Trends in Systemic Antifungal Use in Australia, 2005–2016: a Time-Series Analysis

Invasive fungal infections (IFIs) are associated with significant morbidity and mortality, especially in immunocompromised and critically ill neonatal and pediatric patients. The challenges in establishing a definite diagnosis of IFIs, the lack of consensus in defining high-risk populations and the variability of pharmacokinetics in children have led to the overuse or misuse of antifungals in pediatrics. Inappropriate use of antifungals entails a substantial risk of toxicity and interactions, along with the emergence of resistance. Therefore, antifungal stewardship (AFS) programs need to be developed and implemented to optimize antifungal use, considering the unique needs of pediatric and neonatal populations. ANTIFUNGAL STEWARDSHIP PROGRAMS FOR PEDIATRIC AND NEONATAL PATIENTS A multidisciplinary team of experts comprising an infectious disease specialist, a clinical pharmacist, a microbiologist and a physician involved in antifungal prescription is essential to address the particularities of IFI epidemiology and antifungal use in this vulnerable population. The main principles of AFS can parallel antimicrobial stewardship programs, focusing on improving clinical outcomes by optimizing antifungal use, reducing healthcare costs and preventing the emergence of resistance. A consensus protocol (in the form of guidance and policy), including recent international evidence-based guidelines and local epidemiology, can be created by this expert team to ensure optimization of antifungal use. Practice of antifungal guidelines and their implementation should be the first step in the AFS roadmap (Table 1). TABLE 1. - Targeted Antifungal Stewardship Activities for Neonatal and Pediatric Patients Structure of AFS (System Prerequisites) Team:• Desired expertise in pediatric fungal infections. Leadership commitmentSurveillance systems including IT for tracking and reporting of• Antifungal prescribing: target indications for antifungal prophylaxis and combination antifungal therapy• Adherence to polices and guidelines (what) and audit and feedback (how)• Specific AFS outcome metrics: incidence of Invasive fungal infections (IFI), IFI associated morbidity and mortality AFS activities General• Written policies and guidelines for antifungal use and education ○ Local, national or international• Strategy: Audits and feedback on specific areas of antifungal use ○ Target antifungal indications where more clinical data are available (dose, length of therapy, toxicity)Tailored audits and opportunities for AFS implementation at department level• Neonatal ICUs: ○ Neonatal antifungal prophylaxis ○ Neonatal candidiasis ▪ When and why to start empiric Treatment• Pediatric oncology departments: ○ Antifungal prophylaxis: define risk factors ○ Promote diagnostic-driven treatment ○ Compliance with local/international guidelines for empiric Treatment of Febrile Neutropenia AFS implementation activities Identification of determinants of antifungal prescribing practices• Capacity for organizational change (ie, facilitate AFS activities)• Incentives and resources (ie, dedicated team and surveillance activities)• Guidelines factor (ie, Written policies and standard of procedures for fungal infections)• Individual health professional factors or professional interactions (i.e., multidisciplinary AFS team)• Patient factors (ie, compliance with written guidelines for risk factors)• Social, political and legal factors (ie, AFS program fully supported by institutional administration)Implementation of behavioral change activities in parallel to AFS education Strategies incorporating prior authorization and/or postprescription review and feedback in accordance with the updated 2016 Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America guidelines may be useful.1 Although stringent antifungal policies with formulary restrictions and clinical audits may be time-consuming, they constitute the core components of an effective AFS.2 Clinical audits are a useful means to highlight fields that require attention. Provision of educational programs, prescription evaluation and raising awareness of the proper use of antifungal agents are effective interventions to rationalize and optimize antifungal therapy. Efforts to achieve optimal antifungal use can be evaluated by observing the selection and duration of therapy, using quality indicators. Among volume-based metrics, days of therapy are recommended for monitoring drug consumption, whereas defined daily doses (DDDs) can be an alternative tool, although the latter is not as appropriate for young patients in whom the doses are based on the size of the patient. Moreover, in certain antifungal medications, such as fluconazole, itraconazole and amphotericin B formulations, DDDs can lead to overestimation of their use and can also be less accurate in patients with renal or hepatic insufficiency requiring dose adjustment.3 Although quantitative data are relatively simple to obtain, they do not reflect the appropriateness of prescriptions. Although healthcare-associated IFIs are truly opportunistic infections, they are rare in patients without significantly impaired immunity. AFS programs should predominantly focus on patients in Pediatric Hematology-Oncology (PHO) departments and hematopoietic stem cell transplantation (HSCT) units as well as those in pediatric and neonatal intensive care units.4 Therefore, when implementing an antifungal stewardship program, training and consultative efforts should be aimed at departments with the largest numbers of prescriptions to monitor common prescribing errors and to recognize prevailing practices. Enhancement of judicious antifungal prescriptions improves clinical outcomes and secondarily minimizes unnecessary healthcare costs. To achieve this goal and adequately treat patients with IFIs for which there are few agents with clinical efficacy, antifungal susceptibility testing should be more widely available than it currently is. AFS IN UNITS WITH IMMUNOCOMPROMISED PEDIATRIC PATIENTS The populations most vulnerable to IFIs include pediatric patients with hematologic malignancies, HSCT and recipients of solid organ transplants (SOT). The extensive use of recently approved immunomodulatory therapies, such as CAR T-cell therapy, as well as newer chemotherapeutic drugs, such as tyrosine kinase inhibitors, indicated for pediatric patients, broadens the spectrum of patients at potential risk of developing IFIs.5 Although the term "high risk" is not always clearly defined, it is recommended that patients undergoing HSCT, those with acute myeloid leukemia (AML), or certain patients with acute lymphoblastic leukemia (ALL) (relapsed or refractory ALL) be considered at high risk for IFIs. Moreover, other clinical and laboratory factors that should also be considered include prolonged and profound neutropenia despite underlying malignancy, type of HSCT, steroid exposure, indwelling central venous catheter, parenteral nutrition and prolonged use of broad-spectrum antibiotics. Environmental factors, such as proximity to construction work, are predisposing factors, especially for the development of invasive aspergillosis. The most common indication for administering systemic antifungal medication across European pediatric hematology-oncology or bone marrow/SOT units, as revealed by the CALYPSO study, is prophylaxis.6 Primary antifungal prophylaxis is generally recommended for patients at high risk of IFIs, although specific guidelines issued by the IDSA and the European Conference on Infections in Leukemia (ECIL) for FN in children with cancer are not uniform.7,8 The expert panel of the IDSA does not clearly