RESUMO
The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections.
RESUMO
A pandemia da Covid-19 trouxe enfrentamentos e adaptações ao estilo de vida dos indivíduos, necessitando de estratégias para prevenção da doença, com o isolamento e distanciamento social, o que incluiu o trabalho remoto (TR) e adaptação da rotina e estrutura ocupacional. Esta nova dinâmica repercutiu em impacto biopsicossocial, diminuindo o rendimento durante o trabalho, e gerando agravos físicos, psicológicos e emocionais. Diante deste contexto, faz-se necessário investigar recursos que minimizem estes impactos. Investigou-se o uso das Práticas Integrativas e Complementares em Saúde PICS como recurso de enfrentamento à pandemia da Covid-19 por trabalhadores em atividade remota. Tratou-se de um estudo transversal, realizado por meio da aplicação de um questionário, via ferramenta Google Forms, para indivíduos acima de 18 anos que /estiveram em atividades ocupacionais remotas por pelo menos 3 meses durante a pandemia da Covid-19. Participaram do estudo 186 indivíduos de 20 a 70 anos selecionados aleatoriamente por convite em redes sociais, sendo que estes deveriam preencher os critérios de inclusão e poderiam pertencer a diferentes setores de trabalho. Sobre o impacto da pandemia na saúde, a maioria (40,32%) sentiu de forma "razoável", enquanto o impacto do TR sobre a saúde foi relatado por 37,63% como "não prejudicial". 66,67% dos participantes não praticavam nenhuma PICS antes da pandemia. Destes, 20,91% iniciaram alguma prática durante o isolamento, 78,26% faziam mais de uma modalidade e 21,74% apenas uma. Os motivos relatados para o início da prática foram: dores e/ou lesões ortopédicas, ansiedade e estresse. As práticas mais realizadas foram: meditação (14,5%) e yoga (10,22%). Para quem iniciou alguma prática, a importância em relação à saúde, foi considerada muito importante para 65,22% e quando questionados sobre a utilização das PICS, como estratégia de enfrentamento da pandemia, foi considerado muito importante por 47,83%. Conclui-se que as PICS foram recursos considerados importantes para a saúde e procurados para o enfrentamento da pandemia Covid-19, por trabalhadores em TR, sendo meditação e yoga as terapias mais utilizadas.
The Covid-19 pandemic brought challenges and adaptations to individuals' lifestyles, requiring strategies to prevent the disease, with isolation and social distancing, which included remote work (RW) and adaptation of the routine and occupational structure. This new dynamic had a biopsychosocial impact, reducing performance during work and generating physical, psychological and emotional problems. Given this context, it is necessary to investigate resources that minimize these impacts. The use of Integrative and Complementary Health Practices ICHP was investigated as a resource to combat the Covid-19 pandemic by workers in remote activities. This was a cross-sectional study, carried out by applying a questionnaire, via the Google Forms tool, to individuals over 18 years of age who had been in remote occupational activities for at least 3 months during the Covid-19 pandemic. 186 individuals aged 20 to 70 years old, randomly selected by invitation on social networks, participated in the study, and they had to meet the inclusion criteria and could belong to different work sectors. Regarding the impact of the pandemic on health, the majority (40.32%) felt it was "reasonable", while the impact of RW on health was reported by 37.63% as "not harmful". 66.67% of participants did not practice any ICHP before the pandemic. Of these, 20.91% started some practice during isolation, 78.26% did more than one modality and 21.74% only one. The reasons reported for starting the practice were: pain and/or orthopedic injuries, anxiety and stress. The most common practices were: meditation (14.5%) and yoga (10.22%). For those who started some practice, the importance in relation to health was considered very important by 65.22% and when asked about the use of ICHP, as a strategy to face the pandemic, it was considered very important by 47.83%. It is concluded that PICS were resources considered important for health and sought after to combat the Covid-19 pandemic, by workers in RT, with meditation and yoga being the most used therapies.
