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1.
Sci Rep ; 10(1): 18580, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122675

RESUMO

Surveillance data from Southern Ontario show that a majority of Verona Integron-encoded Metallo-ß-lactamase (VIM)-producing Enterobacteriaceae are locally acquired. To better understand the local epidemiology, we analysed clinical and environmental blaVIM-positive Enterobacteriaceae from the area. Clinical samples were collected within the Toronto Invasive Bacterial Diseases Network (2010-2016); environmental water samples were collected in 2015. We gathered patient information on place of residence and hospital admissions prior to the diagnosis. Patients with and without plausible source of acquisition were compared regarding risk exposures. Microbiological isolates underwent whole-genome sequencing (WGS); blaVIM carrying plasmids were characterized. We identified 15 patients, thereof 11 with blaVIM-1-positive Enterobacter hormaechei within two genetic clusters based on WGS. Whereas no obvious epidemiologic link was identified among cluster I patients, those in cluster II were connected to a hospital outbreak. Except for patients with probable acquisition abroad, we did not identify any further risk exposures. Two blaVIM-1-positive E. hormaechei from environmental waters matched with the clinical clusters; plasmid sequencing suggested a common ancestor plasmid for the two clusters. These data show that both clonal spread and horizontal gene transfer are drivers of the dissemination of blaVIM-1-carrying Enterobacter hormaechei in hospitals and the aquatic environment in Southern Ontario, Canada.


Assuntos
Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Estudos de Casos e Controles , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Ontário/epidemiologia , Sequenciamento Completo do Genoma , beta-Lactamases/genética , beta-Lactamases/metabolismo
2.
Malays J Pathol ; 41(2): 139-148, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31427549

RESUMO

INTRODUCTION: OXA-48, a carbapenem-hydrolysing class D ß-lactamase, and its variant, OXA-181, are increasingly reported worldwide. This study aimed to describe the prevalence and distribution of OXA-48 and OXA-181 carbapenem-resistant Enterobacteriaceae (CRE) in a tertiary medical centre in Malaysia. MATERIALS & METHODS: A total of 13,098 Enterobacteriaceae isolates from various clinical samples were sent to our laboratory between January 2011 and December 2012. Of these, 90 demonstrated reduced susceptibility to at least one carbapenem and were included in this study. Only 88 isolates were successfully subcultured on blood agar (BA). Another 2 isolates failed to grow and were excluded. Of the 88, 2 isolates had the same identification number (repetitive isolates); therefore, 1 isolate was excluded from further analyses. Only 87 isolates were subjected to molecular detection of the blaOXA-48 and blaOXA-181 genes by polymerase chain reaction. RESULTS: Eighty-seven non-repetitive isolates grew following subculture on BA. Of these, 9 (10.34%) were positive for OXA-48 (7 Klebsiella pneumoniae, 2 Escherichia coli). Each isolate originated from different patients. All patients had a history of treatment with at least one cephalosporin and/or carbapenem prior to the isolation of OXA-48 CRE. OXA-181 was detected in one (1.15%) out of the 87 isolates; CONCLUSIONS: The prevalence of OXA-48 and OXA-181 CRE among all Enterobacteriaceae isolates in our institution is 0.069% and 0.008%, respectively. Nevertheless, our findings suggest that OXA-48 and OXA-181 carbapenemases appear to be important and possibly under-recognised causes of carbapenem resistance in Malaysia.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecções por Enterobacteriaceae/genética , beta-Lactamases/genética , Adolescente , Adulto , Proteínas de Bactérias/genética , Estudos Transversais , Infecções por Enterobacteriaceae/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Braz J Infect Dis ; 23(2): 102-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028724

