Rapid respiratory panel testing influences patient management and clinical outcomes

Upper respiratory tract infections (URTIs) are a leading cause of morbidity and mortality worldwide. The desire to control and prevent URTIs has made them a focus of efforts to develop improved diagnostic tests. Several highly-multiplexed molecular respiratory pathogen panels (RPPs) have been developed to simultaneously broaden and streamline testing for viral and some bacterial agents of URTI. Numerous studies have demonstrated improved sensitivity and specificity, broader pathogen coverage, and shortened turnaround time for these tests as compared to standard methods such as culture, direct fluorescent antibody testing, and enzyme immunoassays.¹ 

In many laboratories, RPPs have replaced traditional methods as the primary tool for aiding diagnosis of acute URTIs. Although these tests provide more information—more accurately and more rapidly—than the alternative current best standard practice, potential users and their institutions have rightly appealed for data demonstrating that the generation of this information leads to measurable improvement in health outcomes. Studies addressing this need for quantitative assessment of the impact of RPPs are now becoming available.

The primary outcome of interest for most diagnostic tests is accurate and timely identification of a patient’s condition for which effective treatment is available.^2,3 While few infectious agents targeted by RPPs fall into this category, effective therapeutics can be provided for bacterial targets and for influenza. In a recent study, Xu et al., demonstrated that with implementation of an RPP that was available 24/7, 81% of patients testing positive for influenza were given or prescribed oseltamivir in the emergency department (ED) or within three hours of discharge.⁴

While identification of a treatable condition is vastly important, it is not the only measure of clinical utility for which a diagnostic test can have significant impact for patients and the healthcare system.² Other outcome measures include changes in bed management and infection control procedures, use/duration of unnecessary and potentially harmful therapies, antimicrobial stewardship (e.g., reduction of the high levels of antibiotic use in pediatric URTI patients with primarily viral infections), number of ancillary tests, laboratory/hospital costs, and healthcare consumer satisfaction. New studies suggest that RPPs may aid improvement in several of these areas.

In a pre-post intervention study involving more than 1,000 ED subjects (365 pre-intervention, respiratory season 2011-2012, and 771 post-intervention, respiratory season 2012-2013), Rogers et al., observed that while antibiotic prescription rates were unchanged, duration of antibiotic use was shortened after implementation of the RPP (by 0.4 days; P < .003). ED length of stay (LOS) increased post-intervention (by 26 minutes; P < .002); however, for patients receiving positive test results, the inpatient LOS and length of time spent in isolation were both decreased (by 0.3 days; P < .03).⁵ In contrast to the increased ED LOS observed in this study, Xu et al., estimated that the improved turnaround time provided by an RPP may have saved 900 ED hours within a four-month period.⁴ 

The impacts of RPPs on reduced antibiotic use and decreased LOS/isolation are in line with those previously observed with more limited rapid respiratory pathogen testing. Using rapid antibody-based tests for several respiratory viruses, Barenfanger et al., recorded a decrease in LOS of 5 days for inpatients with positive test results, and Woo et al., recorded a decrease in LOS (0.9 days; P < .05), days of antibiotic use (2.6 days; P < .001), and number of ancillary tests (1.7 investigations per subject; P < .001).^6,7 Mills et al., observed that rapid RSV testing in the ED led to substantial improvement in bed management (i.e., reduced cubicle days), primarily due to the ability to directly admit RSV-positive patients to cohorts from the ED.⁸ 

In addition to improved bed management, the ability to quickly cohort individuals with positive test results is important for preventing the spread of healthcare-acquired infections. The breadth of coverage provided by RPPs becomes important when considering the implications of potentially cohorting a patient with a polymicrobial infection together with other patients already suffering from infection with one pathogen. McGrath et al., found that of 344 patients testing positive by an RPP, 17% harbored greater than one pathogen, more than half of which involved pathogens or combinations of pathogens requiring combined droplet and contact isolation precautions. The RPP results allowed more focused cohorting of these patients.⁹

Financial outcomes have gained greater importance following initiatives to control costs and provide value-driven healthcare strategies. The most extensive cost analysis of RPP implementation to date was developed by Mahony et al., who calculated a saving of Can $291 per inpatient as compared to a previous testing algorithm, resulting in an estimated saving of Can $529,620 per year in direct costs for the four hospitals.¹⁰ Barenfanger’s assessment of implementation of a rapid antibody-based test provided estimated hospital savings of more than $140,000 per year.⁶

The importance of implementing an effective management strategy that encompasses the RPP test itself along with downstream consequences of testing is a theme in many of the studies that realized positive outcome measures and is an established component of clinical utility in many fields.² As an example, shortening of antibiotic duration in Rogers’ study was dependent upon the ED receiving the test results within four hours.⁵ This dependence upon very rapid reporting may explain why other studies of PCR-based respiratory pathogen testing, such as that by Wishaupt et al., where results were returned within 12 to 36 hours, demonstrated no significant changes in admissions, LOS, or antibiotic duration.¹¹

Additional robustly designed studies are needed not only to evaluate health outcomes affected by RPPs, but to provide guidance for which implementation and management strategies are most effective. Outcomes yet to be significantly assessed include those related to patient satisfaction and clinician confidence in the test results and the impact of detecting polymicrobial infections. It is generally accepted that certain populations may realize the benefits of RPP testing to a greater extent than others, e.g., immunocompromised inpatients or older adults who demonstrate atypical presentations of infection. Outcomes studies in these populations are needed to investigate these assumptions.