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.

Use of polymyxins for carbapenem-resistant infections in children and adolescents.

Background: Polymyxins are still used in children in some regions due to limited availability of newer antibiotics. Objectives: To describe our experience in a cohort of children who received polymyxins for suspected or confirmed carbapenem-resistant bacterial infections (CRI), and explore potential factors associated with therapeutic success. Methods: Retrospective, observational study in children and adolescents <18 years who received IV polymyxin B or colistin therapy for suspected or culture-documented CRI and were admitted to a high complexity clinic in Cali, Colombia between 1 September 2016 and 22 June 2020. Patients' demographic, clinical and microbiological characteristics were collected and analysed; associations with therapeutic success were explored using univariate and multivariate models. Results: There were 40 episodes of polymyxin use (polymyxin B, n = 34; colistin, n = 6) in 34 patients with a median age of 10 years (IQR 7-15); 65% were male. There were 17 adverse events: 3 (17.6%) neurotoxic and 14 (82.4%) nephrotoxic. Therapeutic success was achieved in 28 episodes (70%), of which 32% (9/28) had adverse events. Therapeutic success decreased by 35% with each additional year of age (OR 0.65; 95% CI 0.49-0.80) and by 7% for every hour that elapsed between the onset of fever and the start of appropriate antibiotic therapy (OR 0.93; 95% CI 0.8-0.97) and increased with concomitant non-carbapenem treatment (OR 6.87; 95% CI 1.04-71.01) and the use of adequate empirical therapy (OR 121.36; 95% CI 2.90-1147.95). Conclusions: Several factors were associated with the therapeutic success of polymyxins, however, more than half of episodes had therapeutic failure or adverse events. Antibiotics with greater efficacy and safety are needed in regions with high rates of CRI.

Etiology and Risk Factors for Admission to the Pediatric Intensive Care Unit in Children With Encephalitis in a Developing Country.

OBJECTIVE: To describe a cohort of pediatric patients with encephalitis and their risk factors for admission to the pediatric intensive care unit (PICU). STUDY DESIGN: Children (<18 years old), with encephalitis evaluated by conventional microbiology and syndromic, multiplex test in cerebrospinal fluid (CSF) between July 2017 and July 2020, were recruited from 14 hospitals that comprise the Colombian Network of Encephalitis in Pediatrics. Multivariate analyses were used to evaluate risk factors associated with the need for PICU admission. RESULTS: Two hundred two children were included, of which 134 (66.3%) were male. The median age was 23 months (IQR 5.7-73.2). The main etiologies were bacteria (n = 55, 27%), unspecified viral encephalitis (n = 44, 22%) and enteroviruses (n = 27, 13%), with variations according to age group. Seventy-eight patients (38.6%) required management in the PICU. In multivariate analysis, factors associated with admission to the PICU were the presence of generalized seizures (OR 2.73; 95% CI: 1.82-4.11), status epilepticus (OR 3.28; 95% CI: 2.32-4.62) and low leukocyte counts in the CSF (OR 2.86; 95% CI: 1.47-5.57). Compared with enterovirus, bacterial etiology (OR 7.50; 95% CI: 1.0-56.72), herpes simplex encephalitis (OR 11.81; 95% CI: 1.44-96.64), autoimmune encephalitis (OR 22.55; 95% CI: 3.68-138.16) and other viral infections (OR 5.83; 95% CI: 1.09-31.20) increased the risk of PICU admission. CONCLUSIONS: Data from this national collaborative network of pediatric patients with encephalitis allow early identification of children at risk of needing advanced care and can guide the risk stratification of admission to the PICU.

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

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.

Methylation Status of GLP2R, LEP and IRS2 in Small for Gestational Age Children with and without Catch-up Growth

Objective: In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involved in metabolism. Epigenetics may influence the development of metabolic diseases in adulthood. To compare the methylation of leptin (LEP), glucagon-like peptide-2 receptor (GLP2R), insulin receptor substrate-2 (IRS2) in SGA patients with and without catch-up growth. Methods: Observational prospective study of SGA children. Demographical and clinical variables were collected from clinical records and parents' questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient and one parent saliva samples. Results: Forty-eight SGA patients were included. Twenty-six (54.2%) had catch-up growth phenotype and 22 (45.8%) did not. The median age was 5.2 years [RIC 4.1-6.8] without difference between groups (p=0.306). The catch-up group had increased appetite (42.3% vs 9.1%, p=0.008), family history of dyslipidemia (42.3% vs 27.3%) and diabetes (34.6% vs 22.7%) compared to non-catch-up group. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55 cm [RIC 52-58] versus median 49.5 cm [RIC46-52]; p<0.001). LEP and GLP2R were methylated in all samples. IRS2 was methylated in 60% of SGA patients without difference between groups (p=0.520). Conclusion: There is no association between IRS2 methylation and catch-up growth among SGA patients. LEP and GLP2R were methylated in all SGA patients. Gene methylation may be implicated in metabolic disease later in life. More studies should be performed to confirm this hypothesis.