RESUMO

Enterobacteria-producing extended-spectrum ß-lactamases (ESBL) play an important role in healthcare infections, increasing hospitalization time, morbidity and mortality rates. Among several ESBLs that emerge from these pathogens, CTX-M-type enzymes had the most successful global spread in different epidemiological settings. Latin America presents high prevalence of CTX-M-2 in ESBL-producing enterobacterial infections with local emergence of the CTX-M-1 group. However, this high prevalence of the CTX-M-1 group has not yet been reported in Chile. The aim of this study was to identify ESBLs among enterobacteria isolated from clinical samples of critically ill patients from southern Chile. One-hundred thirty seven ESBL-producing bacteria were isolated from outpatients from all critical patient units from Hernán Henríquez Aravena Hospital. Phenotype characterization was performed by antibiogram, screening of ESBL, and determination of minimum inhibitory concentration (MIC). PCR was used for genetic confirmation of resistance. Molecular typing was performed by ERIC-PCR. ESBL-producing isolates were identified as Klebsiella pneumoniae (n=115), Escherichia coli (n=18), Proteus mirabilis (n=3), and Enterobacter cloacae (n=1), presenting multidrug resistance profiles. PCR amplification showed that the strains were positive for blaSHV (n=111/81%), blaCTX-M-1 (n=116/84.7%), blaTEM (n=100/73%), blaCTX-M-2 (n=28/20.4%), blaCTX-M-9 (0.7%), blaPER-1 (0.7%), and blaGES-10 (0.7%). The multiple production of ESBL was observed in 93% of isolates, suggesting high genetic mobility independent of the clonal relationship. The high frequency of the CTX-M-1 group and a high rate of ESBL co-production are changing the epidemiology of the ESBL profile in Chilean intensive care units. This epidemiology is a constant and increasing challenge, not only in Chile, but worldwide.


Assuntos
Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Unidades de Terapia Intensiva/estatística & dados numéricos , beta-Lactamases/genética , Antibacterianos/farmacologia , Chile/epidemiologia , DNA Bacteriano , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Técnicas de Genotipagem , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Prevalência , Valores de Referência , Fatores de Risco , beta-Lactamases/isolamento & purificação
4.
Braz. j. infect. dis ; 23(2): 102-110, Mar.-Apr. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011579

RESUMO

ABSTRACT Enterobacteria-producing extended-spectrum β-lactamases (ESBL) play an important role in healthcare infections, increasing hospitalization time, morbidity and mortality rates. Among several ESBLs that emerge from these pathogens, CTX-M-type enzymes had the most successful global spread in different epidemiological settings. Latin America presents high prevalence of CTX-M-2 in ESBL-producing enterobacterial infections with local emergence of the CTX-M-1 group. However, this high prevalence of the CTX-M-1 group has not yet been reported in Chile. The aim of this study was to identify ESBLs among enterobacteria isolated from clinical samples of critically ill patients from southern Chile. One-hundred thirty seven ESBL-producing bacteria were isolated from outpatients from all critical patient units from Hernán Henríquez Aravena Hospital. Phenotype characterization was performed by antibiogram, screening of ESBL, and determination of minimum inhibitory concentration (MIC). PCR was used for genetic confirmation of resistance. Molecular typing was performed by ERIC-PCR. ESBL-producing isolates were identified as Klebsiella pneumoniae (n = 115), Escherichia coli (n = 18), Proteus mirabilis (n = 3), and Enterobacter cloacae (n = 1), presenting multidrug resistance profiles. PCR amplification showed that the strains were positive for blaSHV (n = 111/81%), blaCTX-M-1 (n = 116/84.7%), blaTEM (n = 100/73%), blaCTX-M-2 (n = 28/20.4%), blaCTX-M-9 (0.7%), blaPER-1 (0.7%), and blaGES-10 (0.7%). The multiple production of ESBL was observed in 93% of isolates, suggesting high genetic mobility independent of the clonal relationship. The high frequency of the CTX-M-1 group and a high rate of ESBL co-production are changing the epidemiology of the ESBL profile in Chilean intensive care units. This epidemiology is a constant and increasing challenge, not only in Chile, but worldwide.


Assuntos
Humanos , beta-Lactamases/genética , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Valores de Referência , beta-Lactamases/isolamento & purificação , DNA Bacteriano , Testes de Sensibilidade Microbiana , Chile/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Técnicas de Genotipagem , Antibacterianos/farmacologia
5.
BMC Res Notes ; 11(1): 624, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157960

RESUMO

OBJECTIVE: Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae infection is an emerging problem in paediatric populations leading to increased mortality. The purpose of this study was to determine the prevalence, risk factors and clinical outcomes of ESBL-producing Enterobacteriaceae in paediatric blood stream infections (BSIs). A retrospective review of paediatric patients diagnosed with Enterobacteriaceae bacteremia was performed at Phramongkutklao Hospital from 2010 to 2017. RESULTS: Among 97 non-duplicated blood isolates, the prevalence of ESBL-producing Enterobacteriaceae was 53.6% (28.9% Escherichia coli and 25.8% Klebsiella spp. isolates). The study indicated that the prevalence of ESBL infection was higher among patients with chronic illness, especially hematologic malignancies, than among patients without underlying disease (P = 0.01). No differences were observed in the prior use of any antibiotics, the use of extended-spectrum cephalosporin, neutropaenia or the presence of an indwelling central venous catheter. Mortality in the ESBL group was significantly higher than that in the non-ESBL group, with observed mortalities of 38.9% and 13.3%, respectively (P < 0.05). In conclusion, BSIs with ESBL-producing Enterobacteriaceae tended to increase infection rates and impact survival rates among paediatric patients.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , beta-Lactamases/metabolismo , Criança , Pré-Escolar , Enterobacteriaceae , Infecções por Enterobacteriaceae/enzimologia , Escherichia coli/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Klebsiella/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Tailândia , Resultado do Tratamento
6.
Infect Immun ; 86(9)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986890

