RESUMO
BACKGROUND: We aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains in Estonian hospitals. METHODS: Ninety-two non-duplicated carbapenem- and/or multidrug-resistant P. aeruginosa strains were collected between 27th March 2012 and 30th April 2013. Clinical data of the patients was obtained retrospectively from the medical charts. Clonal relationships of the strains were determined by whole genome sequencing and analyzed by multi-locus sequence typing. The presence of resistance genes and beta-lactamases and their origin was determined. Combined-disk method and PCR was used to evaluate carbapenemase and metallo-beta-lactamase production. RESULTS: Forty-three strains were carbapenem-resistant, 11 were multidrug-resistant and 38 were both carbapenem- and multidrug-resistant. Most strains (54%) were isolated from respiratory secretions and caused an infection (74%). Over half of the patients (57%) were ≥ 65 years old and 85% had ≥1 co-morbidity; 96% had contacts with healthcare and/or had received antimicrobial treatment in the previous 90 days. Clinically relevant beta-lactamases (OXA-101, OXA-2 and GES-5) were found in 12% of strains, 27% of which were located in plasmids. No Ambler class B beta-lactamases were detected. Aminoglycoside modifying enzymes were found in 15% of the strains. OprD was defective in 13% of the strains (all with CR phenotype); carbapenem resistance triggering mutations (F170 L, W277X, S403P) were present in 29% of the strains. Ciprofloxacin resistance correlated well with mutations in topoisomerase genes gyrA (T83I, D87N) and parC (S87 L). Almost all strains (97%) with these mutations showed ciprofloxacin-resistant phenotype. Multi-locus sequence type analysis indicated high diversity at the strain level - 36 different sequence types being detected. Two sequence types (ST108 (n = 23) and ST260 (n = 18)) predominated. Whereas ST108 was associated with localized spread in one hospital and mostly carbapenem-resistant phenotype, ST260 strains occurred in all hospitals, mostly with multi-resistant phenotype and carried different resistance genotype/machinery. CONCLUSIONS: Diverse spread of local rather than international P. aeruginosa strains harboring multiple chromosomal mutations, but not plasmid-mediated Ambler class B beta-lactamases, were found in Estonian hospitals. TRIAL REGISTRATION: This trial was registered retrospectively in ClinicalTrials.gov ( NCT03343119 ).
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Idoso , Ciprofloxacina/uso terapêutico , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Surtos de Doenças , Estônia/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Sequenciamento Completo do Genoma , beta-Lactamases/genéticaRESUMO
A plasmid carrying the colistin resistance gene mcr-1 was isolated from a pig slurry sample in Estonia. The gene was present on a 33,311-bp plasmid of the IncX4 group. mcr-1 is the only antibiotic resistance gene on the plasmid, with the other genes mainly coding for proteins involved in conjugative DNA transfer (taxA, taxB, taxC, trbM, and the pilX operon). The plasmid pESTMCR was present in three phylogenetically very different Escherichia coli strains, suggesting that it has high potential for horizontal transfer.
Assuntos
Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , beta-Lactamases/genética , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Estônia , Fazendas , Feminino , Esterco/microbiologia , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Suínos/microbiologiaRESUMO
BACKGROUND: The aim of our study was to investigate and control an outbreak and identify risk factors for colonization and infection with Serratia marcescens in two departments in Tartu University Hospital. METHODS: The retrospective case-control study was conducted from July 2005 to December 2006. Molecular typing by pulsed field gel electrophoresis was used to confirm the relatedness of Serratia marcescens strains. Samples from the environment and from the hands of personnel were cultured. RESULTS: The outbreak involved 210 patients, 61 (29%) developed an infection, among them 16 were invasive infections. Multivariate analysis identified gestational age, arterial catheter use and antibiotic treatment as independent risk factors for colonization and infection with Serratia marcescens. Molecular typing was performed on 83 Serratia marcescens strains, 81 of them were identical and 2 strains were different. CONCLUSIONS: Given the occasionally severe consequences of Serratia marcescens in infants, early implementation of aggressive infection control measures involving patients and mothers as well as the personnel is of utmost importance.
Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Serratia/epidemiologia , Serratia marcescens/isolamento & purificação , Estudos de Casos e Controles , Infecção Hospitalar/microbiologia , Eletroforese em Gel de Campo Pulsado , Microbiologia Ambiental , Estônia/epidemiologia , Feminino , Mãos/microbiologia , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Tipagem Molecular , Fatores de Risco , Infecções por Serratia/microbiologia , Serratia marcescens/classificação , Serratia marcescens/genéticaRESUMO
In this study, we aimed to characterize the population structure, drug resistance mechanisms, and virulence genes of Enterococcus isolates in Estonia. Sixty-one Enterococcus faecalis and 34 Enterococcus faecium isolates were collected between 2012 and 2014 across the country from various sites and sources, including farm animals and poultry (n = 53), humans (n = 12), environment (n = 24), and wild birds (n = 44). Clonal relationships of the strains were determined by whole-genome sequencing and analyzed by multi-locus sequence typing. We determined the presence of acquired antimicrobial resistance genes and 23S rRNA mutations, virulence genes, and also the plasmid or chromosomal origin of the genes using dedicated DNA sequence analysis tools available and/or homology search against an ad hoc compiled database of relevant sequences. Two E. faecalis isolates from human with vanB genes were highly resistant to vancomycin. Closely related E. faecalis strains were isolated from different host species. This indicates interspecies spread of strains and potential transfer of antibiotic resistance. Genomic context analysis of the resistance genes indicated frequent association with plasmids and mobile genetic elements. Resistance genes are often present in the identical genetic context in strains with diverse origins, suggesting the occurrence of transfer events.
RESUMO
We have attempted to define the prevalence and risk factors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-Enterobacteriaceae) carriage, and to characterize antimicrobial susceptibility, beta-lactamase genes, and major types of isolated strains in volunteers, with a specific focus on humans in contact with animals. Samples were collected from 207 volunteers (veterinarians, pig farmers, dog owners, etc.) and cultured on selective agar. Clonal relationships of the isolated ESBL-Enterobacteriaceae were determined by whole genome sequencing and multi-locus sequence typing. Beta-lactamases were detected using a homology search. Subjects filled in questionnaires analyzed by univariate and multiple logistic regression. Colonization with ESBL-Enterobacteriaceae was found in fecal samples of 14 individuals (6.8%; 95%CI: 3.75-11.09%). In multiple regression analysis, working as a pig farmer was a significant risk factor for ESBL-Enterobacteriaceae carriage (OR 4.8; 95%CI 1.2-19.1). The only species isolated was Escherichia coli that distributed into 11 sequence types. All ESBL-Enterobacteriaceae isolates were of CTX-M genotype, with the blaCTX-M-1 being the most prevalent and more common in pig farmers than in other groups. Despite the generally low prevalence of ESBL-Enterobacteriaceae in Estonia, the pig farmers may still pose a threat to transfer resistant microorganisms. The clinical relevance of predominant blaCTX-M-1 carrying E. coli is still unclear and needs further studies.
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Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.
Assuntos
Antivirais , Desenvolvimento de Medicamentos , Descoberta de Drogas , Animais , Antivirais/uso terapêutico , Humanos , Viroses/tratamento farmacológicoRESUMO
With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010â»2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region.
Assuntos
Temperatura Baixa , Aquecimento Global , Influenza Humana/epidemiologia , Orthomyxoviridae/efeitos da radiação , Raios Ultravioleta , Linhagem Celular , Sobrevivência Celular , Células Cultivadas , Europa (Continente)/epidemiologia , Humanos , Umidade , Macrófagos/virologia , Noruega/epidemiologia , Suécia/epidemiologia , VentoRESUMO
According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.
Assuntos
Antivirais/farmacologia , Vírus de DNA/efeitos dos fármacos , Vírus de RNA/efeitos dos fármacos , Viroses/tratamento farmacológico , Reposicionamento de Medicamentos , HumanosRESUMO
Wohlfahrtiimonas chitiniclastica is a rare human pathogen mostly associated with parasitic flies. This is the report on W. chitiniclastica infection in the soft tissue and bone at a 58°N latitude in the northern temperate climate zone. The importance of correct identification of clinically relevant bacteria is highlighted.
Assuntos
Infecções por Bactérias Gram-Negativas/microbiologia , Osteomielite/microbiologia , Infecções dos Tecidos Moles/microbiologia , Xanthomonadaceae/isolamento & purificação , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Estônia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Infecções dos Tecidos Moles/complicações , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Xanthomonadaceae/classificaçãoRESUMO
Sepsis caused by multidrug-resistant microorganisms is one of the most serious infectious diseases of childhood and poses significant challenges for pediatricians involved in management of critically ill children. This review discusses the use of pharmacokinetic/dynamic principles (i.e., prolonged infusion of ß-lactams and vancomycin, once-daily administration of aminoglycosides and rationale of therapeutic drug monitoring) when prescribing antibiotics to critically ill patients. The potential of 'old' agents (i.e., colistin, fosfomycin) and newly approved antibiotics is critically reviewed. The pros and cons of combination antibacterial therapy are discussed and finally suggestions for the treatment of sepsis caused by multidrug-resistant organisms are provided.