Fungal-related Mortality Research Articles

Invasive Fungal Disease in Patients with Myeloid Malignancies: A Retrospective Cohort Study of a Diagnostic-Driven Care Pathway Withholding Mould-Active Prophylaxis

Objectives: Patients receiving remission induction therapy for acute myeloid leukaemia (AML) are at high risk of developing invasive fungal disease (IFD). Newer therapies with targeted antileukemic agents and the emergence of azole resistance pose a challenge to the strategy of primary antifungal prophylaxis. We report the experience of a diagnostic-driven care pathway (DCP) for the management of IFD in these patients, using only culture-directed mould inactive prophylaxis. Methods: Retrospectively, we used a single-centre study of consecutive patients receiving intensive chemotherapy for myeloid malignancies between 2014 and 2021. DCP consisted of serial cultures and serum galactomannan (sGM) screening, CT imaging, and bronchoscopy to direct targeted antifungal treatment. IFD was classified according to the 2020 EORTC/MSGERC criteria. Results: A total of 192 patients with myeloid malignancies received 300 courses of intensive chemotherapy. There were 14 cases of invasive yeast infections and 18 of probable/proven invasive mould disease (IMD). The incidence of probable/proven IMD during the first cycle of remission-induction chemotherapy was 4.6% (n = 9). sGM remained negative in all cases of invasive aspergillosis (IA), with positive mycology findings in bronchoalveolar lavage. All-cause mortality was 9.4% (n = 18) 100 days after starting chemotherapy and was comparable between patients with or without IFD. The fungal-related mortality was 1% (n = 2). Conclusion: Diagnostic-driven based management without universal mould active prophylaxis is a feasible strategy in the management of IFD and limits unnecessary antimould treatment during intensive chemotherapy. The poor performance of serial serum galactomannan screening in detecting IA warrants further investigation.

Prevalence of Cryptococcus gattii in Ugandan HIV-infected patients presenting with cryptococcal meningitis.

IntroductionCryptococcal meningitis (CM) is a life threatening disease and leading cause of opportunistic fungal-related mortality in HIV/AIDS. Most CM infections are caused by C. neoformans species complexes but the prevalence of Cryptococcus gattii species complexes in Uganda is unknown however, it is known in a few other parts of Africa. We estimated the prevalence of C. gattii in patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda.MethodsCryptococcus isolates (n = 200) obtained from cerebrospinal fluid of patients with CM recruited at the Infectious Diseases Institute, Kampala, Uganda, were tested by phenotypic methods. The Cryptococcus isolates were sub-cultured on Sabouraud Dextrose Agar plates for 48 hours. The yeast colonies were examined by India ink stain, urea hydrolysis, and C. gattii was identified by blue pigmentation on CGB agar. The results were analyzed for frequency of C. gattii. Patient demographic characteristics were collected from the case record forms.ResultsFrom the 200 patients’ case record forms, 87 (43.5%) were female and 113 (56.5%) were male. The median age was 35 (19–64) years. Most patients, 93% (187/200) were from Central Uganda in the districts of Kampala and Wakiso. 97.51% (157/161) of the patients had absolute CD4 lymphocyte counts of less than 200 cells per cubic millimeter; 1.86% (3/161) 200–350 cells per cubic millimeter and 0.62% (1/161) above 500 cells per cubic millimeter. 45.4% (74/163) were not yet on HAART and 54.6% (89/163) were on HAART. 66.7% (58/87) had poor adherence to HAART treatment and 33.3% (29/87) had reported good adherence to HAART treatment. A total of 200 clinical isolates of Cryptococcus isolates were tested. No (0% (0/200) C. gattii was identified among the Cryptococcus isolates.ConclusionIn this study among patients living with HIV and a diagnosis of cryptococcal meningitis in Uganda, we found no C. gattii infections.

Association of Age-adjusted Charlson Comorbidity Index With Orbital Fungal Disease Outcomes.

