Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia.

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Clinical inertia in newly diagnosed type 2 diabetes mellitus among patients attending selected healthcare institutions in Colombia.

BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.

Solvent-Free Nonthermal Destruction of PFAS Chemicals and PFAS in Sediment by Piezoelectric Ball Milling.

Studies on the destruction of solid per- and polyfluoroalkyl substances (PFAS) chemicals and PFAS-laden solid wastes significantly lag behind the urgent social demand. There is a great need to develop novel treatment processes that can destroy nonaqueous PFAS at ambient temperatures and pressures. In this study, we develop a piezoelectric-material-assisted ball milling (PZM-BM) process built on the principle that ball collisions during milling can activate PZMs to generate ∼kV potentials for PFAS destruction in the absence of solvents. Using boron nitride (BN), a typical PZM, as an example, we successfully demonstrate the complete destruction and near-quantitative (∼100%) defluorination of solid PFOS and perfluorooctanoic acid (PFOA) after a 2 h treatment. This process was also used to treat PFAS-contaminated sediment. Approximately 80% of 21 targeted PFAS were destroyed after 6 h of treatment. The reaction mechanisms were determined to be a combination of piezo-electrochemical oxidation of PFAS and fluorination of BN. The PZM-BM process demonstrates many potential advantages, as the degradation of diverse PFAS is independent of functional group and chain configurations and does not require caustic chemicals, heating, or pressurization. This pioneering study lays the groundwork for optimizing PZM-BM to treat various PFAS-laden solid wastes.

The impact of universal varicella vaccination on the clinical burden of varicella in Colombia: A National database Analysis, 2008-2019.

In 2015, one-dose universal varicella vaccination (UVV) was introduced in the Colombian National Immunization Program targeting children aged 12 months, expanding to a two-dose program in 2019. This study aimed to examine the effect of one-dose UVV on the burden of varicella in Colombia. A retrospective study was conducted using national databases to estimate incidence and mortality for the target (1-4 years old), non-target (less than 1 and 5 years and older) and overall (all age groups) populations from the pre-UVV period (January 2008-June 2015) to the post-UVV period (July 2015-December 2019). A time-series analyses with ARIMA modeling was used to project expected varicella incidence and mortality in the absence of UVV in the post-UVV period. UVV impact was estimated by comparing predicted and observed values, providing point estimates and prediction intervals (PI). Overall vaccination coverage rate was over 90 % from 2016-2019. Following UVV introduction, mean annual incidence rates reduced from 743.6 to 676.8 per 100,000 in the target population and from 203.2 to 198.1 per 100,000 in the overall population. Our study estimated a reduction in varicella incidence from 2017, with the highest reduction of 70.5 % (95 % PI: 78.2-54.2) and 54.8 % (95 % PI: 65.0-36.4) observed in 2019 for the target and the overall populations, respectively. The ARIMA model estimated UVV in Colombia to have prevented 198,236 varicella cases from 2015 to 2019. Mortality reduced in the overall population from 0.8 per 1,000,000 to 0.5 per 1,000,000 and from 1.3 per 1,000,000 to 0.5 per 1,000,000 in the target population, in the pre-UVV and post-UVV periods, respectively. However, these differences were not statistically significant. Our study showed a significant reduction in varicella incidence after implementation of a one-dose UVV program in Colombia, increasing over time. Further assessment is needed to evaluate the impact of a two-dose UVV program in Colombia.

Invasive Pneumococcal Disease Characterization in Adults and Subgroups aged < 60 years and ≥ 60 years in Bogota, Colombia.

Background: There is scarce information on the burden of invasive pneumococcal disease (IPD) among adults in low- and middle-income countries. This study aimed to describe the clinical outcomes and microbiological characteristics associated with IPD in adults and subgroups aged 18-59 years and ≥60 years in Colombia. Methods: A retrospective chart review study was conducted in five institutions of Bogotá from January 2011 to December 2017. Analyses were carried out for overall population and stratified by age group (18-59; ≥ 60 years). Results: There were 169 IPD cases; median age was 58 years, 51.5% were male, and 80.5% had at least one comorbidity. Bacteremic pneumonia was the most common presentation (63.9%). The median length of hospital stay was 12 days with high healthcare resource utilization (HCRU): 58.6% required ICU and 53.3% inotropic support. Overall case-fatality rate (CFR) was 41.4%. Clinical outcomes were worse in patients ≥60 years old with significantly higher CFR and HCRU (ICU admission, mechanical ventilation, and inotropic support) compared to those aged 18-59 years. The most frequent serotypes were 3, 6 A/C, 14, and 19A. The sensitivity to penicillin in meningitis and non-meningitis isolates were 75% and 89.1% respectively. Conclusions: IPD was associated with a substantial burden in adults and worse clinical outcomes and HCRU in older adults in Colombia. Surveillance data combined with clinical outcomes have the potential to inform age-based pneumococcal vaccination policies.

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.

Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production.

After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.

Cost-effectiveness of ceftolozane/tazobactam for the treatment of complicated intraabdominal and urinary tract infections in Colombia / Costo-efectividad de ceftolozano/tazobactam para el tratamiento de las infecciones intraabdominales e infecciones del tracto urinario complicadas en Colombia

Objective: To evaluate the cost-effectiveness of ceftolozane/tazobactam + metronidazole (C/T+M) and ceftolozane/tazobactam (C/T) compared with 8 alternatives used in the treatment of complicated intraabdominal infection (cIAI) and complicated urinary tract infection (cUTI) respectively. Methods: A Monte Carlo simulation decision model was used for the estimation and comparison of treatment-related costs, and quality adjusted life years for patients with cIAI treated with C/T+M in comparison with cefepime + metronidazole, ciprofloxacin + metronidazole, doripenem, levofloxacin + metronidazole, meropenem, piperacillin/tazobactam, ceftazidime + metronidazole or imipenem/cilastatin and patients with cUTI treated with C/T in comparison with cefepime, ciprofloxacin, doripenem, levofloxacin, meropenem, piperacillin/tazobactam, ceftazidime or imipenem/cilastatin. Local costs were estimated using base cases identified by experts and consulting local databases. Sensitivity values of the PACTS (Program to Assess Ceftolozane/Tazobactam Susceptibility) study in Latin America were used in the model. Results: C/T+M and C/T obtained incremental cost-effectiveness ratios (ICER) that were below the Colombian cost-effectiveness threshold (3 GDP per capita) in most comparisons, and were dominated by meropenem, considering only gram-negative microorganisms. Sensitivity assessments were also carried out, in which only the population with P. aeruginosa infections was considered, showing positive results for C/T+M and C/T (cost-effective or dominant with regards to all comparators). Conclusions: C/T+M and C/T could be cost-effective alternatives in the treatment of CIAI and CUTI in Colombia, when there is an adequate and rational use of antibiotics. The results of the sensitivity analyses showed dominance and cost-effectiveness with regards to every comparator in patients infected with P. aeruginosa

Objetivo: Evaluar la costo-efectividad de ceftolozano/tazobactam + metronidazol (C/T + M) y ceftolozano/tazobactam (C/T) en comparación con 8 alternativas utilizadas en el tratamiento de las infecciones intraabdominales complicadas (IAAc) e infecciones del tracto urinario complicadas (ITUc) respectivamente. Métodos: Se usó un modelo de decisión de simulación de Monte Carlo para la estimación y comparación de los costos relacionados con el tratamiento y los años de vida ajustados por calidad para pacientes con IAAc tratados con C/T + M, en comparación con cefepima + metronidazol, ciprofloxacina + metronidazol, doripenem , levofloxacina + metronidazol, meropenem, piperacilina / tazobactam, ceftazidima + metronidazol o imipenem/cilastatina, y pacientes con ITUc tratados con C/T en comparación con cefepime, ciprofloxacina, doripenem, levofloxacina, meropenem, piperacilina / tazobactam, ceftazidima o imipenem/cilastatina . Los costos locales se estimaron por medio de casos base identificados por expertos y consultando bases de datos locales. Se utilizaron los valores de sensibilidad bacteriana del estudio PACTS (Programa para evaluar la susceptibilidad al ceftolozano/tazobactam) en América Latina para poblar el modelo. Resultados: C/T + M y C/T obtuvieron razones de costo-efectividad incrementales (RCEI) que estaban por debajo del umbral de costo-efectividad colombiano (3 PIB per cápita) en la mayoría de las comparaciones, y fueron dominados por meropenem, considerando solo microorganismos gran-negativos También se llevaron a cabo análisis de sensibilidad, en los que solo se consideró la población con infecciones por P. aeruginosa, mostrando resultados positivos para C/T + M y C/T (costo efectivo o dominante con respecto a todos los comparadores). Conclusiones: C/T + M y C/T podrían ser alternativas costo efectivas en el tratamiento de IAAc e ITUc en Colombia, cuando existe un uso adecuado y racional de antibióticos. Los resultados de los análisis de sensibilidad mostraron dominio y costo-efectividad en relación con todos los comparadores en pacientes infectados con P. aeruginosa.

