trimethoprim--sulfamethoxazole-drug-combination and Hemolytic-Uremic-Syndrome

Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This review addressed the interventions aimed at secondary prevention of HUS in patients with diarrhoea who were infected with a bacteria that increase the risk of HUS.. Our objective was to evaluate evidence regarding secondary preventative strategies for HUS associated with STEC infections. In doing so, we sought to assess the effectiveness and safety of interventions as well as their potential to impact the morbidity and death associated with this condition.. We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. Studies were considered based on the methods, participants, and research goals. Only randomised controlled trials were considered eligible for inclusion. The participants of the studies were paediatric and adult patients with diarrhoeal illnesses due to STEC. The primary outcome of interest was incidence of HUS.. We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. We identified four studies (536 participants) for inclusion that investigated four different interventions including antibiotics (trimethoprim-sulfamethoxazole), anti-Shiga toxin antibody-containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if trimethoprim-sulfamethoxazole reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11-2.81, very low certainty evidence). Adverse events relative to this review, need for acute dialysis, neurological complication and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low certainty evidence). The need for acute dialysis, neurological complications or death were not reported. It is uncertain whether Synsorb Pk reduces the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low certainty evidence). Adverse events relevant to this review, need for acute dialysis, neurological complications or death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) reduced the incidence of HUS compared to placebo (very low certainty evidence). Low certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. There were 25 serious adverse events reported in 18 patients: 10 in the placebo group, and 9 and 6 serious adverse events in the 1.0 mg/kg and 3.0 mg/kg urtoxazumab groups, respectively. It is unclear how many patients experienced these adverse events in each group, and how many patients experienced more than one event. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low certainty evidence). Need for acute dialysis wa. The included studies assessed antibiotics, bovine milk, and Shiga toxin inhibitor (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the efficacy of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the efficacy of interventions to prevent development of HUS in patients with diarrhoea due to STEC infection.

Topics: Adult; Animals; Antibodies, Monoclonal, Humanized; Bias; Cattle; Child; Colostrum; Diarrhea; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Humans; Incidence; Organosilicon Compounds; Placebos; Randomized Controlled Trials as Topic; Secondary Prevention; Shiga-Toxigenic Escherichia coli; Trimethoprim, Sulfamethoxazole Drug Combination; Trisaccharides

Hemolytic Uremic Syndrome (HUS) may follow infection with Shiga-toxin-producing organisms, principally E. coli O157: H7 (STEC), causing high morbidity and mortality. Our aim was to identify interventions to prevent diarrhea-associated HUS.. Systematic search of the literature for relevant systematic reviews (SRs), randomised controlled trials (RCTs) and public health guidelines.. Of 1097 animal and 762 human studies, 18 animal studies (2 SRs, 2 reviews, plus 14 RCTs) and 6 human studies (3 SRs, plus 3 RCTs) met inclusion criteria. E. coli O157: H7 Type III secreted protein vaccination decreased fecal E. coli O157 shedding in cattle (P = 0.002). E. coli O157: H7 siderophore receptor and porin proteins (SRP) vaccines reduced fecal shedding in cows (OR 0.42 (95% CI 0.25 to 0.73) and increased anti-E. coli 0157: H7 SRP antibodies in their calves (P < 0.001). Bacterin vaccines had no effect. Probiotic or sodium chlorate additives in feeds reduced fecal E. coli O157 load as did improved farm hygiene (P < 0.05). Solarization of soil reduced E. coli O157: H7 contamination in the soil (P < 0.05). In an RCT examining the role of antibiotic treatment of E. coli O157: H7 diarrhea, HUS rates were similar in children treated with Trimethoprim-sulfamethoxazole and controls (RR 0.57; 95% CI 0.11 to 2.81). In another RCT, HUS rates were similar in children receiving Synsorb-Pk and placebo (RR 0.93; 95% CI 0.39 to 2.22). In one SR, hand washing reduced diarrhea by 39% in institutions (IRR 0.61; 95% CI 0.40 to 0.92) and 32% in community settings (IRR 0.68; 95% CI 0.52 to 0.90) compared to controls. Guidelines contained recommendations to prevent STEC transmission from animals and environments to humans, including appropriate food preparation, personal hygiene, community education, and control of environmental contamination, food and water quality.. Animal carriage of STEC is decreased by vaccination and improved farm practices. Treatment of STEC diarrhea with antibiotics and toxin-binders did not prevent HUS. Public health interventions are the key to preventing STEC-associated diarrhea and HUS.

Topics: Animal Husbandry; Animals; Anti-Infective Agents; Cattle; Child; Diarrhea; Escherichia coli Infections; Escherichia coli O157; Hemolytic-Uremic Syndrome; Humans; Meat; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination

Post-transplant hemolytic uremic syndrome characterized by microangiopathic hemolysis, thrombocytopenia, and renal failure is an infrequent but potentially serious complication in organ transplant recipients. Hemolytic uremic syndrome developed in 2% (2/100) of our consecutive liver transplants. We report our patients and review a total of 91 cases of hemolytic uremic syndrome in adult solid organ transplant recipients reported in the literature. Ninety percent were observed in renal transplant recipients, 8% in liver, and 1% each in lung and heart transplant recipients. Eighty percent and 96% of cases occurred within 90 days and 1 year, respectively, post-transplantation. In renal transplant recipients, 23% of cases were due to post-transplant recurrence of hemolytic uremic syndrome. In 50% of renal transplant recipients and in all nonrenal solid-organ transplant recipients, hemolytic uremic syndrome was attributed to cyclosporin or tacrolimus therapy. Notably, infections were not a significant precipitating factor for post-transplant hemolytic uremic syndrome. Graft loss attributable to hemolytic uremic syndrome occurred in 43% of renal transplant recipients while renal transplantation and hemodialysis were required in the lung and heart transplant recipients due to hemolytic uremic syndrome induced renal failure. The overall mortality was 13% (12/91). Physicians caring for transplant recipients need to be aware of this potentially severe graft and life-threatening disorder since prompt recognition and removal of identifiable risk factors is critical in the management of post-transplant hemolytic uremic syndrome.

