1 clinical evaluation of abs: diagnostic considerations carl n. kraus, m.d. medical officer division...

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Clinical Evaluation of ABS: Diagnostic Clinical Evaluation of ABS: Diagnostic ConsiderationsConsiderations

Carl N. Kraus, M.D.Carl N. Kraus, M.D.Medical OfficerMedical Officer

Division of Special Pathogen and Immunologic Drug ProductDivision of Special Pathogen and Immunologic Drug ProductOffice of Drug Evaluation IVOffice of Drug Evaluation IV

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and ResearchU.S. Food and Drug AdministrationU.S. Food and Drug Administration

2Although common, it is difficult to differentiate bacterial sinusitis Although common, it is difficult to differentiate bacterial sinusitis

from other causes of acute sinusitisfrom other causes of acute sinusitis

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(+) Imaging

(+) Symptoms

Which individuals have bacteria in their sinuses?

Need for Population DefinitionNeed for Population Definition

Enriched population with greatest potential Enriched population with greatest potential to benefit from antimicrobial therapyto benefit from antimicrobial therapy

(+) Culture

What evidence is present in the What evidence is present in the literature correlating specific literature correlating specific

diagnostic criteria for individuals diagnostic criteria for individuals that have acute bacterial sinusitis that have acute bacterial sinusitis

(ABS)? (ABS)?

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Criteria EvaluatedCriteria Evaluated

1.1.Symptom DurationSymptom Duration

2.2.Symptom CharacteristicsSymptom Characteristics

3.3.RadiographyRadiography

4.4.EndoscopyEndoscopy

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Search StrategySearch StrategySought studies that specified inclusion criteria and had a sinus Sought studies that specified inclusion criteria and had a sinus puncture with culture as part of the initial evaluationpuncture with culture as part of the initial evaluation. .

• Illness duration at time of inclusion Illness duration at time of inclusion

• Antimicrobial use prior to study inclusionAntimicrobial use prior to study inclusion

• Percent of patients that underwent sinus puncturePercent of patients that underwent sinus puncture

• Study populationStudy population

• Use of a microbiologic cutoffUse of a microbiologic cutoff

• Specified inclusion criteria (signs, symptoms, radiography)Specified inclusion criteria (signs, symptoms, radiography)

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General Search MethodologyGeneral Search Methodology

MeSH SearchMeSH Search1966 to Present1966 to Present

KeywordKeywordSearchSearch

Article Article ReferencesReferences

Abstract Abstract EvaluationEvaluation

Full Article Full Article ReviewReview

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Studies IdentifiedStudies Identified

Symptom durationSymptom duration: : 0 studies identified0 studies identified

Symptom characterSymptom character: : 5 studies identified5 studies identified

RadiographyRadiography:: 12 studies identified12 studies identified

EndoscopyEndoscopy:: 2 studies identified2 studies identified

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Approaches to Population EnrichmentApproaches to Population Enrichment

1. Symptom Duration1. Symptom Duration2. Symptom Characteristics2. Symptom Characteristics3. Radiography3. Radiography4. Endoscopy4. Endoscopy

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1. Symptom Duration

Symptoms thought to be related to viral rhinosinusitistypically have a median duration of 1 week

Gwaltney et.al., JAMA. 1967;202(6):494-500.

90% of patient with the common cold have (+) CT. Gwaltney et. al., NEJM,

1994; 330:25-30

Bacterial sinusitis is seen in only 20% of patients withsymptoms less than 7 days

Comments in Hickner JM et. al., Ann Intern Med. 2001;134(6):498-505

No studies evaluating the timing of sinus taps and No studies evaluating the timing of sinus taps and microbiology identified in the literature.microbiology identified in the literature.

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Reporting VariationsReporting Variations

Patient Based Patient Based ReportingReporting

Sinus Based Sinus Based ReportingReporting

Aspirate Based Aspirate Based ReportingReporting

30 patients30 patients

15 with (+) cultures15 with (+) cultures

50% (+) Culture Rate50% (+) Culture Rate


60 sinus punctures60 sinus punctures

40 (+) cultures40 (+) cultures



80 sinus aspirates80 sinus aspirates

60 (+) cultures60 (+) cultures


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Symptom Characteristics (2)Symptom Characteristics (2)34%34%11 60%60%22 65%65%33

11van Buchem L, Eur J Gen Pract, 1995. 1: 155-60.van Buchem L, Eur J Gen Pract, 1995. 1: 155-60. 22Hamory, B.H., et al., J Infect Dis, 1979. 139(2): 197-202.Hamory, B.H., et al., J Infect Dis, 1979. 139(2): 197-202.33Savolainen, S., et al., Acta Otolaryngol Suppl, 1997. 529: p. 148-52.Savolainen, S., et al., Acta Otolaryngol Suppl, 1997. 529: p. 148-52.44Berg O, et. al., Scand J Infect Dis 20: 511-516, 1988Berg O, et. al., Scand J Infect Dis 20: 511-516, 1988

xx

x

xx

xxxxxxx

87%87%44

Inclusion: “clinical Inclusion: “clinical symptoms and symptoms and signs of sinusitis signs of sinusitis indicating indicating diagnostic and diagnostic and therapeutic therapeutic puncture” and puncture” and “prevailing antral “prevailing antral secretion at secretion at aspiration”aspiration”

