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1.
PLoS One ; 15(7): e0235345, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32667930

RESUMEN

This study was carried out to investigate the risks of simultaneous exposure to pesticide residues and bacteria contaminants in locally produced fresh vegetables and vegetables in Tanzania. A total of 613 samples were analyzed for pesticide residues, out of which 250 were also analyzed for bacterial contamination. Overall, 47.5% had pesticide residues, 74.2% exceeded Maximum Residue Levels (MRLs). Organophosphorus (95.2%), organochlorines (24.0%), pyrethroids (17.3%), and carbamates (9.2%) residues dominated. MRL values were mostly exceeded in tomatoes, onions, watermelons, cucumbers, Chinese cabbage, and sweet paper. Tetramethrin (0.0329-1.3733 mg/kg), pirimiphos-methyl (0.0003-1.4093 mg/kg), permethrin (0.0009-2.4537 mg/kg), endosulfan (beta) (0.0008-2.3416 mg/kg), carbaryl (0.0215-1.5068 mg/kg), profenofos (0.0176-2.1377 mg/kg), chlorpyrifos (0.0004-1.2549 mg/kg) and dieldrin (0.0011-0.5271 mg/kg) exceeded MRLs. The prevalence of bacteria contamination was high (63.2%). Enterobacter (55.6%) Pseudomonas aeruginosa (32.4%), E. coli (28.2%), Citrobacter (26.8%), Klebsiella oxytoca (14.8%), and Salmonella (7.7%) were isolated. Furthermore, 46.4% tested positive for both pesticide residues and bacterial contaminants. Vegetables from farms (60.7%) contained more dual contaminants than market-based vegetables (41.8%). This may have resulted from excessive pesticide use and unhygienic handling of fresh fruits and vegetables at production level. Binary logistic regression showed that fresh fruits and vegetables with pesticide residues were 2.231 times more likely to have bacteria contaminants (OR: 2.231; 95% CI: 0.501, 8.802). The contamination levels of pesticide residues and bacterial contaminants could be perceived as a serious problem as most fresh fruits and vegetables recorded values of pesticide residues far above the MRLs with pathogenic bacteria isolated in higher proportions. MRLs was higher in most vegetables consumed raw or semi-cooked such as watermelons, carrots, cucumber, tomatoes, onion and sweet paper. There is an urgent need to develop pesticide monitoring and surveillance systems at farmer level, educating farmers and promoting the use of greener pesticides to mitigate the health effects of pesticides and bacterial contaminants.


Asunto(s)
Contaminación de Alimentos/análisis , Frutas/efectos adversos , Plaguicidas/efectos adversos , Verduras/efectos adversos , Citrobacter/aislamiento & purificación , Citrobacter/patogenicidad , Enterobacter/aislamiento & purificación , Enterobacter/patogenicidad , Frutas/química , Frutas/microbiología , Humanos , Hidrocarburos Clorados/efectos adversos , Hidrocarburos Clorados/química , Klebsiella oxytoca/aislamiento & purificación , Klebsiella oxytoca/patogenicidad , Residuos de Plaguicidas/efectos adversos , Residuos de Plaguicidas/química , Plaguicidas/química , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/patogenicidad , Piretrinas/efectos adversos , Piretrinas/química , Salmonella/aislamiento & purificación , Salmonella/patogenicidad , Verduras/química , Verduras/microbiología
2.
J Gastrointest Cancer ; 51(3): 855-860, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31659674

