Role Of Antifungal Prophylaxis Research Articles

Role of Antifungal Prophylaxis in Invasive Fungal Infection in Children with Acute Lymphoblastic Leukemia—A Retrospective Cross-Sectional Study

AbstractIntroduction Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Its outcome in India is not as good as that in the western world. One of the important reasons for lesser survival rates is opportunistic infections, including invasive fungal infections (IFIs). Antifungal prophylaxis (AFP) in ALL children is routinely not followed. However, owing to its incidence in high-risk ALL, this study is focused on the use of AFP in those children.Objectives This retrospective study investigated the role of AFP in newly diagnosed children with high-risk ALL on intensive blocks of therapy on regimens B and C of the United Kingdom Acute Lymphoblastic Leukemia 2003 protocol.Materials and Methods The study was conducted in a tertiary care center from 1st December 2013 to 31st December 2019 and included children with ALL from 1 to 18 years of age. Routine AFP with voriconazole was commenced for high-risk ALL children from 1st July 2017 onward in our center. We analyzed data of all IFIs in children before and after AFP with National Cancer Institute high-risk status who had been started on regimen B induction and regimen B or C consolidation and intensification phases.Results A total of 55 children with high-risk ALL were included in the study. The median age was 4 years, with the majority being between the age of 1 and 10 years (38 out of 55; 65%) and predominantly male (36 out of 55; 69%). Total incidence of IFI in our cohort was 51% (28 out of 55). A significant number of children (16 out of 22 [70%]) who were not on prophylaxis developed IFI versus children (12 out of 33 [28%]) on prophylaxis (p = 0.008). The most common organisms isolated were Candida parapsilosis and Candida tropicalis. Children not receiving AFP were found to be 4.7 times (95% confidence interval: 1.44–15.13) more likely to get IFI than the ones receiving AFP. The presence of concurrent bacterial infection increases the risk of IFI (p = 0.04).Conclusion The incidence of IFI was high in high-risk ALL children who were not on AFP. The introduction of routine AFP reduced the incidence of IFI.

Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: Results from SEIFEM 2016-B survey.

In patients with relapsed/refractory acute myeloid leukaemia (R/R AML) who received salvage chemotherapy, limited and not updated studies explored the incidence of invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP). The aims of this multicentre retrospective 'SEIFEM 2016-B' study were as follows: (1) to evaluate the current rate and the outcome of proven/probable IA and (2) to assess the efficacy of AP, in a large 'real life' series of patient with R/R AML submitted to salvage chemotherapy. Of 2250 R/R AML patients, a total of 74 cases of IA (5.1%) were recorded as follows: 10 (0.7%) proven and 64 (4.3%) probable. Information about AP were available in 73/74 (99%) patients. Fifty-eight (79%) breakthrough infections occurred, mainly during AP with posaconazole [25 (43%)]. The patients who received AP during salvage chemotherapy showed a benefit from antifungal therapy (AT) than patients who did not received AP [43 (86%) vs 7 (14%); p<.033]. In a multivariate analysis, AP and absence of severe mucositis had a significant favourable effect on overall response rate. Our data demonstrated that the incidence of IA during the salvage chemotherapy is similar to the past. Nevertheless, the attributable mortality rate (AMR) appears to be lower than that previously reported in R/R AML. Further prospective studies should be performed to confirm our preliminary observation and understand and the why a decreased AMR is reported in this setting of high-risk patients.

Palatal mucormycosis in neutropenic children: A Case Report with Review of Literature

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.

Epidemiology, risk factors, and association of antifungal prophylaxis on early invasive fungal infection in heart transplant recipients.

