The document discusses diagnosing respiratory tract infections using the Binax NOW test for Streptococcus pneumoniae and Legionella pneumophila. It provides 3 key points: 1. S. pneumoniae and L. pneumophila are leading causes of community-acquired pneumonia but are difficult to diagnose using traditional methods like blood and sputum cultures that have low sensitivity. 2. The Binax NOW test provides rapid, sensitive, and specific detection of S. pneumoniae and L. pneumophila antigens in urine, allowing accurate diagnosis in 15 minutes without invasive sampling. 3. Published studies demonstrate the Binax NOW test outperforms traditional diagnostics, with sensitivity of 86% for S. pneumoniae and 95%

1. Binax NOW ® RTI Products
義大醫院
2008.06.13
1 臨床病理科

2. WHO comments:
– “More than any other infectious disease,
pneumonia remains the number one
killer worldwide.”
– Streptococcus pneumoniae and Haemophilus influenzae
are the top two bacterial causes of acute respiratory infections.
– Both viral and bacteria respiratory infections present the same
clinical symptoms and can often only be distinguished by
laboratory tests
– 80% of pneumonia patients may unnecessarily
be given antibiotics - contributing to
antibiotic resistance
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3. Case Review
• Respiratory Tract Infection (RTI) cases
– very large cases
– several diseases with similar symptoms
• Target cases
– Community-acquired pneumonia
– Nosocomial pneumonia cases
– Acute ‘Flu-like’ cases
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4. Community - Acquired
Pneumonia
~12 million cases treated annually
worldwide
S. pneumoniae is the leading cause of
bacterial pneumonia -
up to 65% of cases in some studies
Legionella also a leading cause of community-acquired
pneumonia - up to 15%
S. pneumoniae and Legionella pneumonia have high
mortality rates - as high as 30%
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5. Acute ‘Flu-like’ Cases
• Clinical symptoms of lower RTI diseases
(pneumonia, acute influenza and acute
bronchitis) similar
• Bacterial pneumonia can be a complication of
acute influenza or acute bronchitis
• Significantly increases overall case potential
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6. Disease Overview
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7. Causative Agents of
Community-Acquired Pneumonia
Bacterial Viral
Streptococcus pneumoniae Influenza A & B
Legionella pneumohila RSV
Haemophilus influenza type B Adenovirus
Non typable Haemophilus Para Influenza
Staphlococcus aureus
Moraxella catarrhalis
Pseudomonas aeruginosa
Chlymydia pneumonia
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Mycoplasma pneumonia 7

8. Community-Acquired Pneumonia
CAP
• S. pneumoniae is the leading cause of bacterial
pneumonia and CAP - up to 65% of all cases in
some studies
• Legionella also a leading cause of community-acquired
pneumonia - up to 15%
• S. pneumoniae and Legionella pneumonia have high
mortality rates - as high as 30%
• Bacterial infections can occur as a complication
of influenza
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9. Community-Acquired Pneumonia
• Transmission: person to person by direct contact
with infectious secretions
• Risk groups • Symptoms
– elderly – fever, chills
– children under 2 and / – chest pain, pleurisy,
or attending day care difficulty breathing
– patients with – blood-tinged sputum
underlying illness – headache
– immunocompromised – cough (often non-
patients productive)
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10. Community-Acquired Pneumonia
• Treatment
– Pathogen-specific diagnosis -
• help direct the most cost-effective treatment
• minimizes the risk of increasing antibiotic resistance
– Empirical treatment
• may not always be the most cost-effective treatment
• increases the risk of antibiotic resistance
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11. Community-Acquired Pneumonia
• many strains of S. pneumoniae have intermediate
sensitivity and resistance to penicillin and
resistance to single or multiple broad-spectrum
antibiotics (Goldstein and Acar, 1996)
• accurate diagnosis required allowing specific
antibiotic therapy
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12. Diagnostics
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13. Diagnostics
• Blood Culture
• Sputum Culture
• Sputum Gram Stain
• PCR / DFA
• NOW® ICT Urinary Antigen Test
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14. Diagnostics
• Blood Culture
– Advantages
• positive = confirmation patient is bacteremic