Headache

Nasal Symptoms

Purulence

Facial Pain

Post Nasal Drip

Upper Jaw Pain

Nasal Obstruction

Impaired Smell

(+) Sinus Cultures

(N=113)(N=113) (N=81)(N=81) (N=132)(N=132)

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Symptom Characteristics (4)Symptom Characteristics (4)

1 other study identified (24 adult pts, 17 with acute 1 other study identified (24 adult pts, 17 with acute symptoms)symptoms)

Specific signs/symptoms not provided but:Specific signs/symptoms not provided but:

“ “ quality, radiation, intensity of facial pain, purulence quality, radiation, intensity of facial pain, purulence of nasal discharge or presence of fever did not of nasal discharge or presence of fever did not accurately predict the presence of infection as accurately predict the presence of infection as determined by aspiration”determined by aspiration”

Evans FO et. al., NEJM 293: 735-739, 1975

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Symptom Characteristics (3)Symptom Characteristics (3)• No maximum symptom duration cutoffNo maximum symptom duration cutoff• No minimum duration of symptomsNo minimum duration of symptoms• No exclusion secondary to antimicrobial useNo exclusion secondary to antimicrobial use• patient based reporting of datapatient based reporting of data• 4% patients enrolled but not punctured4% patients enrolled but not punctured--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

--• (+) maximum symptom duration cutoff(+) maximum symptom duration cutoff• No minimum duration of symptomsNo minimum duration of symptoms• Sinus based reporting of dataSinus based reporting of data• 4% patients enrolled but not punctured4% patients enrolled but not punctured

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------• No maximum symptom duration cutoffNo maximum symptom duration cutoff• No minimum duration of symptoms No minimum duration of symptoms • Patient based reporting of dataPatient based reporting of data• 18% patients enrolled but not punctured18% patients enrolled but not punctured

Van BuchemVan BuchemN=113N=113

HamoryHamoryN=105 (81 subjects)N=105 (81 subjects)

SavolainenSavolainenN=132N=132

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Radiography (1)Radiography (1)

• The percentage of subject with sinus The percentage of subject with sinus puncture cultures ranged from 30-puncture cultures ranged from 30-77%.77%.

• Extreme heterogeneity of clinical Extreme heterogeneity of clinical inclusions criteria.inclusions criteria.

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• No antibiotic No antibiotic exclusionexclusion•many patients with many patients with confounding illnessesconfounding illnesses• No duration cutoffNo duration cutoff

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

InclusionsInclusionsReportingReporting(+) Sinus Cultures: 30-54%

Antila, J., J. Suonpaa, and O.P. Lehtonen,. Antila, J., J. Suonpaa, and O.P. Lehtonen,. Acta OtolaryngolActa Otolaryngol Suppl, 1997. 529:162-4. Suppl, 1997. 529:162-4.Johnson, P.A., et al., J Otolaryngol, 1999. 28(1): p. 3-12Johnson, P.A., et al., J Otolaryngol, 1999. 28(1): p. 3-12Pahor, A.L, Ear Nose Throat J, 1978. 57(10): p. 451-4.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. 1668-75Talbot, G.H., et al., Clin Infect Dis, 2001. 33(10): p. 1668-75

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Facial PainFacial Pain (+) antibiotic (+) antibiotic exclusionexclusion (+) purulence(+) purulence No duration cutoffNo duration cutoff

3 studies (adult)3 studies (adult) 3 sinus based 3 sinus based reportingreporting 0 patient based 0 patient based reportingreporting

InclusionsInclusionsReportingReporting

(+) Sinus Cultures: 60-6660-66 %

Penttila, M., et al., Penttila, M., et al., Acta OtolaryngolActa Otolaryngol Suppl, 1997. 529: p. 165-8. Suppl, 1997. 529: p. 165-8.Camacho, A.E., et al., Am J Med, 1992. 93(3): p. 271-6.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.Hamory, B.H., et al., J Infect Dis, 1979. 139(2): 197-202.

