Clinical Outcomes of Treated and Untreated C. difficile PCR-Positive/Toxin-Negative Adult Hospitalized Patients: a Quasi-Experimental Noninferiority Study.

Clostridioides difficile infection (CDI) is routinely diagnosed by PCR, with or without toxin enzyme immunoassay testing. The role of therapy for positive PCR and negative toxin remains unclear. The objective of this study was to determine whether clinical outcomes of PCR+/cycle threshold-based toxin (CT-toxin)- individuals vary by result reporting and treatment strategy. We performed a quasiexperimental noninferiority study comparing clinical outcomes of PCR+/CT-toxin- individuals by reporting PCR result only (most patients treated) with reporting CT-toxin result only (most patients untreated) in a single-center, tertiary academic hospital. The primary outcome was symptomatic PCR+/CT-toxin+ conversion at 8 weeks. Secondary outcomes included 7-day diarrhea resolution, hospital length of stay, and 30-day all-cause mortality. A total of 663 PCR+/CT-toxin- test results were analyzed from 632 individuals with a median age of 61 years (interquartile range [IQR], 44 to 72) and 50.4% immunocompromised. Individuals in the preintervention group were more likely to have received CDI therapy than those in the intervention group (91.5 versus 15.1%; P < 0.001). Symptomatic toxin conversion at 8 weeks and hospital length of stay failed to establish the predefined thresholds for noninferiority. Lack of diarrhea resolution at 7 days and 30-day all-cause mortality was similar and established noninferiority (20.0 versus 13.7%; adjusted odds ratio [aOR], 0.57; 90% confidence interval [CI], 0.32 to 1.01; P = 0.1; and 8.6 versus 6.5%; aOR, 0.46; 90% CI, 0.20 to 1.04; P = 0.12). These data support the safety of withholding antibiotics for selected hospitalized individuals with suspected CDI but negative toxin.

Dual Reporting of Clostridioides difficile PCR and Predicted Toxin Result Based on PCR Cycle Threshold Reduces Treatment of Toxin-Negative Patients without Increases in Adverse Outcomes.

Nucleic acid amplification tests are commonly used to diagnose Clostridioides difficile infection (CDI). Two-step testing with a toxin enzyme immunoassay is recommended to discriminate between infection and colonization but requires additional resources. Prior studies showed that PCR cycle threshold (CT ) can predict toxin positivity with high negative predictive value. Starting in October 2016, the predicted toxin result (CT-toxin) based on a validated cutoff was routinely reported at our facility. To evaluate the clinical efficacy of this reporting, all adult patients with positive GeneXpert PCR results from October 2016 through October 2017 underwent a chart review to measure the recurrence of or conversion to a CT-toxin+ result and 30-day all-cause mortality. There were 482 positive PCR tests in 430 unique patients, 282 CT-toxin+ and 200 CT-toxin- Patient characteristics were similar at testing, though CT-toxin+ patients had higher white blood cell (WBC) counts (12.5 × 103 versus 9.3 × 103 cells/µl; P = 0.001). All cases (n = 21) of fulminant CDI had a CT-toxin+ result. Index CT-toxin+ patients were significantly more likely to have a CT-toxin+ result within 90 days than CT-toxin- patients (17.4% [n = 49] versus 8.0% [n = 16], respectively; P = 0.003). Thirty-day all-cause mortality was higher in CT-toxin- patients (11.1% versus 6.8%; P = 0.1), though no deaths in CT-toxin- patients were directly attributable to CDI. Of the 200 CT-toxin- patients, 51.5% (n = 103) were treated for CDI. The rates of conversion to a CT-toxin+ result (8.8% versus 7.2%; P = 0.8) and all-cause mortality (8.8% versus 13.4%; P = 0.3) were similar between treated and untreated CT-toxin- patients, respectively. CT -based toxin prediction may identify patients at higher risk for CDI-related complications and reduce treatment among CT-toxin- patients.

Low Yield of FilmArray GI Panel in Hospitalized Patients with Diarrhea: an Opportunity for Diagnostic Stewardship Intervention.

