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1.
Medicine (Baltimore) ; 98(39): e17339, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574872

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Tigeciclina/uso terapêutico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Escherichia coli/microbiologia , Humanos , Lactente , Transplante de Fígado/efeitos adversos , Masculino , Complicações Pós-Operatórias/microbiologia
3.
Rev Med Suisse ; 15(661): 1545-1550, 2019 Sep 04.
Artigo em Francês | MEDLINE | ID: mdl-31496187

RESUMO

Pyelonephritis is a frequent infection mostly found in women. Urine must be collected for culture before beginning antibiotherapy. The predominant pathogen identified is E coli. Ciprofloxacin may be used right away if the E. coli susceptibility to this antibiotic is at least 90% in the local population. Otherwise, a dose of ceftriaxone or amikacin (outside pregnancy) should be administered. For inpatient care, initial treatment is different according to clinical severity. In case of complication, specialists of urology and infectiology should be consulted. An antibiotic de-escalation should be considered if permitted by the clinical evolution and the antibiogram; in favor of amoxicillin in women and ciprofloxacin in men. In case of history of ESBL infection or carriage, the empirical treatment should be adapted.


Assuntos
Assistência ao Paciente , Pielonefrite/tratamento farmacológico , Antibacterianos/uso terapêutico , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Pielonefrite/microbiologia
4.
BMC Vet Res ; 15(1): 234, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286936

RESUMO

BACKGROUND: Enterotoxigenic Escherichia coli K88 (E. coli K88) are considered as a major cause of diarrhea and death in newly weaned piglets. Oral passive immunization with chicken egg yolk immunoglobulins (IgY) have attracted considerable attention for treatment of gastrointestinal infection due to its high specificity. In this study it was estimated the protective effect of anti-K88 fimbriae IgY against E. coli K88 adhesion to piglet intestinal mucus in vitro and to investigate the potential use of IgY for controlling E. coli-induced diarrhea in weaned piglets in vivo. RESULTS: E. coli K88 was incubated with IgY for 24 h, and the bacterial growth profiles showed that specific IgY with a concentration higher than 5 mg/mL was observed to significantly inhibit the growth of E. coli K88 compared to nonspecific yolk powder in a liquid medium. Moreover, pretreatment with 50 mg/mL of IgY was found to significantly decrease the adhesion ability of E. coli K88 to porcine jejunal and ileal mucus, further supported by the observations from our immunofluorescence microscopic analysis. In vivo, administration of IgY successfully protected piglets from diarrhea caused by E. coli K88 challenge. Additionally, IgY treatment efficiently alleviated E. coli-induced intestinal inflammation in piglets as the gene expression levels of inflammatory cytokines TNF-α, IL-22, IL-6 and IL-1ß in IgY-treated piglets remained unchanged after E. coli K88 infection. Furthermore, IgY significantly prevented E. coli K88 adhering to the jejunal and ileal mucosa of piglets with E. coli infection and significantly decreased E. coli and enterotoxin expression in colonic contents. CONCLUSION: Outcome of the study demonstrated that IgY against the fimbrial antigen K88 was able to significantly inhibit the growth of E. coli K88, block the binding of E. coli to small intestinal mucus, and protect piglets from E. coli-induced diarrhea. These results indicate that passive immunization with IgY may be useful to prevent bacterial colonization and to control enteric diseases due to E. coli infection. The study has great clinical implication to provide alternative therapy to antibiotics in E coli induced diarrhea.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Diarreia/etiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/complicações , Imunoglobulinas/farmacologia , Animais , Antígenos de Bactérias/imunologia , Citocinas/genética , Diarreia/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/imunologia , Proteínas de Fímbrias/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunização Passiva , Imunoglobulinas/uso terapêutico , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Ligação Proteica/efeitos dos fármacos , Suínos
5.
Cell Prolif ; 52(5): e12663, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347748

RESUMO

OBJECTIVE: Induction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages. METHODS: RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array. RESULTS: Both cisplatin and doxorubicin dose-dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP-ribose) polymerase. Consistent with caspase-3 activation, GSDME was cleaved to generate its N-terminal fragment (GSDME-NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase-3 significantly attenuated the generation of GSDME-NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase-3 activation and GSDME-NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection. CONCLUSION: Chemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase-3/GSDME-mediated secondary necrosis.


