Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19.

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

A predictive score at admission for respiratory failure among hospitalized patients with confirmed 2019 Coronavirus Disease: a simple tool for a complex problem.

Coronavirus Disease 2019 (COVID-19) pandemic has implacably stricken on the wellness of many countries and their health-care systems. The aim of the present study is to analyze the clinical characteristics of the initial wave of patients with COVID-19 attended in our center, and to identify the key variables predicting the development of respiratory failure. Prospective design study with concurrent data retrieval from automated medical records of all hospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rRT-PCR assay performed on respiratory samples from March 2nd to 18th, 2020. Patients were followed up to May 1st, 2020 or death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mm Hg or the need for mechanical ventilation (either non-invasive positive pressure ventilation or invasive mechanical ventilation). We included 521 patients of whom 416 (81%) had abnormal Chest X-ray on admission. Median age was 64.6 ± 18.2 years. One hundred eighty-one (34.7%) developed respiratory failure after a median time from onset of symptoms of 9 days (IQR 6-11). In-hospital mortality was 23.8% (124/521). The modeling process concluded into a logistic regression multivariable analysis and a predictive score at admission. Age, peripheral pulse oximetry, lymphocyte count, lactate dehydrogenase and C-reactive protein were the selected variables. The model has a good discriminative capacity with an area under the ROC curve of 0.85 (0.82-0.88). The application of a simple and reliable score at admission seems to be a useful tool to predict respiratory failure in hospitalized COVID-19 patients.

Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study.

BACKGROUND: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. METHODS: A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. RESULTS: Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups. CONCLUSIONS: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Effectiveness of anakinra for tocilizumab-refractory severe COVID-19: A single-centre retrospective comparative study.

OBJECTIVES: A subgroup of patients with SARS-CoV-2 infection was thought to have developed cytokine release syndrome and were treated with tocilizumab; however, a significant percentage of patients evolved. This study aimed to determine the usefulness of anakinra as a rescue treatment for patients with tocilizumab-refractory COVID-19 disease. METHODS: A prospective cohort of patients with COVID-19 pneumonia who received anakinra as salvage therapy after failure of tocilizumab were compared (1:1) with selected controls in a historical cohort of patients treated with tocilizumab. Cases and controls were matched by age, comorbidities, pulse oximetry oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at baseline, and time elapsed since the initiation of treatment with tocilizumab. The primary outcome was the improvement in clinical status measured by a 6-point ordinal scale, from baseline to day 21. RESULTS: The study included 20 cases and 20 controls (mean age 65.3 ± 12.8 years, 65% males). No differences were found in the clinical improvement rates at 7, 14 and 21 days of follow-up. The in-hospital mortality rate for patients receiving anakinra was 55% vs. 45% in the control group (P = 0.527). CONCLUSIONS: Treatment with anakinra was not useful in improving the prognosis of patients with tocilizumab-refractory severe COVID-19.

Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

IL-6-based mortality risk model for hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. OBJECTIVE: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. METHODS: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. RESULTS: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. CONCLUSION: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.

Shigella sonnei bacteraemia in a cystic fibrosis patient: case report and literature review.

>INTRODUCTION: Shigellosis has a gastrointestinal presentation of variable severity in which bacteraemia is uncommon. We describe the first reported case of Shigella sonnei bacteraemia and intestinal coinfection with Clostridioides difficile in a cystic fibrosis patient. The literature on S. sonnei bacteraemia in adult and paediatric populations is also reviewed. CASE PRESENTATION: A 29-year-old male with cystic fibrosis presented with profuse acute watery diarrhoea, abdominal pain, shivering and fever. The patient showed mixed cardiogenic and septic shock. Despite antibiotic therapy, volume replacement therapy and vasoactive drugs, the patient showed biventricular dysfunction and multiple organ failure requiring implantation of an intra-aortic balloon pump (IABP) with extracorporeal membrane oxygenation (ECMO). C. difficile and S. sonnei were detected in the stools. Escherichia coli was identified in the blood by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, although after re-evaluation with biochemical and antiserum agglutination tests, the isolate was confirmed as S. sonnei. After adjustment of the antibiotic therapy to vancomycin, meropenem, amikacin and metronidazole and continuing with ECMO and IABP support for 8 days, the patient improved and was finally discharged after 44 days. CONCLUSION: S. sonnei bacteraemia is an unusual entity that should be kept in mind because of the severity of its presentation and high mortality. In acute gastroenteritis and fever, especially in paediatric patients under 5 years old and adults with criteria for immunosuppression or chronic diseases, blood and stool cultures provide simple information that is nonetheless very important for the management and prognosis of these patients.

DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure.

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

Síndrome DRESS secundario a ibuprofeno como causa de fallo hepático hiperagudo / DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

El fallo hepático agudo presenta alta mortalidad, siendo su primera etiología en España la viral. Presentamos un caso de fallo fulminante secundario a una reacción idiosincrásica a ibuprofeno, englobado en el síndrome de DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Dicho síndrome constituye un diagnóstico clave en el diagnóstico diferencial del fracaso hepático agudo, ya que su curso infausto obliga en muchas ocasiones a la realización de trasplante hepático como única terapéutica útil. Este caso es un buen ejemplo de la necesidad de la rapidez y la eficiencia en la coordinación a nivel intrahospitalario y entre centros sanitarios como factor clave en la mejoría del pronóstico (AU)

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis (AU)

Effectiveness of liposomal amphotericin B in patients admitted to the ICU on renal replacement therapy.

INTRODUCTION: This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT). METHODS: Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated. RESULTS: A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%. CONCLUSIONS: Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

Impact of liposomal amphotericin B on renal function in critically ill patients with renal function impairment

Objetivo: Evaluar la tolerabilidad de anfotericina B liposomal (L-AmB) en pacientes críticos con concentraciones elevadas de creatinina sérica (Cr) (> 1,5 mg/dL) al inicio del tratamiento con L-AmB. Métodos: Estudio retrospectivo, multicéntrico y comparativo de dos cohortes de pacientes críticos tratados con L-AmB durante tres o más días, que se diferenciaban según el nivel de creatinina al inicio del tratamiento. Se estableció como punto de corte un valor de Cr de 1,5 mg/dL. Se excluyeron los pacientes con técnicas de depuración extrarrenal antes o 48 horas después del inicio de L-AmB. La variable principal fue la diferencia entre el valor de creatinina al final comparado con el inicio de tratamiento con L-AmB. Otros parámetros secundarios fueron: abandonos relacionados con el tratamiento, necesidad de técnicas de depuración extrarrenal (TDE) y acontecimientos adversos graves (AAG) relacionados con el tratamiento. Se recogieron datos demográficos, enfermedad subyacente, motivo de prescripción, factores concomitantes de riesgo de nefrotoxicidad y estado vital al alta de UCI y del hospital. Resultados: Se reclutaron 122 pacientes en 26 UCI (Cr > 1,5 g/dL, n= 16; Cr normal, n= 106). Los motivos principales por los que se indicó L-AmB en ambos grupos fueron el amplio espectro y la presencia de inestabilidad hemodinámica. Se administró como tratamiento de 1ª línea en el 68,8% de los pacientes con Cr elevada y en el 52,8% con Cr normal. La puntuación APACHE II al ingreso en UCI fue 25 en pacientes con Cr elevada y 17 en aquellos con Cr normal (p< 0,001). La duración del tratamiento con L-AmB fue 16 y 12 días en pacientes con Cr elevada y normal y una dosis media de 3,5 vs 3,9 mg/kg/día. El uso concomitante de otros fármacos nefrotóxicos, la tasa de mortalidad, y la estancia en UCI y hospitalaria fueron similares en ambas cohortes. En los pacientes con función renal alterada al inicio de L-AmB se observó una reducción absoluta de Cf-Ci de 1,08 mg/dl (P<0,001). La Cr bajó a valores normales en el 50% de los pacientes, descendió pero sin llegar a valores normales en el 37,5% y sólo se elevó en 1 (6,25%) paciente. En ningún paciente se suspendió L-AmB por nefrotoxicidad ni se precisaron técnicas de depuración extrarrenal. No se reportaron AAG relacionados con el tratamiento. Conclusiones: El tratamiento con L-AmB en pacientes críticos con función renal deteriorada tuvo un impacto mínimo en la función renal. L-AmB puede utilizarse para el tratamiento de infecciones fúngicas en pacientes críticos independientemente de la función renal al inicio del tratamiento(AU)

