The cefazolin inoculum effect is associated with increased mortality in methicillin-susceptible staphylococcus aureus bacteremia

Background. Recent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated. Methods. We prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates. Results. A total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10-6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage. Conclusions. In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.Fil: Goss, William Miller. University of Texas; Estados UnidosFil: Seas, Carlos. Universidad Peruana Cayetano Heredia; PerúFil: Carvajal, Lina P.. Universidad El Bosque; ColombiaFil: Diaz, Lorena. Universidad El Bosque; Colombia. UTHealth McGovern Medical School; Estados UnidosFil: Echeverri, Aura M.. Universidad El Bosque; ColombiaFil: Ferro, Carolina. Universidad El Bosque; ColombiaFil: Rios, Rafael. Universidad El Bosque; ColombiaFil: Porras, Paola. Universidad El Bosque; ColombiaFil: Luna, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gotuzzo, Eduardo. Universidad Peruana Cayetano Heredia; PerúFil: Munita, Jose M.. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Carcamo, Cesar. Universidad Peruana Cayetano Heredia; PerúFil: Reyes, Jinnethe. Universidad El Bosque; ColombiaFil: Arias, Cesar A.. University of Texas; Estados Unido

ATIVIDADE LEISHMANICIDA in vitro DE FRAÇÕES DO EXTRATO HIDROALCOÓLICO DAS FOLHAS DE Chenopodium ambrosioides L.

A leishmaniose é uma doença infecciosa causada por protozoários do gênero Leishmania e representa sério problema de saúde pública em paises da África, Ásia e América Latina. Chenopodium ambrosioides L.,  popularmente conhecido como mastruz, tem sido utilizado no Maranhão para o tratamento tópico de úlceras leishmanióticas. O trabalho avaliou a eficácia das frações do extrato hidroalcoólico das folhas de C. ambrosioides contra formas promastigotas da espécie Leishmania amazonensis. O fracionamento foi realizado pela partição sequencial do extrato hidroalcoólico de folhas de C. ambrosioides com solventes de polaridade crescente (hexano, clorofórmio e acetato de etila). As formas promastigotas foram cultivadas em meio RPMI 1640 com e sem as frações. Após 24h de incubação a 26ºC, o número de promastigotas viáveis foi contado pelo método direto em câmara de Neubauer. As concentrações que inibem o crescimento de 50% (CI50 ) das promastigotas de L. amazonensis foram calculadas a partir da avaliação da mortalidade das promastigotas in vitro. De acordo com escores padrões nas frações de acetato de etila e hidroalcoólica remanescente não foi observada atividade leishmanicida significativa, mas as frações hexânica e clorofórmica apresentaram-se ativas. Os resultados obtidos demonstram uma ação leishmanicida promissora das frações. Estudos futuros são necessários para investigar a eficácia destas frações no tratamento da leishmaniose em modelos experimentais in vivo.Descritores: Chenopodium ambrosioides L.; Mastruz; Leishmaniose; in vitro. Abstract:  In vitro leishmanicidal activity of fractions obtained from hydroalcoholic extracts of  Chenopodium ambrosioides’  leaves. Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania and represents serious public health problem in Africa, Asia and Latin America. Chenopodium ambrosioides, popularly known as “mastruz”, has been used in Maranhão for the topical treatment of leishmanial ulcers. The study evaluated the effectiveness of the fractions from hydroalcoholic extract of C. ambrosioides’  leaves against the promastigotes of Leishmania amazonensis. Fractionation as accomplished by partition sequential extract of leaves of C. ambrosioides with solvents of increasing polarity (hexane, chloroform and ethyl acetate). The promastigotes forms were cultured in supplemented RPMI 1640 with or without fractions. After 24h incubation at 26°C, the number of viable promastigotes was counted by the direct method in a Neubauer chamber. The concentrations that inhibit growth of 50% (IC50 ) of L. amazonensis’ promastigotes were calculated from the assessment of the mortality of promastigotes in vitro. According to standard scores, in the ethyl acetate and hydroalcoholic remaining fractions there was no leishmanicidal activity, while the hexane and chloroform fractions were actives. The results showed a promissor leishmanicidal activity of fraction. Future studies are necessary to investigate the effectiveness of these fractions in the treatment of these fractions in experimental models in vivo.Descriptors: Chenopodium ambrosioides L.; Mastruz; Leishmaniasis; in vitro

Estimating mortality and disability in Peru before the COVID-19 pandemic: a systematic analysis from the Global Burden of the Disease Study 2019

"Background: Estimating and analyzing trends and patterns of health loss are essential to promote efficient resource allocation and improve Peru’s healthcare system performance. Methods: Using estimates from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study (2019), we assessed mortality and disability in Peru from 1990 to 2019. We report demographic and epidemiologic trends in terms of population, life expectancy at birth (LE), mortality, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by the major diseases and risk factors in Peru. Finally, we compared Peru with 16 countries in the Latin American (LA) region. Results: The Peruvian population reached 33.9 million inhabitants (49.9% women) in 2019. From 1990 to 2019, LE at birth increased from 69.2 (95% uncertainty interval 67.8–70.3) to 80.3 (77.2–83.2) years. This increase was driven by the decline in under-5 mortality (−80.7%) and mortality from infectious diseases in older age groups (+60 years old). The number of DALYs in 1990 was 9.2 million (8.5–10.1) and reached 7.5 million (6.1–9.0) in 2019. The proportion of DALYs due to non-communicable diseases (NCDs) increased from 38.2% in 1990 to 67.9% in 2019. The all-ages and age-standardized DALYs rates and YLLs rates decreased, but YLDs rates remained constant. In 2019, the leading causes of DALYs were neonatal disorders, lower respiratory infections (LRIs), ischemic heart disease, road injuries, and low back pain. The leading risk factors associated with DALYs in 2019 were undernutrition, high body mass index, high fasting plasma glucose, and air pollution. Before the COVID-19 pandemic, Peru experienced one of the highest LRIs-DALYs rates in the LA region. Conclusion: In the last three decades, Peru experienced significant improvements in LE and child survival and an increase in the burden of NCDs and associated disability. The Peruvian healthcare system must be redesigned to respond to this epidemiological transition. The new design should aim to reduce premature deaths and maintain healthy longevity, focusing on effective coverage and treatment of NCDs and reducing and managing the related disability.

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran\u27s eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R$^{2}$ = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R$^{2}$ = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions

Estimating the global conservation status of more than 15,000 Amazonian tree species

Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict thatmost of the world’s >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Aim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

AimAmazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.LocationAmazonia.TaxonAngiosperms (Magnoliids; Monocots; Eudicots).MethodsData for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.ResultsIn the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.Main ConclusionNumerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions