[Strategies and recommendations to face respiratory syncytial virus disease in 2024]. / Estrategias y recomendaciones para enfrentar la enfermedad por virus respiratorio sincicial el año 2024.

During the winter of 2023, Chile faced a complex situation related to the respiratory syncytial virus (RSV). After experiencing a decline in RSV circulation during the years of the SARS-CoV-2 pandemic, a late outbreak was observed in the spring of 2022 and an early onset of the outbreak in 2023, with a significant increase in the number of serious cases. The ineffectiveness of strategic planning and risk communication contributed to the complexity of the situation. To avoid the above next winter, measures such as active surveillance, unification of definitions for acute respiratory infections, identification of RSV variants, public education about infections and advance preparation regarding hospital beds and health personnel are suggested. The importance of immunization and intersectoral collaboration to acquire new preventive alternatives is highlighted, as well as the need for early communication about the importance of immunization and identification of high-risk groups, improvement in training of medical personnel and strategic planning of the Ministry of Health. seeking a proactive and collaborative approach to address the complex RSV situation in future winters. The Chilean Immunization Advisory Committee has already carried out an analysis and recommendation on a new prevention alternative. This working group will support any decision of the Ministry of Health in public policies that attempt a change in the paradigm of control of this disease for the health of the children of our country.

O-versus S-Metal Coordination of the Thiocarboxylate Group: An NMR Study of the Two Tautomeric Forms of the Ga(III)-Photoxenobactin E Complex.

Photoxenobactin E (1) is a natural product with an unusual thiocarboxylic acid terminus recently isolated from an entomopathogenic bacterium. The biosynthetic gene cluster associated with photoxenobactin E, and other reported derivatives, is very similar to that of piscibactin, the siderophore responsible for the iron uptake among bacteria of the Vibrionaceae family, including potential human pathogens. Here, the reisolation of 1 from the fish pathogen Vibrio anguillarum RV22 cultured under iron deprivation, its ability to chelate Ga(III), and the full NMR spectroscopic characterization of the Ga(III)-photoxenobactin E complex are presented. Our results show that Ga(III)-photoxenobactin E in solution exists in a thiol-thione tautomeric equilibrium, where Ga(III) is coordinated through the sulfur (thiol form) or oxygen (thione form) atoms of the thiocarboxylate group. This report represents the first NMR study of the chemical exchange between the thiol and thione forms associated with thiocarboxylate-Ga(III) coordination, including the kinetics of the interconversion process associated with this tautomeric exchange. These findings show significant implications for ligand design as they illustrate the potential of the thiocarboxylate group as a versatile donor for hard metal ions such as Ga(III).

Ammonium concentration in stream sediments resulting from decades of discharge from a wastewater treatment plant.

A study of ammonium pollution in the sediments of a stream that receives wastewater treatment plant (WWTP) discharge has been carried out. It is urgently necessary to find environmental indicators that can help prevent and detect potential contamination of water, as water is an increasingly scarce resource. To understand the behaviour of ammonium ions introduced by a historical (50-year) contamination process, vertical boreholes were drilled in the stream banks to depths between 30 and 120 cm. Moisture, pH, ammonium (soluble and exchangeable), and clay fraction content were analysed. The variation profile of these parameters was evaluated as a function of depth to determine factors related to the distribution of ammonium in several locations along the stream banks. The ammonium concentration was asymmetrically distributed among samples collected in near-surface locations, with ammonium concentrations between 0.3048 mmol/kg soil and 0.0007 mmol/kg soil. Ammonium was typically concentrated at sediment depths of 30-40 cm, which also exhibited the highest clay fraction content. High positive correlations were detected (r > 0.8; p < 0.0001) among the different ammonium variables (exchanged and dissolved species). No contamination effect was observed below 60-70 cm depth, which was due to ammonium retention in a natural barrier layer of clayey sediment. The clays in our study area (previously identified as smectite, a 2:1 sheet silicate) were able to control the contamination by retaining ammonium in the interlayers, which retarded nitrification. It is suggested that clay could serve as a geo-indicator of ammonium pollution evolution.

Synergistic antileishmanial activity of erythrodiol, uvaol, and oleanolic acid isolated from olive leaves of cv. Chemlali.

This study aimed to assess the antileishmanial activity of biomolecules obtained from Olea europaea L. leaves and twigs recovered from eight Tunisian cultivars. The extraction was first carried out with 80% methanol, and then the obtained extract was fractionated using three solvents of increasing polarity: cyclohexane (CHX), dichloromethane (DCM) and ethyl acetate (EtOAc). The antileishmanial activity was determined against leishmanial strains responsible for cutaneous, visceral, and mucocutaneous leishmaniasis. The cyclohexane fraction of the leaves of cv. Chemlali from the region of Sidi-Bouzid exhibited the strongest leishmanicidal activity against all the tested leishmanial strains. The inhibition concentrations (IC50) were 16.5, 14.5, and 7.4 µg mL-1 for Leishmania mexicana (cutaneous), Leishmania braziliensis (mucocutaneous), and Leishmania donovani (visceral), respectively. Interestingly, low cytotoxicity was observed on THP-1 cells with selective indexes (SI) ranging from 22.8 to 50.5. HPLC-HRMS and full-house NMR analysis allowed the identification of three triterpenic compounds, oleanolic acid (IC50 = 64.1 µg mL-1), erythrodiol (IC50 = 52.0 µg mL-1), and uvaol (IC50 = 53.8 µg mL-1). Antileishmanial activity of uvaol and oleanolic acid has been previously reported. However, this work constitutes the first report of the antileishmanial activity of erythrodiol which showed combinatorial interaction with uvaol (IC50 = 26.1 µg mL-1) against Leishmania tropica. The mixture of the three compounds, as major ones, exhibited an enhanced activity against Leishmania tropica (IC50 = 16.3 µg mL-1) compared to erythrodiol alone or the combination of uvaol and erythrodiol. This finding is of great importance and needs further investigation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03825-3.

Multistage Detection of Tetrodotoxin Traces in Diodon hystrix Collected in El Salvador.

This study describes a multistage methodology to detect minute amounts of tetrodotoxin in fishes, a plan that may be broadened to include other marine organisms. This methodology was applied to porcupinefish (Diodon hystrix) collected in Punta Chiquirín, El Salvador. A three-stage approach along with post-acquisition processing was employed, to wit: (a) Sample screening by selected reaction monitoring (HPLC-MS/MS-SRM) analyses to quickly identify possible toxin presence via a LC/MS/MS API 3200 system with a triple quadrupole; (b) HPLC-HRFTMS-full scan analyses using an ion trap-Orbitrap spectrometer combined with an MZmine 2-enhanced dereplication-like workflow to collect high-resolution mass spectra; and (c) HPLC-HRMS2 analyses. This is the first time tetrodotoxin has been reported in D. hystrix specimens collected in El Salvador.

Datura stramonium Flowers as a Potential Natural Resource of Bioactive Molecules: Identification of Anti-Inflammatory Agents and Molecular Docking Analysis.

The present study investigated the antioxidant, antibacterial, antiviral and anti-inflammatory activities of different aerial parts (flowers, leaves and seeds) of Datura stramonium. The plant material was extracted with 80% methanol for about 24 h. The sensitivity to microorganisms analysis was performed by the microdilution technique. Antioxidant tests were performed by scavenging the DPPH and ABTS radicals, and by FRAP assay. Anti-inflammatory activity was evaluated through the inhibition of nitric oxide production in activated macrophage RAW 264.7 cells. Cell viability was assessed with an MTT assay. Results show that the flower extract revealed a powerful antimicrobial capacity against Gram-positive bacteria and strong antioxidant and anti-inflammatory activities. No significant cytotoxicity to activated macrophages was recorded. High resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analysis identified two molecules with important anti-inflammatory effects: 12α-hydroxydaturametelin B and daturametelin B. Molecular docking analysis with both pro-inflammatory agents tumor necrosis factor alpha and interleukin-6 revealed that both compounds showed good binding features with the selected target proteins. Our results suggest that D. stramonium flower is a promising source of compounds with potential antioxidant, antibacterial, and anti-inflammatory activities. Isolated withanolide steroidal lactones from D. stramonium flower extract with promising anti-inflammatory activity have therapeutic potential against inflammatory disorders.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort.