Burden of genital warts in Colombia: an observational study / Carga das verrugas genitais na Colômbia: um estudo observacional

Introduction: Genital warts are benign lesions caused by sexual transmission of human papillomavirus types 6 and 11, with significant impact on healthcare resource use and patients' quality of life. Objective: To describe the epidemiology of genital warts in adults visiting a physician office for any reason, physician practice patterns, and healthcare resource use and costs in Colombia. Methods: Participants were a convenience sample of 53 physicians in 5 specialties: primary care (15), gynecology (24), urology (12), proctology (1), and dermatology (1). Physicians completed a survey and daily log of all patients 18-60 years old seen over 10 days in their practices in 2016-2017. The physician survey recorded genital warts consultation and management patterns. The daily log recorded patient demographic information and genital warts diagnosis. Results: Among 6,393 patients logged by physicians, the genital warts prevalence was 2.03% (95%CI 1.69­2.38) and incidence 1.30% (95%CI 1.02­1.58). Primary care physicians referred most of their genital warts cases for treatment (female: mean 63.3%, SD=44.8; male: mean 58.3%, SD=43.8). Treatment of non-resistant episodes (<6-month duration) lasted an average of 37.4 days (SD=29.4) and required an average of 4.0 (SD=1.9) office visits for females and 3.0 (SD=1.7) for males. The overall mean cost of an episode of care was USD558.13 (SD=507.30). Conclusion: Genital warts cases reported by most participant physicians were mainly direct-consult, but patients were typically treated by specialists. Much of the genital warts health care utilization and costs reported could be prevented by immunization with the quadrivalent or nonavalent HPV vaccine.

Introdução: As verrugas genitais são lesões benignas, de transmissão sexual, causadas pelo papilomavírus humano tipos 6 e 11 e que causam impacto significativo no uso de recursos de saúde e na qualidade de vida dos pacientes. Objetivo: Descrever a epidemiologia das verrugas genitais em adultos que buscaram atendimento médico ambulatorial por qualquer motivo, incluindo padrões de prática médica, uso de recursos de saúde e custos na Colômbia. Métodos: foi utilizada uma amostra de conveniência composta por 53 médicos em 5 especialidades: clínico geral (15), ginecologia (24), urologia (12), proctologia (1) e dermatologia (1). Os médicos completaram um questionário e registros diários de todos os pacientes com idade entre 18 e 60 anos atendidos durante 10 dias em seus consultórios em 2016-2017. O questionário registrou os padrões de prática médica e de tratamento de verrugas genitais. Os registros diários continham informações demográficas do paciente e o diagnóstico de verrugas genitais. Resultados: Entre 6.393 atendimentos médicos, a prevalência das verrugas genitais foi de 2,03% (IC95% 1,69­2,38) e a incidência de 1,30% (IC95% 1,02­1,58). Os clínicos gerais encaminharam a maioria dos pacientes com verrugas genitais para tratamento (mulheres: média de 63,3%, DP=44,8; homens: média de 58,3%, DP=43,8). O tratamento dos casos não-persistentes (<6 meses de duração) durou em média 37,4 dias (DP=29,4) e requereu uma média de 4,0 (DP=1,9) consultas para mulheres e 3,0 (DP=1,7) para homens. O custo médio geral do tratamento foi de US$ 558,13 (SD=507,30). Conclusão: Os casos de verrugas genitais relatados pela maioria dos médicos participantes derivaram-se principalmente de atendimentos primários e os pacientes foram tratados geralmente por especialistas. Grande parte da utilização de recursos e custos relacionados a verrugas genitais poderia ser evitada pela imunização com a vacina papilomavírus humano 4-valente ou 9-valente.

Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient.

PURPOSE: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9. METHODS: We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. RESULTS: The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. CONCLUSION: We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.

Fungemia due to Kodamaea ohmeri in a young infant and review of the literature.

Fungal infections have become an important cause of morbidity and mortality in hospitalized children due to many complicating and underlying conditions. We present the case of a newborn infant with fungemia due to Kodamaea ohmeri who had a good outcome of the infection after using the combination of antifungal treatment and central venous catheter removal.

Síndrome de Casamassima / Casamassima syndrome

El síndrome de Cassamasima se caracteriza por una triada que consiste en alteraciones costo vertebrales, atresia anal y alteraciones genitourinarias, siendo un síndrome de presentación rara y cuya supervivencia estará determinada por la gravedad de las alteraciones. Presentamos el caso de un niño con características típicas de este síndrome.

Cassamasima syndrome is characterized by a triad consisting costo vertebral alterations, anal atresia, and genito urinary disorders, being rare and whose survival is determined by the severity of the disturbances. We report the case of a child with typical features of this syndrome.