Invasive fungal infection (IFI) in heart transplant recipients is associated with poor outcomes. Estimated risk of 1-year IFI in heart transplant recipients is 3.4-8.6% with risk factors inconsistently identified in previous studies. The role of antifungal prophylaxis is unclear. The transplant program at Mayo Clinic provides 6 months of universal azole prophylaxis for those heart transplant recipients in Arizona. We sought to define risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. We conducted a retrospective cohort study of patients undergoing heart transplantation at Mayo Clinic from January 2000 to March 2019. We analyzed demographics, details of transplant hospitalization, antifungal prophylaxis, and fungal infection. Multivariable Cox analyses were performed to identify risk factors of 1-year IFI and impact of IFI on posttransplant mortality. A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62). A total of 444 patients received antifungal prophylaxis. Over 1-year follow-up, 62 patients developed IFI with a cumulative incidence of 6.4%. In multivariable analysis, factors associated with IFI were renal replacement therapy (RRT) (HR 3.24, 95% CI 1.65-6.39), allograft rejection (HR 2.33, 95% CI 1.25-4.34), and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96). RRT was also associated with invasive mold infection (HR 3.00, 95% CI 1.29-6.97). RRT and allograft rejection after transplantation are associated with 1-year IFI, and RRT is also associated with invasive mold infection. Antifungal prophylaxis appears to be protective and further study is needed in the heart transplant population.

1086. Epidemiology, Risk Factors, and Effect of Antifungal Prophylaxis on Early Invasive Fungal Infection in Heart Transplant Recipients

BackgroundInvasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis.MethodsWe conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI.ResultsA total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI.ConclusionRenal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding.Disclosures All Authors: No reported disclosures

Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Treatment.

Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Treatment.

The Role of Antifungal Prophylaxis After Receipt of a Positive Donor Rim Fungal Culture: The Case for Not Routinely Treating Prophylactically.

Studies conducted in the United States suggest that 1% to 2% of corneal donor rims culture positive for fungus; the fungal agent is usually Candida, and the risk of an endothelial keratoplasty recipient developing an intraocular fungal infection is approximately 7% (1 in 15) if the donor rim was culture-positive. Routine culturing of corneal donor rims is useful because a positive fungal culture alerts the surgeon to carefully monitor the keratoplasty recipient for any signs of fungal infection. However, routine implementation of antifungal prophylaxis on receipt of a positive culture is problematic because there is a lack of definitive data regarding the optimal route of administration, necessary duration of prophylaxis, and relative efficacy of different antifungal agents. The use of topical prophylaxis alone has not been proven to be effective, and the systemic agents that are effective against Candida typically involve an azole, which has many side effects, including liver toxicity and potential interactions with other drugs. The data suggest that routine antifungal prophylaxis would needlessly expose 14 patients to systemic side effects for each person who would directly benefit. Treatment of postkeratoplasty fungal infection typically involves graft replacement, but selective removal of the involved area(s) has been used successfully with Descemet membrane endothelial keratoplasty.

'Real-life' analysis of the role of antifungal prophylaxis in preventing invasive aspergillosis in AML patients undergoing consolidation therapy: Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM) 2016 study.

We evaluated the incidence of proven/probable invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP) in a 'real-life' setting of patients with AML receiving intensive consolidation therapy. Cases of IA, observed during consolidation in adult/paediatric patients with AML between 2011 and 2015, were retrospectively collected in a multicentre Italian study. Of 2588 patients, 56 (2.2%) developed IA [43 probable (1.7%) and 13 proven (0.5%)]. IA was diagnosed in 34 of 1137 (2.9%) patients receiving no AP and in 22 of 1451 (1.5%) who were given AP (P = 0.01). Number-needed-to-treat calculation indicates that, on average, 71 patients should have received AP (instead of no AP) for one additional patient to not have IA. Initial antifungal therapy was 'pre-emptive' in 36 (64%) patients and 'targeted' in 20 (36%) patients. A good response to first-line therapy was observed in 26 (46%) patients, mainly those who received AP [16 of 22 (73%) versus 10 of 34 (29%); P = 0.001]. The overall mortality rate and the mortality rate attributable to IA by day 120 were 16% and 9%, respectively. In multivariate analysis, age ≥60 years (OR = 12.46, 95% CI = 1.13-136.73; P = 0.03) and high-dose cytarabine treatment (OR = 10.56, 95% CI = 1.95-116.74; P = 0.04) independently affected outcome. In our experience, AP appears to prevent IA from occurring during consolidation. However, although the incidence of IA was low, mortality was not negligible among older patients. Further prospective studies should be carried out particularly in elderly patients treated with high-dose cytarabine to confirm our data and to identify subsets of individuals who may require AP.

Risk factors and predictors of mortality of candidaemia among critically ill patients: role of antifungal prophylaxis in its development and in selection of non-albicans species.

