antifungal prophylaxis
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Author(s):  
Alessandro Busca ◽  
Natascia Cinatti ◽  
Jessica Gill ◽  
Roberto Passera ◽  
Chiara Maria Dellacasa ◽  
...  

BackgroundAllogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are exposed to an increased risk of invasive fungal infections (IFIs) due to neutropenia, immunosuppressive treatments, graft-versus-host disease (GvHD) and incomplete immune reconstitution. Although clinical benefit from antifungal prophylaxis has been demonstrated, IFIs remain a leading cause of morbidity and mortality in these patients. In the last decades, attention has also been focused on potential risk factors for IFI to tailor an antifungal prevention strategy based on risk stratification.Aim of the StudyThis retrospective single-center study aimed to assess the epidemiology and the prognostic factors of IFI in a large cohort of allo-HSCT patients.MethodsBetween January 2004 and December 2020, 563 patients with hematological malignancies received an allo-HSCT at the Stem Cell Transplant Unit in Turin: 191 patients (34%) received grafts from a matched sibling donor, 284 (50.5%) from a matched unrelated donor, and 87 (15.5%) from an haploidentical family member. The graft source was peripheral blood in 81.5% of the patients. Our policy for antifungal prophylaxis included fluconazole in matched related and unrelated donors, while micafungin was administered in patients receiving haploidentical transplant. According to this practice, fluconazole was administered in 441 patients (79.6%) and micafungin in 62 (11.2%), while only 9 patients received mold-active prophylaxis. Galactomannan testing was routinely performed twice a week; patients with persisting fever unresponsive to broad spectrum antibiotics were evaluated with lung high-resolution computed tomography (HRCT) scan. In case of imaging suggestive of IFI, bronchoalveolar lavage (BAL) was performed whenever feasible.Statistical AnalysisOnly probable/proven IFI (PP-IFI) occurring during the first 12 months after transplant have been evaluated. IFIs were classified as probable or proven according to the new revised European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) consensus criteria. Multivariate competing risk regression, binary logistic, and proportional hazard models were performed to identify risk factors for PP-IFI.ResultsA total of 58 PP-IFIs (n = 47 probable; n = 11 proven) occurred in our patients resulting in a cumulative incidence of 4.1%, 8.1%, and 9.6% at 30, 180, and 365 days, respectively. Molds were the predominant agents (n = 50 Aspergillus; n = 1 Mucor), followed by invasive candidemia (n = 5 non-albicans Candida; n = 1 Candida albicans; n = 1 Trichosporon). Lung was the most frequent site involved in patients with mold infections (47/51, 92.2%). Median time from HSCT to IFI was 98.44 days (0–365 days). Only 34.5% of patients with IFI were neutropenic at the time of infection. The presence of IFI had a significant impact on overall survival at 1 year (IFI, 32.8% vs. non-IFI, 54.6%; p < 0.001). IFI-related mortality rate was 20.7% in the overall population, 17% in patients with probable IFI, and 36% in patients with proven IFI. Multivariate competing risk regression revealed that donor type was the factor significantly associated to the risk of IFI [subdistribution hazard ratio (SDHR), 1.91, IC 1.13–3.20; p = 0.015]. BAL was informative in a consistent number of cases (36/57, 63.2%) leading to the identification of fungal (21), bacterial (4), viral (3), and polymicrobial (8) infections. Overall, 79 patients (14%) received a diagnostic-driven treatment, and 63 patients (11.2%) received a fever-driven treatment. Liposomal amphoteric B was the drug used in the majority of patients receiving diagnostic-driven therapy (30/79, 38%), while caspofungin was administered more frequently in patients who received a fever-driven strategy (27/63, 42.9%).ConclusionAccording to our experience, a non-mold active prophylaxis in patients undergoing allo-HSCT is feasible when combined with an intensive diagnostic work-up including CT scan and BAL. BAL performed at the onset of the disease may provide informative results in most patients. A diagnostic-driven treatment strategy may contribute to limit the use of costly antifungal therapies.


2021 ◽  
Vol 27 (1) ◽  
pp. 57-62
Author(s):  
Julio Maquera-Afaray ◽  
Medalit Luna-Vilchez ◽  
Blanca Salazar-Mesones ◽  
Diana Portillo-Alvarez ◽  
Luis Uribe-Ramirez ◽  
...  

OBJECTIVE Prophylaxis with posaconazole (PP) is effective in the prevention of invasive fungal infections in immunocompromised adult patients. However, evaluation of its effectiveness and safety in children is limited. The aim of the study was to describe the use of posaconazole as antifungal prophylaxis in children. METHODS We reviewed the medical records of immunocompromised patients younger than 13 years with hematologic diseases and post hematopoietic stem cell transplant (HSCT) who received antifungal PP at the Instituto Nacional de Salud del Niño San Borja (INSN-SB) in Lima, Peru, from January 2014 to December 2018. RESULTS Fifty-six courses of PP were identified in 47 patients with a median age of 7.5 years (IQR, 4–10), 51.6% (n = 24) of whom were female. The main underlying medical conditions were aplastic anemia (n = 19, 33.9%), acute lymphoblastic leukemia (n = 18, 32.1%), acute myeloid leukemia (n = 14, 25.0%), and 34.1% had undergone HSCT. The median dose of posaconazole was 13.62 mg/kg/day (IQR, 12.0–16.8), and the median duration of PP was 24 days (IQR, 16–82). Gastrointestinal symptoms included abdominal pain (17.9%), nausea (16.1%), diarrhea (7.1%), and vomiting (3.6%). Elevated alanine aminotransferase and aspartate aminotransferase levels were observed in 9/35 patients (25.7%) and 10/51 (19.6%) patients, respectively. Five cases of breakthrough fungal infection were identified (8.9%). CONCLUSIONS Patients younger than 13 years who received PP showed an increase in transaminase values, and the development of breakthrough fungal infections.


Author(s):  
Jose F. Camargo ◽  
Ra'ed Jabr ◽  
Anthony D. Anderson ◽  
Lazaros Lekakis ◽  
Meilin Diaz-Paez ◽  
...  

Invasive aspergillosis is the most common invasive mold infection following a hematopoietic cell transplant. Widespread use of antifungal prophylaxis has led to increasing incidence of cryptic Aspergillus species. Aspergillus calidoustus is one of those emerging species and is notorious for multidrug resistance to antifungals. Here we report a case of disseminated A. calidoustus infection in a hematopoietic stem cell transplant recipient, who was successfully treated with combination therapy that included a novel antifungal.


Author(s):  
Ashish Lanjekar ◽  
Pranada Deshmukh ◽  
Devendra Palve ◽  
Monal Kukde ◽  
Isha Madne ◽  
...  

Aims: To evaluate the effect of topical antifungal Clotrimazole on candida colonies and its correlation with clinical candidiasis in patients undergoing radiotherapy. Study Design: Randomised Clinical Trial Place and Duration of Study: Rashtrasant Tukdoji Maharaj Cancer Institute, Nagpur between June 2020 and July 2021. Methodology: 64 patients (52 males and 12 females) undergoing Co60 teletherapy for cervicofacial malignancies were randomly divided in two groups. 32 patients referred to as study group were put on antifungal treatment (1% Clotrimazole) for topical application and other group was the control group and was not given antifungal medication. During the radiotherapy and 6 weeks after the completion of radiotherapy, patients were examined every week for possible oral changes for clinical candidiasis, and swabs were taken at every end of the week for determining candidal colonies. Results: The overall incidence of clinical oral candidiasis was 46.9% throughout RT in the control group and there was no incidence of clinical candidiasis in the study group. Patients with clinical candidiasis 6-week post-radiation therapy showed continuous symptoms of clinical candidiasis but with the reduction in candidal colonies.22% of patients were oral carriers for candidal colonies. Also, the study group showed not a single patient with clinical candidiasis. Conclusion: During radiotherapy, although with the use of clotrimazole some patients with negative culture may also become positive for Candida albicans and there may be some increase in the several colonies of Candida albicans (very less in number as compared to the control group), but its use prevents the development of clinical candidiasis. Antifungal prophylaxis is useful in combating clinical candidiasis.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6285
Author(s):  
Raeseok Lee ◽  
Sung-Yeon Cho ◽  
Dong-Gun Lee ◽  
Hyeah Choi ◽  
Silvia Park ◽  
...  

Although venetoclax (VEN)-based combination chemotherapy in patients with acute myeloid leukemia (AML) results in prolonged and profound neutropenia, data regarding infectious complications and antimicrobial prophylaxis are lacking. We investigated the infectious complications in 122 adult patients with AML under the same standard of care for prevention. The prophylaxis protocol was fluconazole 400 mg/d without antibacterial agents. The incidence of proven or probable invasive fungal infections (IFIs) was 6.6/100 cycles, and 22 patients (18.0%) were diagnosed (median, second cycle; interquartile range, 1–2). All IFIs were caused by Aspergillus and significantly influenced the overall mortality (odds ratio (OR), 2.737; 95% confidence interval (CI), 1.051–7.128; p = 0.034). In the multivariate analysis, secondary or therapy-related AML was an independent risk factor for IFIs (OR, 3.859; 95% CI, 1.344–11.048, p = 0.012). A total of 39 bloodstream infection (BSIs) episodes occurred in 35 patients (28.7%), with an incidence of 12.7/100 cycles. High-dose steroid administration within 90 days was associated with the occurrence of BSIs (OR, 7.474; 95% CI; 1.661–3.631, p = 0.008), although BSIs themselves did not have an impact on the outcomes. Our findings suggest evidence for the need for mold-active antifungal agents as antifungal prophylaxis, rather than fluconazole, especially in patients with secondary or therapy-related AML.


