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1.
Bratisl Lek Listy ; 120(12): 935-940, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31855054

RESUMEN

OBJECTIVES: We focused on detecting the most frequent resistance mechanisms in selected multidrug-resistant (MDR) strains and determining their antimicrobial resistance. BACKGROUND: MDR pathogens pose urgent public health threat due to limited treatment options, rigorous control measures and significant mortality. METHODS: We confirmed extended-spectrum ß-lactamase (ESBL) and carbapenemase producing Enterobacteriaceae through guidelines, as well following ß-lactamases: AmpC by cloxacillin, class A carbapenemase with phenylboronic acid, class B metallo-ß-lactamase with ethylenediaminetetraacetic acid. Multilocus sequence typing was used to investigate 20 Escherichia coli strains. RESULTS: Overall 205 mostly ESBL Escherichia coli demonstrated resistance against amikacin (4.7 %), tigecycline (1.2 %), and no resistance to ceftazidime/avibactam, meropenem, nitrofurantoin and fosfomycin. Out of 41 Klebsiella species (spp.), 37 (90.2 %) showed carbapenemase activity, 13 (35.1 %) of class A and 24 (64.9 %) of class B. Resistance was following: meropenem 66.7 %, tigecyclin 10.2 % and colistin 0 %. From Enterobacter spp. 21 strains, 14 (66.7 %) were ESBL, 5 produced ESBL and/or AmpC and 2 were MDR. We ascertained 14 (70 %) E. coli sequence type - ST131. CONCLUSIONS: The study revealed various resistance mechanisms in concert with different agents and association of specific ST131 within E. coli. These characteristics considerably contribute to emergence of antimicrobial resistance (Tab. 4, Ref. 30).


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae/enzimología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Klebsiella pneumoniae/efectos de los fármacos , beta-Lactamasas/metabolismo , Adulto , Anciano , Proteínas Bacterianas/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/enzimología , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Farmacorresistencia Bacteriana , Enterobacteriaceae/clasificación , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , beta-Lactamasas/genética
2.
BMC Infect Dis ; 19(1): 979, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752702

RESUMEN

BACKGROUND: Fluoroquinolones are commonly recommended as treatment for urinary tract infections (UTIs). The development of resistance to these agents, particularly in gram-negative microorganisms complicates treatment of infections caused by these organisms. This study aimed to investigate antimicrobial resistance of different Enterobacteriaceae species isolated from hospital- acquired and community-acquired UTIs against fluoroquinolones and correlate its levels with the existing genetic mechanisms of resistance. METHODS: A total of 440 Enterobacteriaceae isolates recovered from UTIs were tested for antimicrobial susceptibility. Plasmid-mediated quinolone resistance (PMQR) genes and mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were examined in quinolone-resistant strains. RESULTS: About (32.5%) of isolates were resistant to quinolones and (20.5%) were resistant to fluoroquinolones. All isolates with high and intermediate resistance phenotypes harbored one or more PMQR genes. QnrB was the most frequent gene (62.9%) of resistant isolates. Co-carriage of 2 PMQR genes was detected in isolates (46.9%) with high resistance to ciprofloxacin (CIP) (MICs > 128 µg/mL), while co-carriage of 3 PMQR genes was detected in (6.3%) of resistant isolates (MICs > 512 µg/mL). Carriage of one gene only was detected in intermediate resistance isolates (MICs of CIP = 1.5-2 µg/mL). Neither qnrA nor qnrC genes were detected. The mutation at code 83 of gyrA was the most frequent followed by Ser80-Ile in parC gene, while Asp-87 Asn mutation of gyrA gene was the least, where it was detected only in high resistant E. coli isolates (MIC ≥128 µg/mL). A double mutation in gyrA (Lys154Arg and Ser171Ala) was observed in high FQs resistant isolates (MIC of CIP < 128 µg/mL). CONCLUSION: FQs resistance is caused by interact between PMQR genes and mutations in both gyrA and parC genes while a mutation in one gene only can explain quinolone resistance. Accumulation of PMQR genes and QRDR mutations confers high resistance to FQs.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/genética , Quinolonas/farmacología , Infecciones Urinarias/microbiología , Adulto , Proteínas Bacterianas/metabolismo , Ciprofloxacino/farmacología , Enterobacteriaceae/clasificación , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/aislamiento & purificación , Femenino , Fluoroquinolonas/farmacología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Plásmidos/genética , Plásmidos/metabolismo , Adulto Joven
3.
Medicine (Baltimore) ; 98(39): e17339, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31574872

