• Antibiotic-associated diarrhoea in emergency department observation unit patients

      Haran, John P.; Wu, Gregory; Bucci, V.; Fischer, A.; Keang, L.; Boyer, Edward W.; Hibberd, P. L. (2016-07-01)
      Clostridium difficile diarrhoea is an urgent threat to patients, but little is known about the role of antibiotic administration that starts in emergency department observation units (EDOUs). We studied risk factors for antibiotic-associated diarrhoea (AAD) and C. difficile infection (CDI) in EDOU patients. This prospective cohort study enrolled adult patients discharged after EDOU antibiotic treatment between January 2013 and 2014. We obtained medical histories, EDOU treatment and occurrence of AAD and CDI over 28 days after discharge. We enrolled and followed 275 patients treated with antibiotics in the EDOU. We found that 52 (18.6%) developed AAD and four (1.5%) had CDI. Patients treated with vancomycin [relative risk (RR) 0.52, 95% confidence interval (CI) 0.3-0.9] were less likely to develop AAD. History of developing diarrhoea with antibiotics (RR 3.11, 95% CI 1.92-5.03) and currently failing antibiotics (RR 1.90, 95% CI 1.14-3.16) were also predictors of AAD. Patients with CDI were likely to be treated with clindamycin. In conclusion, AAD occurred in almost 20% of EDOU patients with risk factors including a previous history of diarrhoea with antibiotics and prior antibiotic therapy, while the risk of AAD was lower in patients receiving treatment regimens utilizing intravenous vancomycin.
    • Carotid Flow Time Test Performance for the Detection of Dehydration in Children With Diarrhea

      Mackenzie, David C.; Nasrin, Sabiha; Atika, Bita; Modi, Payal; Alam, Nur H.; Levine, Adam C. (2017-11-09)
      OBJECTIVES: Unstructured clinical assessments of dehydration in children are inaccurate. Point-of-care ultrasound is a noninvasive diagnostic tool that can help evaluate the volume status; the corrected carotid artery flow time has been shown to predict volume depletion in adults. We sought to determine the ability of the corrected carotid artery flow time to identify dehydration in a population of children presenting with acute diarrhea in Dhaka, Bangladesh. METHODS: Children presenting with acute diarrhea were recruited and rehydrated according to hospital protocols. The corrected carotid artery flow time was measured at the time of presentation. The percentage of weight change with rehydration was used to categorize each child's dehydration as severe ( > 9%), some (3%-9%), or none ( < 3%). A receiver operating characteristic curve was constructed to test the performance of the corrected carotid artery flow time for detecting severe dehydration. Linear regression was used to model the relationship between the corrected carotid artery flow time and percentage of dehydration. RESULTS: A total of 350 children (0-60 months) were enrolled. The mean corrected carotid artery flow time was 326 milliseconds (interquartile range, 295-351 milliseconds). The area under the receiver operating characteristic curve for the detection of severe dehydration was 0.51 (95% confidence interval, 0.42, 0.61). Linear regression modeling showed a weak association between the flow time and dehydration. CONCLUSIONS: The corrected carotid artery flow time was a poor predictor of severe dehydration in this population of children with diarrhea.
    • Etiology of Diarrhea, Nutritional Outcomes, and Novel Intestinal Biomarkers in Tanzanian Infants

