January 20, 2016
4 min read

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.