RESUMEN

INTRODUCTION: During the past decade, the rate of carbapenem resistance among Enterobacteriaceae, mostly in Escherichia coli and Klebsiella pneumoniae, has significantly increased worldwide. It is a great challenge for the choice of drug treatment especially in children.Tigecycline is the first drug in the glycylcycline class of antibiotics. For children, the China Food and Drug Administration and US Food and Drug Administration postulated that tigecycline is not recommended. It must be used only as salvage therapy for life-threatening infections in critically ill children who have no alternative treatment options. PATIENT CONCERNS: A male pediatric case of 4.5 months was blood stream infection after liver transplantation. The blood cultures obtained grew Gram-negative rods, which reportedly grew a strain of extended-spectrum ß-lactamase and carbapenemases-producing Escherichia coli within 10 hours. All bacterial isolates were found to be resistant to all antimicrobial agents except aminoglycosides and tigecycline. DIAGNOSES: Complicated intra-abdominal infection, central line-associated blood stream infection. INTERVENTIONS: The blood stream infection with carbapenem-resistant Escherichia coli after liver transplantation was cured by tigecycline. OUTCOMES: The patient's condition continued to improve, then transferred to general ward. CONCLUSION: The following report, to our knowledge, is the youngest liver transplantation patient who used tigecycline treatment around the world. It provides reference and experience for the use of tigecycline in infants with severe infections.


Asunto(s)
Antibacterianos/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Complicaciones Posoperatorias/tratamiento farmacológico , Tigeciclina/uso terapéutico , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Escherichia coli/microbiología , Humanos , Lactante , Trasplante de Hígado/efectos adversos , Masculino , Complicaciones Posoperatorias/microbiología
4.
Environ Pollut ; 255(Pt 1): 113143, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31541827

RESUMEN

Environmental reservoirs of antibiotic resistance (AR) are a growing concern that are gathering more attention as potential sources for human infection. Carbapenem-resistant Enterobacteriaceae (CRE) are extremely dangerous, as carbapenems are often drugs of last resort that are used to treat multi-drug resistant infections. Among the genes capable of conferring carbapenem resistance to bacteria, the most transferrable are those that produce carbapenemase, an enzyme that hydrolyzes carbapenems and other ß-lactam antibiotics. The goal of this review was to comprehensively identify global environmental reservoirs of carbapenemase-producing genes, as well as identify potential routes of transmission to humans. The genes of interest were Klebsiella pneumoniae carbapenemase (KPC), New Delhi Metallo-ß-lactamase (NDM), Oxacillinase-48-type carbapenemases (OXA-48), and Verona Integron-Mediated Metallo-ß-lactamase (VIM). Carbapenemase genes have been reported in the environment on almost every continent. Hospital and municipal wastewater, drinking water, natural waterways, sediments, recreational waters, companion animals, wildlife, agricultural environments, food animals, and retail food products were identified as current reservoirs of carbapenemase-producing bacteria and genes. Humans have been recorded as carrying CRE, without recent admittance to a hospital or long-term care facility in France, Egypt, and China. CRE infections from the environment have been reported in patients in Montpellier, France and Cairo, Egypt. This review demonstrates the need for 1) comprehensive monitoring of AR not only in waterways, but also other types of environmental matrices, such as aerosol, dusts, periphyton, and surfaces in indoor environments; and 2) action to reduce the prevalence and mitigate the effects of these potentially deadly resistance genes. In order to develop an accurate quantitative model for environmental dimensions of AR, longitudinal sampling and quantification of AR genes and bacteria are needed, using a One Health approach.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana/genética , Enterobacteriaceae/efectos de los fármacos , beta-Lactamasas/genética , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/transmisión , Genes Bacterianos , Salud Global , Humanos
5.
Ann Agric Environ Med ; 26(3): 405-408, 2019 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-31559794