Topics: Adult; Graft Rejection; Heart Transplantation; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Liver Transplantation; Lung Transplantation; Male; Organ Transplantation; Recurrence; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We undertook a prospective, controlled study to evaluate the effect of trimethoprim-sulfamethoxazole in children with proven Escherichia coli O157:H7 enteritis on the duration fo symptoms, on fecal excretion of pathogen, and on the risk of progression to hemolytic-uremic syndrome. There was no statistically significant effect of treatment on progression of symptoms, fecal pathogen excretion, or the incidence of HUS (2/22 vs 4/25; p = 0.67). Our results suggest that a multicentric trial using rapid diagnostic methods to permit early randomization should be carried out.

Topics: Child; Child, Preschool; Enteritis; Escherichia coli; Escherichia coli Infections; Feces; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a fatal case of haemolytic uraemic syndrome in a young woman with AIDS, and disseminated adenovirus (ADV) and cytomegalovirus (CMV) co-infection. We hypothesize that ADV/CMV co-infection may have a causative role in this clinical picture.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Adenovirus Infections, Human; Colitis; Cytomegalovirus Infections; Enteritis; Fatal Outcome; Female; Foscarnet; Ganciclovir; Hemolytic-Uremic Syndrome; Humans; Respiratory Distress Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to evaluate epidemiological, clinical and laboratory data of shigellosis in children from northern Greece, hospitalized in our department during the period 1971-96. In total, 422 cases of shigellosis, aged 1 month to 14 y (238M, 184F) were hospitalized during the study period. The annual distribution was approximately stable until 1990, the mean number of cases per year being about 20. During the last 4 y the incidence significantly decreased. Shigella was serotyped in 138/422 cases. Seventy six of the strains were S. flexneri (55%) and 56 S. sonnei (40%). In the majority of cases the clinical picture was mild. Severe dehydration was seen in only 6 patients. Ninety four patients (22%) had extra-intestinal manifestations. Most common of these were convulsions (16%) and, less frequently, disturbances of consciousness (n = 26), rash (n = 9), shock and disseminated intravascular coagulopathy (n = 2), nerve paralysis (n = 2), severe anaemia (n = 2) and haemolytic-uraemic syndrome (n = 1). Nine patients had acute encephalopathy of 12 h to 12 d duration. It is important to note that all these cases recovered completely with no residual neurological deficit, except for 1 girl who developed temporal epilepsy 8 y later. Spinal fluid was normal in all 42 examined patients. Antibiotics were given to 212 of 422 patients, mainly during the first half of the study period. Shigella resistance to antibiotic was significant for cotrimoxazole (24%) and ampicillin (16%). All patients were cured. Shigellosis is a mild disease in our area, with a decreasing prevalence.

Topics: Adolescent; Ampicillin; Anemia; Anti-Bacterial Agents; Child; Child, Preschool; Consciousness Disorders; Dehydration; Disseminated Intravascular Coagulation; Drug Resistance, Microbial; Dysentery, Bacillary; Exanthema; Female; Greece; Hemolytic-Uremic Syndrome; Humans; Incidence; Infant; Male; Paresis; Penicillins; Seizures; Shigella; Shock; Trimethoprim, Sulfamethoxazole Drug Combination

Children with gastrointestinal infections caused by Escherichia coli O157:H7 are at risk for the hemolytic-uremic syndrome. Whether antibiotics alter this risk is unknown.. We conducted a prospective cohort study of 71 children younger than 10 years of age who had diarrhea caused by E. coli O157:H7 to assess whether antibiotic treatment in these children affects the risk of the hemolytic-uremic syndrome and to assess the influence of confounding factors on this outcome. Estimates of relative risks were adjusted for possible confounding effects with the use of logistic-regression analysis.. Among the 71 children, 9 (13 percent) received antibiotics and the hemolytic-uremic syndrome developed in 10 (14 percent). Five of these 10 children had received antibiotics. Factors significantly associated with the hemolytic-uremic syndrome were a higher initial white-cell count (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.5), evaluation with stool culture soon after the onset of illness (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.8), and treatment with antibiotics (relative risk, 14.3; 95 percent confidence interval, 2.9 to 70.7). The clinical and laboratory characteristics of the 9 children who received antibiotics and the 62 who did not receive antibiotics were similar. In a multivariate analysis that was adjusted for the initial white-cell count and the day of illness on which stool was obtained for culture, antibiotic administration remained a risk factor for the development of the hemolytic uremic syndrome (relative risk, 17.3; 95 percent confidence interval, 2.2 to 137).. Antibiotic treatment of children with E. coli O157:H7 infection increases the risk of the hemolytic-uremic syndrome.

Topics: Anti-Bacterial Agents; Cephalosporins; Child; Child, Preschool; Diarrhea; Escherichia coli Infections; Escherichia coli O157; Feces; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Logistic Models; Male; Prospective Studies; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Drug Combinations; Drug Resistance, Microbial; Dysentery, Bacillary; Female; Hemolytic-Uremic Syndrome; Humans; Shigella dysenteriae; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination