Empirical Antifungal Therapy Research Articles

P-1722. Short versus Long Duration of Empiric Antifungal Use Among Patients with Sepsis or Septic Shock

Abstract Background Invasive candidiasis is associated with high mortality rates among critically ill patients. There are currently no data to guide duration of empiric antifungal therapy (EAT) when indicated in high-risk patients with sepsis. The aim of this study was to evaluate clinical outcomes associated with a short versus long course of EAT in patients with sepsis or septic shock. Methods This was a retrospective cohort study of adults admitted to the medical ICU who received > 2 days of EAT with fluconazole or caspofungin for sepsis or septic shock. Patients were excluded if they expired within 48 hours, had a positive fungal culture from a sterile site, were exposed to a systemic antifungal for > 48 hours in the 14 days preceding treatment, received prophylactic antifungals, or were neutropenic. In addition, patients who expired within 96 hours of EAT initiation were excluded from the primary outcome analysis. Patients were grouped according to receipt of EAT for ≤ 4 days (short duration) or > 4 days (long duration). The primary outcome was 30-day all-cause mortality. Secondary outcomes included time to mortality, hospital and ICU length of stay (LOS), vasopressor-free days over 14 days, and 30-day new proven fungal infection. Results Of 135 included patients, 79 patients received short course EAT vs. 56 patients long course (Figure 1). Baseline variables were well balanced between groups apart from older age and lower body weight observed in the short duration group (Table 1). The primary outcome, evaluable in a total of 114 patients, was observed in 33 (56.9%) patients who received a short duration and 26 (46.4%) patients who received a long duration (p=0.263; OR 1.52, 95% CI [0.73 – 3.19]). There were no significant differences in all-cause inpatient mortality or time to mortality (Figure 2). Among patients who were discharged alive, there were no significant differences in secondary outcomes with the exception of fewer vasopressor-free days in the short course group (Table 2). Conclusion Most clinical outcomes were not significantly different between patients with sepsis or septic shock who received a short versus long course of EAT. Duration of EAT is an important target for stewardship programs. This study adds to knowledge in the area, though a randomized trial may be necessary to substantiate our findings. Disclosures All Authors: No reported disclosures

The Role of Empiric Antifungal Therapy in Patients With Perforated Peptic Ulcer: An Updated Systematic Review and Meta-Analysis.

Fungal growth is common in intraoperative cultures of patients with perforated peptic ulcer (PPU) leading to the common use of empiric antifungal therapy, with current evidence not clearly supporting this practice. The goal of this updated systematic review and meta-analysis was to synthesize the effect of empiric antifungals in patients with PPU. Eligible studies were identified through a comprehensive literature search in the MEDLINE (PubMed) and EMBASE databases, following the PRISMA 2020 statement. A total of eight studies were identified reporting on 1802 patients. The population consisted of 67.3% males (n = 121/1802), with a mean age of 59.1 ± 13.2 years. Most of the population underwent surgery (n = 1763/1802, 97.8%), which was most frequently omental patch (n = 1169/1411, 82.8%), while 12.8% (n = 140/1096) underwent laparoscopic repair. Intraoperative cultures were obtained in 73.7% (n = 1262/1713); blood cultures were obtained in 54.5% (n = 467/857) and were positive for fungus in 44.1% (n = 558/1262) and in 5.6% (n = 26/467), respectively. Empiric antifungal treatment was administered in 19.6% (n = 353/1802). The most common agent was fluconazole reported in 6 studies. At a mean follow-up of 34.4 ± 9.9 days, 191/1787 (10.7%) patients died. Patients with fungus-positive intraoperative cultures had significantly increased odds of having diabetes mellitus (OR: 1.55; 95% CI: 1.05-2.30), history of malignancy (OR: 2.80; 95% CI: 1.22-6.45), being on steroids (OR: 5.13; 95% CI: 1.37-19.3), and increased mortality (OR: 2.49; 95% CI: 1.67-3.70). Empiric antifungal therapy did not significantly decrease the odds for death (OR: 1.45; 95% CI: 0.33-6.41). The presence of fungi in the peritoneal fluid is associated with increased risk of death, that is not affected by administration of empiric antifungal therapy.