The FilmArray GI panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex, on-demand, sample-to-answer, real-time PCR assay for the syndromic diagnosis of infectious gastroenteritis that has become widely adopted and, in some instances, has replaced conventional stool culture and parasite exams. Conventional testing has historically been restricted among hospitalized patients due to low diagnostic yield, but it is not known whether use of the FilmArray GI panel should be circumscribed. Cary-Blair stool samples submitted for FilmArray GI panel in adult patients admitted to an academic hospital from August 2015 to January 2017 were included in this study. Of 481 tests performed >72 h after admission, 29 (6.0%) were positive, all for a single target, excluding Clostridium difficile When follow-up tests beyond the first positive per hospitalization were excluded, 20 (4.8%) of 414 tests were positive. There was no difference in yield by immune status. Most targets detected were viral (79% of all positives [n = 23] and 70% in unique patients [n = 14]). All four cases positive for a bacterial target could not be confirmed and presentation was atypical, suggesting possible false positives. After removing potential false positives and chronic viral shedders, the yield was 3.0% (12/406). Repeat testing performed >72 h after admission and following a negative result within the first 72 h was done in 19 patients and 100% (22/22) remained negative. The FilmArray GI panel has low yield in adult patients hospitalized for >72 h, similar to conventional stool microbiology tests, and it is reasonable to restrict its use in this population.

Is Follow-Up Testing with the FilmArray Gastrointestinal Multiplex PCR Panel Necessary?

The FilmArray gastrointestinal (GI) panel (BioFire Diagnostics, Salt Lake City, UT) is a simple, sample-to-answer, on-demand, multiplex, nucleic acid amplification test for syndromic diagnosis of infectious gastroenteritis. The aim of this study was to measure the yield of follow-up testing with FilmArray GI panel within 4 weeks of an initial test. Consecutive adult and pediatric patients tested at an academic institution between August 2015 and June 2016 were included in this study. Of 145 follow-up tests in 106 unique patients with an initial negative result, 134 (92.4%) tests and 98 (92.5%) patients remained negative upon follow-up testing. Excluding targets that are not reported at this institution (Clostridium difficile, enteroaggregative Escherichia coli, enteropathogenic E. coli, and enterotoxigenic E. coli), 137 (94.5%) follow-up tests and 101 (95.3%) patients remained negative. Weekly conversion rates were not significantly different across the 4-week follow-up interval. No epidemiological or clinical factors were significantly associated with a negative to positive conversion. Of 80 follow-up tests in patients with an initial positive result, 43 (53.8%) remained positive for the same target, 34 (42.5%) were negative, and 3 were positive for a different target (3.8%). Follow-up testing with FilmArray GI panel within 4 weeks of a negative result rarely changed the initial result, and the follow-up test reverted to negative less than half the time after an initial positive result. In the absence of clinical or epidemiological evidence for a new infection, follow-up testing should be limited and FilmArray GI panel should not be used as a test of cure.

Effective Approaches to Diagnostic Stewardship of Syndromic Molecular Panels.

BACKGROUND: Syndromic molecular panels for the diagnosis of gastroenteritis, meningitis/encephalitis, and pneumonia are becoming routinely used for patient care throughout the world. CONTENT: These rapid, sample-to-answer assays have great potential to improve patient care, infection control, and antimicrobial stewardship. However, diagnostic stewardship is essential for their optimal use and accuracy, and interventions can be applied at all phases of the diagnostic process. SUMMARY: The aim of this review article is to describe effective approaches to diagnostic stewardship for syndromic molecular panels to ensure appropriate test utilization and quality assured results.

Impact of cascade reporting of antimicrobial susceptibility on fluoroquinolone and meropenem consumption at a Veterans' Affairs medical center.

