The impact of implementing an antifungal stewardship with monitoring of 1‐3, β‐D‐glucan values on antifungal consumption and clinical outcomes

Ito-Takeichi, Syuri; Niwa, Takashi; Fujibayashi, Ayasa; Suzuki, Keiko; Ohta, Hiroyuki; Niwa, Ayumi; Tsuchiya, Mayumi; Yamamoto, Masayo; Hatakeyama, Daijiro; Suzuki, Akio; Baba, Hisashi; Murakami, Nobuo; Itoh, Yoshinori

doi:10.1111/jcpt.12809

Cited by 14 publications

(25 citation statements)

References 26 publications

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“…When available, such a rapid test could decrease the time to more targeted therapy, which positively impacts patient outcomes including length of hospitalization and mortality [ 27 – 29 ]. It could also promote improved antimicrobial stewardship by reducing the amount of time a patient is exposed to inappropriate antimicrobials [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

et al. 2021

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Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. Methods In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. Results Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). Conclusions Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

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Section: Introductionmentioning

confidence: 99%

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

et al. 2021

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“…A few other studies have shown significant decrease in costs [ 26 , 30 ] and adverse events [ 31 ], without a different impact on survival. However, some of them identified a very small sample size [ 30 , 32 ], and most of them focused on optimizing only high-cost antifungal treatment [ 26 ]. Few studies incorporated therapeutic drug monitoring (TDM) measurement into AFS programs.…”

Section: Discussionmentioning

confidence: 99%

“…Several papers have previously demonstrated a very high negative predictive value of BDG, and clinicians can use a negative result to discontinue empiric antifungal therapy. However, only one published study has shown results on the implementation of BDG within AFS programs [ 32 ]. In the present study, negative BDG results were used to discontinue antifungals in 14 of 43 patients in the intervention phase (32.5%).…”

Section: Discussionmentioning

confidence: 99%

Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis

et al. 2021

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Background and Objectives: Overtreatment with antifungal drugs is often observed. Antifungal stewardship (AFS) focuses on optimizing the treatment for invasive fungal diseases. The objective of the present study was to evaluate the utility of a post-prescription audit plus beta-D-glucan (BDG) assessment on reducing echinocandin use in persons with suspected invasive candidiasis. Materials and Methods: This is a prospective, pre-post quasi-experimental study of people starting echinocandins for suspected invasive candidiasis. The intervention of the study included review of each echinocandin prescription and discontinuation of treatment if a very low probability of fungal disease or a negative BDG value were found. Pre-intervention data were compared with the intervention phase. The primary outcome of the study was the duration of echinocandin therapy. Secondary outcomes were length of hospital stay and mortality. Results: Ninety-two echinocandin prescriptions were reviewed, 49 (53.3%) in the pre-intervention phase and 43 (46.7%) in the intervention phase. Discontinuation of antifungal therapy was possible in 21 of the 43 patients in the intervention phase (48.8%). The duration of echinocandin therapy was 7.4 (SD 4.7) in the pre-intervention phase, 4.1 days (SD 2.9) in persons undergoing the intervention, and 8.6 (SD 7.3) in persons in whom the intervention was not feasible (p at ANOVA = 0.016). Length of stay and mortality did not differ between pre-intervention and intervention phases. Conclusions: An intervention based on pre-prescription restriction and post-prescription audit when combined with BDG measurement is effective in optimizing antifungal therapy by significantly reducing excessive treatment duration.

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“…The University Medical Center Groningen, the Netherlands No 64% was the adequate posaconazole exposure; in the longitudinal analysis from all the confounders, only dose had a significant effect on posaconazole concentrations Low Kawaguchi et al [ 41 ] Single-centre, observational Candida species Antifungal stewardship programs (AFSPs) 1–3 years Patients who received systemic antifungals at the Osaka City University Hospital (980-bed, tertiary-care teaching hospital) Yes As the appropriate selection of antifungals increases, a decrease in antifungal usage and cost reduction also occurs. This trend leads to improved prognoses of patients with candidemia Low Ito-Takeichi et al [ 42 ] Single-institutional prospective cohort Candida species 1‐3, β - d -glucan (βDG) testing 1–2 days In patients receiving intravenous antifungals at the 614-bed Gifu University Hospital No Parental antifungal use was significantly reduced Low Cavalieri et al [ 46 ] Retrospective Candida species MALDI-TOF mass spectrometry / Vitek 2 1–2 days Hospitalized patients Yes An average 18 h faster microbial ID and antimicrobial susceptibility test results Low Steuber et al [ 18 ] Single-centre, retrospective, observational Candida species T2 Candida Panel (T2CP) 3 years Patients with positive or negative T2CP at a 971-bed community hospital No Antifungal optimization occurred in 54% of patients who had antifungal orders at the time of T2CP test Low Hashemi et al [ 45 ] ...…”

Section: Methodsmentioning

confidence: 99%

Healthcare Utilization and Impact of Antifungal Stewardships Within Respiratory Care Settings: A Systematic Literature Review

Aldossary

2021

Mycopathologia

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Introduction Fungal infection and sensitization are common in chronic respiratory patient populations such as bronchiectasis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) and are often associated with prolonged antifungal therapy (Hohmann et al. in Clin Infect Dis 15:939–940, 2010; Vissichelli et al. in Infect Prev Pract 1:100029, 2019), morbidity, and mortality. Although the use of antifungal stewardship (AFS) is increasing within an invasive fungal disease setting, its use and impact within a chronic respiratory setting have not been defined. Methods A systematic literature review was conducted using PRISMA guidelines to evaluate the use of antifungal stewardship within a chronic respiratory care setting. Three databases have been searched, Medline via Ovid, Embase and GlobalHealth, for papers published between 1949 and 2020. Results The initial search identified 987 papers from Medline, 1761 papers from Embase, and 481 papers from GlobalHealth. Only 28 papers met the criteria for inclusion in this systematic literature review. The included studies were subjected to CASP and GRADE assessments to rank their quality and applicability. Only two studies were focussed on Aspergillus species infection. Conclusion Although antifungal stewardship is increasing, its applications are still limited in chronic respiratory care settings despite the prolonged requirement for antifungal therapy and high antimicrobial resistance.

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The impact of implementing an antifungal stewardship with monitoring of 1‐3, β‐D‐glucan values on antifungal consumption and clinical outcomes

Cited by 14 publications

References 26 publications

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

Post-Prescription Audit Plus Beta-D-Glucan Assessment Decrease Echinocandin Use in People with Suspected Invasive Candidiasis

Healthcare Utilization and Impact of Antifungal Stewardships Within Respiratory Care Settings: A Systematic Literature Review

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