Influenza places a significant burden on healthcare, with ∼18 million related visits and 400,000 associated hospitalizations annually. 1 Most patients experiencing influenza-like illnesses present to outpatient settings with nonspecific symptoms that mimic other respiratory infections, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Reference Chi, Dai and Jiang2 Consequently, differentiating influenza from other respiratory pathologies based on presentation often proves unreliable; thus, diagnosis usually requires laboratory testing. Reference Dugas, Valsamakis and Gaydos3 However, highly sensitive tests, such as traditional influenza reverse-transcriptase polymerase chain reaction (TF-PCR), have limited utility due to long turnaround times (TATs). Reference Dugas, Valsamakis and Gaydos3 Alternatively, antigen detection tests with fast TATs lack sensitivity, which ranges from 10% to 69%. Reference Balish, Warnes and Wu4 Because neither test yields quick and reliable results, clinicians either begin a regimen of broad-spectrum antibiotics and antivirals or delay treatment until results are available. The former may result in unnecessary prescriptions, contributing to antibiotic resistance, while the latter can adversely affect clinical outcomes. Reference Steurer, Held and Spaar5,Reference Aoki, Macleod and Paggiaro6
To address this gap, companies have developed rapid PCR tests (XT-PCR), such as Xpert Flu (Cepheid, Sunnyvale, CA). In December 2018, XT-PCR replaced TF-PCR as the diagnostic test for influenzas A and B at a tertiary healthcare system in Detroit, Michigan. In this study, our primary objective was to quantify the effects of implementing XT-PCR on admission rates, antimicrobial use, and length of stay (LOS). Reducing these metrics during the current coronavirus disease 2019 (COVID-19) pandemic is of paramount importance as hospitals continue to experience patient surges and resource shortages (eg, staffing, bed, etc). Reference Jaklevic7
Methods
Study type
We conducted a comparative retrospective cohort study within a tertiary healthcare system during the 2017–2018 and 2018–2019 influenza seasons to determine the impact of implementing a XT-PCR test on admission rates, antimicrobial use, and LOS. The following exclusion criteria were applied: (1) patients only tested by antigen detection, (2) patients tested by both TF-PCR and XT-PCR, (3) patients tested outside of influenza season (June–August), and (4) pediatric patients. Institutional review board approval was obtained.
Data collection
Nasopharyngeal swabs for influenza testing were collected at the time of presentation at the discretion of clinicians. Tests were analyzed using TF-PCR or XT-PCR according to the manufacturer’s instructions. PCR influenza results, antimicrobial use, and vital signs were retroactively extracted from medical records using the TheraDoc surveillance system (Theradoc, Charlotte, NC).
Statistical analysis
Patients were divided into 2 cohorts based on diagnostic test: TF-PCR (2017–December 2019) or XT-PCR (December 2019–May 2020). Data were stratified based on admission status. Additionally, a nested model within admitted patients was created based on unit type, namely intensive care unit versus acute-care unit. The χ2 test was used to compare categorical variables. For continuous variables, the t test (equal variance) and the Satterthwaite test (unequal variance) were used. A P value < .05 was considered statistically significant. SAS software (SAS Institute, Cary, NC) was used for computations.
Results
Influenza status
Overall, 10,042 patients were tested for influenza and 1,891 individuals (18.8%) were positive. Of the 4,764 patients (47.4%) tested by TF-PCR, 816 (17.1%) were positive. The remaining 5,278 patients (52.6%) were tested by XT-PCR, yielding 1,075 (20.4%) positive results (Table 1).
Patient Demographic and Crude Outcome Data by Type of Influenza Diagnostic Test
Note. RT-PCR, rapid influenza reverse transcriptase polymerase chain reaction; TF-PCR, traditional influenza reverse transcriptase polymerase chain reaction; SD, standard deviation.
a Statistically significant findings at P value < .05 are shown in bold.
b Only patients that received antibiotics were included in denominator for calculations.
c Some patients received multiple antibiotics.
TAT and length of stay
On average, TAT decreased from 24.2 hours with TF-PCR to 2.0 hours with XT-PCR (P < .001). The admission rate within the TF-PCR group was 49.2% (2,346 of 4,764 patients) compared to 31.7% (1,671 of 5,278 patients) in the XT-PCR cohort (P < .001) (Table 1). The average LOS in influenza positive patients decreased from 2.5 days to 1.1 days (P < .001).