OBJECTIVE: To determine whether cascade reporting is associated with a change in meropenem and fluoroquinolone consumption. DESIGN: A quasi-experimental study was conducted using an interrupted time series to compare antimicrobial consumption before and after the implementation of cascade reporting. SETTING: A 399-bed, tertiary-care, Veterans' Affairs medical center. PARTICIPANTS: Antimicrobial consumption data across 8 inpatient units were extracted from the Center for Disease Control and Prevention (CDC) National Health Safety Network (NHSN) antimicrobial use (AU) module from April 2017 through March 2019, reported as antimicrobial days of therapy (DOT) per 1,000 days present (DP). INTERVENTION: Cascade reporting is a strategy of reporting antimicrobial susceptibility test results in which secondary agents are only reported if an organism is resistant to primary, narrow-spectrum agents. A multidisciplinary team developed cascade reporting algorithms for gram-negative bacteria based on local antibiogram and infectious diseases practice guidelines, aimed at restricting the use of fluoroquinolones and carbapenems. The algorithms were implemented in March 2018. RESULTS: Following the implementation of cascade reporting, mean monthly meropenem (P =.005) and piperacillin/tazobactam (P = .002) consumption decreased and cefepime consumption increased (P < .001). Ciprofloxacin consumption decreased by 2.16 DOT per 1,000 DP per month (SE, 0.25; P < .001). Clostridioides difficile rates did not significantly change. CONCLUSION: Ciprofloxacin consumption significantly decreased after the implementation of cascade reporting. Mean meropenem consumption decreased after cascade reporting was implemented, but we observed no significant change in the slope of consumption. cascade reporting may be a useful strategy to optimize antimicrobial prescribing.

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

OBJECTIVES: Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin. METHODS: A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective. RESULTS: For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs. CONCLUSIONS: Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

Effect of rapid methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction screening on vancomycin use in the intensive care unit.

PURPOSE: To determine the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screen on vancomycin duration in critically ill patients with suspected pneumonia. METHODS: This was a retrospective, quasi-experimental study at a 613-bed academic medical center with 67 intensive care beds. Adult patients admitted to the intensive care unit (ICU) between 2017 and 2019 for 24 hours or longer and empirically started on intravenous vancomycin for pneumonia were included. The primary intervention was the implementation of a MRSA nasal PCR screen protocol. The primary outcome was duration of empiric vancomycin therapy. Secondary outcomes included the rate of acute kidney injury (AKI), the number of vancomycin levels obtained, the rate of resumption of vancomycin for treatment of pneumonia, ICU length of stay, hospital length of stay, the rate of ICU readmission, and the rate of in-hospital mortality. RESULTS: A total of 418 patients were included in the final analysis. The median vancomycin duration was 2.59 days in the preprotocol group and 1.44 days in the postprotocol group, a reduction of approximately 1.00 day (P < 0.01). There were significantly fewer vancomycin levels measured in the postprotocol group than in the preprotocol group. Secondary outcomes were similar between the 2 groups, except that there was a lower rate of AKI and fewer vancomycin levels obtained in the postprotocol group (despite implementation of area under the curve-based vancomycin dosing) as compared to the preprotocol group. CONCLUSION: The implementation of a pharmacist-driven MRSA nasal PCR screen was associated with a decrease in vancomycin duration and the number of vancomycin levels obtained in critically ill patients with suspected pneumonia.

Reproducibility of positive results for rare pathogens on the FilmArray GI Panel.

Though the FilmArray GI Panel has a reported aggregate specificity and reproducibility of >97% and > 99%, respectively, the reproducibility is less understood in clinical practice. We measured the reproducibility of positive results for low-prevalence pathogens. Samples with positive results for selected targets were repeated using a different FilmArray module. Overall, 331 of 373 (89%) results were reproducible. Giardia lamblia (57/57, 100%), Cryptosporidium spp. (61/63, 97%), Cyclospora cayetanensis (34/35, 97%), Plesiomonas shigelloides (17/18, 94%), and Rotavirus A (76/77, 99%) were highly reproducible, while Adenovirus F40/41 (38/54, 70%), Vibrio spp. (8/10, 80%), V. cholerae (3/8, 37.5%), and Yersinia enterocolitica (36/50, 72%) were poorly reproducible. Review of 38 patients with nonreproducible results showed that 19 (50%) had evidence of gastroenteritis and only 6 (16%) had possible infection with the organism that showed a nonreproducible result. Higher false-positive rates with certain targets on FAGP emphasize the need for diagnostic stewardship.