Clones de alto risco de Klebsiella pneumoniae produtores de ESBL colonizando pacientes de UTI em Natal, Nordeste do Brasil

Background and objectives: colonization by extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in Intensive Care Unit (ICU) patients is considered a risk factor for infections, and poses as a source of spreading these strains in hospital facilities. This study aimed to perform the genetic characterization of ESBL-producing K. pneumoniae isolates recovered from surveillance swabs in an ICU in northeastern Brazil. Methods: the isolates were recovered between 2018-2019 from the nasal, axillary, and rectal sites of 24 patients admitted to the ICU. Bacterial identification was performed by traditional biochemical tests. Antimicrobial susceptibility was assessed by disk diffusion, and ESBL phenotype was detected by double-disc synergy test. Polymerase chain reaction (PCR) for blaCTX-M, blaSHV, and blaTEM genes, PFGE, and MLST were carried out in representative isolates. Results: a total of 27 isolates were recovered from 18 patients (75%). The ESBL production was detected in 85% of isolates. Resistance to ciprofloxacin, sulfamethoxazole/trimethoprim and most of the β-lactams tested was recurrent, except for carbapenems. The blaSHV, blaTEM, and blaCTX-M genes were found in high frequency, and the CTX-M-(1, 2 and 9) groups were identified. Seven sequence types (ST11, ST14, ST17, ST395, ST709, ST855, and ST3827) were described, most of them considered high-risk. Conclusion: these findings emphasize the potential threat of well-established high-risk clones in an ICU, and highlight the importance of monitoring these clones to prevent infections.Justificación y objetivos: la colonización por Klebsiella pneumoniae productora de β-lactamasas de espectro extendido (BLEE) en pacientes de Unidades de Cuidados Intensivos (UCI) se considera un factor de riesgo para infecciones, y se presenta como una fuente de propagación de estas cepas en instalaciones hospitalarias. Este estudio tuvo como objetivo realizar la caracterización genética de aislamientos de K. pneumoniae productores de BLEE recuperados de hisopos de vigilancia en una UCI en el noreste de Brasil. Métodos: los aislamientos se recuperaron entre 2018-2019 de sitios nasales, axilares y rectales de 24 pacientes ingresados en la UCI. La identificación bacteriana se realizó mediante pruebas bioquímicas tradicionales. La susceptibilidad antimicrobiana se evaluó mediante difusión en disco, y el fenotipo BLEE se detectó mediante la prueba de sinergia de doble-disco. La polymerase chain reaction (PCR) para los genes blaCTX-M, blaSHV y blaTEM, PFGE y MLST se llevaron a cabo en aislamientos representativos. Resultados: se recuperaron 27 aislamientos de 18 pacientes (75%). La producción de ESBL se detectó en 85% de los aislamientos. La resistencia a ciprofloxacino, sulfametoxazol/trimetoprima y a la mayoría de los β-lactámicos evaluados fue recurrente, excepto a los carbapenémicos. Los genes blaSHV, blaTEM y blaCTX-M se encontraron en alta frecuencia, y se identificaron los grupos CTX-M-(1, 2 y 9). Se describieron siete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 y ST3827), la mayoría consideradas de alto riesgo. Conclusión: estos hallazgos enfatizan la amenaza potencial de los clones de alto riesgo bien establecidos en una UCI, y resaltan la importancia de monitorear estos clones para prevenir infecciones.Justificativa e objetivos: a colonização por Klebsiella pneumoniae produtora de β-lactamase de espectro estendido (ESBL) em pacientes de Unidade de Terapia Intensiva (UTI) é considerada um fator de risco para infecções, e representa uma fonte de disseminação dessas cepas em instalações hospitalares. Este estudo objetivou realizar a caracterização genética de isolados de K. pneumoniae produtores de ESBL recuperados de swabs de vigilância em uma UTI no Nordeste do Brasil. Métodos: os isolados foram recuperados entre 2018-2019 dos sítios nasal, axilar e retal de 24 pacientes internados na UTI. A identificação bacteriana foi realizada por testes bioquímicos tradicionais. A suscetibilidade antimicrobiana foi avaliada por disco-difusão, e o fenótipo ESBL foi detectado pelo teste de sinergia de duplo-disco. Polymerase chain reaction (PCR) para os genes blaCTX-M, blaSHV e blaTEM, PFGE e MLST foram realizados em isolados representativos. Resultados: foram recuperados 27 isolados de 18 pacientes (75%). A produção de ESBL foi detectada em 85% dos isolados. A resistência à ciprofloxacina, sulfametoxazol/trimetoprima e à maioria dos β-lactâmicos testados foi recorrente, exceto para os carbapenêmicos. Os genes blaSHV, blaTEM e blaCTX-M foram encontrados em alta frequência, e os grupos CTX-M-(1, 2 e 9) foram identificados. Sete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 e ST3827) foram descritos, a maioria deles considerados de alto risco. Conclusão: esses achados enfatizam a ameaça potencial de clones de alto risco bem estabelecidos em uma UTI, e destacam a importância do monitoramento desses clones para prevenir infecções