Objectives: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. Methods: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. Results: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS > 15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR] = 3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR = 1.303, CI 1.137-1.493), and with 28-days mortality (OR = 1.024, CI 1.006-1.042). LUS > 15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS ≤ 7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS > 20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). Conclusions: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS ≤ 7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS > 15 would be the point which better discriminates mild from severe disease.

Objetivos: Establecer diferentes puntos de corte basados en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos: Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron la mala evolución y la mortalidad a los 28 días. Resultados: De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS > 15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR] = 3,636, intervalo de confianza [IC] 1,411-9,374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, el LUS se asoció estadísticamente con mala evolución (OR = 1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR = 1,024, IC 1,006-1,042). LUS > 15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS ≤ 7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS > 20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones: LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS ≤ 7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥ 20 con neumonía grave. Si se utilizara un único punto de corte, LUS > 15 sería el que mejor discriminaría la enfermedad leve de la grave.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort / Puntos de corte de gravedad del Lung Ultrasound Score en la neumonía COVID-19. Revisión sistemática de la literatura y cohorte de validación

Objectives Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. Methods Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. Results From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS>15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR]=3.636, confidence interval [CI] 1.411–9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR=1.303, CI 1.137–1.493), and with 28-days mortality (OR=1.024, CI 1.006–1.042). LUS>15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS≤7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695–0.955), while LUS>20 revealed high specificity to predict poor outcome (0.86, CI 0.776–0.917). Conclusions LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS≤7 cut-off point is associated with mild pneumonia, LUS 8–20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS>15 would be the point which better discriminates mild from severe disease (AU)

Objetivos Establecer diferentes puntos de corte basados en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron la mala evolución y la mortalidad a los 28 días. Resultados De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS>15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR]=3,636, intervalo de confianza [IC] 1,411-9,374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, el LUS se asoció estadísticamente con mala evolución (OR=1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR=1,024, IC 1,006-1,042). LUS>15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS≤7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS>20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS≤7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥20 con neumonía grave. Si se utilizara un único punto de corte, LUS>15 sería el que mejor discriminaría la enfermedad leve de la grave (AU)

Structural Requirements for Ga3+ Coordination in Synthetic Analogues of the Siderophore Piscibactin Deduced by Chemical Synthesis and Density Functional Theory Calculations.

Stereoselective total synthesis of several analogues of piscibactin (Pcb), the siderophore produced by different pathogenic Gram-negative bacteria, was performed. The acid-sensitive α-methylthiazoline moiety was replaced by a more stable thiazole ring, differing in the configuration of the OH group at the C-13 position. The ability of these Pcb analogues to form complexes with Ga3+ as a mimic of Fe3+ showed that the configuration of the hydroxyl group at C-13 as 13S is crucial for the chelation of Ga3+ to preserve the metal coordination, while the presence of a thiazole ring instead of the α-methylthiazoline moiety does not affect such coordination. A complete 1H and 13C NMR chemical shift assignment of the diastereoisomer mixtures around C9/C10 was done for diagnostic stereochemical disposition. Additionally, density functional theory calculations were performed not only for confirming the stereochemistry of the Ga3+ complex among the six possible diastereoisomers but also for deducing the ability of these to form octahedral coordination spheres with gallium. Finally, the lack of antimicrobial activity of Pcb and Pcb thiazole analogue Ga3+ complexes against Vibrio anguillarum agrees with one of the roles of siderophores in protecting pathogens from metal ion toxicity. The efficient metal coordination shown by this scaffold suggests its possible use as a starting point for the design of new chelating agents or vectors for the development of new antibacterials that exploit the "Trojan horse" strategy using the microbial iron uptake mechanisms. The results obtained will be of great help in the development of biotechnological applications for these types of compounds.

Assessment of Neuromuscular Fatigue 24 hours After a Futsal Simulated Protocol in University Female Athletes.

