Antifungal stewardship: the Latin American experience.

Antifungal stewardship is a critical component of healthcare management that focuses on optimizing the use of antifungal medications to improve patient outcomes, minimize resistance, and reduce healthcare costs.  In resource-limited settings, the prevalence of fungal infections remains a significant health concern, often exacerbated by factors such as compromised immune systems, inadequate diagnostic capabilities, and limited access to antifungal agents. This paper reviews the current state of antifungal stewardship practices in developing countries, addressing the unique socioeconomic and healthcare landscape.

COVID-19 patients display changes in lymphocyte subsets with a higher frequency of dysfunctional CD8lo T cells associated with disease severity.

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3+ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB+ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8+ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8hi and CD8lo T cells within the CD8+ population in HD are similar, a significant increase was observed in CD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8hi T cells. Interestingly, the frequency of CD8lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8hi/CD8lo index helped to significantly improve the patient's clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8hi/CD8lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.

The Argentinian landscape of mycological diagnostic capacity and treatment accessibility.

Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.

Different cytokine and chemokine profiles in hospitalized patients with COVID-19 during the first and second outbreaks from Argentina show no association with clinical comorbidities.

Background: COVID-19 severity has been linked to an increased production of inflammatory mediators called "cytokine storm". Available data is mainly restricted to the first international outbreak and reports highly variable results. This study compares demographic and clinical features of patients with COVID-19 from Córdoba, Argentina, during the first two waves of the pandemic and analyzes association between comorbidities and disease outcome with the "cytokine storm", offering added value to the field. Methods: We investigated serum concentration of thirteen soluble mediators, including cytokines and chemokines, in hospitalized patients with moderate and severe COVID-19, without previous rheumatic and autoimmune diseases, from the central region of Argentina during the first and second infection waves. Samples from healthy controls were also assayed. Clinical and biochemical parameters were collected. Results: Comparison between the two first COVID-19 waves in Argentina highlighted that patients recruited during the second wave were younger and showed less concurrent comorbidities than those from the first outbreak. We also recognized particularities in the signatures of systemic cytokines and chemokines in patients from both infection waves. We determined that concurrent pre-existing comorbidities did not have contribution to serum concentration of systemic cytokines and chemokines in COVID-19 patients. We also identified immunological and biochemical parameters associated to inflammation which can be used as prognostic markers. Thus, IL-6 concentration, C reactive protein level and platelet count allowed to discriminate between death and discharge in patients hospitalized with severe COVID-19 only during the first but not the second wave. Conclusions: Our data provide information that deepens our understanding of COVID-19 pathogenesis linking demographic features of a COVID-19 cohort with cytokines and chemokines systemic concentration, presence of comorbidities and different disease outcomes. Altogether, our findings provide information not only at local level by delineating inflammatory/anti-inflammatory response of patients but also at international level addressing the impact of comorbidities and the infection wave in the variability of cytokine and chemokine production upon SARS-CoV-2 infection.

Invasive Candidiasis: Update and Current Challenges in the Management of This Mycosis in South America.

Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30-70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.

The incidence, risk factors and impact of acute kidney injury in hospitalized patients due to COVID-19.

The incidence of acute kidney injury (AKI) in hospitalized patients with COVID-19 is variable, being associated with worse outcomes. The objectives of the study were to evaluate the incidence, risk factors (considering demographic characteristics, comorbidities, initial clinical presentation and associated complications) and impact of AKI in subjects hospitalized for COVID-19 in two third-level hospitals in Córdoba, Argentina. A retrospective cohort study was conducted. We included 448 adults who were consecutively hospitalized for COVID-19 between March 3 and October 31, 2020 and were followed throughout the hospitalization. The incidence of AKI was 19% (n = 85; stage I = 43, stage II = 17, and stage III = 25, 18 required renal replacement therapy). In the multivariate analysis, the variables that were independently associated with AKI were: age (for every 10 years, adjusted odd ratio [95%CI] = 1.30 [1.04-1.63], p = 0.022), history of chronic kidney disease -CKD- (9.92 [4.52-21.77], p < 0.001), blood neutrophil count at admission -BNCA- (for every increase of 1000 BNCA, 1.09 [1.01-1.18], p = 0.037) and requirement for mechanical ventilation -MV- (6.69 [2.24-19.90], p = 0.001). AKI was associated with longer hospitalization, higher admission (63.5 vs. 29.7%; p < 0.001) and longer stay in the intensive care unit, a positive association with respiratory bacterial superinfection, sepsis, respiratory distress syndrome, MV requirement and mortality (mortality without AK I = 12.4% vs with AKI = 47.1%; stage I = 26%, stage II = 41% and stage III = 88%; p < 0.001). AKI was independently associated with higher mortality (3.32 [1.6-6.9], p = 0.001). In conclusion, the incidence of AKI in adults hospitalized for COVID-19 was 19% and had a clear impact on morbidity and mortality. The independent risk factors for AKI were: Age, CKD, BNCA and MV.

