fosfomycin and Hemolytic-Uremic-Syndrome

Topics: Anti-Bacterial Agents; Dialysis; Electrolytes; Escherichia coli Infections; Escherichia coli O157; Fluid Therapy; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Prognosis; Shiga Toxins

Escherichia coli O157:H7 is a foodborne pathogen causing haemorrhagic colitis, which is sometimes complicated by haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura.. To review the available evidence regarding the question of whether antibiotics are effective or harmful for the treatment of patients infected with E. coli O157:H7 infection.. We searched in the PubMed for relevant laboratory and clinical studies published between 1982 and 2005.. In vitro studies have shown that most E. coli O157:H7 isolates are susceptible to various antibiotics, although certain antibiotics, especially at sublethal concentrations, have been found to increase the release of Shiga-like toxins, which have been associated with the development of haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura in humans. No clinical studies have indicated that antibiotics are effective in reducing the duration of E. coli O157:H7 infection or the duration of diarrhoea or bloody diarrhoea specifically, while a few studies have supported that some antibiotics, especially quinolones and fosfomycin, may prevent the development of haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura. On the other hand, there are some clinical studies that associate antibiotics with a higher risk for haemolytic uraemic syndrome and/or longer duration of diarrhoea, even with high mortality.. More randomized controlled trials are necessary in order to elucidate whether antibiotics are effective in reducing the morbidity and mortality of E. coli O157:H7 infection, rather than having a detrimental effect.

Topics: Animals; Anti-Bacterial Agents; Diarrhea; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Quinolones; Shiga Toxins; Treatment Outcome

Verocytotoxin producing Escherichia coli(VTEC) causes gastrointestinal infections worldwide. In at most 8% of the children in Japan who are infected with VTEC, hemolytic-uremic syndrome(HUS) develops soon after the onset of diarrhea. Treatment with antibiotics does not ameliorate VTEC infections, and in some studies from western countries, it has been associated with worse clinical outcomes. It was recently indicated in Japan that early administration of fosfomycin to the patients with VTEC infection can decrease the risk of HUS. Moreover, early administration of Synsorb-Pk with high affinity to verocytotoxin to the patients with gastrointestinal VTEC infection was demonstrated to decrease the incidence of very mild and mild HUS, but it did not decrease the risk of moderate and severe HUS. In the developing stage of HUS, intravenous administration of fluid and electrolytes should be determined cautiously to prevent hyponatremia and systemic congestion.

Topics: Animals; Electrolytes; Escherichia coli Infections; Escherichia coli O157; Fluid Therapy; Fosfomycin; Gastroenteritis; Hemolytic-Uremic Syndrome; Humans; Hyponatremia; Organosilicon Compounds; Risk; Trisaccharides

To clarify the effect of early fosfomycin treatment, an antimicrobial agent in common use in Japan, on children with E. coli O157 with the aim of preventing hemolytic uremic syndrome (HUS).. Non-randomized prospective study for development of HUS among inpatients with E. coli O157.. The hospitals where the 292 inpatients were treated.. A total of 292 inpatients aged six to eleven years with E. coli O157 infection, 36 (12.3%) of whom were HUS cases.. Most of the HUS inpatients (91.7%) developed this complication between the sixth and ninth day of illness. We therefore analyzed the effects of antimicrobial therapy, especially that of fosfomycin, on prevention of HUS within the first five days of illness, because fosfomycin was the most frequently used (88.0%). To clarify the effect of fosfomycin alone on prevention of HUS, we carried out an analysis using the data for 130 inpatients who received fosfomycin alone or did not receive any antimicrobial agents, within the first five days of illness. multivariate analysis, controlled for age, gender and presence of fever, showed that all adjusted odds ratios for the development of HUS with the use of fosfomycin within the first three days of illness were less than 1.0, with the use of fosfomycin on the second day of illness achieving statistical significance (adjusted OR, 0.09; 95% CI, 0.01-0.79). Furthermore, inpatients who took fosfomycin within the first two days of illness developed HUS significantly less often than those who did not (adjusted OR, 0.15; 95% CI, 0.03-0.78). On the other hand, fosfomycin therapy on and after the third day of illness was not associated with the prevention of HUS.. The early use of fosfomycin within the first two days of illness might prevent the development of HUS.

