Introduction
Norovirus is a highly infectious virus causing up to 12.5–60 cases of gastroenteritis per 1,000-person-years. Reference Carlson, Dilley and O’Grady1 In outbreak scenarios, the attack rate has been reported up to 53.2% for patients and 24.5% for healthcare providers. Reference Carlson, Dilley and O’Grady1 From 2009 to 2013, of 2,475 reported outbreaks, 144 (3.6%) occurred in hospital facilities. Reference Vega, Barclay and Gregoricus2 Patients with cancer may experience prolonged symptoms, duration of shedding or more severe infections and may require longer periods of contact isolation. Moreover, side effects of anti-neoplastic therapy such as diarrhea, nausea, or vomiting share similar presentations to norovirus infection, clouding diagnosis. Reference Kondapi, Ramani and Estes3 False-positive results can lead to downstream effects including overtreatment, reduced patient satisfaction due to unnecessary isolation precautions, increased healthcare costs, exposure to potential side effects or toxicity from unnecessary therapeutics, and inappropriate resource utilization. They also may lead to diagnostic delays, such as gastrointestinal graft-versus-host disease in hematopoietic cell transplant recipients, adverse events from chemotherapeutics, or other infectious causes of diarrhea.Reference Kondapi, Ramani and Estes 3
Treatment options for norovirus are limited; reduction of immunosuppression is a mainstay. Reference Kondapi, Ramani and Estes3 For many, it may not be feasible or have potential adverse consequences. Other options, such as oral immunoglobulin or nitazoxanide, have limited, conflicting, and mostly anecdotal data demonstrating efficacy. Reference Florescu, Hermsen and Kwon4,Reference Rossignol and El-Gohary5 More recently, a phase 2, prospective, double-blind, multi-center, randomized control trial sponsored by the National Institutes of Health in patients with solid organ or bone marrow transplantation failed to show a reduction in duration of clinical symptoms or time to negative viral load. Reference Boutin, Callegari and Florescu6 Nevertheless, nitazoxanide is often employed in patients with norovirus infection and has an estimated cost of up to $3,944 in retail US pharmacies for a 14-day course. Reference Kondapi, Ramani and Estes3,Reference Pepperrell, Pilkington and Owen7
Healthcare facilities employ multiplex polymerase chain reaction (PCR) panels of stool samples to identify infectious causes of diarrhea. For some assays, norovirus false-positive rates were reported up to 27%–36%. Reference Matic, Lawson and Young8,Reference Caza, Kuchinski and Locher9 Additionally this rate may be higher in specialized cancer centers and associated with cross-reactivity with gut microbiota. Reference Reed, Mauer and Mack10 This potential high rate carries significant far-reaching implications for patient care, inappropriate utilization of Infection Control Program (ICP) resources, and unnecessary financial expenditures. In this longitudinal quality improvement initiative, we aimed to improve the diagnosis of norovirus and reduce nitazoxanide utilization by 40% compared to fiscal year (FY) 25 (09/2024-08/2025), measured as doses administered per 1,000 patient-days over a 6-month period.
Methods
A multi-disciplinary team including members from Infectious Diseases, Infection Control, Antimicrobial Stewardship, Clinical Microbiology, and Pharmacy was formed at an NCI-designated comprehensive cancer center to evaluate nitazoxanide utilization, develop an interventional initiative and monitor key performance metrics over a 6-month period between 11/01/2025 and 04/22/2026. This was part of a longitudinal Clinical Safety & Effectiveness Program supported by the Office of Performance Improvement under the Chief Quality Office at the institution. A cause-and-effect diagram (Supplemental Figure 1) and process flowchart (Supplemental Figure 2) detail this investigation and workflow prior to the intervention. A process flowchart of the intervention is shown in Figure 1.
Flowchart of the quality improvement intervention.
Testing platforms and intervention
The Biofire ® FilmArray ® gastrointestinal (GI) multiplex PCR panel (GIMP) (bioMérieux, Marcy-l’Étoile, France) is the predominant testing platform used at our institution to diagnose norovirus. This test is performed internally with a rapid turnaround time (TAT) within a couple of hours. In the study, GIMP samples positive for norovirus were sent for a separate confirmatory standalone PCR test at a reference lab (Eurofins Viracor, Lenexa, KS) with an average TAT of 3.21 days. Positive sample results for norovirus by multiplex PCR were not released into the electronic medical record (EMR), but a comment was reported guiding clinicians to refer to separate confirmatory testing.
Infection control
Patients were kept under contact isolation while awaiting confirmatory testing if the GIMP detected norovirus. If confirmatory testing was negative, then contact isolation could be removed. Days of contact isolation were tracked, and clinical norovirus infections were monitored.
Key performance metrics and return on investment
Administrations, or doses, of nitazoxanide were measured through the EMR and compared with prior quarters of FY25. A control chart was utilized to monitor the impact of changes, and rates of discordant testing were analyzed. A return on investment was calculated by measuring costs of increased testing with potential savings from drug costs and reduction of resources used in contact isolation (eg. gowns, gloves).