Invasive fungal disease in patients with cancer in a tertiary care pediatric hospital

Abstract Background In the last two decades, the raise in invasive fungal diseases (IFD) has been associated with increased morbidity and mortality in immunosuppressed hosts. Its incidence varies between 2 to 21% and depends on the host´s underlying disease, the intensity of immunosuppressive treatment and the presence of comorbidities. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of IFD in patients with hematology-oncology disease. Methods Retrospective, descriptive study. Patients under 18 years of age with acute leukemias, lymphomas and solid tumors with a diagnosis of proven IFD (according to EORTC-MSG 2019 criteria) were included during the period from January 2020 to November 2023 in a tertiary care pediatric hospital. Results During the study period, 304 patients were under follow-up. 14 episodes of proven IFD were identified in 13 patients.The median age was 120 months. Male sex predominated (69.2%). The recognized factors associated were neutropenia (69.2%), use of corticosteroids in the last 3 months (61.5%) and use of previous antibiotics (92.3%). The most common underlying disease was Acute Lymphoblastic Leukemia (ALL) in 11 cases (78.5%), of which 3 were in relapse. The 21.4% of the episodes occurred in solid tumors (1 osteosarcoma of the tibia, 1 abdominal germ cell tumor, 1 neuroblastoma). Patients receiving primary prophylaxis for filamentous fungi were 3/14 (21.4%), according to the European Conference on Infections in Leukemia (ECIL-8). All received voriconazole. The fungal isolates identified were: 1 Rhizopus spp. (eye biopsy, paranasal sinuses) 1 Penicillum spp. (lung biopsy), 1 Exserohilum rostratum (skin biopsy), 1 Trichophyton asahii (blood cultures), 1 Purpuracillum lilacinus (skin biopsy), 1 Aspergillus fumigatus (Bronchoalveolar lavage, BAL),: 3 Candida parapsilosis (blood cultures), 1 Candida tropicalis (blood cultures), 1 Candida spp (blood cultures), 1 Malassezia (BAL). The patients with invasive molds infections were six, all of them with pathological chest tomography. Galactomannans (GM) were positive in 66% (4/6). BAL with positive GM was performed in 2 of them. The primary focus were: cutaneous (3/6), pulmonary (2/6) and orbital-rhinosinusal (1/6). Regarding IFD due to yeast fungi: all Candida infections were associated with central venous catheters fungemia. Malassezia infection presented with pulmonary involvement. Fungal co-infection was observed in 1 patient with documentation of Aspergillus fumigatus in BAL and Candida tropicalis in blood and urine cultures. Empirical antifungal therapy was liposomal amphotericin in 76.9 % of the patients. Two patients died (15.4%) at 30 days of follow-up. Conclusion Early diagnosis and timely antifungal therapy represent the main strategies to increase the survival of patients with IFD. Antifungal prophylaxis is postulated as an effective prevention measure and its indication should be defined according to the patient’s characteristics and the incidence of IFD at the treating center. We consider that patients with suspected IFD and clinical focus should undergo the corresponding tissue biopsy for culture, histological evaluation, and molecular biology, to direct the appropriate treatment. Candida species represent the most frequent isolates, however, Aspergillus and Rhizopus infections are associated with higher morbidity and mortality.

Species distribution, antifungal susceptibility pattern and associated factors of Candida blood stream infections in Sri Lanka from 2018 to 2022

