Management Of Invasive Fungal Infections Research Articles

Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa.

Invasive fungal infections (IFIs) such as cryptococcosis, disseminated histoplasmosis, and chronic pulmonary aspergillosis are significant causes of morbidity and mortality in Africa. Lack of laboratory infrastructure and laboratory personnel trained in diagnostic mycology hamper prompt detection and management of IFIs on the continent. Point-of-care tests (POCT) obviate the need for complex infrastructure, skilled technicians, and stable electricity and have had major impacts on the diagnosis of bacterial, viral, and parasitic infections in low- and middle-income countries. Over the last 10 years, POCTs for IFIs have become increasingly available and they have the potential to revolutionize the management of these infections if scaled up in Africa. At the beginning of 2021, the World Health Organization (WHO) Essential Diagnostic List (EDL) included a cryptococcal antigen test for the diagnosis of cryptococcosis, Histoplasma antigen test for the diagnosis of disseminated histoplasmosis, and Aspergillus-specific test for the diagnosis of chronic pulmonary aspergillosis. All of these are available in formats that may be used as POCTs and it is hoped that this will improve the diagnosis of these life-threatening IFIs, especially in low- and middle-income countries. This perspective review discusses commercially available POCTs and outlines strategies of a blueprint to achieve their roll-out in Africa. The strategies include raising awareness, conducting research that uncovers the exact burden of IFIs, increasing advocacy, integrating diagnosis of IFIs into existing public health programs, adoption of the WHO EDL at country levels, and improving logistics and supply chains.

Fungal infections in hematopoietic stem-cell transplant patients: a review of epidemiology, diagnosis, and management.

The advent of bone marrow transplant has opened doors to a different approach and offered a new treatment modality for various hematopoietic stem-cell-related disorders. Since the first bone marrow transplant in 1957, there has been significant progress in managing patients who undergo bone marrow transplants. Plasma-cell disorders, lymphoproliferative disorders, and myelodysplastic syndrome are the most common indications for hematopoietic stem-cell transplant. Despite the advances, invasive fungal infections remain a significant cause of morbidity and mortality in this high-risk population. The overall incidence of invasive fungal infection in patients with hematopoietic stem-cell transplant is around 4%, but the mortality in patients with allogeneic stem-cell transplant is as high as 13% in one study. Type of stem-cell transplant, conditioning regimen, and development of graft-versus-host disease are some of the risk factors that impact the risk and outcomes in patients with invasive fungal infections. Aspergillus and candida remain the two most common organisms causing invasive fungal infections. Molecular diagnostic methods have replaced some traditional methods due to their simplicity of use and rapid turnaround time. Primary prophylaxis has undoubtedly shown to improve outcomes even though breakthrough infection rates remain high. The directed treatment has seen a significant shift from amphotericin B to itraconazole, voriconazole, and echinocandins, which have shown better efficacy and fewer adverse effects. In this comprehensive review, we aim to detail epidemiology, risk factors, diagnosis, and management, including prophylaxis, empiric and directed management of invasive fungal infections in patients with hematopoietic stem-cell transplant.

Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections.

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.

Establishing essential metrics for antifungal stewardship in hospitals: the results of an international Delphi survey.

Guidance on assessment of the quantity and appropriateness of antifungal prescribing is required to assist hospitals to interpret data effectively and structure quality improvement programmes. To achieve expert consensus on a core set of antifungal stewardship (AFS) metrics and to determine their feasibility for implementation. A literature review was undertaken to develop a list of candidate metrics. International experts were invited to participate in sequential web-based surveys to evaluate the importance and feasibility of metrics in the area of AFS using Delphi methodology. Three surveys were completed. Consensus was predefined as ≥80% agreement on the importance of each metric. Eighty-two experts consented to participate from 17 different countries. Response rate for each survey was >80%. The panel included adult and paediatric physicians, microbiologists and pharmacists with diverse content expertise. Consensus was achieved for 38 metrics considered important to routinely include in AFS programmes, and related to antifungal consumption (n = 5), quality of antifungal prescribing and management of invasive fungal infection (IFI) (n = 24), and clinical outcomes (n = 9). Twenty-one consensus metrics were considered to have moderate to high feasibility for routine collection. The identified core AFS metrics will provide a framework to comprehensively assess the quantity and quality of antifungal prescribing within hospitals to develop quality improvement programmes aimed at improving IFI prevention, management and patient-centred outcomes. A standardized approach will support collaboration and benchmarking to monitor the efficacy of current prophylaxis and treatment guidelines, and will provide important feedback to guideline developers.