RESUMEN

INTRODUCTION: Carbapenemase-producing Enterobacteriaceae have spread rapidly through the countries and continents to become a global concern. One of the main reservoirs of NDM-1 positive strains from the Enterobacteriaceae family is the Indian subcontinent (Bangladesh, Pakistan, India). MATERIAL AND METHODS: During June 2017 - June 2018, rectal swab samples were collected routinely in all patients returning to Poland from South and South-East Asia. During molecular examinations gene blaNDM-1 encoding NDM-1 carbapenemase was detected. RESULTS: 31 patients were examined after returning to Poland from a trip to South and South-East Asia. The presence of New Delhi Metallo-ß-lactamase-1 producing Escherichia coli and Klebsiella pneumoniae was confirmed in three patients (9.7%) returning to Poland from travels to India. All the positive patients were hospitalized during the trip in a New Delhi hospital. CONCLUSIONS: Digestive tract carriage of NDM in a group of Polish travelers is a significant health and epidemiological problem. The study confirms the necessity for screening for carbapenemase-producing Enterobacteriaceae (CPE), particularly among travellers. Rectal swabs should be collected in every case of patients returning from international trips, and the possibility of environment-associated infections should be emphasized.


Asunto(s)
Proteínas Bacterianas/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/enzimología , Klebsiella pneumoniae/enzimología , Viaje , beta-Lactamasas/metabolismo , Adulto , Proteínas Bacterianas/genética , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Femenino , Humanos , India , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana , Polonia , beta-Lactamasas/genética
6.
Microbiol Res ; 229: 126325, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31563838

RESUMEN

Edwardsiella bacteria cause economic losses to a variety of commercially important fish globally. Human infections are rare and result in a gastroenteritis-like illness. Because these bacteria are evolutionarily related to other Enterobacteriaceae and the host cytoskeleton is a common target of enterics, we hypothesized that Edwardsiella may cause similar phenotypes. Here we use HeLa and Caco-2 infection models to show that microtubules are severed during the late infections. This microtubule alteration phenotype was not dependant on the type III or type VI secretion system (T3SS and T6SS) of the bacteria as ΔT3SS and ΔT6SS mutants of E. piscicida EIB202 and E. tarda ATCC15947 that lacks both also caused microtubule disassembly. Immunolocalization experiments showed the host katanin catalytic subunits A1 and A like 1 proteins at regions of microtubule severing, suggesting their involvement in the microtubule disassembly events. To identify bacterial components involved in this phenotype, we screened a 2,758 transposon library of E. piscicida EIB202 and found that 4 single mutations in the atpFHAGDC operon disrupted microtubule disassembly in HeLa cells. We then constructed three atp deletion mutants; they all could not disassemble host microtubules. This work provides the first clear evidence of host cytoskeletal alterations during Edwardsiella infections.


Asunto(s)
Edwardsiella/fisiología , Infecciones por Enterobacteriaceae/veterinaria , Células Epiteliales/metabolismo , Enfermedades de los Peces/metabolismo , Microtúbulos/metabolismo , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Células CACO-2 , Edwardsiella/genética , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Células Epiteliales/microbiología , Enfermedades de los Peces/microbiología , Regulación Bacteriana de la Expresión Génica , Células HeLa , Interacciones Huésped-Patógeno , Humanos , Operón , Sistemas de Secreción Tipo III/genética , Sistemas de Secreción Tipo III/metabolismo , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismo
7.
BMC Infect Dis ; 19(1): 678, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31370804