Introduction: Candidemia can be life-threatening in immunocompromised individuals thus, prompt diag-nosis and treatment with antifungal agents is mandatory for successful outcome.Surveillance data on species distribution, antifungal susceptibility and associated factors of candidemia is utmost important to decide on empiric antifungal therapy, to impose infection control measures as well to promote antifungal stewardship in a country.Therefore, this study was aimed at retrospective review of data on candidemia at Mycology Reference Laboratory in Sri Lanka for 5 years duration to identify the species causing candidemia, their antifungal susceptibility pattern and associated factors.Results: A twofold rise in candidemia cases were seen during this 5-year duration compared to previous 7 years (2011-2017). Predominant species causing candidemia was C. tropicalis (35%) followed by C. parapsilosis (33%). C. albicans was the 3rd commonest species causing candidemia in Sri Lanka.There were 3% C. glabrata cases, 2% C. guilliermondii and 1% C. famata and C. krusei cases. Importantly two sequencing confirmed C. auris cases were identified for the first time in Sri Lanka in 2021.Overall good antifungal susceptibility was seen for both fluconazole and amphotericin B and there were only 7%and 1.6% resistance respectively.Long term hospital stay (47%) was commonly seen in this study group followed by use of broad-spectrum antibiotics (24%) and involvement of gastro-intestinal tract (21%).Conclusion: Candida tropicalis is the commonest species causing candidemia in Sri Lanka. Common Candida species had good susceptibility to antifungals. Long term hospital stay was associated with candidemia in majority of patients.

Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Creation of a Multi-Year Pediatric Candidemia Antibiogram in Georgia Identifies Changing Epidemiology and Resistance Trends

Background: Invasive candidiasis, including candidemia, is a significant cause of morbidity and mortality in medically complex and immunocompromised children. Understanding the epidemiology and antifungal susceptibility patterns of Candida infections could help guide empiric antifungal therapy. Methods: This fungal antibiogram was created at a large quaternary children’s health system in Georgia. Blood isolates positive for Candida spp. from 2019 through 2023 were included. The number and percentage of isolates for each Candida spp was recorded by year and then as the combined 5-year total. The Clinical and Laboratory Standards Institute (CLSI) antifungal interpretative criteria were used, and we only included one unique Candida spp isolate per patient. Due to the limited number of isolates, the combined 5 years of isolates were used to create the fungal antibiogram. Data are shown as percent susceptible using CLSI interpretative criteria and number of isolates. Results: Between 2019 and 2023 there were 124 unique blood isolates of Candida spp identified. The most common isolates were C. albicans (33%), C. parapsilosis (27%), C. glabrata (14%) and C. tropicalis (11%). Over the 5 years of the study, the percentage of C. albicans isolates decreased from 47% to 21%. The change in epidemiology was not driven by a single Candida species but varied from year to year. For C. albicans, susceptibility was 100% for fluconazole and micafungin. For C. parapsilosis, susceptibility to fluconazole and micafungin was 97% and 94%, respectively. Fluconazole susceptibility was lowest for C. glabrata (88%) and C. krusei (0%). Using CLSI epidemiological cutoff values (ECV) to evaluate the amphotericin B results, none of the isolates had results greater than the CLSI ECVs. Comparing 2019 and 2023, the percentage of Candida blood isolates resistant to fluconazole increased from 5% to 18.5%. Conclusion: C. albicans was the most frequently identified cause of candidemia in children, but there was a gradual increase in fungemia caused by other Candida spp. over the past 5 years including Candida with fluconazole resistance. Overall, our findings demonstrate high susceptibility rates to fluconazole and echinocandins in Candida spp. blood isolates. Further research is needed to identify risk factors for antifungal resistant candidemia in pediatric patients.Disclosure: Mark Gonzalez: Honoria for a one time consulation with NaviDx consulting in May of 2022. Honoria from the American Society for Microbiology for writing of a chapter in the Clinical Microbiology Procedures Handbook.

A Diagnostic Stewardship Intervention to Improve Utilization of 1,3 β-D-Glucan Testing at a Single Academic Center: Five-Year Experience.