Assuntos
Caspase 3/metabolismo , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Piroptose/efeitos dos fármacos , Receptores Estrogênicos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/mortalidade , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/veterinária , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores Estrogênicos/antagonistas & inibidores , Receptores Estrogênicos/genética , Taxa de Sobrevida
6.
Rev Soc Bras Med Trop ; 52: e20180499, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271618

RESUMO

INTRODUCTION: : Escherichia coli ranks among the most common sources of urinary tract infections (UTI). METHODS: Between November 2015 and August 2016, 90 isolates of E. coli were isolated from patients at Rize Education and Research Hospital in Turkey. Antibiotic susceptibility was determined for all isolates using the Kirby-Bauer disk diffusion method. These E. coli isolates were also screened for virulence genes, ß-lactamase coding genes, quinolone resistance genes, and class 1 integrons by PCR. RESULTS: With respect to the antibiotic resistance profile, imipenem and meropenem were effective against 98% and 90% of isolates, respectively. A high percentage of the isolates showed resistance against ß lactam/ß lactamase inhibitor combinations, quinolones, and cephalosporins. PCR results revealed that 63% (57/90) of the strains carried class 1 integrons. In addition, a high predominance of extended-spectrum ß-lactamases (ESBLs) was observed. The qnrA, qnrB, and qnrS genes were found in 24 (26.6%), 6 (6.6%), and 3 (3.3%), isolates, respectively. The most common virulence gene was fim (82.2%).The afa, hly, and cnf1 genes were detected in 16.6%, 16.6%, and 3.3% of isolates, respectively. Moreover, we observed eleven different virulence patterns in the 90 E. coli isolates. The most prevalent pattern was fim, while hly-fim, afa-aer-cnf-fim, aer-cnf, afa-aer, and afa-cnf-fim patterns were less common. CONCLUSIONS: Most of the E. coli virulence genes investigated in this study were observed in E. coli isolates from UTI patients. Virulence genes are very important for the establishment and maintenance of infection.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/genética , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções Urinárias/tratamento farmacológico , Fatores de Virulência/genética , Escherichia coli/isolamento & purificação , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Quinolonas , Turquia , Infecções Urinárias/microbiologia , beta-Lactamases
7.
Chem Biol Interact ; 310: 108711, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31207224

RESUMO

Gastrointestinal infections are considered a serious public health problem in view of their high incidence and the increasing antibiotic resistance of the microorganisms involved in their pathogenesis, namely Escherichia coli. Consequently, finding new ways to prevent and/or threat these infections is urgent. In this study we investigated whether a well-characterised polyphenolic red wine extract is able to inhibit the cytotoxic effects induced by a clinical pathogenic Escherichia coli strain (E. coli 270) against HT-29 colon epithelial cells. Firstly, we provide evidences showing that the E. coli strain triggered the death of the intestinal epithelial cells through the production and release of a toxin. Then we support that, in a concentration dependent way, RWE through both, a direct interaction with bacterial exotoxin and the epithelial cells, prevented the action of the toxin on the cells, significantly reducing cell death. This intends to constitute a position paper as detailed mechanisms for the inhibition of E. coli-induced toxicity by polyphenols are yet to be completely unraveled. However, considering that the amount of red wine polyphenols used can be easily achieved in a normal diet, this study suggests that RWE may provide a readily available dietary product with potential benefit for the prevention and/or treatment of intestinal infections induced by intestinal pathogenic bacteria and may open new therapeutic avenues for the development of potential natural antimicrobial agents.


Assuntos
Infecções por Escherichia coli/prevenção & controle , Gastroenteropatias/prevenção & controle , Polifenóis/uso terapêutico , Vinho , Morte Celular/efeitos dos fármacos , Células Epiteliais/patologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Células HT29 , Humanos , Polifenóis/farmacologia
8.
Int J Med Inform ; 127: 127-133, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31128824

