Impact of antimicrobial stewardship in organisms causing nosocomial infection among COVID-19 critically ill adults.

OBJECTIVE: To evaluate the implementation of an antibiotic stewardship program in critically ill COVID-19 patients and to establish risk factors for coinfection. Secondary objective was to analyze the evolution of the etiology of respiratory nosocomial infections. METHODS: Single-center observational cohort study of consecutive patients admitted to ICU due to COVID-19 pneumonia from March 2020 to October 2022. An antibiotic stewardship program was implemented at the end of the second wave. RESULTS: A total of 878 patients were included during 6 pandemic waves. Empirical antibiotic consumption decreased from the 96% of the patients during the first pandemic wave, mainly in combination (90%) to the 30% of the patients in the 6th pandemic wave most in monotherapy (90%). There were not differences in ICU and Hospital mortality between the different pandemic periods. In multivariate analysis, SOFA at admission was the only independent risk factor for coinfection in critically ill COVID-19 patients (OR 1,23 95%CI 1,14 to 1,35). Differences in bacterial etiology of first nosocomial respiratory infection were observed. There was a progressive reduction in Enterobacteriaceae and non- fermentative Gram Negative Bacilli as responsible pathogens, while methicillin-sensitive Staphylococcus aureus increased during pandemic waves. In the last wave, however, a trend to increase of potentially resistant pathogens was observed. CONCLUSIONS: Implementation of an antibiotic stewardship program was safe and not associated with worse clinical outcomes, being severity at admission the main risk factor for bacterial coinfection in covid-19 patients. A decline in potentially resistant pathogens was documented throughout the pandemic.

Factor Structure and Psychometric Properties of Emotional Eater Questionnaire (EEQ) in Spanish Colleges.

Emotional eating (EE) patterns have been shown to play a relevant role in the development of overweight problems. However, there is a gap in research aimed at validating questionnaires to assess EE in specific populations. The aim of the study was to analyze factor structure and psychometric properties of Emotional Eater Questionnaire (EEQ) in Spanish universities. EEQ, state-anxiety subscale of STAI and a questionnaire about health habits were filled out by 295 students. Exploratory Factor Analysis (EFA) by using Unweight Least Squares (ULS) method was carried out. To determine factor numbers we used eigenvalues, parallel analysis, and goodness of fit statistics. Cronbach's alpha and Spearman correlations were used to analyze reliability, convergent, and concurrent validity. The parallel analysis and goodness of fit statistics showed that unifactorial structure of seven items was the most appropriate what accounted for 57% of the variance. Internal consistency was good (α = 0.753), as well as convergent validity (r = 0.317; p < 0.001). Concurrent validity was significant for three of the five criteria (r = -0.224; p < 0.001 and r = -0.259; p < 0.001). The results suggest some differences in the structure of the psychometric assessment of EE in sub-clinical population in comparison with previous studies carried on with an overweight population, what could be relevant to obesity prevention.

Results from the CLUES study: a cluster randomized trial for the evaluation of cardiovascular guideline implementation in primary care in Spain.