Objetive: To assess the tolerability of liposomal amphotericin B (L-AmB) in critically ill patients with elevated serum creatinine concentrations (Cr) (> 1.5 mg/dL) at starting L-AmB therapy. Methods: Retrospective, multicenter, comparative study of two cohorts of critically ill patients treated with L-AmB during 3 or more days, the difference between them was the level of Cr at the beginning of treatment. A cutoff value of Cr of 1.5 mg/dL was established. Patients undergoing extrarenal depuration procedures before or 48 hours after starting L-AmB were excluded. The primary endpoint was the difference between Cr values at the end of treatment as compared with Cr at starting L-AmB. Secondary endpoints were treatment-related withdrawals, need of extrarenal depuration techniques, and treatment-related severe adverse events. Demographic data, underlying illness, indication of L-AmB therapy, concomitant risk factors of nephrotoxicity, and vital status at ICU and hospital discharge were recorded. Results: A total of 122 patients admitted to 26 ICUs (16 with Cr > 1.5 g/dL; 106 with normal Cr levels) were recruited. Main reasons for the use of L-AmB in both groups were the broad spectrum of the drug and the presence of hemodynamic instability. L-AmB was administered as first-line treatment in 68.8% of patients with elevated Cr and in 52.8% with normal Cr. The APACHE II score on ICU admission was 25 in patients with elevated Cr and 17 in those with normal Cr values (p < 0.001). Duration of treatment with L-AmB was 16 and 12 days in patients with elevate and normal Cr values, respectively, with a mean dose of 3.5 vs 3.9 mg/kg/day. The use of concomitant nephrotoxic drugs, mortality rate, and ICU and hospital length of stay were similar in both cohorts. In patients with renal function impairment at the initiation of L-AmB treatment, an absolute decrease of Cf-Ci of 1.08 mg/dL was observed (P < 0.001). A decrease of Cr levels to normal limits was observed in 50% of the patients; in 37.5% of patients there was a decrease but normal levels were not achieved, whereas a Cr increased occurred in only one (6.25%) patient. None of the patients required withdrawal of L-AmB or use of extrarenal depuration procedures. Treatment-related severe adverse events were not reported. Conclusions: In critically ill patients with impaired renal function, the impact of L-AmB on renal function was minimal. L-AmB can be used for the treatment of fungal infections in critically ill patients independently of renal function at the initiation of treatmen(AU)

Acinetobacter baumannii multirresistente: «un reto universal» / Multiresistant Acinetobacter baumannii: An universal challenge

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Isolation of Aspergillus lentulus in Spain from a critically ill patient with chronic obstructive pulmonary disease.

Aspergillus lentulus was first described in the year 2005, and since it cannot be phenotypically distinguished from Aspergillus fumigatus, it is conceivable that earlier descriptions (before 2005) could be attributed to this new species. Currently invasive infections caused by A. lentulus are rare and very few cases have been previously published in neutropenic patients, all of them with fatal outcome. Here we report a critically ill non neutropenic patient with chronic obstructive pulmonary disease (COPD) who was admitted to the medical intensive care unit with an exacerbation of COPD and who had been treated with long term corticosteroids. A. fumigatus was cultured from two bronchial aspirates and in a third bronchial aspirate both A. lentulus and A. fumigatus were isolated. On two consecutive days detection of galactomannan in serum was negative whilst detection of (1-3) beta-D glucan was positive (> 518 pg/ml). Minimal inhibitory concentrations (MIC) for itraconazole, voriconazole, caspofungin and amphotericin B were high for this strain of A. lentulus. Given the high MIC values of A. lentulus to available antifungals, the accurate identification of this new species is warranted. To our knowledge, this is the first report of the isolation of A. lentulus in a non-neutropenic critically ill patient, although we note that since it was isolated only once from respiratory specimens, its implication as an etiologic agent of infection for this patient remains to be established.