The purpose of this study was to identify changes in neuromuscular performance variables evaluated through the countermovement jump test before and after (0 hours, after session and 24h post) of a simulated futsal protocol in young university female athletes. Fourteen eumenorrheic, healthy and experienced female futsal players were randomly assigned to an intervention group n = 7) or a control group (n = 7). Both groups performed three countermovement jumps before and after the protocol using an inertial system device. The intervention group completed a short-term functional agility and fatigue protocol that simulated the characteristics of futsal, while the control group did not perform any exercise. The results showed a reduction in peak flight time (p = 0.049; d = 0.586), peak concentric work (p = 0.03; d = 1.819) and peak maximum force (p = 0.02; d = 0.782) comparing experimental and control group. No changes in other variables examined were noted between conditions (p > 0.05). These findings indicate that the changes in neuromuscular performance variables, evaluated through a simulated protocol, are established as determinants in the definition of peripheral fatigue in futsal practitioners until 24 h after a demanding intervention.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia.

Objective: To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods: This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results: There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions: While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017-2019.

Objectives: To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence. Methods: This was a cross-sectional study of secondary data from the Colombian Integrated Social Protection Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1-4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, direct payment, pay per case, pay for event). Results: Of 215 925 cases of community-acquired pneumonia reported during 2017-2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guidelines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion: In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

Adherence to guidelines on the use of amoxicillin for treatment of ambulatory pneumonia in children younger than 5 years, Colombia, 2017–2019

[ABSTRACT]. Objectives. To determine the level of adherence to clinical guidelines in prescribing amoxicillin to children younger than 5 years with pneumonia in outpatient settings in Colombia from 2017 to 2019, and assess the factors associated with adherence Methods. This was a cross-sectional study of secondary data from the Colombian Integrated Social Protec- tion Information System database. Adherence was defined as prescription of oral amoxicillin for bacterial and unspecified pneumonia and non-prescription for viral pneumonia. Variables examined included: age (< 1 year, 1–4 years) of child; sex; cause of pneumonia (bacterial, viral, unspecified); region (Andean, Amazonian, Pacific, Caribbean, Insular, Orinoquian); and payment mechanism (without prior authorization, capitation, dir- ect payment, pay per case, pay for event). Results. Of 215 925 cases of community-acquired pneumonia reported during 2017–2019, 64.8% were from the Andean region, 73.9% were bacterial pneumonia and 1.8% were viral pneumonia. Adherence to guide- lines was observed in 5.8% of cases: this was highest for children diagnosed with viral (86.0%) compared with bacterial (2.0%) pneumonia. For children diagnosed with bacterial pneumonia, 9.4% were prescribed any antibiotic. A greater proportion of children covered by capitated payments (22.3%) were given treatment consistent with the guidelines compared with payment for event (1.3%). Conclusion. In this first study from Colombia, adherence to guidelines for outpatient treatment of children with bacterial pneumonia was low and was better for viral pneumonia. Further qualitative studies are needed to explore the reasons for this lack of adherence and why bacterial pneumonia was the most commonly reported etiology.

[RESUMEN]. Objetivos. Determinar el nivel de adherencia a las directrices clínicas al momento de prescribir amoxicilina a menores de 5 años con neumonía en entornos de atención ambulatoria en Colombia entre el 2017 y el 2019, así como evaluar los factores asociados con la adherencia. Métodos. Este fue un estudio transversal de datos secundarios de la base de datos del Sistema Integral de Información de la Protección Social de Colombia. La adherencia se definió como la prescripción de amox- icilina por vía oral para las neumonías bacterianas y no especificadas, y la ausencia de prescripción para las neumonías virales. Las variables examinadas incluyeron: edad (< 1 año, 1 a 4 años); sexo; causa de la neumonía (bacteriana, viral, no especificada); región (andina, amazónica, Pacífico, Caribe, insular, Orinoco); y mecanismo de pago (sin autorización previa, capitación, pago directo, pago por caso, pago por evento). Resultados. De 215 925 casos de neumonía adquirida en la comunidad notificados durante el período 2017- 2019, el 64,8% correspondieron a la región andina, el 73,9% a neumonía bacteriana y el 1,8% a neumonía viral. Se observó la adherencia a las directrices en el 5,8% de los casos: esta cifra fue más alta para la población infantil diagnosticada con neumonía viral (86,0%) que para la diagnosticada con neumonía bacte- riana (2,0%). En el caso de la población infantil diagnosticada con neumonía bacteriana, al 9,4% se le recetó algún antibiótico. La proporción de población infantil cubierta por pagos capitados (22,3%) que recibió un tratamiento en consonancia con las directrices fue mayor que la de la población cubierta por pagos por evento (1,3%). Conclusión. En este primer estudio de Colombia, la adherencia a las directrices sobre el tratamiento ambula- torio de la población infantil con neumonía bacteriana fue bajo, en tanto que resultó superior en el caso de la neumonía viral. Se necesitan más estudios cualitativos para indagar sobre los motivos de esta falta de adher- encia y las razones por las cuales la neumonía bacteriana fue la etiología notificada con mayor frecuencia.

