Invasive Fungal Infections In Adults Research Articles

Update on therapeutic approaches for invasive fungal infections in adults.

Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as Scedosporium spp., Fusarium spp., Trichosporon asahii, and Candida auris. We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.

Invasive Fungal Infections after CAR T-Cell Therapy for B-Cell Lymphoma: A Study from the French Descart Registry

Introduction: Chimeric antigen receptor (CAR) T cell therapy has emerged as an important treatment option for patients with B-cell malignancies. Despite its major clinical impact, CAR T cell therapy holds a potential risk of increased susceptibility to infections, including invasive fungal infections (IFI). Since data about the prevalence and impact of fungal infections in this population are limited, we aimed to provide a comprehensive overview of IFI using real-world data from the national DESCAR-T registry. Methods: We performed a multi-center retrospective cohort study, quering the French DESCAR-T registry (NCT04328298), to describe type, frequency and outcomes of IFI in adults with refractory or relapsed (R/R) B cell lymphomas. In addition, healthcare providers were contacted to declare any missing cases. Demographic, biological and clinical characteristics were collected retrospectively. Each IFI case was reviewed by an infectious disease specialist and a microbiologist, and classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria (Donnelly et al. Clinical Infect Dis 2020). Results: Among the 1144 patients included in the registry from 2018 to 2022, we identified 57 suspected IFI cases. After exclusion of 25 patients not adjudicated for IFI, 32 patients (3%) were identified as having presented a proven (n = 14), probable (n = 12), or possible (n = 6) IFI. DLBCL was the primary diagnosis for 30 patients and axi-cel was the most frequent CAR T product (23/32, 72%). Seven patients (22%) had received a previous hematopoietic stem cell transplantation. All patients experienced cytokine release syndrome (including 8 grade ≥ 3) and 21 (66%) experienced immune effector cell-associated syndrome (including 13 grade ≥ 3). Overall, 27 (84%), 21 (66%), and 5 (16%) received tocilizumab (median 960mg, range 120-2880mg), corticosteroids, and anakinra, respectively. Among known risk factors for IFI, grade 4 neutropenia and late neutropenia (< 1g/L) at day 28 after infusion were identified in 25 (78%) and 14 (44%) patients respectively. Overall, 8 (25%) patients received antifungal prophylaxis, posaconazole was used for 4 of them. Over half of the IFI cases occurred between 0 and 30 days after CAR T-cell infusion (18/32, 56%), with a median onset time of 29.5 days (IQR 16.5 - 79.5). The most frequently observed infections were invasive Aspergillosis (n = 13), with pulmonary involvement in 10/13 (77%) of patients, leading to a fatal issue in 3/13 patients (23%). Other mold infections included Mucormycosis (n = 5), with pulmonary involvement in 4/5 patients and a fatal outcome in 1/5, as well as Fusariosis (n = 1). Yeast infections (n = 12) were mostly identified as Candidemia (92%) with a mortality rate of 3/12 (27%). The median overall survival of patients with IFI was 186.5 days (IQR 79-506), 7 deaths being related to IFI and 3 to lymphoma relapse. Median progression-free survival was 94 days (IQR 31 - 252). Conclusions: This study represents one of the largest investigations about IFI in B-cell lymphoma patients treated with CAR T-cells. Even though IFI represent a rare complication after CAR T-cell therapy, the related-mortality is high. Selective antifungal prophylaxis may benefit high-risk patients, while rapid preemptive diagnostic workup, particularly for lung involvement, is mandatory. Analysis to define potential risk factors for IFI are ongoing.

Invasive Fungal Infections in Children with Hematological Malignancy

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with haematolgical malignancies. Factors that appear to be associated with IFIs in both children and adults in this severely immunosuppressed population are the underlying malignancies, presence of profound and long lasting neutropenia, high intensity of the therapeutic regimens, hematopoietic stem cell transplantation and previous antibiotic therapy. In patients with hematological malignancy most invasive fungal infections are caused by Candida and Aspergillous species. Though the incidence of IFI in adult may be as high as 30 % and the mortality up to 50 %, the true incidence in children and its outcome are more difficult to assess because of the growing trends towards more invasive chemotherapeutic regimens, the development and introduction of new antifungal drugs and prophylactic antifungal strategies and difference in design and patient populations among the various studies. In general the incidence rate in children appears to be lower than in adults. The diagnosis are based on the basis of microbiological and radioimagings with the criteria defined by the EORTC/MSG. Caspofungin, Liposomal amphotericin B and Voriconazole are often the first line empirical antifungal agents
 BANGLADESH J CHILD HEALTH 2021; VOL 45 (1) : 34-40

Assessment of the Role of 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Fungal Infections in Adults.