RESUMO

BACKGROUND: In general practice, many infections are treated empirically prior to or without microbiological confirmation. Prediction of antimicrobial susceptibility could optimise prescribing thus improving patient outcomes. Decision tree models are a novel idea to predict AMR at the time of clinical presentation. This study aims to apply a prediction model using a decision tree approach to predict the antimicrobial resistance (AMR) of pathogens causing urinary tract infections (UTI) for patients over 65 years based on pre-existing routine laboratory data. METHODS: Data were extracted from the database of the microbiological laboratory of the University Hospitals Galway (UHG). All urine results from patients over 65 years, their microbiological analysis and susceptibility (AST) results from January 2011 to December 2015 were included. The primary endpoint was culture result and resistance to antimicrobials (nitrofurantoin, trimethoprim, ciprofloxacin, co-amoxiclav, and amoxicillin) commonly used to treat UTI. A non-parametric regression tree analysis i.e. a decision tree model was generated with the 75% of the dataset (training set) and validated with the remaining 25% (test set). The model performance was evaluated measuring Area Under the Curve Receiver Operating Characteristic (AUC_ROC) curve. RESULTS: A total of 99,101 urine samples of patients over 65 years were submitted for culture over the five years and 27% had significant bacteriuria (≥104 cfu/ml) and AST. The most common identified causative organisms were E.coli, Klebsiella spp. and Proteus spp. E.coli was more often resistant to amoxicillin (66%) followed by Proteus spp. (41%). Klebsiella spp. and Proteus spp. were more often resistant to trimethoprim (78% and 54% respectively). E. coli resistance to nitrofurantoin is low (<10%). The decision tree model showed an AUC-ROC score of 0.68 for culture and in between 0.60 to 0.97 for antimicrobial resistance of the pathogens, with the inclusion of patient's descriptors only. Including the uropathogen in the model did not change model performance. CONCLUSIONS: The decision tree models using patient descriptors available at the time of presentation showed fair to excellent performance in predicting culture and antimicrobial resistance. The presented models provide an alternative approach to decision making on antimicrobial prescribing for UTIs. Increasing more predictors in the model could improve the model performance. Prospective data collection, validation and feasibility testing of the model including data from other laboratories will progress the practical implementation of similar models.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções Urinárias/tratamento farmacológico , Idoso , Árvores de Decisões , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos
9.
Artigo em Inglês | MEDLINE | ID: mdl-31083597

RESUMO

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.


Assuntos
Infecções por Escherichia coli/tratamento farmacológico , Gastroenterite/tratamento farmacológico , Microbioma Gastrointestinal , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Probióticos/uso terapêutico , Escherichia coli Shiga Toxigênica/fisiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Gastroenterite/complicações , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Incidência
10.
J Med Microbiol ; 68(6): 837-847, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31084700

RESUMO

INTRODUCTION: The last few years have seen the emergence of multi-drug resistant (MDR) Gram-negative infections, which are associated with high morbidity and mortality. The indiscriminate use of colistin has led to the development of resistance, which can be diagnosed effectively by broth microdilution. Studies from India are limited, and this study was conducted in order to determine the prevalence and risk factors associated with colistin resistance. METHODS: Urine samples from patients admitted with urinary tract infection (UTI), growing MDR Escherichia coli and Klebsiella pneumoniae, were tested for the minimum inhibitory concentration (MIC) of colistin by broth microdilution. Isolates with an MIC >2 µg ml-1 (resistant) were subjected to polymerase chain reaction (PCR) for the mcr1, mcr2 and mgrB genes. A case-control study with 21 cases (resistant) and 42 matched controls (sensitive) was designed to evaluate risk factors and outcomes (recurrent UTI, readmission and hospital stay >2 weeks). RESULTS: Two hundred and fifty MDR isolates (E. coli=142/2319 and K.pneumoniae=108/775) from 216 patients were selected from the 25 046 isolates screened. Twenty-five isolates (20 K.pneumoniae and 5 E. coli) were resistant to colistin, with a prevalence of 3.52  % in E. coli and 18.5  % in K. pneumoniae among the MDR isolates. PCR for the mcr1 and mcr2 genes was negative. Multivariate regression showed that multiple episodes of hospitalization, hospital stay >2 weeks, exposure to >three antibiotic classes and abnormality/surgery of the lower urinary tract were the significant risk factors for colistin resistance. Previous use of colistin and colistin resistance had a significant effect on all outcomes. CONCLUSIONS: K. pneumoniae show six times higher prevalence of colistin resistance than E. coli, and the emergence of resistant organisms has led to an increase in morbidity in infected patients.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/genética , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Infecções Urinárias/epidemiologia , Adulto , Proteínas de Bactérias/genética , Estudos de Casos e Controles , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Índia/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Adulto Jovem
11.
J Med Microbiol ; 68(5): 711-719, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30994430

RESUMO

PURPOSE: Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population. METHODOLOGY: We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option). RESULTS: Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum ß-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination. CONCLUSION: Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.