      Gosselin, Kerri B.; Aboud, Said; McDonald, Christine M.; Moyo, Sabrina; Khavari, Nasim; Manji, Karim; Kisenge, Rodrick; Fawzi, Wafaie; Kellogg, Mark; Tran, Hao Q.; et al. (2017-01-01)
      OBJECTIVE: Diarrheal diseases are a leading cause of morbidity and mortality worldwide, but the etiology of diarrhea and its relation to nutritional outcomes in resource-limited settings is poorly defined. We sought to determine the etiology of community-acquired diarrhea in Tanzanian infants and to assess the association with anthropometrics and novel intestinal biomarkers. METHODS: A convenience sample of infants in a trial of zinc and/or multivitamin supplementation in Tanzania was selected. Subjects were enrolled at age 6 weeks and studied for 18 months. Stool samples were obtained from children with acute diarrhea. A novel, polymerase chain reaction-based TaqMan array was used to screen stool for 15 enteropathogens. A subset of subjects had serum gastrointestinal biomarkers measured. RESULTS: One hundred twenty-three subjects with diarrhea were enrolled. The mean +/- SD age at stool sample collection was 12.4 +/- 3.9 months. Thirty-five enteropathogens were identified in 34 (27.6%) subjects: 11 rotavirus, 9 Cryptosporidium spp, 7 Shigella spp, 3 Campylobacter jejuni/coli, 3 heat stable-enterotoxigenic Escherichia coli, and 2 enteropathogenic E coli. Subjects with any identified enteropathogen had significantly lower weight-for-length z scores (-0.55 +/- 1.10 vs 0.03 +/- 1.30, P = 0.03) at the final clinic visit than those without an identified pathogen. Fifty of the 123 subjects (40.7%) had serum analyzed for antibodies to lipopolysaccharide (LPS) and flagellin. Subjects with any identified enteropathogen had lower immunoglobulin (IgA) antibodies to LPS (0.75 +/- 0.27 vs 1.13 +/- 0.77, P = 0.01) and flagellin (0.52 +/- 0.16 vs 0.73 +/- 0.47, P = 0.02) than those without an identified pathogen. CONCLUSIONS: This quantitative polymerase chain reaction method may allow identification of enteropathogens that place children at higher risk for suboptimal growth. IgA anti-LPS and flagellin antibodies hold promise as emerging intestinal biomarkers.
    • Management of microscopic colitis: challenges and solutions

      Shor, Julia; Churrango, Gustavo; Hosseini, Nooshin; Marshall, Christopher (2019-02-27)
      Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of both subtypes is the same, with treatment goal of reducing the number of bowel movements and improving consistency. First-line treatment involves counseling the patient about decreasing their risk factors, like discontinuing smoking and avoiding medications with suspected association such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide is considered first-line treatment for MC given its favorable side effect profile and good efficacy, though relapse rates are high. Systemic glucocorticoids should be reserved to patients unable to take budesonide. In glucocorticoid refractory disease, medications that have been tried include cholestyramine, bismuth salicylate, antibiotics, probiotics, aminosalicylates, immunomodulators, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease.
    • Oral administration of an anti-CfaE secretory IgA antibody protects against Enterotoxigenic Escherichia coli diarrheal disease in a non-human primate model [preprint]

      Stoppato, Matteo; Gaspar, Carlos; Regeimbal, James; Nunez, Gladys; Giuntini, Serena; Gawron, Melissa A.; Pondish, Jessica R.; Martin III, Joseph C.; Schneider, Matthew; Schiller, Zachary A.; et al. (2019-08-28)
      Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in the Aotus nancymaae non-human primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged with 5.0×1011 cfu of H10407 on Day 0. Group 1 received a dIgA2 68-61 subcutaneously on day 0. Group 2 received a SIgA2 68-61 orally on days −1, 0, and +1, and Group 3 received an irrelevant SIgA2 antibody orally on days −1, 0, and +1. All animals were observed for symptoms of diarrhea, and stools were collected for ETEC colony counts. SIgA2 treatment significantly lowered the attack rate, resulting in a protective efficacy of 71.4% (p=0.025) in Group 2 as compared to Group 3. Anti-CfaE dIgA2 treatment group reduced the diarrheal attack rate, although the reduction did not reach significance (57.1%; P=0.072) as compared to the irrelevant SIgA2 Group 3. Our results demonstrated the feasibility of oral administration of SIgA as a potential immunoprophylaxis against enteric infections. To our knowledge, this is the first study to demonstrate the efficacy of administrated SIgA in a non-human primate model.