D-index as a Risk Factor for Invasive Fungal Infections in Patients With Acute Lymphoblastic Leukemia From a Reference Hematology Center in Bogota.

Introduction Patients with hematologic malignancies are susceptible hosts for the development of invasive fungal infection (IFI), one of the main life-threatening infectious complications faced by these patients. Currently, we have antifungal prophylaxis strategies and antifungal treatment schemes and we recognize that the main risk factor involved is profound and prolonged neutropenia. D-index and cumulative D-index are quantitative parameters, which determine the magnitude of neutropenia, as a function of duration and depth and their value correlates with the occurrence of IFI. Material and methods A case-control study in patients older than 18 years with acute lymphoblastic leukemia (ALL) was admitted between 2009 and 2019 at the National Cancer Institute for induction, consolidation and salvage chemotherapy. Results A total of 167 patients were included, who received 288 cycles of chemotherapy, the latter were considered the unit of analysis. A generalized estimating equations (GEE) model was designed to analyze correlated data; three quantitative and continuous variables of interest were included in this model: age (years), D-index and deep neutropenia (days). For the population D-index, an odds ratio (OR) = 1.000227 (95% CI 1.0002-1.0004); p < 0.001 was obtained. Conclusion D-index is associated with the development of IFI in patients with ALL, with an exponential increase in OR as the absolute value of the D-index increases.

Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy.

Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against K. pneumoniae and P. aeruginosa, and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels.

Respuesta a la carta de Faccini et al / Reply to Faccini et al

Sr. Editor, Agradecemos los aportes en relación con nuestra publicación. El objetivo del artículo "Enfoque clínico del síndrome febril agudo en Colombia" fue el de considerar los posibles diagnósticos etiológicos que se enmarquen dentro de la definición de la duración de la fiebre en el tiempo, definiendo como aguda aquella que tiene una duración de hasta 7 días. Sin embargo, el cuadro de Chagas agudo incluye en su definición de caso probable "Fiebre continua o prolongada mayor de 7 días, acompañado o no de alguno de los siguientes síntomas. . .". Este criterio ha sido utilizado en los estudios de brotes referenciados en Colombia. Por esta razón, no fue incluido como parte de la revisión

Mr. Editor, We appreciate the contributions in relation to our publication. The aim of the article "Clinical approach to acute febrile syndrome in Colombia" was to consider the possible etiological diagnoses that fall within the definition of the duration of fever over time, defining as acute that which has a duration of up to 7 days. However, acute Chagas disease includes in its probable case definition "Continuous or prolonged fever greater than 7 days, accompanied or not by any of the following symptoms . . .". This criterion has been used in outbreak studies referenced in Colombia. For this reason, it was not included as part of the review.

Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy.

INTRODUCTION: Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. METHODS: This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. RESULTS: We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm³ (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133 mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h); half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12-827.16 mg · h/L. CONCLUSION: Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL.

Valor diagnóstico del galactomanano y proteína C reactiva (PCR) en pacientes con neoplasia hematolinfoide y neutropenia con factor de riesgo de aspergilosis invasiva / Diagnostic value of galactomannan and C reactive protein (CRP) in patients with neutropenia and hematolymphoid neoplasia risk factor for invasive aspergillosis

Introducción: Es importante tener herramientas serológicas que permitan un diagnóstico precoz de la aspergilosis invasiva. Se evaluó el valor diagnóstico del galactomanano y la PCR en 36 pacientes con neoplasias hematolinfoides y neutropenia, y con factor de riesgo de aspergilosis invasiva. Métodos: Estudio observacional descriptivo de serie de casos, de pacientes neutropénicos, con títulos serológicos de galactomanano y PCR, y seguimiento por 30 días. La detección del antígeno galactomanano fue mediante de Platelia® Aspergillus, donde una DO superior a 0,550 ng/ml fue considerada positiva, y la detección de PCR, de Products VITROSchemistry®, donde resultados >1,0 mg/dl se consideraron elevados. Resultados: De acuerdo con los criterios EOR-TC, 23 pacientes fueron calificados como “sin sospecha”; 11, como “posibles”; y 2, como “probadas”. Respecto a los títulos séricos de galactomanano, 7 de los pacientes presentaron títulos >0,550 ng/ml, por lo cual se los consideró como positivos. Al comparar las funciones de supervivencia se encontró un pronóstico menos favorable en el grupo con resultados positivos. En las funciones de supervivencia, en relación con los resultados de PCR tuvieron un mejor pronóstico los miembros del grupo con PCR negativa. De los 7 pacientes que tuvieron títulos séricos positivos para galactomanano, 85,7% tuvieron títulos mayores de 9 mg/dl de PCR, lo que sugiere una relación entre estas 2 pruebas. Conclusiones: El uso de la detección de galactomanano y la PCR es útil para el diagnóstico de aspergilosis invasiva, ya que existe una correlación entre sus resultados y la evidencia clínica para el diagnóstico de la infección invasiva.

Valor diagnóstico del título serológico del manano de Candida y proteína C reactiva (PCR) en pacientes con neoplasia hematolinfoide y neutropenia con factor de riesgo de candidiasis invasiva (CI) / Diagnostic value of serological titre of Candida mannan and C reactive protein (CRP) in patients with neutropenia and hematolymphoid neoplasia risk factor for invasive candidiasis (IC)

Introducción: Este estudio tiene como fin establecer la utilidad diagnóstica de la detección de los títulos serológicos de antígenos de manano junto a la PCR, para el diagnóstico de CI en pacientes oncológicos. Métodos: Los títulos serológicos se determinaron como: negativos < 0,25 ng/ml; intermedios: entre 0,25 y 0,5 ng/ml; positivos: > 0,5 ng/ml. La PCR se analizó como: negativa < 9 mg/dl; positiva > 9 mg/dl. El gold estándar utilizado fueron: imágenes diagnósticas, cultivos microbiológicos y las historias clínicas en su conjunto. Resultados: Los títulos positivos de manano mostraron una relación no significativa de mortalidad en los pacientes del estudio. El título serológico de manano y la PCR fueron positivos en 20% de los pacientes, lo cual muestra una asociación no significativa. El aislamiento del agente etiológico en 51,42% de los pacientes fue diferente de Candida spp, un aislamiento en urocultivo de C. albicans. Ningún paciente se clasificó como IFI probada; 29% fueron probables; 17%, posibles; y 54%, sin sospecha, según los criterios de la EORTC-MSG.Conclusiones: Títulos antigénicos de manano para Candida spp, PCR, imágenes diagnósticas, cultivos microbiológicos y la patología de base del paciente pueden esclarecer el diagnóstico de CI.