BACKGROUND: The implementation of evidence-based clinical practice guidelines (CPG) can improve patients care. To date, the impact of implementation strategies has not been evaluated in our context. This study is aimed to evaluate the effectiveness of a multifaceted tailored intervention targeting clinician education for the implementation of three cardiovascular risk-related CPGs (type 2 diabetes, hypertension and dyslipidemia) in primary care at the Basque Health Service compared with usual implementation. METHODS: We conducted a cluster randomized controlled trial in two urban districts with 43 primary care units (PCU). Data from all patients diagnosed with diabetes, hypertension and all those eligible for coronary risk (CR) assessment were included. In the control group, guidelines were introduced in the usual way (by email, intranet and clinical meetings). In the intervention group, the implementation also included a specific website and workshops. Primary endpoints were annual HbA1c testing (diabetes), annual general laboratory testing (hypertension) and annual CR assessment (dyslipidemia). Secondary endpoints were process, prescription and clinical endpoints related with guideline recommendations. Analysis was performed at a PCU level weighted by cluster size. RESULTS: Significant differences between groups were observed in primary outcomes in the dyslipidemia CPG: increased CR assessment for both women and men (weighted mean difference, WMD, 13.58 and 12.91%). No significant differences were observed in diabetes and hypertension CPGs primary outcomes. Regarding secondary endpoints, annual CR assessment was significantly higher in both diabetic and hypertensive patients in the intervention group (WMD 28.16 and 27.55%). Rates of CR assessment before starting new statin treatments also increased (WMD 23.09%), resulting in a lower rate of statin prescribing in low risk women. Diuretic prescribing was higher in the intervention group (WMD 20.59%). Clinical outcomes (HbA1c and blood pressure control) did not differ between groups. CONCLUSIONS: The multifaceted implementation proved to be effective to increase the CR assessment and to improve prescription, but ineffective to improve diabetes and hypertension related outcomes. In order to obtain real improvements when cardiovascular issues are tackled, perhaps other or additional interventions need to be implemented besides education of professionals. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN 88876909 (retrospectively registered on January 13, 2009).

The CLUES study: a cluster randomized clinical trial for the evaluation of cardiovascular guideline implementation in primary care.

BACKGROUND: The appropriate care for people with cardiovascular risk factors can reduce morbidity and mortality. One strategy for improving the care for these patients involves the implementation of evidence-based guidelines. To date, little research concerning the impact of such implementation strategies in our setting has been published. Aims. To evaluate the effectiveness of a multifaceted tailored intervention in the implementation of three cardiovascular risk-related guidelines (hypertension, type 2 diabetes and dyslipidemia) in primary care in the Basque Health Service compared with usual implementation. METHODS/DESIGN: A two-year cluster randomized clinical trial in primary care in two districts in the Basque Health Service. All primary care units are randomized. Data from all patients with diabetes, hypertension and those susceptible to coronary risk screening will be analyzed.Interventions. The control group will receive standard implementation. The experimental group will receive a multifaceted tailored implementation strategy, including a specific web page and workshops for family physicians and nurses.Endpoints. Primary endpoints: annual request for glycosylated hemoglobin, basic laboratory tests for hypertension, cardiovascular risk screening (women between 45-74 and men between 40-74 years old). Secondary endpoints: other process and clinical guideline indicators. ANALYSIS: Data will be extracted from centralized computerized medical records. ANALYSIS will be performed at a primary care unit level weighted by cluster size. DISCUSSION: The main contribution of our study is that it seeks to identify an effective strategy for cardiovascular guideline implementation in primary care in our setting. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN88876909.

Efficacy of petrolatum jelly for the prevention of diaper rash: a randomized clinical trial.

PURPOSE: To assess the efficacy of petrolatum jelly for the prevention of diaper rash and to evaluate the relationship between the occurrence of diaper rash and certain treatments and type of nutrition. DESIGN AND METHODS: A randomized clinical trial was carried out with two parallel groups (n = 213) at the neonatal care unit of Donostia University Hospital in San Sebastián, Guipuzcoa Province, Spain. RESULTS: There was a lower incidence of diaper rash in the experimental group with petrolatum jelly (17.1%) than the control group (22.2%), but the difference was not statistically significant (p =.39). The use of antibiotics and oral 50% glucose as well as an increased number of stools are associated with a higher incidence of diaper rash, while breastfeeding and phototherapy are protective factors. PRACTICE IMPLICATIONS: Prevention is strengthened by a better understanding of the risk factors.