Author(s):  
K. Devaraja ◽  
Neethu V. Krishnan ◽  
Vasudeva K. Bhat ◽  
Kailesh Pujary ◽  
Archana M. Venkatagiri ◽  
...  

AbstractPalatal involvement in mucormycosis is mostly secondary to rhino-orbito-cerebral disease, but rarely can be a primary disease of the oral mucosa. This report presents two rare cases of the isolated palatal mucormycosis in neutropenic children and highlights some of the peculiar features of the primary palatal disease and management-related issues in children. A 12-year-old child, who had completed the dexamethasone-based induction phase of chemotherapy for Near Early T cell precursor acute lymphoblastic leukemia, and a 9-year-old boy with a Late Isolated Medullary relapse of B cell acute lymphoblastic leukemia, who was to receive salvage induction chemotherapy, developed palatal discoloration without any other major complaints. Both had neutropenia and were on antifungal prophylaxis. In vitro staining of the discolored mucosa suggested mucormycosis, which was confirmed by pathological examination of the debrided tissue. Computed tomography, done before debridement, showed no significant sinonasal disease enabling us to proceed with the transoral approach. With the help of adjuvant antifungal therapy, the infection could be contained in both cases. This report, along with the reviewed literature, shows that limited palatal mucormycosis can be effectively treated by early diagnosis and debridement and appropriate antifungal therapy. Also, the role of antifungal prophylaxis amongst neutropenic patients has been briefly discussed here.


Acta Medica ◽  
2021 ◽  
pp. 1-4
Author(s):  
Melda Bahap ◽  
Pinar Bakir Ekinci ◽  
Sehnaz Alp ◽  
Serife Gul Oz ◽  
Kutay Demirkan

Three formulations of amphotericin B are available: liposomal, lipid complex and conventional. The liposomal amphotericin B is more preferred agent than other formulations because of its tolerability, safety and potent antifungal activity. However, the liposomal amphotericin B can cause infusion-related reactions. In this case report, we aimed to report a patient who developed infusion-related reactions during the treatment with the liposomal amphotericin B but eventually tolerated the prolonged infusion. In this case report, we present a patient who developed an infusion-related reaction during The liposomal amphotericin B treatment. A 26-year-old male patient with acute promyelocytic leukemia was hospitalized for the third course of chemotherapy. Due to the invasive fungal infection history in previous hospitalizations, the liposomal amphotericin B 400 mg (IV, 5 mg/kg) once daily was initiated as secondary antifungal prophylaxis. Swelling in infusion site and chest pain were reported within 10 minutes of the liposomal amphotericin B administration, and the infusion rate was slowed down to 400 mg/6 hours from 400 mg/2 hours. All these reactions disappeared with prolonged infusion time. The patient received a total of 7 liposomal amphotericin B doses subsequently without any reaction during the chemotherapy cycle. In our experience, the liposomal amphotericin B-induced infusion-related reactions can be resolved by prolonging the infusion time.


2021 ◽  
pp. 089686082110576
Author(s):  
Caroline Kempf ◽  
Johannes Holle ◽  
Susanne Berns ◽  
Stephan Henning ◽  
Philip Bufler ◽  
...  

Background: Peritoneal dialysis (PD) is the preferred dialysis modality for paediatric patients with end-stage kidney disease. Frequently, malnutrition is encountered. Percutaneous endoscopic gastrostomy (PEG) is the preferred mode of feeding because of its minimal invasive mode of placement and easy handling in daily life. However, reports of a high risk for early post-interventional peritonitis hampered this procedure during PD and controlled studies on the benefit of peri-interventional management to prevent peritonitis are lacking. Here, we report the safety profile of PEG insertion among a cohort of children on PD by using a prophylactic antibiotic and antifungal regimen as well as modification of the PD programme. Methods: We performed a single-centre analysis of paediatric PD patients receiving PEG placement between 2015 and 2020. Demographic data, peri-interventional prophylactic antibiotic and antifungal treatment as well as modification of the PD programme were gathered and the incidence of peritonitis within a period of 28 days after PEG was calculated. Results: Eight PD patients (median weight 6.7 kg) received PEG insertion. Antibiotic and antifungal prophylaxis were prescribed for median time of 4.0 and 5.0 days, respectively. After individual reduction of PD intensity, all patients continued their regular PD programme after a median of 6 days. One patient developed peritonitis within 24 h after PEG insertion and simultaneous surgery for hydrocele. Conclusions: Applying an antibiotic and antifungal prophylactic regime as well as an adapted PD programme may reduce the risk for peritonitis in paediatric PD patients who receive PEG procedure.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4126-4126
Author(s):  
Evan C. Chen ◽  
Yiwen Liu ◽  
Eric S. Winer ◽  
Marlise R. Luskin ◽  
Martha Wadleigh ◽  
...  

