Lindsey V. Wood

Furazolidone versus ampicillin in the treatment of traveler's diarrhea

Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible.

Efficacy of Bicozamycin in Preventing Traveler's Diarrhea

Bicozamycin was compared with a placebo in a prospective, randomized, double-blind study of the prevention of acute diarrhea among 30 American travelers newly arrived in Guadalajara, Mexico. None of the 11 subjects given bicozamycin orally for 3 wk at a dosage of 500 mg four times a day developed diarrhea as compared with an incidence of 53% diarrhea (10 of 19 subjects) in the placebo group (p = 0.003). Bicozamycin was well tolerated. Studies of changes in predominant aerobic fecal flora among the 11 subjects treated with bicozamycin showed the appearance of only one highly resistant Citrobacter freundii at the end of 1 wk of therapy and only a total of six resistant isolates at the end of 3 wk. All resistant isolates failed to transfer this resistance to a recipient Escherichia coli. Bicozamycin seems to be well suited and safe as a prophylactic agent against travelers diarrhea.

Serum Antibody Response Induced in Mice after Oral Administration of Three Different Antigens of Enterotoxigenic Escherichia coli in Enteric Coated Microparticles

BACKGROUND Gastric digestion of these antigens plays an important role, decreasing the ability to deliver antigens to the gut-associated lymphoid tissue. To overcome this obstacle, microencapsulated antigens from enterotoxigenic Escherichia coli (ETEC) were evaluated for oral immunization of mice. METHODS Four groups of 10 each received 3 series of 3 doses each of (1) B subunit of cholera toxin (CTB), similar to heat-labile toxin of ETEC, (2) formalin-killed whole cell ETEC H10407 (FK-ETEC), (3) crude preparation of colonization factor antigen I (CFA/I), or (4) placebo. Serum antibody was measured on day 0 and 60 by ELISA. RESULTS In group 1 a CTB antibody response was induced in all mice, 3 with 1:105 titer and 7 with 1:106. These antibodies neutralized cholera toxin-induced steriodogenesis of Y-1 adrenal cells. In group 2, 8 mice developed a whole H10407 bacteria antibody titer of 1:100, one 1:200 and one showed no immune response. In the same group, an anti-CFA/I response was observed in 6 mice and anti-LPS in 4 mice as determined by Western blot. All mice in group 3 showed > 1:104 anti-CFA/I antibody titer. Group 4 mice did not develop an immune response to any ETEC antigens. CONCLUSIONS Microencapsulation appears to be a suitable approach for oral vaccination against ETEC and Vibrio cholerae.

Su1146 Awareness Amongst Patents With Inflammatory Bowel Disease for the Need for Vaccinations Whilst on Immunosuppressive Therapy

BackgroundWith the ever increasing use of immunosuppressive therapy for the management of inflammatory bowel disease (IBD), patients are being exposed to infections which can be prevented by vaccinations administered prior to or during therapy. The European Crohns and Colitis Organisation guidelines currently recommend that IBD patients who receive immunosuppressive medications should be vaccinated yearly with the influenza vaccine and a pneumococcal vaccination 3-5 yearly. Several studies have demonstrated that despite guidelines many patients were still not being vaccinated for preventable disease. Method An audit was carried out within our department to assess our patients knowledge and uptake of such vaccines. Patients were identified from an established database and those receiving immunosuppressive therapy were invited to complete a questionnaire. Data gathered included age, gender, current treatment, awareness and uptake of vaccinations. Results A cohort of 88 patients on immmunosuppressive therapy were analysed. 61% of patients were female and 39% male. Patients ranged between 16-21 years (11%), 22-30 years (18%), 31-50 years (40%), 51-70 years (24%) and above 70 (7%). 59 (67%) patients had Crohns disease, 26 (29.5%) ulcerative colitis and 3 (3.5%) had indeterminate colitis. The majority of patients received immunomodulators including Azathioprine or Mycophenolate (n=48, 54%). 13 (15%) were treated with biologics alone (Infliximab or Adalimumab), 21 (24%) with combination of biologics and immunomodulators and 6 patients (7%) received immunomodulators with a reducing dose of steroids. 77% of patients were aware of recommended vaccinations but as many as 23% were not. 42% were aware of the importance of receiving dual vaccinations, 35% only aware of either the influenza or pneumococcal vaccine, with 23% unaware of the need for either. 54 (61%) patients had already had or were planning to have the influenza vaccine this year. Patients between the ages of 31-50 years had the highest awareness of the recommended vaccines (86%), with the majority of uptake of vaccines seen in the 31-50 year group (63%). Unfortunately 39% of patients were not receiving recommended vaccinations with more than half (56%) of patients being unaware of the need to avoid live vaccinations. Conclusions Our data suggest that a significant proportion of patients within our cohort are still not receiving vaccinations that were recommended to them. Although 77 % were aware of a form of recommended vaccine, 39% were not receiving them. Wider education of our IBD patients as well as their primary care doctors should be implemented to increase awareness and uptake of vaccines to provide adequate protection to this vulnerable group.