Brote de escabiosis profesional / Human scabies or scabies is a contagious infestation transmitted by intimate contact between people

La sarna humana o escabiosis es una infestación contagiosa transmitida por el contacto íntimo entre las personas. El objetivo de este trabajo es describir un brote de sarna ocurrido en trabajadores de una planta de hospitalización del Complexo Hospitalario Universitario de Ourense (CHUO), cuyo origen fue una paciente de 85 años ingresada con la enfermedad. Una vez detectado el brote, la Unidad de Prevención de Riesgos Laborales (UPRL), integrada en el Servicio de Medicina Preventiva llevó a cabo las actuaciones para el control del mismo. Se produjeron 17 casos de sarna en personal sanitario. La rápida adopción de medidas preventivas fue clave para el control del brote, evitando la transmisión de la enfermedad entre el personal sanitario y demás contactos de los casos diagnosticados (AU)

This study describes an outbreak of scabies among employees of the University Hospital Complex of Ourense (CHUO). The index case was a 85 years old patient who had been as a inpatient and suffered from Norwegian scabies. There were 17 diagnoses of scabies among healthcare workers. Once detected the outbread, the Unit for the Prevention of Occupational Risks, integrated at Preventive Medicine Unit implemented control measures. The early preentive measures were essential for the control measures. The early preventive measures were essential for the control of the outbreak and the prevention od disease transmission to health workers, as well as their contacts (AU)

Time frames for analysis of inflammatory mediators in acute pancreatitis: improving admission triage.

Improving the outcome of acute pancreatitis through prognostic markers has been a matter of ample research. We evaluate the clinical usefulness of four serum markers in comparison to Ranson's score. Serum measurements of C-reactive protein (CRP), interleukin-6, -10 (IL-6, IL-10), and pancreatitis-associated protein (PAP) were performed. The usefulness of each marker for predicting severity was compared with that of Ranson's score. Time of evolution was considered for improving their usefulness. Seventy-one patients were studied. Severe cases had higher levels of all markers, although only IL-10 had better accuracy than Ranson's. In patients admitted during the first 48 h, IL-6, IL-10, and PAP had improved accuracy over Ranson's; however, after this time frame, only CRP outperformed Ranson's score. Analysis of time frames improved the accuracy of all markers. Therefore, time of evolution should be considered when using these parameters for a better prognosis.

High prevalence of celiac disease in Mexican Mestizo adults with type 1 diabetes mellitus.

BACKGROUND AND AIMS: Recent studies have shown that celiac disease (CD) could affect 0.5% to 3% of the general population, including Mexican Mestizos, which represents a complex mixture of genetics, and constitutes the core of Mexican and Latin American populations. However, the association between CD and other conditions, specifically type-1 diabetes mellitus, in this population remains unknown. Thus, our aim was to determine the prevalence of both serologic and biopsy proven CD in Mexican Mestizo adults with type-1 diabetes. METHODS: Over a 6-month period, serum samples obtained from consecutive Mexican Mestizo adult patients (age >or=18 y) with type-1 diabetes were tested with a new generation human recombinant protein based IgA tissue transglutaminase enzyme-linked immunosorbent assay commercial kit. All patients with positive serologic test results underwent upper gastrointestinal endoscopy and small intestinal biopsies to confirm CD. RESULTS: Eighty-four type-1 diabetic patients were included (62 women, mean age 28.9+/-9 y). Overall, 9 patients (9/84) were positive for IgA tissue transglutaminase with a point prevalence of 10.7% (95% CI, 4%-17%). Seven patients agreed to undergo endoscopy. Five subjects had biopsy-proven CD (5.9%, 95% CI, 1.9%-13.3%). One patient had chronic diarrhea and other abdominal bloating; whereas the remaining 3 were asymptomatic. CD associated type-1 diabetic patients tended to have higher hemoglobin A1c levels (P=0.07), reflecting poor glycemic control. CONCLUSIONS: As in other populations, we demonstrated a high prevalence of biopsy-proven CD (5.9%) among Mexican Mestizo patients with type-1 diabetes. Clinicians should be aware of this common association in this ethnic group.

Amino acid composition and antioxidant capacity of Spanish honeys.