Abstract Introduction: The Phase 3 VIALE-A study established the combination of venetoclax and a hypomethylating agent (VEN/HMA) as a new standard of care option for acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy due to age (≥ 75 years) or comorbidities. The NCCN recommends antifungal prophylaxis (AFP) for relapsed/refractory AML patients receiving VEN/HMA, but its role in newly diagnosed AML patients treated with VEN/HMA remains controversial. Additionally, the impact of VEN dose-reduction due to concomitant azole use on AML outcomes and rates of fungal infection remains unclear. We evaluated the pattern of AFP use and its association with infectious and AML outcomes in patients receiving VEN/HMA at our institution. Methods: Consecutive patients aged ≥18 who received frontline VEN/HMA for newly diagnosed AML at the Dana-Farber Cancer Institute between 2016-2021 were identified in the Hematologic Malignancy Data Repository for retrospective chart review. Antibacterial and antifungal prophylaxis use at any time during VEN/HMA therapy and reasons for hospitalizations were recorded. Invasive fungal infections (IFIs) were adjudicated as "possible," "probable," or "proven" according to consensus guidelines (Donnelly, Clin Infect Dis 2020). Rates of complete remission (CR) and CR with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) criteria were determined. Descriptive statistics on patient characteristics were compared between groups via nonparametric testing including Wilcoxon rank-sum, chi-squared, and the Fisher's Exact tests. Overall survival (OS) was estimated using the method of Kaplan and Meier, and log-rank tests were used to compare survival between groups. Multivariable Cox proportional-hazards models were used to obtain hazard ratios between groups. Results: 131 patients met inclusion criteria, of which 22 patients (16%) received AFP at any time. For the entire cohort, the median age at AML diagnosis was 72 (range 22-89), and the majority of patients were <75 years old (66%), had ELN adverse risk (70%), and had secondary AML (sAML)/sAML-like disease (73%; "sAML-like" defined per Lindsley, Blood 2015). Frequently mutated genes include TP53 (37%), ASXL1 (22%), and RUNX1 (19%). These baseline characteristics did not differ between patients who did and did not receive AFP. However, compared to patients who never received AFP, patients receiving AFP at any time were more likely to have received HMA therapy for an antecedent hematologic malignancy (41% vs. 13%, p=0.004) and concomitant antibacterial prophylaxis at any time (82% vs. 54%, p=0.016). Among the 171 hospitalizations that occurred in 90/131 patients, bacterial infection was suspected or identified in 139 admissions, and possible/probable/proven IFIs were identified in 21. Receiving AFP prior to admission was not associated with fewer hospitalizations in which an IFI was suspected or identified (Table, p=0.36). 3/21 IFIs were deemed "probable" or "proven." All 21 IFIs prompted antifungal therapy. No patient experienced more than one hospitalization involving an IFI. After a median of two cycles (range 1-15), best response (CR/CRi) for the entire cohort was 49%. Receiving AFP at any time was associated with lower CR/CRi than never receiving AFP (57% vs. 32%, p=0.014). The median OS for the entire cohort was 11.0 months (95% CI 8.8-14.6) and did not differ based on AFP use (11.9 months for patients without AFP, 8.1 months for those receiving AFP; p=0.23). In a multivariable model that included patient age, ELN risk, and AML ontogeny, AFP use was not significantly associated with OS (HR 1.40, p=0.22). Conclusion: AFP use and incidence of invasive fungal infection were overall low at our institution. Receiving AFP was not associated with improved OS nor with decreased number of hospitalizations for a suspected or confirmed IFI. At an institution where the incidence of fungal infections is low, there is presently no clear role for antifungal prophylaxis in newly-diagnosed AML patients receiving HMA with venetoclax. Figure 1 Figure 1. Disclosures Winer: Takeda: Consultancy; Novartis: Consultancy; Abbvie: Consultancy. Lane: AbbVie: Research Funding; Stemline Therapeutics: Research Funding; Qiagen: Consultancy, Honoraria; N-of-One: Consultancy, Honoraria. Neuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Other: Stock ownership. DeAngelo: Blueprint Medicines Corporation: Consultancy; Takeda: Consultancy; GlycoMimetics: Research Funding; Autolus: Consultancy; Abbvie: Research Funding; Shire: Consultancy; Amgen: Consultancy; Agios: Consultancy; Forty-Seven: Consultancy; Pfizer: Consultancy; Incyte Corporation: Consultancy; Jazz: Consultancy; Novartis: Consultancy, Research Funding. Stone: Syros: Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy; GlaxoSmithKline: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Aprea: Consultancy; Actinium: Membership on an entity's Board of Directors or advisory committees; BerGen Bio: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Janssen: Consultancy; Gemoab: Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy; Novartis: Consultancy, Research Funding; Syndax: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Foghorn Therapeutics: Consultancy; Elevate Bio: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Research Funding; Boston Pharmaceuticals: Consultancy; Syntrix/ACI: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Celgene: Consultancy; Macrogenics: Consultancy. Garcia: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Research Funding; Pfizer: Research Funding; Genentech: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1215-1215
Author(s):  
Simone M Chang ◽  
Mason Holt ◽  
Lauren Hernandez ◽  
Natalie Slone ◽  
Jun Zhao ◽  
...  

