Incidence of transaminitis in adults with cystic fibrosis taking elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator modulators are a cornerstone of CF treatment. However, many patients develop CF liver disease (CFLD) over time, and previous data indicate a risk for transaminase elevation with modulator use. Elexacaftor/tezacaftor/ivacaftor is a commonly prescribed modulator with broad efficacy among CF genomic profiles. Theoretically, elexacaftor/tezacaftor/ivacaftor drug-induced liver injury could exacerbate and further worsen CFLD, but holding modulators can cause a decline in clinical status. OBJECTIVES: This study was designed to determine the real-world incidence of transaminase elevations in adult patients with CF taking elexacaftor/tezacaftor/ivacaftor. METHODS: This exploratory, retrospective descriptive study included all adults with CF-prescribed elexacaftor/tezacaftor/ivacaftor at our institution's outpatient CF clinic. We explored transaminase elevations in 2 separate outcomes: incidence of transaminase elevations of more than 3 times the upper limit of normal (ULN), and transaminase elevations of 25% or more above baseline. RESULTS: 83 patients were prescribed elexacaftor/tezacaftor/ivacaftor. Nine patients (11%) experienced an elevation of more than 3 times ULN and 62 (75%) experienced an elevation of 25% or more above baseline. The median days to transaminase elevation were 108 and 135 days, respectively. Therapy was not discontinued due to transaminase elevations in any of the patients. CONCLUSION: Transaminase elevations among adults taking elexacaftor/tezacaftor/ivacaftor were common but did not result in discontinuation of therapy. Pharmacists should be reassured of the liver safety profile of this important medication for patients with CF.

Impact of Accelerate Pheno and BacT/Alert Virtuo on Clinical Processes and Outcomes in Patients with Sepsis and Concurrent Gram-Negative Bacteremia.

The Accelerate Pheno and BacT/Alert Virtuo systems may improve bacteremia management. Here, we evaluated the impact of both devices on outcomes in patients with sepsis and concurrent Gram-negative bacteremia. This quasiexperimental study included a retrospective preimplementation and a prospective postimplementation group. Patients ≥18 years old with Gram-negative bacteremia were included. Patients with neutropenia, pregnant patients, those who were transferred from an outside hospital with active bloodstream infections, and those with polymicrobial bacteremia were excluded. Blood culture incubation in the BacT/Alert 3D device and microdilution antimicrobial susceptibility testing from culture plate growth were used prior to implementation of the BacT/Alert Virtuo and Accelerate Pheno systems. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) identification directly from blood culture was used pre- and postimplementation. Time to Gram stain results, identification, susceptibility reporting, initiation of narrow-spectrum Gram-negative therapy at 72 h, 30-day inpatient mortality, sepsis resolution, and length of hospital stay were evaluated. A total of 116 patients were included (63 preimplementation, 53 postimplementation). Median times to Gram stain and susceptibility results were significantly shorter postimplementation (P < 0.001). The postimplementation group had an improved hazard ratio for narrow-spectrum Gram-negative therapy at 72 h (hazard ratio [HR], 2.685 [95% confidence interval {CI}, 1.348 to 5.349]), a reduced hazard ratio for 30-day inpatient mortality (adjusted HR [aHR], 0.150 [95% CI, 0.026 to 0.846]), and improved sepsis resolution (92.5% versus 77.8% [P = 0.030]). The length of hospital stay was unchanged after implementation. We conclude that implementation of the BacT/Alert Virtuo and Accelerate Pheno systems improved microbiology laboratory processes, antibiotic utilization processes, and clinical outcomes. These data support the use of rapid diagnostics in sepsis with concurrent Gram-negative bacteremia.

Time to clinical response in sepsis associated with an algorithm for blood-culture pathogen identification using matrix-assisted laser desorption ionization time-of-flight mass spectroscopy.

PURPOSE: Antimicrobial stewardship programs (ASPs) can be aided by using rapid diagnostics (RDT). However, there are limited data evaluating the impact of ASPs and RDT on sepsis outcomes in the setting of the new Sepsis-3 guidelines. This study evaluates the impact of a low-resource method for ASPs with RDT on sepsis outcomes. METHODS: This was a prospective, quasi-experimental study with a retrospective double pretest. Patients ≥ 18 years old with sepsis and concurrent bacteremia or fungemia were included; patients who were pregnant, had polymicrobial septicemia or who were transferred from an outside hospital were excluded. In the first pretest (O1), polymerase chain reaction was used to identify Staphylococcal species from positive blood cultures, and traditional laboratory techniques were used to identify other species. Matrix-assisted laser desorption ionization time-of-flight mass spectroscopy and FilmArray were implemented in the second pretest (O2), and twice daily blood culture review was implemented in the posttest (O3). RESULTS: A total of 394 patients (157 in O1, 176 in O2, 61 in O3) were enrolled. Clinical response was 73.2%, 83.5%, and 88.5% in O1, O2, and O3, respectively, p = 0.013. By Cox regression, the O3 was associated with improved time to clinical response (hazard ratio, 1.388; 95% confidence interval, 1.004-1.919) as compared with O1. Mortality, hospital length of stay, and intensive care unit length of stay were unchanged between groups. CONCLUSION: Twice-daily blood culture review may be useful for implementing rapid diagnostics within low-resource ASPs. Further research is needed to identify the optimal method of blood culture follow-up within low-resource settings.