The aim of the present study is to identify risk factors for development and predictors of mortality of candidaemia among critically ill patients. A 1:7 case-control study was conducted during a 4-year period (2012-2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2 Advanced Expert System. Epidemiologic data were collected from the ICU computerized database and patients' chart reviews. Fifty-three patients developed candidaemia with non-albicans species being the predominant ones (33 patients, 62.3%). Multivariate analysis found that prior emergency surgery, malignancy, hospitalization during summer months, prior septic shock by KPC-producing Klebsiella pneumoniae and number of antibiotics administered were independently associated with candidaemia, while, prior administration of azole was a protective factor. Non-albicans candidaemia was associated with number of antibiotics administered and prior administration of echinocandin. Mortality of 14 days was 28.3% (15 patients) and was associated with SOFA score upon infection onset and septic shock, while, appropriate empirical antifungal treatment was associated with better survival. Prophylactic azole administration prevents development of candidaemia, while, echinocandin administration predisposes to non-albicans candidaemia. Empirical administration of an appropriate antifungal agent is associated with better survival.

Celebrating 40 years of progress in bone marrow transplantation: a report from the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation.

The European Society for Blood and Marrow Transplantation was established in 1974 to enable scientists and physicians involved in clinical bone marrow transplantation to share their experience and develop cooperative studies. The organization celebrated its 40th anniversary with a meeting that considered hematopoietic stem cell transplantation not as a standalone procedure, but as part of a complex therapeutic program managed by a multidisciplinary professional team. The role of antifungal prophylaxis, emerging resistance in Aspergillus, the management of mucormycosis and new guidelines on antifungal therapy were among the topics discussed by the physicians, nurses, allied health professionals and scientists attending the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation.

FLUCONAZOLE MONITORING IN LIVER TRANSPLANT RECIPIENTS

P832 Aims: The role of antifungal prophylaxis in liver transplantation (OLTx) is accepted for the high risk of fungal infections due to Candida spp. in OLTx recipients. However, the extensive use of fluconazole, still considered the gold standard drug, can determinate microbiological drug resistance or shift to Candida non albicans species. A low drug exposition, intended as both patient’s under-exposition and population’s over-use, represents one of the principal factors in the genesis of fungal resistance or shift to fluconazole resistant strains of Candida spp. Considering that pharmacodinamic characteristics of the azoles determinate their time dependant action, to optimize the use of fluconazole is important to maintain a pre-dose plasmatic concentration of the drug (Cmin) always over the MIC of sensible strains. Methods: All OLTx recipients receiving prophylaxis with fluconazole at a dosage of 200-400 mg/die, underwent monitoring of plasmatic concentration (TDM) since to post-treatment day two, in order to obtain Cmin levels ≥ 8 mg/L (in vitro sensibility breakpoint for Candida spp.) HPCL was used for determination of C-min levels. We retrospectively analyzed the levels of exposition obtained by dose of fluconazole, and by renal function. Results: 14 patients, 9 with normal renal function (group 1) (median CLCR 0.52-0.76 mL/min/kg), and 5 patients needing CVVH (group 2) (median CLCR 0.40-0.56 mL/min/Kg). In group 1 the optimal dose of fluconazole (range Cmin 9.33-12.48 mg/L), during prophylaxis administration (range 5-24 days), was 4.07-5.01 mg/Kg during the first 48-72 hours and 1.76-3.45 mg/Kg subsequently. In group 2, similar average doses of fluconazole (3.54-4.25 mg/Kg during the first 48-72 hours, and 2.62-3.90 mg/Kg thereafter), did not allow to maintain stable plasmatic concentration range of fluconazole (Cmin 5.10-12.54 mg/L) during the study period (6-14 days). Conclusions: our preliminary data, although limited to a small group of patients, suggest that a initial dose of 400 mg of fluconazole, followed by 200 mg/die, could be adequate to prevent Candida spp. infection for patients with normal renal function after OLTx. Thereafter in case of epidemiological settings of a low incidence of resistant or dose-dependant non albicans species it seems not useful to administer higher dosage. In patients with alterated renal function necessitating CVVH, there was a marked variability of fluconazole plasmatic concentration and a higher dosage of fluconazole is needed. This data is of particular clinical interest, since CVVH is frequently compared to haemodialysis with subsequent tendency to reduce the dosage of the drug while in that condition an increment of the dose is quite almost always necessary.