Abstract Background In pediatric hematologic malignancy, the incidence of invasive fungal infections (IFI) is ~ 5-10% and leads to significant morbidity and mortality. Acute lymphoblastic leukemia (ALL) accounts for the largest group at risk and has the largest absolute number of IFI. Antifungal prophylaxis has the potential to mitigate risk of invasive infections in ALL but is not currently standard of care due to the paucity of data in ALL subgroups. A recent systematic review showed a significant reduction in proven/probable IFI and fungal infection-related mortality in pediatric patients when using a mold active agent compared with fluconazole, therefore an echinocandin was selected for systemic antifungal prophylaxis in our institution. In this study we investigate the incidence of IFI in patients with ALL in a highly endemic area (Ohio River Valley) and describe the impact of echinocandin prophylaxis in this population. Methods We conducted a retrospective cohort study of consecutive patients <25 years with ALL from 2015 to 2021 at Norton Children's Hospital, Louisville, KY. IFI was classified as possible, probable, or proven as defined by the 2020 European Organization for Research and Treatment of Cancer/ Mycoses Study Group Consensus Group. Patients were then analyzed in 2 subgroups based on prophylaxis with caspofungin. Inpatient administration of caspofungin was given to patients with high-risk B-ALL (HR B-ALL) and T-ALL as outlined in Table 1. Patient and IFI characteristics were collected, and cumulative incidence analyses used for subgroup comparisons. Results Demographics and patient characteristics are summarized in Table 2. Between 2015 to 2020 we identified 100 patients with ALL. Mean age at diagnosis was 7.2 years and 43% were female. We identified 14 unique cases of IFI in 13 patients with ALL who did not receive prophylaxis with caspofungin during 2015 to 2020 (14%). Prior to the implementation of prophylaxis, IFI occurred in 0% (0/43) of the SR B-ALL group, 18.2% (6/33) in HR B-ALL group and 35% (8/23) in T-ALL group. IFI incidence was highest in induction and consolidation phases (71.4%) and implicated species during these phases included Aspergillus, Candida, Fusarium, and Papulasopora. From April 2020 to July 2021, there were 22 newly diagnosed patients with ALL, 11 (50%) of whom received inpatient prophylaxis with caspofungin. There was 1 case (4.5%) of reported IFI during delayed intensification (no prophylaxis at the time of infection). As seen in Figure 1, patients with HR B-ALL and T-ALL who were hospitalized and received caspofungin during induction saw a notable decrease in the cumulative incidence of IFI, from 18.3% to 0% at 6 months into treatment before reaching similar levels in the patients who did not receive prophylaxis. Conclusion In our pediatric population, patients with T-ALL and HR B-ALL were more likely to develop IFI than those with SR B-ALL. Prophylaxis with caspofungin and inpatient hospitalization during induction were effective strategies for reducing the incidence of IFI in induction and consolidation for our high-risk leukemia population. This approach should be validated in larger studies with special consideration being given to patients in fungal endemic areas. Figure 1 Figure 1. Disclosures Raj: Terumo Medical Corporation: Honoraria, Speakers Bureau; Forma therapeutics: Consultancy; Global biotherapeutics: Speakers Bureau.


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