Tuberculosis Caused by Mycobacterium tuberculosis Complex in a Captive Tapir (Tapirus terrestris)

Background: Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis complex has already been identified in a great number of wild species. Captive animals may have a potential source for zoonoses, because is related to factors such as cohabitation, direct contact with the public, presence of biological vectors, nutritional deficiencies, absence of sanitary barriers, precautionary hygienic measures and sanitary vigilance. In Brazil, there is little information on tuberculosis in captivity animals, and little attention is given to the risks of disease transmission from humans. The aim of this study was to report the first diagnosed case of tuberculosis Tapirus terrestris in Brazilian Amazon region.Case: One Tapirus terrestris was kept by local zoobotanic foundation in city of Marabá, Southeast of Pará state, Brazilian Amazon, and became ill. Physical examination revealed cough, sneezing, nasal outflow, dyspnea, hyperthermia and lethargy, leading to death. Necropsy demonstrated severe pulmonary alterations: thickening of the inter-alveolar septa, alveolar emphysema, and miliary nodules with dimensions up to 5 mm, which were yellowish-white, caseous, and sometimes calcified. Additionally, large areas of caseous compaction of the parenchyma, characteristic of caseous tuberculosis. Histopathological analysis revealed a process characteristic of mycobacterial infection, with alveoli filled with caseous exudate and thickened septa and fibrocytes, in addition to recently formed tubercles, some with caseous necrosis, calcifications and Langhans cells. In the Ziehl-Neelsen staining, alcohol-acid resistant bacilli were observed in the mesenteric lymph nodes. No mycobacterial growth was observed in Lowenstein-Jensen culture medium. A nested PCR followed by a sequencing assay targeting the hsp65 gene and M. tuberculosis complex member was detected. Water and M. tuberculosis H37Rv were used as negative and positive controls, respectively.Discussion: This article reports the first case of tuberculosis in T. terrestris in Amazonia. The case of infection was caused by a complex of Mycobacterium tuberculosis, as well as reports of other studies described in wild animals. This record presented clinical and pathological similarity with the cases of a tapir and coati at the zoo of Curitiba, and non-human primates in bioteries in Belém. The disease was reported, also, in a T. indicus female in Bangkok, Thailand. In another study with two tapirs there was positivity of tuberculin test result in a Swedish zoo. In necropsy findings of tuberculosis in a Malayan tapir showed multiple white, caseous nodules spread throughout the lungs. Studies have shown that lesions can be in various organs, among them the mediastinal and mesenteric lymph nodes, liver, spleen, kidneys, ovaries, serosa, diaphragm, intestines and uterus. For exemple in a case of disseminated tuberculosis caused by M. tuberculosis in a Malayan tapir were described multiple granulomes, some coalescent, characterized by necrotic caseous centers, with some Langhans giant cells and a discrete fibrotic zone. In the present work, the results of the anatomopathological and molecular assays confirmed the clinical suspicion of respiratory infection and established the conclusive diagnosis of pulmonary tuberculosis caused by M. tuberculosis complex member. It is worth noting that tuberculosis is an important zoonotic disease affecting survival of the species, posing an extinction threat and also a public health concern

