Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Risks of Adverse Childhood Outcomes According to Prenatal Time of Exposure to Zika Virus: Assessment in a Cohort Exposed to Zika During an Outbreak in Colombia.

Late gestational exposure to Zika increases the odds of delay in the Bayley-II mental developmental index (MDI) in children with normal baseline neurologic assessments; 9-fold when comparing third and first trimester exposure. Risk of MDI developmental delay increases by 8% for each week of gestational age at time of exposure.

Outcomes of Congenital Zika Virus Infection During an Outbreak in Valle del Cauca, Colombia.

BACKGROUND: Despite increasing information in the literature regarding congenital Zika infection, gaps remain in our knowledge of its clinical manifestations. METHODS: We did a prospective observational study of exposed fetuses and infants whose mothers developed symptomatic and confirmed Zika infection during pregnancy in Valle del Cauca, Colombia. We performed neurological, ophthalmologic and audiologic evaluations, and classified outcomes as possibly or uncertainly related to Zika. Frequencies of outcomes were compared according to the trimester of pregnancy when infection occurred. RESULTS: We evaluated 171 products of gestation including 17 pregnancy losses and 154 patients evaluated postnatally. Ninety (52.6%) pregnancies presented an adverse outcome, 36% possibly related with Zika and the remaining 64% of uncertain relation. Infection in the first trimester had the highest frequencies of adverse outcomes possibly related with Zika compared with the second and third trimesters (39% vs. 12.5% vs. 12%) with risk ratios of adverse outcomes possibly related to Zika in pregnancies infected in the first versus second or third trimester of 3.1 (95% CI: 2.4-4.1) and 3.3 (95% CI: 2.5-4.2), respectively. The frequencies of pregnancy loss and microcephaly were 9.4% and 4.5%, respectively. Auditory and ophthalmic abnormalities possibly related with Zika were present in 3% and 6% of the patients evaluated, respectively. CONCLUSIONS: We observed a high frequency of gestational and neonatal complications in pregnant women who acquired Zika infection, especially in early pregnancy, resulting in a broad spectrum of clinical manifestations. Preventive measures are urgently needed to reduce the clinical burden during future Zika outbreaks.

Criptococosis congénita en un neonato expuesto a VIH: presentación de un caso / Congenital cryptococcosis in a newborn exposed to HIV: A case report

La criptococosis puede afectar niños de todas las edades, especialmente aquellos inmunocomprometidos. Usualmente se adquiere a través de la inhalación de esporas del medio ambiente, aunque existen otras formas de transmisión. Describimos un caso de criptococosis congénita adquirido de una madre con síndrome de inmunodeficiencia adquirida (SIDA) y tratado en forma exitosa con combinación de antimicoticos.

Cryptococcosis may affect children of all ages, specially those who are inmunocompromised. It is usually acquired from the inhalation of environmental spores, although other sources of transmission exist. We describe a case of congenital cryptococcosis transmitted from a mother with acquired immunodeficiency syndrome (AIDS), which was successfully treated with combination antifungal agents.

[Evaluation of the genotoxic effect of malaria in a cohort of patients in Medellín and Quibdó]. / Evaluación del efecto genotóxico en pacientes con malaria de una región de Colombia.

INTRODUCTION: During malaria infection, both parasite and host are under the effects of oxidative stress due to the increased production of reactive oxygen species, which can induce DNA damage by its genotoxic effects. OBJECTIVE: To evaluate genotoxic effects in human lymphocytes in a cohort of patients with malaria from Medellin and Quibdó. METHODS: We performed an observational cross sectional study in 100 individuals with malaria and 100 healthy controls. Patients infected with Plasmodium consulting the Institute Colombiano of Medicina Tropical of Medellin and the Hospital Ismael Roldán Valencia of Quibdó were included. Genotoxic effects (genetic damage) was analysed by electrophoresis using alkaline single cell gel (Commet assay). RESULTS: The average of tail length of malaria samples (26.9±9.8) was significantly higher than of controls (14.8±3.2) (p<0.01). CONCLUSION: In our study population, malaria infection was associated with increased genotoxicity, while other variables such as smoking, antimalarial treatment, and occupation were not.

Evaluación del efecto genotóxico en pacientes con malaria de una región de Colombia / Evaluation of the genotoxic effect of malaria in a cohort of patients in Medellín and Quibdó

Introduction: During malaria infection, both parasite and host are under the effects of oxidative stress due to the increased production of reactive oxygen species, which can induce DNA damage by its genotoxic effects. Objective: To evaluate genotoxic effects in human lymphocytes in a cohort of patients with malaria from Medellin and Quibdó. Methods: We performed an observational cross sectional study in 100 individuals with malaria and 100 healthy controls. Patients infected with Plasmodium consulting the Institute Colombiano of Medicina Tropical of Medellin and the Hospital Ismael Roldán Valencia of Quibdó were included. Genotoxic effects (genetic damage) was analysed by electrophoresis using alkaline single cell gel (Commet assay). Results: The average of tail length of malaria samples (26.9 ± 9.8) was significantly higher than of controls (14.8 ± 3.2) (p < 0.01). Conclusion: In our study population, malaria infection was associated with increased genotoxicity, while other variables such as smoking, antimalarial treatment, and occupation were not.