Clinical Usefulness of Susceptibility Breakpoints for Yeasts in the Treatment of Candidemia: A Noninterventional Study.

This prospective noninterventional study evaluated whether antifungal susceptibility data (MIC) provided for Candida clinical isolates on the basis of recently established breakpoints are taken into account by clinicians to guide their treatment decision making process, and assessed the response in MIC- and non-MIC-based treatment groups. During a six month period, the usage of systemic antifungals was recorded in detail and compared with mycological data (Candida species and MICs) in candidemia patients. Patients were assigned to a susceptible or resistant infection group based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints; treatment decisions were under the professional discretion of the treating physicians. 123 patients were evaluated with Candida albicans accounting for 59%, Candida glabrata for 19%, Candida parapsilosis for 15%, Candida tropicalis for 4% and Candida krusei for 3%. Antifungal treatment correlated with species and MICs in 80% (n = 99 patients), high MICs and species-dependent guideline recommendations were ignored in 20% (n = 24 patients); the overall outcome of candidemia cases in our study population was excellent, as by day 14, all patients were cleared from fungal blood stream infection (mean 5.6 days, range 2–12). The current variability in antifungal usage and the delay in initiating appropriate therapy indicate a need for antifungal stewardship to improve the management of invasive fungal infections.

Variability in antifungal stewardship strategies among Society for Healthcare Epidemiology of America (SHEA) Research Network facilities.

To characterize antifungal stewardship among antimicrobial stewardship programs (ASPs) at a diverse range of hospitals and to correlate antifungal stewardship with hospital characteristics. Cross-sectional survey. ASP physician and/or pharmacist members at Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) hospitals. An electronic survey administered August-September 2018 via the SRN to 111 hospitals. The χ2 test was used to test associations between ASP and hospital characteristics and use of antifungal stewardship strategies. Of 111 hospitals, 45 (41%) responded; most were academic medical centers (65%) caring for stem-cell patients (73.3%) and solid-organ transplant patients (80.0%). Most hospitals have large, well-established ASPs: 60% had >5 team members and 68.9% had a duration ≥6 years. In 43 hospitals (95.6%), ASPs used antifungal stewardship strategies, most commonly prospective audit and feedback (73.3%) by a pharmacist (71.4%). Half of ASPs (51.1%) created guidelines for invasive fungal infection (IFI) management. Most hospitals (71.1%) offered rapid laboratory tests to diagnose IFI, but polymerase chain reaction (PCR) testing and antifungal susceptibility testing varied. Also, 29 ASPs (64.4%) perform surveillance of antifungal utilization, but only 9 (31%) reported to the CDC National Healthcare Safety Network. ASP size, duration, and presence of transplant populations were not associated with a higher likelihood of using antifungal stewardship strategies (P > .05 for all). The use of antifungal stewardship strategies was high at SRN hospitals, but they mainly involved audit and feedback. ASPs should be encouraged (1) to disseminate guidelines for IFI management, (2) to promote access to laboratory tests for rapid and accurate IFI diagnosis, and (3) to perform surveillance for antifungal utilization with reporting to the CDC.

Evaluation of knowledge and awareness of invasive fungal infections amongst resident doctors in Nigeria.