RESUMO

Bacteria utilize type III secretion systems (T3SS) to deliver effectors directly into host cells. Hence, it is very important to identify the functions of bacterial (T3SS) effectors to understand host-pathogen interactions. Edwardsiella piscicida encodes a functional T3SS effector, EseK, which can be translocated into host cells and affect bacterial loads. Here, it was demonstrated that an eseK mutant (the ΔeseK mutant) significantly increased the phosphorylation levels of p38α, c-Jun NH2-terminal kinases (JNK), and extracellular signal-regulated protein kinases 1/2 (ERK1/2) in HeLa cells. Overexpression of EseK directly inhibited mitogen-activated protein kinase (MAPK) signaling pathways in HEK293T cells. The ΔeseK mutant consistently promoted the phosphorylation of MAPKs in zebrafish larva infection models. Further, it was shown that the ΔeseK mutant increased the expression of tumor necrosis factor alpha (TNF-α) in an MAPK-dependent manner. Importantly, the EseK-mediated inhibition of MAPKs in vivo attenuated bacterial clearance in larvae. Taken together, this work reveals that the E. piscicida T3SS effector EseK promotes bacterial infection by inhibiting MAPK activation, which provides insights into the molecular pathogenesis of E. piscicida in fish.


Assuntos
Infecções por Enterobacteriaceae/enzimologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Sistemas de Secreção Tipo III/metabolismo , Peixe-Zebra/microbiologia , Animais , Edwardsiella , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Larva/microbiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Fosforilação , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Sistemas de Secreção Tipo III/genética
7.
Actas urol. esp ; 42(3): 170-175, abr. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-172868

RESUMO

Objetivos: Analizar las infecciones por enterobacterias productoras de carbapenemasas (EPC) y describir características y posibles factores de riesgo asociados con los pacientes de un servicio de urología. Material y métodos: Estudio observacional y retrospectivo. El criterio de inclusión fue haber estado ingresado en nuestro servicio de urología entre agosto de 2013 y diciembre de 2016. Se analizaron aquellos que presentaron positividad para EPC en al menos un cultivo. Se revisaron características basales y factores de riesgo. Asimismo se revisaron variables como presencia de infecciones urinarias previas, reingresos posteriores, el microorganismo, tipo de EPC, tratamiento administrado, un origen hospitalario o comunitario y la mortalidad. Resultados: De los 5.657 pacientes que cumplían criterio de inclusión, en 12 casos se aisló una EPC. Las infecciones por EPC representaron un 3,6% del total de infecciones relacionadas con la asistencia sanitaria y un 9,7% de las producidas por enterobacterias. Los factores analizados asociados a infección por EPC en nuestra serie son: presencia de catéteres urinarios (100%), haber sido sometido a tratamiento quirúrgico (58,3%), ingreso previo en UCI (8,3%) e inmunosupresión (16,6%). Con relación a la mortalidad, un 8,3% de los pacientes que presentaron infección por EPC fallecieron durante el ingreso. Conclusiones: Aproximadamente un 10% de las enterobacterias presenta patrón de resistencia a carbapenemasas en el paciente urológico de nuestro medio. Ser portador de catéter urinario y/o someterse a una cirugía son factores de riesgo asociados al desarrollo de estas infecciones en el paciente urológico de nuestro medio. La infección por una EPC eleva la morbimortalidad


Objectives: To analyse infections by carbapenemase-producing enterobacteriaceae (CPE) and describe the characteristics and potential risk factors associated with patients of a department of urology. Material and methods: Observational and retrospective study. The inclusion criterion was hospitalisation in our department of Urology between August 2013 and December 2016. We analysed those patients who were positive for CPE in at least 1 culture. We reviewed their baseline characteristics, risk factors and variables such as the presence of previous urinary tract infections, subsequent readmissions, the microorganism, type of CPE, treatment, origin (hospital or community) and mortality. Results: Of the 5,657 patients who met the inclusion criterion, a CPE was isolated in 12 cases. CPE infections represented 3.6% of all healthcare-associated infections and 9.7% of those caused by enterobacteria. The analysed factors associated with CPE infection in our series were the presence of urinary catheters (100%), undergoing surgery (58.3%), previous ICU admission (8.3%) and immunosuppression (16.6%). In terms of mortality, 8.3% of the patients who presented CPE infection died during hospitalisation. Conclusions: Approximately 10% of enterobacteria present a carbapenemase-resistance pattern in urological patients in our setting. Carrying a urinary catheter and/or undergoing surgery are risk factors associated with the development of these infections in urological patients in our setting. CPE infections increase morbidity and mortality


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fatores de Risco , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/enzimologia , Infecções Relacionadas a Cateter/enzimologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Estudos Retrospectivos , Indicadores de Morbimortalidade , Infecções Relacionadas a Cateter/epidemiologia
8.
Rev Esp Quimioter ; 30(6): 458-463, 2017 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-29141402

RESUMO

OBJECTIVE: In Spain, the overall prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing. We describe the epidemiological, clinical and microbiological characteristics features of patients with colonization or infection due to CRE in two hospitals in the north-west of Madrid during two years. One hospital was a community acute hospital and the second one was a non-acute rehabilitation hospital. METHODS: A total of 197 CPE isolates were detected during 2013-2014. Microbiological, epidemiological and clinical data were collected, since the first isolate was found in March 2013. RESULTS: A 33.5% of patients with CRE had symptomatic infection and the remaining 66.5% were colonizations. Klebsiella pneumoniae (87.8%) was the most prevalent species and OXA-48 the most frequent carbapenemase (91.9%). We found intra-interhospital spread and some differences in the epidemiology of CRE depending on the hospital, such as more genetic variability in the non-acute rehabilitation hospital. CONCLUSIONS: Studying the CRE transmission we founded an increased incidence in a short period of time and a rapid dissemination of strains between both hospitals. This highlights the need to standardize screening measures for potential carriers and infection control programs in our hospitals.


Assuntos
Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Doença Aguda , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Feminino , Hospitais Comunitários/estatística & dados numéricos , Humanos , Incidência , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Centros de Reabilitação , Fatores Sexuais , Espanha/epidemiologia , beta-Lactamases/genética
9.
Rev Esp Quimioter ; 30(6): 450-457, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29115369

RESUMO

OBJECTIVE: The aim of this study is to know epidemiologic and clinical differences among those patients colonized or infected by carbapenemase-producing Enterobacteriaceae (CPE) and develop a predictive model to facilitate the clinical approach concerning to start antimicrobial therapy. METHODS: Observational retrospective cohort study was performed involving all patients with Urine carbapenemase-producing Enterobacteriaceae isolation (UCPEI) between November 2013 and July 2015. Patients were classifieds as colonized or infected considering Center for Disease Control and Prevention (CDC) definition for urinary tract infection (UTI). RESULTS: A total of 72 patients were included, mean age 76.4 (IQR 23-99) years and 40 (55.6%) were women. Thirty-four (47.2%) were colonized and 38 (52.8%) met the criteria of UTI and were considered infected. The independent variables associated to infection were female sex, peripheral vascular disease, admission in medical ward, permanent urinary catheter carrier, previous antimicrobial therapy, and length of stay. Isolation of OXA-48 carbapenemase-producing Enterobacteriaceae behaved as a non UTI (colonization) factor in comparison with KPC or VIM CPE. The developed predictive model showed an area under the curve (AUC) of 0.901 (95% CI: 0.832-0.970; p < 0.001). CONCLUSIONS: The predictive model that includes all this factors has demonstrated a good accuracy for infection diagnosis in these patients, an important issue considering that establishing the diagnosis of infection is not always easy in the profile of patients in which a CPE is isolated.