(1,3)- β-D-glucan (BDG) testing is one of the noninvasive tests to aid diagnosis of invasive fungal infections (IFIs). The study results have been heterogenous, and diagnostic performance varies depending on the risks for IFI. Thus, it is important to select appropriate patients for BDG testing to prevent false-positive results. An algorithmic diagnostic stewardship intervention was instituted at a single academic medical center to improve BDG test utilization. The BDG test order in the electronic health record was replaced with the BDG test request order, which required approval to process the actual test order. The approval criteria were (1) immunocompromised or intensive care unit patient and (2) on empiric antifungal therapy, or inability to undergo invasive diagnostic procedures. A retrospective observational study was conducted to evaluate the efficacy of the intervention by comparing the number of BDG tests performed between 1 year pre- and post-intervention. Safety was assessed by chart review of the patients for whom BDG test requests were deemed inappropriate and rejected. The number of BDG tests performed per year decreased by 85% from 156 in the pre-intervention period to 24 in the post-intervention period. The average monthly number of BDG tests performed was significantly lower between those periods (P = .002). There was no delay in IFI diagnosis or IFI-related deaths in the patients whose BDG test requests were rejected. The sustained effectiveness of the intervention was observed for 5 years. Institution of the diagnostic stewardship intervention successfully and safely improved BDG test utilization.

Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study

BackgroundCurrent guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery.MethodsA retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France. Patients treated with early empirical antifungals for HC-IAI after abdominal surgery were compared with controls who did not receive such antifungals. The primary endpoint was the death rate at 90 days, and the secondary endpoints were the death rate at 1 year and composite criteria evaluated at 30 days following the HC-IAI diagnosis, including the need for re-intervention, inappropriate antimicrobial therapy and death, whichever occurred first.ResultsAt 90 days, the death rate was significantly decreased in the patients treated with empirical antifungals compared with the control group (11.4% and 20.7%, respectively, p = 0.02). No differences were reported for the secondary outcomes.ConclusionThe use of early empirical antifungal therapy was associated with a decreased death rate at 90 days, with no effect on the death rate at 1 year, the death rate at 30 days, the rate of re-intervention, the need for drainage, and empirical antibiotic and antifungal therapy failure at 30 days.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning.

Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. This study aimed to provide evidence for the early warning and management of fungal infections. We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit

BackgroundThe global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species.Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed.MethodsUsing a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%.ResultsA total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). ConclusionThe results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). This systematic review was undertaken to compare these approaches in children. We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Rapid identification,fluconazole and micafungin susceptibility testing of Candida species from blood culture by a short incubation method

This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.

Unveiling the emerging of fluconazole-resistant Candida albicans in preterm with acute kidney injury: a growing challenge at Vajira hospital

This case presents a challenging scenario in a preterm female newborn born at 25 weeks gestation,who developed respiratory distress syndrome, followed by pneumonia, sepsis, subsequent renal complications, and candida albicans infection. Despite initial susceptibility to fluconazole, the emergence of fluconazole-resistant candida albicans led to a shift in antifungal treatment to amphotericin B in an acute kidney injury neonate. This case underscores the growing concern of drug-resistant candida albicans in neonates, highlighting the importance of judicious selection of empirical antifungal therapy and comprehensive management strategies, especially in the context of acute kidney injury.

Comparison of The Effect of Candida Score and Candida Colonization Index on Decrease in Candidemia Incidence in Our Intensive Care Unit

Aim: Since candidemia is an important cause of mortality and morbidity in hospitals, especially in intensive care units (ICU), those hospitalized in the ICU; In patients with risk factors such as invasive device use and undergoing abdominal surgery, early empirical antifungal therapy is recommended to reduce mortality according to the results of candida score (CS) and candida colonization index (CCI). In this study, the data of the patients who were followed up in the ICU, who were started on empirical treatment according to KS and CCI, were evaluated and their effects on the incidence of candidemia were analyzed. Method: Cultures taken from 100 patients hospitalized in the intensive care unit where adult patients were followed between 01.06.2018 and 01.08.2021 were examined. While investigating the colonization index of each patient, swab samples were taken once during the hospitalization from five main sites: mouth, nose, skin, perineum, and catheter. Samples taken with sterile swabs were inoculated on Sabouraud dextrose agar (SDA) plates and the plates were incubated at 35°C for 48 hours. The yeast colonies formed were defined according to their microscopic appearance and biochemical properties. CCI and CS of the patients were evaluated and fluconazole prophylaxis was started in patients with KS ≥3 or CCI ≥0.5. Results: A total of 500 culture samples from 100 non-neutropenic adult patients were analyzed (Mean of 5 cultures/patient). No growth was detected in any of the samples in 32 (32 %) of 100 patients, and growth was detected in at least one of the samples taken from 68 patients (68 %). Reproduction was detected from a total of 118 samples. Of the yeasts, 104 were identified as Candida albicans, 10 as Candida glabrata and 4 as Candida inconspicua. CS≥ 3 and CCI ≥0.5 in 11 (11%) patients, and CS≥3, CCI

