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Clinical mycology is in continuous development. The appearance of new clinical guidelines has made it possible to improve the approach to opportunistic fungal infections, especially in immunosuppressed patients (oncohematological and/or transplant recipients). At the same time, the development of new diagnostic tools and new antifungals with a greater spectrum of action and fewer side effects have led to faster diagnoses and treatments that are more effective. Along with these advances, there has been a change in the epidemiology of invasive fungal infection (IFI), with the appearance of new patients (e.g., COPD, liver cirrhosis, post-influenza) and new microorganisms (Candida auris, Lomentospora prolificans, mucorales), and resistant fungi (isolates of Aspergillus resistant to azoles) which the clinician must take into account when choosing the treatment of a patient with an IFI. In this paper we will briefly review the advances in recent decades and the emerging problems., (Copyright © 2021 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Febrile neutropenia is a very common complication in patients with hematological malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria have become a therapeutic challenge in this high-risk patient population, since inadequate initial empirical treatment can seriously compromise prognosis. However, reducing antimicrobial exposure is one of the most significant cornerstones in the fight against resistance. The objective of these new guidelines is to update recommendations for the initial management of hematological patients who develop febrile neutropenia in this scenario of multidrug resistance. The two participating Societies (the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [Spanish Society of Infectious Diseases and Clinical Microbiology] and the Sociedad Española de Hematología y Hemoterapia [Spanish Society of Haematology and Haemotherapy]), designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on bacterial infections. Other aspects related to opportunistic infections, such as those caused by fungi or other microorganisms, especially in hematopoietic stem cell transplantation, are also touched upon., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Over the last decade, there have been important developments in the treatment of lymphoproliferative disorders. Apart from conventional chemotherapy, a wide array of therapies has been developed, with different indications. The aim of this review is to evaluate the risk of infection associated with these therapies, as well as establishing prevention recommendations. In all cases, the patient's underlying disease as well as concomitant or previous therapies have an impact on the risk of infection. Anti-CD20 antibodies (rituximab, ofatumumab and obinutuzumab) have been associated with a higher risk of bacterial and viral infection, as well as reactivation of latent infections and opportunistic infections. Alemtuzumab is associated with severe, protracted immunosuppression. Ibrutinib and acalabrutinib have been linked to bacterial infections (especially respiratory infections), invasive fungal infections and opportunistic infections. Idelalisib carries a higher risk of Pneumocystis jirovecii and infection and cytomegalovirus reactivation. Venetoclax is associated with respiratory infections and neutropenia. Immune checkpoint inhibitors are not directly associated with a higher risk of infection; nevertheless, the use of corticosteroids and immunosuppressants to control immune-related adverse events results in an increase of the risk of infection. Brentuximab, lenalidomide and histone deacetylase inhibitors do not seem to be associated with a higher risk of infections. Although data are scarce, a higher number of infections have been observed with cellular therapies, mostly in patients with more than 3 previous antineoplastic treatments or those receiving tocilizumab or corticosteroids for managing the cytokine release syndrome. In all patients, we recommend appropriate vaccination, screening for latent infections, and individualized prophylaxis recommendations., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Aspergillus infection is a significant cause of morbi-mortality in an at-risk population. The Study Group of Fungal Infections (GEMICOMED) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has reviewed announcements made in invasive aspergillosis management. We have organized our recommendations in such a way as to provide a guide in resolving different clinical situations concerning the entire spectrum of invasive diseases caused by Aspergillus in various populations. Diagnostic approach, treatment and preventions strategies are outlined. It is not our aim that these guidelines supplant clinical judgment with respect to specific patients; however, it is our objective to perform a comprehensive summary of quality of care evidence for invasive aspergillosis management in different settings., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Infections due to zygomycetes, caused by mucorales and entomophthorales, are characterized by angioinvasion and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous or disseminated infection and its spread is favored by several diseases (such as diabetes or chronic kidney disease) and risk factors (neutropenia, immunosuppression, iron overload). They have a high mortality rate, and the key to success in their treatment are early diagnosis, prompt administration of antifungal treatment, and extensive surgical debridement. Currently, isavuconazole constitutes an option for the treatment of those mucormycosis refractory to liposomal amphotericin B. Due to its pharmacokinetic and pharmacodynamic characteristics and its low toxicity, it is also the best choice for maintenance therapy., (Copyright © 2018 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis., (Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital., Methods: A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5μg/mL., Results: The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1μg/mL in 10 (19.2%) and >5.5μg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1μg/mL at the first TDM had a successful outcome (96%)., Conclusions: Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics., (Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper., (Copyright © 2014. Published by Elsevier Espana.)

Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be implemented to improve the current situation., (Copyright © 2014 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

These guidelines are an update of the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) that were issued in 2004 (Enferm Infecc Microbiol Clin. 2004, 22:32-9) on the treatment of Invasive Candidiasis and infections produced by other yeasts. This 2010 update includes a comprehensive review of the new drugs that have appeared in recent years, as well as the levels of evidence for recommending them. These guidelines have been developed following the rules of the SEIMC by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. It provides a series of general recommendations regarding the management of invasive candidiasis and other yeast infections, as well as specific guidelines for prophylaxis and treatment, which have been divided into four sections: oncology-haematology, solid organ transplantation recipients, critical patients, and paediatric patients., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the last few decades. Despite the development of new antifungal agents, these infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. To reduce these figures, several therapeutic strategies have been proposed, including combination therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue therapy; in addition there are many patients with possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination therapy has significantly higher efficacy than monotherapy; however, combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among the combinations, the association of an echinocandin--the group that includes micafungin--with voriconazole or liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Febrile neutropenia is a common complication in pediatric oncohematological patients. It is defined by fever > or = 38.3 degrees C or > or = 38 for more than one hour together with a neutrophil count of < or = 500/microl(3). These children are usually admitted to hospital and receive empirical broad-spectrum antibiotic therapy. Recent studies support the possibility of early discharge or outpatient management in selected cases of febrile neutropenia. This translates into a lower risk of nosocomial infections and a reduction in the discriminate use of broad-spectrum antibiotics, with a consequent reduction in resistance, toxicity and costs. All of these factors would improve the patient's quality of life. The estimated incidence of bacteremia in children with febrile neutropenia is 10-36%. However, the experience of multiple centers suggests that not all children have the same risk of complications or death due to infection and that the risk is much lower than that in adults.