Los objetivos del estudio fueron evaluar la incidencia, los factores de riesgo (considerando características demográficas, comorbilidades, presentación clínica inicial y complicaciones asociadas) y el impacto de la lesión renal aguda ­LRA­ en sujetos hospitalizados por COVID-19 en dos instituciones de alta complejidad de Córdoba, Argentina. Se realizó un estudio de cohorte retrospectivo. Se incluyeron 448 adultos que fueron hospitalizados por COVID-19 entre el 3 de marzo y el 31 de octubre del 2020 con seguimiento durante toda la hospitalización. La incidencia de LRA fue 19% (estadio I = 43, estadio II = 17 y estadío III = 25, 18 requirieron diálisis). Las variables que se asociaron de manera independiente con el LRA fueron: edad (por cada 10 años, odd ratio ajustado [IC95%] = 1.30 [1.04-1.63], p = 0.022), enfermedad renal crónica ­ERC­ (9.92 [4.52-21.77], p < 0.001), recuento de neutrófilos sanguíneos al ingreso ­NSI­ (por cada incremento de 1000 NSI, 1.09 [1.01­1.18], p = 0.037) y asistencia respiratoria mecánica ­ARM­ (6.69 [2.24­19.90], p = 0.001). Los sujetos con LRA presentaron una internación más prolongada, mayor requerimiento (63.5 vs. 29.7%; p < 0.001) y estadía más prolongada en unidad de cuidados intensivos, una asociación positiva con sobreinfección respiratoria bacteriana, sepsis, síndrome de distrés respiratorio, requerimiento de ARM y mortalidad (mortalidad sin LRA 12.4% vs. con LRA 47.1%; estadio I = 26%, estadio II = 41% y estadio III = 88%; p < 0.001). LRA se asoció de manera independiente a mayor mortalidad (3.3 [1.6­6.9], p = 0.001). En conclusión, la incidencia de LRA en adultos hospitalizados por COVID-19 fue del 19% y tuvo un claro impacto en la morbi-mortalidad. Los factores de riesgo independientes de LRA fueron: edad, ERC, NSI y ARM.

Clinical and epidemiological characteristics of patients hospitalized for SARS-CoV-2 infection in two hospitals in Córdoba. / [Características clínicas y epidemiológicas de pacientes hospitalizados por infección por SARS-CoV-2 en dos hospitales en Córdoba.]

Introduction: COVID-19 disease shows a marked heterogeneity in its clinical course, with descriptions of some factors associated with a worse prognosis. Knowledge of the disease behavior in the local scenario is relevant to allow a better approach. Methods: Retrospective study in two hospitals in the city of Córdoba, Argentina, with patients aged 18 years or more, hospitalized for active SARS-CoV-2 infection, from March to October, 2020. Results: 448 patients were included, of which 95.75% corresponded to COVID-19 pneumonia. Most of the episodes occurred in men (63.6%), the median age was 63 years (IQR: 53-75), and the most frequent comorbidities were arterial hypertension (55.1%), obesity (31.7%) and diabetes mellitus (28.1%). 162 patients (36.2%) needed admission to the intensive care unit and 66 (14.7%) were placed on mechanical ventilation. 67 patients (15%) died within the first 30 days of follow-up. In the multivariate analysis, the only independent variable predictive of mortality at 30 days was age (adjusted Odds ratio [aOR] = 1.08, 95% CI = 1.04-1.11, p <0.001). The 4C-Score and CALL-Score prognostic scores showed good discrimination (Area under the curve [AUC] = 0.766, 95% CI = 0.72-0.80 and AUC = 0.785, 95% CI = 0.70-0.85 respectively) and the predicted percentages of mortality were quite close to what was observed in the present study. Conclusions: Most of the patients hospitalized with SARS-CoV-2 infection presented comorbidities and were admitted with pneumonia, associated with high mortality. The prognostic scores with the best performance to predict complications were the 4C-score and the CALL-score.

