Antifungal Consumption Research Articles

Improving management and antimicrobial stewardship for bacterial and fungal infections in hospitalized patients with COVID-19.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection is being one of the most significant challenges of health care systems worldwide. Bacterial and fungal infections in hospitalized patients with coronavirus disease 2019 (COVID-19) are uncommon but consumption of antibiotics and antifungals has increased dramatically during the ongoing pandemic resulting in increased selective pressure for global antimicrobial resistance. Nosocomial bacterial superinfections appear to be more frequent than community-acquired coinfections, particularly among patients admitted to the intensive care unit (ICU) and those receiving immunosuppressive treatment. Fungal infections associated with COVID-19 might be missed or misdiagnosed. Existing and new antimicrobial stewardship (AMS) programmes can be utilized directly in COVID-19 pandemic and are urgently needed to contain the high rates of misdiagnosis and antimicrobial prescription. The aim of this review is to describe the role of bacterial and fungal infections and possible strategies of AMS to use in daily practice for optimal management of COVID-19.

Intensive Care Antifungal Stewardship Programme Based on T2Candida PCR and Candida Mannan Antigen: A Prospective Study.

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non-neutropenic sepsis and a high risk of IC from two large tertiary ICUs were prospectively included, during a one-year period. IC was classified as proven, likely, possible or unlikely. The AFSP, diagnostic values of T2Candida and MAg, and the consumption of antifungals were evaluated. An amount of 219 patients with 504 T2Candida/MAg samples were included. IC was classified as proven in 29 (13.2%), likely in 7 (3.2%) and possible in 10 (5.5%) patients. Sensitivity/specificity/PPV/NPV values, comparing proven/likely versus unlikely IC, were 47%/100%/94%/90% for BC alone, 50%/97%/75%/90% for T2Candida alone, and 39%/96%/67%/88% for MAg alone. For the combination of T2Candida/MAg taken ≤3 days after AFT initiation, sensitivity/specificity/PPV/NPV was 70%/90%/63%/93%. T2Candida/MAg contributed to early (<3 days) AFT initiation in 13%, early AFT discontinuation in 25% and abstaining from AFT in 24% of patients. No reduction in overall use of AFT during the study period compared with the previous year was observed. An AFSP based on T2Candida and MAg screening contributed to a reduction of unnecessary treatment, but not overall AFT use. The diagnostic performance of T2Candida was lower than previously reported, but increased if T2Candida was combined with MAg.

1162. Antifungal Use in Immunocompromised Children in Europe: a 12-week Multicenter Modified Point prevalence Study (CALYPSO)

Abstract Background While antifungal consumption in immunocompromised patients appears high, data on children are limited. We analyzed antifungal use in hospitalized immunocompromised children across Europe in order to better organize a European pediatric antifungal stewardship programs (pAFS). Methods A multicenter 12-wk modified point-prevalence study was conducted. All patients hospitalized in hematology-oncology (HO) or bone marrow/solid organ transplant (BMT/SOT) units across Europe and receiving systemic antifungals were included. Data on ward demographics and policies were collected once at the beginning; weekly ward and patient data were prospectively collected during the 12-wk study period and entered in REDCap. Systemic antifungals administered were recorded (doses, duration, reason for administration or discontinuation). Results Twenty-one HO and 10 BMT/SOT units from 18 hospitals in 11 European countries participated in the study and 572 antifungal prescriptions were recorded. The most common underlying conditions were: 69% malignancy (81% hematologic, 19% solid tumors), 20% BMT, 6% hematologic diseases except malignancy and 4% primary immunodeficiency. Indication of antifungals was prophylaxis for 439 (77%) and treatment for 133 (23%) prescriptions (62 empirical, 43 pre-emptive, 28 targeted). Most common reasons for empirical, pre-emptive and targeted treatment were antibiotic-resistant febrile neutropenia (52%), abnormalities on chest-CT with/without positive galactomannan (72%) and candidiasis (82%), respectively. For targeted treatment, the most frequent pathogens were C. albicans (50%), C. parapsilosis (11%) and A. fumigatus (11%). Overall, fluconazole and liposomal amphotericin B were the most frequently prescribed agents both for prophylaxis (31% and 21%) and treatment (32% and 23%). However, in BMT patients the most frequently prescribed antifungal agents were fluconazole or micafungin for prophylaxis and caspofungin and voriconazole for treatment (Table). Antifungal agents used per underlying condition Antifungal agents used per underlying condition Conclusion Most systemic antifungal prescribing across European HO and BMT/SOT units is for prophylaxis, and fluconazole is the main antifungal prescribed. Results from this multicenter study can be a first step to guide a Europe-wide pAFS. Disclosures Emmanuel Roilides, MD, PhD, ECMM (Research Grant or Support, Other Financial or Material Support, ECMM grant for this study)

