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Comprehensive molecular testing improves pathogen detection for CAP
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A comprehensive molecular testing method assessing multiple bacterial and viral pathogens improved detection in patients with suspected community-acquired pneumonia and may reduce broad-spectrum antibiotic use, according to findings published in Clinical Infectious Diseases.
“Due to the range of pathogens responsible for [community-acquired pneumonia (CAP)], in moderate or severe infection, broad-spectrum antimicrobial cover should be initiated before de-escalating to narrow-spectrum, pathogen-directed agents once a microbiological diagnosis has been made,” Naomi J. Gadsby, PhD, from the department of laboratory medicine at the Royal Infirmary of Edinburgh, and colleagues wrote. “Unfortunately, de-escalation is uncommon in practice because current diagnostic methods may identify a pathogen in only 30% to 40% of patients with CAP.”
Prior research has highlighted the need for more rapid and sensitive diagnostic methods for CAP, particularly for identifying bacteria, the researchers wrote. Current multiplex real-time PCR assays screen a wide range of viral and atypical bacterial pathogens; however, a similar approach has not been developed for typical bacterial pathogens.
In response, Gadsby and colleagues developed an assay capable of measuring bacterial loads of eight typical bacterial pathogens from a single lower respiratory tract (LRT) specimen. They evaluated a single sputum (96%) or endotracheal aspirate (4%) specimen collected from 323 adults (median age, 67 years) who presented with suspected CAP at one of two tertiary care hospitals in Edinburgh, United Kingdom, from September 2012 to February 2014 to compare the diagnostic effectiveness of routine culture vs. a multiplex PCR assay encompassing 26 respiratory bacterial and viral pathogens and bacterial quantification.
The comprehensive molecular testing method identified a bacterial pathogen in 86.7% of patients with CAP vs. 39.3% of patients with routine culture alone, according to the researchers. The most common bacteria identified were Haemophilus influenzae (40.2%) and Streptococcus pneumoniae (35.6%). In addition, viral pathogens were detected in 30.3% of patients, most of whom (81.6%) were coinfected with bacteria. The most frequent combination was rhinovirus with H. influenzae and/or S. pneumoniae (37.5%).
Nearly 85% of patients with available information received antimicrobials during the 72 hours before a LRT specimen was collected. Among them, 77.6% had a bacterial pathogen identified through PCR, but only 32.1% were culture-positive (P < .0001).
Considering the high bacterial detection capability, the high rate of broad-spectrum antibiotic usage in the cohort and knowledge of local antimicrobial resistance patterns, the researchers estimated that physicians using molecular testing could de-escalate treatment in 77.2% of patients.
“Our study illustrates the feasibility of providing the physician with significantly more information on which to base treatment decisions than is currently available and suggest that comprehensive PCR testing including bacterial load quantification should be one of the inputs to future prospective studies in this area,” Gadsby and colleagues wrote. “Testing can be carried out within 1 working day to enable reporting of results in a clinically relevant time-frame, requires only a single LRT specimen, and is not negatively impacted by antibiotic administration prior to sampling.”
Based on the researchers’ significantly greater sensitivity of the comprehensive approach, the technology may become the standard method for microbiological diagnosis in patients hospitalized with CAP, according to Daniel M. Musher, MD, from Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center.
“Diagnostic techniques that can identify causative organisms at the time a patient is hospitalized for CAP are an important tool for the medical profession,” Musher wrote in a related editorial. “Regarding utility and cost-analysis … the charges for hospitalization in the U.S. are so high that the addition of a laboratory test to identify a causative organism of pneumonia would add minimally; some of that additional cost would be recouped through appropriate antibiotic stewardship.” – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopPaul Schreckenberger, PhD, D(ABMM), F(AAM)
Paul Schreckenberger
Gadsby and colleagues evaluated a lab-developed, fast, multiplex real-time PCR assay that targets 26 bacterial and viral pathogens causing community acquired pneumonia (CAP). The assay was performed on 323 specimens (310 sputum, 13 endotracheal aspirates) collected from patients being evaluated for CAP. The 26 pathogen targets included eight nonfastidious bacteria, five atypical bacteria and 13 viruses. In addition bacterial quantification is included for the nonfastidious bacteria detected in the assay. Results obtained by molecular testing were compared with culture-based methods. Molecular testing detected pathogens in 87% of CAP patients, compared with 39% with culture-based methods. Bacteria were detected by molecular testing in 262 (81.1%) specimens. PCR detected significantly more H. influenza, S. pneumonia, Moraxella catarrhalis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia than the culture-based method. When a quantitative cut-off of ≥105 CFU/mL was applied, bacteria were detected in specimens from 231 (71.5%) patients. Using a quantitative cutoff of ≥105 CFU/mL is important in order to eliminate detection of organisms found in low numbers in the oropharyngeal flora. Quantitation of the bacteria present is a key strength of this method in order to distinguish colonization from infection. The authors’ point out that molecular testing had the potential to enable de-escalation in the number and/or spectrum of antimicrobials in 77% of patients. This study demonstrates that the use of a comprehensive multibacterial, multiviral, quantitative molecular testing panel can more than double the pathogen detection in patients with CAP. This will allow physicians to target therapy for the specific etiologic agent of disease and will potentially lead to shorter duration of symptoms, decreased lengths of stay in ICUs, decreased lengths of stay in the hospital, less time lost from work and school, decreased pharmacy costs and decreased overall costs for the disease episode. Broad-range multiplex such as is described in this study should be used as first-line tests for diagnosing CAP.
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