Introductionit has been estimated that about 11.8% of the Nigerians suffer serious fungal infections annually. A high index of suspicion with early diagnosis and institution of appropriate therapy significantly impacts on the morbidity and mortality of invasive fungal infections (IFIs).Methodswe conducted a cross-sectional multicentre survey across 7 tertiary hospitals in 5 geopolitical zones of Nigeria between June 2013 and March 2015. Knowledge, awareness and practice of Nigerian resident doctors about the diagnosis and management of invasive fungal infections were evaluated using a semi-structured, self-administered questionnaire. Assessment was categorized as poor, fair and good.Results834(79.7%) of the 1046 participants had some knowledge of IFIs, 338(32.3%) from undergraduate medical training and 191(18.3%) during post-graduate (specialty) residency training. Number of years spent in clinical practice was positively related to knowledge of management of IFIs, which was statistically significant (p < 0.001). Only 2 (0.002%) out of the 1046 respondents had a good level of awareness of IFIs. Only 4(0.4%) of respondents had seen > 10 cases of IFIs; while 10(1%) had seen between 5-10 cases, 180(17.2%) less than 5 cases and the rest had never seen or managed any cases of IFIs. There were statistically significant differences in knowledge about IFIs among the various cadres of doctors (p < 0.001) as level of knowledge increased with rank/seniority.Conclusionknowledge gaps exist that could militate against optimal management of IFIs in Nigeria. Targeted continuing medical education (CME) programmes and a revision of the postgraduate medical education curriculum is recommended.

Invasive pulmonary aspergillosis in a patient with cirrhosis.

Aspergillus molds are ubiquitous environmental molds that can cause devastating invasive infections in immunocompromised patients. These infections often go unrecognized in critically ill patients. This case describes a 68 year-old female resident of a long-term nursing facility with history of dementia, nonalcoholic fatty liver disease with cirrhosis, chronic kidney disease stage III and insulin-dependent type 2 diabetes who presented with vomiting, diarrhea and leg swelling. She developed hypotension and was treated for sepsis but found to have negative routine infectious workup. Chest imaging showed nodular densities and bilateral opacities. She developed acute renal failure and hypoxic respiratory failure followed by acute decompensated cirrhosis with refractory volume overload and hypotension and was eventually transitioned to comfort care measures. Autopsy ultimately showed invasive pulmonary aspergillosis. Here we review the diagnosis and management of invasive fungal infections in critically ill patients without typical risk factors or clinical findings for invasive fungal disease. Invasive fungal infections are frequently missed and carry high mortality rates, therefore warranting consideration in critically ill populations.

1980. Variability in Antifungal Stewardship Strategies Among Society for Healthcare Epidemiology of America (SHEA) Research Network Facilities

BackgroundThe incidence of invasive fungal infections (IFI) and antifungal utilization is increasing in many healthcare settings. Little is known regarding antifungal stewardship strategies within broader antimicrobial stewardship programs (ASPs). This survey aimed to identify the use of antifungal stewardship at a diverse range of hospitals.MethodsA cross-sectional electronic survey of the SHEA Research Network (SRN) was completed August–September 2018 by a physician or pharmacist ASP leader. The SRN is a consortium of >100 hospitals participating in multicenter healthcare epidemiology research projects. Survey questions pertained to various aspects of antifungal stewardship, including audit and feedback, laboratory testing, and surveillance. Chi-square tested associations between ASP and hospital characteristics and use of antifungal stewardship strategies.Results45/111 (41%) facilities responded, including 10 international sites. Most facilities are academic medical centers (64.6%) and care for stem cell (73.3%) and solid-organ transplant (80.0%) patients. Most facilities have large, well established ASPs (60.0% > 5 members; 68.9% duration ≥6 years). 43 (95.6%) facilities use antifungal stewardship strategies in their ASP; most commonly prospective audit and feedback (33/43, 73.3%) performed by a pharmacist (23/33, 71.4%). Only half of ASPs (51.1%) create guidelines for IFI management. Most (71.1%) facilities offer rapid laboratory tests to diagnose IFI, but availability of PCR for fungal speciation and antifungal susceptibility testing varies (Figure 1). 29 ASPs (64.4%) perform surveillance of antifungal utilization, but only 9 (31.0%) report data to CDC’s National Healthcare Safety Network (NHSN). ASP size, ASP duration, and presence of transplant populations were not associated with a higher likelihood of using antifungal stewardship strategies (P > 0.05 for all).ConclusionUse of antifungal stewardship strategies is high at SRN hospitals, but mainly involves audit and feedback. ASPs should be encouraged to disseminate guidelines for IFI management, to promote access to laboratory-based tests for rapid and accurate IFI diagnosis, and to perform surveillance for antifungal utilization with data reporting to NHSN. Disclosures All authors: No reported disclosures.