• allows for drug susceptibility testing
– Disadvantages
• only 10-30% of all pneumonia cases are
bacteremic - positive culture result in only 25%
of cases (Musher, 1992)
• potential errors by technician
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15. Diagnostics
• Blood Culture
– Disadvantages
• can also be positive in patients with meningitis,
otitis media, septic arthritis, etc
• 24-48 hours incubation
• requires experienced technicians to perform and
interpret results
• expensive
– technician time
– instrumentation (incubators)
• invasive for the patient
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16. Diagnostics
• Sputum Culture
– Advantages
• supplies and reagents relatively inexpensive
• non-invasive for the patient
• allows for drug susceptibility testing
– Disadvantages
• samples must be taken prior to antibiotic therapy
• sample required from lower respiratory tract;
difficult to obtain (non-productive cough, children,
elderly)
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17. Diagnostics
• Sputum Culture
– Disadvantages
• samples must be processed immediately
– delays reduce isolation rates of the organism
– high false positive rates (carrier)
– low sensitivity and specificity
• normally 48 hours for positive identification
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18. Diagnostics
• Sputum Culture
– Disadvantages
• expensive
– technician time
– equipment
– experienced personnel are needed to perform and
interpret results
• Difficult to identify infecting organism
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19. Diagnostics
• Sputum Gram Stain
– Advantages
• inexpensive reagents and supplies
• non-invasive for the patient
• rapid test time
– Disadvantages
• requires sample from lower respiratory tract;
difficult to obtain
• samples must be processed immediately
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20. Diagnostics
• Sputum Gram Stain
– Disadvantages
• high false positive rate
• low sensitivity and specificity; large numbers of
organisms must be present
• does not allow for drug susceptibility testing
• requires experienced personnel
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21. Diagnostics
• PCR / DFA
– Advantages
• same day results
• specificity
– Disadvantages
• requires sample from lower respiratory tract;
difficult to obtain
• expensive - equipment, skilled technician
• sensitivity
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22. Diagnostics
• NOW® ICT Urinary Antigen
– Technology
• detects antigen, which is a common component of
the cell wall within the species
– S. pneumoniae - C-polysaccharide antigen, common to
all serotypes within the species
– Legionella - lipopolysaccharide portion of the serogroup
1 cell wall
• rabbit anti-species antibody as capture component
• rabbit anti-species antibody conjugated to colloidal
gold as detection component
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23. Technology
• Absorbent
• Control Line--Goat
anti-rabbit IgG
• Sample Line--Rabbit
anti-S. pneumoniae
antibody
• Conjugate Pad
• Sample Pad
( patent No. 91/214051).
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24. Intellectual Property
• 12 Issued Patents
– 4 ICT platform
– 7 Magnetic particles
– 1 Meningitis test
• 11 Patents Applied For
– respiratory, meningitis, and bacteria screen area
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25. Diagnostics
• NOW® ICT Urinary Antigen
– Advantages
• rapid results - 15 minutes
• non-invasive sample - urine
• easy test to run and interpret results
• accurate
– Limitations
• Susceptibility cannot be performed
• Single bacteria test
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27. Diagnostics
• NOW® ICT Urinary Antigen
– Performance Data
• S. pneumoniae
– Sensitivity 86%
– Specificity 94%
• Legionella
– Sensitivity 95%
– Specificity 95%
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28. Diagnostics
Comparison of Streptococcus pneumoniae Test Methods
Methods Sample Type Sensitivity Specificity Time
1 1
Binax NOW® Urine 86% 94% 15 mins
PCR Blood 52% 100% 4 hrs
2
Blood Culture Blood 10-30% >95% 48 hrs
Sputum Culture Sputum 50-60% 50-80% 48 hrs
Sputum Gram Stain Sputum 50-60% 50-80% 15 mins
1-Retrospective study data -- blood culture used as reference method.
2-Numbers reflect percent of pneumonia patient population estimated to be bacteremic.
Note: Sensitivity and specificity data on blood culture, sputum culture, and sputum Gram stain taken from various
published studies. References available upon request.