[RESUMO]. Objetivos. Determinar o nível de adesão às diretrizes clínicas para prescrição de amoxicilina em regime ambulatorial para crianças menores de 5 anos com pneumonia na Colômbia, de 2017 a 2019, e avaliar os fatores associados à adesão. Métodos. Estudo transversal de dados secundários do banco de dados do Sistema Integrado de Informação sobre Proteção Social da Colômbia. Definiu-se adesão como prescrição de amoxicilina oral para pneumonia bacteriana e não especificada, e não prescrição para pneumonia viral. As variáveis examinadas incluíram: idade da criança (< 1 ano, 1–4 anos), sexo, etiologia da pneumonia (bacteriana, viral, não especificada), região (Andina, Amazônica, Pacífica, Caribenha, Insular, Orinoco) e mecanismo de pagamento (sem autor- ização prévia, capitação, pagamento direto, pay-per-case, pay-for-event). Resultados. Dos 215.925 casos de pneumonia adquirida na comunidade notificados nos anos 2017-2019, 64,8% ocorreram na região Andina, 73,9% foram pneumonia bacteriana e 1,8% foram pneumonia viral. A adesão às diretrizes foi observada em 5,8% dos casos. Foi maior para crianças com diagnóstico de pneu- monia viral (86,0%) em comparação com pneumonia bacteriana (2,0%). Para as crianças com diagnóstico de pneumonia bacteriana, 9,4% receberam algum antibiótico. Uma proporção maior de crianças cobertas por pagamentos capitados (22,3%) recebeu tratamento compatível com as diretrizes, contra apenas 1,3% no esquema de pay-for-event. Conclusão. Neste primeiro estudo da Colômbia, a adesão às diretrizes para tratamento ambulatorial de cri- anças com pneumonia bacteriana foi baixa, sendo melhor para pneumonia viral. Mais estudos qualitativos são necessários para explorar as razões dessa falta de adesão e por qual motivo a pneumonia bacteriana foi a etiologia mais comumente notificada.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia

[ABSTRACT]. Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resis- tant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all anti- biotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in commu- nity-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