Safety and efficacy of pre-emptive antifungal therapy versus empirical therapy in patients with febrile neutropenia – A meta-analysis

Febrile neutropenia is a life-threatening complication usually seen in cancer chemotherapy patients. Bacterial agents are the most common etiology of sepsis in febrile neutropenia and warrants empirical antibiotic treatment. However, the efficacy of pre-emptive therapy over empirical therapy is debatable. The objectives of this study were to evaluate the efficacy (difference in mortality rate) of pre-emptive antifungal therapy in patients with febrile neutropenia compared to empirical antifungal therapy and to evaluate the safety (antifungal exposure, adverse effects, and duration of hospital stay) of pre-emptive antifungal therapy. The data source used for the study is only PubMed. Only full-text articles in English language since the year 2000 were included. Unpublished studies will not be sought. Searches will be re-run before analysis. Data extraction was guided by a predetermined checklist. Using RevMan 5 software, the effect of intervention is null (95% CI 0.66–1.91, P = 0.57)]. An insignificant Q statistic (P &gt; 0.66) indicates the absence of heterogeneity (I2 = 0%) as there is not much difference in the mortality rates between two groups. Data analyses were performed from June 2023 to August 2023. The primary outcome is an insignificant Q statistic (P &gt; 0.66) indicates the absence of heterogeneity (I2 = 0%) as there is not much difference in the mortality rates between two groups. Hence, pre-emptive therapy can be considered in place of empirical therapy to avoid over treatment with antifungal agents in patients with febrile neutropenia. A meta-analysis of five eligible comparative studies involving 588 subjects who had pre-emptive antifungal therapy and 587 subjects who had empirical therapy signifies the effect of intervention is null (95% CI 0.66–1.91, P = 0.57). An insignificant Q statistic (P &gt; 0.66) indicates the absence of heterogeneity (I2 = 0%) as there is not much difference in the mortality rates between two groups. Hence, pre-emptive therapy can be considered in place of empirical therapy to avoid over treatment with antifungal agents in patients with febrile neutropenia. This systematic review and meta-analysis demonstrated that pre-emptive therapy can be considered in place of empirical therapy to avoid over treatment with antifungal agents in patients with febrile neutropenia. Trial Registration: PROSPERO receipt number-443707.

Clinical Characteristics of Patients with Hematologic Malignancies and Invasive Aspergillosis: A Cross-sectional Clinical Report from Iran

Background: The incidence of invasive aspergillosis (IA) has significantly increased in recent decades. In patients with hematologic malignancies (HM), IA is associated with higher mortality rates. Objectives: This study aimed to assess the clinical features of IA in patients with HM. Methods: In this retrospective study, we used the hospital information system (HIS) database to extract clinical and paraclinical characteristics of patients with various HMs who received a diagnosis of probable or proven IA during their hospitalization at Imam Khomeini Hospital Complex in Tehran, Iran, between March 2018 and March 2022. Results: After evaluating 350 patients with HM, 51 patients with IA (14.6%) were identified, of whom 40 cases (78.4%) were probable and 11 (21.6%) were proven. Among these, 34 individuals (66.7%) were male. The most common symptoms were fever (n = 23, 62.7%), cough (n = 20, 39.2%), and fever that did not respond to antibiotic therapy (n = 16, 31.4%). The most prevalent malignancies were AML (n = 28, 54.9%), ALL (n = 16, 31.4%), and lymphoma (n = 7, 13.7%). Out of the 51 patients with HM and IA, 48 (94.1%) had abnormal findings on chest CT scans, with the majority (n = 31, 72.1%) showing a nodule with a halo sign. Aspergillus flavus (n = 19/24, 79.2%) was the most commonly isolated species. Initially, patients received liposomal amphotericin B or caspofungin as empiric antifungal therapy, which was then switched to voriconazole once the diagnosis of IA was probable or proven. Eight patients (15.6%) died. Conclusions: Patients with HM presenting with fever and cough should undergo close monitoring for IA. A higher incidence of IA is observed in AML patients, and voriconazole could be considered as antifungal prophylaxis in HM patients. A. flavus is likely the most frequent cause of IA in Iranian patients with HM.

