# Presentation: 243234

## 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***

## Although common, it is difficult to differentiate bacterial sinusitis from other causes of acute sinusitis

##  Need for Population Definition

**(+) Imaging**

**(+) Symptoms**

- Which individuals have bacteria in their sinuses?

-  Need for Population Definition

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

**(+)      Culture**

## What evidence is present in the literature correlating specific diagnostic criteria for individuals that have acute bacterial sinusitis (ABS)? 

## Criteria Evaluated

- Symptom Duration
- Symptom Characteristics
- Radiography
- Endoscopy

## 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)

## General Search Methodology

**MeSH Search**
**1966 to Present**

**Keyword**
**Search**

**Article References**

**Abstract Evaluation**

**Full Article Review**

## Studies Identified

_**Symptom duration**_**:  ****	****0 studies identified**
_**Symptom character**_**: ****	****5 studies identified**
_**Radiography**_**:****	****	****12 studies identified**
_**Endoscopy**_**:****	****	****	****2 studies identified**
**	**

## Approaches to Population Enrichment

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

## 1. Symptom Duration 

- Symptoms thought to be related to viral rhinosinusitis
- typically 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 with
- symptoms 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 microbiology identified in the literature.

## Approaches to Population Enrichment

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

## Reporting Variations

- _Patient Based Reporting_

-  _Sinus  Based Reporting_

- _Aspirate Based Reporting_

- 30 patients
- 15 with (+) cultures
- _50% (+) Culture Rate_

- 30 patients
- 60 sinus punctures
- 40 (+) cultures
- _67% (+) Culture Rate_

- 30 patients
- 80  sinus aspirates
- 60 (+) cultures
- _75% (+) Culture Rate_

## Symptom Characteristics (2)

***34%******1***

**60%****2**

**65%****3**

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

**87%****4**

**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**

_**(+) Sinus Cultures**_

- (N=113)

- (N=81)

- (N=132)

## 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*

## 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**

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

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

**Van Buchem**
**N=113**

**Hamory**
**N=105 (81 subjects)**

**Savolainen**
**N=132**

## Approaches to Population Enrichment

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

## Radiography (1)

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

## Radiography (2)

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

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

- _Inclusions_

- _Reporting_

_**(+) Sinus Cultures: 30-54%**_

**Antila, J., J. Suonpaa, and O.P. Lehtonen,. *****Acta Otolaryngol***** Suppl, 1997. 529:162-4.**
**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**

## Radiography (2)

**  ****Facial Pain**
** ****(+) antibiotic exclusion**
** ****(+) purulence**
** ****No duration cutoff**

** ****3 studies (adult)**
-  **3 sinus based reporting**
** ****0 patient  based reporting**

- _Inclusions_

- _Reporting_

_**(+) Sinus Cultures: **__**60-66**__** %**_

**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.**

## Radiography (2)

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

- _Inclusions_

- _Reporting_

_**(+) Sinus Cultures: **__**70-77**__** %**_

**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**

## 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. **

## 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.**

## Approaches to Population Enrichment

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

## Endoscopy (1)

- 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

****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 >5mm or AFL included, (+) minimum symptom duration noted, (+) antimicrobial exclusion, (+) chronic sinusitis exclusion, (+) dilutions noted on semiquantative microbiology***

## 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 (+) 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*)

**Vogan**

**Talbot**

## 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)***

## 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.