[RESUMEN]. Objetivo. Evaluar los cambios en la resistencia a los antibióticos de ocho de las combinaciones de fármacos y agentes patógenos incluidos en la lista prioritaria de la Organización Mundial de la Salud y el consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropenem, ciprofloxacina, vancomicina) antes de la pandemia de COVID-19 (de marzo del 2018 a julio del 2019) y durante la pandemia (de marzo del 2020 a julio del 2021) en 31 hospitales del Valle del Cauca (Colombia). Métodos. En este estudio se analiza el antes y el después empleando datos recopilados de forma rutinaria. Para el consumo de antibióticos, se compararon las dosis diarias definidas (DDD) por 100 días-cama. Resultados. Hubo 23 405 cepas bacterianas aisladas prioritarias con datos sobre la resistencia a los antibióti- cos. El número total de cepas aisladas aumentó de 9 774 antes de la pandemia a 13 631 durante la pandemia. Si bien la resistencia disminuyó significativamente en las cuatro combinaciones seleccionadas de agentes patógenos y fármacos (Klebsiella pneumoniae, productora de betalactamasa de espectro extendido [BLEE], de 32% a 24%; K. pneumoniae, resistente a los carbapenémicos, de 4% a 2%; Pseudomonas aeruginosa, resistente a los carbapenémicos, de 12% a 8%; Acinetobacter baumannii, resistente a los carbapenémicos, de 23% a 9%), el nivel de resistencia de Enterococcus faecium a la vancomicina aumentó significativamente (de 42% a 57%). No hubo cambios en la resistencia en las tres combinaciones restantes (Staphylococcus aureus, resistente a la meticilina; Escherichia coli, productora de BLEE; E. coli, resistente a los carbapenémi- cos). El consumo de todos los antibióticos aumentó. Sin embargo, el consumo de meropenem disminuyó en los entornos de las unidades de cuidados intensivos (de 8,2 a 7,1 DDD por 100 días-cama). Conclusiones. Aunque el consumo de antibióticos aumentó, se observó una disminución en la resistencia a los antibióticos de cuatro combinaciones de agentes patógenos y medicamentos durante la pandemia, que posiblemente se debió a un aumento en las infecciones adquiridas en la comunidad. Es necesario vigilar el aumento de la resistencia de E. faecium a la vancomicina. Los resultados de este estudio son esenciales para que sirvan de orientación en los programas de optimización del uso de los antibióticos en los entornos hospitalarios de Colombia y en contextos similares en otros lugares.

[RESUMO]. Objetivo. Avaliar as mudanças na resistência a antibióticos em oito das combinações microrganismo/anti- microbiano prioritárias da Organização Mundial da Saúde e o consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropeném, ciprofloxacino, vancomicina) antes (março de 2018 a julho de 2019) e durante (março de 2020 a julho de 2021) a pandemia de COVID-19 em 31 hospitais em Valle del Cauca, Colômbia. Métodos. Este foi um estudo antes/depois utilizando dados coletados rotineiramente. Para avaliar o consumo de antibióticos, foram comparadas doses diárias definidas (DDD) por 100 leitos-dias. Resultados. Havia dados sobre resistência a antibióticos para 23.405 isolados bacterianos prioritários. O número total de isolados aumentou de 9.774 para 13.631 antes e durante a pandemia, respectivamente. Embora a resistência tenha diminuído significativamente para quatro das combinações microrganismo/antimi- crobiano selecionadas (Klebsiella pneumoniae, produtora de betalactamase de espectro estendido [ESBL], 32% a 24%; K. pneumoniae, resistente a carbapenêmicos, 4% a 2%; Pseudomonas aeruginosa, resistente a carbapenêmicos, 12% a 8%; Acinetobacter baumannii, resistente a carbapenêmicos, 23% a 9%), o nível de resistência de Enterococcus faecium a vancomicina aumentou significativamente (42% a 57%). Não houve mudança na resistência para as três combinações restantes (Staphylococcus aureus, resistente a meticilina; Escherichia coli, produtora de ESBL; E. coli, resistente a carbapenêmicos). O consumo de todos os antibióti- cos aumentou. Entretanto, o consumo de meropeném nas unidades de terapia intensiva diminuiu (de 8,2 para 7,1 DDD por 100 leitos-dias). Conclusões. Embora o consumo de antibióticos tenha aumentado, observou-se uma diminuição na resistên- cia a antibióticos de quatro combinações microrganismo/antimicrobiano durante a pandemia. Isso ocorreu possivelmente devido a um aumento nas infecções adquiridas na comunidade. O aumento da resistência de E. faecium à vancomicina deve ser monitorado. Os achados deste estudo são essenciais para guiar os pro- gramas de gerenciamento de antimicrobianos em ambientes hospitalares da Colômbia e em outros contextos similares.

Efficacy and moderators of short-term psychodynamic psychotherapy for depression: A systematic review and meta-analysis of individual participant data.

