Pharmacokinetics of ampicillin during venovenous extracorporeal membrane oxygenation: A case report.

The presence of extracorporeal membrane oxygenation (ECMO) in addition to underlying critical illness can affect the pharmacokinetics and pharmacodynamics of drugs that are often required to treat this patient population. While ampicillin is the preferred agent for the treatment of susceptible Enterococcus faecalis infections, there are no in vivo pharmacokinetic studies regarding ampicillin dosing in patients receiving ECMO. This case report consists of two patients on venovenous ECMO with E. faecalis bloodstream infections in which ampicillin serum concentrations were measured. Pharmacokinetic parameters were calculated using a one compartment open model. Ampicillin trough levels were 5.87 and 39.2 mg/L for patients A and B, respectively. Based on these results, ampicillin concentrations were found to be above the minimum inhibitory concentration (MIC) for 100% of the dosing interval. The findings of this case report demonstrate that therapeutic concentrations of ampicillin can be obtained in patients on ECMO and therapeutic drug monitoring can be utilized to ensure adequate serum concentrations are achieved.

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.

Enhanced Detection of Community-Acquired Pneumonia Pathogens With the BioFire® Pneumonia FilmArray® Panel.

BACKGROUND: Although most observational studies identify viral or bacterial pathogens in 50% or less of patients hospitalized with community-acquired pneumonia (CAP), we previously demonstrated that a multi-test bundle (MTB) detected a potential pathogen in 73% of patients. This study compares detection rates for potential pathogens with the MTB versus the Biofire® Pneumonia FilmArray® panel (BPFA) multiplex PCR platform and presents an approach for integrating BPFA results as a foundation for subsequent antibiotic stewardship (AS) activities. METHODS: Between January 2017 to March 2018, all patients admitted for CAP were enrolled. Patients were considered evaluable if all elements of the MTB and the BPFA were completed, and they met other a priori inclusion criteria. The primary endpoint was the percentage of potential pathogens detected using the MTB (8 viral and 6 bacterial targets) versus the BPFA (8 viral and 18 bacterial targets). Blood and sputum cultures were performed on all patients. Two or more procalcitonin (PCT) levels assisted clinical assessments as to whether detected bacteria were invading or colonizing. RESULTS: Of 585 enrolled patients, 274 were evaluable. A potential viral pathogen was detected in 40.5% with MTB versus 60.9% of patients with BPFA with an odds ratio (95% CI) of 9.00 (4.12 to 23.30) p<0.01. A potential bacterial pathogen was identified in 66.4% with the MTB vs 75.5% with the BPFA odds ratio (95% CI) of 2.09 (1.24 to 3.59), p 0.003). Low PCT levels helped identify detected bacteria as colonizers.