Oseltamivir use
Overall, oseltamivir use decreased from 20.3% in the TF-PCR cohort to 10.9% in the XT-PCR cohort (P < .001) (Table 1). For admitted, influenza-negative patients, oseltamivir administration rates decreased from 19.7% (399 of 2,022 patients) in the TF-PCR cohort to 1.6% (24 of 1,471 patients) in the XT-PCR cohort (P < .001) (Table 2). A greater decrease was observed in influenza-negative patients admitted to an intensive care unit. Of 348 patients in the TF-PCR cohort, 140 (40.2%) received oseltamivir compared to 6 of 220 (2.7%) patients in the XT-PCR group, representing a 174.8% reduction (P < .001) (Supplementary Table 2 online). Furthermore, the time interval from presentation to administration of the first dose of oseltamivir decreased from 15.2 hours in the TF-PCR group to 4.7 hours in the XT-PCR cohort (P < .001).
Effects of Implementing Rapid Influenza PCR on Antibiotic Administration and Oseltamivir Use Adjusted for Test Results (Negative Versus Positive), Stratified by Admission Status
Note. RT-PCR, rapid influenza reverse transcriptase polymerase chain reaction; TF-PCR, traditional influenza reverse transcriptase polymerase chain reaction; CI, confidence interval.
aStatistically significant findings at P < .05 are shown in bold.
Antibiotic use
Overall, antibiotic use decreased from 45.1% in the TF-PCR cohort to 16.6% in the XT-PCR cohort, representing a 63.2% decrease (P < .001) (Table 1). We observed decreases in azithromycin, doxycycline, and moxifloxacin use for patients tested by XT-PCR relative to TF-PCR (P < .05) (Table 1). The greatest reduction in antibiotic use occurred in the unadmitted, influenza positive cohort: 17.3% of patients (85 of 492 patients) tested by TF-PCR received antibiotics compared to 3.7% patients (32 of 875 patients) tested by XT-PCR (P < .001) (Table 2). A decrease in antibiotic use was also observed among admitted patients, regardless of unit type (P < .001) (Supplementary Table 2 online).
Discussion
Patients positive for influenza by XT-PCR received the first dose of oseltamivir 10.5 hours earlier than TF-PCR cohort counterparts, likely due to the significantly faster TAT of XT-PCR. Early initiation of antiviral treatment can reduce symptom severity and associated complications. Reference Aoki, Macleod and Paggiaro6 By controlling for modifiable influenza-related outcomes through XT-PCR testing, resources become available to care for the growing number of COVID-19 patients.
Additionally, the results demonstrated a statistically significant decrease in broad-spectrum respiratory antibiotics and oseltamivir use. Readily available PCR results from XpertFlu likely allowed clinicians to differentiate influenza from bacterial pneumonia and, thus, to make more judicious treatment decisions. Reference Steurer, Held and Spaar5 Eliminating unnecessary antibiotic prescriptions is of utmost importance as antimicrobial resistance continues to threaten modern medicine. Reference Steurer, Held and Spaar5 Moreover, a similar reduction of unnecessary treatments may extend to other respiratory infections with influenza-like presentations and concomitant pharmaceuticals, such as SARS-CoV-2 and remdesivir. Reference Jaklevic7,8
Our study had several limitations. First, the 2 influenza seasons differed by severity and illness burden. The Center for Disease Control and Prevention classified the 2017–2018 influenza season as highly severe, whereas the 2018–2019 influenza season was moderately severe. 1 This difference may have contributed to the higher admission and mortality rates in the TF-PCR cohort. Additionally, we excluded patients treated at the healthcare system’s pediatric hospital due to different testing guidelines, which may influence the generalizability of these findings to younger patient populations.
XT-PCR influenza testing allows for earlier initiation of antiviral treatment, thereby decreasing disease severity. Reference Aoki, Macleod and Paggiaro6 This association likely explains shorter LOS observed within the XT-PCR cohort. By reducing these outcomes, influenza-positive patients require fewer resources for clinical management. Increasing available resources as hospitals continue to face staff fatigue and unprecedented patient surges is critical during the COVID-19 pandemic. Reference Jaklevic7 Similar benefits of rapid testing would likely be observed in expedited SARS-CoV-2 testing because earlier antiviral treatment within this patient population correlates with better outcomes. Reference Wu, Li and Shi9 Notably, several companies have recently gained emergency approval from the Food and Drug Administration for rapid SARS-CoV-2 PCR testing. 10 In this report, we have presented favorable evidence for implementing XT-PCR for influenza testing, and we have provided data likely applicable for point-of-care testing for other viral illnesses.
Acknowledgments
Financial support
No financial support was provided relevant to this article.
Conflicts of interest
All authors report no conflicts of interest relevant to this article.
Supplementary material
To view supplementary material for this article, please visit https://doi.org/10.1017/ice.2021.86