RESUMEN

BACKGROUND: Fecal colonization with carbapenem-resistant Enterobacteriaceae (CRE) is a risk factor for bacterial translocation resulting in subsequent endogenous infections. The purpose of this study is to investigate the prevalence of CRE strains colonization in stool samples of outpatient in a tertiary pediatric hospital of Shanghai, China. METHODS: In a retrospective study, fecal samples were consecutively obtained from patients in 2016 and screening test for CRE was conducted by using home-made MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and ß-lactamases were characterized by polymerase chain reaction (PCR) assays and DNA sequencing. Multilocus sequence typing (MLST) was performed for the genetic relationships of the isolates. RESULTS: A total of 880 fecal samples were included for this screening test and 32 CRE strains were identified in 32 non-duplicate fecal samples from 32 children (1.3 ± 1.5 years), with a carriage rate of 3.6%. These strains mainly distributed in Klebsiella pnuemoniae (37.5%) and Escherichia coli (37.5%). All CRE strains showed high resistance to most of the routinely used antibiotics (> 90%) except for polymyxin B and tigecycline. The blaNDM gene was the major carbapenemase gene harbored by gastrointestinal CRE strains, followed by blaKPC-2, blaIMP-26, and blaIMP-4. Other ß-Lactamase genes including blaCTX-M, blaSHV, blaTEM-1, and blaDHA-1 were also detected. MLST analysis revealed that various sequence types (STs) were detected in these strains, with ST11 and ST37 being more prevalent in K.pneumoniae and ST101 in E.coli. CONCLUSIONS: This study revealed the prevalence of CRE fecal carriage in children from outpatient and urgent implementation of infection control measure should be conducted to limit the spread of CRE strains.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/patogenicidad , Infecciones por Enterobacteriaceae/epidemiología , Heces/microbiología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Preescolar , China/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/genética , Femenino , Humanos , Lactante , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Pacientes Ambulatorios/estadística & datos numéricos , Prevalencia , Estudios Retrospectivos , beta-Lactamasas/genética
8.
J Fish Dis ; 42(10): 1409-1417, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31424570

RESUMEN

Bacillary necrosis of Pangasius (BNP), caused by Edwardsiella ictaluri, is one of the most devastating diseases in striped catfish farming. To date, quantitative genetic inheritance of BNP resistance is not known in striped catfish Pangasianodon hypophthalmus. The main aim of this study was to estimate genetic parameters for BNP resistance in a breeding population of striped catfish undergoing four generations of selection for high growth. Specifically, the study examined whether BNP resistance is heritable to enable family selection and whether genetic improvement for enhanced BNP resistance may have detrimental effects on growth and survival rate. To test these hypotheses, 720 full- and half-sib families were challenged with E. ictaluri pathogen using injection and cohabitation methods over four years, from 2010 to 2012 and 2015. In total, the data included 398,234 animals in the pedigree, from which 18,849 animals had disease challenge test records and 39,103 siblings had growth performance. Both univariate and bivariate sire-dam linear and threshold mixed models were used to estimate (co)variance components for BNP resistance, survivals and growth traits. The estimates of heritability for the BNP resistance recorded as death or survival were low regardless of models used (0.10-0.16), whereas survival time (days post-challenge test) showed moderate heritability (0.35). The survival rate during hapa rearing had medium heritability (0.33-0.52). The genetic correlations of BNP resistance with body weight and survival were all positive (0.03-0.53), suggesting that selection of increased BNP resistance may have positive impacts on growth and survival traits, and these traits could be easily improved simultaneously in the selective breeding programme for striped catfish.


Asunto(s)
Cruzamiento , Bagres , Resistencia a la Enfermedad/genética , Infecciones por Enterobacteriaceae/veterinaria , Enfermedades de los Peces/genética , Animales , Edwardsiella ictaluri/fisiología , Infecciones por Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Enfermedades de los Peces/microbiología
9.
Biomed Res Int ; 2019: 6736897, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31467906

RESUMEN

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6')-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The bla NDM-1 gene was always identified on a 70-kb plasmid, whereas the bla VIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6']-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.