RESUMEN

OBJECTIVE: Biofilm formation has made the therapy of bacterial infections more difficult. The objective our study was assessment of pan-drug-resistant (PDR) Klebsiella oxytoca pathogenicity and virulence factors causing AAHC in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Among a total of 300 healthy and 300 patients with antibiotic-associated hemorrhagic colitis (AAHC) and CRC, 200 K. oxytoca were identified during May 2015-January 2019. The virulence properties and biofilm formation among the isolates were investigated by phenotypic, PCR, and real-time PCR (RT-qPCR) techniques. RESULTS: The blaCTX-M1 (20%), blaSHV (11%), blaTEM1 (33%), and AmpC encoding CIT (2%) ESBL genes, carbapenemase-encoding genes blaIM (4%) and blaOXA-48 (2%), and colistin-resistant mcr-1 gene (2.5%) were detected. The virulence-encoding genes including fimA (80%), pilQ (100%), matB (100%), mrkA (80%), and npsB (100%) were amplified. Therefore, PDR K. oxytoca containing adhesins and toxin-encoding genes with ability of biofilm formation causing AAHC and CRC were isolated. There was a significant difference between healthy and patients with CRC regarding the presence of K. oxytoca (p = 00.221). CONCLUSION: Bacterial enteric pathogens possibly play a role in CRC. Biofilm formation by K. oxytoca strains prevents the efficient infection elimination; therefore, rapid identification and control measure are chief requirements. Additionally, more investigations are necessary with this regard.


Asunto(s)
Antibacterianos/farmacología , Colitis/microbiología , Neoplasias Colorrectales/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Klebsiella oxytoca/patogenicidad , Adulto , Anciano , Antibacterianos/uso terapéutico , Biopelículas/efectos de los fármacos , Estudios de Casos y Controles , Colitis/inducido químicamente , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Genes Bacterianos/genética , Voluntarios Sanos , Células Hep G2 , Humanos , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/genética , Klebsiella oxytoca/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Virulencia/genética , Factores de Virulencia/genética , Factores de Virulencia/aislamiento & purificación
3.
Artículo en Inglés | MEDLINE | ID: mdl-31345843

RESUMEN

The recent development of new antimicrobials active against carbapenemase-producing Enterobacteriales (CPE) has brought new hope for the treatment of infections due to these organisms. However, the evolving epidemiology of bacteria with carbapenemases may complicate management, as providers are faced with treating patients colonized by bacteria producing multiple carbapenemases. Here, we present the clinical course and treatment of Raoultella planticola bacteremia in a cirrhotic patient known to be colonized with both blaKPC- and blaOXA-48-carrying organisms.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/genética , Adulto , Proteínas Bacterianas/genética , Enterobacteriaceae/aislamiento & purificación , Enterobacteriaceae/patogenicidad , Escherichia coli/aislamiento & purificación , Fibrosis/complicaciones , Humanos , Klebsiella oxytoca/genética , Klebsiella oxytoca/patogenicidad , Masculino , beta-Lactamasas/genética
4.
Am J Infect Control ; 47(7): 840-842, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30723029

RESUMEN

Advances in neonatal care have led to the increasing survival of smaller and sicker infants, but nosocomial infections continue to be a serious problem, associated with increased mortality rates, immediate and long-term morbidity, prolonged hospital stay, and increased cost of care. We report a case of hospital-acquired sepsis in a preterm baby secondary to Klebsiella oxytoca, resulting from contaminated intravenous fluid.


Asunto(s)
Infección Hospitalaria/diagnóstico , Fluidoterapia/efectos adversos , Infecciones por Klebsiella/diagnóstico , Klebsiella oxytoca/patogenicidad , Sepsis/diagnóstico , Administración Intravenosa , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/etiología , Infección Hospitalaria/microbiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/etiología , Infecciones por Klebsiella/microbiología , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/aislamiento & purificación , Masculino , Sepsis/tratamiento farmacológico , Sepsis/etiología , Sepsis/microbiología
5.
Proc Natl Acad Sci U S A ; 116(9): 3774-3783, 2019 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-30808763