The amino acid composition of 53 honey samples from Spain, consisting of 39 floral, 5 honeydew, and 9 blend honeys, has been determined. Physicochemical characteristics, polyphenolic content, amino acid composition, and estimation of the radical scavenging capacity against the stable free radical DPPH of the honey samples were analyzed. The resulting data have been statistically evaluated. The results showed that pH, acidity, net absorbance, electrical conductivity, and total polyphenolic contents of the honeys showed a strong correlation with the radical scavenging capacity. The correlation between the radical scavenging capacity of honey and amino acid contents was high with 18 of the 20 amino acids detected, with correlation values higher than those obtained for polyphenolic content. These results suggest that the amino acid composition of honey is an indicator of the sample's scavenging capacity.

Association of alcohol-metabolizing genes with alcoholism in a Mexican Indian (Otomi) population.

Association studies provide a powerful approach to link DNA variants and genetic predisposition to complex diseases. In this study, we determined the genotype and allelic frequencies of genes encoding enzymes involved in alcohol metabolism in alcoholic and nonalcoholic subjects of related ethnicity. A total of 118 individuals of Otomi Mexican Indian ancestry were included. Fifty-nine were chronic alcoholics according to WHO criteria and alcohol dependents according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria. They were compared to 59 teetotalers or alcohol consumers of <10 g per day. The restriction fragment length polymorphisms analyzed were ADH1B/MaeIII, ALDH2/MboII, CYP2E1/DraI, CYP2E1/RsaI, and CYP2E1/TaqI. Of the studied polymorphisms, a significant difference between alcoholic and nonalcoholic Otomies was observed only in the CYP2E1/TaqI. The common genotype in alcoholics was A1/A2 (54%), and in nonalcoholics the homozygous A2/A2 (63%) (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.13-0.60; P=.002). The frequency of the mutant allele A1 was significantly higher in alcoholics than in nonalcoholics (41 vs. 21%; OR: 2.4; 95% CI: 1.3-4.3; P=.003). This documents the presence of a polymorphism of CYP2E1 that is overexpressed in alcoholic Otomies, in which the variant allele (A1 of CYP2E1/TaqI) is associated with increased susceptibility to alcoholism. The appreciation that this finding may be an additional factor contributing to the high frequency of liver cirrhosis in Otomies requires further investigation.

Celiac disease could be a frequent disease in Mexico: prevalence of tissue transglutaminase antibody in healthy blood donors.

INTRODUCTION/AIM: In North America and Europe, the prevalence of celiac disease (CD) might be much greater than expected in previous estimates. Until recently, the prevalence of CD in Latin America remained largely unknown. So far, information regarding CD in Mexico is limited, and it is still considered a rare disease. Our aim was to determine the prevalence of tTGA in a large group of apparently healthy blood donors. SUBJECTS AND METHODS: Serum samples from 1009 consecutive blood donors, who attended a third level referral center in Mexico City, were collected between June 2004 and December 2004. Only Mexican Mestizo individuals were included. All sera were tested with a new generation human recombinant protein based tTGA-IgA ELISA commercial kit (Aeskulisa tTG-IgA, Wendelsheim, Germany). The cut-off value provided by the manufacturer was 15 U/mL. RESULTS: The mean age of the blood donors was 34+/-10 years and 68% (n=683) were men. Six hundred fifty two subjects (65%) were born in Mexico City; and from the remaining 357 subjects, at least one was born in each of the 31 different states in our country. Twenty-seven (2.7%) blood donors were positive for tTGA-IgA; all of them with tTGA-IgA values above 30 U/mL (range 36 to 1639). Overall prevalence was 1:37 [27/1009, 95% confidence interval (CI)=1.6-3.7]. The prevalence among women was 1:33 (10/326, 95% CI=1.04-5.09) and for men 1:40 (17/683, 95% CI=1.24-3.73). CONCLUSIONS: On the basis of a well-recognized serologic screening method performed to blood donor samples, we demonstrated an unexpectedly high prevalence of tTGA positivity (2.6%) in the adult Mexican Mestizo population. Thus, the prevalence of CD in Mexico could be higher or similar to that observed in other countries. This observation contributes to increase the awareness for this under diagnosed disease in clinical practice and to consider CD as a global health problem.