Candidaemia: A 9-Year Retrospective Analysis of Epidemiology and Antimicrobial Susceptibility in Tertiary Care Hospitals in Western China.

This investigation endeavors to scrutinize the resistance profiles to antifungal agents, alongside the clinical distribution of Candida isolates that yielded positive results in blood cultures at Suining Central Hospital spanning the years 2015 to 2023. The objective is to provide crucial epidemiological insights that may aid in early clinical intervention and judicious deployment of antifungal therapies. This retrospective analysis analyses data on 182 different Candida strains with positive clinical blood cultures obtained from the Microbiology Laboratory of Suining Central Hospital over a period of nine consecutive years. The study involved identification of Candida species and assessment of resistance patterns to fungal drugs. Our analysis revealed that the median age of patients diagnosed with Candidaemia from the 182 strains was 62 years, with a distribution of 63.7% females and 36.3% males. Within the cohort of 182 Candida strains, Candida albicans constituted 32.4%, while non-albicans Candida species comprised 67.6% of the cases. Specifically, Candida tropicalis represented 37.4%, Candida glabrata 12.1%, Candida parapsilosis 11.0%,Candida guilliermondii 3.8%, and both Candida krusei and Candida Dublin accounted for 1.6% each. These Candida species were predominantly identified in intensive care units (ICU), hematology, gastroenterology, neurology centers, and endocrine metabolism units. The findings of this investigation suggest a shift in the prevalence of non-Candida albicans species, notably C. tropicalis, as the predominant cause of Candidaemia at Suining Central Hospital, surpassing C. albicans. Although instances of antifungal resistance are infrequent, there has been a notable rise in resistance to azoles. This study provides important insights into the local epidemiology, which will be essential for informing the selection of empirical antifungal therapy and contributing to the global surveillance of antifungal resistance.

Chronic Infectious Laryngitis: The Role of Empirical Therapy and Biopsy: A Report of 5 Cases

Chronic infectious laryngitis is a clinical mimic of laryngeal carcinoma which can be due to bacterial or fungal aetiology. Both conditions present with non-specific symptoms with leucoplakia on examination. The role of biopsy of laryngeal lesions in the absence of risk factors of laryngeal carcinoma is debatable as it responds to antifungal therapy. This study aimed to review the predisposing factors and role of biopsy in chronic infectious laryngitis. A retrospective review of all cases of chronic infectious laryngitis presented to our centre between 2018 and 2021 were conducted. Clinical features, risk factors, antifungal therapy and its response were reviewed. All cases of chronic infectious laryngitis avoided the need of biopsy while had successful empirical antifungal therapy except for one refractory case. Biopsy of the refractory case was negative for malignancy and the culture-proven Staphylococcus aureus laryngitis was successfully treated with antibiotics. Empirical antifungal therapy in cases of chronic infectious fungal laryngitis with close serial follow-up had good outcome. Biopsy should be reserved for refractory cases to exclude malignancy and guide further antimicrobial therapy.

Epidemiology and antifungal susceptibility of fungal infections from 2018 to 2021 in Shandong, eastern China: A report from the SPARSS program