Assuntos
Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/urina , Infecções Urinárias/enzimologia , Infecções Urinárias/urina , beta-Lactamases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Contagem de Colônia Microbiana , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Infecções Urinárias/diagnóstico , Doenças Vasculares/complicações , Doenças Vasculares/epidemiologia , Adulto Jovem
10.
J Chemother ; 29(6): 344-350, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28486840

RESUMO

We aimed to characterize carbapenem-resistant isolates in a tertiary hospital in Istanbul, Turkey, high-prevelance area for OXA-48 producers. About 76 Enterobacteriaceae clinical isolates were included. Carbapenemase production was detected by Carbapenem Inactivation Method and carbapenemase genes were investigated by PCR. The clonal relationships were evaluated by AP-PCR. Nineteen Klebsiella pneumoniae isolates were colistin resistant. About 75 isolates yielded carbapenemase by CIM. 52 OXA-48, 17 NDM-1 and 2 VIM-5 carbapenemase genes were detected. Co-production of 'OXA-48 and NDM-1' and 'OXA-48 and VIM-5' were demonstrated in two Klebsiella pneumoniae isolates. The total clustering rate was 20.2%. About 69 Klebsiella pneumoniae yielded 60 profiles and 12 isolates formed five clusters. We have demonstrated the presence of OXA-48 carbapenemases in the majority of isolates in a large collection of carbapenemase-producing isolates from a single hospital. The relatively high rates of NDM-1-producing isolates and colistin resistance is noteworthy.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Resistência Microbiana a Medicamentos/fisiologia , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Adolescente , Adulto , Idoso , Proteínas de Bactérias/biossíntese , Carbapenêmicos , Criança , Pré-Escolar , Colistina , Doenças Endêmicas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Turquia/epidemiologia , Adulto Jovem , beta-Lactamases/biossíntese
11.
J Chemother ; 29(3): 150-153, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27347714

RESUMO

The increase in carbapenem-resistant gram-negative bacteria is a matter of concern due to the limited therapeutic options available. In severe infections caused by these isolates, the rapid detection of the mechanisms of resistance is vital. We described a slightly modified version of the Blue-Carba test, rapid Blue-Carba test, which allows the detection of carbapenemases at 4 h of incubation from a haze of bacterial growth obtained from a positive blood culture. It was able to detect carbapenemase-producing isolates (Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii) with a sensitivity and specificity of 98.1 and 100%, respectively. It is a rapid, easy-to-perform and an inexpensive technique that can be applied to routine laboratories, together with the simultaneous identification by mass spectrometry which would help to screen non-enzymatic carbapenem resistance; this method allows the detection of clinically relevant multidrug-resistant bacteria and the early implementation of accurate therapeutic interventions.


Assuntos
Infecções por Acinetobacter/enzimologia , Bacteriemia/enzimologia , Proteínas de Bactérias/sangue , Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae/enzimologia , Infecções por Pseudomonas/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/sangue , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/crescimento & desenvolvimento , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Argentina , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Carbapenêmicos/metabolismo , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/crescimento & desenvolvimento , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Hospitais Universitários , Humanos , Inativação Metabólica , Tipagem Molecular , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/isolamento & purificação , Sensibilidade e Especificidade , Fatores de Tempo , beta-Lactamases/genética
12.
Afr Health Sci ; 16(1): 153-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27358627

RESUMO

BACKGROUND: The emergence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases is rare. We report an occurrence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases in a Chinese tertiary care hospital from November 2010 to December 2012. METHODS: The clinical characteristics of 30 patients were described. The genetic relationship of isolates was determined by pulsed-field gel electrophoresis (PFGE). Carbapenemases were detected by modified Hodge test (MHT) and polymerase chain reactions (PCRs). Amplicons were sequenced and blasted to determine the genotype. RESULTS: Most infected patients were from intensive care unit and had complex and serious underlying illnesses requiring mechanical ventilation. PFGE revealed that Klebsiella pneumoniae showed two major PFGE types. Two Klebsiella oxytoca had an indistinguishable PFGE pattern, while four Enterobacter cloacae were different strains. The sequencing studies showed Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in the 23 infected patients. The majority of patients had infections with the carbapenemase-producing Enterobacteriaceae (CPE) strain, most were successfully treated with a range of antibiotics and discharged. CONCLUSION: It is important to maintain a high index of suspicion to screen for carbapenemase-producing Enterobacteriaceae strains. Rapid identification of these strains and implementation of stringent procedures are the key to prevent major outbreaks in a hospital setting.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Infecções por Enterobacteriaceae/enzimologia , Enterobacteriaceae/enzimologia , beta-Lactamases/isolamento & purificação , Adulto , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pré-Escolar , China/epidemiologia , Eletroforese em Gel de Campo Pulsado , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/genética , Feminino , Humanos , Recém-Nascido , Klebsiella/enzimologia , Klebsiella/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Centros de Atenção Terciária
13.
J Biol Chem ; 291(35): 18232-8, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27387501