RESUMEN

Establishing causal links between bacterial metabolites and human intestinal disease is a significant challenge. This study reveals the molecular basis of antibiotic-associated hemorrhagic colitis (AAHC) caused by intestinal resident Klebsiella oxytoca Colitogenic strains produce the nonribosomal peptides tilivalline and tilimycin. Here, we verify that these enterotoxins are present in the human intestine during active colitis and determine their concentrations in a murine disease model. Although both toxins share a pyrrolobenzodiazepine structure, they have distinct molecular targets. Tilimycin acts as a genotoxin. Its interaction with DNA activates damage repair mechanisms in cultured cells and causes DNA strand breakage and an increased lesion burden in cecal enterocytes of colonized mice. In contrast, tilivalline binds tubulin and stabilizes microtubules leading to mitotic arrest. To our knowledge, this activity is unique for microbiota-derived metabolites of the human intestine. The capacity of both toxins to induce apoptosis in intestinal epithelial cells-a hallmark feature of AAHC-by independent modes of action, strengthens our proposal that these metabolites act collectively in the pathogenicity of colitis.


Asunto(s)
Enterocolitis Seudomembranosa/genética , Enterotoxinas/metabolismo , Interacciones Microbiota-Huesped/genética , Klebsiella oxytoca/genética , Animales , Benzodiazepinonas/metabolismo , Benzodiazepinonas/toxicidad , Daño del ADN/efectos de los fármacos , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/patología , Enterotoxinas/biosíntesis , Células Epiteliales/microbiología , Células Epiteliales/patología , Humanos , Intestinos/microbiología , Intestinos/patología , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/microbiología , Klebsiella oxytoca/metabolismo , Klebsiella oxytoca/patogenicidad , Ratones , Microtúbulos/efectos de los fármacos , Oxiquinolina/análogos & derivados , Oxiquinolina/metabolismo , Oxiquinolina/toxicidad , Péptidos/metabolismo , Péptidos/toxicidad
6.
Acta Paediatr ; 108(1): 76-82, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30238492

RESUMEN

AIM: Klebsiella spp. have been stated to be the most frequent cause of neonatal intensive care unit (NICU) outbreaks. We report an outbreak of Klebsiella oxytoca in a NICU at a tertiary care hospital in Norway between April 2016 and April 2017. This study describes the outbreak, infection control measures undertaken and the molecular methods developed. METHODS: The outbreak prompted detailed epidemiological and microbial investigations, where whole-genome sequencing (WGS) was particularly useful for both genotyping and development of two new K. oxytoca-specific real-time PCR assays. Routine screening of patients, as well as sampling from numerous environmental sites, was performed during the outbreak. A bundle of infection control measures was instigated to control the outbreak, among them strict cohort isolation. RESULTS: Five neonates had symptomatic infection, and 17 were found to be asymptomatically colonised. Infections varied in severity from conjunctivitis to a fatal case of pneumonia. A source of the outbreak could not be determined. CONCLUSION: This report describes K. oxytoca as a significant pathogen in a NICU outbreak setting and highlights the importance of developing appropriate microbiological screening methods and implementing strict infection control measures to control the outbreak in a setting where the source could not be identified.


Asunto(s)
Infección Hospitalaria/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Unidades de Cuidado Intensivo Neonatal , Infecciones por Klebsiella/epidemiología , Klebsiella oxytoca/patogenicidad , Estudios de Cohortes , ADN Bacteriano/análisis , Femenino , Mortalidad Hospitalaria , Hospitales Universitarios , Humanos , Recién Nacido , Control de Infecciones/organización & administración , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/tratamiento farmacológico , Masculino , Noruega , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Estudios Retrospectivos , Medición de Riesgo
7.
Sci Rep ; 8(1): 12321, 2018 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-30120320