Asunto(s)
Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana/genética , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Klebsiella/tratamiento farmacológico , beta-Lactamasas/genética , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/patogenicidad , Infecciones por Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/microbiología , Femenino , Humanos , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Arabia Saudita/epidemiología
10.
BMC Infect Dis ; 19(1): 742, 2019 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-31443635

RESUMEN

BACKGROUND: Trends in antimicrobial resistance help inform infection control efforts. We examined trends in resistance for Enterobacteriaceae and Acinetobacter spp. from 2013 to 2017 in hospitalized US patients. METHODS: We analyzed antimicrobial susceptibility of non-duplicate isolates in hospitalized patients (not limited to hospital-acquired infections) in the US BD Insights Research Database. Resistance profiles of interest were extended-spectrum beta-lactamase (ESBL)-producing, multidrug resistant (MDR), and carbapenem-nonsusceptible (Carb-NS) phenotypes of Enterobacteriaceae, and MDR and Carb-NS Acinetobacter spp. Time series models were used to evaluate the patterns of resistance trends in rate per 100 hospital admissions and proportion per isolates tested. RESULTS: More than 1 million Enterobacteriaceae isolates were obtained from 411 hospitals; 12.05% were ESBL, 1.21% Carb-NS, and 7.08% MDR. Urine was the most common source. For Acinetobacter spp. (n = 19,325), 37.48% were Carb-NS, 47.66% were MDR, and the most common source was skin/wound cultures. Trend analyses showed that the rates of ESBL and Carb-NS Enterobacteriaceae per 100 hospital admissions increased significantly between 2013 and 2017. Rates of MDR Enterobacteriaceae and Carb-NS and MDR Acinetobacter spp. decreased during this time period. Trends in proportions of resistant isolates generally mirrored trends in rates per 100 hospital admissions. MDR Enterobacteriaceae and Carb-NS and MDR Acinetobacter spp. were more common in winter than summer. CONCLUSIONS: In this large-scale study of patients in US hospitals, rates of ESBL and Carb-NS Enterobacteriaceae per 100 hospital admissions increased between 2013 and 2017. MDR Enterobacteriaceae and MDR and Carb-NS Acinetobacter spp. isolates decreased over this period. These data support continuing infection control and stewardship efforts and the development of new therapeutic options.


Asunto(s)
Infecciones por Acinetobacter/epidemiología , Acinetobacter/efectos de los fármacos , Farmacorresistencia Bacteriana/efectos de los fármacos , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/efectos de los fármacos , Acinetobacter/genética , Acinetobacter/aislamiento & purificación , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Hospitales/estadística & datos numéricos , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Estados Unidos/epidemiología , beta-Lactamasas/metabolismo
11.
Nature ; 571(7766): 565-569, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31316206

RESUMEN

Parkinson's disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles1,2. An early-onset form of Parkinson's disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes3. PINK1 and Parkin (encoded by PRKN) are involved in the clearance of damaged mitochondria in cultured cells4, but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo5-8. It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens9, which suggests that autoimmune mechanisms participate in the aetiology of Parkinson's disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1-/- mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8+ T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with L-DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut-brain axis in the disease10.


Asunto(s)
Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/fisiopatología , Intestinos/microbiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/microbiología , Proteínas Quinasas/deficiencia , Proteínas Quinasas/genética , Animales , Presentación de Antígeno/inmunología , Autoantígenos/inmunología , Axones/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Citrobacter rodentium/inmunología , Citrobacter rodentium/patogenicidad , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/inmunología , Neuronas Dopaminérgicas/patología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/patología , Femenino , Intestinos/inmunología , Intestinos/patología , Levodopa/uso terapéutico , Masculino , Ratones , Mitocondrias/inmunología , Mitocondrias/patología , Neostriado/inmunología , Neostriado/microbiología , Neostriado/patología , Neostriado/fisiopatología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Proteínas Quinasas/inmunología , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/inmunología
12.
PLoS Pathog ; 15(7): e1007917, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31314784

RESUMEN

It is important that bacterium can coordinately deliver several effectors into host cells to disturb the cellular progress during infection, however, the precise role of effectors in host cell cytosol remains to be resolved. In this study, we identified a new bacterial virulence effector from pathogenic Edwardsiella piscicida, which presents conserved crystal structure to thioredoxin family members and is defined as a thioredoxin-like protein (Trxlp). Unlike the classical bacterial thioredoxins, Trxlp can be translocated into host cells, mimicking endogenous thioredoxin to abrogate ASK1 homophilic interaction and phosphorylation, then suppressing the phosphorylation of downstream Erk1/2- and p38-MAPK signaling cascades. Moreover, Trxlp-mediated inhibition of ASK1-Erk/p38-MAPK axis promotes the pathogenesis of E. piscicida in zebrafish larvae infection model. Taken together, these data provide insights into the mechanism underlying the bacterial thioredoxin as a virulence effector in downmodulating the innate immune responses during E. piscicida infection.


Asunto(s)
Proteínas Bacterianas/metabolismo , Edwardsiella/patogenicidad , Infecciones por Enterobacteriaceae/etiología , MAP Quinasa Quinasa Quinasa 5/metabolismo , Tiorredoxinas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Cristalografía por Rayos X , Edwardsiella/inmunología , Edwardsiella/metabolismo , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Células HeLa , Interacciones Microbiota-Huesped/inmunología , Humanos , Inmunidad Innata , Sistema de Señalización de MAP Quinasas , Modelos Moleculares , Transducción de Señal , Tiorredoxinas/química , Tiorredoxinas/genética , Virulencia , Factores de Virulencia/química , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
14.
Microb Pathog ; 135: 103620, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31310833

RESUMEN

NDM-1-producing Enterobacteriaceae are multidrug-resistant bacteria, also called superbacteria, that have become important global human health threats in recent years. However, data about NDM-1-producing bacteria in animals are rare. In this study, an NDM-1-producing Escherichia coli isolate (designated E120413) was obtained from pigs in Henan province, China in 2012. The susceptibility of E. coli E120413 to antimicrobial agents was determined using Kirby-Bauer disk diffusion and micro-dilution methods. Susceptibility tests indicated that E. coli E120413 was resistant to almost all common antibiotics with high MIC values obtained for most antibiotics tested. E. coli E120413 was detected in the heart, liver, spleen, lung, kidney, brain, stomach, duodenum, mesenteric lymph nodes, and fecal samples of piglets in both cohabitation and experimental groups and the bacteria persisted for more than 2 weeks. However, no obvious clinical symptoms or serious pathological lesions were observed. This is the first investigation of NDM-1-producing E. coli isolate from pigs in China. Although no significant pathological lesions were observed, NDM-1-producing E. coli was found to be highly transmissible and to cause persistent infection in pigs.


Asunto(s)
Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Porcinos/microbiología , beta-Lactamasas/biosíntesis , Animales , Antibacterianos/farmacología , China , Modelos Animales de Enfermedad , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Enterobacteriaceae/patología , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Heces/microbiología , Pruebas de Sensibilidad Microbiana , Virulencia , beta-Lactamasas/genética
15.
J Hosp Infect ; 103(2): 115-120, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31279758

