Fidaxomicin to prevent recurrent Clostridioides difficile: what will it cost in the USA and Canada?

Importance: Recent changes in guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as a first-line treatment. Objective: To estimate the net cost of first-line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving for the prevention of recurrence. Data sources and study selection: We identified randomized, placebo-controlled trials directly comparing fidaxomicin with vancomycin that reported on recurrence. Medication costs were obtained from the Veterans Affairs Federal Supply Schedule (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country. Data extraction synthesis and outcome measures: For efficacy, data on CDI recurrence at day 40 were pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect May 2022 dollars. These were used to estimate the net cost per recurrence prevented with fidaxomicin and the price point below which fidaxomicin would be cost saving. Results: The estimated mean system costs of a CDI recurrence were $15 147USD and $8806CAD, respectively. Preventing one recurrence by using first-line fidaxomicin over vancomycin would cost $38 222USD (95%CI $30 577-$57 332) and $13 760CAD (95%CI $11 008-$20 640), respectively. The probability that fidaxomicin was cost saving exceeded 95% if priced below $1140USD or $860CAD, respectively. Conclusions and Relevance: An increased drug expenditure on fidaxomicin may not be offset through recurrence prevention unless the fidaxomicin price is negotiated.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

Assessment of Piperacillin-Tazobactam-Meropenem Synergy against Serine Carbapenemase-Producing Enterobacterales Using Time-Kill Assays.

Synergy between piperacillin-tazobactam and meropenem against KPC-producing Klebsiella pneumoniae was recently demonstrated. We sought to test the combination against a broader range of serine carbapenemase producers. We tested the combination against 10 KPC-producing Escherichia coli and 10 OXA-48 family-producing K. pneumoniae isolates. Antibiotic concentrations used are achievable in critically ill patients. The combination was synergistic against 7 of 10 KPC producers and 9 of 10 OXA-48 producers. There was no synergy detected in control isolates producing NDM-1.

Hepatitis B testing practices at a tertiary care centre and their associated costs: A retrospective analysis.

BACKGROUND: Hepatitis B is a viral infection requiring specific serologic testing to diagnose the stage of the disease. There are many tests which can be ordered in a variety of combinations. This study aimed to assess routine Hepatitis B screening practices in a tertiary care centre and determine the diagnostic and economic benefits of protocolized ordering. METHODS: We evaluated all measurements of Hepatitis B total core antibodies, core IgM antibodies, surface antibodies and surface antigens performed at our institution between January 1, 2015 and December 31, 2015. We also recorded secondary testing (envelope antigens and antibodies, and viral DNA). Costs were estimated using provincial insurance reimbursement values. Using the subset of patients who received complete testing, we developed a reflexive screening protocol to minimize costs while simultaneously improving diagnostic utility. RESULTS: 30,335 hepatitis B tests were performed at an estimated total cost of $584,683. 53.9% of patients were screened with a single test. 29% of patients who received secondary testing had no evidence of exposure on primary testing. Using the protocol of initial testing of total core antibody and surface antibody with reflexive testing, we would save an estimated $181,632 (95% CI $154,201.90 -$208,910.50) per year while providing more complete information. INTERPRETATION: Screening practices for Hepatitis B are frequently inadequate to diagnose and stage the infection and often included unnecessary testing. Protocolization of Hepatitis B testing could limit this practice while resulting in significantly lower costs.

Evaluation of the cost-effectiveness of evolocumab in the FOURIER study: a Canadian analysis.