Isolation of Aspergillus lentulus in Spain from a critically ill patient with chronic obstructive pulmonary disease

Aspergillus lentulus es un hongo de reciente descripción (año 2005) ypracticamente idéntico a Aspergillus fumigatus; posibles aislamientos deA. lentulus anteriores a 2005 eran identificados como A. fumigatus.Actualmente se han publicado muy pocos casos de infecciones invasorascausadas por A. lentulus, todos ellos con evolución fatal, en pacientesneutropénicos. Comunicamos el caso de un paciente crítico no neutropénicocon enfermedad pulmonar obstructiva crónica (EPOC) admitido en la unidadde cuidados intensivos médicos con una exacerbación de EPOC y quehabía sido sometido a un tratamiento prolongado con corticosteroides. Se aisló A. fumigatus en dos aspirados bronquiales, y A. lentulus y A. fumigatusde un tercero. En dos días consecutivos la detección de galactomanano ensuero fue negativa, mientras que la detección de (1-3) beta-D glucano fuepositiva (>518 pg/ml). Los valores de concentración mínima inhibitoria (CMI)obtenidos con el itraconazol, el voriconazol, la caspofungina y la anfotericinaB fueron altos para A. lentulus. Dado lo elevado de estos valores enA. lentulus, es necesaria la identificación precisa de esta nueva especie enaislamientos clínicos. A nuestro entender, este es el primer aislamiento de A.lentulus en un paciente crítico no-neutropénico, aunque como su aislamientose realizó una sola vez de secreciones respiratorias (dada la dificultad de laobtención de biopsias en este enfermo por su situación comprometida), suimplicación como agente etiológico de infección es dudosa en este enfermo(AU)

Aspergillus lentulus was first described in the year 2005, and since it cannotbe phenotypically distinguished from Aspergillus fumigatus, it is conceivablethat earlier descriptions (before 2005) could be attributed to this new species.Currently invasive infections caused by A. lentulus are rare and very few caseshave been previously published in neutropenic patients, all of them with fataloutcome. Here we report a critically ill non neutropenic patient with chronicobstructive pulmonary disease (COPD) who was admitted to the medicalintensive care unit with an exacerbation of COPD and who had been treatedwith long term corticosteroids. A. fumigatus was cultured from two bronchialaspirates and in a third bronchial aspirate both A. lentulus and A. fumigatuswere isolated. On two consecutive days detection of galactomannan in serumwas negative whilst detection of (1-3) beta-D glucan was positive(> 518 pg/ml). Minimal inhibitory concentrations (MIC) for itraconazole,voriconazole, caspofungin and amphotericin B were high for this strain ofA. lentulus. Given the high MIC values of A. lentulus to available antifungals,the accurate identification of this new species is warranted. To our knowledge,this is the first report of the isolation of A. lentulus in a non-neutropeniccritically ill patient, although we note that since it was isolated only once fromrespiratory specimens, its implication as an etiologic agent of infection for thispatient remains to be established(AU)

[Prevention of invasive candidiasis in the critically ill non neutropenic patient]. / Medidas de prevención de la candidiasis invasora en el paciente crítico no neutropénico.

Prevention of invasive candidiasis (IC) in the setting of critically ill non neutropenic patients should be based on evidenced-based recommendations, namely improved hand hygiene, optimal catheter care, and rational and reduced use of broad-spectrum antibiotics. Concomitant interventions aimed at reducing risk factors are important to decrease IC.

[Systemic antifungals. Pharmacodynamics and pharmacokinetics]. / Antifúngicos sistémicos. Farmacodinamia y farmacocinética.

Invasive fungal infections are important causes of morbidity and mortality in critically ill non neutropenic patients. For many years, amphotericin B and flucytosine have been the only available antifungal agents for invasive fungal infections. Fortunately, the antifungal armamentarium has increased during the past two decades with the addition of several new agents. In addition to itraconazole and fluconazole, lipid formulations of amphotericin B, voriconazole, and caspofungin have been recently licensed. These various antifungal agents differ in their pharmacokinetic and pharmacodynamic profile.

Medidas de prevención de la candidiasis invasora en el paciente crítico no neutropénico / Prevention of invasive candidiasis in the critically ill non neutropenic patient

La prevención de la candidiasis invasora (CI) en el enfermo crítico no neutropénicodebe sustentarse en recomendaciones basadas en la evidencia: medidashigiénicas de manos; optimización en los cuidados de catéteres vasculares centralesy utilización racional de antibióticos de amplio espectro. Otras intervencionesconcomitantes con la finalidad de disminuir los factores de riego sonimportantes para reducir la incidencia de la CI

Prevention of invasive candidiasis (IC) in the setting of critically ill non neutropenicpatients should be based on evidenced-based recommendations, namelyimproved hand hygiene, optimal catheter care, and rational and reduced use ofbroad-spectrum antibiotics. Concomittant interventions aimed at reducing riskfactors are important to decrease IC