Community-acquired pneumonia is among the most common reasons for emergency department (ED) visits and can be caused by both viral and bacterial pathogens. A clear understanding of the likely pathogens is essential for the rapid institution of adequate antiviral or antibiotic therapy. Due to the indistinguishable clinical symptoms between viral and bacterial pathogens, patients with viral respiratory infection are usually undervalued while unnecessary antibacterial agents are more likely to be administered. The principal bacterial causes of CAP are well described, with Streptococcus pneumoniae being the most important pathogen in all age groups. Recent studies and our previous work showed viral associated CAP can be responsible for 20 to 30% of CAP. Therefore, laboratory tests providing accurate and timely determination of the infectious agents associated with CAP are important. A broad array of tests is available to detect viral respiratory agents. Rapid antigen tests are available for influenza A and B, and respiratory syncytial virus (RSV), but these tests have low sensitivity and specificity.
Molecular diagnostic tests using the polymerase chain reaction (PCR) method to detect RNA or DNA of the infectious agents have improved the ability to detect both viral and bacterial pathogens in clinical samples, but are technically challenging and time consuming. The advent of sensitive point-of-care (POC) molecular detection methods has made rapid diagnosis of respiratory virus infections possible. A POC systems that automates the real-time PCR process and integrates sample preparation, amplification, detection, and analysis into one complete process has been developed and approved by the FDA. Initial studies demonstrated that such POC multiplex PCR systems' identified previously under-evaluated viral or atypical infections in ED dyspneic patients. Despite the availability of highly accurate viral testing results, discontinuation of de-escalation of antibiotics still raises concerns because polymicrobial infections involving bacterial and viral pathogens is common in the older adults. An ideal pathogen diagnostic tool for CAP that can guide precise prescription of antibiotics should therefore include the following three features: first, including a wide array of both common viral and bacterial pathogens for CAP, second, including common drug resistance genes for bacterial pathogens, and lastly, easy operation with quick turnaround time and high accuracy.
Such diagnostic tool has recently been developed. The BIOFIRE® FILMARRAY® Pneumonia Panel plus tests for 18 bacteria (11 Gram negative, 4 Gram positive and 3 atypical), 7 antibiotic resistance markers, and 9 viruses that cause pneumonia and other lower respiratory tract infections. The target bacteria included Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Moraxella catarrhalis, Proteus spp., Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes. Seven antibiotics genes include ESBL (CTX-M), Carbapenemases (KPC, NDM, Oxa48-like, VIM, IMP, Methicillin Resistance (mecA/mecC and MREJ). The atypical pathogens include Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia pneumoniae. The virus included Influenza A, Influenza B, Adenovirus, Coronavirus, Parainfluenza virus, Respiratory Syncytial virus, Human Rhinovirus/Enterovirus, Human Metapneumovirus, and even Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The Filmarray system is a US FDA system that integrates sample preparation, nucleic acid extraction and purification, amplification, detection and analysis into one simple system that requires just 2 minutes of hands-on time, with a total run time of about one hour. Currently, the overall sensitivity and specificity for bronchoalveolar (BAL)-like samples of 96,2% and 98.3%, respectively, and for sputum samples a sensitivity and specificity of 96.3% and 97.2%, respectively.
In this study, we aim to assess the impact of implementation of POC molecular testing for pneumonia pathogens in conjunction with procalcitonin tests on elderly patients presenting to the ED with severe acute respiratory illness. We will conduct a prospective cohort study in the EDs of two urban medical centers. Clinical impact will be evaluated through the comparison between the experimental cohort with a randomly selected control cohort in a parallel fashion. In addition to POC molecular test, we will also test procalcitonin on these patients. With a highly sensitive POC molecular test, it is likely the detection of colonized pathogens will greatly increase. PCT is a precursor of calcitonin that is constitutively secreted by C cells of the thyroid gland and K cells of the lung. In healthy individuals, PCT is normally undetectable (below 0.01 ng/mL). When stimulated by endotoxin, PCT is rapidly produced by parenchymal tissue throughout the body. Unlike C-reactive protein, PCT does not respond to sterile inflammation or viral infection. Multiple randomized controlled trials have demonstrated that procalcitonin levels of under 0.25 µg/L can guide the decision to withhold antibiotics or stop therapy early. In addition, a procalcitonin levels of under 0.1 µg/L can indicate colonization. We hypothesize the new diagnostic approach would better guide the antibiotic treatment and ultimately improve patient's outcome.
