Etiología, clínica y evolución de infecciones fúngicas invasoras en pacientes con neoplasias hematológicas en un hospital universitario de Argentina

Introducción: Las infecciones fúngicas invasoras (IFI) en pacientes con neoplasias hematológicas (NH) representan un desafío diagnóstico y terapéutico. Objetivos: Describir la etiología, características clínicas, diagnóstico y evolución de los episodios de IFI probadas y probables en pacientes con NH y trasplante de progenitores hematopoyéticos (TPH). Pacientes y Métodos: Estudio descriptivo, retrospectivo y de cohorte que incluyó IFI probadas y probables en pacientes adultos con NH y TPH. Se realizó seguimiento hasta el día 90. Resultados: Se incluyeron 80 episodios de IFI: 49% probadas y 51% probables, 67,5% por hongos filamentosos (HF), 30% por hongos levaduriformes (HL) y 2,5% por hongos dimorfos. Los tipos de IFI más frecuentes fueron aspergilosis invasoras pulmonares (AP) y candidiasis invasoras (CI), en su mayoría por Candida spp. no albicans. Todos los casos de AP se diagnosticaron por detección de galactomanano en sangre y/o lavado broncoalveolar, y solamente 22,2% presentaban nódulos con halo en la tomografía computada (TC) de tórax, siendo los infiltrados inespecíficos los hallazgos más frecuentes. Tuvieron coinfección bacteriana y viral el 30 y 17,5%, respectivamente. El 50% fueron IFI de brecha, y la mortalidad global y mortalidad relacionada a la IFI fue 51 y 24%, respectivamente. Conclusión: Los HF fueron la principal causa de IFI, con una gran proporción de IFI de brecha, y presentaron elevada mortalidad. Para el diagnóstico, resulta importante la utilización de biomarcadores y jerarquizar cualquier imagen patológica en la TC.

Background: Invasive fungal infections (IFI) in patients with hematological malignancies (HM) represent a diagnostic and therapeutic challenge. Aim: To describe the etiology, clinical characteristics, diagnosis and evolution of proven and probable IFI episodes in patients with HM and hematopoietic stem cell transplantation (HSCT). Methods: Retrospective, descriptive, cohort study performed in adult patients with HM and HSCT, who developed proven and probable IFI. Follow-up was carried out until day 90. Results: A total of 80 IFI episodes were included: 49% proven and 51% probable, 67,5% due to mold (M), 30% to yeast-like fungi (Y) and 2,5% to dimorphic fungi. The most frequent causes were probable pulmonary aspergillosis (PA) and invasive candidiasis (IC), mainly due to non-albicans Candida species. PA were all diagnosed by detection of galactomannan (GM) in blood and bronchoalveolar lavage, and only 22,2% presented halo sign on chest CT. Bacterial and viral coinfections were reported in 30% and 17,5% respectively. Breakthrough IFI occurred in 50%, and global and IFI-related mortality were 51% and 24% respectively. Conclusion: Mold was the main cause of IFI, with a large proportion of breakthrough IFI, presenting high mortality. The use of biomarkers and the classification of any pathological image on CT contribute to the diagnosis.

Proposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients

ABSTRACT Introduction: Multidrug-resistant gram-negative rods (MDR GNR) represent a growing threat for patients with cancer. Our objective was to determine the characteristics of and risk factors for MDR GNR bacteremia in patients with cancer and to develop a clinical score to predict MDR GNR bacteremia. Material and Methods: Multicenter prospective study analyzing initial episodes of MDR GNR bacteremia. Risk factors were evaluated using a multiple logistic regression (forward-stepwise selection) analysis including variables with a p < 0.10 in univariate analysis. Results: 394 episodes of GNR bacteremia were included, with 168 (42.6 %) being MDR GNR. Five variables were identified as independent risk factors: recent antibiotic use (OR = 2.8, 95 % CI 1.7-4.6, p = 0.001), recent intensive care unit admission (OR = 2.9, 95 % CI 1.1-7.8, p = 0.027), hospitalization ≥ 7 days prior to the episode of bacteremia (OR = 3.5, 95 % CI 2-6.2, p = 0.005), severe mucositis (OR = 5.3, 95 % CI 1.8-15.6, p = 0.002), and recent or previous colonization/infection with MDR GNR (OR = 2.3, 95 % CI 1.2-4.3, p = 0.028). Using a cut-off value of two points, the score had a sensitivity of 66.07 % (95 % CI 58.4-73.2 %), a specificity of 77.8 % (95 % CI 71.4-82.7 %), a positive predictive value of 68 % (95 % CI 61.9-73.4 %), and a negative predictive value of 75.9 % (95 % CI 71.6-79.7 %). The overall performance of the score was satisfactory (AUROC 0.78; 95 % CI 0.73-0.82). In the cases with one or none of the risk factors identified, the negative likelihood ratio was 0.18 and the post-test probability of having MDR GNR was 11.68 %. Conclusions: With the growing incidence of MDR GNR as etiologic agents of bacteremia in cancer patients, the development of this score could be a potential tool for clinicians.

Profilaxis con levofloxacina en pacientes neutropénicos / Levofloxacin prophylaxis in neutropenic patients

La profilaxis con fluorquinolonas ha demostrado utilidad en la prevención de infecciones en pacientes neutropénicos de alto riesgo. Nuestro objetivo fue describir y comparar las características clínicas, microbiológicas, terapéuticas y la evolución en pacientes durante el primer episodio de neutropenia febril, según hubieran o no recibido profilaxis con levofloxacina. Fue un estudio prospectivo observacional, que incluyó los episodios de internados por neutropenia febril, (febrero 1997 a noviembre 2014), y los primeros episodios en un mismo paciente en diferentes internaciones; en total fueron 946 episodios. En 821 el episodio de neutropenia febril fue de alto riesgo, y en 264 (27.9%) se administró profilaxis con levofloxacina. Este grupo estaba compuesto por mayor proporción de neutropenias febriles de alto riesgo (99.2% vs. 82.3%, p = 0.0001) y casos con trasplante de células progenitoras hematopoyéticas (67.8% vs. 29.3%, p = 0.0001) comparado con los que no recibieron profilaxis, y presentó una frecuencia similar de infecciones clínicamente documentadas pero una menor proporción de infecciones microbiológicamente documentadas (28.8% vs. 37.5%, p = 0.012). Las bacteriemias en el grupo con quimioprofilaxis fueron más frecuentemente causadas por organismos multirresistentes (OMR) (34.5% vs. 17.3%, p = 0.007) y por enterobacterias productoras de beta lactamasas de espectro extendido (19.0% vs. 3.8%, p = 0.0001). En ese grupo con profilaxis la proporción que recibió tratamiento antibiótico empírico adecuado fue menor (69.7% vs. 83.7%, p = 0.009). La evolución fue similar en ambos grupos. Sugerimos que cuando se observe un aumento en la frecuencia de infecciones por OMR en esta población se considere la interrupción de la profilaxis antibiótica con levofloxacina.

Fluorquinolone-prophylaxis has proven useful in preventing infections in high risk neutropenic patients. The objective of this study was to describe the clinical, microbiological and therapeutic characteristics, and outcome of patients in the first episode of febrile neutropenia, comparing those who received levofloxacin prophylaxis with those who didn't. It was a prospective observational study that included all the episodes of inpatients with febrile neutropenia (February 1997- November 2014), also including the first episode in a same patient in different hospitalizations. Of 946 episodes here included, 821 presented high risk febrile neutropenia. A total of 264 cases (27.9%) received levofloxacin prophylaxis. This group consisted of a higher proportion of high risk febrile neutropenia (99.2% vs. 82.3%, p = 0.0001) and patients that had received an hematopoietic stem cell transplant (67.8% vs. 29.3%, p = 0.0001) compared to those who didn't receive prophylaxis. Those who received levofloxacin prophylaxis presented a similar frequency of clinically diagnosed but a lower proportion of microbiologically documented infections (28.8% vs. 37.5%, p = 0.012) than those who didn´t receive prophylaxis. The episodes of bacteremia that occurred in the first group were more frequently caused by multidrug resistant bacteria (MDRB) (34.5% vs. 17.3%, p = 0.007) and by extended spectrum beta lactamase producing Enterobacteriaceae (19% vs. 3.8%, p = 0.0001). The group that received prophylaxis had a lower proportion of adequate empirical antibiotic treatment (69.7% vs. 83.7%, p = 0.009), with similar outcomes in both groups. We suggest that levofloxacin prophylaxis should be stopped whenever there is a rise in the frequency of MDRB infections in this population.