differentiate between adult and pediatric patients. However, pediatric-specific ECIL recommendations are based on randomized trials in adults, pediatric pharmacokinetics and safety data and regulatory approval of the appropriate doses. The leading causes of IFIs in children with pediatric malignancies include yeasts, such as Candida species, Aspergillus species and Mucorales. Prophylactic strategies generally use azole-based regimens, mainly fluconazole for low-risk patients and posaconazole, itraconazole or voriconazole with therapeutic drug monitoring (TDM) for high-risk patients. In leukemia patients, neurotoxicity impacts and narrows the therapeutic index of azoles, especially voriconazole. Therefore, alternative prophylactic schemes using echinocandins (caspofungin) or liposomal amphotericin B (L-AmB) have been described.9 In the future, oral or weekly intravenous administration of active antifungals may be a better solution. All 3 echinocandins and L-AmB are recommended and approved as empirical therapy for persistent febrile neutropenia and treatment of candidemia and invasive aspergillosis, respectively.10 Although challenging, the pre-emptive approach may be considered an alternative to empirical therapy in pediatric patients, leading to decreased antifungal exposure. Real-time surveillance of the evolving epidemiology of IFIs in pediatric oncology patients is an important tool for developing an effective prophylactic strategy. Confronted with the dilemma of the most suitable approach, the choice of the appropriate regimen should incorporate information of modifiers, such as the local epidemiology, comorbidities, toxicity profile and specific treatment modalities. Although antifungal drug combinations (AFCs) may be appealing for pediatric oncologists striving to improve the dismal outcomes among patients with IFIs, these approaches have not been broadly studied in clinical settings where host factors may greatly impact the final efficacy and pharmacokinetic disposition of drugs. Discordant results were yielded when AFC were studied in vivo, and antagonism among antifungal agents might occur. Infectious disease specialists play an important role in guiding and reminding prescribing doctors that CAF may increase potential for drug interactions and drug toxicities without proven clinical benefit. The use of CAF should be considered in unique settings such as refractory mucormycosis or salvage therapy for invasive aspergillosis, still with marginal strength recommendation. Only in cryptococcosis, CAF is well established and based on significant evidence. Until more core concrete evidence on CAF is available, caution is warranted when employing these strategies. NEONATAL CRITICALLY ILL PATIENTS Antifungal agents are frequently used in neonates for both the prophylaxis and treatment of IFIs. Invasive candidiasis is the leading IFI in this population and has been associated with high morbidity and mortality in this vulnerable population. Neonatal antifungal prophylaxis is a common strategy used in NICUs, mainly for high-risk neonates such as those with extremely low birth weight (ELBW). A recent study conducted in 12 centers in England found that systemic antifungal agents were prescribed in up to one-fifth of neonates admitted to neonatal wards.11 Almost 8 of 10 prescriptions were indicated as antifungal prophylaxis. A similarly high prevalence of antifungal prophylaxis was documented in a multicenter European study with 26 participating NICUs.12 In both studies, ELBW premature neonates constituted less than half of all the cases of antifungal prophylaxis. This could be a target for AFS and assess opportunities for the improvement of antifungal prophylaxis in NICUs. Current data on the appropriateness and benefits of neonatal antifungal prophylaxis suggest a more optional, customized and risk-based approach in NICUs.13 Fluconazole is the most used antifungal agent for both prophylaxis and treatment of neonates.12 However, significant variability in fluconazole dosing has been documented in several neonatal studies, and this could be another reasonable AFS opportunity for NICUs. In addition, neonatal AFS programs should encourage surveillance of local susceptibility patterns for fungal pathogens, especially when antifungal prophylaxis is recommended.11 Current evidence on the association between the use of antifungal prophylaxis in neonates and subsequent development of antifungal resistance is hampered by differences in local fungal epidemiology and study methodologies (ie, sample size).13 IMPROVING DIAGNOSTICS AND ANTIFUNGAL THERAPEUTIC DRUG MONITORING: TWO MAJOR CAPACITIES TO INCORPORATE AFS ACTIVITIES The absence of microbiological data limits opportunities to discontinue or de-escalate antifungals, contributing to prolonged courses of antifungal agents. Although intensive stewardship practices may be more effective in decreasing antibiotic utilization, it is unknown whether they are effective in restricting unnecessary antifungal exposure. Since the pathogen is not often identified in cultures, empiric treatment is the main treatment strategy. Although blood culture is the gold standard for de-escalation of therapy, it is time-consuming. The need for rapid results is of utmost importance in the effort to shift from empiric to pre-emptive antifungal treatment, which is a diagnostic-driven approach. Restraining empirical antifungal use relies mainly on the improvement of diagnostics. Close cooperation with clinical microbiology can ensure the utilization of rapid molecular identification methods, including matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) spectrometry, multiplex polymerase chain reaction and peptide nucleic acid fluorescent in situ hybridization for Candida and Aspergillus. Rapid molecular identification, when available, and nonculture-based diagnostics as a surrogate for culture data are valuable tools. Noninvasive fungal markers, such as serum galactomannan (GM) enzyme immunoassay (EIA), 1,3 β-D glucan (BDG) assays and fungal PCR, together with computed tomography and/or magnetic resonance tomography, exhibit excellent negative predictive values when invasive aspergillosis is excluded. Recent studies provide evidence that surveillance testing with GM EIA and BDG alone or in combination during periods of neutropenia, especially if patients are receiving antifungal prophylaxis, may not be necessary.14 The pediatric population shows pharmacokinetic and pharmacodynamic variability, which affects the target therapeutic levels. Therapeutic drug monitoring (TDM) of azole medications is important for mitigating adverse events and optimizing antifungal usage. A pharmacokinetic program with expert guidance from pharmacists or AFS members is an important strategy for AFS programs. Documentation of the dose optimization strategy for each antifungal agent using TDM may facilitate the timely attainment of therapeutic concentrations and overcome interpatient variability. Moreover, knowledge of azole resistance could counteract azole antifungals as a first-line choice for invasive candidemia given the emerging antifungal resistance of Candida spp. Among pediatric patients with malignancy, Candida albicans is the most prevalent colonizer, and azoles remain the most effective choice when used wisely. Especially in immunocompromised patients, susceptibility patterns may change over time, necessitating continuous surveillance of colonization patterns. CONCLUSION The development and validation of an effective AFS is challenging and entails the complexity of diagnosis, nonspecificity of clinical presentation and emergence of resistance in the context of the lack of new antifungal drugs in development.

Globally, invasive fungal diseases (IFDs) have a significant impact in human health. With an increasing pediatric population at risk of IFD, effective antifungal drugs access and affordability should be ensured universally. The aim of our study was to characterize the global antifungal drug use in neonates and children and its variability between countries in different income groups. Data were extracted from the Global Antimicrobial Resistance, Prescribing and Efficacy in Neonates and Children Point Prevalence Survey project, consisting in 1 pilot and four 1-day Point Prevalence Survey between 2015 and 2017. The data had been entered through a study-specific web-based data collection tool. From a total of 13,410 children included, 7.8% (1048/13,410) received at least 1 systemic antifungal drug: 9.5% (95% confidence interval: 8.9%-10.1%) in high income countries (HIC) versus 5.0% (95% confidence interval: 4.4%-5.6%) in low-middle income countries (LMIC) (P < 0.01). A significant proportion of patients on antifungals belonged to high-risk group for IFD (67.4%; 706/1048); most of these were managed in HIC (72.8%, P < 0.01). The likelihood of receiving antifungals being in high-risk group was higher in HIC compared with LMIC (ratio of 5.8 vs. 3.4, P < 0.01). Antifungal prophylaxis was more likely prescribed in HIC (67.2% vs. 30.4%, P < 0.01). Fluconazole was the most frequently prescribed drug. The proportional use of fluconazole was higher in LMIC compared with HIC. A significant variability of antifungal prescribing patterns was observed. The proportional use of systemic antifungals was twice as high in HIC compared with LMIC. More detailed data on access and antifungal use in limited-resource settings should be explored.

Background: Invasive fungal infections significantly contribute to mortality and morbidity rates. Despite the presence of all four major classes of antifungal medications, it is estimated that these infections result in the death of 1.5 million people each year, and death rates are increasing at an alarming rate. With increasing concerns about the emergence of antifungal resistance, there is a growing consideration in many countries to incorporate antifungal stewardship into existing antimicrobial stewardship programs. This approach aims to address issues hindering the appropriate use of antifungal drugs and to optimize their utilization. Methods: An analytical retrospective study of 48 hospitalized patients was conducted to assess factors related to the use of systemic antifungals and develop and implement an internal protocol to improve its use. Results: All patients with severe comorbidity had SOFA scores linked with a mortality risk of more than 10%. Based on 48 evaluations of antifungal orders, 62.5% were considered appropriate, 14.6% were considered debatable, and 22.9% were considered inappropriate. Infectious disease physicians made most of the prescriptions considered appropriate in this study. Conclusions: Comorbidities and risk factors in patients receiving systemic antifungals can be associated with the development of more serious fungal infections; hence, the implementation of antifungal stewardship as a complement to antimicrobial stewardship programs can help facilitate decision-making when dealing with a suspected case of fungal infection.

Neonatal fungal infections are associated with substantial mortality and morbidity. Although prophylactic use of several antifungals has been proposed, this practice remains controversial. In order to evaluate the use of fluconazole prophylaxis in European NICUs, we conducted a cross-sectional survey by means of a structured questionnaire that was sent to European level II and III neonatal intensive care units, over a 9-month period, as part of a neonatal research FP7 European project. A total of 193 questionnaires from 28 countries were analysed. Use of antifungal prophylaxis was reported by 55% of the responders, and the most frequently used antifungal agent was fluconazole (92%). Main indications for prophylaxis were low gestational age (<28 weeks) and birth weight (<1,000 g). A dose of 3 mg/kg was used in 66% of NICUs using fluconazole, with an administration interval of 72 h in 52% of them. All responders acknowledged the need for additional trials on the efficacy of prophylactic fluconazole. Non-users of fluconazole prophylaxis were more likely to be influenced by the local incidence of candidiasis, the risk of increasing antifungal resistance and the absence of specific recommendations by paediatric societies. Conclusions: Major concerns about the use of fluconazole prophylaxis include its efficacy, the risk of emergence of resistant species and the absence of clear consensus to support routine use. Future studies that address these issues will contribute to a more rational use of fluconazole prophylaxis.

Antifungal prescription practices have changed over the last decade, and the impact of these changes is unclear. Our objective here was to evaluate the effect of antifungal drug use on the distribution and drug susceptibility of Candida spp. in a French intensive care unit (ICU). Antifungal drug use was measured as the number of defined daily doses per 1000 hospital days (DDDs/1000HD). The distribution of Candida spp. over a 6 year period (2004-09) and the MICs of antifungal drugs over 2007-09 were determined. Statistical analyses were performed to assess relationships between antifungal drug use, Candida spp. distribution and MIC changes over time. Of 26,450 samples from 3391 patients, 1511 were positive for Candida spp. Candida albicans predominated (52.5%), followed by Candida glabrata (16.6%) and Candida parapsilosis (7.5%). C. parapsilosis increased significantly, from 5.7% in 2004 to 12.5% in 2009 (P = 0.0005). Caspofungin use increased significantly between 2004 (17.9 DDDs/1000HD) and 2009 (69.9 DDDs/1000HD) (P < 0.0001). Between 2007 and 2009, the increase in caspofungin use correlated significantly with the increase in caspofungin MICs displayed by C. parapsilosis (P < 0.0001) and C. glabrata (P = 0.03). Amphotericin B consumption changed over time and correlated with an increase in amphotericin B MICs for C. albicans (P = 0.0002) and C. glabrata (P = 0.0005). Significant declines occurred in both fluconazole use (P < 0.0001) and fluconazole MICs of C. albicans (P < 0.001) Antifungal drug use in the ICU is associated with major changes in the distribution and drug susceptibility of Candida spp.

Invasive fungal infection remains a serious postoperative complication in lung transplant recipients and is associated with significant morbidity and mortality. Although most lung transplant centers use antifungal prophylaxis, consensus on the strategy, choice of antifungal agent(s), route of administration, and duration of prophylaxis have not been established. This review provides an overview of the epidemiology and risk factors for common fungal infections seen in lung transplant recipients, evaluates the clinical efficacy and toxicity of the various antifungal agents used to prevent infection, and offers recommendations and opportunities for future research. Currently available data evaluating the efficacy of antifungal prophylaxis strategies is limited by a lack of prospective, randomized clinical trial data and variability in patient populations, prophylactic and immunosuppressive strategies, dosing, durations of use of antifungal agents, and definitions of invasive infection. There is controversy regarding significant risk factors for invasive fungal infection, which has limited the development and validation of targeted prophylactic strategies. Inhaled formulations of amphotericin B remain the most widely studied option for universal prophylaxis and have been shown to be effective in reducing the incidence of invasive Aspergillosis as compared with no prophylaxis. Concern over early postoperative extrapulmonary infection may suggest a benefit of initial prophylaxis with a systemic azole. Long-term use of systemic antifungals is not optimal due to emerging evidence of long-term toxicities. Multicenter, randomized trials are needed to ascertain the optimal prophylactic strategy in lung transplant recipients. New agents and delivery mechanisms may offer additional opportunities for comparative research.

Use of antifungal agents and predictors of total antifungal use among adult inpatients at U.S. academic health centers was characterized. Claims data obtained from a geographically representative sample of U.S. nonprofit academic health centers were analyzed to characterize use of systemic antifungals during the period 2004-08. Aggregate data were analyzed to identify trends in use of three antifungal classes (azoles, polyenes, echinocandins), as well as individual antifungal agents. Multivariate regression analysis was employed to investigate predictors of total antifungal use and interhospital variability in antifungal use. Aggregate antifungal use at health centers included in the data analysis increased from (mean ± S.D.) 82 ± 36 days of therapy (DOT) per 1000 patient-days in 2004 to 88 ± 39 DOT per 1000 patient-days in 2007 and then declined to 77 ± 36 DOT per 1000 patient-days in 2008. Use of voriconazole increased significantly during the study period (p < 0.0001), while use of caspofungin decreased significantly (p < 0.0001). Higher use of third- or fourth- generation cephalosporins was a significant predictor of higher total antifungal use (p = 0.0005); performance of more stem cell or bone marrow transplants was also significantly associated with greater antifungal use. Total antifungal use at a sample of U.S. academic health centers increased from 2004 to 2007 but decreased to below baseline in 2008. Azoles were the most commonly used agents. In 2008, total antifungal use at the centers ranged from 29 to 334 DOT per 1000 patient-days.

The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.

ObjectivesTo describe the use of antifungal medicines in English hospitals in adults with life-limiting illness and to investigate the association between socio-demographic variables and the use of high-cost formulations.MethodsPseudonymised patient-level...

BackgroundAntifungal drug resistance is an emerging problem during patient treatment, probably caused by incorrect use of antimicrobial agents.PurposeTo check the relationship between antifungal use and candidiasis, including related costs, between...

We evaluated the impact of education and an antifungal stewardship program for candidiasis on prescribing practices, antifungal consumption, Candida species infections, and estimated costs at a Thai tertiary care hospital. A hospital-wide, quasi-experimental study was conducted for 1.5 years before the intervention and 1.5 years after the implementation of an antifungal stewardship program. Inpatient antifungal prescriptions were prospectively observed, and patients' demographic, clinical, and administrative-cost data were collected. Interventions included education, introduction of an antifungal hepatic and/or renal dose adjustment tool, antifungal prescription forms, and prescription-control strategies. After the intervention, there was a 59% reduction in antifungal prescriptions (from 194 to 80 prescriptions per 1,000 hospitalizations; P<.001). Inappropriate antifungal use decreased (from 71% to 24%; P<.001), a sustained reduction in antifungal use was observed (r=0.83; P<.001), and fluconazole use decreased (from 242 to 117 defined daily doses per 1,000 patient-days; P<.001). Reductions in the incidence of infection with Candida glabrata (r=0.69; P<.001) and Candida krusei (r=0.71; P<.001) were observed, whereas the incidence of infection with Candida albicans (r=-0.81; P<.001) increased. Total cost savings were US$31,615 during the 18-month postintervention period. Implementation of an antifungal stewardship program was associated with appropriate antifungal drug use, improved resource utilization, and cost savings.

Audit for antifungal treatment usage in adults with invasive fungal infection: A prospective observational study.

BackgroundFungemia by yeast is a life-threatening infection that occurs in patients with special conditions. It is often identified by its morphology, triggering the empiric therapy. However, the management can be difficult as identification and susceptibility tests require several days, and evidence on management and outcomes in pediatric patients is limited. Thus, this study aimed to characterize pediatric fungemia by yeast and assess their outcomes to help optimize management.Risk factor analysis for overall mortality following fungemia by yeastMethodsThis is a single-center, retrospective observational study at the largest tertiary children’s hospital in Japan. Electronic medical records of pediatric patients < 18 years who developed fungemia by yeast from April 2014 to March 2024 were reviewed. To simplify, the data on the first fungemia by yeast was collected on patients with multiple episodes, along with patient characteristics, details of identified organisms, use of antifungals, and prognosis. Breakthrough fungemia was defined when it occurred during the use of systemic antifungals for ≥ 3 days. Descriptive data, the risk for overall mortality and survival following fungemia were analyzed using chi-square test and Kaplan-Meier curve analysis with a p-value < 0.05 being considered significant.Overall survival following fungemia by yeast according to prior use of antifungalsResultsOverall, 55 episodes of fungemia by yeast were identified in 43 patients. 28/43 (65%) patients were immunocompromised. Candida parapsilosis was the most frequently detected (20/43, 47%), followed by C. albicans (11/43, 26%). Breakthrough fungemia occurred in 17/43 (40%) cases. Mortality was significantly higher in patients with breakthrough fungemia compared to those without prior antifungals (8/17 (47%) vs. 2/26 (8%), p< 0.01). In addition, when the source of fungemia was clinically undetermined, the overall mortality rate was high (8/17, 47%, p< 0.01) (Table). Further, the survival curve after the onset of fungemia by yeast depicted the worse outcomes in patients with breakthrough fungemia (p< 0.01) (Figure).ConclusionIn pediatric patients with fungemia by yeast, the mortality rate was higher in breakthrough fungemia and fungemia with unknown sources. Therefore, it is crucial to recognize the importance of breakthrough fungemia and identifying the source of infection to pursue appropriate source control.DisclosuresChikara Ogimi, MD, PhD, AstraZeneca: Honoraria|bioMerieux Japan Ltd.: Honoraria|ELSEVIER: Honoraria|KYORIN: Honoraria|Miyarisan: Honoraria|MSD: Honoraria|NOVARTIS: Honoraria|Pfizer: Honoraria

In the present work, we examined the consumption of systemic antifungals (fluconazole, itraconazole, and terbinafine) in outpatients in the four provinces of Galicia, Spain, between 2019 and 2022. We also described the variability in the use of these types of drugs between these provinces. In addition, we detected any deviation in consumption at a seasonal level and analyzed possible changes during the study period. A descriptive, cross-sectional, and retrospective study of the use of antifungals, expressed in terms of a defined daily dose per 1000 inhabitants per day, was carried out. The results obtained revealed statistically significant differences between provinces and by the active principle consumed in the four Galician provinces (p < 0.001), which can be explained by multiple factors. This study also revealed that there was stable consumption during the study period, with no significant seasonal differences observed. This study represents a contribution to the knowledge about the consumption of antifungals for systemic use in Galicia and serves as a basis for subsequent studies. This will allow us to understand the consumption patterns of these types of drugs and, ultimately, will help to establish stewardship strategies and prevent the development of resistance.