RESUMEN

Cancer cachexia is a complex multi-organ syndrome characterized by body weight loss, weakness, muscle atrophy and fat depletion. With a prevalence of 1 million people in Europe and only limited therapeutic options, there is a high medical need for new approaches to treat cachexia. Our latest results highlighted microbial dysbiosis, characterized by a bloom in Enterobacteriaceae and altered gut barrier function in preclinical models of cancer cachexia. They also demonstrated the potential of targeting the gut microbial dysbiosis in this pathology. However, the exact mechanisms underlying the gut microbiota-host crosstalk in cancer cachexia remain elusive. In this set of studies, we identified Klebsiella oxytoca as one of the main Enterobacteriaceae species increased in cancer cachexia and we demonstrated that this bacteria acts as a gut pathobiont by altering gut barrier function in cachectic mice. Moreover, we propose a conceptual framework for the lower colonization resistance to K. oxytoca in cancer cachexia that involves altered host gut epithelial metabolism and host-derived nitrate boosting the growth of the gut pathobiont. This set of studies constitutes a strong progression in the field of gut microbiota in cancer cachexia, by dissecting the mechanism of emergence of one bacterium, K. oxytoca, and establishing its role as a gut pathobiont in this severe disease.


Asunto(s)
Caquexia/microbiología , Caquexia/patología , Klebsiella oxytoca/patogenicidad , Neoplasias/microbiología , Neoplasias/patología , Animales , Línea Celular Tumoral , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/patología , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/patología , Masculino , Ratones
8.
BMC Microbiol ; 18(1): 38, 2018 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-29673319

RESUMEN

BACKGROUND: Carbapenemases-producing Enterobacteriaceae (CPE) are a worldwide public health emergency. In Mexico, reports of CPE are limited, particularly in the pediatric population. Here, we describe the clinical, epidemiological, and molecular characteristics of seven consecutive cases in a third-level pediatric hospital in Mexico City over a four-month period during 2016. RESULTS: The Enterobacteriaceae identified were three Escherichia coli strains (producing OXA-232, NDM-1 and KPC-2), two Klebsiella pneumoniae strains (producing KPC-2 and NDM-1), one Klebsiella oxytoca strain producing OXA-48 and one Enterobacter cloacae strain producing NDM-1. The majority of patients had underlying disesases, three were immunocompromised, and three had infections involved the skin and soft tissues. Half patients died as a result of CPE infection. CONCLUSIONS: This study represents the first report of E. coli ST131-O25b clone producing NDM-1 in Latin America. In addition, this study is the first finding of K. oxytoca producing OXA-48 and E. coli producing OXA-232 in Mexican pediatric patients.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/enzimología , Enterobacteriaceae Resistentes a los Carbapenémicos/patogenicidad , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Adolescente , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Niño , Preescolar , Enterobacter cloacae/enzimología , Enterobacter cloacae/genética , Enterobacter cloacae/aislamiento & purificación , Enterobacter cloacae/patogenicidad , Infecciones por Enterobacteriaceae/mortalidad , Infecciones por Enterobacteriaceae/fisiopatología , Escherichia coli/enzimología , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Escherichia coli/patogenicidad , Femenino , Genotipo , Hospitales Pediátricos , Humanos , Lactante , Klebsiella oxytoca/enzimología , Klebsiella oxytoca/genética , Klebsiella oxytoca/aislamiento & purificación , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/patogenicidad , América Latina/epidemiología , Masculino , México/epidemiología , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , beta-Lactamasas/metabolismo
9.
Ann Clin Microbiol Antimicrob ; 17(1): 13, 2018 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-29571291

RESUMEN

BACKGROUND: The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a difficult problem in the current clinical anti-infective treatment. We performed a retrospective analysis of prevalence and treatment for CRE infections patients. METHODS: This study was conducted in three tertiary care hospitals from January 1, 2010 to December 30, 2016. Baseline data, treatment, and outcomes were collected in patients with ventilator-associated bacterial pneumonia (VABP), bacteremia, complicated urinary tract infection (cUTI)/acute pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), superficial wound infection (SWI), biliary tract infection (BTI), deep wound infection (DWI) and sterile body fluids infection (SBFI) due to CRE. RESULTS: One hundred twenty-four cases of CRE infection were identified: 31 VABP, 22 bacteremia, 18 cUTI/AP, 16 HABP, 16 SWI, 9 BTI, 7 DWI and 5 SBFI. The patient population had significant immunocompromised (33 of 124, 26.6%) and severe sepsis (43 of 124, 34.7%). The most common CRE pathogens were Klebsiella pneumoniae (84 of 124, 67.7%) and Enterobacter cloacae (24 of 124, 19.4%). And the production of IMP-type carbapenemase was the main antibiotic resistance mechanism. The majority of patients to take monotherapy for empiric therapy and dual therapy for direct treatment. Outcomes were universally poor (28-day mortality was 22.6%, 28 of 124) across all sites of infection. CONCLUSIONS: We identified a large number of cases of CRE infection in 7 years from different parts, most of these pathogens have been confirmed to produce IMP-type carbapenemases. The retrospective analysis of cases of such bacterial infections will help to control future infections of these pathogens. Despite the high mortality rate, we still found that the selection of quinolone antibiotics can be effective in the treatment of CRE producing IMP type enzymes.


Asunto(s)
Antibacterianos/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/patogenicidad , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/patogenicidad , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Enfermedades de las Vías Biliares/tratamiento farmacológico , Enfermedades de las Vías Biliares/epidemiología , Enfermedades de las Vías Biliares/microbiología , Líquidos Corporales/microbiología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , China , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Enterobacter cloacae/patogenicidad , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Femenino , Hospitalización , Hospitales , Humanos , Unidades de Cuidados Intensivos , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/patogenicidad , Masculino , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/epidemiología , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/microbiología , Prevalencia , Pielonefritis/tratamiento farmacológico , Pielonefritis/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Sepsis/tratamiento farmacológico , Sepsis/epidemiología , Centros de Atención Terciaria , Resultado del Tratamiento , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/epidemiología , Adulto Joven
10.
ACS Chem Biol ; 13(3): 812-819, 2018 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-29389112

RESUMEN

Tilvalline is a pyrrolo[4,2]benzodiazepine derivative produced by the pathobiont Klebsiella oxytoca and is the causative toxin in antibiotic associated hemorrhagic colitis (AAHC). Heterologous expression of the tilivalline biosynthetic gene cluster along with in vitro reconstitution of the respective NRPS (NpsA, ThdA, NpsB) was employed to reveal a nonenzymatic indole incorporation via a spontaneous Friedel-Crafts-like alkylation reaction. Furthermore, the heterologous system was used to generate novel tilivalline derivatives by supplementation of respective anthranilate and indole precursors. Finally, it could be shown that salicylic and acetylsalicylic acid inhibit the biosynthesis of tilivalline in K. oxytoca liquid culture, presumably by blocking the peptidyl carrier protein ThdA, pointing toward a potential application in combination therapy to prevent or alleviate the symptoms of AAHC.


Asunto(s)
Benzodiazepinonas/metabolismo , Enterocolitis Seudomembranosa/tratamiento farmacológico , Klebsiella oxytoca/patogenicidad , Benzodiazepinonas/síntesis química , Benzodiazepinonas/química , Citotoxinas/síntesis química , Enterocolitis Seudomembranosa/etiología , Indoles/metabolismo , Klebsiella oxytoca/química , Klebsiella oxytoca/metabolismo , Familia de Multigenes , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , ortoaminobenzoatos/metabolismo
13.
Microb Pathog ; 113: 1-4, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28970173

RESUMEN

BACKGROUND: Klebsiella oxytoca is an opportunistic pathogen which damages intestinal epithelium through producing cytotoxin tilivalline. This toxin plays a role in the pathogenesis of bacteria and is the main virulence factor which leads to antibiotic-associated hemorrhagic colitis progress. MATERIALS AND METHODS: In this study, we collected a total of 75 K. oxytoca strains isolated from the stool, urine, blood, wounds, and sputum and evaluated them in terms of the production of toxins; we detected their cytotoxic effects on HEp-2 cells. RESULTS: Of all the isolates, five K. oxytoca strains isolated from the stool cultures, two strains isolated from the blood cultures, one strains isolated from the wound cultures, and one strains isolated from the urine cultures had cytotoxic effects on HEp-2 cells. The strains isolated from sputum cultures had no cytotoxic effects on HEp-2 cells. CONCLUSIONS: In the current study, the majority of strains isolated from the stool of the patients included cytopathic effects on HEp-2 cells.