Pediatric Antifungal Prescribing Patterns Identify Significant Opportunities to Rationalize Antifungal Use in Children.

Objective:The need for pediatric antifungal stewardship programs has been driven by an increasing consumption of antifungals for prophylactic and empirical use. Drivers and rational of antifungal prescribing need to be identified to optimize prescription behaviors.Methods:A prospective modified weekly Point Prevalence Survey capturing antifungal prescriptions for children (> 90 days to < 18 years of age) in 12 centers in England during 26 consecutive weeks was performed. Demographic, diagnostic and treatment information was collected for each patient. Data were entered into an online REDCap database.Results:One thousand two hundred fifty-eight prescriptions were included for 656 pediatric patients, 44.9% were girls, with a median age of 6.4 years (interquartile range, 2.5–11.3). Most common underlying condition was malignancy (55.5%). Four hundred nineteen (63.9%) received antifungals for prophylaxis, and 237 (36.1%) for treatment. Among patients receiving antifungal prophylaxis, 40.2% did not belong to a high-risk group. In those receiving antifungal treatment, 45.9%, 29.4%, 5.1% and 19.6% had a diagnosis of suspected, possible, probable of proven invasive fungal disease (IFD), respectively. Proven IFD was diagnosed in 78 patients, 84.6% (n = 66) suffered from invasive candidiasis and 15.4% (n = 12) from an invasive mold infection. Liposomal amphotericin B was the most commonly prescribed antifungal for both prophylaxis (36.6%) and empiric and preemptive treatment (47.9%). Throughout the duration of the study, 72 (11.0%) patients received combination antifungal therapy.Conclusions:Antifungal use in pediatric patients is dominated by liposomal amphotericin B and often without evidence for the presence of IFD. A significant proportion of prophylactic and empiric antifungal use was seen in pediatric patients not at high-risk for IFD.

Utilization Trends of Antiviral and Antifungal Agents for Human Systemic Use in Tanzania From 2010 to 2017 Using the World Health Organization Collaborating Centre for Drug Statistics Methodology

IntroductionThe increase in antimicrobial consumption contributes to the emergence of antimicrobial resistance (AMR). Many studies have investigated the patterns of antibacterial consumption and antibacterial resistance. However, there is a paucity of data on the utilization of antivirals and antifungals in low and middle-income countries to serve as a baseline for monitoring and surveillance of AMR. Therefore, this study determined Tanzania’s systemic antifungal and antiviral utilization trends from 2010 to 2017, based on the Tanzania Medicines and Medical Devices Authority (TMDA) medicine importation archives.MethodologyAn analytical, longitudinal retrospective survey covering 2010 to 2017 was conducted. The study utilized the Anatomical Therapeutic and Chemical (ATC) classification and Defined Daily Dose (DDD) developed by the World Health Organization (WHO) Collaborating Centre for Drug Statistics and the WHO Collaboration Centre for International Drug Consumption Monitoring. Human medicine importation data were collected from TMDA headquarters and used to assess the systemic antiviral and antifungal consumption trends. The importation data included the date, generic name, strength, brand name, currency, quantity, ATC classification, supplier country, port of entry and product supplier. The data were cleaned, reorganized and analyzed. Reference was made to the latest revised DDD list to assign antifungals and antivirals to their respective ATC/DDDs and then adjusted to the population estimates from the National Bureau of Statistics of Tanzania.ResultsThere was a high proportion of systemic antivirals and antifungals utilization with 367.1 and 10.8 DDD per 1000 inhabitants per day (DID) respectively over eight years. In regression model, there was a significant increase in both antiviral (p-value = 0.043) and antifungal (p-value = 0.015) agents’ utilization trends in Tanzania in the study period. Fluconazole had the highest proportion of utilization for antifungals, followed by ketoconazole, itraconazole, miconazole and amphotericin B. For systemic antivirals, a high proportion was attributed to antiretrovirals used for HIV infections.ConclusionFindings from this study suggest an increase in the utilization of systemic antiviral and antifungal agents. These findings may be used to further benchmark utilization and AMR studies in Tanzania.

Lessons from an Educational Invasive Fungal Disease Conference on Hospital Antifungal Stewardship Practices across the UK and Ireland.

Invasive fungal disease (IFD) is a growing health burden. High mortality rates, increasing numbers of at-risk hosts, and a limited availability of rapid diagnostics and therapeutic options mean that patients are increasingly exposed to unnecessary antifungals. High rates of prescriptions promote patient exposure to undue toxicity and drive the emergence of resistance. Antifungal stewardship (AFS) aims to guide antifungal usage and reduce unnecessary exposure and antifungal consumption whilst maintaining or improving outcomes. Here, we examine several AFS approaches from hospitals across the UK and Ireland to demonstrate the benefits of AFS practices and support the broader implementation of AFS as both a necessary and achievable strategy. Since the accuracy and turnaround times (TATs) of diagnostic tools can impact treatment decisions, several AFS strategies have included the development and implementation of diagnostic-driven care pathways. AFS informed treatment strategies can help stratify patients on a risk basis ensuring the right patients receive antifungals at the optimal time. Using a multidisciplinary approach is also key due to the complexity of managing and treating patients at risk of IFD. Through knowledge sharing, such as The Gilead Antifungal Information Network (GAIN), we hope to drive practices that improve patient management and support the preservation of antifungals for future use.

Risk factors for isolation of fluconazole and echinocandin non-susceptible Candida species in critically ill patients.

Introduction. Resistance rates to azoles and echinocandins of Candida spp. increased over the last decade.Hypothesis/Gap Statement. Widespread use of antifungals could lead to development and dissemination of resistant Candida spp.Aim. To identify risk factors for isolation of Candida spp. non-susceptible to either fluconazole or echinocandins.Methodology. All patients hospitalized in the Intensive Care Unit (ICU) of the University General Hospital of Patras, Greece with Candida spp. isolated from clinical specimens during a ten-year period (2010-19) were included. Candida isolates were identified using Vitek-2 YST card. Consumption of antifungals was calculated.Results. During the study period, 253 isolates were included. C. non-albicans predominated (64.4 %) with C. parapsilosis being the most commonly isolated (42.3 %) followed by C. glabrata (nomenclatural change to Nakaseomyces glabrataa; 8.7 %) and C. tropicalis (11.9 %). Among all isolates, 45.8 and 28.5 % were non-susceptible and resistant to fluconazole, respectively. Concerning echinocandins, 8.7 % of isolates were non-susceptible to at least one echinocandin (anidulafungin or micafungin) and 3.1 % resistant. Multivariate analysis revealed that hospitalization during 2015-19, as compared to 2010-14, isolate being non-albicans or non-susceptible to at least one echinocandin was associated with isolation of fluconazole non-susceptible isolate. Administration of echinocandin, isolate being C. glabrata or C. tropicalis, or Candida spp. non-susceptible to fluconazole were independently associated with isolation of Candida spp. non-susceptible to at least one echinocandin. Fluconazole's administration decreased during the study period, whereas liposomal-amphotericin B's and echinoncandins' administration remained stable.Conclusion. Fluconazole's non-susceptibility increased during the study period, despite the decrease of its administration. Although echinocandins' administration remained stable, non-susceptibility among Candida spp. increased.