RESUMO
Pediatric liver transplantation (PLTx) is commonly associated with extensive antibiotic treatments that can produce gut microbiome alterations and open the way to dominance by multidrug-resistant organisms (MDROs). In this study, the relationship between intestinal Relative Loads (RLs) of ß-lactamase genes, antibiotic consumption, microbiome disruption, and the extraintestinal dissemination of MDROs among PLTx patients is investigated. 28 PLTx patients were included, from whom 169 rectal swabs were collected. Total DNA was extracted and blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were quantified via quantitative polymerase chain reaction (qPCR) and normalized to the total bacterial load (16SrRNA) through LogΔΔCt to determine the RLs. 16SrRNA sequencing was performed for 18 samples, and metagenomic sequencing was performed for 2. Patients' clinical data were retrieved from the hospital's database. At least one of the genes tested were detected in all of the patients. The RLs for blaCTX-M-1-Family, blaOXA-1, blaOXA-48, and blaVIM were higher than 1% of the total bacterial population in 67 (80.73%), 56 (78.87%), 57 (77.03%) and 39 (61.9%) samples, respectively. High RLs for blaCTX-M-1-Family, blaOXA-1, and/or blaOXA-48, were positively associated with the consumption of carbapenems with trimethoprim-sulfamethoxazole and coincided with low diversity in the gut microbiome. Low RLs were associated with the consumption of noncarbapenem ß-lactams with aminoglycosides (P < 0.05). Extraintestinal isolates harboring the same gene(s) as those detected intraintestinally were found in 18 samples, and the RLs of the respective swabs were high. We demonstrated a relationship between the consumption of carbapenems with trimethoprim-sulfamethoxazole, intestinal dominance by MDROs and extraintestinal spread of these organisms among PLTx patients. IMPORTANCE In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients. Moreover, the high loads of resistance genes were related to the extraintestinal spread of multidrug-resistant organisms. Together, our data show that the tracking of the relative intestinal loads of antibiotic resistance genes can be used as a biomarker that has the potential to stop the extraintestinal spread of antibiotic-resistant bacteria via the measurement of the intestinal dominance of these organisms, thereby allowing for the application of preventive measures.
Assuntos
Farmacorresistência Bacteriana Múltipla , Transplante de Fígado , Humanos , Criança , Farmacorresistência Bacteriana Múltipla/genética , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , beta-Lactamases/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Bactérias Gram-Negativas , Testes de Sensibilidade MicrobianaRESUMO
It is widely accepted that the majority of cancers result from multiple cellular events leading to malignancy after a prolonged period of clinical latency, and that the immune system plays a critical role in the control of cancer progression. Bovine leukemia virus (BLV) is an oncogenic member of the Retroviridae family. Complete genomic sequences of BLV strains isolated from peripheral blood mononuclear cells (PBMC) from cattle have been previously reported. However, a detailed characterization of the complete genome of BLV strains directly isolated from bovine tumors is much needed in order to contribute to the understanding of the mechanisms of leukemogenesis induced by BLV in cattle. In this study, we performed a molecular characterization of BLV complete genomes from bovine B-cell lymphosarcoma isolates. A nucleotide substitution was found in the glucocorticoid response element (GRE) site of the 5' long terminal repeat (5'LTR) of the BLV isolates. All amino acid substitutions in Tax previously found to be related to stimulate high transcriptional activity of 5'LTR were not found in these studies. Amino acid substitutions were found in the nucleocapsid, gp51 and G4 proteins. Premature stop-codons in R3 were observed. Few mutations or amino acid substitutions may be needed to allow BLV provirus to achieve silencing. Substitutions that favor suppression of viral expression in malignant B cells might be a strategy to circumvent effective immune attack.
Assuntos
Leucose Enzoótica Bovina/virologia , Genoma Viral , Vírus da Leucemia Bovina/genética , Linfoma de Células B/veterinária , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Vírus da Leucemia Bovina/química , Vírus da Leucemia Bovina/metabolismo , Linfoma de Células B/virologia , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/veterinária , Alinhamento de Sequência/veterináriaRESUMO
A human respiratory syncytial virus (HRSV) neutralization escape mutant was obtained after 56 serial passages in the presence of a polyclonal antiserum raised against the F protein. Nucleotide sequence analysis of this escape mutant virus revealed two amino acid substitutions: Asn268Ile and Val533Met. When this virus was allowed to grow in the absence of the anti-F polyclonal serum, only the mutation Asn268Ile was stably maintained. Both the double and single escape mutant viruses lost reactivity with mAbs belonging to antigenic site II of the fusion protein of RSV. Mutation Asn268Ile has already been reported in RS viruses that are resistant to mAbs 47F and 11 and palivizumab (PZ). We have thus identified a novel mutation (Val533Met) in the transmembrane domain of the F protein that was selected under immune pressure.