Asunto(s)
Benzodiazepinonas/metabolismo , Citotoxinas/metabolismo , Klebsiella oxytoca/aislamiento & purificación , Klebsiella oxytoca/patogenicidad , Línea Celular , Enterocolitis Seudomembranosa/microbiología , Heces/microbiología , Humanos , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/microbiología , Klebsiella oxytoca/clasificación , Factores de Virulencia
14.
Artículo en Inglés | MEDLINE | ID: mdl-27895014

RESUMEN

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.


Asunto(s)
Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Carbapenémicos/uso terapéutico , Ceftazidima/uso terapéutico , Anciano , Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacología , Ceftazidima/farmacología , Combinación de Medicamentos , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/patogenicidad , Femenino , Humanos , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/patogenicidad , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/patogenicidad , Terapia Recuperativa
15.
Trends Microbiol ; 24(6): 463-476, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26897710

RESUMEN

Antibiotic-associated diarrhoea (AAD) is a common and unintended consequence of antibiotic use. Clostridium difficile is the most common infectious aetiology of AAD; however, only approximately 25% of all AAD cases are associated with C. difficile infection, with the aetiology in the majority of cases remaining undetermined. Numerous other bacterial infectious agents have been implicated in AAD, including Clostridium perfringens, Staphylococcus aureus, and Klebsiella oxytoca. AAD is a complex disease that is influenced by the host, the infectious agent involved, and numerous clinical factors, including antibiotic treatment regimes. This review re-examines AAD and presents current perspectives on this disease, with a particular focus on the current understanding of bacterial causes other than C. difficile and the virulence factors involved in pathogenesis. VIDEO ABSTRACT.


Asunto(s)
Antibacterianos/efectos adversos , Clostridioides difficile/efectos de los fármacos , Clostridioides difficile/patogenicidad , Diarrea/etiología , Diarrea/microbiología , Infecciones por Clostridium/tratamiento farmacológico , Clostridium perfringens/efectos de los fármacos , Clostridium perfringens/patogenicidad , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Diarrea/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Enterotoxinas , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/patogenicidad , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Factores de Virulencia
16.
Braz. j. med. biol. res ; 48(9): 782-789, Sept. 2015. tab, ilus
Artículo en Inglés | LILACS | ID: lil-756407

RESUMEN

We aimed to evaluate the potential virulence of Klebsiellaisolates from enteral diets in hospitals, to support nosocomial infection control measures, especially among critical-care patients. Phenotypic determination of virulence factors, such as capsular expression on the external membrane, production of aerobactin siderophore, synthesis of capsular polysaccharide, hemolytic and phospholipase activity, and resistance to antibiotics, which are used therapeutically, were investigated in strains ofKlebsiella pneumoniae and K. oxytoca. Modular industrialized enteral diets (30 samples) as used in two public hospitals were analyzed, and Klebsiella isolates were obtained from six (20%) of them. The hypermucoviscous phenotype was observed in one of the K. pneumoniae isolates (6.7%). Capsular serotypes K1 to K6 were present, namely K5 and K4. Under the conditions of this study, no aerobactin production, hemolytic activity or lecithinase activity was observed in the isolates. All isolates were resistant to amoxicillin and ampicillin and sensitive to cefetamet, imipenem, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim. Most K. pneumoniae isolates (6/7, 85.7%) from hospital B presented with a higher frequency of resistance to the antibiotics tested in this study, and multiple resistance to at least four antibiotics (3/8; 37.5%) compared with isolates from Hospital A. The variations observed in the antibiotic resistance profiles allowed us to classify theKlebsiella isolates as eight antibiotypes. No production of broad-spectrum β-lactamases was observed among the isolates. Our data favor the hypothesis that Klebsiella isolates from enteral diets are potential pathogens for nosocomial infections.