Assuntos
Antibacterianos/farmacologia , Fosfomicina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bacteriemia/tratamento farmacológico , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pseudomonas/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/microbiologia
12.
Biomed Res Int ; 2019: 3937812, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032344

RESUMO

Urinary tract infection (UTI) and preeclampsia are common among pregnant women and are associated with adverse maternal-fetal and neonatal outcomes. Despite this, limited information exists on the association between UTIs and preeclampsia in Tanzania to guide specific management and thereby averting the adverse outcomes. A 1:2 matched case-control study (by age and gravidity) involving 131 pregnant women with preeclampsia (cases) and 262 without preeclampsia (controls) was conducted. Sociodemographic and clinical information was collected using a questionnaire. Midstream urine samples were collected during admission for culture and antimicrobial susceptibility testing (AST). Out of 393 pregnant women enrolled, 110 (28.0%), 95% CI: 23.8%-32.7%, had significant bacteriuria [cases: 50.4% (66/131) and control: 16.8% (44/262)]. Pregnant women with preeclampsia had 7.7 odds of having significant bacteriuria than those without preeclampsia [OR=7.7, 95% CI (4.11-14.49); p-value <0.001]. Escherichia coli, 50 (45.5%), and Klebsiella spp., 25 (23.6%), predominated, and resistance to gentamicin, ceftriaxone, and piperacillin-tazobactam ranged from 9.0% to 29.0% in these dominant species. Extended spectrum beta lactamases (ESBL) production in Escherichia coli and Klebsiella spp. was 18.0% (9/50) and 15.4% (4/26), respectively. Routine urine culture and AST among pregnant women with preeclampsia should be introduced in the antenatal clinics to ensure prompt management. Delineation of maternal-fetal and neonatal outcomes among pregnant women with preeclampsia and UTIs would be of interest in future studies.


Assuntos
Farmacorresistência Bacteriana Múltipla , Pré-Eclâmpsia/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Adulto , Ceftriaxona/uso terapêutico , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Gentamicinas/uso terapêutico , Hospitais , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Troca Materno-Fetal , Combinação Piperacilina e Tazobactam/uso terapêutico , Pré-Eclâmpsia/microbiologia , Pré-Eclâmpsia/patologia , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/patologia , Tanzânia/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia , Adulto Jovem , beta-Lactamases/química , beta-Lactamases/genética
13.
BMC Public Health ; 19(1): 426, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014305

RESUMO

BACKGROUND: The frequency of antimicrobial resistance has steadily increased worldwide, induced by inappropriate use of antibiotics in a variety of settings. We analyzed the ecological correlation between fluoroquinolone consumption and levofloxacin resistance in Escherichia coli in Japan. METHODS: We collected information on cases of E. coli resistant to levofloxacin in 2015-2016 in all 47 prefectures from the Japan Nosocomial Infections Surveillance system. Information on fluoroquinolone consumption was obtained from pharmaceutical sales data. To address potential confounding, we also collected information on the number of physicians, nurses, and medical facilities per 100,000 individuals. RESULTS: We identified higher fluoroquinolone consumption and higher resistance in western prefectures, and lower consumption and resistance in eastern prefectures. Multivariate analysis identified a positive correlation between fluoroquinolone consumption and levofloxacin resistance in both 2015 and 2016. CONCLUSIONS: Fluoroquinolone consumption and levofloxacin-resistant E. coli are potentially associated on a nationwide scale. The relationship between the two must be elucidated using additional studies with different epidemiological designs, so that any possible counter-measures, including alternative prescription, can be considered in the future.


