Tratamiento antifúngico individualizado en el paciente crítico con infección fúngica invasora

Invasive candidiasis (IC) is the most common invasive fungal infection (IFI) affecting critically ill patients, followed by invasive pulmonary aspergillosis (IPA). International guidelines provide different recommendations for a first-line antifungal therapy and, in most of them, echinocandins are considered the first-line treatment for IC, and triazoles are so for the treatment of IPA. However, liposomal amphotericin B (L-AmB) is still considered a second-line therapy for both clinical entities. Although in the last decade the management of IFI has improved, several controversies persist. The antifungal drugs currently available may have a suboptimal activity, or be wrongly used in certain IFI involving critically ill patients. The aim of this review is to analyze when to provide individualized antifungal therapy to critically ill patients suffering from IFI, emphasizing the role of L-AmB. Drug-drug interactions, the clinical status, infectious foci (peritoneal candidiasis is discussed), the fungal species involved, and the need of monitoring the concentration of the antifungal drug in the patient are considered.     

Hierro e infección fúngica invasiva

Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine –the first approved iron chelator– paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis.     

Infección múltiple fúngica en un paciente diabético

BackgroundMixed fungal infections although undervalued, are more common than mentioned in the scientific literature. These infections have a poor prognosis for the patient.ObjectivesWe present an unusual case of a 61-year-old diabetic male who had a rhino-orbito-sinusal zygomycosis in 2001. After surgical debridement of the infected parts, along with antifungal therapy with liposomal amphotericin B, the patient started improving. Several years later the patient was hospitalized due to a similar problem and was diagnosed of rhino-orbito-cerebral zygomycosis.MethodsIn both episodes, a histopathological examination and cultures were performed on the sinus lesions. Tissue sections were stained with haematoxylin and eosin, Giemsa, periodic acid-Schiff (PAS) and Grocott's methenamine silver, and cultures specific for fungi were performed.ResultsThe histopathology studies revealed the presence of bacteria, actinomyces and a mixed infection by at least four different fungi, all of them well differentiated by their morphology. Despite the rapid diagnosis the patient died due to spreading to the central nervous system.ConclusionsMixed infections by fungi are rare, but due to the high incidence of immunodeficiencies they could occur more often than reported. We would like to alert on the possibility of acquired mixed infection by fungi which have shown to be high aggressive and have a worse prognostic in patients with underlying diseases.     

La infección fúngica en el paciente pediátrico inmunodeprimido

In recent years, immunodeficiency condition has experienced a rise among children, who are at risk of invasive fungal infections (IFI) due to their health condition. Cancer, non-malignant hematological diseases, as primary immunodeficiencies, hematopoietic stem cell transplantation (HSCT), extreme prematurity, or critically ill condition in Pediatric Intensive Care Unit (PICU) are some immunosuppressive situations in children. The use of oncologic therapies, including immunotherapy and monoclonal antibodies, for the treatment of the aforementioned health conditions has led to an increase in morbidity and mortality rates of IFI in children.The underlying diseases and their management, comorbidities, the diagnostic tests used (both molecular and imaging), as well as the treatment used can be significantly different between adult patients and children admitted to PICU or with cancer. In pediatrics, the treatment of IFI is based primarily on pharmacokinetic studies performed in adults. In higher risk patients prophylaxis should be considered and, in the case of an IFI diagnosis, an antifungal treatment should be administered as early as possible, supported by the reversion of the immune dysfunction and surgery when appropriate.     

Candidiasis invasora en el paciente crítico quemado

BackgroundThe advances in burn care therapy have extended considerably the survival of seriously burned patients, exposing them to infectious complications, notably fungal infections. Due to the difficulty in the diagnosis of invasive mycoses and their high associated mortality rates, approaches to prophylactic or pre-emptive antifungal therapy in high-risk burned patients have been proposed, although these guidelines remain controversial. On the other hand, the management of these conditions is a serious problem, especially in critically ill patients with multiorgan failure, including severely ill burn patients due to the shortage of available antifungal agents. However, in the last several years, the range of antifungal agents has been significantly extended, which have led to an improvement in the treatment of invasive fungal infection in this population.Clinical caseWe report a case of invasive candidiasis in a severelly ill burns patient successfully treated with an echinocandin. In this case report, current treatment options are discussed, and a review of the literature of previously published cases is made.ConclusionsThere are still significant gaps in our knowledge of the optimal diagnostic and management approach for invasive candidiasis in burn patients. Prospective studies are needed in this population to optimise management and improve outcomes in this state of high morbidity and mortality.     

Evolución de la infección fúngica invasora en los últimos 30 años

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.     

Primer caso de infección fúngica invasora por Candida fabianii en un paciente pediátrico no neonatal

BackgroundInvasive fungal diseases have increased in recent years. Candida species are the most common aetiology. Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei are the cause of most of them. The aim of this work is to describe the first isolation of Candida fabianii in the blood of a non-neonatal paediatric patient.Case reportA 2 year-old male with short bowel syndrome, severe malnutrition, and hypophosphataemic rickets deficiency was admitted to paediatric intensive care due to a respiratory tract infection and suspicion of an intestinal pseudo-obstruction. He received several cycles of broad-spectrum antibiotics for several infections due to Pseudomonas aeruginosa and Escherichia coli. After the surgical correction of the intestinal disorder he suffered a new episode of sepsis where yeasts were isolated by culture. The species identification was performed by means of mass spectrometry (MALDI-TOF system, Bruker Daltonic). The identity of the isolate was C. fabianii (anamorph)/Pichia fabianii (teleomorph) with a score of 2.149. Antifungal treatment with caspofungin was prescribed, with good progress of the patient.ConclusionsMolecular techniques are important for the identification of these species, although mass spectrometry offered a reliable and rapid diagnosis. Treatment with caspofungin was effective.     