Asunto(s)
Humanos , Antibacterianos/farmacología , Nutrición Enteral , Microbiología de Alimentos , Alimentos Formulados/microbiología , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/patogenicidad , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/aislamiento & purificación , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Fenotipo , Virulencia
17.
Braz J Med Biol Res ; 48(9): 782-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26176307

RESUMEN

We aimed to evaluate the potential virulence of Klebsiella isolates from enteral diets in hospitals, to support nosocomial infection control measures, especially among critical-care patients. Phenotypic determination of virulence factors, such as capsular expression on the external membrane, production of aerobactin siderophore, synthesis of capsular polysaccharide, hemolytic and phospholipase activity, and resistance to antibiotics, which are used therapeutically, were investigated in strains of Klebsiella pneumoniae and K. oxytoca. Modular industrialized enteral diets (30 samples) as used in two public hospitals were analyzed, and Klebsiella isolates were obtained from six (20%) of them. The hypermucoviscous phenotype was observed in one of the K. pneumoniae isolates (6.7%). Capsular serotypes K1 to K6 were present, namely K5 and K4. Under the conditions of this study, no aerobactin production, hemolytic activity or lecithinase activity was observed in the isolates. All isolates were resistant to amoxicillin and ampicillin and sensitive to cefetamet, imipenem, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim. Most K. pneumoniae isolates (6/7, 85.7%) from hospital B presented with a higher frequency of resistance to the antibiotics tested in this study, and multiple resistance to at least four antibiotics (3/8; 37.5%) compared with isolates from Hospital A. The variations observed in the antibiotic resistance profiles allowed us to classify the Klebsiella isolates as eight antibiotypes. No production of broad-spectrum ß-lactamases was observed among the isolates. Our data favor the hypothesis that Klebsiella isolates from enteral diets are potential pathogens for nosocomial infections.


Asunto(s)
Antibacterianos/farmacología , Nutrición Enteral , Microbiología de Alimentos , Alimentos Formulados/microbiología , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/patogenicidad , Humanos , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/aislamiento & purificación , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Fenotipo , Virulencia
18.
BMC Res Notes ; 7: 827, 2014 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-25417012

RESUMEN

BACKGROUND: The giant panda (Ailuropoda melanoleuca) is an endangered species well-known for ingesting bamboo as a major part of their diet despite the fact that it belongs to order Carnivora. However, the giant panda's draft genome shows no direct evidence of enzymatic genes responsible for cellulose digestion. To explore this phenomenon, we study the giant panda's gut microbiota using genomic approaches in order to better understand their physiological processes as well as any potential microbial cellulose digestion processes. RESULTS: A complete genome of isolated Klebsiella oxytoca HKOPL1 of 5.9 Mb has been successfully sequenced, closed and comprehensively annotated against various databases. Genome comparisons within the Klebsiella genus and K. oxytoca species have also been performed. A total of 5,772 genes were predicted, and among them, 211 potential virulence genes, 35 pathogenicity island-like regions, 1,615 potential horizontal transferring genes, 23 potential antibiotics resistant genes, a potential prophage integrated region, 8 genes in 2,3-Butanediol production pathway and 3 genes in the cellulose degradation pathway could be identified and discussed based on the comparative genomic studies between the complete genome sequence of K. oxytoca HKOPL1 and other Klebsiella strains. A functional study shows that K. oxytoca HKOPL1 can degrade cellulose within 72 hours. Phylogenomic studies indicate that K. oxytoca HKOPL1 is clustered with K. oxytoca strains 1686 and E718. CONCLUSIONS: K. oxytoca HKOPL1 is a gram-negative bacterium able to degrade cellulose. We report here the first complete genome sequence of K. oxytoca isolated from giant panda feces. These studies have provided further insight into the role of gut microbiota in giant panda digestive physiology. In addition, K. oxytoca HKOPL1 has the potential for biofuel application in terms of cellulose degradation and potential for the production of 2,3-Butanediol (an important industrial raw material).