To determine whether the age-adjusted Charlson comorbidity index (age-CCI) in sino-orbital fungal disease patients correlates with disease-specific mortality. Hospital billing systems at 2 academic institutions were queried for patients with ICD-9, ICD-10, and CPT codes used in fungal disease who also had orbital disease and significant visual loss. Thirty-two patients at Institution A and 18 patients at Institution B met the inclusion criteria of microbiologic or pathologic confirmation of fungal infection and completion of inpatient ophthalmology evaluation. Patients without radiographic abnormality in the sinus or orbit were excluded. Demographic, diagnostic, treatment, and outcome variables were recorded. Our primary outcome was death due to fungal disease. Of the 50 medical records examined, 44 patients met the criteria for fungal-related death outcome on multivariate analysis. The regression coefficient for age-CCI and fungal-related mortality was 0.242 (95% CI, 0.012-0.779) with a p value of 0.038. Age-CCI is significantly associated with fungal-related mortality. This relationship remains significant when controlling for 5 covariates of fungal organism phylum, presence or absence of CNS disease, exenteration, local treatment use, and presence or absence of an immunosuppressive diagnosis. Age-CCI shows promise as a clinical and research tool in the evaluation of invasive fungal disease involving the orbit.

Evaluation of Two Entomopathogenic Fungi for Control of Culex quinquefasciatus (Diptera: Culicidae) in Underground Storm Drains in the Coachella Valley, California, United States.

Commercially available formulations of two entomopathogenic fungi, Beauveria bassiana (Bals.-Criv.) Vuill. (Hypocreales: Clavicipitaceae) and Metarhizium anisopliae (Metchnikoff) Sorokin (Hypocreales: Clavicipitaceae), were assessed for control of Culex quinquefasciatus Say (Diptera: Culicidae) in underground storm drain systems (USDS) in the Coachella Valley of southern California. Each of three treatments, the two fungi or a water control, was applied to 1 m2 of vertical wall at eight USDS sites in spring and autumn of 2015. Fungal infectivity and lethality were assessed at 1 d and 1, 2, and 4 wk post-application. Overnight bioassays using adult lab-reared female mosquitoes were carried out on the treated USDS wall areas and then mosquitoes were held in the laboratory for up to 21 d to allow fungal infections to be expressed. Postmortem fungal sporulation was assessed up to 2 wk at 100% humidity. Mosquito-fungal interactions also were assessed in bioassays of the three treatments on filter paper exposed to USDS conditions during autumn. Metarhizium anisopliae killed mosquitoes faster than B. bassiana; nevertheless, both freshly applied formulations caused greater than 80% mortality. Fungal persistence declined significantly after 1 wk under USDS conditions, but some infectivity persisted for more than 4 wk. Beauveria bassiana was more effective against Cx. qinquefasciatus in the spring, while M. anisopliae was more effective in the cooler conditions during autumn. USDS environmental conditions (e.g., temperature, relative humidity, standing water) influenced fungal-related mortality and infection of Cx. quinquefasciatus. The utility of these fungal formulations for mosquito abatement in the Coachella Valley and implications for fungal control agents in USDS environments are discussed.

Invasive fungal infections in pediatric hematopoietic stem cell transplant patients

Background: Pediatric hematopoietic stem cell transplant (HSCT) recipients are at high risk of invasive fungal infections (IFIs). Methods: To characterize IFIs and changes in fungal organisms over time in pediatric HSCT patients, we performed a retrospective cohort study of all HSCTs performed in pediatric patients at UCLA between 1991 and 2006. Results: In all, 318 patients underwent 324 HSCT transplants over the 15-year period and 69 unique fungal infections were identified in 47 transplant patients. The overall incidence of fungal infections in HSCT recipients was 14.5%, with predominant organisms including Candida species (51%) and Aspergillus species (26%), with Candida albicans accounting for 18.8% of all fungal species. The distribution of organisms over time demonstrated a strong trend towards an increase in rare molds in more recent years. The respiratory tract was the main site of infection (52.6%), with urine and blood also noted as significant sites. Of all deaths in the patients with IFIs, fungal-related mortality accounted for 67.6% of deaths. Conclusions: HSCT patients have a much higher risk of fungal infections with rarer organisms becoming more prevalent, a finding likely linked to evolving antifungal practices over time. This emphasizes the need for the development and implementation of improved diagnostic, prophylactic, and therapeutic strategies to improve patient survival.