Introducción: La enfermedad COVID-19 muestra una marcada heterogeneidad en su curso clínico, habiéndose descripto algunos factores que se asocian un peor pronóstico. El conocimiento del comportamiento de la enfermedad en el escenario local es de gran relevancia para permitir un mejor abordaje. Métodos: Estudio retrospectivo en dos hospitales de la ciudad de Córdoba, Argentina, de pacientes de 18 años o más hospitalizados por infección activa por SARS-CoV-2, desde marzo a octubre del año 2020. Resultados: Se incluyeron 448 pacientes, de los cuales el 95.75% correspondieron a neumonía COVID-19. La mayoría de los episodios ocurrieron en hombres (63.6%), la mediana de edad fue 63 años (RIC:53-75), y las comorbilidades más frecuentes fueron hipertensión arterial (55.1%), obesidad (31.7%) y diabetes mellitus (28.1%). Requirieron ingreso a unidad de cuidados intensivos 162 pacientes (36.2%) y 66 (14.7%), asistencia respiratoria mecánica. Fallecieron 67 pacientes (15%) dentro de los primeros 30 días de seguimiento. En el análisis multivariado la única variable independiente predictora de mortalidad a los 30 días fue la edad (Odds ratio ajustado [ORa]=1.08, IC95%=1.04-1.11, p<0.001). Los scores pronósticos 4C-Score y CALL-Score presentaron muy buena discriminación (Área bajo la curva [ABC]=0.766, IC95%=0.72-0.80 y ABC=0.785, IC95%=0.70-0.85, respectivamente) y los porcentajes predichos de mortalidad se aproximaron bastante a lo observado en el presente estudio. Conclusiones: La mayoría de los pacientes hospitalizados por infección por SARS-CoV-2 presentaban comorbilidades y se presentaron como neumonía, asociada a una elevada mortalidad. Los scores pronósticos con mejor rendimiento para predecir complicaciones fueron el 4C-Score y el CALL score.

Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos / Clinical and microbiological characteristics of bloodstream infections in adult neutropenic patients

RESUMEN Las infecciones del torrente sanguíneo (IS) en pacientes oncológicos neutropénicos constituyen una patología de relevancia y se asocian a un aumento de la morbimortalidad. El objetivo de este estudio fue determinar las características epidemiológicas y microbiológicas de los episodios de IS en pacientes adultos neutropénicos con neoplasias hematológicas (NH) y neoplasias sólidas (NS). Se realizó un estudio retrospectivo en dos hospitales de tercer nivel entre 2009 y 2016. Se incluyeron todos los pacientes neutropénicos mayores de 18años con NH y NS que presentaron episodios de IS. Se excluyeron aquellos con neoplasias dermatológicas no melanoma. Se identificaron 143 episodios de IS, de los cuales el 80,4% fueron en personas con NH. El 97,9% de los pacientes tuvieron neutropenia de alto riesgo, sin diferencia entre los grupos NH y NS. Los orígenes más frecuentes de IS fueron bacteriemia primaria (46,9%) e infección asociada a catéter (21%), sin diferencias significativas entre grupos. El 74,1% de los aislamientos fueron bacilos gram negativos yEscherichiacolifue el microorganismo más frecuente (32,1%). El coco gram positivo más frecuentemente aislado fueStaphylococcusaureus(28,1%), seguido del grupo de los estafilococos coagulasa negativos (ECN), sin diferencias entre ambos tipos de neoplasias. El 67,5% de los ECN fueron multirresistentes; solo el 11,1% de los aislamientos deS. aureusfue resistente a la meticilina. El 17,6% de los aislamientos deE. coliy el 27,6% de los deKlebsiellapneumoniaefueron multirresistentes. No hubo diferencias en la frecuencia de aislamientos multirresistentes al comparar entre ambos tipos de neoplasia. Como conclusión, las IS en pacientes neutropénicos fueron más frecuentes en pacientes con NH y las causaron, principalmente, bacilos gram negativos. Se observó una elevada mortalidad en los pacientes neutropénicos con IS.

ABSTRACT Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, beingEscherichia colithe most frequent (32.8%). Among the gram positive cocci,Staphylococcus aureus(28.1%) was the most frequent isolated, followed by coagulase-negativeStaphylococci(CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of theE. coliand 27.6% of theKlebsiella pneumoniaewere multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

The incidence, risk factors and impact of acute kidney injury in hospitalized patients due to COVID-19 / Incidencia, factores de riesgo e impacto de la lesión renal aguda en pacientes hospitalizados por COVID-19

Abstract The incidence of acute kidney injury (AKI) in hospitalized patients with COVID-19 is variable, being associated with worse outcomes. The objectives of the study were to evaluate the incidence, risk factors (considering demographic characteristics, comorbidities, initial clinical presentation and associated complications) and impact of AKI in subjects hospitalized for COVID-19 in two third-level hospitals in Córdoba, Argentina. A retrospective cohort study was conducted. We included 448 adults who were consecutively hospitalized for CO VID-19 between March 3 and October 31, 2020 and were followed throughout the hospitalization. The incidence of AKI was 19% (n = 85; stage I = 43, stage II = 17, and stage III = 25, 18 required renal replacement therapy). In the multivariate analysis, the variables that were independently associated with AKI were: age (for every 10 years, adjusted odd ratio [95%CI] = 1.30 [1.04-1.63], p = 0.022), history of chronic kidney disease -CKD- (9.92 [4.52-21.77], p < 0.001), blood neutrophil count at admission -BNCA- (for every increase of 1000 BNCA, 1.09 [1.01-1.18], p = 0.037) and requirement for mechanical ventilation -MV- (6.69 [2.24-19.90], p = 0.001). AKI was associated with longer hospitalization, higher admission (63.5 vs. 29.7%; p < 0.001) and longer stay in the intensive care unit, a positive association with respiratory bacterial superinfection, sepsis, respiratory distress syndrome, MV requirement and mortality (mortality without AK I = 12.4% vs with AKI = 47.1%; stage I = 26%, stage II = 41% and stage III = 88%; p < 0.001). AKI was independently associated with higher mortality (3.32 [1.6-6.9], p = 0.001). In conclusion, the incidence of AKI in adults hospitalized for COVID-19 was 19% and had a clear impact on morbidity and mortality. The independent risk factors for AKI were: Age, CKD, BNCA and MV.

Resumen Los objetivos del estudio fueron evaluar la incidencia, los factores de riesgo (consi derando características demográficas, comorbilidades, presentación clínica inicial y complicaciones asociadas) y el impacto de la lesión renal aguda -LRA- en sujetos hospitalizados por COVID-19 en dos instituciones de alta complejidad de Córdoba, Argentina. Se realizó un estudio de cohorte retrospectivo. Se incluyeron 448 adul tos que fueron hospitalizados por COVID-19 entre el 3 de marzo y el 31 de octubre del 2020 con seguimiento durante toda la hospitalización. La incidencia de LRA fue 19% (estadio I = 43, estadio II = 17 y estadío III = 25, 18 requirieron diálisis). Las variables que se asociaron de manera independiente con el LRA fueron: edad (por cada 10 años, odd ratio ajustado [IC95%] = 1.30 [1.04-1.63], p = 0.022), enfermedad renal crónica -ERC- (9.92 [4.52-21.77], p < 0.001), recuento de neutrófilos sanguíneos al ingreso -NSI- (por cada incremento de 1000 NSI, 1.09 [1.01-1.18], p = 0.037) y asistencia respiratoria mecánica -ARM- (6.69 [2.24-19.90], p = 0.001). Los sujetos con LRA presentaron una internación más prolongada, mayor requerimiento (63.5 vs. 29.7%; p < 0.001) y estadía más prolongada en unidad de cuidados intensivos, una asociación positiva con sobreinfección respi ratoria bacteriana, sepsis, síndrome de distrés respiratorio, requerimiento de ARM y mortalidad (mortalidad sin LRA 12.4% vs. con LRA 47.1%; estadio I = 26%, estadio II = 41% y estadio III = 88%; p < 0.001). LRA se asoció de manera independiente a mayor mortalidad (3.3 [1.6-6.9], p = 0.001). En conclusión, la incidencia de LRA en adultos hospitalizados por COVID-19 fue del 19% y tuvo un claro impacto en la morbi-mortalidad. Los factores de riesgo independientes de LRA fueron: edad, ERC, NSI y ARM.

Candidiasis invasora: un enfoque a la infección en el sistema nervioso central

Resumen La candidemia es la micosis invasora más frecuente en los pacientes internados en hospitales de alta complejidad en el mundo. La infección fúngica en el sistema nervioso central constituye una complicación potencialmente mortal que agrava el pronóstico de los pacientes. El presente artículo aborda aspectos relevantes sobre las características clínicas de esta enfermedad, los mecanismos de invasión del hongo, la respuesta inmunitaria local frente a Candida albicans y el impacto de los defectos genéticos en receptores de la inmunidad innata, que aumentan la susceptibilidad a la neurocandidiasis.

[Clinical and microbiological characteristics of bloodstream infections in adult neutropenic patients]. / Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos.

Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, being Escherichia coli the most frequent (32.8%). Among the gram positive cocci, Staphylococcus aureus (28.1%) was the most frequent isolated, followed by coagulase-negative Staphylococci (CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of the E. coli and 27.6% of the Klebsiella pneumoniae were multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

Candida albicans Modulates Murine and Human Beta Defensin-1 during Vaginitis.

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. ß-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.

[Invasive candidiasis: A view to central nervous system infection]. / Candidiasis invasora: un enfoque a la infección en el sistema nervioso central.

Candidemia is the most frequent invasive mycosis in hospitalized patients worldwide. Fungal infection in central nervous system is a life-threatening complication which aggravates patients' prognosis. This article summarizes relevant aspects on the clinical characteristics of this pathology, mechanisms of fungus invasion, local immune response to Candida albicans and the impact of genetic defects on innate immune receptors that increase susceptibility to the acquisition of this form of mycosis.