Assuntos
Antibacterianos/provisão & distribução , Farmacorresistência Bacteriana , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/provisão & distribução , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Bases de Dados de Produtos Farmacêuticos/estatística & dados numéricos , Infecções por Escherichia coli/tratamento farmacológico , Geografia , Humanos , Japão/epidemiologia , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana
14.
J Anim Sci ; 97(6): 2342-2356, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30958881

RESUMO

Bacterial infection causes nutrient malabsorption in small intestine. KR-32, a kind of synthetic antimicrobial peptide, has the bacteriostatic effect. In the present study, 2 experiments were designed to analyze the effects of KR-32 on fat absorption of piglets with or without Escherichia coli infection. In Exp. 1, 12 weaning piglets (21 d old) were allocated to 2 groups: piglets with an intraperitoneal (i.p.) injection of antimicrobial peptide KR-32 (APK) and piglets with an i.p. injection of an equivalent volume (1 mL) of phosphate-buffered saline (PBS) (CON-1). Results showed that after 7 d of growth, KR-32 did not significantly change growth performance and apparent total tract digestibility (ATTD) of feed nutrients of normal pigs. To confirm whether KR-32 affects those of enterotoxigenic Escherichia coli (ETEC) K88-challenged pigs, we performed Exp. 2, in which 18 piglets (28 d old) were divided into the following 3 groups: 1) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of 0.6 mg/kg KR-32 (K88 + APK); 2) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of an equivalent volume (1 mL) of PBS (K88); and 3) piglets with an oral administration of fresh Luria-Bertani broth (50 mL) followed by an i.p. injection of an equivalent volume of PBS (CON-2). Results showed that ETEC K88 challenge led to poor ADFI, ADG, and G:F in piglets; decreased ATTD of feed nutrients, especially CP and ether extract (EE); and intestinal morphology disorder. After i.p. injection of KR-32, ADG and ATTD of CP and EE were greatly increased, G:F was significantly reduced (P < 0.05), and, especially, ATTD of EE returned to a normal level compared with group CON-2. Fatty acid absorption also highly increased after KR-32 injection. Then we focused on fat digestion and fatty acid uptake. The pH in the intestine and pancreas lipase showed no difference among the 3 treatment groups, whereas fatty acid transporter protein 4 (FATP4) expression was remarkably improved (P < 0.05) and the epithelial barrier was recovered after i.p. injection of KR-32. In conclusion, KR-32, given to ETEC K88-challenged piglets, improved growth performance, ATTD of EE, fatty acid absorption, and intestinal morphology, which indicated that KR-32 was likely to improve the expression of FATP4 and by repairing the epithelial barrier, thereby alleviating fatty acid malabsorption.


Assuntos
Anti-Infecciosos/farmacologia , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/veterinária , Proteínas de Transporte de Ácido Graxo/genética , Ácidos Graxos/metabolismo , Doenças dos Suínos/tratamento farmacológico , Animais , Digestão/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Transporte de Ácido Graxo/efeitos dos fármacos , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/sangue , Fezes/microbiologia , Feminino , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/ultraestrutura , Peptídeos/farmacologia , Distribuição Aleatória , Suínos , Doenças dos Suínos/microbiologia , Doenças dos Suínos/patologia , Desmame
15.
ACS Appl Mater Interfaces ; 11(16): 14597-14607, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30938506

RESUMO

Along with the rapid appearance of superbacteria with multidrug resistance, it is a challenge to develop new antibacterial materials to address this big issue. Herein, we report a novel amine group-modified fullerene derivative (C70-(ethylenediamine)8 abrr. C70-(EDA)8), which reveals a high performance in killing superbacteria, and most importantly, it shows negligible toxicity to the mammalian cells. The strong antibacterial ability of this material was attributed to its unique molecular structure. On one hand, amino groups on the EDA part make it easy to affix onto the outer membrane of multidrug resistance Escherichia coli by electrostatic interactions. On the other hand, the hydrophobic surface on the C70 part makes it easy to form a strong hydrophobic interaction with the inner membrane of bacteria. Finally, C70-(EDA)8 leads to the cytoplast leakage of superbacteria. In contrast, the C70-(EDA)8 is nontoxic for mammalian cells due to different distributions of the negative charges in the cell membrane. In vivo studies indicated that C70-(EDA)8 mitigated bacterial infection and accelerated wound healing by regulating the immune response and secretion of growth factors. Our amine group-based fullerene derivatives are promising for clinical treatment of wound infection and offer a new way to fight against the superbacteria.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Escherichia coli , Escherichia coli/crescimento & desenvolvimento , Fulerenos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos , Animais , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Fulerenos/química , Fulerenos/farmacocinética , Fulerenos/farmacologia , Células HEK293 , Humanos , Masculino , Ratos , Ratos Wistar , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
16.
Comp Immunol Microbiol Infect Dis ; 63: 117-126, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30961806