Antimicrobial Consumption among 66 Acute Care Hospitals in Catalonia: Impact of the COVID-19 Pandemic.

Background: Antimicrobials have been widely used during the COVID-19 pandemic. This study aimed to analyze the impact of the COVID-19 pandemic on the antimicrobial consumption of 66 hospitals in Catalonia. Methods: Adult antibacterial and antimycotic consumption was calculated as defined daily doses (DDD)/100 bed-days and DDD/100 discharges. Firstly, overall and ICU consumption in 2019 and 2020 were compared. Secondly, observed ICU 2020 consumptions were compared with non-COVID-19 2020 estimated consumptions (based on the trend from 2008–2019). Results: Overall, antibacterial consumption increased by 2.31% and 4.15% DDD/100 bed-days and DDD/100 discharges, respectively. Azithromycin (105.4% and 109.08% DDD/100 bed-days and DDD/100 discharges, respectively) and ceftriaxone (25.72% and 27.97% DDD/100 bed-days and DDD/100 discharges, respectively) mainly accounted for this finding. Likewise, antifungal consumption increased by 10.25% DDD/100 bed-days and 12.22% DDD/100 discharges, mainly due to echinocandins or amphotericin B. ICU antibacterial and antimycotic consumption decreased by 1.28% and 4.35% DDD/100 bed-days, respectively. On the contrary, antibacterial and antifungal use, expressed in DDD/100 discharges, increased by 23.42% and 19.58%. Azithromycin (275.09%), ceftriaxone (55.11%), cefepime (106.35%), vancomycin (29.81%), linezolid (31.28%), amphotericin B (87.98%), and voriconazole (96.17%) use changed the most. Observed consumption of amphotericin B, azithromycin, caspofungin, ceftriaxone, vancomycin, and voriconazole were higher than estimated values. Conclusions: The consumption indicators for most antimicrobials deviated from the expected trend pattern. A worrisome increase in antibacterial and antifungal consumption was observed in ICUs in Catalonia.

Impact of the SARS-CoV-2 Pandemic in Candidaemia, Invasive Aspergillosis and Antifungal Consumption in a Tertiary Hospital.

In addition to the increase in fungal infections that has been observed in the last few decades, it has been reported that severe clinical COVID-19 can increase the risk of invasive fungal infections. The main objective of this study was to evaluate if there had been an increase in candidaemia and invasive pulmonary aspergillosis (IPA) cases since the onset of the SARS-CoV-2 pandemic. Data were retrospectively collected from April 2019 to March 2021, from patients admitted to Consorcio Hospital General Universitario de Valencia (Spain). A total of 152 candidaemia cases (56 of which were due to Candida auris) and 108 possible IPA cases were detected. A great increase in candidaemia cases was produced during the first and the third epidemic waves of the SARS-CoV-2 pandemic (June 2020, and January 2021, respectively), while an increase in IPA cases was produced during the third wave. The 28-day mortality rates in patients affected by candidaemia and IPA increased in 2020 and 2021. C. auris has displaced the other Candida species, becoming the most isolated Candida species in blood cultures since the onset of the SARS-CoV-2 pandemic. Antifungal consumption increased in 2020 when compared to 2019, especially echinocandins, voriconazole and isavuconazole.

The impact of pharmacist‐led antifungal stewardship interventions in the hospital setting: a systematic review

AbstractAimTo summarise the evidence on pharmacist‐led antifungal stewardship (AFS) programs in the hospital setting and to evaluate their impact on the quality of antifungal prescribing and infection management, antifungal usage and clinical outcomes.Data sourcesA systematic review of English‐language studies identified in MEDLINE and EMBASE was performed on 27 November 2020 and conducted in accordance with PRISMA. Search terms included ‘antifungal agent’, ‘invasive fungal infection’, ‘antimicrobial stewardship’, ‘patient care bundles’ and ‘pharmacist’.Study selectionEligible studies describing pharmacist‐led quality improvement intervention(s) implemented in the hospital setting targeted at optimising systemic antifungal prescribing.ResultsSix hundred and forty‐six studies were identified, and seven met inclusion criteria. Five were dedicated to optimising candidaemia management, one at optimising intensive care unit prescribing of caspofungin and one on antifungal prescribing in haematology and oncology units. All studies measured varied metrics relating to quality of prescribing and infection management, reporting improvement in proportion of effective antifungal therapy (n = 1/1), appropriate antifungal selection (n = 1/1), dosing (n = 2/3), management of drug–drug interactions (n = 1/1) and reduced time to antifungal initiation (n = 4/4). Studies that implemented a candidaemia bundle of care reported improvements in composite bundle adherence (n = 2/2), with greatest improvement in ophthalmological consultation (n = 4/4), echocardiography (n = 2/2) and infectious diseases consultation (n = 3/3). There was reduction in antifungal expenditure (n = 4/4) and consumption (n = 2/4). Pharmacist‐led AFS programs did not influence clinical outcomes.ConclusionAvailable evidence suggests that pharmacist‐led AFS interventions can improve the quality and timeliness of antifungal prescribing and reduce antifungal usage. Further research is required to assess the impact on clinical and microbiological outcomes.

Impact of a non-compulsory antifungal stewardship program on overuse and misuse of antifungal agents in a tertiary care hospital

Objectives: To assess the impact of an antifungal stewardship (AFS) program on appropriate use, consumption and acquisition costs of antifungals, and on clinical outcomes (in-hospital-mortality, in-hospital-length-of-stay).Methods: The study was conducted at a 535-bed tertiary-care hospital and had three consecutive periods. A) Observational period (10 months): all antifungal prescriptions were prospectively evaluated. B) Educational intervention to increase the awareness on proper antifungals use. C) Implementation of a non-compulsory AFS program (10 months) based on prospective audit and feedback. Interrupted time series analysis has been used to assess the impact of the intervention.Results: During the pre-interventional period 198 AF prescriptions for 147 patients, have been evaluated compared to 181 prescriptions in 138 patients during the AFS period. Statistical analysis showed a significant immediate drop of inappropriate prescriptions after intervention with a significantly declining trend thereafter, and a significant drop of the total consumption of antifungals immediately after the intervention with a significant declining trend thereafter. All-cause, in-hospital- mortality was stable during the pre-intervention period with a significant declining trend after the AFS program implementation, although no immediate intervention effect could be established. Comparison of pre-and post-interventional periods showed significant reduction in acquisition costs (-26.8%, p<0.001) but no difference regarding the total number of bed-days (107,654 vs. 102,382), and mean length of hospital-stay (5.19 vs. 4.96 days, p=NS).Conclusions: The implementation of a non-compulsory AFS program resulted in significant improvement in the quality of prescriptions and reduction in antifungals consumption and acquisitions costs, without affecting the overall in-hospital-mortality and mean in-hospital-length-of-stay.

Clinical features and para-clinical findings of cryptococcal meningitis in the North of Iran during 2011-19.