Infections in the first year after renal transplant / Infecciones en el primer año post-trasplante renal

Abstract Infections are frequent complications of kidney transplants. We aimed at determining the frequency and type of infections that occur in renal transplant recipients during the early (0-1 month), intermediate (1-6 months) and late (6-12 months) post-transplant period and analyzing the risk factors for infection. To this aim, we conducted a retrospective cohort study on 1-year post-transplant follow-up in two third-level university hospitals in Cordoba city. All consecutive recipients of renal transplants performed between 2009 and 2015 were included, except those with multiple solid organ transplantation and pediatric patients. We included 375 recipients, of which 235 (62.7%) had at least one episode of infection during follow-up. There were 504 episodes of infection, of which 131 (26%) occurred in the early, 272 (53.9%) in the intermediate, and 101 (20.1%) in the late post-transplant period. The most frequent infections in all periods were caused by bacteria (mainly urinary tract infections), and the most frequent viral infection was caused by Cytomegalovirus (mainly in the second and third period). In the multivariate analysis, infection risk factors were: age > 60 years (adjusted odds ratio [aOR] = 1.92; 95% CI = 1.05-3.49), organ transplantation from deceased donor (aOR = 8.19; 95% CI = 2.32-28.9), use of pigtail catheter for urinary tract drainage (aOR = 4.06; 95% CI = 1.27-12.9), and number of days in hospital after transplant (aOR = 1.05; 95% CI = 1.01-1.11). In conclusion, infections in renal transplant recipients represent a very frequent health problem in our hospitals. Understanding the local epidemiology of infection and the potential risk factors for infection acquires utmost importance.

Resumen Las infecciones son complicaciones frecuentes de los trasplantes renales. Los objetivos del estudio fueron determinar la frecuencia y el tipo de infecciones que ocurren en el período post-trasplante temprano (0-1 mes), intermedio (1-6 meses) y tardío (6-12 meses) en nuestro medio y analizar los factores de riesgo de infección. Se realizó un estudio de cohorte retrospectivo que incluyó todos los pacientes con trasplantes renales realizados entre 2009 y 2015 en dos hospitales universitarios de tercer nivel de la ciudad de Córdoba, excluidos los receptores de trasplante simultáneo de múltiples órganos sólidos y los menores de 18 años. Fueron incluidos 375 pacientes, de los cuales 235 (62.7%) tuvieron al menos un episodio de infección. Hubo 504 episodios de infección: 131 (26%) ocurrieron en el período temprano, 272 (53.9%) en el intermedio y 101 (20.1%) en el tardío. La mayoría de las infecciones fueron de origen bacteriano (principalmente del tracto urinario). La mayoría de las infecciones virales ocurrieron en el segundo y el tercer período y Citomegalovirus fue el responsable más frecuente. En el análisis multivariado, los factores de riesgo de infección post-transplante renal fueron: edad > 60 años (odds ratio ajustado [aOR] 1.92; IC95% 1.05-3.49), donante cadavérico (aOR 8.19; IC95% 2.32-28.9), uso de catéter pigtail (aOR 4.06; IC95% 1.27-12.9) y número de días internado postrasplante (aOR 1.05; IC95% 1.01-1.11). En conclusión, confirmamos que las infecciones en pacientes con trasplante renal son muy frecuentes en nuestro medio, por lo cual es importante conocer la epidemiología local y los factores de riesgo.

Infections in the first year after renal transplant.

Infections are frequent complications of kidney transplants. We aimed at determining the frequency and type of infections that occur in renal transplant recipients during the early (0-1 month), intermediate (1-6 months) and late (6-12 months) post-transplant period and analyzing the risk factors for infection. To this aim, we conducted a retrospective cohort study on 1-year post-transplant follow-up in two third-level university hospitals in Cordoba city. All consecutive recipients of renal transplants performed between 2009 and 2015 were included, except those with multiple solid organ transplantation and pediatric patients. We included 375 recipients, of which 235 (62.7%) had at least one episode of infection during follow-up. There were 504 episodes of infection, of which 131 (26%) occurred in the early, 272 (53.9%) in the intermediate, and 101 (20.1%) in the late post-transplant period. The most frequent infections in all periods were caused by bacteria (mainly urinary tract infections), and the most frequent viral infection was caused by Cytomegalovirus (mainly in the second and third period). In the multivariate analysis, infection risk factors were: age > 60 years (adjusted odds ratio [aOR] = 1.92; 95% CI = 1.05-3.49), organ transplantation from deceased donor (aOR = 8.19; 95% CI = 2.32-28.9), use of pigtail catheter for urinary tract drainage (aOR = 4.06; 95% CI = 1.27-12.9), and number of days in hospital after transplant (aOR = 1.05; 95% CI = 1.01-1.11). In conclusion, infections in renal transplant recipients represent a very frequent health problem in our hospitals. Understanding the local epidemiology of infection and the potential risk factors for infection acquires utmost importance.

