Point-of-care testing for community-acquired pneumonia
Authors: Michel Drancourt, Charlotte A Gaydos, James T Summersgill, Didier Raoult
Journal: The Lancet Infectious Diseases (2013)

Community-acquired pneumonia is a life-threatening disease. An estimated 8% of patients are admitted to intensive care and overall estimated 30 day mortality is 4–11%.1Myint PK Kwok CS Majumdar SR et al.The International Community-Acquired Pneumonia (CAP) Collaboration Cohort (ICCC) study: rationale, design and description of study cohorts and patients.BMJ Open. 2012; 2: e001030Crossref Scopus (14) Google Scholar Many bacteria and viruses cause community-acquired pneumonia (and can co-infect), and the causative pathogen (or pathogens) cannot be predicatively identified by any clinical, radiological, or biological methods.2Eliakim-Raz N Robenshtok E Shefet D et al.Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults.Cochrane Database Syst Rev. 2012; 9 (CD004418.)PubMed Google Scholar Accordingly, antibiotic treatment is empirical, and guidelines recommend a combination of a β lactam with a macrolide.2Eliakim-Raz N Robenshtok E Shefet D et al.Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults.Cochrane Database Syst Rev. 2012; 9 (CD004418.)PubMed Google Scholar, 3Asadi L Sligl WI Eurich DT et al.Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis.Clin Infect Dis. 2012; 55: 371-380Crossref PubMed Scopus (122) Google Scholar Identification of the causative pathogen is usually delayed because clinical specimens are processed in a core laboratory, which is often in a different centre from the patient and the doctor. Culturing, if done, can also take several days. To avoid this delay, we introduced point-of-care (POC) microbiology laboratories near emergency departments where patients with community-acquired pneumonia are seen first.4Cohen-Bacrie S Ninove L Nougairède A et al.Revolutionizing clinical microbiology laboratory organization in hospitals with in situ point-of-care.PLoS One. 2011; 6: e22403Crossref PubMed Scopus (63) Google Scholar POC laboratories have a rapid turnaround time (<1·5 h) and deliver results as text messages directly to doctors' mobile phones.4Cohen-Bacrie S Ninove L Nougairède A et al.Revolutionizing clinical microbiology laboratory organization in hospitals with in situ point-of-care.PLoS One. 2011; 6: e22403Crossref PubMed Scopus (63) Google Scholar POC testing could be implemented in medical centres in large cities, where specimen transport delays diagnosis, and in remote areas without full microbiological facilities. However, it should be noted that not all pathogens that can cause community-acquired pneumonia can be detected by POC tests, and molecular tests for Staphylococus aureus have not been approved by the US Food and Drug Administration (FDA) or the European Conformity (CE). In the emergency department, community-acquired-pneumonia POC kits, comprising a plastic bag containing prelabelled tubes for clinical samples, prelabelled laboratory forms, and an informed consent form, can be used to take nasal or pharyngeal swabs and urine and serum samples. These samples can be used for the entire panel of POC tests. POC diagnosis of community-acquired pneumonia relies on immunochromatographic assays for the rapid antigen detection of pathogen-specific antigen and real-time PCR tests detecting pathogen-specific genomic sequences. Three RT-PCR-based POC tests have been approved by the FDA—GeneXpert Flu A/B (Cepheid, Sunnyvale, CA, USA), Simplexa Flu A/B&RSV (Focus Diagnostics, Cypress, CA, USA), and FilmArray RVP (Biofire, Salt Lake City, UT, USA). The appendix lists FDA-approved and CE-approved tests. Procalcitonin, a useful biomarker in bacterial community-acquired pneumonia,5Dusemund F Bucher B Meyer S et al.Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance.Eur J Clin Microbiol Infect Dis. 2013; 32: 51-60Crossref PubMed Scopus (20) Google Scholar can be rapidly semiquantified (in 30 min) in serum via immunochromatographic testing. Urinary rapid antigen detection of Legionella pneumophila serotype 1 and Streptococcus pneumoniae can be done in 20 min. A meta-analysis6Shimada T Noguchi Y Jackson JL et al.Systematic review and metaanalysis: urinary antigen tests for Legionellosis.Chest. 2009; 136: 1576-1585Crossref PubMed Scopus (144) Google Scholar showed that urinary detection of L pneumophila had a pooled sensitivity of 0·74 and a specificity of 0·99. Urinary detection of S pneumoniae had a specificity of 0·96 and positive predictive value of 0·88–0·96, allowing clinicians to use a narrower spectrum of antibiotics.7Sordé R Falcó V Lowak M et al.Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy.Arch Intern Med. 2011; 171: 166-172Crossref PubMed Scopus (103) Google Scholar Rapid antigen detection of the influenza virus in nasal or pharyngeal swabs (done in 30 min) has a low sensitivity of less than 0·60; sensitivity correlates with viral load.8Cho CH Woo MK Kim JY et al.Evaluation of five rapid diagnostic kits for influenza A/B virus.J Virol Methods. 2013; 187: 51-56Crossref PubMed Scopus (62) Google Scholar However, specificity is around 1·00, resulting in a positive predictive value of more than 0·98—high enough to make a positive result reliable for medical decisions. A negative result does not rule out the presumptive diagnosis of the physician, which should be checked by a second-line molecular test in a core laboratory. POC tests have to be operator-independent, and thus we do not recommend implementation of microscope-based tests, such as direct fluorescent antibody tests, for which skilled microscopists are needed. However, a liquid direct fluorescent antibody format (Fast-Point; Diagnostic Hybrids, Athens, OH, USA) is available for POC testing (appendix). It has not been approved by the FDA or the CE, but detects influenza virus, respiratory syncytial virus, adenovirus, coronavirus, and parainfluenza virus in 25 min. The latest generation real-time PCR kits can complete molecular testing of swabs for bacterial and viral pathogens in 60 min.9Hammond SP Gagne LS Stock SR et al.Respiratory virus detection in immunocompromised patients with FilmArray respiratory panel compared to conventional methods.J Clin Microbiol. 2012; 50: 3216-3221Crossref PubMed Scopus (60) Google Scholar New generation real-time PCR kits are typically multiplexed assays testing as many as 22 potential pathogens in parallel.9Hammond SP Gagne LS Stock SR et al.Respiratory virus detection in immunocompromised patients with FilmArray respiratory panel compared to conventional methods.J Clin Microbiol. 2012; 50: 3216-3221Crossref PubMed Scopus (60) Google Scholar This new capacity of POC tests increases the number of diagnoses11Parola P Colson P Dubourg G et al.Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in south east England.Euro Surveill. 2011; 17: 16Google Scholar and underscores that community-acquired pneumonia can result from co-infection with several pathogens,10Van den Bergh MR Biesbroek G Rossen JW et al.Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria.PLoS One. 2012; 7: e47711Crossref PubMed Scopus (164) Google Scholar which will challenge common notions about causation and management. For example, we propose that influenza and S pneumoniae have to be tested for in parallel irrespective of which one is the presumed causative pathogen. Furthermore, detection by POC testing of an abnormal increase in group A streptococci might suggest co-infection with influenza.11Parola P Colson P Dubourg G et al.Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in south east England.Euro Surveill. 2011; 17: 16Google Scholar Procalcitonin concentrations greater than 0·5 ng/mL suggest bacterial co-infection in influenza—a major risk factor for death. POC results could affect the major decisions that doctors have to make in emergency departments—eg, whether to admit the patient (the usual action for community-acquired pneumonia), which antibiotic (such as balancing the advantages of β-lactam and macrolides12Yu VL A clinical solution to antimicrobial resistance in community-acquired pneumonia: narrowing the spectrum of antimicrobial therapy: comment on "Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy".Arch Intern Med. 2011; 171: 172-173Crossref PubMed Scopus (16) Google Scholar) or antiviral to prescribe, isolation of contagious patients. Although barriers to the implementation of POC tests in developing countries have been identified, POC tests have been successfully implemented in remote areas—eg, rural Senegal, where patients and health-care providers are in close contact.13Sokhna C Mediannikov O Fenollar F et al.Point-of-care laboratory pathogens diagnosis in rural Senegal.PLoS Neglect Trop Dis. 2013; 7: e1999Crossref PubMed Scopus (98) Google Scholar Furthermore, assessment of the numbers of POC tests done on a weekly basis could help to predict epidemics even before the causative organism is known. MD and DR have deposited a brand name, Pocramé, for the concept of mobile POC laboratories. CAG and JTS declare that they have no conflicts of interest. Download .pdf (.21 MB) Help with pdf files Supplementary appendix