PurposeWe analyzed the pathogenic fungal epidemiology and antifungal susceptibility from 2018 to 2021 in Shandong Province, China, to provide the basis for empiric antifungal therapy. MethodsFungal isolates were collected from 54 hospitals in Shandong province from 2018 to 2021 through the Shandong Province Pediatric bacterial & fungal Antimicrobial Resistance Surveillance System (SPARSS), WHONET v5.6 and SPSS software v20.0 were used for statistical analysis. ResultsA total of 15,348 strains of fungi were collected, with Candida accounting for 78.25 %, followed by Aspergillus at 15.45 %, and other species at 6.27 %. Candida albicans was the predominant Candida species, but more than half of the Candida isolates were non-albicans species, with C. tropicalis being the most dominant (22.74 %), followed by C. glabrata (17.50 %) and C. parapsilosis (11.02 %). The composition of fungi varied significantly among different age groups. Children had a higher proportion of C. albicans (47.30 %) compared to non-children (32.06 %). The non-wild-type phenotype rate of Candida for Amphotericin B was less than 3 %, while Cryptococcus neoformans was 16.67 %. In addition, less than 6 % of C. albicans and C. parapsilosis were resistant to fluconazole and voriconazole, and 96.30 % of C. glabrata were SDD to fluconazole. We also found that 80.56 % of C. glabrata and 83.70 % of C. krusei were voriconazole WT/susceptibility phenotype. However, the susceptibility rates of C. tropicalis to fluconazole/voriconazole decreased from 70.40 %/46.40 % in 2018 to 62.30 %/35.20 % in 2021. The comprehensive susceptibility rate to fluconazole of C. albicans, C. tropicalis, C. parapsilosis and C. glabrata isolated from the blood has decreased from 69.36 % to 56.62 %. ConclusionsThe study reveals that the composition and antifungal susceptibility of pathogenic fungi in Shandong Province differ from other regions. Moreover, the resistance to azoles is more severe, especially in C. tropicalis. These findings indicate the need for region-specific antifungal treatment strategies to combat fungal infections effectively.

Multilocus Sequence Typing of Emerging Azole-Resistant Candida auris Isolates from Critically Ill Patients in a New York City Medical Center

Abstract Candida auris has developed into a slow-moving global pandemic since its emergence in 2009, particularly as a source of nosocomial infection amongst immunocompromised and critically-ill patients. According to CDC data, C. auris emergence has accelerated in the US during the COVID-19 pandemic and has garnered particular attention for its high level of resistance to multiple classes of antifungals. C. auris has been categorized into five genetically diverse clades, each with unique antifungal drug resistance patterns. We have observed a sharp increase in cases identified at our tertiary medical center in New York City over the past three years. In this study, we designed a set of C. auris-specific oligonucleotides to determine the clonality of isolates through Multilocus Sequence Typing (MLST) of four genetic loci known to have a high level of divergence amongst Candida species. From 2020 through 2022 we identified 22 patients with C. auris bloodstream infection at our institution by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and performed MLST on isolates that were available from 19 patients. We assessed four genetic loci: ITS1/ITS2, D1/D2, RPB1 and RPB2; ERG11 was included to assess for mutations associated with fluconazole resistance. We found that the number of blood stream infections increased from 2 cases in 2020 to 12 in 2022. Our MLST results showed that all C. auris isolates from blood and body fluids belong to CDC-defined Clade 1c, which carries the ERG11 gene mutation resulting the amino acid substitution K143R in 14-α-Demethylase associated with fluconazole resistance. These isolates also demonstrated fluconazole resistance by in vitro testing (19/19), amphotericin resistance was present in 44% of isolates with available data (7/16), and all isolates were susceptible to micafungin (19/19). Of 19 patients with blood cultures positive for C. auris, 13 (68%) were in a critical care setting at time of collection, 17 (89%) had been in an ICU during the same admission, and 8 (42%) expired within 3 months of C. auris positivity. MLST is considered a relatively fast and inexpensive method of sequence-based strain typing and has recently been applied to assessing the clonality of C. auris isolates. We show that the use of C. auris-specific oligonucleotides for sequencing, rather than those derived from other Candida species, produces high quality data for MLST, as well as the detection of specific mutations involved in antifungal resistance, such as ERG11. Further assessment is needed by the gold standard in sequence typing, Whole Genome Sequencing (WGS), to confirm our analysis of clonality here. MLST may therefore represent a useful tool in understanding the interrelatedness of invasive C. auris infections in hospitalized patients as well as inform clinical decision-making around infection control and empiric antifungal therapy.