RESUMEN

BACKGROUND: Detection of faecal carriers of carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant Enterococci (VRE) has become a routine medical practice in many countries. In an outbreak setting, several public health organizations recommend three-weekly rectal screenings to rule-out acquisition in contact patients. This strategy, associated with bed closures and reduction of medical activity for a relatively long time, seems costly. AIM: The objective of this study was to test the positive and negative predictive values of reverse transcription polymerase chain reaction (RT-PCR; GeneXpert®) carried-out at Day 0, compared with conventional three-weekly culture-based rectal screenings, in identifying, among contact patients, those who acquired CPE/VRE. METHODS: A multicentre retrospective study was conducted from January2015 to October2018. All contact patients (CPs) were included identified from index patients (IPs) colonized or infected with CPE/VRE, incidentally discovered. Each CP was investigated at Day 0 by PCR (GeneXpert®), and by the recommended three-weekly screenings. FINDINGS: Twenty-two IPs and 159 CPs were included. An average of 0.77 secondary cases per patient was noted, with a mean duration of contact of 10 days (range 1-64). Among the 159 CPs, 16 (10%) had a CPE/VRE-positive culture during the monitoring period. Rectal screenings were positive at Day 0 (10 patients), Day 7 (two patients), Day 14 (four patients). Thirteen of 16 patients with positive culture had a positive PCR at Day 0. Overall, a concordance of 97.5% (155/159) was observed between the three-weekly screenings and Day 0 PCR results. When performed on CPs at Day 0 of the identification of an IP, PCR (GeneXpert®) allowed the reduction in turnaround time by five to 27 days, compared to three-weekly screenings. Positive predictive value and negative predictive value were 100% and 98%, respectively. CONCLUSIONS: The use of RT-PCR (GeneXpert®) can avoid the three-weekly rectal samplings needed to rule-out acquisition of CPE/VRE.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Infecciones por Enterobacteriaceae/diagnóstico , Monitoreo Epidemiológico , Infecciones por Bacterias Grampositivas/diagnóstico , Clausura de las Instituciones de Salud/estadística & datos numéricos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Enterobacteriaceae/microbiología , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Hospitales , Humanos , Hallazgos Incidentales , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/métodos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto Joven
16.
Diagn Microbiol Infect Dis ; 95(2): 119-124, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31272742

RESUMEN

Many Escherichia albertii isolates, an emerging pathogen of human and birds, might have been misidentified due to the difficulty of differentiating this bacterium from Escherichia coli and Shigella spp. by routine biochemical tests, resulting in underestimation of E. albertii infections. We have developed a polymerase chain reaction (PCR) assay that targets E. albertii cytolethal distending toxin (Eacdt) genes, which include the genes previously identified as Escherichia coli cdt-II. This assay could generate a single 449-bp PCR product in each of 67 confirmed E. albertii strains but failed to produce PCR product from any of the tested non-E. albertii enteric strains belonging to 37 different species, indicating 100% sensitivity and specificity of the PCR assay. The detection limit was 10 CFU per PCR tube and could detect 105 CFU E. albertii per gram of spiked healthy human stool. The Eacdt gene-based PCR could be useful for simple, rapid, and accurate detection and identification of E. albertii.


Asunto(s)
Toxinas Bacterianas/genética , Infecciones por Enterobacteriaceae/diagnóstico , Escherichia/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa , ADN Bacteriano/genética , Infecciones por Enterobacteriaceae/microbiología , Escherichia/genética , Heces/microbiología , Humanos , Límite de Detección , Sensibilidad y Especificidad
17.
Braz J Microbiol ; 50(3): 657-662, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31270693

RESUMEN

The emergence of carbapenem-resistant Enterobacterales (CRE) is a matter of public health concern. Carbapenemases are the main mechanism of resistance among CRE, and its rapid detection is essential. The detection of carbapenemases usually requires culture-based methods and molecular assays, which may be costly and need long turnaround times. Recently, an easy and rapid immunochromatographic assay for carbapenemases (OXA-48, KPC, and NDM) detection based in lateral flow immunoassay with specific monoclonal antibodies on a nitrocellulose membrane has been developed. We aimed to evaluate the RESIST-3 O.K.N. in colonies from pure culture as well as in spiked blood cultures with Enterobacterales. All carbapenemase producers (CP) presenting the OXA-48-like, KPC, and NDM enzymes presented positive results in both pure colonies and spiked blood cultures. None of the carbapenemase non-producers (CNP) presented positive results in the tests. A total of 97% CP isolates presented positive results in pure colonies in less than 5 min. For CP directly from blood culture, the mean time to positivity for OXA-48-like and KPC was 1 min, whereas it was 25 min for NDM. Our results indicate that this immunoassay can be used to detect carbapenemases directly from blood culture bottles in a routine diagnostic laboratory, which would reduce the turnaround time of CP detection.