Orbital mycoses in a pediatric subtropical population: a case series

To report our experience in the diagnosis and management of invasive fungal infections with orbital involvement in children from a subtropical population. The medical records of children (<18years of age) with orbital mycosis and treated by the senior author (TJS) from 1995 to 2017 in multiple pediatric tertiary centers were reviewed retrospectively. Six patients (aged 12weeks to 15years) were included in this series. Four patients had confirmed infection with isolated pathogens, including mucormycosis (3) and Exserohilum (2). One patient rapidly deteriorated and died before biopsy could be performed; however, the patient was presumed to have invasive fungal disease. Four patients had underlying hematological malignancy, and 1 presented in diabetic ketoacidosis. Orbital apex syndrome was observed in one patient. All patients received liposomal amphotericin B and five underwent at least one debridement surgery. One patient proceeded to orbital exenteration and survived. The overall survival rate was 67%. Orbital mycoses can affect children of all ages. Immunocompromised patients are particularly at risk, and mortality rates are high. In a subtropical population, these infections may be caused by a different spectrum of fungi compared to other climate zones. We believe extensive surgical debridement, including exenteration may still be necessary in the management of this disease in a young population, particularly if there is extensive orbital involvement.

Cost-effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant.

Invasive fungal infection (IFI) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is also associated with excess healthcare costs. Current approaches include universal antifungal prophylaxis, preemptive therapy based on biomarker surveillance, and empiric treatment initiated in response to clinical signs/symptoms. However, no study has directly compared the cost-effectiveness of these treatment strategies for an allogeneic HSCT patient population. We developed a state transition model to study the impact of treatment strategies on outcomes associated with IFIs in the first 100days following myeloablative allogeneic HSCT. We compared three treatment strategies: empiric voriconazole, preemptive voriconazole (200mg), or prophylactic posaconazole (300mg) for the management of IFIs. Preemptive treatment was guided by scheduled laboratory surveillance with galactomannan (GM) testing. Endpoints were cost and survival at 100days post-HSCT. Empiric treatment was the least costly ($147482) and was equally effective (85.2% survival at 100days) as the preemptive treatment strategies. Preemptive treatments were slightly more costly than empiric treatment (GM cutoff≥1.0 $147910 and GM cutoff≥0.5 $148108). Preemptive therapy with GM cutoff≥1.0 reduced anti-mold therapy by 5% when compared to empiric therapy. Posaconazole prophylaxis was the most effective (86.6% survival at 100days) and costly ($152240) treatment strategy with a cost of $352415 per life saved when compared to empiric therapy. One preemptive treatment strategy reduced overall anti-mold drug exposure but did not reduce overall costs. Prevention of IFI using posaconazole prophylaxis was the most effective treatment strategy and may be cost-effective, depending upon the willingness to pay per life saved.

Surgical management of invasive fungal infections in adult leukemia patients: experience from a large tertiary center in Southeast-Asia.

