Epidemiology Of Invasive Fungal Diseases Research Articles

Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections

BackgroundInvasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time.MethodsRetrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome.ResultsTwenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment.Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674).ConclusionsIn this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients.

Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20-30 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a different setting with more vulnerable hosts. Patients admitted to an ICU tend to have older age and higher severity of disease. Moreover, the number of patients being treated in ICU are often immunosuppressed as a result of the widespread use of immunomodulatory agents, such as corticosteroids, chemotherapy, and biological agents. The development of Invasive Pulmonary aspergillosis (IPA) reflects a different clinical trajectory to affected patients. The increasing use of corticosteroids would probably explain the higher incidence of IPA especially in critically ill patients. In refractory septic shock, severe community-acquired pneumonia (SCAP), and acute respiratory distress syndrome (ARDS), the use of corticosteroids has re-emerged in order to decrease unacceptably high mortality rates associated with these clinical conditions. It is also pertinent to note that different reports have used different diagnosis criteria, and this might explain the different incidence rates. Another layer of complexity to better understand current IPA data is related to more aggressive acquisition of samples through invasive respiratory examinations.

Emerging and re-emerging fungal threats in Africa.

The emergence of deadly fungal infections in Africa is primarily driven by a disproportionately high burden of human immunodeficiency virus (HIV) infections, lack of access to quality health care, and the unavailability of effective antifungal drugs. Immunocompromised people in Africa are therefore at high risk of infection from opportunistic fungal pathogens such as Cryptococcus neoformans and Pneumocystis jirovecii, which are associated with high morbidity, mortality, and related socioeconomic impacts. Other emerging fungal threats include Emergomyces spp., Histoplasma spp., Blastomyces spp., and healthcare-associated multi-drug resistant Candida auris. Socioeconomic development and the Covid-19 pandemic may influence shifts in epidemiology of invasive fungal diseases on the continent. This review discusses the epidemiology, clinical manifestations, and current management strategies available for these emerging fungal diseases in Africa. We also discuss gaps in knowledge, policy, and research to inform future efforts at managing these fungal threats.

Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018).

ABSTRACTThe French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% (P < 0.0001). Yeast fungemia (n = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia (n = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P < 0.0001). Invasive aspergillosis (n = 1,661) and mucormycosis (n = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools.

Epidemiology of invasive fungal diseases in adults with newly diagnosed acute myeloid leukemia

Invasive fungal diseases (IFDs) are common in patients with acute myeloid leukemia (AML), but no recent data on incidence without antifungal prophylaxis are available. We evaluated the incidence of IFDs in patients with AML undergoing induction chemotherapy at Stanford University Hospital from 2012 to 2017, for up to 12 weeks after induction. We also analyzed factors associated with IFD development. Thirty-six of 240 patients (13%) developed at least one proven or probable IFD. Seventy-eight percent of the proven or probable IFDs were due to Candida or Aspergillus species. Infection due to Fusarium and Mucorales was uncommon. Absolute neutrophil count (ANC) of <500 µL/L at the start of induction was associated with an increased risk of IFD. One hundred and eighty-seven patients (78%) were started on systemic antifungal drugs, even without microbiologic evidence of an IFD. IFDs remain frequent in AML patients undergoing induction chemotherapy without antifungal prophylaxis.

Changing Epidemiology of Invasive Fungal Disease in Allogeneic Hematopoietic Stem Cell Transplantation.

Invasive fungal disease (IFD) is a common cause of morbidity and mortality in patients with hematologic malignancies, especially among those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The epidemiology of IFD in HSCT patients has been evolving over the last decades, mainly in relation to changes in HSCT therapies such as antifungal prophylaxis. A progressive decrease in Candida albicans infection has been documented, alongside a progressive increase in infections caused by non-albicans Candida species, filamentous fungi, and/or multidrug-resistant fungi. Currently, the most frequent IFD is invasive aspergillosis. In some parts of the world, especially in north Central Europe, a high percentage of Aspergillus fumigatus isolates are azole-resistant. New diagnostic techniques have documented the existence of cryptic Aspergillus species with specific characteristics. An increase in mucormycosis and fusariosis diagnoses, as well as diagnoses of other rare fungi, have also been described. IFD epidemiology is likely to continue changing further due to both an increased use of mold-active antifungals and a lengthened survival of patients with HSCT that may result in hosts with weaker immune systems. Improvements in microbiology laboratories and the widespread use of molecular diagnostic tools will facilitate more precise descriptions of current IFD epidemiology. Additionally, rising resistance to antifungal drugs poses a major threat. In this scenario, knowledge of current epidemiology and accurate IFD diagnoses are mandatory in order to establish correct prophylaxis guidelines and appropriate early treatments.

Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach.

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative.

Epidemiology of invasive fungal disease in haematologic patients.

Invasive fungal disease (IFD) is frequent in patients with haematologic malignancies and in recipients of haematopoietic cell transplantation (HCT). An epidemiologic study conducted in Brazil reported a high incidence of IFD in haematologic patients, and invasive fusariosis was the leading IFD. A limitation of that study was that galactomannan was not available for at least half of the study period. In order to characterise the epidemiology and burden of IFD in three cohorts, HCT, acute myeloid leukaemia (AML) or myelodysplasia (MDS), and acute lymphoid leukaemia (ALL), we conducted a prospective multicentre cohort study in four haematologic Brazilian centres. From August 2015 to July 2016, all patients receiving induction chemotherapy for newly diagnosed or relapsed AML, MDS or ALL, and all HCT recipients receiving conditioning regimen were followed during the period of neutropenia following chemotherapy or the conditioning regimen. During a 1-year period, 192 patients were enrolled: 122 HCT recipients (71 allogeneic, 51 autologous), 46 with AML, and 24 with ALL. The global incidence of IFD was 13.0% (25 cases, 11 proven and 14 probable). Invasive aspergillosis (14 cases) was the leading IFD, followed by candidemia (6 cases) and fusariosis (3 cases). The incidence of IFD was 26.1% in AML/MDS, 16.7% in ALL, 11.3% in allogeneic HCT, and 2.0% in autologous HCT. The burden of IFD in haematologic patients in Brazil is high, with a higher frequency in AML and ALL. Invasive aspergillosis is the leading IFD, followed by invasive candidiasis and fusariosis.

Epidemiology of invasive fungal disease by filamentous fungi in the period 2005 to 2015, in a university hospital in Santiago, Chile

Invasive fungal disease (IFD) due to filamentous fungi is increasingly common. To study the epidemiology of EFI in hospitalized adults in our center. Retrospective study of adult patients of a university hospital in Santiago, Chile, with EFI due to filamentous fungi between January 2005 and December 2015. 125 episodes were identified, being 48% proven, 40% probable and 11% possible according to EORTC/MSG criteria, overall incidence was 0.47/1,000 admissions, 57% male patients and age 50 ± 16 years. 66.4% had hematological pathology, 11.2% solid organ transplant, 11.2% rheumatology diseases, 11.2% other conditions. The risk factors were neutropenia 44%, corticosteroid therapy 21%, immunosuppressants 13%. The most frequent mould identified were Aspergillus spp (53.6%), Mucorales (16%), Fusarium spp (8.8%), Alternaria spp (5.6%) and other filamentous (3.2%). All received antifungals, 82% monotherapy, 18% combined therapy, there was surgical defocation in 90% of mucormycosis. The overall mortality was 42%. When comparing 2005-2009 vs 2010-2015, there was a significant increase in incidence and a tendency to lower mortality in the second period. Over a period of 10 years, we observed an increase in the incidence of EFI by filamentous, aspergillosis was the most frequent etiology and the overall mortality was 42%.