RESUMO

Interferon signaling plays important roles in both intestinal homeostasis and in the host response to pathogen infection. The extent to which bacterial pathogens inhibit this host pathway is an understudied area of investigation. We characterized Citrobacter rodentium strains bearing deletions in individual type III secretion system effector genes to determine whether this pathogen inhibits the host type I IFN response and which effector is responsible. The NleB effector limited host IFN-ß production by inhibiting Lys(63)-linked ubiquitination of TNF receptor-associated factor 3 (TRAF3). Inhibition was dependent on the glycosyltransferase activity of NleB. GAPDH, a target of NleB during infection, bound to TRAF3 and was required for maximal TRAF3 ubiquitination. NleB glycosyltransferase activity inhibited GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination. Collectively, our data reveal important interplay between GAPDH and TRAF3 and suggest a mechanism by which the NleB effector inhibits type I IFN signaling.


Assuntos
Proteínas de Bactérias , Citrobacter rodentium , Infecções por Enterobacteriaceae , Glicosiltransferases , Interferon Tipo I/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Fatores de Virulência , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Citrobacter rodentium/enzimologia , Citrobacter rodentium/genética , Citrobacter rodentium/patogenicidade , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/genética , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Células HeLa , Humanos , Ubiquitinação , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
14.
Cell Host Microbe ; 19(5): 651-63, 2016 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-27173933

RESUMO

NOX/DUOX family of NADPH oxidases are expressed in diverse tissues and are the primary enzymes for the generation of reactive oxygen species (ROS). The intestinal epithelium expresses NOX1, NOX4, and DUOX2, whose functions are not well understood. To address this, we generated mice with complete or epithelium-restricted deficiency in the obligatory NOX dimerization partner Cyba (p22(phox)). We discovered that NOX1 regulates DUOX2 expression in the intestinal epithelium, which magnified the epithelial ROS-deficiency. Unexpectedly, epithelial deficiency of Cyba resulted in protection from C. rodentium and L. monocytogenes infection. Microbiota analysis linked epithelial Cyba deficiency to an enrichment of H2O2-producing bacterial strains in the gut. In particular, elevated levels of lactobacilli physically displaced and attenuated C. rodentium virulence by H2O2-mediated suppression of the virulence-associated LEE pathogenicity island. This transmissible compensatory adaptation relied on environmental factors, an important consideration for prevention and therapy of enteric disease.


Assuntos
Citrobacter rodentium/metabolismo , Infecções por Enterobacteriaceae/enzimologia , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/enzimologia , Mucosa Intestinal/microbiologia , NADPH Oxidases/metabolismo , Animais , Disbiose , Infecções por Enterobacteriaceae/microbiologia , Doença Granulomatosa Crônica/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lactobacillus , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/deficiência , Espécies Reativas de Oxigênio/metabolismo , Simbiose
15.
J Perinatol ; 35(11): 907-12, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26507147

RESUMO

OBJECTIVE: To study (i) the prevalence and risk factors for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant women, (ii) the maternal-neonatal transmission rate of ESBL-E at birth and (iii) the prevalence of ESBL-E in expressed breast milk of colonized mothers. STUDY DESIGN: In this cross-sectional, population-based study with case follow-up on maternal-neonatal transmission of ESBL-E, women were screened for rectal ESBL-E colonization at 36 weeks of pregnancy and delivery. Possible risk factors for colonization were studied by logistic regression. Infants of ESBL-E-positive mothers were screened for ESBL-E during their first weeks of life. ESBL-encoding genes were detected by PCR and clonal relatedness was investigated by pulsed-field gel electrophoreses. RESULTS: In total, 26 out of 901 (2.9%) women were colonized by ESBL-producing Escherichia coli at 36 weeks of pregnancy. One of the women carried an additional ESBL Klebsiella pneumoniae strain. Adjusted for traveling, African or Asian nationality was a risk factor for colonization; OR=5.62 (2.21, 14.27) (LR-p=0.003). Fourteen women remained ESBL-E carriers at delivery. ESBL-E strains indistinguishable from the strains isolated from their respective mothers were detected in 5 (35.7%) infants during their first days of life (median day 3; range=2 to 8). A total of 146 expressed milk samples were cultured from 25 out of 26 colonized mothers, all were ESBL-E negative. CONCLUSIONS: The prevalence of ESBL-E carriage among pregnant women was low in our region, but the high maternal-neonatal transmission rate suggests that colonized mothers represent a substantial risk for infant colonization.