Objectives:Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT). Surgical interventions may be necessary to improve the survival outcomes of these patients. The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients, median age 46 years (range 19–65), underwent 20 surgical procedures as management for IFI. Three patients had proven IFI diagnoses prior to surgery. Sixteen patients underwent surgery for both diagnostic and therapeutic purposes. Post-surgery, the diagnostic yield for proven IFI increased by a factor of 5, and 15 patients had definitive IFI diagnoses. Surgical complications included 2 pleural effusions, 4 pneumothoraxes, and 1 hydropneumothorax. The median duration of hospitalization for patients with complications was 9 days (range 3–64). Thirteen patients benefited overall from the procedure, 3 had temporary clinical benefits, and 2 had progression of IFI. After surgery, the 3-month and 2-year overall survival rates were 89.5% and 57.9%, respectively. The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients, as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk, thereby allowing patients to proceed with curative chemotherapy and HSCT.

Epidemiology and treatment approaches in management of invasive fungal infections in hematological malignancies: Results from a single-centre study.

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.

Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center

BackgroundInvasive fungal infections are a major cause of morbidity and mortality. Newer antifungals may provide similar efficacy with improved safety compared to older more established treatments. This study aimed to compare clinically relevant safety and efficacy outcomes in real world patients treated with isavuconazole, voriconazole, or posaconazole.MethodsThis single center retrospective matched cohort study evaluated adults between January 2015 and December 2017. The primary outcome was a composite safety analysis of antifungal related QTc prolongation, elevated liver function tests (> 5 times ULN), or any documented adverse drug event. Key secondary outcomes included: individual safety events, 30-day readmissions, magnitude of drug interactions with immunosuppressive therapy, and overall cost.ResultsA total of 100 patients were included: 34 patients in the voriconazole group and 33 patients within each of the isavuconazole and posaconazole groups. The composite safety outcome occurred in 40% of the total cohort and was different between isavuconazole (24.2%), voriconazole (55.9%), and posaconazole (39.4%; p = 0.028). Change in QTc (p < 0.01) and magnitude of immunosuppression dose reduction (p = 0.029) were different between the three groups. No differences in mortality, length of stay, readmission, or infection recurrence were observed between groups (p > 0.05 for all). The overall medication cost, when including therapeutic drug monitoring, was not different between treatments (p = 0.36).ConclusionsPatients treated with isavuconazole resulted in fewer composite safety outcomes, driven by decreased incidence of QTc prolongation, compared to patients treated with voriconazole or posaconazole. Overall drug cost was not significantly different between the treatment therapy options.

Standards of CARE: what is considered ‘best practice’ for the management of invasive fungal infections? A haematologist’s and a mycologist’s perspective

Patients at risk of, or diagnosed with, an invasive fungal infection benefit from an early antifungal intervention. Different strategies have been explored, each with particular strengths and weaknesses. The use of broad-spectrum antifungal prophylaxis seems logical, but selective use is important given its potential for major collateral damage, including interference with diagnostic assays, selection of resistance, toxicity and drug interactions. Hence, anti-mould prophylaxis should be restricted to well-defined high-risk groups. An empirical approach is still widely applied but incurs the clinical and cost penalties associated with overtreatment. Nowadays there is a growing interest in delaying antifungal treatment until an invasive fungal infection is highly suspected ('pre-emptive' management) or confirmed, prompted by the development of more-sensitive diagnostic techniques. While pre-emptive treatment looks appealing, the necessary monitoring and detailed treatment algorithms can be rather complex and often require a multidisciplinary effort. This article aims to bring together different perspectives on 'best practice' for the management of invasive fungal infections, using haematology patients as a model.

Effectiveness and Safety of Micafungin in Managing Invasive Fungal Infections among Patients in Greece with Hematologic Disorders: The ASPIRE Study.