Las infecciones son complicaciones frecuentes de los trasplantes renales. Los objetivos del estudio fueron determinar la frecuencia y el tipo de infecciones que ocurren en el período post-trasplante temprano (0-1 mes), intermedio (1-6 meses) y tardío (6-12 meses) en nuestro medio y analizar los factores de riesgo de infección. Se realizó un estudio de cohorte retrospectivo que incluyó todos los pacientes con trasplantes renales realizados entre 2009 y 2015 en dos hospitales universitarios de tercer nivel de la ciudad de Córdoba, excluidos los receptores de trasplante simultáneo de múltiples órganos sólidos y los menores de 18 años. Fueron incluidos 375 pacientes, de los cuales 235 (62.7%) tuvieron al menos un episodio de infección. Hubo 504 episodios de infección: 131 (26%) ocurrieron en el período temprano, 272 (53.9%) en el intermedio y 101 (20.1%) en el tardío. La mayoría de las infecciones fueron de origen bacteriano (principalmente del tracto urinario). La mayoría de las infecciones virales ocurrieron en el segundo y el tercer período y Citomegalovirus fue el responsable más frecuente. En el análisis multivariado, los factores de riesgo de infección post-transplante renal fueron: edad > 60 años (odds ratio ajustado [aOR] 1.92; IC95% 1.05-3.49), donante cadavérico (aOR 8.19; IC95% 2.32-28.9), uso de catéter pigtail (aOR 4.06; IC95% 1.27-12.9) y número de días internado postrasplante (aOR 1.05; IC95% 1.01-1.11). En conclusión, confirmamos que las infecciones en pacientes con trasplante renal son muy frecuentes en nuestro medio, por lo cual es importante conocer la epidemiología local y los factores de riesgo.

[Bloodstream infections in cancer patients]. / Infecciones del torrente sanguíneo en pacientes oncológicos.

Bloodstream infections (BI) are an important cause of morbidity and mortality in cancer patients. A retrospective study was performed in two hospitals aimed to evaluate characteristics of BI episodes occurred in adult patients with hematologic (HN) and solid (SN) neoplasia other than non-melanoma skin cancers in the period 2009-2016. A total of 467 episodes of bacteremia and 16 of fungemia were identified. A total of 200 (41.4%) bacteremias occurred in patients with HN and 283 (58.6%) in patients with SN. The most frequent SN and HN were colon cancer (18.7%) and non-Hodgkin lymphoma (27%), respectively. The main risk factors for BI were a previous surgical procedure in SN and chemotherapy in the previous 30 days and use of central venous catheter in HN. Infections were mainly acquired in the hospital environment and the most frequent presentation was bacteremia without focus, mostly in HN (38% vs. 20.8%, p < 0.001). Gram negative bacilli (GNB) were isolated in 336 (69.5%) episodes and predominated over Gram positive cocci (GPC) in both groups. Escherichia coli was the most frequent GNB isolated in both SN (24.7%) and HN patients (20.5%). The most frequent GPC was Staphylococcus aureus. Multidrug-resistance was found in 15% of the isolates in SN and 18% in HN. The overall mortality was 40.5% in patients with HN and 37.5% in patients with SN, with the majority of deaths occurring in the first 30 days.

Las infecciones del torrente sanguíneo (ITS) son una importante causa de morbimortalidad en pacientes oncológicos. Los objetivos del estudio fueron evaluar las características de las ITS en pacientes con neoplasia hematológica (NH) y sólida (NS) en un estudio retrospectivo realizado en dos hospitales, entre 2009 y 2016. Fueron incluidos todos los episodios de ITS en adultos con neoplasias activas, excepto cáncer de piel no melanoma. Fueron identificados 467 episodios de bacteriemia y 16 de fungemia. Un total de 200 (41.4%) bacteriemias ocurrieron en pacientes con NH y 283 (58.6%) en pacientes con NS. Las NS y NH más frecuentes fueron cáncer de colon (18.7%) y linfoma no Hodgkin (27%), respectivamente. Los principales factores de riesgo de ITS fueron el antecedente de procedimiento quirúrgico para NS y quimioterapia en los 30 días previos y uso de catéter venoso central para NH. Las infecciones fueron adquiridas principalmente en el medio intrahospitalario y la presentación más frecuente fue la bacteriemia sin foco, fundamentalmente en NH (38.0% vs. 20.8%, p < 0.001). En un total de 336 (69.5%) aislamientos predominaron bacilos Gram negativos (BGN) sobre cocos Gram positivos (CGP) sin diferencias entre grupos. Escherichia coli fue el BGN más frecuente en NS (24.7%) y NH (20.5%). El CGP más frecuente fue Staphylococcus aureus. El 15% y el 18% de los aislamientos fue multirresistente en NS y NH, respectivamente. La mortalidad global fue 40.5% en pacientes con NH y 37.5% en pacientes con NS. La mayoría de las muertes ocurrió en los primeros 30 días.