Assuntos
Infecções por Enterobacteriaceae/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/diagnóstico , Diagnóstico Pré-Natal , beta-Lactamases/metabolismo , Adulto , Portador Sadio/epidemiologia , Estudos Transversais , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/enzimologia , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Noruega/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Terceiro Trimestre da Gravidez , Prevalência , Medição de Risco
16.
Antimicrob Agents Chemother ; 59(11): 7080-3, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282410

RESUMO

Carbapenem-resistant Enterobacteriaceae carrying New Delhi metallo-ß-lactamase 1 (NDM-1) have rarely been reported in Latin America. We report of an outbreak caused by a blaNDM-1-harboring plasmid spread through different bacterial species, including Escherichia coli (ST617) and Enterobacter cloacae (ST182) isolates from the same patient and three Klebsiella pneumoniae isolates (ST22) derived from three epidemiologically related patients. IncFII plasmids were found in all strains. Measures to control the outbreak were applied successfully.


Assuntos
Enterobacteriaceae/enzimologia , Enterobacteriaceae/fisiologia , Plasmídeos/genética , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Surtos de Doenças , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/enzimologia , Feminino , Genótipo , Humanos , Masculino , México , Atenção Terciária à Saúde , beta-Lactamases/genética
17.
PLoS One ; 10(6): e0131372, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26110660

RESUMO

To establish the role of local transmission versus possible pathogen import due to previous foreign exposure in infections caused by carbapenem non-susceptible Enterobacteriaceae in the Arabian Peninsula, 200 independent isolates collected in 16 hospitals of Saudi Arabia, Kuwait, Oman and the United Arab Emirates were studied. All strains were multidrug resistant; 42.5% of them also qualified as extremely drug resistant. The frequency of various carbapenemases varied according to the participating countries, but in the collection, as a whole, blaNDM-1 was the most frequently encountered carbapenemase gene (46.5%) followed by blaOXA-48-like gene (32.5%). A comparatively high rate (8.9%) of multi-clonal strains carrying both blaNDM and blaOXA-48-like genes in the United Arab Emirates, representing the most resistant subgroup, was encountered. No KPC-expressing isolates were detected. Three major clones of blaNDM-1 carrying Klebsiella pneumoniae of ST152 (n = 22, Saudi Arabia), ST14 (n = 7, United Arab Emirates) and ST147 types (n = 9, Oman) were identified, the latter two clones carrying similar, but not identical HI1b incompatibility type plasmids of >170 kb. While from 78.6% of the cases with documented foreign hospitalization blaNDM positive strains were isolated, these strains formed only 25.6% of all the isolates expressing this enzyme. In fact, 56.8% of the NDM, 75.7% of OXA-48-like and 90.9% of VIM positive strains were recovered from patients without documented foreign exposure, neither in the form of travel or prior hospitalization abroad, suggesting a high rate of autochthonous infections. This, considering the extensive links of these countries to the rest of the world, predicts that trends in the local epidemiology of carbapenem resistant strains may increasingly affect the spread of these pathogens on the global scale. These results call for improved surveillance of carbapenem resistant Enterobacteriaceae in the countries of the Arabian Peninsula.


Assuntos
Proteínas de Bactérias , Carbapenêmicos , Infecções por Enterobacteriaceae , Enterobacteriaceae , Resistência beta-Lactâmica , beta-Lactamases , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/transmissão , Feminino , Humanos , Masculino , Oriente Médio , beta-Lactamases/genética , beta-Lactamases/metabolismo
18.
Gene ; 570(1): 122-31, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26055087

