Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016–2019

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016–2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

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

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)

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.

Species Distribution of Candidemia and Their Susceptibility in a Single Japanese University Hospital: Prior Micafungin Use Affects the Appearance of Candida parapsilosis and Elevation of Micafungin MICs in Non-parapsilosis Candida Species

Introduction: Micafungin is a recommended echinocandin antifungal agent for candidemia treatment and prophylaxis. However, overuse of echinocandin antifungals may cause resistance. There is currently no information available regarding the low susceptibility associated with using micafungin. This study investigated the effect of micafungin use on changes in the detected Candida species and low susceptibility. Methods: We conducted a retrospective survey and included records of Candida spp. detected in blood cultures from January 2010 to December 2018 in our hospital. Survey items included clinical outcomes at 30 days after positive cultures, patient characteristics, and drug prescription status. Patient background information included gender, previous hospitalization, stay in the intensive care unit, comorbidities, and history of surgery (within 90 days before candidemia onset) and drug exposure. Species detected and their minimum inhibitory concentrations (MICs) and amount of antifungal prescriptions by department were investigated. Risk factors for detecting C. parapsilosis and for low susceptibility to micafungin were evaluated using multivariate analysis. Results: A total of 153 Candida clinical blood isolates were collected and C. albicans was the most prevalent species, followed by C. parapsilosis and C. glabrata. In the analysis by department, antifungal use and non-albicans Candida species were most frequently detected in the hematology department. Multivariate analysis showed that prior micafungin use increased the risk of C. parapsilosis (odds ratio (OR) 4.22; 95% confidence interval (CI) 1.39–12.79; p = 0.011). MIC90 of micafungin on C. glabrata and C. parapsilosis was 1.0 μg/mL. Prior micafungin use was clarified as a risk factor resulting in MIC > 0.06 μg/mL for micafungin in non-parapsilosis Candida species (OR 13.2; 95% CI 3.23–54.2; p < 0.01). Conclusion: Prior micafungin use increased the risk of C. parapsilosis and the MIC > 0.06 μg/mL of micafungin in non-parapsilosis Candida species. Since there are only a few antifungal options, further antifungal stewardship considering azole antifungal agents use is required.

Implementation of Pharmacist-driven Antifungal Stewardship Program in A Tertiary Care Hospital

Objectives: Antifungal stewardship (AFS) is recommended to reduce the inappropriate use of antifungal drugs. In this study, the role of AFS in providing appropriate antifungal therapy was evaluated. Methods: This study included three periods as observation, feedback/education, and daily AFS activities. In observation period, the use of systemic antifungals was evaluated for a baseline measurement of appropriateness. In second period, monthly meetings were organized to provide feedback and education to physicians regarding antifungal therapy and the rate of adherence to the clinical guidelines. In final period, a clinical pharmacist participated in daily ward rounds to evaluate appropriateness of the antifungal therapy. A scoring system for appropriateness was used for comparison between the three periods. Results: Four hundred and eighteen episodes of antifungal therapy were evaluated. Baseline demographics of patients were similar in all three periods for age, gender, and the number of comorbidities. The indications for antifungal use were for prophylaxis in 22.7%, Candida infections in 58.6%, and invasive mould infections in 18.7%. During the third period, 157 (78.9%) recommendations were made and 151 (96.2%) were accepted. The overall appropriateness of antifungal use increased significantly for prophylaxis (30.8%, 17.9%, 46.3%, p=0.046) and treatment of fungal diseases (27.8%, 32.4%, 71.9%, p<0.001) between the first, second and third periods, respectively. A 30-day mortality was not significantly changed between the three periods (19%, 15.6% and 27.5%; p=0.050). Conclusions: Appropriateness in antifungal therapy can be augmented by the integration of an AFS program. A team-based evaluation of fungal infections and assessment of patients by a clinical pharmacist with a therapeutic perspective may help to increase the quality of antifungal therapy.

COVID-19 Associated Pulmonary Aspergillosis: Systematic Review and Patient-Level Meta-Analysis

Rationale Pulmonary aspergillosis may complicate COVID-19 and contribute to excess mortality in intensive care unit (ICU) patients. The incidence is unclear because of discordant definitions across studies. Objective We sought to review the incidence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA), and compare research definitions. Methods We systematically reviewed the literature for ICU cohort studies and case series including ≥3 patients with CAPA. We calculated pooled incidence. Patients with sufficient clinical details were reclassified according to 4 standardized definitions (Verweij, White, Koehler, and Bassetti). Measurements Correlations between definitions were assessed with Spearmans rank test. Associations between antifungals and outcome were assessed with Fishers Exact test. Main Results 38 studies (35 cohort studies and 3 case series) were included. Among 3,297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (pooled incidence 9.5%). 197 patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ=0.330 to 0.621, p<0.001). 38.6% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 9 days (interquartile range 5-14) in ICUs. Tracheobronchitis occured in 5.3% of patients examined with bronchoscopy. The mortality rate (50.0%) was high, irrespective of antifungal use (p=0.28); this remained true even when the analysis was restricted to patients meeting standardized definitions for CAPA. Conclusions The reported incidence of CAPA is exaggerated by use of non-standard definitions. Further research should focus on identifying patients likely to benefit from antifungals.

The Current State of Antifungal Stewardship in Immunocompromised Populations

Inappropriate antifungal use is prevalent and can lead to drug-resistant fungi, expose patients to adverse drug events, and increase healthcare costs. While antimicrobial stewardship programs have traditionally focused on antibiotic use, the need for targeted antifungal stewardship (AFS) intervention has garnered interest in recent years. Despite this, data on AFS in immunocompromised patient populations is limited. This paper will review the current state of AFS in this complex population and explore opportunities for multidisciplinary collaboration.