Detection of 1,3-β-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.

Risk of Invasive Fungal Infections in Patients with High-Risk MDS and AML Receiving Hypomethylating Agents

IntroductionAcute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients are at risk of invasive fungal infection (IFI) due to prolonged neutropenia related to the underlying diseases and the induction chemotherapy required to treat them. The risk of IFI specifically in AML or MDS patients treated with hypomethylating agents (HMA) has not been fully elucidated, with previous publications reporting various prophylaxis practices and IFI incidences from 3.3% to 14.4%. We sought to characterize the incidence of IFI in patients with MDS and AML who received azacitidine (AZA) or decitabine (DAC) at our institution.MethodsA retrospective cohort study was performed to evaluate the incidence of IFI in adults receiving between 10/1/10 and 10/1/17. Patients were included if they received at least two cycles of either drug and were diagnosed with AML, MDS with a revised international prognostic scoring system (R-IPSS) score of at least 3.5, or chronic myelomonocytic leukemia (CMML) categorized as intermediate 2 or higher risk using CMML-specific prognostic scoring system (CPSS). Patients were excluded if they received mold-active antifungal prophylaxis at any time during HMA therapy prior to the development of an IFI, or if they received mold-active antifungal treatment when starting a HMA. The primary endpoint was the incidence of IFI, defined as proven, probable, or possible using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria (EORTC).ResultsSix hundred and fifty-one consecutive patients were screened, and 203 patients met inclusion criteria. The three most common reasons for exclusion were incomplete data (n=158), receipt of fewer than two cycles of a HMA (n=138), and receipt of mold-active antifungal treatment at the time of HMA initiation or mold-active antifungal prophylaxis at any point during HMA therapy (n=86). Six patients had two distinct episodes of HMA therapy separated by either an allogeneic stem cell transplant or a treatment other than HMA; thus 209 episodes of treatment occurred amongst 203 patients. Overall, the study population was elderly with the median age of 69, and 59% of the patients were male. Fifty-one percent of patients had AML, while 49% had MDS or CMML; 72% received AZA. The median number of cycles of HMA utilized was five. Most patients were treatment-naïve (59% AML and 87% MDS had no prior therapy). A significant portion of the group (25.8%) was neutropenic on cycle 1 day 1 (C1D1) of HMA. Other pertinent baseline characteristics of the study population are displayed in Table 1. We identified 20 cases of IFI, with an overall incidence of 9.6%. Most IFI were possible cases according to the EORTC criteria (13/20, 65%), but there were 3 culture-proven cases. The possible cases all met the host criterion of neutropenia and 12 of 13 met the clinical criterion of lower respiratory tract infection based on imaging. Organisms isolated on culture included Aspergillus spp., Fusarium spp., and Scedosporium spp. A diagnosis of IFI was made at a median of 3 cycles of HMA, with the majority (85%) diagnosed within the first four cycles. Among the 20 cases of IFI, 12 were diagnosed while receiving AZA and 8 were receiving DAC. More than half of the patients who developed IFI were neutropenic on C1D1. These patients had a significantly higher risk of IFI compared to non-neutropenic patients (20.4% vs. 5.8%, p=0.0051). When other baseline characteristics were analyzed, patients with therapy-related MDS (t-MDS) compared to de novo MDS were more likely to have an IFI (20.8% vs. 5.1%, p=0.0314). Patients with de novo AML also had a higher incidence of IFI compared to AML from an antecedent MDS/MPN (15.4% vs. 2.4%), however this did not reach statistical significance (p=0.07). Additional comparisons are described in Table 2.ConclusionIFI occurred in 9.6% of patients treated with HMA, but was observed in 20.4% of those who were neutropenic on C1D1 of HMA. Another potential risk factor identified was t-MDS versus de novo MDS. Prospective evaluation of mold-active antifungal prophylaxis in patients with MDS or AML who are neutropenic at the start of HMA therapy is warranted. DisclosuresFrey:Novartis: Consultancy; Servier Consultancy: Consultancy. Perl:Arog: Consultancy; NewLink Genetics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Porter:Kite Pharma: Other: Advisory board; Novartis: Other: Advisory board, Patents & Royalties, Research Funding; Genentech: Other: Spouse employment.