Bloodstream infections in cancer patients / Artículo original

Resumen Las infecciones del torrente sanguíneo (ITS) son una importante causa de morbimortalidad en pacientes oncológicos. Los objetivos del estudio fueron evaluar las características de las ITS en pacientes con neoplasia hematológica (NH) y sólida (NS) en un estudio retrospectivo realizado en dos hospitales, entre 2009 y 2016. Fueron incluidos todos los episodios de ITS en adultos con neoplasias activas, excepto cáncer de piel no melanoma. Fueron identificados 467 episodios de bacteriemia y 16 de fungemia. Un total de 200 (41.4%) bacteriemias ocurrieron en pacientes con NH y 283 (58.6%) en pacientes con NS. Las NS y NH más frecuentes fueron cáncer de colon (18.7%) y linfoma no Hodgkin (27%), respectivamente. Los principales factores de riesgo de ITS fueron el antecedente de procedimiento quirúrgico para NS y quimioterapia en los 30 días previos y uso de catéter venoso central para NH. Las infecciones fueron adquiridas principalmente en el medio intrahospitalario y la presentación más frecuente fue la bacteriemia sin foco, fundamentalmente en NH (38.0% vs. 20.8%, p < 0.001). En un total de 336 (69.5%) aislamientos predominaron bacilos Gram negativos (BGN) sobre cocos Gram positivos (CGP) sin diferencias entre grupos. Escherichia coli fue el BGN más frecuente en NS (24.7%) y NH (20.5%). El CGP más frecuente fue Staphylococcus aureus. El 15% y el 18% de los aislamientos fue multirresistente en NS y NH, respectivamente. La mortalidad global fue 40.5% en pacientes con NH y 37.5% en pacientes con NS. La mayoría de las muertes ocurrió en los primeros 30 días.

Abstract Bloodstream infections (BI) are an important cause of morbidity and mortality in cancer patients. A retrospective study was performed in two hospitals aimed to evaluate characteristics of BI episodes occurred in adult patients with hematologic (HN) and solid (SN) neoplasia other than non-melanoma skin cancers in the period 2009-2016. A total of 467 episodes of bacteremia and 16 of fungemia were identified. A total of 200 (41.4%) bacteremias occurred in patients with HN and 283 (58.6%) in patients with SN. The most frequent SN and HN were colon cancer (18.7%) and non-Hodgkin lymphoma (27%), respectively. The main risk factors for BI were a previous surgical procedure in SN and chemotherapy in the previous 30 days and use of central venous catheter in HN. Infections were mainly acquired in the hospital environment and the most frequent presentation was bacteremia without focus, mostly in HN (38% vs. 20.8%, p < 0.001). Gram negative bacilli (GNB) were isolated in 336 (69.5%) episodes and predominated over Gram positive cocci (GPC) in both groups. Escherichia coli was the most frequent GNB isolated in both SN (24.7%) and HN patients (20.5%). The most frequent GPC was Staphylococcus aureus. Multidrug-resistance was found in 15% of the isolates in SN and 18% in HN. The overall mortality was 40.5% in patients with HN and 37.5% in patients with SN, with the majority of deaths occurring in the first 30 days.

[Covid-19 disease. Report of the first confirmed case in Córdoba (Argentina) and literatura review]. / Enfermedad covid-19. Reporte del primer caso confirmado en Córdoba (Argentina) y revisión de la literatura.

Introduction: COVID-19 disease is an acute viral pneumonia caused by SARS-CoV-2. Its main means of transmission is from person to person through respiratory droplets. It presents as a febrile condition with respiratory symptoms and high transmissibility rate. There is no vaccine, so the clinical suspicion and immediate isolation of the patient are essential Objective: The purpose of this work is to report the first confirmed case of COVID-19 disease in Córdoba (Argentina), highlighting telemedicine as a novel form of outpatient management. Methodology: We describe the first confirmed case of COVID-19 disease in Córdoba (Argentina), which presented in a patient without comorbidities in good clinical condition, and therefore ambulatory management using telemedicine was decided, which was satisfactory. Results: Outpatient management using telemedicine turned out to be optimal, avoiding the use of beds and the transmission of the virus within the hospital through management at home. Conclusion: Outpatient management of selected patients avoids virus transmission within the hospital and saturation of beds. Telemedicine is an effective and novel strategy for this situation.