RESUMO

The aims of this study were to investigate the prevalence, antibiotic resistance, presence of class 1 and 2 integrons, Extended Spectrum ß-Lactamases (ESBL) genes, phylogenetic group and epidemiological relationships of EPEC, ETEC and EHEC pathotypes isolated from patients with diarrhea and farm animals in south east region of Iran. A total of 671 diarrheagenic E. coli (DEC) were collected from stool samples of 395 patients with diarrhea and 276 farm cattles and goats. Presence of EPEC, ETEC and EHEC were identified using multiplex-PCR employing primers targeted the shiga toxin (stx), intimin (eae), bundle forming pili (bfp), and enterotoxins (lt and st) genes. The highest proportion of the patients (64%) were children under age 1-15 year (p ≤ 0.05). Among the isolates, atypical EPEC was detected in 26 patients and 14 animal stool samples, while typical EPEC was found in 2 cattles. ETEC isolates were detected in stools of 13 patients and 4 EHEC was identified in 3 goats and one cattle. The isolates were checked for susceptibility to 14 antibiotics. 50% (n = 13) of EPEC and 61.5% (n =8) of ETEC showed multi-drug resistance (MDR) profiles and one EPEC was found to be extensive drug resistant (XDR). In contrast, EHEC isolates were susceptible to the majority of antimicrobial agents. The MDR isolates were positive for blaTEM and blaCTX-M ESBL genes and carried class 1 integrons. Further study on the biofilm formation indicated that, 3 out of 4 EHEC isolates showed strong biofilm, while other pathotypes had either moderate, weak or no biofilm activity. Majority of EPEC isolates were belonged to phylogenetic group B1, all except one ETEC were classified as phylogenetic group A and two EHEC were belonged to phylogroup D, respectively. A multilocus variable tandem repeat analysis (MLVA) exhibited 22 distinct patterns. In conclusion, MLVA data showed high clonal diversity. Presence of EHEC in animal origins pose public health concern in this region.


Assuntos
Diarreia/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli Êntero-Hemorrágica/isolamento & purificação , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/veterinária , Adesinas Bacterianas/genética , Adolescente , Animais , Animais Domésticos/microbiologia , Antibacterianos/uso terapêutico , Bovinos , Doenças dos Bovinos , Criança , Pré-Escolar , Escherichia coli Êntero-Hemorrágica/efeitos dos fármacos , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Enteropatogênica/efeitos dos fármacos , Escherichia coli Enteropatogênica/genética , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Escherichia coli Enterotoxigênica/genética , Enterotoxinas/genética , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Fímbrias Bacterianas/genética , Doenças das Cabras , Cabras , Humanos , Lactente , Integrons/genética , Irã (Geográfico) , Testes de Sensibilidade Microbiana , Tipagem Molecular , Toxina Shiga/genética , beta-Lactamases/genética
17.
J Dairy Sci ; 102(6): 5438-5457, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981475