Authentication of the botanical and geographical origin of honey by mid-infrared spectroscopy.

The potential of Fourier transform mid-infrared spectroscopy (FT-MIR) using an attenuated total reflectance (ATR) cell was evaluated for the authentication of 11 unifloral (acacia, alpine rose, chestnut, dandelion, heather, lime, rape, fir honeydew, metcalfa honeydew, oak honeydew) and polyfloral honey types (n = 411 samples) previously classified with traditional methods such as chemical, pollen, and sensory analysis. Chemometric evaluation of the spectra was carried out by applying principal component analysis and linear discriminant analysis, the error rates of the discriminant models being calculated by using Bayes' theorem. The error rates ranged from <0.1% (polyfloral and heather honeys as well as honeydew honeys from metcalfa, oak, and fir) to 8.3% (alpine rose honey) in both jackknife classification and validation, depending on the honey type considered. This study indicates that ATR-MIR spectroscopy is a valuable tool for the authentication of the botanical origin and quality control and may also be useful for the determination of the geographical origin of honey.

Is leptin related to systemic inflammatory response in acute pancreatitis?

AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis. METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-alpha, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria. RESULTS: Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058). CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

BACKGROUND: Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours. AIM: To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours. METHODS: HYNIC was conjugated to the epsilon-amino group of Lys 3 residue at the N-terminal region of bombesin via succinimidyl-N-Boc-HYNIC at pH 9.0. 99mTc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer pH 7.0 to a lyophilized formulation. Stability studies were carried out by reversed phase HPLC and ITLC-SG analyses in serum and cysteine solutions. In-vitro internalization was tested using human prostate cancer PC-3 cells with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in PC-3 tumour-bearing nude mice. RESULTS: 99mTc-EDDA/HYNIC-[Lys 3]-bombesin was obtained with radiochemical purities >93% and high specific activity ( approximately 0.1 GBq.nmol). Results of in-vitro studies demonstrated a high stability in serum and cysteine solutions, specific cell receptor binding and rapid internalization. Biodistribution data showed a rapid blood clearance, with predominantly renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas and PC-3 tumours. CONCLUSION: 99mTc-EDDA/HYNIC-[Lys 3]-bombesin obtained from lyophilized kit formulations has promising characteristics for the diagnosis of malignant tumours that over-express the GRP receptor.

Usefulness of amino acid composition to discriminate between honeydew and floral honeys. Application to honeys from a small geographic area.

With the aim of finding methods that could constitute a solid alternative to melissopalynological and physicochemical analyses to determine the botanical origin (floral or honeydew) of honeys, the free amino acid content of 46 honey samples has been determined. The honeys were collected in a small geographic area of approximately 2000 km(2) in central Spain. Twenty-seven honey samples were classified as floral and 19 as honeydew according to their palynological and physicochemical analyses. The resulting data have been subjected to different multivariant analysis techniques. One hundred percent of honey samples have been correctly classified into either the floral or the honeydew groups, according to their content in glutamic acid and tryptophan. It is concluded that free amino acids are good indicators of the botanical origin of honeys, saving time compared with more tedious analyses.

Infección por Helicobacter pylori y cáncer gástrico en México. Un reto para la prevención y el control poblacional / Helicobacter pylori infection and gastric cancer in Mexico. A challenge for prevention and population control