Changing face of Candida colonization pattern in pediatric patients with hematological malignancy during repeated hospitalizations, results of a prospective observational study (2016\u20132017) in shiraz, Iran

BackgroundSurveillance of current changes in the epidemiology of Invasive Fungal Diseases (IFDs) as an important component of the antifungal stewardship programs (ASP), requires careful regular monitoring, especially in high-risk settings such as oncology centers. This study aimed to examine Candida colonization status and corresponding current changes in children with malignancy during repeated admissions and also investigate the possible epidemiological shifts after the implementation of ASP.MethodsIn this prospective observational study, all eligible patients younger than 18 years were recruited during 2016–2017 at Amir Medical Oncology Center (AMOC) in Shiraz, Iran. Totally, 136 patients were enrolled and 482 samples were collected from different sites (oral/nasal discharges, urine and stool). Weekly regular sampling was carried out during hospitalization. Candida colonization status and epidemiological changes were monitored during repeated admissions. Samples were cultivated on Sabouraud Dextrose agar medium and identified by Polymerase Chain Reaction -Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsEstimated Candida colonization incidence was 59.9% (82/136) in our patients. Candida colonization was found to be higher in oral cavity and rectum than that in nasal cavity. Among those long-term follow ups and repetitive hospitalizations, a significant number of patients exhibited changes in their colonization patterns (37.7%). Candida colonization did not reveal any significant relationship with age, sex, oncologic diseases and degree of neutropenia. C. albicans (72.0%) was found as the most common Candida species in colonized patients, followed by C. krusei, C. kefyr, C. glabrata and C. parapsilosis.ConclusionGiven the high incidence of Candida infections in children with cancers, close monitoring of epidemiologic changes is essential for judicious management, based on local surveillance data and improvement of overall quality of care in high risk patients.

Clinical features in proven and probable invasive fungal disease in children and adolescents at a pediatric referral center: a 5-year experience.

There is limited information concerning the overall epidemiology of invasive fungal disease (IFD) in children. The aim of this study was to clarify the clinical features of IFD in a tertiary pediatric care hospital. Patients diagnosed with proven or probable IFD at our hospital between 2011 and 2015 were retrospectively reviewed. Proven and probable IFD were defined according to the European Organization for Research and Treatment of Cancer/Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group consensus. Patients with possible IFD were excluded. The incidence of proven or probable IFD was 26 of 20,079 hospitalized patients (0.13%). The predominant underlying disease was malignancy (54%) and congenital anomaly (27%). The most common diagnosis was candidemia among the patients with proven IFD (8 of 13, 62%). All the isolated pathogens in the candidemia patients were non-albicans Candida spp. The most common site of infection was the lungs in patients with probable IFD (11 of 13 patients, 85%). In probable IFD episodes, positive β-D-glucan and galactomannan were found in 12 of 13 (92%) and 5 of 13 (38%) patients, respectively. All but one patient (96%) received empirical antifungal therapy. No patients underwent surgical resection of residual lesions. The overall mortality was 23% and the attributable mortality of IFD was 12%. Our results suggest the emergence of non-albicans Candida species as important pathogens in childhood IFD.

Epidemiology of Invasive Fungal Disease by Aspergillus in a University Hospital in Santiago – Chile, During the Period 2005–2015

Background In Chile, there is little information on invasive fungal disease (IFD) due to filamentous fungi. A study of our institution showed 41 episodes in hemato oncological patients between the years 2004 and 2008, being the main cause Aspergillus, but the epidemiological characteristics of this infection in Chilean patients are not currently known. The objective describes the epidemiology of IFD by Aspergillusin our center.Methods Retrospective study in adults patients hospitalized in our center, diagnosed with IFD by Aspergillus between 2005 and 2015. Medical records of identified cases were review, incidence were calculated with the discharges numbers and total numbers of IFD. The study was approved by the Institutional Ethics Committee.ResultsSixty-seven cases were identified, with an incidence of 2.53 per 10,000 discharges between 2005 and 2015, with 35 cases of IFD in the period 2005–2010 and 32 cases in the period 2011–2015. The etiologies were A. fumigatus 42%, A. flavus 7%, A. terreus 7%, A. niger 3%, and Aspergillus spp. 40%. According EORTC/MSG criteria, 39% were proven, 52% probable, and 9% possible. The 55% of patients were male, the mean ± SD age was 51 ± 18 years, 57% had hematological conditions, mainly acute leukemias, rheumatological conditions in 15% and solid organ transplant in 13%, neutropenia under 500/mm3 in 37% and serum galactomannan test >0.5 in 67%. The clinical focus was 73% pulmonary and 17% rhinosinusal. The treatment was 81% monotherapy, 73% with voriconazole, 15% with liposomal amphotericin B and 6% with caspofungin. The 30 days mortality was 39%.Conclusion The epidemiology of IFD by Aspergillus is similar to that described in developed countries, in highly vulnerable patients with a mortality close to 40%. More epidemiological information from other hospitals is necessary to complete the epidemiology of Aspergillus infections in our country.Disclosures All authors: No reported disclosures.