BACKGROUND: Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease. We also sought to estimate the price threshold at which evolocumab might be considered cost-effective for secondary prevention in Canada. METHODS: We calibrated the Cardio-metabolic Model, a well-validated tool for predicting cardiovascular events and life expectancy, to the reduction in nonfatal events seen in the FOURIER trial. Assuming that long-term treatment will eventually result in mortality benefits, we estimated YOLSs and cost per YOLS with evolocumab treatment plus a statin compared to a statin alone. We then estimated the annual drug costs that would provide a 50% chance of being cost-effective at willingness-to-pay values of $50 000 and $100 000. RESULTS: In secondary prevention in patients similar to those in the FOURIER study, evolocumab treatment would save an average of 0.34 (95% confidence interval [CI] 0.27-0.41) life-years at a cost of $101 899 (95% CI $97 325-$106 473), yielding a cost per YOLS of $299 482. We estimate that to have a 50% probability of achieving a cost per YOLS below $50 000 and $100 000 would require annual drug costs below $1200 and $2300, respectively. INTERPRETATION: At current pricing, the use of evolocumab for secondary prevention is unlikely to be cost-effective in Canada.

Mindfulness-Based Laboratory Reduction: Reducing Utilization Through Trainee-Led Daily 'Time Outs'.

BACKGROUND: Overuse of laboratory investigations is widely prevalent in hospitalized patients, leads to discomfort, and increases direct and indirect costs. OBJECTIVE: We implemented a simple, inexpensive, mindfulness strategy on our inpatient medical clinical teaching unit to reduce unnecessary laboratory orders through education, a forcing function, and daily structured laboratory "time outs." METHODS: On a 26-bed unit in an academic hospital center, the per-period laboratory costs per patient were compared pre- and postintervention using segmented regression analysis of an interrupted time series. RESULTS: The average cost per admitted patient decreased from $117 to $66, with an estimated savings of $50,657 over 985 admissions. After adjusting for fiscal period and the presence of our intervention, there was a significant reduction in the per-patient number of total tests, complete blood counts, and electrolyte panels performed (P <.001 for all level and time trend changes). CONCLUSION: This trainee-designed and -led intervention, centered around structured, mindfulness-based laboratory test ordering, was successful at decreasing the overuse of common daily blood work in hospitalized patients.

Antibiotic self-stewardship: trainee-led structured antibiotic time-outs to improve antimicrobial use.

BACKGROUND: Antibiotic use is an important quality improvement target. Nearly 50% of antibiotic use is unnecessary or inappropriate. To combat overuse, the Centers for Disease Control and Prevention (CDC) proposed "time-outs" to reevaluate antibiotics. OBJECTIVE: To optimize antibiotic use through trainee-led time-outs. DESIGN: Before-after study. SETTING: Internal medicine (2 units, 46 beds) at a university hospital. PATIENTS: Inpatients (n = 679). INTERVENTION: From January 2012 until June 2013, while receiving monthly education on antimicrobial stewardship, resident physicians adjusted patients' antibiotic therapy through twice-weekly time-out audits using a structured electronic checklist. MEASUREMENTS: Antibiotic costs were standardized and compared in the year before and after the audits. Use was measured as World Health Organization defined daily doses (DDDs) per 1000 patient-days. Total antibiotic use and the use of moxifloxacin, carbapenems, antipseudomonal penicillins, and vancomycin were compared by using interrupted time series. Rates of nosocomial Clostridium difficile infection were compared by using incidence rate ratios. RESULTS: Total costs in the units decreased from $149,743CAD (January 2011 to January 2012) to $80,319 (January 2012 to January 2013), for a savings of $69,424 (46% reduction). Of the savings, $54,150 (78%) was related to carbapenems and $15,274 (22%) was due to other antibiotic classes. Adherence with the auditing process was 80%. In the time-series analyses, the only reliable and statistically significant change was a reduction in the rate of moxifloxicin use, by -1.9 DDDs per 1000 patient-days per month (95% CI, -3.8 to -0.02; P = 0.048). Rates of C. difficile infection decreased from 24.2 to 19.6 per 10,000 patient-days (incidence rate ratio, 0.8 [CI, 0.5 to 1.3]). LIMITATION: Other temporal factors may confound the findings. CONCLUSIONS: An antibiotic self-stewardship bundle to implement the CDC's suggested time-outs seems to have reduced overall costs and targeted antibiotic use. PRIMARY FUNDING SOURCE: None.