BACKGROUND: Short-term psychodynamic psychotherapy (STPP) is frequently used to treat depression, but it is unclear which patients might benefit specifically. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses and identify patient-level moderators. This IPD meta-analysis examined the efficacy and moderators of STPP for depression compared to control conditions. METHODS: PubMed, PsycInfo, Embase, and Cochrane Library were searched September 1st, 2022, to identify randomized trials comparing STPP to control conditions for adults with depression. IPD were requested and analyzed using mixed-effects models. RESULTS: IPD were obtained from 11 of the 13 (84.6%) studies identified (n = 771/837, 92.1%; mean age = 40.8, SD = 13.3; 79.3% female). STPP resulted in significantly lower depressive symptom levels than control conditions at post-treatment (d = -0.62, 95%CI [-0.76, -0.47], p < .001). At post-treatment, STPP was more efficacious for participants with longer rather than shorter current depressive episode durations. CONCLUSIONS: These results support the evidence base of STPP for depression and indicate episode duration as an effect modifier. This moderator finding, however, is observational and requires prospective validation in future large-scale trials.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort.

OBJECTIVES: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. METHODS: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. RESULTS: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS>15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR]=3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR=1.303, CI 1.137-1.493), and with 28-days mortality (OR=1.024, CI 1.006-1.042). LUS>15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS≤7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS>20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). CONCLUSIONS: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS≤7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS>15 would be the point which better discriminates mild from severe disease.

Antifungal Potential of Marine Organisms of the Yucatan Peninsula (Mexico) against Medically Important Candida spp.

Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

Antibiotic resistance and consumption before and during the COVID-19 pandemic in Valle del Cauca, Colombia / Resistencia antibiótica y consumo de antibióticos antes y durante la pandemia de COVID-19 en el Valle del Cauca, Colombia / Resistência a antibióticos e consumo de antibióticos antes e durante a pandemia de COVID-19 no Valle del Cauca, Colômbia

ABSTRACT Objective. To assess changes in antibiotic resistance of eight of the World Health Organization priority bug-drug combinations and consumption of six antibiotics (ceftriaxone, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, vancomycin) before (March 2018 to July 2019) and during (March 2020 to July 2021) the COVID-19 pandemic in 31 hospitals in Valle del Cauca, Colombia. Methods. This was a before/after study using routinely collected data. For antibiotic consumption, daily defined doses (DDD) per 100 bed-days were compared. Results. There were 23 405 priority bacterial isolates with data on antibiotic resistance. The total number of isolates increased from 9 774 to 13 631 in the periods before and during the pandemic, respectively. While resistance significantly decreased for four selected bug-drug combinations (Klebsiella pneumoniae, extended spectrum beta lactamase [ESBL]-producing, 32% to 24%; K. pneumoniae, carbapenem-resistant, 4% to 2%; Pseudomonas aeruginosa, carbapenem-resistant, 12% to 8%; Acinetobacter baumannii, carbapenem-resistant, 23% to 9%), the level of resistance for Enterococcus faecium to vancomycin significantly increased (42% to 57%). There was no change in resistance for the remaining three combinations (Staphylococcus aureus, methicillin-resistant; Escherichia coli, ESBL-producing; E. coli, carbapenem-resistant). Consumption of all antibiotics increased. However, meropenem consumption decreased in intensive care unit settings (8.2 to 7.1 DDD per 100 bed-days). Conclusions. While the consumption of antibiotics increased, a decrease in antibiotic resistance of four bug-drug combinations was observed during the pandemic. This was possibly due to an increase in community-acquired infections. Increasing resistance of E. faecium to vancomycin must be monitored. The findings of this study are essential to inform stewardship programs in hospital settings of Colombia and similar contexts elsewhere.