Epidemiology of Invasive Fungal Disease in Children.

Considerable progress has been made in the prevention, diagnosis, and management of pediatric patients with invasive fungal disease (IFD). The reported decreasing trend in the incidence of invasive candidiasis (IC) over the past 15 years in both neonates and children has been encouraging. Nevertheless, due to the growing number of immunocompromised children at risk for IFD, this disease continues to be associated with significant morbidity and death and with increased financial burden to the health care system. Therefore, it is important to understand the contemporary epidemiology of IFD. Incidence rates of IFD in children are affected by geographical, population, and time variability. There is an ongoing effort to constantly document and update the incidence of IFD and species distribution among different pediatric populations as a means to direct preventative, diagnostic, and therapeutic resources to the most appropriate subset of patients. Children with a hematologic malignancy or a primary or secondary immunodeficiency, those undergoing solid organ or hematopoietic stem cell transplantation, and premature neonates are the major subsets of pediatric patients at risk of developing IFD. In this review, we focus on fungal disease epidemiology with a specific emphasis on the 2 most common pediatric IFDs, IC and invasive aspergillosis (IA).

Epidemiology of invasive fungal diseases in children with solid tumours undergoing autologous haematopoietic stem cell transplantation: a 10-year experience in a tertiary Italian centre.

The objective of the study was to determine the incidence of invasive fungal disease (IFD) in children undergoing autologous haematopoietic stem cell transplantation (auHSCT) for solid tumours (ST). Retrospective study on auHSCT was performed in children with ST (January 2006-December 2015). Data on the number of patient-days at risk (pdr) during the first 30 and 90days after auHSCT and cases of proven/probable IFDs were collected. Infection rate (IR, episodes/1000 pdr) and proportions and cumulative risk (CR) of IFD were evaluated. In 186 patients, 270 auHSCT were performed, for a total of 8327 pdr during the first 30days and 24366 up to day 90. Median age was 5years (interquartile range 2;8), 63% were male. At day 30, seven procedures were complicated by IFD, with an IR of 0.84 (95% CI 0.66-1.02) and aCR of 2.6% (95% CI 1.4-5.4) at 18days after HSCT. Within day 90, two further IFDs were detected with an IR of 0.37 (95% CI -0.49 to 1.23) and a CR of 3.3% (95% CI 1.7-6.3) at day 69. Children undergoing auHSCT for ST have a low incidence of IFDs in the first 90days after the procedure.

Changes in the epidemiological landscape of invasive mould infections and disease.

Although a wide variety of pathogens are associated with invasive mould diseases, Aspergillus spp. have historically been one of the most common causative organisms. Most invasive mould infections are caused by members of the Aspergillus fumigatus species complex and an emerging issue is the occurrence of azole resistance in A. fumigatus, with resistance to amphotericin B documented in other Aspergillus spp. The epidemiology of invasive fungal disease has shifted in recent years as non-A. fumigatus Aspergillus spp. and other moulds have become progressively more important, although there are no consolidated data on the prevalence of less common species of moulds. The incidence of mucormycosis may have been underestimated, which is a potential concern since species belonging to the order Mucorales are more resistant to antifungal agents than Aspergillus spp. All species of Mucorales are unaffected by voriconazole and most show moderate resistance in vitro to echinocandins. Fusarium spp. may be the second most common nosocomial fungal pathogen after Aspergillus in some tertiary hospitals, and show a susceptibility profile marked by a higher level of resistance than that of Aspergillus spp. Recently, Scedosporium aurantiacum has been reported as an emerging opportunistic pathogen, against which voriconazole is the most active antifungal agent. Other mould species can infect humans, although invasive fungal disease occurs less frequently. Since uncommon mould species exhibit individual susceptibility profiles and require tailored clinical management, accurate classification at species level of the aetiological agent in any invasive fungal disease should be regarded as the standard of care.