Background and Purpose: Cryptococcal meningitis (CM) is a serious fungal infection that especially affects patients with human immunodeficiency virus (HIV). In this regard, the present retrospective study aimed to analyze the clinical and laboratory features and therapeutic outcomes of patients with CM admitted to two teaching referral centers in the north of Iran during 2011-19. Materials and Methods: This study was performed on all the hospitalized patients diagnosed with CM in two therapeutic centers of infectious diseases in the north of Iran. The required data, such as demographic characteristics and clinical and paraclinical features of patients, were extracted and entered in the information forms. Finally, the collected data were analyzed in SPSS software (version 16). Results: For the purpose of the study, records of 12 confirmed CM patients were evaluated in this research. Based on the results, 75% of the patients were male. Moreover, the average age of the subjects was 40.33± 8.93 years old and 66.6% of them (n=8) were HIV-positive. Other underlying diseases among HIV-positive patients included infection with hepatitis C virus (25%) and a history of tuberculosis (25%). In total, three HIV-negative patients suffered from Hodgkin lymphoma (25%), sarcoidosis (25%), and asthma (25%) and one patient (25%) had no underlying disease. Headache (75%), weakness, and fatigue (75%) were the most common symptoms among the participants. The cluster of differentiation 4 (CD4) count in all HIV-positive patients was less than 100 cells/μl. There was no significant difference between symptoms in HIV-positive and HIV-negative patients. Besides, no significant difference was observed between the groups of HIV-positive and HIV-negative patients regarding the period between the onset of symptoms and diagnosis of CM, the length of hospital stay, and the duration of antifungal medication consumption. In total, three patients (25%) expired, and six patients recovered. The CM recurred in two HIV-negative and one HIV-positive subjects; the two HIV-negative patients were treated, while the HIV-positive patient expired due to this recurrence. Conclusion: Clinical features and cerebrospinal fluid parameters were not different in HIV-positive and HIV-negative participants. Despite the fact that CM is not common in Iran, due to the increasing number of immunosuppressive patients, the differential diagnosis of CM should be considered for patients with signs and symptoms of infection in the central nervous system.

Establishing essential metrics for antifungal stewardship in hospitals: the results of an international Delphi survey.

Guidance on assessment of the quantity and appropriateness of antifungal prescribing is required to assist hospitals to interpret data effectively and structure quality improvement programmes. To achieve expert consensus on a core set of antifungal stewardship (AFS) metrics and to determine their feasibility for implementation. A literature review was undertaken to develop a list of candidate metrics. International experts were invited to participate in sequential web-based surveys to evaluate the importance and feasibility of metrics in the area of AFS using Delphi methodology. Three surveys were completed. Consensus was predefined as ≥80% agreement on the importance of each metric. Eighty-two experts consented to participate from 17 different countries. Response rate for each survey was >80%. The panel included adult and paediatric physicians, microbiologists and pharmacists with diverse content expertise. Consensus was achieved for 38 metrics considered important to routinely include in AFS programmes, and related to antifungal consumption (n = 5), quality of antifungal prescribing and management of invasive fungal infection (IFI) (n = 24), and clinical outcomes (n = 9). Twenty-one consensus metrics were considered to have moderate to high feasibility for routine collection. The identified core AFS metrics will provide a framework to comprehensively assess the quantity and quality of antifungal prescribing within hospitals to develop quality improvement programmes aimed at improving IFI prevention, management and patient-centred outcomes. A standardized approach will support collaboration and benchmarking to monitor the efficacy of current prophylaxis and treatment guidelines, and will provide important feedback to guideline developers.

Comparison of the defined daily dose and days of treatment methods for evaluating the consumption of antibiotics and antifungals in the intensive care unit

ObjectiveTo compare the measurement of antimicrobial consumption by defined daily dose (DDD) versus by days of therapy (DOT). DesignRetrospective analysis of clinical and administrative data from patients admitted to a polyvalent ICU. SettingICU at a University Hospital in Spain. PatientsAll patients admitted to the ICU. InterventionsNone. Main variables of interestFor the DDD method, the World Health Organization (WHO)-assigned DDD was determined for the all the prescribed antimicrobials. For the DOT method, one DOT represented the administration of a single agent on a given day regardless of the number of doses administered. To express aggregate use, total DDDs and total DOTs were normalized to 100 patient-days. ResultsDuring the study period, 2393 adult patients were admitted to the ICU. Total median antimicrobial drugs measured by DDDs was 535.3 (IQR 319.8–845.5) vs. 344.0 (IQR 117.2–544.5) when measured by DOTs, p<0.001. When antimicrobial consumption was normalized to 100 patient-days, median antimicrobial consumption was also higher when measured by DDDs [2.98/100 patient-days (IQR 1.76–5.25) vs. 1.89/100 patient-days (IQR 0.64–3.0) when measured by DOTs, p<0.001]. ConclusionsFor most antibacterial and antifungal drugs used in critically ill patients, estimates of aggregate antibiotic use by DDDs per 100 patient-days and DOTs per 100 patient-days are discordant because the administered dose is dissimilar from the WHO-assigned DDD. DOT methods should be recommended to avoid the overestimation that occurs with DDDs in adult critically ill patients.