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radiographic criteriaradiographic criteria (+) antibiotic exclusion(+) antibiotic exclusion (+) use of microbiologic (+) use of microbiologic cutoffcutoff duration cutoff in 1 duration cutoff in 1 subgroupsubgroup

InclusionsInclusionsReportingReporting(+) Sinus Cultures: 70-7770-77 %

3 studies (2 pediatric)3 studies (2 pediatric) 2 patient based 2 patient based

reportingreporting 1 sinus based reporting1 sinus based reporting

Wald, E.R., et al.,. Wald, E.R., et al.,. N Engl J MedN Engl J Med, 1981. 304(13): p. 749-54., 1981. 304(13): p. 749-54.Wald, E.R., et al., Wald, E.R., et al., J PediatrJ Pediatr, 1984. 104(2): p. 297-302, 1984. 104(2): p. 297-302Rantanen, T, et al, Rantanen, T, et al, Acta OtolaryngolActa Otolaryngol, 1973. 76(1): p. 58-62, 1973. 76(1): p. 58-62

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34 culture positive sinuses:34 culture positive sinuses:16/34 (47%) 16/34 (47%) Air Fluid LevelAir Fluid Level10/34 (29%)10/34 (29%) opacityopacity8/34 (24%)8/34 (24%) mucosal thickeningmucosal thickening

Hamory, B.H., et al., J Infect Dis, 1979. 139(2): p. 197-202. Hamory, B.H., et al., J Infect Dis, 1979. 139(2): p. 197-202.

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Radiography (6)Radiography (6)Only 1 study identified with sinus Only 1 study identified with sinus

puncture data and CT:puncture data and CT:Requirments for study entry: Clinical ImpressionRequirments for study entry: Clinical Impression174 subjects completed study174 subjects completed study122 with abnormal CTs122 with abnormal CTs92 subjects met CT criteria for Acute Sinusitis92 subjects met CT criteria for Acute Sinusitis61 found to have pathogenic bacteria (61/92; 61 found to have pathogenic bacteria (61/92; 66%)66%)

Hansen, J.G., et al., BMJ, 1995. 311(6999): p. 233-6.Hansen, J.G., et al., BMJ, 1995. 311(6999): p. 233-6.

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Endoscopy (1)Endoscopy (1)

Talbot, G.H., et al., Clin Infect Dis, 2001. 33(10): 1668-75Talbot, G.H., et al., Clin Infect Dis, 2001. 33(10): 1668-75Vogan, J.C. et.al. Otolaryngol Head Neck Surg, 2000. 122(3): 370-3Vogan, J.C. et.al. Otolaryngol Head Neck Surg, 2000. 122(3): 370-3

Procedure Population NVogan, 2000 endoscopy adult 13*Talbot, 2001 endoscopy adult 53**

*13 patients, 16 sinuses; 13 sinuses with previous antibiotic use, diagnositic *13 patients, 16 sinuses; 13 sinuses with previous antibiotic use, diagnositic criteria for acute sinusitis not stated, only patients with AFL on radiography criteria for acute sinusitis not stated, only patients with AFL on radiography included, no dilutions noted on semiquantitative microbiologyincluded, no dilutions noted on semiquantitative microbiology

**symptoms at time of inclusion well described, patients with >5mm or AFL **symptoms at time of inclusion well described, patients with >5mm or AFL included, (+) minimum symptom duration noted, (+) antimicrobial exclusion, included, (+) minimum symptom duration noted, (+) antimicrobial exclusion, (+) chronic sinusitis exclusion, (+) dilutions noted on semiquantative (+) chronic sinusitis exclusion, (+) dilutions noted on semiquantative microbiologymicrobiology

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Endoscopy (2)Endoscopy (2)

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 > 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 (+) endoscopyOverall, 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)

VoganVogan TalbotTalbot

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Conclusions(1)Conclusions(1)Does the literature adequately describe specific criteria for the diagnosis of ABSDoes the literature adequately describe specific criteria for the diagnosis of ABS??

Symptom durationSymptom duration: : 0 studies identified0 studies identified

Symptom characterSymptom character: : 5 studies identified5 studies identified60-65% (2 studies)60-65% (2 studies)

RadiographyRadiography:: 12 studies identified12 studies identified30-77% (12 studies)30-77% (12 studies)

EndoscopyEndoscopy:: 2 studies identified2 studies identified 39-50% (2 studies)39-50% (2 studies)

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SymptomsSymptoms

RadiographyRadiography

CultureCulture

• Symptoms are necessary, Symptoms are necessary, but not sufficient for ABS but not sufficient for ABS diagnosis.diagnosis.

• Radiography is not Radiography is not necessary or sufficient but necessary or sufficient but may help enrich a may help enrich a population for ABS.population for ABS.

• Given symptoms, cultures Given symptoms, cultures are sufficient and, since are sufficient and, since there is no validated, or there is no validated, or reproducible, or reproducible, or standardized surrogate in standardized surrogate in the literature, necessary.the literature, necessary.

Conclusions (2)Conclusions (2)

1 clinical evaluation of abs: diagnostic considerations carl n. kraus, m.d. medical officer division...

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