Results
During the study period, 1,677 GIMP tests were performed in 1,319 unique patients (range 1–9 tests per patient) with 122 (7.3%) detecting norovirus. Of these 115 (94.3%) were in the inpatient setting and the remaining 7 collected outpatient. These were submitted for confirmatory testing. Testing was discordant in 85 (69.7%) samples. There were 148 administrations of nitazoxanide over 133,230 patient-days present, with a rate of 1.11 administrations/1,000 days present compared to 7.13 administrations/1,000 days present over FY25. This calculated an 84.4% reduction and predicted approximately 1,690 administrations avoided over a year compared to FY25. A control chart is included (Figure 2). At the average wholesale price of $165.21 per tablet, 11 $279,204.90 in annualized drug cost savings is estimated. On average, patients with concordant testing were under contact isolation for 5.37 days compared to 4.93 days with discordant testing, estimating approximately $6,770.26 in annual savings from personal protective equipment (PPE) materials. This was calculated based on an internal cost estimate of $85.80/day for gowns and gloves based on a cost of $0.65 for 1 gown and 1 set of gloves and a measured median 5.5 entries per hour. An institutional cost was incurred due to the additional standalone PCR testing, but accounting for this would yield a return on investment of approximately 517%.
Control chart of nitazoxanide utilization. Upper confidence level and lower confidence level presented at 2 standard deviations.
Discussion
The GIMP provides tremendous advantages, most importantly rapid testing of potential pathogens. Crucially, this may diagnose patients, provide interventional opportunities, and appropriate ICP measures, which are more critical in immunocompromised populations. For norovirus, a false positive test may lead to overtreatment, healthcare system and utilization costs, or unnecessary infection control resources. Standalone PCRs in conjunction with a multiplex PCR platform may remedy these issues and allow for intervention for alternative pathogens but may not be generalizable to other testing platforms. Additional limitations may be the potential higher rate of discordant testing in a specialized oncologic patient population and seasonal variations in norovirus incidence. While no other intervention occurred prior to this quality improvement project, a pilot study of tandem testing in cellular therapy patients to support this quality improvement initiative found a high-level of discordant testing. Reference Handley, Borjan and Vuong12 This general awareness of a potential high-level of discordant testing results, seasonal variations, or other unknown factors may have contributed to a potential start of decrease in utilization prior to the implementation of the quality improvement initiative. However, an automated and standardized lab-based intervention will have more sustained effectiveness than general educational initiatives. Limitations include additional test costs and increased TAT. For norovirus, there is very low patient risk in waiting for confirmation, as randomized trial data have not demonstrated efficacy of nitazoxanide, and the mainstay of treatment is supportive care. While generally well tolerated, potential gastrointestinal side effects, headache or chromaturia should be considered. The average TAT from sample collection to result in our population was 3.21 days compared to 0.16 days for the multiplex PCR, but internal testing could decrease this window, but with increased overhead costs. In the 85 patients with discordant testing, there was an estimated unrealized savings of $23,410.53 accounting for PPE expended while awaiting confirmatory testing; however, overall by implementation of this process (Figure 1), we estimate greater than $285,000 in annual savings.
High attack rates require strict infection control measures. In the case of true infections, an outbreak would be unacceptable. We ensured isolation precautions were maintained pending testing. None of the 85 patients developed clinical norovirus infection within the 60 days following test submission, and no outbreaks were detected during the study period at our institution. Our PPE cost savings were modest, in part due to the testing TAT. Additionally, patients with cancer have increased rates of concomitant organisms requiring contact isolation such as extended beta-lactamase producers, vancomycin-resistant enterococcus, or Clostridioides difficile. They may have ongoing diarrhea from medications, other infections, or their underlying malignancy, which can prolong the contact isolation period. In populations where these factors are less frequent, cost savings may be greater. This study demonstrates the effectiveness, antimicrobial stewardship, and cost savings of a multidisciplinary quality improvement initiative to enhance the diagnosis of norovirus in patients with cancer, without compromising patient care or placing patients or healthcare staff at risk of nosocomial spread of infection.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ice.2026.10605.
Acknowledgments
None.
Financial support
No external financial support was received for this quality improvement initiative.
Competing interests
JB reports advisory roles with Invivyd and consulting roles with bioMérieux. AA receives research support from Sanofi; has received consulting fees or participated in advisory boards for CSL Berring, Sanofi, and Incyte Corp.; has served as a speaker for Therakos; and serves on the adjudicating committee for Orca Bio and the DSMB for the Chronic GVHD Consortium. MB reports consulting roles for bioMérieux and advisory roles for Eurofins Viracor. RFC received research grants paid to his institution from the NIH/NCI (RO1), Aicuris, Ansun Biopharma, Genentech, Karius, Symbio, Merck and Co., Oxford Immunotec, Pulmotect, Takeda, and Eurofins Viracor and honoraria/consulting fees from Ansun Biopharma, Merck and Co./MSD, Oxford Immunotec, Takeda, Shionogi, Assembly Bio, IntegerBio, Symbio, InflaRx, Gilead, Pfizer, Moderna, Invyvid, Eurofins Viracor, and Karius. GH, CTW, AF, PM, AM, SC, NV, JA, and AS have no reported conflicts of interest to report.
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