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.

Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016.

Arboviruses are responsible for a large burden of disease globally and are thus subject to intense epidemiological scrutiny. However, a variable notably absent from most epidemiological analyses has been the impact of violence on arboviral transmission and surveillance. Violence impedes surveillance and delivery of health and preventative services and affects an individual's health-related behaviors when survival takes priority. Moreover, low and middle-income countries bear a disproportionately high burden of violence and related health outcomes, including vector borne diseases. To better understand the epidemiology of arboviral outbreaks in Cali, Colombia, we georeferenced chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viral cases from The National System of Surveillance in Public Health between October 2014 and April 2016. We extracted homicide data from the municipal monthly reports and kernel density of homicide distribution from IdeasPaz. Crucially, an overall higher risk of homicide is associated with increased risk of reported DENV, lower rates of acute testing, and higher rates of lab versus clinical discordance. In the context of high violence as a potential barrier to access to preventive health services, a community approach to improve health and peace should be considered.

Acute gastroenteritis in a pediatric population from Cali, Colombia in the post rotavirus vaccine era.

BACKGROUND: Epidemiological data from Latin America on acute gastroenteritis (AGE) in the post rotavirus vaccine era obtained using highly sensitive molecular techniques are scarce. METHODS: This prospective surveillance study was performed between March 15, 2015 and March 19, 2016 in two municipal health networks (MHNs) in Cali, Colombia to detect AGE in children <5 years of age. Consecutive sampling was performed simultaneously in all health facilities belonging to both MHNs until completion of the required sample size. Stool samples from AGE patients were tested with a nucleic acid assay for 16 pathogens. Detection frequency and incidence rates were obtained for specific pathogens according to age-group in children with AGE leading to hospitalization or outpatient care. RESULTS: Overall incidence rates of AGE-related hospitalization and outpatient care were 20 and 237 per 1000 children <5 years of age, respectively. Despite almost complete rotavirus vaccine uptake, rotavirus was the most common etiology overall, including hospitalization and outpatient treatment of 0-23-month-olds, with incidence rates of 12 and 108 per 1000 children, respectively. Norovirus incidence rates were similar to rotavirus rates in this age group and associated with high Vesikari scores. Shigella predominated in 24-59-month-olds. CONCLUSIONS: AGE remains an important cause of morbidity in children under 5 years of age, especially in those under 2 years. Rotavirus remains the leading AGE-associated pathogen, followed closely by norovirus in younger children. Preventive measures, including novel vaccination strategies, are necessary in this population to further reduce AGE-related morbidity.

Trasplante autológo de células madre hematopoyéticas en pacientes con diagnóstico de neuroblastoma de alto riesgo en la Fundación Valle del Lili, Cali - Colombia / Autologous Haematopoietic Stem-cell Transplantation in Patients with High Risk Neuroblastoma in the Valle del Lili Foundation Hospital, Cali, Colombia

Resumen Objetivo: Describir la experiencia en el manejo de los pacientes con diagnóstico de neuroblastoma de alto riesgo manejados con trasplante autólogo de células madre hematopoyéticas en la Fundación Valle de Lili. Pacientes y métodos: Estudio descriptivo, tipo serie de casos de pacientes con diagnóstico de neuroblastoma de alto riesgo que recibieron trasplante autólogo de células madre hematopoyéticas entre 2001 y 2015. Los desenlaces de este estudio fueron: supervivencia global; supervivencia libre de evento; tiempo de injerto de plaquetas y neutrófilos, e incidencia acumulada de enfermedad veno oclusiva. Se realizó un análisis estadístico descriptivo para todas las variables consideradas en el análisis y para subgrupos seleccionados. El análisis de supervivencia se hizo con el método Kaplan-Meier. Resultados: Entre 2001 y 2015 quince pacientes con diagnóstico de neuroblastoma recibieron trasplante autólogo de células madre hematopoyéticas. La supervivencia globala3y5anos fue del 55% y la supervivencia libre de evento fue del 47%, donde 14 pacientes injertaron neutrófi los entre el día8y19 postrasplante e injerto de plaquetas entre los 9 y 91 días y 2 pacientes desarrollaron enfermedad venooclusiva hepatica como toxicidad a los fármacos quimioterapéuticos de acondicionamiento. Al momento del último seguimiento 10 pacientes permanecen vivos, de los cuales 8 no presentan evidencia clínica y/o paraclínica de la enfermedad. De los 5 pacientes que fallecieron, 2 fue por toxicidad al trasplante en los primeros 100 díasy3por progresión de la enfermedad. Conclusión: El trasplante autólogo de células madre hematopoyéticas es una alternativa facti ble como tratamiento en nuestro medio para pacientes con diagnóstico de neuroblastoma de alto riesgo, el cual ha contribuido a mejorar la supervivencia en este grupo de pacientes.