RESUMO

The thioredoxin (Trx) system plays a significant role in cellular antioxidative defense by dismutating the surpluses of reactive oxygen species. Thus, the role of thioredoxin reductase (TrxR) cannot be ignored, owing to its participation in initiating the Trx enzyme cascade. Here, we report the identification and molecular characterization of a teleostean TrxR (RbTrxR-3) ortholog that showed high similarity with the TrxR-3 isoforms of other vertebrates. The complete RbTrxR-3 coding sequence comprised 1800 nucleotides, encoding a 600-amino acid protein with a predicted molecular mass of ~66 kDa. RbTrxR-3 consisted of 16 exons separated by 15 introns and had a total length of 12,658 bp. In silico analysis of the RbTrxR-3 protein sequence revealed that it possesses typical TrxR domain architecture. Moreover, using multiple sequence alignment and pairwise sequence alignment strategies, we showed that RbTrxR-3 has high overall sequence similarity to other teleostean TrxR-3 proteins, including highly conserved active site residues. Phylogenetic reconstruction of RbTrxR-3 affirmed its close evolutionary relationship with fish TrxR-3 orthologs, as indicated by its clustering pattern. RbTrxR-3 transcriptional analysis, performed using quantitative polymerase chain reaction (qPCR), showed that RbTrxR-3 was ubiquitously distributed, with the highest level of mRNA expression in the blood, followed by the gill, and liver. Live bacterial and viral stimuli triggered the modulation of RbTrxR-3 basal transcription in liver tissues that correlated temporally with that of its putative substrate, rock bream thioredoxin1 under the same conditions of pathogenic stress. Finally, resembling the typical function of TrxR protein, purified recombinant RbTrxR-3 showed detectable dose-dependent thiol reductase activity against 5,5'-dithiobis (2-nitrobenzoic) acid. Taken together, these results suggest that RbTrxR-3 plays a role in the host Trx system under conditions of oxidative and pathogenic stress.


Assuntos
Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/enzimologia , Proteínas de Peixes/genética , Peixes/genética , Tiorredoxina Dissulfeto Redutase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Edwardsiella tarda/imunologia , Infecções por Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/imunologia , Doenças dos Peixes/sangue , Doenças dos Peixes/microbiologia , Proteínas de Peixes/biossíntese , Peixes/imunologia , Peixes/microbiologia , Regulação Enzimológica da Expressão Gênica , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , Alinhamento de Sequência , Estresse Fisiológico , Tiorredoxina Dissulfeto Redutase/biossíntese
19.
Am J Obstet Gynecol ; 213(5): 650-2, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25771212

RESUMO

Extended-spectrum ß-lactamases (ESBLs) are rapidly evolving plasmid transferrable enzymes that confer unique patterns of antibiotic resistance on various bacterial species. Such organisms pose special challenges to laboratory identification, as well as antibiotic selection, administration, and follow-up. Although such infections are increasingly common in the obstetric population, issues surrounding ESBLs are not widely recognized by practicing obstetricians, and controversies exist regarding diagnosis and management. This article provides the practitioner with a summary of clinically pertinent information that will assist in the proper care of pregnant patients with ESBL infection.


Assuntos
Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/enzimologia , Infecções por Escherichia coli/enzimologia , Complicações Infecciosas na Gravidez/enzimologia , beta-Lactamases/metabolismo , Adulto , Cefalosporinas/uso terapêutico , Feminino , Humanos , Testes de Sensibilidade Microbiana , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/enzimologia
20.
J Intern Med ; 277(5): 501-12, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25556628

RESUMO

The prevalence of carbapenem-resistant Gram-negative bacilli is on the rise worldwide, posing a major public health threat. Previously, this was mostly a problem in Pseudomonas and Acinetobacter, but during the last decade, carbapenem resistance has escalated in medically important species such as Klebsiella pneumoniae and Escherichia coli. In particular, the rising trend in E. coli is of concern, as this may lead to almost untreatable community-acquired infections. Resistance is conferred by carbapenemases, which are beta-lactamases that can breakdown essentially all beta-lactams. Moreover, bacteria carrying these resistance determinants are often resistant to other treatment options, due to the frequent co-acquisition of non-beta-lactam resistance genes located on the same mobile genetic elements. The detection of carbapenemase-producing Enterobacteriaceae (CPE) is a challenge, because some carbapenemases produce relatively discrete levels of carbapenem resistance. Current clinical evidence for treatment guidance is limited and based on retrospective observational studies and case reports. Existing data support the use of combination therapy for treatment of severe infections caused by CPE. Combination regimens including colistin, carbapenems, tigecycline, aminoglycosides and fosfomycin have been used. Randomized controlled studies of combination regimens are ongoing and may help to determine the optimal therapy. Novel beta-lactamase inhibitors may also have a role in future treatment of these infections. Strict infection control measures including isolation or cohort care of affected patients as well as contact tracing and active screening are needed to curb the spread of CPE. In this review, we provide a clinical perspective on the management of patients infected or colonized with CPE.


Assuntos
Proteínas de Bactérias/biossíntese , Infecções por Enterobacteriaceae/prevenção & controle , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/biossíntese , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/enzimologia , Saúde Global , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/enzimologia , Infecções por Klebsiella/prevenção & controle , Klebsiella pneumoniae
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