General Supporting Evidence MEEHAN – 1997 CAP is the only acute respiratory tract infection in which delayed antibiotic therapy has been associated with increased risk of death1 HOUCK – 2004 15% reduction in mortality in the patients who received antibiotic therapy within 4 hours of admission2 ZISS – 2003 Patients treated for CAP within 4 hours of arrival at hospital had a significantly shorter inpatient length of stay, compared to patients who received antibiotics more than 4 hours after arrival3 Quality of Care, Process and Outcomes in Elderly Patients with Pneumonia - Meehan et al, JAMA 1997 278 (23) 2080-2084 Antibiotic administration in community-acquired pneumonia – Houck et al, Chest 2004 126 (1) 320-1 CAP: compliance with centers for Medicare and Medicaid services, national guidelines, and factors associated with outcomes – Ziss et al, SouthMedJ. 2003: 96 (10) 949-59 1

Targeted Treatment for CAP Penicillin is drug of choice for pneumococcal pneumonia ‘Penicillin resistant strains’ CLSI modification of MIC breakpoints Cheaper, more effective and better for patient Macrolide for Legionella pneumonia 2

BinaxNOW S. pneumoniae: Supporting Evidence KANAVAKI - 2002 Diagnostic investigation of 66 severe cases of CAP of unknown etiology Sample No tested Acceptable Microscopy Culture BinaxNOW Sputum 64/66 45 (70%) 7 (10.9%) 3 (6.7%) Blood 36/66 1 (2.7%) Urine 66/66 14 (21.2%) BinaxNOW is a considerable alternative for microbiological diagnosis of pneumococcal pneumonia BinaxNOW should be incorporated into the test algorithms Alternative microbiological methods for the diagnosis of pneumococcal Alternative microbiological methods for the diagnosis of pneumococcal pneumonia - Kanavaki et al, PNEUMON 2002 2 (15) 3

BinaxNOW S. pneumoniae: Supporting Evidence KOBASHI – 2007 156 cases of CAP Blood culture 3 positive results Sputum culture 20 positive results Conventional total 23 positive results BinaxNOW 44 positive results BinaxNOW increased the yield of pneumococcal pneumonia patients leading to shorter hospital stay reduction in medical costs By positively determining appropriate antibiotics for CAP patients Evaluating the Use of a Streptococcus pneumoniae Urinary Antigen Detection Kit for the Management of community acquired pneumonia in Japan - Kobashi et al Respir 2007; 74 (4) 387-393 4

BinaxNOW S. pneumoniae: Supporting Evidence Matta, 2009 541 patients, 233 patients with pneumonia BinaxNOW 58/233 positive results 25% yield of pneumococcal pneumonia Sputum/Blood culture 17 positives 8% yield of pneumococcal pneumonia Increase in amoxicillin treatment following Binax positive result Binax detected an additional 17 % of pneumococcal pneumonia Sensitivity and specificity of Binax allows change of antibiotic therapy. Recommend use of Binax for diagnosis and implementing treatment guidelines Do Clinicians Consider the Results of Binax NOW Streptococcus pneumoniae Urinary Antigen to Adapt Antibiotic Regimen in Pneumonia Patients? Clinical Microbiology and Infection. Accepted Article 2009 Oct 5

BinaxNOW S. pneumoniae: Supporting Evidence Sorde´ 2010 474 cases of CAP (S. pneumoniae 171, (36%) Blood culture 53/171 (30.9%) Sputum culture/Gram 38/171 (22.2%), Pleural fluid 5/171 (2.9%) BinaxNOW 130/153 (85%) BinaxNOW diagnosed 75 additional cases of pneumococcal pneumonia BinaxNOW results allowed a change in antibiotic treatment BinaxNOW High specificity, High Sensitivity and High PPV UAT is a useful tool in the treatment of adults with CAP and should be incorporated into Clinical Guidelines Current and Potential Usefulness of Pneumococcal Urinary Antigen Detection in Hospitalized Patients With Community-Acquired Pneumonia to Guide Antimicrobial Therapy 6

BinaxNOW S. pneumoniae: Supporting Evidence Weatherall 2008 Evaluated BinaxNOW testing with nurses in the ED 98% Concordance Results available within 4 hours Rapid results would allow initial targeted treatment Reduce antibiotic resistance and reduce costs. Point-of-care urinary pneumococcal antigen test in the emergency department for community acquired pneumonia 7

Conclusion BinaxNOW S. pneumoniae UAT Simple to Use (ED testing) Easy to collect sample Results enable early appropriate treatment Increases the yield of pneumococcal pneumonia Results not affected by previous antibiotic treatment Advocated by many Worldwide CAP Guidelines 8

CAP Guidelines Advocating use of UAT Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults   British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009   Brazilian guidelines for community-acquired pneumonia in immunocompetent adults – 2009 (French Guidelines) Prise en charge des infections des voies respiratoires basses de l’adulte immunocompétent   (European) Guidelines for the management of adult lower respiratory tract infections Swedish guidelines for the management of community-acquired pneumonia in immunocompetent adults Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR)   Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia: An Evidence- Based Update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society Infectious Disease Society of America/American Thoracic Society CAP Guidelines 2007

IDSA/ATS CAP Guidelines 2007 Great enthusiasm for developing guidelines Avoidance of inappropriate antibiotic therapy has been associated with lower mortality rate All adult patients with severe CAP, should have blood culture, sputum culture, Legionella UAT and S. pneumoniae UAT Initial treatment for most patients will be empirical however urinary antigen tests will allow for specific antibiotic treatment Infectious Disease Society of America/American Thoracic Society CAP Infectious Disease Society of America/American Thoracic Society CAP Guidelines 2007

IDSA/ATS CAP Guidelines 2007 Diagnostic testing to determine etiology of CAP is justified as follows: Antibiotic treatment can be narrowed, broadened or completely changed Increased mortality is common with inappropriate antibiotic therapy Management of initial antibiotic therapy is greatly facilitated by etiological diagnosis at admission General recommendation of the committee is to strongly encourage diagnostic testing whenever the result is likely to change individual antibiotic management. The variety of methods is shown in table 5 but only the urine antigen tests can deliver results in a window to allow clinical decisions Infectious Disease Society of America/American Thoracic Society CAP Guidelines 2007

IDSA/ATS CAP Guidelines 2007 Infectious Disease Society of America/American Thoracic Society CAP Guidelines 2007

IDSA/ATS CAP Guidelines 2007 Rapid Urinary antigen Tests Pneumococcal urinary antigen test Vey useful when sputum cannot be collected or when antibiotic therapy has commenced Only 50% of Binax positive results can be detected by conventional methods. Legionella Urinary antigen test Plouffe study suggested that therapy with a macrolide alone is adequate for hospitalised patients with CAP who test positive with Legionella urinary antigen tests. Infectious Disease Society of America/American Thoracic Society CAP Guidelines 2007

Legionella Disease Burden Legionnaire’s disease is a serious pneumonia infection caused by inhaling Legionella bacteria (through aerosols) Water is the major natural reservoir e.g. cooling towers, hotel water systems, spas, air conditioning units, showers 20% of cases of Legionnaires disease detected in Europe are travel related. First recognised in 1976 in people (American Legion Convention) attending a hotel conference in the USA 14

Legionella Disease Burden Predominantly caused by Legionella pneumophila with serogroup 1 accounting for 70-90% Legionella pneumophila can account for 2-15% of CAP and Nosocomial pneumonia Legionnaires disease can account for >30% CAP cases requiring admission to ICU High Mortality rate (25-40%) Known risk factors 15