RESUMO

The objective of this negatively controlled, randomized clinical trial was to examine clinical outcomes of 2-d or 8-d treatment using an approved intramammary (IMM) product containing ceftiofur hydrochloride compared with no antimicrobial treatment of nonsevere, gram-negative cases of clinical mastitis (CM). Additionally, we contrasted clinical outcomes of cases caused by Escherichia coli (n = 56) or Klebsiella pneumoniae (n = 54). Cases (n = 168) of nonsevere (abnormal milk or abnormal milk and udder) CM were randomly assigned to receive 2 d (n = 56) or 8 d (n = 56) of IMM ceftiofur or assigned to a negative control group (n = 56). At enrollment, quarter milk samples were collected and used for on-farm culture, somatic cell count (SCC), and confirmatory microbiological analysis. Quarter milk samples were collected weekly from 7 to 28 d after enrollment for microbiological and SCC analysis. Clinical outcomes were followed for 90 d or until the end of lactation (follow-up period, FUP). Overall, no significant differences in quarter-level recurrence of CM (32% for negative control, 34% for the 2-d treatment, and 32% for the 8-d treatment), culling (18% for negative control, 12% for 2-d treatment, and 11% for 8-d treatment), voluntary dry-off of affected quarters (20% for negative control, 30% for 2-d treatment, and 27% for 8-d treatment), days until return to normal milk (4.2 days for negative control, 4.8 days for 2-d treatment, 4.5 days for 8-d treatment), weekly quarter-SCC during the FUP (6.1, 6.3, and 6.0 log10SCC for the negative control, 2-d, and 8-d treatments, respectively), or daily milk yield during the FUP (37.1, 36.3, and 37.6 kg/cow per day for the negative control, 2-d, and 8-d treatments, respectively) were observed among experimental groups. Days of discarded milk were greater for cows assigned to 8-d IMM ceftiofur (11.1 d) than for cows assigned to 2-d (6.9 d) or cows assigned to negative control (5.6 d). Bacteriological cure (BC) at 14 and 21 d after enrollment was greater in cows assigned to 8-d (89%) and 2-d (84%) treatment than in cows assigned to negative control (67%), but this outcome was confounded by pathogen. For CM caused by Kleb. pneumoniae, BC was greater for quarters assigned to receive treatment (combined 2-d and 8-d groups; 74% BC) than for quarters assigned to negative control (18%). In contrast, no differences in BC were observed for CM caused by E. coli (97-98%). Culling and voluntary dry-off of affected quarters were significantly greater for cows with quarters affected by Kleb. pneumoniae (22% culled, 39% voluntary dry-off of quarters) than for cows with quarters affected with E. coli (7% culled, 11% voluntary dry-off of quarters). Overall, use of IMM ceftiofur did not result in improvement of most clinical outcomes, but differences between E. coli and Kleb. pneumoniae were evident. In contrast to E. coli, Kleb. pneumoniae caused chronic intramammary infection and induced worse clinical outcomes. Intramammary antibiotic treatment of most mild and moderate cases of CM caused by E. coli is not necessary, but more research is needed to identify which quarters affected by Kleb. pneumoniae may benefit from antimicrobial therapy.


Assuntos
Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Mastite Bovina/tratamento farmacológico , Leite/microbiologia , Animais , Bovinos , Indústria de Laticínios , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Fazendas , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Lactação , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/microbiologia , Distribuição Aleatória
18.
J Bronchology Interv Pulmonol ; 26(2): 132-136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30908392

RESUMO

Chronic pleural infection is characterized by thickened pleura and nonexpandable lung often requiring definitive surgical intervention, such as decortication and/or pleural obliteration procedures. Such procedures are associated with significant morbidity and require proper patient selection for a successful outcome. We report a cohort of 11 patients with pleural space infection and a nonexpandable lung treated with tunneled pleural catheters (TPCs). Following placement, hospital discharge and TPC removal occurred after a median of 5 and 36 days, respectively. Three patients presented with residual loculated effusion that resolved with instillation of intrapleural fibrinolytic therapy. One patient eventually required open window thoracostomy for ongoing pleural infection due to poor medical compliance with TPC care and drainage instructions. TPCs represent an alternative option for drainage of an infected pleural space in nonsurgical candidates with a nonexpandable lung. Their use, as a compliment to traditional treatment, may facilitate prompt hospital discharge and ambulatory management in patients with limited life expectancy.


Assuntos
Cateteres , Infecção/cirurgia , Pleurisia/cirurgia , Toracostomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/cirurgia , Tubos Torácicos , Drenagem , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/cirurgia , Feminino , Fluoroscopia , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/cirurgia , Humanos , Infecção/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pleurisia/tratamento farmacológico , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/cirurgia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/cirurgia , Cirurgia Torácica Vídeoassistida , Toracoscopia
19.
J Ethnopharmacol ; 237: 300-306, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-30904704