Asunto(s)
Proteínas Bacterianas/sangre , Infecciones por Enterobacteriaceae/sangre , Enterobacteriaceae/enzimología , Inmunoensayo/métodos , beta-Lactamasas/sangre , Antibacterianos/farmacología , Cultivo de Sangre , Brasil , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/microbiología , Humanos
18.
Rev Esc Enferm USP ; 53: e03474, 2019 Jul 04.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-31291394

RESUMEN

OBJECTIVE: To study the epidemiological profile of Healthcare-associated Infections caused by Enterobacteria which carry the Klebsiella pneumoniae Carbapenemase gene (blaKPC) in the hospital environment. METHOD: A descriptive study was conducted in a private hospital in Belo Horizonte, MG, Brazil, which included all patients with infections caused by Enterobacteriaceae which carry the Klebsiella pneumoniae Carbapenemase gene. The data were collected by the Automated System of Hospital Infection Control and analyzed by descriptive statistics by the Epi Info 7 program. RESULTS: Eighty-two (82) patients participated in the study. Klebsiella pneumoniae was the most frequent species (68%) isolated in blood (30%), bronchoalveolar lavage (22%) and urine (18%), while catheter-associated bloodstream infection (30%) predominated regarding topography. A case fatality rate of 62% is highlighted in evaluating the outcome. CONCLUSION: The resistance genes spread rapidly, limiting the antimicrobial options for treating infectious diseases. The epidemiological profile of Healthcare-Associated Infections found in this study can be prevented by prevention and infection control programs.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Infección Hospitalaria/epidemiología , Infecciones por Enterobacteriaceae/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Brasil , Infección Hospitalaria/microbiología , Infecciones por Enterobacteriaceae/microbiología , Femenino , Hospitales Privados , Humanos , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Persona de Mediana Edad
19.
Bull World Health Organ ; 97(7): 486-501B, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31258218

RESUMEN

Objective: To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum ß-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific. Methods: Up to June 2018 we searched online databases for published studies of infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in individuals aged 0-21 years. We included case-control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data. Findings: Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infection with extended-spectrum ß-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce. Conclusion: Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific.


Asunto(s)
Farmacorresistencia Microbiana , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , beta-Lactamasas/metabolismo , Asia Sudoriental/epidemiología , Niño , Enterobacteriaceae/enzimología , Infecciones por Enterobacteriaceae/microbiología , Humanos , Islas del Pacífico/epidemiología , Factores de Riesgo
20.
Rev Soc Bras Med Trop ; 52: e20180460, 2019 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-31271617

RESUMEN

INTRODUCTION: The objective of this study was to characterize genes of aminoglycoside modifying enzymes (AMEs) in colonizing and infecting isolates of E. aerogenes harboring bla KPC from patients at a public hospital in Recife-PE, Brazil. METHODS: We analyzed 29 E. aerogenes clinical isolates resistant to aminoglycosides. AMEs genes were investigated by PCR and sequencing. RESULTS: Colonizing and infecting isolates mainly presented the genetic profiles aac(3)-IIa/aph(3')-VI or ant(2")-IIa/aph(3')-VI. This is the first report of aph(3')-VI in E. aerogenes harboring bla KPC in Brazil. CONCLUSIONS: The results highlight the importance in establishing rigorous methods for the surveillance of resistance genes, especially in colonized patients.


Asunto(s)
Aminoglicósidos/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Enterobacter aerogenes/genética , Infecciones por Enterobacteriaceae/microbiología , Brasil , Enterobacter aerogenes/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Fenotipo , Reacción en Cadena de la Polimerasa
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