Diarrea aguda en trasplantes renales y reno-pancreáticos

La diarrea es una complicación frecuente y potencialmente grave del trasplante renal. Se describen aquí, en un estudio de corte transversal, las características epidemiológicas y microbiológicas de la diarrea aguda y persistente en pacientes internados con trasplante renal o reno-páncreas. Se incluyeron 52 pacientes internados en un hospital de la Ciudad de Buenos Aires, 42 (80.8%) habían recibido un trasplante renal y 10 (19.2%) reno-páncreas. La diarrea fue el motivo de ingreso en 34 casos (65.4%). La etiología de la diarrea pudo estudiarse en 50 pacientes: en 25 (50%) no se arribó a un diagnóstico etiológico y en 18 (36%) se constató diarrea con causa microbiológica específica: 3 (6%) enfermedad por citomegalovirus, 6 (12%) diarrea atribuida a citomegalovirus, 5 (10%) a rotavirus y 4 (8%) a Clostridium difficile. En 7 (14%) la diarrea fue atribuida a fármacos (mofetil micofenolato y sirolimus). Aquellos con diarrea con causa microbiológica habían recibido recientemente inmunosupresores a altas dosis con mayor frecuencia que el resto (p = 0.048). Los pacientes con diarrea atribuida a fármacos recibían más frecuentemente mofetil micofenolato (p = 0.039). En 16 (30.8%) se realizaron modificaciones de los inmunosupresores como medida terapéutica, y a 47 (90.4%) se les indicó antibioticoterapia empírica. La mediana de duración de internación fue de 6 días y 7 pacientes (14.6%) persistieron con diarrea al quinto día. Todos tuvieron resolución de la diarrea al alta y un tercio persistió con insuficiencia renal. La información de este estudio puede servir para mejorar las medidas preventivas, diagnósticas y terapéuticas en estos pacientes.

Diarrhea is a frequent and potentially severe complication of kidney transplantation. We describe here, in a cross-sectional study, the epidemiological and microbiological characteristics of acute and persistent diarrhea in 52 inpatients with kidney and kidney-pancreas transplant in a hospital in Buenos Aires, 42 (80.8%) of whom had received a kidney and 10 (19.2%) a kidney-pancreas transplant. Diarrhea was the reason of admission of 34 cases (65.4%). The etiology could be studied in 50 patients: 25 (50%) had no etiological diagnosis of diarrhea and 18 (36%) had a specific infectious etiology: 3 (6%) cytomegalovirus disease, 6 (12%) diarrhea attributed to cytomegalovirus, 5 (10%) to rotavirus and 4 (8%) to Clostridium difficile. In 7 (14%) diarrhea was attributed to drugs (mycophenolate mofetil and sirolimus). Patients with infectious diarrhea had recently received high doses of immunosuppressive therapy more frequently than the rest (p = 0.048). Those with diarrhea attributed to drugs were more frequently on mycophenolate mofetil than the rest (p = 0.039). Empirical modification of the immunosuppressive treatment was done in 16 (30.8%) and empirical antibiotic therapy was given to 47 patients (90.4%). Median length of hospital stay was 6 days. Seven patients (14.6%) persisted with diarrhea at the fifth day of admission. At hospital discharge all cases had complete resolution of symptoms and one third persisted with kidney failure. Information provided in this study can be useful as a starting point for improving preventive, diagnostic and therapeutic measures in these patients.