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Apium graveolens (celery) are used traditionally in Persian and European medicine for the treatment of uncomplicated urinary tract infections. AIM OF THE STUDY: The study aimed at identifying potential antiadhesive compounds from celery extracts to provide strategies for improved standardization of the herbal material. MATERIALS AND METHODS: Decoction, hydroalcoholic and acetone extracts were prepared from celery fruits. Bioassay-guided fractionation was performed by Fast Centrifugal Partition Chromatography and preparative HPLC, followed by LC-MS and NMR investigations for structure elucidation. The antiadhesive activity of extracts, fractions and purified compounds was assessed by flow cytometry, evaluating the adhesion of fluorescent-labelled uropathogenic bacteria (UPEC NU14) to T24 bladder cells; mannose served as positive control. Influence of the extract on gene expression of selected adhesins and fitness genes was monitored by qPCR. RESULTS: Concentration-dependent antiadhesive activity was found for the hydroalcoholic and even more for the acetone extract AE (IC50 85 µg/mL) from celery fruits. Bioassay-guided fractionation revealed the presence of the phthalides senkyunolide (1, inactive) and sedanenolide (2, IC50 790 µM). 2 is assessed as the main antiadhesive compound, which accounts for 4.0% in the water extract, for 18% in the hydroethanolic extract and for 71% in AE. Additionally a similar phthalide, Z-ligustilide (5), was shown to exert an IC50 of 611 µM. Furthermore, AE caused a significant upregulation of fimH and sfaG in free floating, non-attached UPEC and significantly down-regulated these genes in adherent bacteria. CONCLUSIONS: Phthalides were identified as the main active compounds in polar and semi-polar extracts, which exert strong antiadhesive activity against uropathogenic E. coli. The current findings support the traditional use in phytotherapy for urinary tract infections and provide a base for standardization of the herbal material.


Assuntos
Antibacterianos/farmacologia , Apium , Extratos Vegetais/farmacologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular Tumoral , Infecções por Escherichia coli/tratamento farmacológico , Frutas , Humanos , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/fisiologia
20.
Prev Vet Med ; 165: 52-62, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30851928

RESUMO

The purpose of this longitudinal study was to describe the occurrence of antibiotic resistance in faecal Escherichia coli isolated from pigs between birth and slaughter and its association with antibiotic treatment. Four objectives were addressed: comparison of antibiotic resistance in isolates from a) treated vs. non-treated pigs, b) follow-up vs. initial samples of treated and non-treated pigs, c) pigs receiving treatments via different administration routes and d) sows and their piglets. Each comparison addressed the following antibiotic groups used for treatment: beta-lactams, tetracyclines, polymyxins and macrolides, and the susceptibility of E. coli isolates to the respective agents: ampicillin, tetracycline, colistin and azithromycin. Between 2014 and 2016, 406 focal animals from 29 commercial breeding herds were followed from birth to the end of the relevant fattening periods. All antibiotic treatments in these pigs were documented. Faecal samples were collected from the focal pigs once while suckling, once after weaning and three times during fattening, and from their dams once around farrowing. Escherichia coli isolated from these samples was tested for antibiotic susceptibility. In total, 264 animals from 19 breeding herds were treated with an antibiotic at least once during their lifetime. Beta-lactams, tetracyclines and colistin were used most frequently. Piglets were treated individually by injection (n = 108 treatments) or via drench (9); weaners via feed (192) or water (56) and fatteners via feed (30) or injection (15). Resistance to ampicillin and tetracycline in E. coli was already common prior to antibiotic treatment. Resistance proportions were higher for beta-lactam-, tetracycline-, colistin- and macrolide-treated pigs compared to untreated pigs at different sampling periods (p < 0.05; Fisher's exact test). In the logistic analysis, the difference was confirmed for beta-lactam-treated vs. untreated pigs. In E. coli from macrolide-untreated pigs, resistance to azithromycin was more frequent compared to pre-treatment values. Route of application did not affect rates of antibiotic resistance in the logistic analysis even though Fisher's exact test indicated associations for beta-lactams (feed/water vs. injection), tetracyclines (feed/water vs. non-treatment) and macrolides (tulathromycin-injection vs. tylosin in feed). Piglets were more likely to carry an E. coli resistant to ampicillin or azithromycin if their dams did so as well. Our results suggest further research on resistance effects by administration routes is required. Reducing antibiotic resistance in sows might lead to a lower level of beta-lactam or macrolide-resistant E. coli among their progeny. To preserve treatment options for bacterial infections, antibiotic use should be restricted to necessary cases.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/veterinária , Escherichia coli/efeitos dos fármacos , Doenças dos Suínos/prevenção & controle , Animais , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Fezes/microbiologia , Estudos Longitudinais , Fatores de Risco , Suínos/microbiologia , Doenças dos Suínos/tratamento farmacológico , Doenças dos Suínos/epidemiologia
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