IntroductionInvasive candidiasis (IC) can be a life-threatening infection in immunocompromised patients, particularly those with cancer, hematologic diseases and/or hematopoietic stem cell transplantation (HSCT) recipients. The objective of this study was to evaluate the effectiveness of micafungin in patients with hematologic malignancies or HSCT recipients, relevant to clinical presentation of IC, in real-life practice in Greece.MethodsASPIRE was a phase IV, multicenter, non-interventional, prospective cohort study, conducted at ten tertiary hospitals in Greece, in adults with hematologic disease. Micafungin treatment for IC or prophylaxis for Candida infection was administered per standard clinical practice until a clinical outcome (success or failure) was reached. Treatment success was defined by the EORTC/MSG criteria for invasive fungal infections (IFI) and was assessed by the investigator. Treatment discontinuation and safety were also evaluated.ResultsOne hundred forty-three patients were enrolled. Median age was 62; 85 (59.4%) patients were male, and 133 (93.0%) had Greek ethnicity. One hundred twenty-six (88.1%) patients had hematologic malignancies, and 21 (14.7%) had received HSCT. Prophylaxis was administered to 74 (51.7%) patients [median (range) dose: 50 (50–150) mg/day] with no signs of IFI. Overall, 52 (36.4%) patients with possible IFI at baseline received micafungin treatment [100 (50–125) mg/day] versus 12 (17.2%) with probable [100 (75–150) mg/day] and 5 (3.5%) with confirmed [125 (100–150) mg/day] IFI. Treatment success was 91.6% (95% CI 85.80–95.59; n = 131) overall and 90.5% (n = 67) in patients receiving prophylaxis. Median time on treatment was 13 days. Treatment discontinuation (n = 26; 18.2%) was not related to adverse events. No treatment-related serious adverse events were reported.ConclusionMicafungin treatment for IC or prophylaxis for Candida infection was effective and well tolerated in patients with hematologic disorders in clinical practice in Greece. These results demonstrate that micafungin could be used more widely for prophylaxis. Further work is required to determine the efficacy and safety of micafungin for the management of IFIs in hematologic settings.FundingAstellas Pharma Inc.

Thesaurus for off-label indications for systemic antifungal agents

ObjectivesFollowing the removal of temporary treatment protocol procedures, we developed a thesaurus for off-label indications for systemic antifungals at our facility to update clinical practices and to control off-label prescriptions. Materials and methodsClinical practice guidelines and literature data were analyzed. This work was part of an antifungal stewardship program. ResultsOff-label wording (prophylaxis, preemptive, empirical, curative) and corresponding antifungals and references were validated by the multidisciplinary group for antifungal agents under the aegis of the Commission for the use of drugs and sterile medical devices and of the anti-infective committee. ConclusionConsidering the complexity of invasive fungal infection management, this thesaurus needs to be shared and used as a helping tool to review off-label situations.

The Role of Antifungals in Pediatric Critical Care Invasive Fungal Infections.

Invasive fungal infections (IFIs) have seen considerable increase in pediatric intensive care units over the past several decades. IFIs are predominantly caused by Candida species, and candidemia is the third most common cause of healthcare-associated bloodstream infections (BSIs) in children. IFIs are opportunistic infections that affect pediatric patients in critical care resulting in significant morbidity and mortality especially in those with a compromised immune system. IFIs are the leading cause of death in children with comorbidities such as immunosuppression, and pediatric ICU admission has been shown to be an independent risk factor for mortality. Management of IFI and fungal sepsis is broad and encompasses several key components that include prompt initiation of therapy and rapid source identification and control. This study reviews important antifungals in the pediatric critical care setting including the pharmacologic properties, antifungal spectrum, adverse effects, and clinical uses of agents belonging to the four major classes of antifungals—the polyenes, azoles, echinocandins, and pyrimidine analogue flucytosine. The polyenes and azoles are the most often used classes of antifungals. The echinocandins are a relatively newer class of antifungal agents that offer excellent Candida activity and are currently recommended as the first-line therapy for invasive candidiasis.

Monetary costs and hospital burden associated with the management of invasive fungal infections in Mexico: a multicenter study

BackgroundInvasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim To report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. MethodsThis was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. ResultsTwo-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p<0.0001). The overall incidence of IFIs was 4.8 cases (95% CI=0.72–8.92) per 1000 discharges and 0.7 cases (95% CI=0.03–1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI=−1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI=−3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI=−0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). ConclusionsIFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

Management of Invasive Fungal Infections in Adult Patients with Hematological Malignancies in Greece during the Financial Crisis: Challenges and Recommendations.

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece.