMJ, 1995. 311(6999) p.
233-6.
23
Approaches to Population Enrichment
1. Symptom Duration 2. Symptom
Characteristics 3. Radiography 4. Endoscopy
24
Endoscopy (1)
13 patients, 16 sinuses 13 sinuses with
previous antibiotic use, diagnositic criteria for
acute sinusitis not stated, only patients with
AFL on radiography included, no dilutions noted
on semiquantitative microbiology symptoms at
time of inclusion well described, patients with
gt5mm or AFL included, () minimum symptom
duration noted, () antimicrobial exclusion, ()
chronic sinusitis exclusion, () dilutions noted
on semiquantative microbiology
Talbot, G.H., et al., Clin Infect Dis, 2001.
33(10) 1668-75 Vogan, J.C. et.al. Otolaryngol
Head Neck Surg, 2000. 122(3) 370-3
25
Endoscopy (2)
Vogan
Talbot
No minimum duration of symptoms sinus punctures
() in 14/16 sinuses only 4/16 sinuses () with
more stringent micro cutoff Only 2 endoscopic
cultures with gt 1 bacteria Overall, 8/16
(50) sinuses studied had () endoscopic cultures
with the same pathogen as the sinus puncture.
(including any colony count and the pathogens S.
pnemoniae, M. catarrhalis, and H. influenzae)
No minimum duration of symptoms 23/46 (50) with
() sinus punctures 31/46 (67) patients with ()
endoscopy Overall, 12/31 (39) patients with ()
endoscopy had sinus puncture () cultures with
the same pathogen. (including any colony count
and the pathogens S. pnemoniae, M. catarrhalis,
and H. influenzae)
26
Conclusions(1)

• Does the literature adequately describe specific
  criteria for the diagnosis of ABS?
• Symptom duration 0 studies identified
• Symptom character 5 studies identified
• 60-65 (2 studies)
• Radiography 12 studies identified
• 30-77 (12 studies)
• Endoscopy 2 studies identified
• 39-50 (2 studies)

27
Conclusions (2)

• Symptoms are necessary, but not sufficient for
  ABS diagnosis.
• Radiography is not necessary or sufficient but
  may help enrich a population for ABS.
• Given symptoms, cultures are sufficient and,
  since there is no validated, or reproducible, or
  standardized surrogate in the literature,
  necessary.