RESUMEN Objetivo. Evaluar los cambios en la resistencia a los antibióticos de ocho de las combinaciones de fármacos y agentes patógenos incluidos en la lista prioritaria de la Organización Mundial de la Salud y el consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropenem, ciprofloxacina, vancomicina) antes de la pandemia de COVID-19 (de marzo del 2018 a julio del 2019) y durante la pandemia (de marzo del 2020 a julio del 2021) en 31 hospitales del Valle del Cauca (Colombia). Métodos. En este estudio se analiza el antes y el después empleando datos recopilados de forma rutinaria. Para el consumo de antibióticos, se compararon las dosis diarias definidas (DDD) por 100 días-cama. Resultados. Hubo 23 405 cepas bacterianas aisladas prioritarias con datos sobre la resistencia a los antibióticos. El número total de cepas aisladas aumentó de 9 774 antes de la pandemia a 13 631 durante la pandemia. Si bien la resistencia disminuyó significativamente en las cuatro combinaciones seleccionadas de agentes patógenos y fármacos (Klebsiella pneumoniae, productora de betalactamasa de espectro extendido [BLEE], de 32% a 24%; K. pneumoniae, resistente a los carbapenémicos, de 4% a 2%; Pseudomonas aeruginosa, resistente a los carbapenémicos, de 12% a 8%; Acinetobacter baumannii, resistente a los carbapenémicos, de 23% a 9%), el nivel de resistencia de Enterococcus faecium a la vancomicina aumentó significativamente (de 42% a 57%). No hubo cambios en la resistencia en las tres combinaciones restantes (Staphylococcus aureus, resistente a la meticilina; Escherichia coli, productora de BLEE; E. coli, resistente a los carbapenémicos). El consumo de todos los antibióticos aumentó. Sin embargo, el consumo de meropenem disminuyó en los entornos de las unidades de cuidados intensivos (de 8,2 a 7,1 DDD por 100 días-cama). Conclusiones. Aunque el consumo de antibióticos aumentó, se observó una disminución en la resistencia a los antibióticos de cuatro combinaciones de agentes patógenos y medicamentos durante la pandemia, que posiblemente se debió a un aumento en las infecciones adquiridas en la comunidad. Es necesario vigilar el aumento de la resistencia de E. faecium a la vancomicina. Los resultados de este estudio son esenciales para que sirvan de orientación en los programas de optimización del uso de los antibióticos en los entornos hospitalarios de Colombia y en contextos similares en otros lugares.

RESUMO Objetivo. Avaliar as mudanças na resistência a antibióticos em oito das combinações microrganismo/antimicrobiano prioritárias da Organização Mundial da Saúde e o consumo de seis antibióticos (ceftriaxona, cefepima, piperacilina/tazobactam, meropeném, ciprofloxacino, vancomicina) antes (março de 2018 a julho de 2019) e durante (março de 2020 a julho de 2021) a pandemia de COVID-19 em 31 hospitais em Valle del Cauca, Colômbia. Métodos. Este foi um estudo antes/depois utilizando dados coletados rotineiramente. Para avaliar o consumo de antibióticos, foram comparadas doses diárias definidas (DDD) por 100 leitos-dias. Resultados. Havia dados sobre resistência a antibióticos para 23.405 isolados bacterianos prioritários. O número total de isolados aumentou de 9.774 para 13.631 antes e durante a pandemia, respectivamente. Embora a resistência tenha diminuído significativamente para quatro das combinações microrganismo/antimicrobiano selecionadas (Klebsiella pneumoniae, produtora de betalactamase de espectro estendido [ESBL], 32% a 24%; K. pneumoniae, resistente a carbapenêmicos, 4% a 2%; Pseudomonas aeruginosa, resistente a carbapenêmicos, 12% a 8%; Acinetobacter baumannii, resistente a carbapenêmicos, 23% a 9%), o nível de resistência de Enterococcus faecium a vancomicina aumentou significativamente (42% a 57%). Não houve mudança na resistência para as três combinações restantes (Staphylococcus aureus, resistente a meticilina; Escherichia coli, produtora de ESBL; E. coli, resistente a carbapenêmicos). O consumo de todos os antibióticos aumentou. Entretanto, o consumo de meropeném nas unidades de terapia intensiva diminuiu (de 8,2 para 7,1 DDD por 100 leitos-dias). Conclusões. Embora o consumo de antibióticos tenha aumentado, observou-se uma diminuição na resistência a antibióticos de quatro combinações microrganismo/antimicrobiano durante a pandemia. Isso ocorreu possivelmente devido a um aumento nas infecções adquiridas na comunidade. O aumento da resistência de E. faecium à vancomicina deve ser monitorado. Os achados deste estudo são essenciais para guiar os programas de gerenciamento de antimicrobianos em ambientes hospitalares da Colômbia e em outros contextos similares.