Introducción: Durante la infección de la malaria, tanto el parásito como el hospedero están bajo los efectos de estrés oxidativo, dado que se aumenta la producción de especies reactivas del oxígeno, las cuales pueden inducir daños en el ADN debido a su gran efecto genotóxico. Objetivo: Evaluar el efecto genotóxico en linfocitos humanos en una cohorte de pacientes con malaria de Medellín y Quibdó. Métodos: Se realizó un estudio observacional transversal en 100 personas con malaria y 100 controles sanos. Se incluyeron pacientes infectados con Plasmodium, que consultaron en el Instituto Colombiano de Medicina Tropical de Medellín y el Hospital Ismael Roldán Valencia de Quibdó. Se realizó una valoración transversal del efecto (daño genético) mediante electro-foresis en gel de células individuales (ensayo Cometa). Resultados: El promedio de longitud de la cola de los pacientes (26,9 ± 9,8) fue significativamente mayor que la media de los controles sanos (14,8 ± 3,2) (p < 0,01). Conclusión: Se evidenció en la población de estudio que la infección por malaria generó genotoxicidad, no así variables como tabaquismo, tratamiento antimalárico y ocupación.

Evolución clínica y de laboratorio de episodios de neutropenia febril en niños con cáncer, en un hospital de Colombia, período 2007-2009 / Clinical and laboratory evolution of the febrile neutropenia episodes in pediatric patients hospitalized in a Colombian hospital in 2007-2009

Introduction: Neutropenia is one of the most common complications in children with cancer, and it's the most important parameter to determine infection risk. In neutropenic patients the signs and symptoms could be scarce and in occasions fever could be the only symptom. For these reasons all patients with febrile neutropenia (FN) should be considered as if they had a possibly severe disease. Aim: To describe the clinical characteristics and laboratory parameters observed in cancer patients with FN attended at our hospital to perform a more rational management of this complication in the future. Patients and Methods: The clinical files accumulated during 36 months, belonging to patients aged 0 to 15 years that were hospitalized because of cancer and FN were reviewed. Results: In this series the source of fever was found in 48.6% of 105 NF episodes, and bacteria were isolated from blood or urine culture in 38%. The most frequent bacterial species recovered were methicillin susceptible S. aureus (20.8%) and ESBL negative E. coli (20.8%). Piperacillin/tazobactam was the most used first line antibiotic prescribed (87.6%) and meropenem was the second choice (18%). Granulocyte colony stimulating factor was used in 61.9% of the cases and episodes mortality rate was 6.7%. Conclusion: Clinical characteristics and bacteriological findings in our institution do not differ significantly from what has been described for pediatric cancer patients in other series.

Introducción: La neutropenia es una de las complicaciones más comunes en los niños con cáncer y el principal parámetro para determinar el riesgo de infección. Además, en estos pacientes los signos clínicos de infección pueden ser escasos y en ocasiones la fiebre es la única manifestación, por lo que todo paciente neutropénico y febril se debe manejar como si presentara una posible infección grave. Objetivo: Describir el comportamiento clínico y de laboratorio de los pacientes con neutropenia febril (NF) atendidos en nuestra institución para racionalizar el manejo futuro de esta complicación. Pacientes y Métodos : Se revisó los registros clínicos acumulados durante un período de 36 meses, de todos los pacientes de 0 a 15 años internados por cáncer y NF. Resultados: En este estudio se encontró el foco infeccioso en 48,6% de 105 episodios y se logró aislamiento bacteriano por hemocultivos y/o urocultivo en 38%. Las bacterias encontradas con mayor frecuencia fueron S. aureus sensible a meticilina (20,8%) y E. coli no productora de BLEE (20,8%). El antimicrobiano de primera línea más usado fue piperacilina/tazobactam (87,6%) y de segunda línea meropenem (18%). Se usó factor estimulante de colonias de granulocitos en 61,9% de los pacientes. La mortalidad asociada a estos episodios fue de 6,7%. Conclusión: Las características clínicas y hallazgos de laboratorio en nuestra institución no difieren mayormente de lo descrito en población pediátrica en otras series.

[Experience with tigecycline compassionate use in pediatric patients infected with carbapenem resistant Klebsiella pneumoniae]. / Experiencia con el uso compasivo de tigeciclina en pacientes pediátricos infectados por Klebsiella pneumoniae productora de carbapenemasas.