Legionella Disease Burden Water Masterclass – Warsaw 2009 *extrapolated data 16

BinaxNOW Legionella: Supporting Evidence LEPINE – 1998 Introduction of a rapid urinary antigen test improved case ascertainment1 If the urinary antigen test had been available in previous years, more cases of Legionnaire’s Disease may have been reported1 KOOL – 1999 Introduction of the urinary antigen test led to recognition of nosocomial cases2 Evidenced by the temporal relation between the introduction of this test in San Antonio hospitals and the rise in detected Legionellosis cases2 A recurrent Outbreak of Nosocomial Legionnaires’s Disease Detected by Urinary Antigen Testing: Evidence for Long term Colonization of a Hospital Plumbing System Lepine L et al. Infection Control and Hospital Epidemiology December 1998 (12) 905-910 Hospital Characteristics Associated with Colonization of Water Systems by Legionella and Risk of Nosocomial Legionnaires’ Disease; A cohort study of 15 Hospitals, Kool J et al Infection Control and Hospital Epidemiology December 1999 (20) 798-805 17

BinaxNOW Legionella Supporting Evidence KANAVAKI – 2003 88 patients suffering from severe CAP Outcome of Legionnaire’s disease depends on the timely diagnosis Conventional microbiology methods have limitations UAT is an important tool for the diagnosis of Legionnaires' disease highly sensitive results Reliability not affected by prior antibiotics Test is performed on easily obtained specimens Laboratory Diagnosis of Legionnaires' Disease in Patients with Community Acquired Pneumonia (CAP) 18

BinaxNOW Legionella Supporting Evidence ALVAREZ – 2010 No of outbreaks detected increased with the use of the Legionella UAT Early detection and treatment reduced case fatality rate (CFR) by 68% Detection of an outbreak depends on the diagnosis of the first case. Not always a history of risk factors The UAT should be available in all hospitals and all cases of the disease should be reported. Impact of the Legionella urinary antigen test on epidemiological trends in community outbreaks of legionellosis in Catalonia, Spain, 1990—2004 19

Legionella Supporting Evidence CAPNETZ 2010 All cases were sporadic Legionella pneumonia was found to occur at identical frequencies in outpatients and inpatients Challenges the current view that Legionella tends to be associated with more severe pneumonia Appropriate coverage remains mandatory for any patient with LD High rates of initial discordant antimicrobial treatment may be overcome by regular UAT testing for L. pneumophila in all hospitalized patients. Community-Acquired Legionella Pneumonia: New Insights from the German Competence Network for Community Acquired Pneumonia

Legionella Supporting Evidence Yu and Stout 2010 L. pneumophila shown to be one of the commonest causes of CAP Incidence among ambulatory patients (3.7%) was essentially identical to that among hospitalized patients (3.8%) Clinical manifestations are unreliable in diagnosing LD Confining Legionella laboratory testing to “high-risk” patients will overlook a notable number of cases Legionella and S. pneumoniae UAT should be applied to all patients with pneumonia. Community-Acquired Legionnaires Disease: Implications for Underdiagnosis and Laboratory Testing

Legionella UAT Supporting Evidence Yu and Stout 2009 Legionella UAT is one of the most successful diagnostic aids for infectious diseases Most importantly, results affect management at POC The UAT is the most common method to diagnose LD A positive UAT allows targeted anti-Legionella therapy UAT results should be available in 3hr instead of 3 days The ease of use of ICT card-type UAT makes it ideal for use in EDs, long-term care facilities, and physician offices. Rapid Diagnostic Testing for Community-Acquired Pneumonia Can Innovative Technology for Clinical Microbiology be exploited

Conclusion BinaxNOW Legionella UAT Simple to Use (ED testing) Easy to collect sample Most sensitive test on the market Results enable early appropriate detection and treatment Results not affected by previous antibiotic treatment Advocated by many Worldwide CAP Guidelines 23

BinaxNOW UAT: Supporting Evidence Victor Yu 2011 ‘We should halt the widespread practice of empirical antibiotics’ POC tests allow use of narrow spectrum antibiotics Positive S. pneumoniae UAT will allow treatment with Penicillin Legionella UAT has revolutionised diagnosis of Legionnaires’ disease Physician education is necessary to encourage use of narrow spectrum antibiotics UAT’s should be obtained as soon as possible Testing should be performed in the clinic, ED and hospital A clinical Solution to Antimicrobial Resistance in Community-Acquired-Pneumonia Narrowing the Spectrum of Antimicrobial Therapy 24