Optimization of Voriconazole Therapy for the Treatment of Invasive Fungal Infections in Adults.

Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using a drug monitoring approach, which relies on attainment of steady-state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses that can maximize the net benefit (probability of efficacy-probability of adverse events) and ensure therapeutic concentrations, early on during treatment. The label-recommended 200 mg voriconazole dose resulted in attainment of targeted concentrations in ≥80% patients in the case of Candida spp. infections, as compared to only 40-50% patients, with net benefit ranging from 5.8-61.8%, in the case of Aspergillus spp. infections. Voriconazole doses of 300-600 mg were found to maximize the net benefit up to 51-66.7%, depending on the clinical phenotype (due to CYP2C19 status and pantoprazole use) of the patient and type of Aspergillus infection.

Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure: The EMPIRICUS Randomized Clinical Trial.

Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P = .008). Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28. clinicaltrials.gov Idenitfier: NCT01773876.

Comparison of clinical pharmacology of voriconazole and posaconazole.

Despite greater knowledge and possibilities in pharmacotherapy, fungal infections remain a challenge for clinicians. As the population of immunocompromised patients and those treated for their hematologic ailments increases, the number of fungal infections grows too. This is why there is still a quest for new antifungal drugs as well as for optimization of pharmacotherapy with already registered pharmaceutics.Voriconazole and posaconazole are broad-spectrum, new generation, triazole antifungal agents. The drugs are used in the pharmacotherapy of invasive aspergillosis, Candida and Fusarium infections. Voriconazole is also used in infections caused by Scedosporium. Posaconazole is used in the treatment of coccidioidomycosis and chromoblastomycosis. Besides some similarities, the two mentioned drugs also show differences in therapeutic indications, pharmacokinetics (mainly absorption and metabolism), frequency and severity of adverse drug reactions, drug–drug interactions and dosage. As both of the drugs are used in the treatment of invasive fungal infections in adults and children, detailed knowledge of the clinical pharmacology of antifungal agents is the main factor in pharmacotherapy optimization in treatment of fungal infections.The goal of the article is to present and compare the clinical pharmacology of voriconazole and posaconazole as well as to point out the indications and contraindications of using the drugs, determine factors influencing their pharmacotherapy, and provide information that might be helpful in the treatment of fungal infections.

Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens.

With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n=31; 50%) and candidaemia (n=15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n=6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR)=6.0], graft-versus-host disease (OR=5.3), central venous catheter use (OR=5.2) and hypoalbuminaemia (OR=0.3g(-1) dl(-1) increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR=3.5) and stay in an ICU (OR=2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

Prevalence and description of invasive fungal infection in adults with hematological neoplasms

Prevalence and description of invasive fungal infection in adults with hematological neoplasms

Prevalence and description of invasive fungal infection in adults with hematological neoplasms

Prevalence and description of invasive fungal infection in adults with hematological neoplasms

Invasive Fungal Infections in Adults with Newly Diagnosed AML Undergoing Intensive Chemotherapy: Characterization, Risk Factors, and Outcomes in a Single Institution

Abstract 4254 Background:Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML) undergoing chemotherapy treatment. However, the epidemiology, risk factors, and outcomes of IFI in these patients have been poorly described. Methods:A single-center retrospective analysis was performed to study the epidemiology, risk factors, clinical outcomes, and mortality predictors of IFIs in AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST) between January 2005 and June 2010. Newly diagnosed AML patients, with exception of acute promyelocytic leukemia, were studied. IFIs were defined using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Results:254 consecutive patients (57% male; median age 54, range 20–78) were analyzed. 123 (48%) of patients had an IFI; of which, 15 patients (12%) had a proven candidal infection, and 108 patients (88%) had a mould infection (5 proven/probable (5%) and 103 (95%) possible mould infections). 237 (93%) patients received antifungal therapy during their treatment course (median day 8, range day -15 to 30). Of those, 63 (27%) received monotherapy (46% liposomal amphotericin, 44% voriconazole) and the rest received multiple antifungal agents.Significant risk factors and trends for developing +IFI shown from univariate analyses are listed in Table 1. Prolonged neutropenia, duration of mucositis, and concurrent bacterial infections did not significantly affect the development of +IFI. Using multivariate analyses, mortality was impacted by patients' baseline organ function (p=0.002 [1.3,3.1]), specifically, by bilirubin < 2 mg/dL (p=0.003 [1.38,4.57]) and creatinine < 1.5 mg/dL (p=0.01 [1.23,5.4]).Table 1Significant risk factors and trends for development of + IFINo IFI+ IFIP-valueMale Gender (%)50640.023Leukemia from a secondary cancer (%)1540.003Duration of parenteral nutrition (days)*9.5170.057Candida Colonization (%)85930.043Grade 3+ mucositis (%)42590.05*values are median daysPatients with +IFI did not significantly impact overall survival. However, patients with candidal IFIs had a significantly lower overall survival compared to patients with mould IFIs and no IFI (HR 2.01 [1.06, 3.8]) (Figure 1). Candida colonization prior to or during the first week of chemotherapy, and development of mucositis were associated with the development of candidal IFIs (p=0.07). [Display omitted] Conclusion:IFIs, particularly mould infections, remain a significant problem in patients with AML. Although overall survival did not appear to be significantly affected by mould infections, patients with candidal infections were more likely to die. Identification of risk factors for each type of IFIs may help to develop effective targeted preventive antifungal strategies. Disclosures:No relevant conflicts of interest to declare.