Report From the 39th Annual Meeting of the European Group for Blood and Marrow Transplantation, London, 7–10 April 2013

Antifungal prophylaxis reduces the risks of invasive fungal infection (IFI), all-cause mortality and fungal-related mortality in highly immunosuppressed haemato-oncology patients, but questions remain about the role of therapeutic drug monitoring in this patient population. There is also continuing debate concerning the benefits and risks of empirical versus pre-emptive antifungal therapy when breakthrough IFI occurs during prophylaxis. These topics were discussed during the 39th Annual Meeting of the European Group for Blood and Marrow Transplantation, held in London in April 2013.

Prophylaxis with itraconazole is more effective than prophylaxis with fluconazole in neutropenic patients with hematological malignancies: a meta-analysis of randomized-controlled trials

Antifungal prophylaxis using fluconazole or itraconazole has been studied for many years but still no consensus has been reached regarding their safety and effectiveness. We performed a systematic meta-analysis to assess the efficacy of fluconazole compared to itraconazole in neutropenic patients with hematological malignancies. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane-controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 1/2009) searches. Risk ratio (RR) and 95% confidence intervals (CIs) were calculated using the random effect model. Nine RCTs were identified that were published in full text. Significantly, fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (RR 0.45, 95% CI 0.27-0.75, P=0.002). There were statistically significant differences regarding fungal infections (RR 1.34, 95% CI 1.08-1.67, P=0.009) and invasive fungal infections (RR 1.33, 95% CI 1.02-1.73, P=0.03) between the two educations. There were no statistically significant differences regarding overall mortality (RR 0.95, 95% CI 0.77-1.17, P=0.64), fungal-related mortality (RR 1.28, 95% CI 0.80-2.07, P=0.31), and proven fungal infections (RR 1.38, 95% CI 0.75-2.53, P=0.30). The analysis of published evidence reveals that itraconazole administration resulted in significantly fewer episodes of fungal infections and invasive fungal infections compared with fluconazole.

268: Update on Fungal Infections in Pediatric Bone Marrow Transplant Patients at the Mattel Children's Hospital at UCLA from 1991–2006

Objectives: To identify changes in fungal organisms and characteristics of their infections over time in pediatric bone marrow transplant (BMT) patients. Identify differences in fungal species causing infections in different BMT patients. Methods: We performed a retrospective cohort study of all 324 patients on the pediatric hematology and oncology service at UCLA between 1991 and 2006 who underwent bone marrow transplantation. Cultures positive for fungus were identified from both the microbiology lab database as well as medical record review to identify eighty-three unique infections in fifty-four transplant patients. Results: The overall incidence of fungal infections in BMT recipients was 16.7%. The predominant organisms included: Candida species (55%) and Apergillus species (21%), with Candida albicans accounting for 19% of all fungal species. A variety of other fungal species comprised the remainder of infections. The distribution of organisms over time demonstrated a strong trend towards an increase in rare molds in more recent years. The respiratory tract was the main site of infection (41%) with urine (17%) and blood (11%) also noted as significant sites. Upon stratification of the BMT patients who developed fungal infections, the primary diagnoses were ALL (48%) and myeloid malignancy (35%); underlying diagnosis, however, had little impact on the development of a fungal infection in BMT patients. Of all deaths in the studied population, fungal-related mortality of patients analyzed was 44%. Conclusions: Bone marrow transplant patients have a high risk of fungal infections, likely secondary to their severe and prolonged neutropenia. This risk appears to be increasing over time with rarer organisms becoming more prevalent. This emphasizes the need for the development and implementation of improved diagnostic and therapeutic strategies in order to improve survival in this population. Objectives: To identify changes in fungal organisms and characteristics of their infections over time in pediatric bone marrow transplant (BMT) patients. Identify differences in fungal species causing infections in different BMT patients. Methods: We performed a retrospective cohort study of all 324 patients on the pediatric hematology and oncology service at UCLA between 1991 and 2006 who underwent bone marrow transplantation. Cultures positive for fungus were identified from both the microbiology lab database as well as medical record review to identify eighty-three unique infections in fifty-four transplant patients. Results: The overall incidence of fungal infections in BMT recipients was 16.7%. The predominant organisms included: Candida species (55%) and Apergillus species (21%), with Candida albicans accounting for 19% of all fungal species. A variety of other fungal species comprised the remainder of infections. The distribution of organisms over time demonstrated a strong trend towards an increase in rare molds in more recent years. The respiratory tract was the main site of infection (41%) with urine (17%) and blood (11%) also noted as significant sites. Upon stratification of the BMT patients who developed fungal infections, the primary diagnoses were ALL (48%) and myeloid malignancy (35%); underlying diagnosis, however, had little impact on the development of a fungal infection in BMT patients. Of all deaths in the studied population, fungal-related mortality of patients analyzed was 44%. Conclusions: Bone marrow transplant patients have a high risk of fungal infections, likely secondary to their severe and prolonged neutropenia. This risk appears to be increasing over time with rarer organisms becoming more prevalent. This emphasizes the need for the development and implementation of improved diagnostic and therapeutic strategies in order to improve survival in this population.

Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis

To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions. We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data. Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole. Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.

Empirical Versus Pre-Emptive Antifungal Therapy in High-Risk Febrile Neutropenic Patients: A Prospective Randomized Study.

Empirical (E) antifungal therapy (ATF) is a standard of care in febrile neutropenic patients under broad-spectrum antibiotics. However, the safety and cost-effectiveness of the E strategy are challenged, due to better diagnostic methods including galactomannan antigenemia (GM Ag) and efficient therapies for invasive fungal infection (IFI). Previous open studies have evaluated the feasibility of a pre-emptive (PE) strategy where ATF is restricted to patients with clinical symptoms and/or mycological criteria of IFI. This study is the first prospective, randomized trial comparing E vs PE strategy.Objective: The primary objective of the study was to show that a PE strategy was not inferior to a E strategy for overall survival.Patients: 293 adult patients with hematologic malignancies (acute leukemia: 199; lymphoma: 65; others:29), including 91 with autologous stem cell transplant (ASCT) and an expected neutropenia (<500 PMN) of ≥ 10 days following chemotherapy were randomized between E or PE strategy with polyens. All were screened 2/w for GM Ag. E patients were given ATFs in case of persistent or recurrent fever, whatever the accompanying symptoms, while PE patients were given ATFs only in case of pneumonia, severe mucositis, septic shock, sinusitis, or skin lesions evocative of filamentous infection, aspergillus colonization, or positive GM Ag.Methods: This is a multicenter open-label randomized non-inferiority trial. Randomization was stratified according to center, induction vs. consolidation or ASCT, and antifungal prophylaxis. The primary endpoint was the proportion of patients alive either 14 days after recovery from neutropenia or 60 days after inclusion in case of persistent neutropenia or severe complication. Non-inferiority was concluded if survival difference was above the threshold of −8% in intention-to-treat (ITT) and per protocol (PP) analyses. The secondary endpoint was the proportion of patients with IFI (EORTC-MSG definitions).Results: Among the 150 patients of the E group, and the 143 of the PE group, the mean (std) age was 52 (14) y. The mean (std) duration of neutropenia was 21 (11) days (min: 5; max: 69). Survival was not inferior in the PE group (136/143) as compared to the E group (147/150) with a survival difference of −2.9% [95% CI, −6.4% to 0.6%] in ITT (n=293) and −2.9% [95% CI, −6.8% to 0.1%] in PP (n=266) above the threshold of −8%. The IFI-related mortality was not significantly different in the PE group (3/150) and the E group (0/143) (p=0.12). However, significantly more IFI were diagnosed in the PE group (13/143) when compared to the E group (4/150) (p<0.02). The PE patients received significantly less ATFs than the E group (46% v. 66% of patients, p<0.001).Conclusion: A PE strategy based on clinical symptoms and GM Ag did not reduce the overall survival of prolonged neutropenic patients when compared to a E strategy. Although we observed significantly more IFI in the PE than in the E group, this did not translate in a higher fungal-related mortality (Grants: PHRC 2002AOR02028)

Itraconazole for Antifungal Prophylaxis in Neutropenic Patients: An Update of a Meta-Analysis with Now 3846 Patients.

Invasive fungal infections, esp. from Aspergillus spp., still are a major cause of mortality and morbidity in neutropenic patients with haematological malignancies. We have published a meta-analysis on the use of itraconazole for antifungal prophylaxis (Glasmacher et al., JCO 2003; 21: 4615) and now present updated results.Methods: In a continuous search of electronic databases and abstracts we identified randomized clinical trials in neutropenic patients that compared itraconazole with either nothing, oral polyenes or fluconazole. Again, analysis was restricted to proven invasive fungal infections according to EORTC/MSG criteria. Statistical analyses were performed with the Cochrane Review Manager (Version 2.4.8), relative risk ratios (RR) with their 95% confidence intervals (95%CI) and appropriate P values were reported. Subgroups were defined by itraconazole preparation and the comparator. A RR below 1 indicates better results for itraconazole.Results - New Trials: Two new trials with 54 and 195 evaluable patients (pts) were identified and the data of one unpublished trials was updated. Both studies used itraconazole solution (400 mg/d) and compared it to 400 mg/d fluconazole. One study applied intravenous solutions of both drugs if necessary. No study was powered to detect a significant difference in proven invasive fungal infections between the two drugs. One study reported a reduction of fungal-related mortality in the itraconazole arm (fluconazole 9/12, 75%, vs. itraconazole 5/11, 45%; P=0.154).Results - Meta-Analysis: The incidence of proven invasive fungal infection from all studies and arms was 4.1% and 8.3% if suspected infections were included. The reduction in the incidence of proven breakthrough invasive mycosis was significant (Table 1). As in the original analysis, the relative risk is reduced only in the group provided with itraconazole solution and with a relative risk reduction of 46%.Results - Itraconazole vs. Fluconazole: Table 2 reports a comparison of itraconazole solution vs. fluconazole for different relevant outcomes. There is a significant superiority of itraconazole for the reduction of all proven invasive fungal infections and for invasive Aspergillus infections and reductions are in the same range but not significant for the other outcomes.Conclusions: Itraconazole is still and significantly superior to its comparators, including fluconazole, in reducing the rate of breakthrough invasive fungal infections. This effect is only seen with the itraconazole oral or intravenous solution (at least 400 mg/d) which also reduce the rate of proven invasive Aspergillus infections.Table 1:Incidence of proven invasive fungal infectionsSubgroupNo. Pts (Trials)Relative Risk95%CIPAll studies3846 (15)0.620.45–0.770.003Itraconazole capsules735 (5)0.930.51–1.690.81Itraconazole solution3111 (10)0.540.37–0.770.0008Table 2:Comparison of itraconazole solution vs fluconazole (proven only)OutcomeNo. of trialsItraconazole (n/N)Fluconazole (n/N)Relative Risk95%CIPInvasive fungal infections623/88343/8740.520.32–0.840.008Invasive yeast infections69/85116//8540.560.25–1.240.15Invasive Aspergillus infections512/85024/8530.500.26–0.980.04Fungal-related Mortality420/75431/7540.640.38–1.090.10Abbrev.: n= pts. with event; N=total pts.

Efficacy of oral prophylactic antibiotics in neutropenic afebrile oncology patients: A systematic review of randomised controlled trials

The use of oral prophylactic antibiotics in oncology patients is still a matter of debate. A systematic review was performed to assess the evidence for the effectiveness of oral prophylactic antibiotics to decrease bacteraemia and infection-related mortality in oncology patients during neutropenic episodes. Medline, Embase and the Cochrane register of controlled trials were searched from 1966 until 2002. The main outcome was the number of patients with documented bacteraemia (Gram-negative or Gram-positive bacteraemia) and infection related mortality. Data-extraction and quality assessment were performed independently by two reviewers. A total of 22 trials met the inclusion criteria. Seventeen trials compared prophylaxis (quinolones or Trimethoprim/sulfamethoxazole (TMP/SMZ)) to no prophylaxis. The incidence of Gram-negative bacteraemia decreased significantly (pooled OR 0.39, 95% CI 0.24–0.62) without an increase in Gram-positive bacteraemia. Quinolone-based regimens showed a stronger reduction in Gram-negative bacteraemia while TMP/SMZ based regimens were more effective in Gram-positive bacteraemia. Infection related mortality due to bacterial causes decreased with the use of prophylactic antibiotics (pooled OR 0.49, 95% CI 0.27–0.88). No increase in fungaemia or fungal related mortality was seen with the use of oral prophylaxis. In conclusion, this study has shown that oral prophylactic antibiotics decreased Gram-negative bacteraemia and infection related mortality due to bacterial causes during neutropenic episodes in oncology patients.