Invasive Fungal Disease in Renal Transplant Recipients at a Brazilian Center: Local Epidemiology Matters.

Invasive fungal disease (IFD) is an important complication after solid organ transplantation (SOT). A marked geographic variation in the epidemiology of IFD after kidney transplantation (KT) has been suggested by the results of previous studies. Nevertheless, data from Latin American centers are scarce. This study sought to describe the epidemiology of IFD at a Brazilian KT center. This study was a retrospective single-center cohort study that included patients who underwent KT between 1998 and 2009 and were followed up until July 2015. Cases of simultaneous kidney-pancreas transplantation were excluded. The primary study outcome was the occurrence of proven or probable IFD. Among 908 KT recipients, 44 cases of IFD occurred in 42 patients (4.6%). Cryptococcus spp. infection, diagnosed in 16 cases (36.3%), was the leading cause of IFD, followed by histoplasmosis in 10 cases (22.7%) and invasive candidiasis in 10 (22.7%). Sporotrichosis, mucormycosis, invasive aspergillosis, pulmonary Cladophialophora sp. infection, trichosporonosis and Saccharomyces cerevisiae fungemia occurred in 1 recipient each (2.3%). Two additional (4.5%) cases of unspecified mold infections were identified by histopathological analysis. Most cases of IFD (67%) occurred later than 6 months after transplantation. Previous use of antilymphocyte antibodies (P= .008) and corticosteroid pulse therapy (P< .001) were more frequent among cases of IFD occurring within the first 6 months after transplantation. The epidemiology of IFD in this Brazilian cohort was characterized by a large predominance of late infections and a high proportion of cases of cryptococcosis and histoplasmosis. These results highlight the considerable geographic variability of IFD epidemiology after KT.

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality.

The changing face of epidemiology of systemic fungal infections

Invasive fungal diseases (IFDs) are an increasingly common complication in critically ill patients in Europe and are frequently fatal. Because of changes in treatment strategies and the increased use of antifungal prophylaxis, the epidemiology of IFDs has changed substantially in recent years and infections due to Candida species are no longer the majority in many institutions. In contrast, the emergence of non-Candida IFDs such as aspergillosis, ucrmycosis and fusariosis has increased. Rates of IFD-related mortality in Europe depend on the pathogen, geographical location and underlying patient characteristics, with rates ranging from 28 to 59% for Candida infections and from 38 to 80% for invasive aspergillosis. Early initiation of antifungal therapy is critical for improving outcomes; however, this is complicated by the difficulty in diagnosing IFDs rapidly and accurately. Choice between agents should be based on a variety of factors, including spectrum of activity, adverse events, drug interactions, route of administration, clinical efficacy of individual agents and local epidemiology.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19–275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Update on epidemiology of and preventive strategies for invasive fungal infections in cancer patients.

Changes in antineoplastic treatments and transplant practices are driving shifts in the epidemiology of invasive fungal diseases (IFDs). Patients with acute myelogenous leukemia (AML) and those undergoing bone marrow transplant (BMT) are at greatest risk for contracting IFDs. Unfortunately, there are few large population studies that can be used to track trends and help us to better understand why certain individuals within recognized high-risk groups are at greater risks than others for contracting IFDs. The growing use of antifungals in prophylaxis and treatment influences which species will cause an IFD as well as the resistance patterns of these fungi. On the one hand, antifungal prophylaxis has mitigated, but not eliminated, the threat of candidiasis. Furthermore, prophylaxis trials have shown trends of reduced aspergillosis in BMT patients; however, no survival benefits were seen, and 1 trial indicated a lower rate of aspergillosis and survival benefits in patients with AML. Future prophylaxis trials should reduce the heterogeneity of risk in study participants in order to better assess benefit; these trials should also incorporate fungal biomarkers into their design. The threat of emerging fungal resistance in prophylaxis strategies is real and must be monitored.