Introducción: La enfermedad COVID-19 es una neumonía viral aguda causada por el SARS-CoV-2. Su principal medio de transmisión es de persona a persona a través de gotas respiratorias. Se presenta como un cuadro febril con síntomas respiratorios con una alta tasa de transmisibilidad. No existe vacuna, por lo que la sospecha y aislamiento inmediato del enfermo son primordiales. Objetivo: El propósito de este trabajo es informar el primer caso de enfermedad COVID-19 confirmado en Córdoba (Argentina), destacando a la telemedicina como una novedosa forma de manejo ambulatorio. Metodología: Se describe el primer caso confirmado de enfermedad COVID-19 en Córdoba (Argentina), en un paciente sin comorbilidades, con buen estado clínico, manejándose el mismo mediante telemedicina. Resultados: El manejo ambulatorio mediante telemedicina resultó ser óptimo, evitando la utilización de camas y la transmisión del virus intrahospitalaria mediante el manejo en su domicilio. Conclusión: El manejo ambulatorio de pacientes seleccionados evita la transmisión del virus dentro del hospital y la saturación de camas. La telemedicina es una estrategia efectiva y novedosa para esta situación.

[Characteristics of bloodstream infections in adult patients of two third level centers of Córdoba, Argentina.] / Características de las infecciones del torrente sanguíneo en pacientes adultos de dos centros de tercer nivel de Córdoba, Argentina.

Background: Bloodstream infections (BI) are associated with high morbidity and mortality. Objective: To determine epidemiological, microbiological and clinical features of community (CA-BI) and nosocomial bloodstream infections (N-BI). Methods: Bacteremia and fungemia events were retrospectively analyzed in two third-level hospitals between April 2009 and August 2013. Results: We identified 1150 events of bloodstream infections, 53.2% were CA-BI. Gram negative microorganisms were isolated in 61%. The most frequent pathogens were Escherichia coli in CA-BI and Klebsiella pneumoniae in N-BI. Staphylococcus aureus was the most frequent gram positive organism. The main comorbidities were renal disease (39%) and malignancy (38%). There were 26.8% of primary bloodstream infections, and the main infection foci included respiratory (17.04%) and urinary tract (16.86%). A high percentage of gram-negative bacteria of CA-BI and N-BI were resistance to ampicillin sulbactam (40.2% and 57.5%), cephalothin (36.7% and 46.8%), trimethoprim-sulfamethoxazole 32.8% vs 35.5%) and ciprofloxacin (24.6% and 35.3%). Methicillin-resistant Staphylococcus aureus were more frequently into ITS-IH (31.4% vs 11.8%, p = 0.007). Conclusions: Clinical and epidemiological characteristics of CA-BI and N-BI were similar to those reported by other Latin-American studies. We observed some differences in antimicrobial resistance profiles. We emphasize the importance of local epidemiological surveillance to choose appropriate empirical treatments. Conclusions: Clinical and epidemiological characteristics of CA-BI and N-BI were similar to those reported by other Latin-American studies. We observed some differences in antimicrobial resistance profiles. We emphasize the importance of local epidemiological surveillance to choose appropriate empirical treatments.

Introducción: Las infecciones del torrente sanguíneo (ITS) generan elevada morbimortalidad. Objetivo: Determinar características epidemiológicas, microbiológicas y clínicas de ITS adquiridas en la comunidad (ITS-AC) e intrahospitalarias (ITS-IH). Métodos: Se analizaron retrospectivamente eventos de bacteriemia y fungemia en dos hospitales de tercer nivel entre abril de 2009 y agosto de 2013. Resultados: Se identificaron 1150 eventos de ITS, 53% ITS-AC. El 61% de microorganismos aislados fueron gram negativos. Los patógenos más frecuentes fueron Escherichia coli en ITS-AC y Klebsiella pneumoniae en ITS-IH. Staphylococcus aureus fue el gram positivo más frecuente. Las principales comorbilidades fueron enfermedad renal (39%) y neoplasias (38%). El 26,8% de ITS fueron primarias. Los focos infecciosos más frecuentes fueron respiratorio (17%) y urinario (16,9%). Un elevado porcentaje de gram negativos en ITS-AC e ITS-IH fueron resistentes a ampicilina sulbactam (40,2% y 57,5%), cefalotina (36,7% y 46,8%), trimetoprima-sulfametoxazol (32,8% vs 35,5%) y ciprofloxacina (24,6% y 35,3%). Staphylococcus aureus meticilino resistente fue más frecuente en ITS-IH (31,4% vs 11,8%, p=0,007). Conclusiones: Las características clínicas y epidemiológicas de ITS fueron similares a las reportadas por otros estudios latinoamericanos. Pero observamos algunas diferencias en los perfiles de susceptibilidad antimicrobiana. Resaltamos la importancia de la vigilancia epidemiológica local para elegir tratamientos empíricos apropiados.