Hacia el diagnóstico temprano de la candidiasis invasora en el paciente crítico

The management of invasive fungal infections in critically ill patients, from diagnosis to selection of the ther- apeutic protocol, is often a challenge. Early diagnosis and treatment are associated with a better prognosis, but apart from cases with positive cultures from blood or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, and there is a need for specific markers in these diseases. Serodiagnostic assays such as mannan an-tigen, mannan antibodies, Candida albicans germ-tube antibodies or (1→3)-β-D-glucan detection, and mo-lecular techniques for the detection of fungal-specific DNA have been developed with promising results in critical care settings. One of the main features in diagnosis is the evaluation of risk factors for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. The combination of prediction rules and non-culture microbiological tools could be currently be the key to improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.     

Enfermedad fúngica invasora por hongos filamentosos en pacientes hematológicos

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.     

Micafungina en el tratamiento de la infección fúngica en modelos animales

BackgroundMicafungin is an echinocandin antifungal drug recently approved for the treatment of candidiasis. The possibility of its clinical use against other invasive mycoses, has aroused the interest of numerous investigators in evaluating its efficacy in different animal models.ObjectivesTo critically review the current data on the use of micafungin in the treatment of invasive mycoses in animal models.MethodsWe searched the PubMed/Medline data base (National Library of Medicine) from 2005 to 2008, both inclusive, on the use of micafungin in the experimental treatment of the fungal infection.Results and conclusionsSeven, of a total of 18 articles reviewed, were done in animal models of candidiasis and six in animal models of pulmonary or SNC aspergillosis. Similarly to the other echinocandins, caspofungin and anidulafungin, micafungin seems to exert a fungicidal activity against Candida albicans and Candida glabrata and a fungistatic activity against Aspergillus fumigatus. The paradoxical effect observed in lung tissue the experimental caspofungin treatment of aspergillosis has not been seen in the case of micafungin. The available data demonstrate a higher efficacy of micafungin versus fluconazole in the experimental treatment of C. albicans infections caused by strains susceptible in vitro to both drugs. To improve the efficacy of micafungin in the treatment of C. glabrata and A. fumigatus infections, several authors have tested different combined therapies, the combination of micafungin with amphotericin B being that showed the best results.     

Estimación del filtrado glomerular en el paciente anciano. Implicaciones clínicas en el uso de antibióticos

IntroductionIn elderly, impaired kidney function may lead to relevant clinical implications, especially in drug dosage. There is no consensus on the best formula to estimate glomerular filtration rate (GFR) in this context. While the Cockcroft–Gault (CG) equation is the most used one in drug development, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is the most employed by clinical laboratories. The objective of this study is to analyze the differences and implications of using one or another equation when adjusting the dose of antibiotics.Material and methodsCross-sectional study performed in patients older than 80 years admitted to an acute geriatric unit for infectious disease. Socio-demographic, functional, clinic, assistance and laboratory variables were gathered, calculating GFR according to CG and CKD-EPI. A concordance study between both equations, bivariate analysis and multiple linear regression were carried out.Results100 patients were recruited, with mean age 88.5 ± 4.2 years, and 54% women. A relative overestimation of 13.63 mL/min was observed in GFR according to CKD-EPI, with a low-moderate concordance between both formulas. Greater need for dose adjustment of antibiotics with GC than with CKD-EPI was detected (38% vs. 23%; P < .001), as well as dosage discrepancies, especially with levofloxacin.ConclusionsBoth equations are not interchangeable in the elderly. When used to adjust antibiotic dose, CKD-EPI may overestimate GFR and may cause an increase in adverse reactions. Further studies should be carried out with the aim of reaching a consensus on the most appropriate equation for the elderly patient.     

Aspergilosis invasiva en el paciente crítico

Critically ill patients without severe immunosuppression make up a population in which invasive aspergillosis (IA) has been identified as an emergent pathology. Chronic treatment with corticosteroids, chronic obstructive pulmonary disease, and liver cirrhosis are repeatedly identified risk factors. However, due to the non-specificity of the symptoms and signs in the critical patient, and the relative low diagnostic capacity of the complementary tests, the diagnosis of the IA is a challenge for the specialist in critical care medicine. The application of diagnostic algorithms adapted to critical patients, in whom activation will depend on the isolation of Aspergillus in a respiratory specimen, is the most efficient diagnostic methodology in this population. Among the diagnostic approaches, the determination of galactomannan in bronchoalveolar fluid is the most useful diagnostic test. Once the suspicion is established, treatment should be started as soon as possible. Voriconazole, amphotericin B, and isavuconazole are the most effective treatments. Although voriconazole and amphotericin B are the drugs with the most scientific evidence, they are related with adverse effects and pharmacokinetic difficulties. Therefore, isavuconazole, which has shown high efficacy and safety in other populations, is a potential alternative of great interest for critically ill patients.     

Puesta al día en la candidiasis invasora en el paciente crítico no neutropénico

Invasive candidiasis in non-neutropenic critically ill patients remains a challenge for clinicians due to its association with high morbidity and mortality rates, increased incidence, and health-care costs. It is well known that early diagnosis and treatment are associated with a better prognosis. For these reasons a thorough update has been performed in this setting focused on recent Spanish epidemiology, new predictive scores and microbiological tests such as mannan antigen, mannan antibodies, Candida albicans germ-tube antibodies or (1→3)-β-D-glucan detection, molecular techniques for the detection of fungal-specific DNA, advances in antifungal treatment and educational programs in Spain. An early diagnostic and therapeutic algorithm is proposed based on the combination of scores and microbiological test. The aim of this review is to provide physicians with the best information available in order to improve the prognosis of these patients.