How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single-centre study.

We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

Superficial mycoses in Belgium: Burden, costs and antifungal drugs consumption

Monitoring of superficial mycoses requires more attention due to their important incidence, health costs and antifungal drugs consumption. The objectives were to estimate the burden of superficial mycoses in Belgium and to assess trends in associated antifungal consumption. The burden of dermatophytoses (including onychomycosis), as well as skin and genital candidiasis, was estimated using disability-adjusted life years (DALY). Moreover, trends in systemic and topical antifungal consumption in ambulatory care were examined for the period 2010-2017, together with their associated costs. Due to their high incidence and long treatment duration, dermatophytoses represented the bulk of the burden, accounting for 92.2% of the total DALYs of superficial mycoses. Terbinafine was the most prescribed antifungal in terms of doses (35.4% of the total doses) while fluconazole was the most delivered drug in terms of packages (29.1% of the total packages). More than 70% of the prescriptions were made by general practitioners while consumption varied according to age and gender of the patients. A global 12% decrease in antifungal prescriptions was observed between 2011 and 2017. However, this reduction would result mainly from packaging changes and increased self-medication. A significant decrease in itraconazole treatments was notably compensated by an increased prescription of fluconazole packages. This study emphasises that dermatological presentations of superficial mycoses are the most important in terms of both burden and antifungal consumption in Belgium. Further reduction in antifungals use can be achieved by applying the adequate treatment after identification of the causative agent.

Epidemiological Trends of Fungemia in Greece with a Focus on Candidemia during the Recent Financial Crisis: a 10-Year Survey in a Tertiary Care Academic Hospital and Review of Literature.

Updated information on the epidemiology of candidemia, particularly during severe socioeconomic events, is important for proper management of these infections. A systematic literature review on candidemia in Greece and a retrospective surveillance study were conducted in a tertiary university hospital during the years of the recent financial crisis (2009 to 2018) in order to assess changes in incidence rates, patient characteristics, species distribution, antifungal susceptibilities, and drug consumption. The average annual incidence of 429 candidemic episodes was 2.03/10,000 bed days, with 9.88 in adult intensive care units (ICUs), 1.74 in surgical wards, and 1.81 in internal medicine wards, where a significant increase was observed (1.15, 1.85, and 2.23/10,000 bed days in 2009 to 2011, 2012 to 2014, and 2015 to 2018, respectively; P = 0.004). Candida albicans was the most common species (41%), followed by Candida parapsilosis species complex [SC] (37%), Candida glabrata SC (11%), Candida tropicalis (7%), Candida krusei (1%), and other rare Candida spp. (3%). Mixed infections were found in 20/429 (4.7%) cases, while 33 (7%) cases were due to non-Candida spp. Overall, 44/311 (14%) isolates were resistant/non-wild type (WT) to the nine antifungals tested, with 23/113 (20%) C. parapsilosis SC and 2/34 (6%) C. glabrata SC isolates being resistant to fluconazole (1 panechinocandin and 2 panazole resistant). All isolates were susceptible/WT to amphotericin B and flucytosine. While the overall consumption of antifungals diminished (P = 0.02), with a mean of 17.93 defined daily doses (DDD)/100 bed days, increased micafungin use was correlated with the rise in C. parapsilosis SC (P = 0.04). A significant increase of candidemia in internal medicine wards and of C. parapsilosis SC infections was found during the years of financial crisis. Although resistance rates remain low (<14%), fluconazole-resistant C. parapsilosis SC and multidrug-resistant C. glabrata SC isolates are of major concern.