Assuntos
Anticorpos Antivirais/imunologia , Evasão da Resposta Imune , Mutação de Sentido Incorreto , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/genética , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/imunologia , Motivos de Aminoácidos , Células Hep G2 , Humanos , Testes de Neutralização , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Proteínas Virais de Fusão/químicaRESUMO
Herpes simplex virus type-1 (HSV-1) amplicon vectors are versatile and useful tools for transferring genes into cells that are capable of stimulating a specific immune response to their expressed antigens. In this work, two HSV-1-derived amplicon vectors were generated. One of these expressed the full-length glycoprotein D (gD) of bovine herpesvirus 1 while the second expressed the truncated form of gD (gDtr) which lacked the trans-membrane region. After evaluating gD expression in the infected cells, the ability of both vectors to induce a specific gD immune response was tested in BALB/c mice that were intramuscularly immunized. Specific serum antibody responses were detected in mice inoculated with both vectors, and the response against truncated gD was higher than the response against full-length gD. These results reinforce previous findings that HSV-1 amplicon vectors can potentially deliver antigens to animals and highlight the prospective use of these vectors for treating infectious bovine rhinotracheitis disease.
Assuntos
Vetores Genéticos/imunologia , Herpesvirus Bovino 1/imunologia , Herpesvirus Humano 1/imunologia , Rinotraqueíte Infecciosa Bovina/imunologia , Proteínas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Western Blotting/veterinária , Bovinos , Feminino , Herpesvirus Bovino 1/genética , Herpesvirus Humano 1/genética , Imunidade Humoral/imunologia , Imunização/métodos , Imunização/veterinária , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Rinotraqueíte Infecciosa Bovina/virologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização/veterinária , Organismos Livres de Patógenos Específicos , Proteínas Virais/genética , Vacinas Virais/imunologiaRESUMO
Serologic and genetic analyses indicate that a Juquitiba-like hantavirus circulates in Maldonado, Uruguay. This virus is carried by 2 rodent species, Oligoryzomys nigripes and Oxymycterus nasutus. The same hantavirus in 2 nonrelated species can be explained by a spillover infection or a host-switching event.
Assuntos
Orthohantavírus/classificação , Orthohantavírus/isolamento & purificação , Roedores/virologia , Animais , Orthohantavírus/genética , Síndrome Pulmonar por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/virologia , Filogenia , Uruguai/epidemiologiaRESUMO
Outbreaks of human respiratory syncytial virus (HRSV) are the leading cause of serious acute lower respiratory viral disease in many countries in different continents. Data on clinical and epidemiological aspects of HRSV infections in this country have been reported, but there is lack of data regarding the molecular epidemiology of this virus in Salvador. The genetic variability of HRSV isolated during an outbreak in Salvador, Brazil (1999) has been analysed. Partial sequences of the G protein gene of 13 isolates from antigenic group A and 4 isolates from antigenic group B of HRSV were determined. Nucleotide sequences of C-terminal G gene were compared to sequences of HRSV isolates from countries of South America and from the rest of the world available at the GenBank. Brazilian group A and B isolates were clustered into previously characterised genotypes: GA5, GA2, GA7, and GB3, SAB3, respectively. This is the first study of GA7 and SAB3 genotypes circulation in South American countries. It is interesting to point out that viruses isolated in Salvador appear to be closer related with those from Montevideo-Uruguay and Buenos Aires, Argentina strains, suggesting circulation of similar strains among different South American countries in different seasons. Moreover, viruses closely related genetically circulated in the same year in Salvador and distant places such as Mozambique, supporting the previous suggestion on the complexity of HRSV strain circulation patterns, and the high capability of HRSV spreading world-wide.
Assuntos
Variação Genética , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/isolamento & purificação , Antígenos Virais/análise , Brasil/epidemiologia , Pré-Escolar , Genes Virais , Genótipo , Geografia , Humanos , Lactente , Recém-Nascido , Epidemiologia Molecular , Dados de Sequência Molecular , Nasofaringe/virologia , Filogenia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/imunologia , Análise de Sequência , Proteínas Virais/genéticaRESUMO
During 5,230 trapping nights, 672 small mammals were trapped in the areas where most hantavirus pulmonary syndrome (HPS) cases occur in Uruguay. Yellow pygmy rice rats (Oligoryzomys flavescens) were the only rodents that showed evidence of antibodies to hantavirus, with a seroprevalence of 2.6%. The rodents were trapped in all the explored environments, and most of the seropositive rodents were found in habitats frequented by humans. Nucleotide sequences were obtained from four HPS case-patients and four yellow pygmy rice rats of the M genome segment. Sequence comparison and phylogenetic analysis showed that rodent-borne viruses and viruses from three HPS case-patients form a well-supported clade and share a 96.4% identity with the previously characterized Central Plata hantavirus. These results suggest that yellow pygmy rice rat (O. flavescens) may be the host for Central Plata, a hantavirus associated with HPS in the southern area of Uruguay.