Abstract Objective: Describe the experience in the management of patients diagnosed with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation at the Valle de Lili Foundation Hospital. Patients and Methods: A series of cases of patients with a diagnosis of high-risk neuroblastoma who received an autologous haematopoietic stem cell transplantation between 2001 and 2015. The endpoints of this study were: overall survival, event-free survival, platelet and neutrophil graft time and the cumulative incidence of venous-occlusive disease. A descriptive statistical analysis was performed for all the variables considered in the analysis and for the selected subgroups. Survival analysis was performed using the Kaplan-Meier method. Results: A total of 15 patients diagnosed with high risk neuroblastoma received an autologous haematopoietic stem cell transplantation between 2001 and 2015. Overall survival at 3 and 5 years was 55%, and the event-free survival was 47%. 14/15 patients grafted Neutrophils grafted between day 8 and 19 post-transplant in 14/15 patients, with platelet graft between days 9 and 91 days. Hepatic venous-occlusive disease was observed in 2/15 patients as toxicity to conditioning chemotherapeutic drugs. At the time of the last follow-up, 10/15 patients remained alive, 8 of whom had no clinical and/or para-clinical evidence of the disease. Of the 5/15 patients that died, 2 were due to transplant toxicity in the first 100 days, and 3 due to disease progression. Conclusion: We conclude that autologous haematopoietic stem cell transplantation is a viable alternative as a treatment in our setting for patients with high-risk neuroblastoma, and has contributed to improve survival in this group of patients.

Hepatic and Mesenteric Vasculitis as Presenting Manifestation of Mixed Cryoglobulinemia Related to Chronic Hepatitis C Virus Infection in a Female Patient.

Approximately 80% of patients with hepatitis C virus infection develop chronic liver disease as cirrhosis, and 40% develop autoimmune complications as mixed cryoglobulinemia (MC). Gastrointestinal involvement in MC is rare, and even more so is hepatic involvement. We report a case of an 87-year-old woman with a 10-year history of blood transfusion-acquired hepatitis C virus infection, without treatment. She consulted the emergency department for diffuse abdominal pain, associated with vomiting. After 2 weeks of hospitalization in the intensive care unit, a diagnosis of MC was made; cirrhosis and secondary mesenteric and hepatic vasculitis were confirmed by a diagnostic laparoscopy. Unfortunately the condition of the patient worsened with sepsis and resulted in death in the fourth week from admission. This case highlights the importance of having in mind gastrointestinal tract vasculitis as a medical cause of abdominal pain in patients with chronic hepatitis C virus infection and using data laboratory tests, images, and histopathologic studies to aid with the diagnosis.

¿Es importante la cuantificación del flujo de las colaterales sistémico-pulmonares en las cardiopatías congénitas? / How important is the quantification of systemic-to-pulmonary artery collateral flow in congenital heart disease?

Los vasos colaterales sistémico-pulmonares son conexiones vasculares anormales entre las arterias sistémicas y el lecho vascular pulmonar, que surgen como forma alternativa de suministro de sangre ante la disminución del flujo sanguíneo pulmonar. Se dan en pacientes con enfermedades congénitas y adquiridas, y se sospechan en recién nacidos prematuros con enfermedad broncopulmonar, pacientes prematuros que hayan requerido cierre del ducto arterioso persistente (farmacológico o quirúrgico), bronquiectasias y enfermedad inflamatoria crónica. Varían en tamaño, curso, cantidad y distribución, y se originan desde las ramas braquiocefálicas, la pared torácica y la aorta descendente. Algunos mecanismos que contribuyen a su aparición son la hipoxemia, el flujo sanguíneo pulmonar global o regional disminuido y el flujo no pulsátil. Estos mecanismos se observan en formas graves de tetralogía de Fallot, ventrículo único funcional, atresia pulmonar y broncodisplasia pulmonar. En casos específicos como el ventrículo único funcional, su importancia clínica y su óptimaevaluación han sido tema de debate durante las dos últimas décadas