Efficacy and safety of a comprehensive educational antimicrobial stewardship program focused on antifungal use

Few data exist regarding the impact of antimicrobial stewardship programs on antifungal use. We evaluated the efficacy and safety of a comprehensive long-term antimicrobial stewardship program (ASP) focused on antifungal use. During a 9-year period, we quarterly assessed antifungal consumption, incidence density of hospital-acquired candidemia, Candida spp. distribution, antifungal resistance, and crude death rate per 1000 occupied bed days (OBDs) of hospital-acquired candidemia. We performed segmented regression analysis of interrupted time series. A significant change in trend was observed for antifungal consumption, with a sustained reduction of -0.87% per quarter (95% confidence interval [CI], -1.36 -0.38, p<0.001), accounting for a final reduction of -38.4%. The main reduction was produced in fluconazole, with a sustained reduction of -1.37% per quarter (95%CI, -1.96 -0.68, p<0.001). The incidence density of hospital-acquired candidemia decreased, with a change in slope of -5.06% cases per 1000 OBDs per year (95%CI, -8.23 -1.77, p = 0.009). The 14-day crude death rate per 1000 OBDs dropped from 0.044 to 0.017 (-6.36% deaths per 1000 OBDs per year; 95%CI, -13.45 -1.31, p = 0.09). This ASP has succeeded in optimizing the use of antifungal with a long-lasting reduction without increasing the incidence, neither the mortality, of hospital-acquired candidemia.

Neonatal Antifungal Consumption Is Dominated by Prophylactic Use; Outcomes From The Pediatric Antifungal Stewardship: Optimizing Antifungal Prescription Study.

Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population. Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database. Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%. Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Candida blood stream infections observed between 2011 and 2016 in a large Italian University Hospital: A time-based retrospective analysis on epidemiology, biofilm production, antifungal agents consumption and drug-susceptibility.

Candida bloodstream infection (BSI) represents a growing infective problem frequently associated to biofilm production due to the utilization of intravascular devices. Candida species distribution (n = 612 strains), their biofilm production and hospital antifungal drug consumption were evaluated in different wards of a tertiary care academic hospital in Italy during the years 2011–2016. In the considered time window, an increasing number of Candida BSI (p = 0.005) and of biofilm producing strains were observed (p<0.0001). Although C. albicans was the species more frequently isolated in BSI with a major biofilm production, an increased involvement of non-albicans species was reported, particularly of C. parapsilosis that displayed a high frequency in catheter infections, and lower biofilm production compared to C. albicans. Although trends of biofilm production were substantially stable in time, a decreasing biofilm production by C. parapsilosis in the Intensive Care Unit (ICU) was observed (p = 0.0041). Principal component analysis displayed a change in antifungal drugs consumption driven by two mutually independent temporal trends, i.e. voriconazole use in the general medicine wards initially, and fluconazole use mainly in the ICU; these factors explain 68.9% and 25.7% of total variance respectively. Moreover, a significant trend (p = 0.003) in fluconazole use during the whole time period considered emerged, particularly in the ICU (p = 0.017), but also in the general medicine wards (p = 0.03). These trends paralleled with significant increase MIC90 of fluconazole (p = 0.05), particularly for C. parapsilosis in the ICU (p = 0.04), with a general and significant decreased trend of the MIC90 values of caspofungin (p = 0.04), and with significant increased MIC50 values for amphotericin B (p = 0.01) over the study period. In conclusion, drug utilization in our hospital turned out to be a putative influencing factor on the ecology of the species, on the increase in time of the biofilm producing strains and on the Candida antifungal susceptibility profile, thus influencing clinical management.