Asunto(s)
Heces/microbiología , Genoma Bacteriano , Klebsiella oxytoca/genética , Animales , Farmacorresistencia Bacteriana/genética , Secuencias Repetitivas Esparcidas , Klebsiella oxytoca/clasificación , Klebsiella oxytoca/patogenicidad , Filogenia , Ursidae , Virulencia/genética
19.
PLoS One ; 9(7): e100542, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25057966

RESUMEN

Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease.


Asunto(s)
Toxinas Bacterianas/toxicidad , Benzodiazepinonas/toxicidad , Infecciones por Klebsiella/veterinaria , Klebsiella oxytoca/patogenicidad , Animales , Sistemas de Secreción Bacterianos/genética , Toxinas Bacterianas/biosíntesis , Toxinas Bacterianas/química , Toxinas Bacterianas/aislamiento & purificación , Benzodiazepinonas/química , Benzodiazepinonas/aislamiento & purificación , Benzodiazepinonas/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Haplorrinos , Células HeLa , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella oxytoca/efectos de los fármacos , Klebsiella oxytoca/aislamiento & purificación , Klebsiella oxytoca/metabolismo , Ratones , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Glycine max/química , Porcinos
20.
Appl Microbiol Biotechnol ; 97(5): 1997-2007, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22832986

RESUMEN

Klebsiella species are the most extensively studied among a number of 2,3-butanediol (2,3-BDO)-producing microorganisms. The ability to metabolize a wide variety of substrates together with the ease of cultivation made this microorganisms particularly promising for the application in industrial-scale production of 2,3-BDO. However, the pathogenic characteristics of encapsulated Klebsiella species are considered to be an obstacle hindering their industrial applications. Here, we removed the virulence factors from three 2,3-BDO-producing strains, Klebsiella pneumoniae KCTC 2242, Klebsiella oxytoca KCTC1686, and K. oxytoca ATCC 43863 through site-specific recombination technique. We generated deletion mutation in wabG gene encoding glucosyltransferase which plays a key role in the synthesis of outer core lipopolysaccharides (LPS) by attaching the first outer core residue D-GalAp to the O-3 position of the L,D-HeppII residue. The morphologies and adhesion properties against epithelial cells were investigated, and the results indicated that the wabG mutant strains were devoid of the outer core LPS and lost the ability to retain capsular structure. The time profile of growth and 2,3-BDO production from K. pneumoniae KCTC 2242 and K. pneumoniae KCTC 2242 ΔwabG were analyzed in batch culture with initial glucose concentration of 70 g/l. The growth was not affected by disrupting wabG gene, but the production of 2,3-BDO decreased from 31.27 to 22.44 g/l in mutant compared with that of parental strain. However, the productions of acetoin and lactate from wabG mutant strain were negligible, whereas that from parental strain reached to ~5 g/l.


Asunto(s)
Butileno Glicoles/metabolismo , Técnicas de Inactivación de Genes , Klebsiella oxytoca/metabolismo , Klebsiella oxytoca/patogenicidad , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/patogenicidad , Factores de Virulencia/genética , Acetoína/metabolismo , Biotecnología/métodos , Línea Celular , Células Epiteliales/microbiología , Marcación de Gen , Humanos , Klebsiella oxytoca/genética , Klebsiella oxytoca/crecimiento & desarrollo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/crecimiento & desarrollo , Lactatos/metabolismo , Lipopolisacáridos/biosíntesis , Ingeniería Metabólica/métodos , Recombinación Genética , Virulencia
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