PMO-252 Efficacy of infliximab therapy in acute and sub-acute ulcerative colitis

Introduction Ulcerative colitis (UC) has a chronic relapsing course. Infliximab is beneficial in severe disease, but conflicting data exists regarding the subsequent colectomy rates. We aimed to review outcomes post-infliximab usage in acute and sub-acute UC in our clinical practice. Methods We conducted a retrospective review of all patients who had received a maximum of three doses of infliximab for acute or sub-acute exacerbations of UC between January 2010 and October 2011. Medical treatment (initial and subsequent) and colectomy rates were recorded for all patients. Results 21 patients received infliximab during the study period. 12 patients were emergency admissions who had failed to respond to intravenous steroid therapy (acute group). Nine patients had failed to respond to maximum oral therapy, which included immunomodulators and oral prednisolone (sub-acute group). In the acute group, 42% (n=5) of patients had avoided a colectomy at a median follow-up of 467 days (IQR 370–612). The other 58% (n=7) proceeded to colectomy after a median of 69 days (IQR 30–136). Of the patients who proceeded to colectomy, 57% had been prescribed immunomodulator therapy prior to infliximab usage. However, all the patients who avoided colectomy were immunomodulator naive prior to infliximab. In the sub-acute group, only 33% (n=3) of patients required a colectomy after a median follow-up of 153 days (IQR 110–180). The remaining 67% (n=6) were well and off steroids after a median of 303 days (IQR 209–400). Conclusion This review of patient outcomes shows the potential benefits of infliximab for treating both acute and sub-acute UC. After a maximum of three doses of infliximab, 42% of acute and 67% of sub-acute UC patients were able to avoid a colectomy. Our results are comparable to those of Oxford (1 to 7 doses of infliximab as needed) who reported that 43% of acute and 50% of sub-acute were able to avoid a colectomy.1 Furthermore, our results confirm the greater potential benefit of infliximab in acute, immunomodulator naive patients. In addition, all sub-acute patients, who avoided colectomy, were well and off steroids at the end-of follow-up, compared to only 38% from the Oxford group, suggesting additional benefit from planned infliximab doses.1 Competing interests None declared. Reference 1. Jakobovits SL, Jewell DP, Travis SPL. Infliximab for the treatment of ulcerative colitis: outcomes in Oxford from 2000 to 2006. Aliment Pharmacol Ther 2007;25:1055–60.

PTU-115 Efficacy of mycophenolate mofetil therapy in the management of inflammatory bowel disease

Introduction The role of Mycophenolate mofetil (MMF) as an immunomodulatory drug in managing inflammatory bowel disease is yet to be fully defined. We reviewed our experience of the efficacy, safety and tolerability of MMF in treating patients with refractory inflammatory bowel disease. Methods A retrospective analysis was performed of the case records of all patients treated with MMF for inflammatory bowel disease at our institution between 2003 and 2011. Remission was assessed by reviewing clinical, endoscopic and laboratory indices. Results We identified 36 patients, 23 male (64%) with a median age 46 yrs (range 19–75). Disease was classified as Crohns disease in 19, ulcerative colitis 16, indeterminate colitis.1 33 patients (92%) had previously received azathioprine; 32 discontinued this due to side-effects. Five patients had undergone surgery for small bowel Crohns disease. The starting dose of MMF was between 500 mg and 2 g daily, titrated to a dose of 2 g daily as tolerated. 26 patients (72%) were concurrently taking oral corticosteroids, and 18 (50%) were taking an oral 5-aminosalicylate. At 8 weeks, 29 patients (81%) had either achieved acute remission or maintained previous remission. Drug side-effects were experienced by eight patients (22%)—these symptoms were managed successfully by dose reduction in six patients (75%), with discontinuation in two patients. There were no serious haematological or other adverse drug effects. After 6 months of treatment, 33 patients continued to take MMF of which 19 patients (58%) had achieved sustained steroid-free remission. Median length of MMF treatment observed was 21.5 months (IQR 9.7–31.6). At the end of the observation period, 29 patients (81%) remained on MMF. 13 patients (36% of the original treatment group; UC 7, Crohns 5) remained in steroid-free remission with median time of remission 21.4 months (IQR 11.0–30.0). A further 13 patients achieved sustained remission with the addition of corticosteroids and/or anti-TNF therapy. Five patients (14% overall) were refractory to all medical therapy and underwent surgery: colectomy for UC 3, right hemicolectomy for Crohns.2 Conclusion From our experience, MMF may represent a promising alternative treatment for inducing and maintaining remission in patients intolerant of or unable to receive thiopurines. It appears well tolerated with a good safety profile in thiopurine intolerant subjects. Competing interests None declared.

DIARRHEA ASSOCIATED WITH E|[period]| COLI PRODUCING SHIGALIKE CYTOTOXIN

College students spending the summer in Mexico were studied for the development of diarrhea. Stool specimens were collected from sick and asymptomatic students. 188 episodes of gastroenteritis were evaluated for salmonella, shigella, campylobacter, enteropathogenic E. coli, enterotoxigenic E. coli (ST,LT), giardia, E. histolytica, and cryptosporidium. 53 episodes occurred for which no etiologic agent could be defined. E. coli isolated from these students and asymptomatic students were assayed for adherence to HEp-2 cells and production of Shiga-like toxin. HEp-2 adherent E. coli were isolated from ill students more frequently than from those who were well (p < 0.05). 50% of strains from sick students with no known etiology were positive for Shiga-like toxin while only 27% of E. coli from asymptomatic individuals were positive. Strains that were positive for Shiga toxin tended to be positive for HEp-2 adherence and strains that were negative for Shiga or HEp-2 tended to be negative for the other marker (p < 0.02). HEp-2 adherence and Shiga toxin production correlated with presence of gastroenteritis in individuals who had no previously described enteric pathogen. This is the first evidence that Shiga toxin production by E. coli may commonly cause enteritis.