Topics: Anti-Bacterial Agents; Child; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Male; Prospective Studies

Ciprofloxacin, meropenem, fosfomycin, and polymyxin B strongly increase production of outer membrane vesicles (OMVs) in

Topics: Anti-Bacterial Agents; Cell Membrane Structures; Ciprofloxacin; Escherichia coli Infections; Escherichia coli O104; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Meropenem; Microbial Sensitivity Tests; Polymyxin B; Shiga Toxin 2; Thienamycins

The role of antimicrobial therapy for Shiga toxin-producing Escherichia coli (STEC) infection has not been clearly defined. A prospective study identified antibiotic use as a significant risk factor for subsequent development of haemolytic-uraemic syndrome (HUS). However, early treatment with fosfomycin, a bacteriostatic antibiotic, resulted in a significantly decreased risk of HUS. The aim of this study was to evaluate a role of fosfomycin therapy in the development of HUS in children who contracted STEC infection. The study included 118 children who contracted a STEC infection between 1997 and 2013. A pre-defined questionnaire was utilised to collect patient information regarding age, sex, presenting symptoms (fever, abdominal pain, diarrhoea and bloody stool), results of stool culture examination, initial results of white blood cell counts and C-reactive protein (CRP), use of antibiotics, the timing of introduction of antibiotics, and complications including HUS. Of the 118 patients, 64 were diagnosed with HUS and the remaining 54 did not develop HUS. Multivariate analysis showed that three independent factors (age, initial values of CRP and use of fosfomycin) were significantly associated with the occurrence of HUS; of particular note, the adjusted odds ratio for use of fosfomycin was 0.15 (95% confidence interval 0.05-0.45). Use of fosfomycin within the first 5 days of illness may decrease the development of STEC-related HUS in children.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Escherichia coli Infections; Female; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Infant; Infant, Newborn; Male; Shiga-Toxigenic Escherichia coli; Surveys and Questionnaires

It is not clear how Escherichia coli O157 invades human enteric epithelium and causes the haemolytic uraemic syndrome (HUS), and nor has the most appropriate treatment of E. coli O157 infection been established. Verotoxins, leucocytes and proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, are considered essential for the development of HUS. We used the Caco-2 cell monolayer system, well-known as an in-vitro model of human intestinal infection, to determine how E. coli O157 interacts with intestinal epithelial cells and also studied the influence of fosfomycin on the virulence of the bacteria. Results showed that the E. coli O157 used in this study did not penetrate the Caco-2 cell monolayer system, unlike Salmonella typhimurium SL1344, and verotoxin 1 (VT 1), but not VT 2, translocated across the system. In an in-vitro conventional assay, fosfomycin increased the amount of verotoxins but it did not influence penetration of bacteria and translocation of verotoxins in the Caco-2 cell monolayer system. The production of both IL-8 (a potent neutrophil activator) and TNF-alpha in the human monocytic THP-1 cell line was reduced by fosfomycin-treated basolateral medium in this system. These results indicate that fosfomycin may be a potent drug for preventing HUS caused by E. coli O157 infection.

Topics: Anti-Bacterial Agents; Bacterial Toxins; Biological Transport; Caco-2 Cells; Cytokines; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Membrane Potentials; Shiga Toxin 1

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Child; Escherichia coli Infections; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Japan; Organosilicon Compounds; Risk Factors; Surveys and Questionnaires; Trisaccharides

Predictive factors for the development of hemolytic uremic syndrome (HUS) were evaluated in 88 inpatients who suffered from enterohemorrhagic E. coli infections in the outbreak in Sakai, 1996. All in- and outpatients received oral or intravenous fosfomycin within acute phase of hemorrhagic colitis, and HUS complicated 1.4% of them. Persistence of bloody stools and diarrhea were longer in HUS patients than in non-HUS patients, but persistence of abdominal pain was not different in either group. Leukocytosis with leukocyte counts over 15,000/microliters and/or elevated CRP level over 2.0 mg/dl at admission, and fever and/or vomiting in the course of hemorrhagic colitis were more frequent in HUS patients than in non-HUS patients. Early intensive treatments including gammaglobulin, urinastatin, aspirin, and dipyridamole were employed in 34 high risk patients for prevention of HUS. These patients were estimated to be at risk of developing HUS because of incomplete HUS, nephropathy, elevated LDH level, thrombocytopenia, or age younger than two years old. These treatments were clinically effective.

Topics: Abdominal Pain; Adolescent; Age Factors; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Child; Diarrhea; Dipyridamole; Escherichia coli Infections; Female; Fever; Fosfomycin; gamma-Globulins; Glycoproteins; Hemolytic-Uremic Syndrome; Humans; Kidney Diseases; Leukocyte Count; Liver Diseases; Male; Melena; Platelet Aggregation Inhibitors; Risk Factors; Sex Factors; Time Factors