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29. Positioning
• NOW® ICT Features
– Easy to run
– Rapid test - only 15 minute tests for
S. pneumoniae and Legionella available
– Uses non-invasive sample
– No special equipment needed
– Easy to interpret resul
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30. – Accurate results
– U.S. FDA cleared products
– Multiple applications for S. pneumoniae
test - pneumonia, CSF and otitis media
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31. NOW® ICT S. pneumoniae
additional applications
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32. CSF application
• Anti-microbial therapy often initiated empirically because
causative agent not identified in advance
• Sensitivity of CSF gram staining is 75% - decreases to 50% in
patients given anti-microbial therapy
• Latex bacterial antigen assays have low sensitivity in CSF
• Streptococcus pneumoniae is typically the second most
common causative agent of community-acquired acute
bacterial meningitis
• Increasing rates of pneumococcal resistance to penicillin and
third generation cephalosporins
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33. CSF application
• NOW® ICT S. pneumoniae test
– 100% sensitivity and specificity with CSF sample
– published studies
• New Rapid Antigen Test for Diagnosis of Pneumococcal
Meningitis.
Marcos et al, The Lancet 357: 1499-1500, 2001.
• Using the NOW test in Cerebrospinal Fluid for the Rapid
Diagnosis of Pneumococcal meningitis.
Samrai et al, ASM: 114, 2001.
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34. CSF application
• NOW® ICT S. pneumoniae test
– additional application to support bringing the test into a
hospital lab
– only accurate rapid test for detection of a critical
pathogen for bacterial meningitis
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35. Otitis Media application
• NOW® ICT S. pneumoniae test
– Rapid Detection of S. pneumoniae in the Airways of Children
with Acute Otitis Media.
Faden et al, ASM: 113, 2001.
• Sensitivity – 90.0% (18/20) versus culture positive
nasopharangeal samples
• Specificity – 86.9% (21/23) versus culture negative
nasopharangeal samples
– one of three leading causes of otitis media
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36. Reference
• Published Studies - S. pneumoniae
– Evaluation of a Rapid Immunochromatographic Test for the
Detection of Streptococcus pneumoniae Antigen in Urine
Samples from Adults with Community-Acquired Pneumonia
Murdoch et al, ASM: 112, 2001
– Detection of Streptococcus pneumoniae Antigen by a Rapid
Immunochromatographic Assay in Urine Specimens
Dominguez et al: Chest, 119: 243-249, 2001
– Diagnostic Utility of a Rapid Urine Pneumococcal Antigen
Assay
Neuman et al, 2001 Pediatric Academic Societies Meeting
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37. • Published Studies - S. pneumoniae
– Evaluation of Binax NOW®, an Assay for the Detection of
Pneumococcal Antigen in Urine Samples, Performed among
Pediatric Patients
Dowell et al, Clinical Infectious Diseases, 32: 2001
– New Rapid Test for Detecting S. pneumoniae in Lower
Respiratory Tract Infections
Lienhard et al, Clinical Microbiology and Infection 7: 101
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38. Detection of Streptococcus pneumoniae Antigen by a
Rapid Immunochromatogrphic Assay in Urine Samples
CHEST, 119: 243-249, 2001
J.Dominguez et al
♦ Conclusions
(1) Now® S. pneumoniae test is sensitive and specific
(2) Now® S. pneumoniae test is a valuable tool for diagnosing
pneumococcal pneumonia cases, especially nonbacteremic cases,
which are often not diagnosed.
(3) Blood culture is only useful in approximately 25% of
pneumococcal pneumonia cases (i.e. that is the percent of the
population that is bacteremic).
(4) Sputum cultures only provide a probable diagnosis due to
difficulties associated with methodology (obtaining reliable
samples, etc.) and samples for culture are rarely taken
invasively due to concerns with the techniques that must be used.
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39. Evaluation of a Rapid Immunochromatographic Test
for the Detection of Streptococcus pneumoniae Antigen
in Urine Samples from Adults with Community-
Acquired Pneumonia
ASM: 112, 2001
Murdoch et al,
The authors conclude :
“ The Now® S. pneumoniae antigen test is a useful
adjunct to culture for determining the etiology of
community-acquired pneumonia in adults.”
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41. Immuno-Chromatographic Test v.s. Latex Agglutination Test
Now Wellcogen
108 CFU/ml* Positive 108 CFU/ml Positive
107 CFU/ml Positive 107 CFU/ml Negative
106 CFU/ml Positive 106 CFU/ml Negative
105 CFU/ml Positive (weak) 105 CFU/ml Negative
104 CFU/ml Negative 104 CFU/ml Negative
* Adjust cell suspension of S. pneumoniae to 0.5 McFarland ( 108 CFU/ml )
資料來源：林口長庚兒童醫院臨床檢驗組 90.01.05
測試者王碧娥組長
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