Invasive Fungal Infections in Pediatric Oncology Patients

The purpose of this study was to determine the incidence of fungal infections in pediatric hematology and oncology (PHO) patients and to describe variations regarding site of infection, organisms, and mortality. The records of 1,052 patients presenting to the UCLA PHO service with various malignancies from 1991 to 2001 were retrospectively reviewed. No patient received invasive antifungal prophylaxis. Transplant patients were excluded. The 11-year incidence of fungal infections in this pediatric oncology cohort was 4.9%. There was a linear increase in the incidence of fungal infections from 2.9% to 7.8% between 1996 and 2001 (P = 0.001). Patients with acute leukemia represented 36% of the population but had a disproportionate incidence (67%) of fungal infections. Adolescents had twice the expected incidence of infection (P < 0.0001). Overall, Candida sp. was the major pathogen. Over time, a trend of fewer infections caused by Candida and more due to Aspergillus was noted. Blood-borne infections decreased over time, while those in the urinary and respiratory tracts increased (P = 0.04). Sixty-two percent of infections occurred in neutropenic patients. PHO patients had an overall mortality of 21%, but those with fungal infections experienced a 2.6-fold higher mortality that was not attributable to infections alone. Empiric antifungal therapy had no effect on mortality rates. Concurrent nonfungal infections did not increase mortality rates. The incidence of fungal infections increased over time, possibly as a result of advances in antibacterial and chemotherapeutic regimens. Adolescents and patients with leukemia were especially at risk. Fungal infections are a poor prognostic factor, independent of fungal-related mortality. New diagnostic methods allowing for early detection and treatment as well as more effective therapies are needed.

High rate of invasive fungal infections following nonmyeloablative allogeneic transplantation.

Nonmyeloablative allogeneic transplantation is an emerging therapy for hematologic and solid malignancies and potentially offers patients reduced transplant-related toxicity. Data regarding infectious complications of these protocols are limited, but early studies have demonstrated little infectious morbidity, particularly low rates of invasive fungal infections (IFIs). In the present study, 31 consecutive cases of nonmyeloablative transplantation were reviewed over a 2.5-year period, with a specific focus on infectious complications. Twenty-six patients (84%) had at least 1 significant infection during the year after transplantation, and infection-related mortality was 37%. Cytomegalovirus end-organ disease was diagnosed in 3 patients (10%). Ten patients (32%) were given the diagnosis of IFI; 7 (23%) met criteria for proven IFI. Fungal-related mortality was 80% within the group of patients with IFI and accounted for a significant portion of the overall mortality in the study. Severe graft-versus-host disease, high-dose corticosteroid use, recurrent neutropenia, and relapsed or refractory disease were factors associated with development of IFI.

Fluconazole does not reduce systemic fungal infection or fungal related mortality in neutropenic people not receiving bone marrow transplants

Fluconazole does not reduce systemic fungal infection or fungal related mortality in neutropenic people not receiving bone marrow transplants

Antifungal Prophylaxis in Neutropenic Patients with Hematologic Malignancies: Is There a Real Benefit?

Invasive fungal infections have been reported with an increasing incidence over the last 20 years. Fungal infections are an important cause of morbidity and mortality in patients with hematological malignancies. Therefore, in neutropenic patients different regimens of antifungal prophylaxis have been performed for more than 20 years, but the effect of antifungal prophylaxis is controversial. A long duration of neutropenia, impaired cell-mediated immunity as well as continuous corticosteroid therapy and sustained immunosuppression for graft-versus-host disease in patients treated with allogeneic bone marrow transplantation are known risk factors for invasive mycosis. Since early diagnosis of invasive fungal infection is difficult, strategies to prevent fungal infections seem to be attractive. The introduction of triazoles have provided us with a better armamentarium to prevent fungal infections. In this review, the current strategies of antifungal prophylaxis are discussed. Antifungal prophylaxis has been effective in reducing candida infection, however, there has been no proven successful prevention of invasive aspergillosis. In addition, there is no clearly proven benefit of antifungal prophylaxis regarding the reduction in the overall mortality. Thus the best way to reduce invasive fungal-related mortality will be early diagnosis and preemptive therapeutic approaches.