INTRODUCTION: Infections produced by multidrug-resistant pathogens represent a therapeutic challenge because of the few therapeutic options available. Tigecycline is a relatively new antibiotic, with a wide spectrum of activity including some of these resistant bacteria. In adults is prescribed for the treatment of some infections caused by carbapenem resistant K. pneumoniae, however it has not been approved in children because of potential adverse effects in the dental enamel. MATERIALS AND METHODS: Case series study. Medical records were reviewed in all children from 0 to 14 years of age that received tigecycline between January of 2008 and March of 2010. RESULTS: 9 patients received Tigecycline mainly for treatment of peritonitis, bacteremia, pneumonia and sepsis caused by carbapenem resistant K. pneumoniae. A dose of 1 mg/kg q 12 hours was administered to all patients. No adverse events were reported and a total of 6 patients had complete resolution of the infection. CONCLUSIONS: Tigecycline could be considered a therapeutic option for treating infections produced by multidrug-resistant pathogens in children. The use in children is still compassionate and in this series of cases Tigecycline was well tolerated and safe.

Experiencia con el uso compasivo de tigeciclina en pacientes pediátricos infectados por Klebsiella pneumoniae productora de carbapenemasas / Experience with tigecycline compassionate use in pediatric patients infected with carbapenem resistant Klebsiella pneumoniae

Introduction: Infections produced by multidrug-resistant pathogens represent a therapeutic challenge because of the few therapeutic options available. Tigecycline is a relatively new antibiotic, with a wide spectrum of activity including some of these resistant bacteria. In adults is prescribed for the treatment of some infections caused by carbapenem resistant K. pneumoniae, however it has not been approved in children because of potential adverse effects in the dental enamel. Materials and Methods: Case series study. Medical records were reviewed in all children from 0 to 14 years of age that received tigecycline between January of 2008 and March of 2010. Results: 9 patients received Tigecycline mainly for treatment of peritonitis, bacteremia, pneumonia and sepsis caused by carbapenem resistant K. pneumoniae. A dose of 1 mg/kg q 12 hours was administered to all patients. No adverse events were reported and a total of 6 patients had complete resolution of the infection. Conclusions: Tigecycline could be considered a therapeutic option for treating infections produced by multidrug-resistant pathogens in children. The use in children is still compassionate and in this serie of cases Tigecycline was well tolerated and safe.

Introducción: Las infecciones causadas por bacterias multi-resistentes son difíciles de tratar debido a las pocas opciones terapéuticas disponibles. Tigeciclina es un antimicrobiano relativamente nuevo que tiene un amplio espectro de acción, incluyendo algunas de estas bacterias. En adultos se utiliza para el tratamiento de algunas infecciones producidas por Klebsiella pneumoniae productora de carbapenemasas (Kpn KPC). Sin embargo, por pertenecer al grupo de las tetraciclinas, su uso no ha sido aprobado en niños temiendo los posibles efectos adversos sobre el esmalte dental. Material y Métodos: Estudio de serie de casos. Se realizó una revisión de las historias clínicas de todos los niños de 0 a 14 años que recibieron tigeciclina en forma compasiva entre enero de 2008 y marzo de 2010. Resultados: 9 pacientes recibieron tigeciclina para tratamiento de peritonitis, bacteriemia, neumonía y sepsis por Kpn KPC. La dosis utilizada fue de 1 mg/kg/dosis cada 12 horas. No se encontraron efectos adversos importantes. La infección se consideró curada en 6 pacientes. Conclusiones: Tigeciclina puede ser considerada como una alternativa en el tratamiento de infecciones por bacterias multi-resistentes en niños. Su uso en la edad pediátrica sigue siendo compasivo y en esta serie de casos fue seguro.

[Clinical and laboratory evolution of the febrile neutropenia episodes in pediatric patients hospitalized in a Colombian hospital in 2007-2009]. / Evolución clínica y de laboratorio de episodios de neutropenia febril en niños con cáncer, en un hospital de Colombia, período 2007-2009.

INTRODUCTION: Neutropenia is one of the most common complications in children with cancer, and it's the most important parameter to determine infection risk. In neutropenic patients the signs and symptoms could be scarce and in occasions fever could be the only symptom. For these reasons all patients with febrile neutropenia (FN) should be considered as if they had a possibly severe disease. AIM: To describe the clinical characteristics and laboratory parameters observed in cancer patients with FN attended at our hospital to perform a more rational management of this complication in the future. PATIENTS AND METHODS: The clinical files accumulated during 36 months, belonging to patients aged 0 to 15 years that were hospitalized because of cancer and FN were reviewed. RESULTS: In this series the source of fever was found in 48.6% of 105 NF episodes, and bacteria were isolated from blood or urine culture in 38%. The most frequent bacterial species recovered were methicillin susceptible S. aureus (20.8%) and ESBL negative E. coli (20.8%). Piperacillin/tazobactam was the most used first line antibiotic prescribed (87.6%) and meropenem was the second choice (18%). Granulocyte colony stimulating factor was used in 61.9% of the cases and episodes mortality rate was 6.7%. CONCLUSION: Clinical characteristics and bacteriological findings in our institution do not differ significantly from what has been described for pediatric cancer patients in other series.