Innate immunity to SARS-CoV-2 infection: a review

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância Sanitária. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância Sanitária. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality, which is due to factors such as the subversion of the immune response. The aims of the study are to summarise and present the immunopathological relationship of COVID-19 with innate immunity. This is a systematic review conducted by the National Library of Medicine - National Institutes of Health, USA (PUBMED), Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Scientific Electronic Library Online (SCIELO) databases with clinical trials, in vitro assays, case-controls, cohort studies, systematic reviews and meta-analyses between February 2020 and July 2021. The version 2 of the Cochrane risk-of-bias tool for RCTs (RoB 2), Joana Briggs Institute (JBI) Critical Appraisal (for the review articles) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tools were used to evaluate the quality and the risk of bias of the studies included in this review. The innate immune response through the generation of interferons, alternative pathways and complement system lectins and the joint action of innate immune cells and cytokines and chemokines lead to different clinical outcomes, taking into account the exacerbated inflammatory response and pathogenesis. Then, in addition to interacting as a bridge for adaptive immunity, the innate immune response plays an essential role in primary defense and is one of the starting points for immune evasion by SARS-CoV-2

Surgical site infection following caesarean section by acinetobacter species: a report fr om a hyperendemic setting in the brazilian amazon region

This work was supported by the National Institutes of Health of Brazil (Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde) and Fundação de Amparo à Pesquisa do Pará/Universidade do Estado do Pará (FAPESPA/UEPA) [Cooperation grant Nº004/2019].State University of Pará. Center of Biological and Health Sciences. Parasitic Biology in the Amazon Region. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University Center of Pará. Health Education. Belém, PA, Brazil.State University of Pará. Center of Biological and Health Sciences. Parasitic Biology in the Amazon Region. Belém, PA, Brazil.State University of Pará. Center of Biological and Health Sciences. Parasitic Biology in the Amazon Region. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Surgical site infection (SSI) following caesarean section is associated with increased morbidity, mortality, and significant health care costs. This study evaluated the epidemiological, clinical, and microbiological features of Acinetobacter spp. in women with SSIs who have undergone caesarean section at a referral hospital in the Brazilian Amazon region. This study included 69 women with post-caesarean SSI by Acinetobacter spp. admitted to the hospital between January 2012 and May 2015. The 69 Acinetobacter isolates were subjected to molecular species identification, antimicrobial susceptibility testing, detection of carbapenemase-encoding genes, and genotyping. The main complications of post-caesarean SSI by Acinetobacter were inadequate and prolonged antibiotic therapy, sepsis, prolonged hospitalization, and re-suture procedures. A. baumannii, A. nosocomialis and A. colistiniresistens species were identified among the isolates. Carbapenem resistance was associated with OXA-23-producing A. baumannii isolates and IMP-1-producing A. nosocomialis isolate. Patients with multidrug-resistant A. baumannii infection showed worse clinical courses. Dissemination of persistent epidemic clones was observed, and the main clonal complexes (CC) for A. baumannii were CC231 and CC236 (Oxford scheme) and CC1 and CC15 (Pasteur scheme). This is the first report of a long-term Acinetobacter spp. outbreak in women who underwent caesarean section at a Brazilian hospital. This study demonstrates the impact of multidrug resistance on the clinical course of post-caesarean infections

Genomic analysis of Klebsiella pneumoniae high-risk clone ST11 co-harbouring MCR-1.27 and KPC-2 recovered at a paediatric oncologic hospital in the Brazilian Amazon region

Evandro Chagas Institute (IEC), Secretariat for Science, Technology, Innovation and Strategic Health Inputs (SCTIE), Brazilian Ministry of Health (MS). Yan Corrêa Rodrigues’ scholarship is funded by PDPG - Pós-Doutorado Estratégico (PDPG-POSDOC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/ Edital 16/2022).Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Engenharia Biológica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Engenharia Biológica. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância em Saúde. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância em Saúde. Ananindeua, PA, Brasil.Objectives: The horizontal transfer of antibiotic resistance genes in Gram-negative bacteria, mainly through plasmids, is one of the greatest concerns for health systems worldwide and has been a growing threat in hospitals related to healthcare-associated infections by multidrug-resistant bacteria. Here we present phenotypic and genomic characterization of a KPC-2 and MCR-1.27-producing Klebsiella pneumoniae strain isolated from a paediatric patient at an oncologic hospital in Belém, Pará State, Brazilian Amazon region. Methods: Antibiotic susceptibility test, whole genome sequencing, and in silico analysis were used to characterize the bacterial isolate (IEC48020) received in the Evandro Chagas Institute. Results: The isolate was resistant to carbapenems, colistin, polymyxin B, and several other antimicrobials and was susceptible in vitro just to tigecycline, classified as an extensively drug-resistant phenotype. Genomic analysis revealed IEC48020 strain belonged to sequence type 11, clonal complex 258 high-risk clone and the presence of eight plasmids, two of them harbouring mcr-1.27 and blaKPC-2 genes, and the presence of virulence-related genes encoding yersiniabactin, phospholipase D, and traT genes. Conclusions: The presence and dissemination of high-risk clone bacteria with high disseminating plasmids containing antibiotic resistance genes for last resource antibiotics treatment options is a threat to the healthcare system and demands efforts in surveillance and epidemiological research for better knowledge of the actual situation of antibiotic resistance in the healthcare system, especially in the Amazon region, Brazil

The Spread of NDM-1 and NDM-7-Producing Klebsiella pneumoniae Is Driven by Multiclonal Expansion of High-Risk Clones in Healthcare Institutions in the State of Pará, Brazilian Amazon Region

Carbapenem resistance among Klebsiella pneumoniae isolates is often related to carbapenemase genes, located in genetic transmissible elements, particularly the blaKPC gene, which variants are spread in several countries. Recently, reports of K. pneumoniae isolates harboring the blaNDM gene have increased dramatically along with the dissemination of epidemic high-risk clones (HRCs). In the present study, we report the multiclonal spread of New Delhi metallo-beta-lactamase (NDM)-producing K. pneumoniae in different healthcare institutions in the state of Pará, Northern Brazil. A total of 23 NDM-producing isolates were tested regarding antimicrobial susceptibility testing features, screening of carbapenemase genes, and genotyping by multilocus sequencing typing (MLST). All K. pneumoniae isolates were determined as multidrug-resistant (MDR), being mainly resistant to carbapenems, cephalosporins, and fluoroquinolones. The blaNDM-7 (60.9%—14/23) and blaNDM-1 (34.8%—8/23) variants were detected. MLST genotyping revealed the predomination of HRCs, including ST11/CC258, ST340/CC258, ST15/CC15, ST392/CC147, among others. To conclude, the present study reveals the contribution of HRCs and non-HRCs in the spread of NDM-1 and NDM-7-producing K. pneumoniae isolates in Northern (Amazon region) Brazil, along with the first detection of NDM-7 variant in Latin America and Brazil, highlighting the need for surveillance and control of strains that may negatively impact healthcare and antimicrobial resistance

Clinical and microbiological features of infections caused by Pseudomonas aeruginosa in patients hospitalized in intensive care units

Abstract: INTRODUCTION: The spread of multidrug-resistant Pseudomonas aeruginosa in Brazilian hospitals has greatly impacted upon the morbidity and mortality of individuals in intensive care units. Given the lack of information regarding the dynamics of multidrug resistance in northern Brazil, we analyzed the clinical and microbiological features of nosocomial infections caused by P. aeruginosa. METHODS Between January 2010 and March 2012, we conducted a retrospective cohort study of P. aeruginosa isolates from 54 patients who were hospitalized in intensive care units. The clinical and epidemiologic variables were analyzed, including the patients' demographic data and comorbidities, and the lengths of the intensive care unit stays, the classification of the infections as nosocomial, the use of invasive procedures, antimicrobial therapy, and the patients' outcomes. We undertook susceptibility tests, molecular detection of the metallo-β-lactamase genes, and genotypic analyses of the isolates using the repetitive element-polymerase chain reaction. RESULTS: Multidrug resistance occurred most frequently among isolates from adults who had been hospitalized for an average of 87.1 days. The use of mechanical ventilation and urinary catheters were risk factors for infection. The four isolates that harbored the blaSPM-1-like gene showed >95% genetic similarity. CONCLUSIONS This study's findings show that P. aeruginosa has a high death rate, and that inadequate treatment and invasive procedures are risk factors for infection. This is the first report describing the detection of the blaSPM-1-like gene in northern Brazil. These results highlight the need for better monitoring and a greater understanding of nosocomial infections and their public health impacts

Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: a meta-analysis

Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brasil.Universidade do Estado do Pará. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brasil.Universidade do Estado do Pará. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brasil.Universidade do Estado do Pará. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brasil.Universidade do Estado do Pará. Departamento de Patologia. Belém, PA, Brasil.Universidade do Estado do Pará. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Pseudomonas aeruginosa is the leading cause of nosocomial infections with high mortality rates owing to the limited therapeutic options for multidrug-resistant Pseudomonas aeruginosa (MDRPA) and metallo-beta-lactamase (MBL)-producing strains. Herein, we present a meta-analysis exploring the association between MDRPA and São Paulo MBL-1 (SPM-1)-producing strains vs. mortality. Online databases were screened to identify studies published between 2006 and 2016. A total of 15 studies, comprising 3,201 cases of P. aeruginosa infection, were included. Our results demonstrated a higher mortality rate among patients infected with MDRPA (44.6%, 363/813) than those with non-MDRPA infection (24.8%, 593/2,388) [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.70-3.36, p <0.00001]. The risk of mortality in patients with non-SPM-1 strains was four times higher than that observed in the patients of the SPM-1 group; however, no statistically significant difference was observed (p = 0.43). In conclusion, the results of our study demonstrated that patients infected with MDRPA had a significantly higher mortality rate than that of patients infected with non-MDRPA strains, especially patients with bloodstream infection (BSI), immunosuppression, and inadequate antimicrobial therapy. The absence of studies on the molecular aspects of blaSPM-1 and its association with mortality limited the analysis; therefore, our results should be interpreted with caution. Our findings also highlight the need for more studies on the molecular aspects of resistance and the peculiarities of different nosocomial settings

Association of the polymorphism of the vitamin D receptor gene (VDR) with the risk of leprosy in the Brazilian Amazon

Secretariat of Health Surveillance (SVS), Brazilian Ministry of Health (MS), Evandro Chagas Institute (IEC); Coordination for the Improvement of Higher Education Personnel (CAPES/Brazil) and National Council for Scientific and Technological Development (CNPq/Brazil).State University of Para. Program in Parasitic Biology in the Amazon Region. Belem, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University Center of the State of Para. Belem, PA, Brazil.State University of Para. Program in Parasitic Biology in the Amazon Region. Belem, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.State University of Para. Program in Parasitic Biology in the Amazon Region. Belem, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.State University of Para. Program in Parasitic Biology in the Amazon Region. Belem, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância em Saúde. Ananindeua, PA, Brasil.The transmission and evolution of leprosy depends on several aspects, including immunological and genetic factors of the host, as well as genetic factors of Mycobacterium leprae. The present study evaluated the association of single nucleotide polymorphisms (SNPs) on the FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232) regions of the vitamin D receptor (VDR) gene with leprosy. A total of 405 individuals were evaluated, composed by groups of 100 multibacillary (MB) and 57 paucibacillary (PB) patients, and 248 healthy contacts. Blood samples were collected from patients and contacts. The genotyping was performed by sequencing of the interest regions. The alleles of the studied SNPs, and SNP FokI genotypes, were not associated with leprosy. For the SNP on TaqI region, the relationship between the tt genotype, and for the SNP ApaI, the AA genotype, revealed an association with susceptibility to MB form, while Aa genotype with protection. The extended genotypes AaTT and AaTt of ApaI and TaqI were associated with protection against MB form. Further studies analyzing the expression of the VDR gene and the correlation with its SNPs might help to clarify the role of polymorphisms on the immune response in leprosy