Epidemiology, risk factors, and outcomes of invasive fungal infection in adults with acute myelogenous leukemia undergoing intensive induction chemotherapy.

6579 Background: The epidemiology and outcomes of invasive fungal infections (IFI) in patients with acute myelogenous leukemia (AML) have been poorly described. Methods: We performed a single center, retrospective analysis of the epidemiology, risk factors and clinical outcomes of IFIs in newly-diagnosed AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST). Patients did not receive antifungal prophylaxis. IFIs were defined using EORTC/MSG criteria. Results: Of 97 consecutive patients (58% male; median age 53, range 22-72) admitted in 2007 and 2008, 27 (28%) had IFI, of which 7 (26%) were proven, 1 (4%) probable, and 17 (68%) possible with lung CT findings characteristic of fungal (mold) pneumonia. Of 8 proven/probable cases, 4 were due to molds and 4 were due to yeasts. Of 91 (94%) receiving antifungal therapy beginning median day 7 (range day -14 through day 25) of AML treatment; 41 (42%) received monotherapy (66% liposomal amphotericin B, 34% voriconazole) and the rest received multiple antifungals. Using univariate analysis, we identified risk factors for IFIs (Table 1). Occurrence of IFI was associated with lower complete remission rate (52% vs. 70% -IFI, p=0.06) and a decrease in 6 month survival (58% vs. 85% -IFI, p=0.01). Conclusions: AML patients with IFIs are more likely to die within 6 months of beginning intensive induction TST. Through this analysis, we are able to identify risk factors that may be associated with development of IFIs. Such identification may help to develop effective preventive antifungal strategies for high risk AML patients. Risk factors for + IFI cohort (overall), and for IFIs due to yeasts and molds No IFI (N=70) IFI (N=27) P- value IFI- yeasts (N=4) P-value IFI-moulds (N=23) P-value Age > 50 years (%) 49 70 0.07 75 NS 70 0.09 Presenting blast count > 10,000 (%) 26 44 0.09 50 NS 43 0.12 Time to ANC < 100 cells/mm3* 7 5 0.08 4 0.16 5 0.16 Time to recovery of ANC >100 cells/mm3* 22.5 26 0.07 25 NS 27 0.12 Onset of mucositis** 14 11.5 0.03 8.5 0.14 12 0.06 Duration of parenteral nutrition* 10 15 0.04 15 NS 14.5 0.07 NS: Non significant, ANC: Absolute neutrophil count. * Median Days of AML therapy (begins on Day 1) No significant financial relationships to disclose.

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.

Treatment options of invasive fungal infections in adults.

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.

Amphotericin B lipid complex at 3 mg/kg/day for treatment of invasive fungal infections in adults with haematological malignancies.

We treated 10 consecutive adults with a haematological malignancy, and an invasive aspergillosis (n = 8) or invasive candidosis (n = 2), with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Nine patients responded (five complete and four partial responses), and one died with invasive aspergillosis. Treatment was well tolerated, with only 4% of infusions followed by infusion-related adverse events, and the renal function improved in six patients who had an elevated serum creatinine before therapy. These data suggest that lower doses of ABLC may be equally effective but less toxic than higher doses. However, a controlled study is required to confirm these observations.