La Agencia Internacional de Investigación en Cáncer, de la OMS (International Agency for Research on Cancer IARC), ha reconocido una relación causa efecto entre la infección por Helicobacter pylori (Hp) y el cáncer de estómago, de tal magnitud que la presencia de dicha infección aumenta aproximadamante 4 veces el riesgo de padecer cáncer. En este trabajo se presentan los resultados de la asociación de la infección por Hp y la incidencia de cáncer de estómago, que ocupa actualmente el segundo lugar en la mortalidad por neoplasias malignas en la Ciudad de México, los cuales se obtuvieron por medio de un estudio epidemiológico, en el que participaron 109 pacientes de cáncer gástrico y 177 controles hospitlarios. Se estimó que en la población estudiada, la infección por Helicobacter pylori, estuvo presente en el 87.2 por ciento de los casos, comparado con un 82.5 por ciento de los controles. La razón de momios de padecer cáncer de estómago dado que se está infectado por Hp, resultó de 1.44 IC 95 por ciento 0.7 2.8. Además, se calculó que si se erradicara la infección por Hp en la población general, la incidencia de cáncer de estómago se reduciría en al menos 26.6 por ciento. La implementación de mejores condiciones sanitarias y el desarrollo de una vacuna eficaz que prevenga la infección por Hp así como la existencia de tratamientos cada vez más efectivos para erradicar la bacteria representan ahora, un reto para la prevencion y el control poblacional del cáncer gástrico

La tinción con naranja de acridina en la detección de microorganismos / Staining with acridine orange in the detection of microorganisms

La tinción con naranja de acridina de los microorganismos que se cultivan de la sangre o de cualquier otro fluido corporal (líquido céfalorraquídeo, articular o pleural), permite su detección temprana y facilita el tratamiento precoz del paciente. De allí el objetivo de este trabajo en el cual analizamos su grado de positividad en comparación con la tinción gram

Pseudomanas aeruginosa multiresistente en el Hospital Santo Tomás / Multiresistant pseudomonas aeruginosa in the Hospital Santo Tomás

Se estudia un brote epidémico debido a Pseudomonas aeruginosa multiresistente, que se observó en el Hospital Santo Tomás (HST) en diciembre de 1985 y elevó la tasa de infección endémica que era de 5.1% a 25.7%

Origen de las infecciones anaeróbicas severas en el Hospital Santo Tomás / Origin of severe anaerobic infections at the Hospital Santo Tomás

Se estudiaron los expedientes clínicos de 70 pacientes que fueron internados en el Hospital Santo Tomás (HST) por infección con anaerobios. Se observó, en la mayoría de los casos, que la infección fue adquirida en la comunidad, entre mujeres de 16 y 35 años de edad; y que el origen de la infección fue, en la mayoría de los casos, el aparato genital o el gastrointestinal y biliar. Los signos sugestivos de la infección fueron la fetidez, la necrosis y gangrena, la producción de gas y los cultivos aeróbicos negativos. Se aislaron 128 cepas de distintas especies anaeróbicas; las más frecuentes fueron Clostridium perfringens y el Peptostreptococcus. La diabetes mellitus, la neoplasia y la arteriosclerosis generalizada fueron las enfermedades subyacentes, y la septicemia y la peritonitis fueron las complicaciones más frecuentemente observadas. Se revisó el tratamiento prescrito a cada paciente, el cual consistió en l uso de un antibiótico y el debridamiento quirúrgico de la lesión. Se obtuvo un 86.9% de curación con Clindamicina, 80,0% con Metronidazole o Penicilina; el Cloranfenicol fue inefectivo en los pocos casos en que fue prescrito

Candidiasis en el Hospital Santo Tomás / Candidiasis at the Hopsital Santo Tomás

Se estudió la incidencia, sintomatológica y tratamiento de Candidiasis en el Hospital Santo Tomás. En 41 ocasiones se obtuvo el cultivo de un hongo patógeno, del género Candida, en material del tracto digestivo, de la sangre, de la piel y o de la orina de 20 pacientes. Todos ellos sufrían también de una enfermedad subyacente (leucemia, neoplasia sólida, lupus eritematoso sistémico o aplasia medular). La fiebre y las ulceraciones orofaríngeas fueron las hallazgos clínicos más frecuentemente observados. Los pacientes fueron tratados con Ketoconazole y o con Anfotericina B. Se observó que el uso de Ketoconazole produjo más casos de candidemia y mayor mortalidad que el uso de Anfotericina B