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Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice

Aliment Pharmacol Ther 2005; 22: 721–728.
Maintenance therapy with a probiotic in antibiotic-dependentpouchitis: experience in clinical practice B . S H E N * , A . B R Z E Z I N S K I * , V . W . F A Z I O   , F . H . R E M Z I   , J . - P . A C H K A R * , A . E . B E N N E T T à ,K . S H E R M A N * & B . A . L A S H N E R *Departments of *Gastroenteorology/Hepatology,  Colorectal Surgery and àAnatomic Pathology, The Cleveland ClinicFoundation, Cleveland, OH, USA duration of follow-up was 14.5 ± 5.3 months (range: 8–26 months). At the 8-month follow-up, six patients were still on VSL #3 therapy, and the remaining 25 pouchitis is often challenging. Oral bacteriotherapy patients had discontinued the therapy due to either with probiotics (such as VSL #3) as maintenance recurrence of symptoms while on treatment or devel- treatment has been shown to be effective in relapsing opment of adverse effects. All six patients who comple- pouchitis in European trials. However, this agent has ted the 8-month course with a mean treatment period of not been studied in the US, and its applicability in 14.3 ± 7.2 months (range: 8–26 months) had repeat routine clinical practice has not been evaluated.
clinical and endoscopic evaluation as out-patients. At Aim: To determine compliance and efficacy of probiotic the end of 8 months, these six patients had a mean treatment in patients with antibiotic-dependent pouchitis.
Pouchitis Disease Activity Index symptom score of Methods: Thirty-one patients with antibiotic-dependent 0.33 ± 0.52 and a mean Pouchitis Disease Activity pouchitis were studied. VSL #3 is a patented probiotic Index endoscopy score of 1.83 ± 1.72, which was not preparation of live freeze-dried bacteria. All patients statistically different from the baseline Pouchitis Disease received 2 weeks of ciprofloxacin 500 mg b.d. followed Activity Index endoscopy score of 2.83 ± 1.17 (P ¼ by VSL #3 6 g/day for 8 months. Baseline Pouchitis Disease Activity Index scores were calculated. Patients’ Conclusion: This study was conducted to evaluate symptoms were reassessed at week 3 when VSL #3 bacteriotherapy in routine care. The use of probiotics therapy was initiated and at the end of the 8-month has been adopted as part of our routine clinical practice trial. Some patients underwent repeat pouch endoscopy with only anecdotal evidence of efficacy. Our review of patient outcome from the treatment placebo showed Results: All 31 patients responded to the 2-week that only a minority of patients with antibiotic-depend- ciprofloxacin trial with resolution of symptoms and ent pouchitis remained on the probiotic therapy and in they were subsequently treated with VSL #3. The mean symptomatic remission after 8 months.
for patients who have medically refractory ulcerative colitis (UC) or UC with dysplasia or cancer, and for Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice Pouchitis is the most common long-term complicationof IPAA in patients with underlying UC.1–4 The etiology Correspondence to: Dr B. Shen, Department of Gastroenterology/ and pathogenesis of pouchitis are poorly understood.
Hepatology-Desk A30, The Cleveland Clinic Foundation, 9500 Euclid Ave, Luminal microflora play a major role in the etiology of Cleveland, OH 44195, USA.
E-mail: shenb@ccf.org inflammatory bowel disease (IBD) and pouchitis, and it is likely that bacteria perpetuate the inflammatory toms quickly recurred after stopping the antibiotics; mucosal reaction in genetically susceptible patients.
(ii) the patients with frequent episodes or recurrence Given this association, antibiotics and probiotics have of pouchitis required long-term continuous low-dose been used to treat patients with pouchitis. Pouchitis can antibiotic therapy or frequent pulse antibiotic therapy be classified into three categories based on the patient to stay on remission; and (iii) patients who are response to antibiotic therapy: (i) antibiotic-responsive; currently symptomatic while having been off any (ii) antibiotic-dependent; and (iii) antibiotic-refractory.5 antibiotics or probiotics for at least 2 weeks. Exclusion The pathogenesis, treatment, and prognosis of these criteria were patients with antibiotic-refractory pouch- categories of pouchitis may be different.
itis (defined as failure to respond to a 2-week course Management of antibiotic-dependent pouchitis can be of metronidazole or ciprofloxacin) or antibiotic-respon- challenging. Typically, patients initially respond to a sive pouchitis (defined as fewer than four episodes of short course of antibiotics, but symptoms quickly pouchitis per year which quickly responded to anti- return after the antibiotic is stopped, and thus long- term maintenance therapy with antibiotics is often ciprofloxacin or any brand of probiotics; concurrent needed. However, there are concerns about bacterial pouchitis and cuffitis; irritable pouch syndrome; and resistance in patients who are on long-term mainten- Crohn’s disease of the pouch. The study was approved ance antibiotics. Alternatively, probiotics, as antibiotic- sparing agents, have been used to prevent episodes of A clinical and endoscopic evaluation was conducted at pouchitis. A randomized, double-blind, placebo-con- the entry of the trial. The Pouchitis Disease Activity trolled trial of a probiotic named VSL #3 (Yovis; Index (PDAI) instrument10 was used for the diagnosis of Sigma-Tau, Pomezia, Italy) was conducted for the pouchitis (as defined PDAI >7). The 18-point PDAI maintenance therapy of relapsing pouchitis after remis- measures components of symptoms (increased stool sion induced by using ciprofloxacin and rifaximin6 and frequency, bleeding, fecal urgency or abdominal cramps VSL #3 contains viable lyophilized bacteria of four and fever), endoscopy (edema, granularity, friability, strains of Lactobacillus, three Bifidobacterium species, loss of vascular pattern, mucous exudates, ulceration) Streptococcus salivarius subsp. Thermophillus. The agent and histology (polymorphic nuclear leucocyte infiltra- was shown to be highly effective in maintaining tion and ulceration). Each component has a maximum remission in patients with relapsing pouchitis6, 7 and of six points. Patients who had routinely used non- in preventing the initial episodes of pouchitis after steroidal anti-inflammatory drugs (NSAID) at the entry IPAA.8 The promising results from prior work have of the study were asked to discontinue these agents.
generated continued interest in the use of probiotics in Patients were treated with ciprofloxacin 500 mg PO BID pouchitis. VSL #3 has become commercially available for 2 weeks to induce remission, and then started VSL and patients in the US were able to purchase the agent #3 to maintain remission. During the treatment period online. Our study was done to determine whether VSL with ciprofloxacin, the patients obtained VSL #3 from #3 was effective when used in clinical practice.
the company’s web sites (http://www.vsl3.com orhttp://www.questcor.com) and made the agent avail-able for use immediately after the 2-week ciprofloxacin therapy. Patients were advised to follow the manufac- Thirty-one consecutive UC patients with antibiotic- turer’s instructions, including appropriate refrigeration dependent pouchitis were recruited from our clinic of the agent. Patients were informed that probiotics are March 2002 to December 2004. We approached the usually not covered by insurance policies. Only patients patients as we normally would, diagnosing and who were willing to purchase and take the agent were managing their disease according to our standard of enrolled in the trial. Upon finishing the 2-week cipro- practice at our clinic. In order to qualify for the study, floxacin trial, all patients were contacted either via patients needed to meet each of the three inclusion e-mail or telephone by the primary investigator and criteria: (i) patients with antibiotic-dependent pouchitis, treating physician (B.S.) for the assessment of their defined as patients with four or more episodes of symptoms and the assurance of their compliance with pouchitis per year who quickly responded to a 2-week the next phase of therapy involving VSL #3. If course of ciprofloxacin or metronizazole, but symp- symptoms had been resolved by the end of the 2 week Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 P R O B I O T I C T H E R A P Y I N P O UC H I T I S course of ciprofloxacin, patients were instructed to start symptoms and endoscopic inflammation that responded taking VSL #3 at a dose of 6 g/day immediately (within quickly to ciprofloxacin or metronidazole with recur- 1–3 days) following the antibiotic therapy. Patients rence of symptoms soon (1.1 ± 1.0 weeks) after dis- who did not respond to the 2 weeks of ciprofloxacin continuation of the antibiotics. During the current were excluded from the protocol. If patients experienced study, all 31 patients who were treated with a 2-week unusual symptoms while on VSL #3 such as intolerable course of ciprofloxacin 500 mg PO BID responded to constipation, bloating, bleeding, or worsening abdom- therapy with improvement in symptoms with a PDAI inal pain or diarrhea, patients were asked to decrease symptom scores £ 1 point and all patients were in the dose to 3 g daily. If these symptoms persisted for remission at week 3 when VSL #3 was started. The more than 2 weeks, patients were instructed to discon- mean follow-up was 14.5 ± 5.3 months (range: 8– tinue VSL #3. Patients who experienced symptoms 26 months). At the 8-month follow-up, only six suggestive of a recurrent episode of pouchitis were patients (19.4%) were still on VSL #3 (designated as advised to discontinue VSL #3. Subsequent treatment Group A). The remaining 25 patients had discontinued was determined by the patients’ gastroenterologists.
the therapy because of either recurrence of symptoms or Patients who failed to respond to VSL #3 therapy were development of adverse effects (designated as Group B).
asked to return to clinic for evaluation with pouch The demographic and clinical data of Groups A and B are shown in Table 1. There were no statistically Patients were contacted again by the primary inves- significant differences in age, gender, duration of UC tigator at week 7. At week 7, patients, on VSL #3, who and IPAA, indication for IPAA, type and stage of IPAA, had a symptomatic response with PDAI symptom scores NSAID use at the entry of the study, smoking, frequency remaining £ 1 point continued the therapy. If patients of primary sclerosing cholangitis, or family history of tolerated the VSL #3 therapy, they were periodically IBD between the two groups. During the study period, contacted (every 1–3 months) by the primary investi- none of the patients reported NSAID or other antibiotic gator for the assessment of symptoms and assurance of compliance. The VSL #3 trial was designed to last for a At the end of the study period, all six patients, in Group duration of 8 months. Up to or after 8 months or later, A, who continuously received VSL #3 as a maintenance patients were scheduled to have out-patient clinical and therapy for a mean period of 14.3 ± 7.2 months (range: 8–26 months) had repeat clinical and endo-scopic evaluations. While the six patients were insymptomatic remission with a mean PDAI symptom score of 0.33 ± 0.52, there was evidence of mild or The primary outcome measurement was the number of moderate endoscopic pouch inflammation with a mean patients who were still on VSL #3 at the end of PDAI endoscopy score of 1.83 ± 1.72, which was not 8 months. The secondary outcomes included: (i) assess- statistically different from the baseline PDAI endoscopy ment of symptom response to the antibiotic and score of 2.83 ± 1.17 (P ¼ 0.27). This finding suggests probiotic therapy; (ii) assessment of clinical factors that that VSL #3 use in these patients may help maintain would predict patients’ response to VSL #3; and symptomatic remission, but to a lesser degree VSL #3 (iii) assessment of adverse effects to VSL #3.
use may improve endoscopic inflammation (Table 2).
Similar to Group A, all 25 patients in Group B reached symptomatic remission after the 2-week course of ciprofloxacin and initiated VSL #3 therapy (Table 2).
The Student t, chi-squared, Fisher’s exact tests were used However, VSL #3 was discontinued in all 25 patients by to compare pre- and post-treatment variables. P values 8 months into the study. Of the 25 patients, 23 <0.05 were considered as statistically significant.
discontinued the agent because of recurrence of symp-toms and two discontinued because of the developmentof adverse effects (Table 3). The mean duration of VSL #3 use in the Group B was 1.2 ± 1.2 months (range: All 31 patients who were classified as antibiotic- 0.5–6.5 months). By week 7, nine patients (36%) had dependent pouchitis had a typical history of clinical discontinued VSL #3 because of either relapse of Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 clinical data between Group A and Group B * Baseline vs. starting VSL #3 and on VSL #3 P < 0.001.
  Baseline and on VSL #3 vs. starting VSL #3 P < 0.001.
à Nine patients in the group B had repeat pouch endoscopy at week 7 for evaluation ofrecurrent symptoms.
symptoms or development of adverse effects. At week 7, pouch endoscopy at week 7 because of persistent the majority of patients in the group became sympto- symptoms and the mean PDAI endoscopy score was 2.11 ± 2.09, which was not statistically different from 2.83 ± 1.43, which was not statistically different from the baseline endoscopy score of 2.89 ± 1.73 (P ¼ the baseline score of 3.17 ± 1.49 at the initiation of the 0.29). At the time of repeat pouch endoscopy at Week sequential ciprofloxacin-VSL #3 therapy (P ¼ 0.43).
7, all the nine patients were already back on antibiotic The nine patients in the Group B underwent repeat therapy after they discontinued VSL #3. According toour clinical practice algorithm, the re-administration of antibiotics was allowed if patients discontinued VSL #3because of recurrence of symptoms or development of adverse effects of VSL #3. The re-administration of Discontinued because of reported recurrent symptoms 23 (74.2) antibiotics might have resulted in falsely improved PDAI symptom and endoscopy scores (Table 2). The remain- ing 16 patients (64%) discontinued VSL #3 after week 7, with the longest duration of treatment with VSL #3 Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 P R O B I O T I C T H E R A P Y I N P O UC H I T I S of 6.5 months in Group B (Table 2). The 16 patients follow-up pouch endoscopy showed inflammation with were back on antibiotics when follow-up PDAI symp- a mean PDAI endoscopy score of 1.83 ± 1.72, which toms were recalculated. Again, the antibiotic use might was not statistically different from that of the baseline have caused falsely improved symptom scores. How- (2.83 ± 1.17). The discrepancy between symptomatic ever, this would not affect the primary or secondary and endoscopic responses may reflect the known lack of correlation between symptoms and endoscopic findings The PDAI symptom score was used to assess response at the end of the 2-week of ciprofloxacin trial (i.e. at While most patients with acute pouchitis respond the beginning of the probiotic) and at the end of promptly to antibiotic therapy, 5–19% develop refract- 8-month trial. Unfortunately, accurate PDAI symptom ory or rapidly relapsing symptoms that require protrac- scores were available only in six patients who were ted therapy.13–15 Of the patients with acute pouchitis, still on VSL #3 at the end of 8 months (Table 2).
39% have a single acute episode that responds to Although the PDAI symptom scores were available in treatment with antibiotics whereas the remaining 61% the 25 patients in Group B at the end of 8 months of patients go on to develop at least one recurrence.16 (Table 2), the scores might have been falsely improved, Treatment and prevention of relapsing pouchitis or as all the 25 patients were on antibiotics rather than antibiotic-dependent pouchitis are often challenging.
These patients require frequent antibiotic treatment, to VSL #3 was generally well tolerated, and only two keep the disease in remission, either with a low-dose patients experienced intolerable adverse effects. One maintenance therapy or with a full-dose pulse therapy.
patient developed bloody bowel movements immediately However, this approach to maintain remission is after starting VSL #3; and one patient experienced empiric and there are no published trials of long-term severe constipation, bloating, and gas. The main reason antibiotic therapy. Probiotic therapy would be a good for discontinuation of VSL #3 was recurrent symptoms alternative given that it would eliminate the concern of development of bacterial resistance because of chronicantibiotic use. During the 9-month trial of 40 patientswith relapsing pouchitis (defined as >3 relapses per year), only three of 20 patients (15%) in the VSL #3 Pouchitis likely represents a spectrum of disease pro- group relapsed during the follow-up, whereas all 20 cesses ranging from an acute antibiotic-responsive type patients (100%) in the placebo group relapsed.6 Patients to a chronic antibiotic-refractory entity. Management of who received VSL #3 had better quality of life scores pouchitis, especially antibiotic-dependent pouchitis and than those who received placebo.7 In another trial, the antibiotic-refractory pouchitis, is often challenging. For same group of investigators studied 40 patients to patients with antibiotic-dependent pouchitis, probiotics determine the efficacy of VSL #3 in the primary may be beneficial in correcting luminal microbial prophylaxis for initial episodes of pouchitis after IPAA.8 imbalance, which is considered to play an important Within 1 week after ileostomy closure, 40 patients with role in its pathogenesis.11,12 Previous randomized, IPAA were randomized to receive either placebo or VSL placebo-controlled trials showed that a probiotic agent #3. Of the 20 patients in the placebo group, eight (40%) VSL #3 was safe and highly effective in preventing had an episode of acute pouchitis during the 1-year pouchitis.6–8 This open-labelled study was intended follow-up while only two or the 20 patients (10%) in the to incorporate those promising results into routine VSL #3 group had such an occurrence.8 However, in clinical practice. This study showed that all patients our clinical practice, the majority of patients with with antibiotic-dependent pouchitis achieved symptom antibiotic-dependent pouchitis discontinued its use remission by means of a 2-week course of ciprofloxacin, because of lack of clinical efficacy. We have attempted but the majority of patients (80.6%) were not able to to optimize the clinical practice model for the manage- continue the probiotic therapy because of reported ment of the disease, by means of endoscopic evaluation relapse of symptoms or development of adverse effects.
and frequent contact with the patients. Prior to entering Only six of 31 patients (19.4%) were able to continue the study, it was established that all 31 patients had a the long-term use of the agent. However, even in the six history of antibiotic-dependent pouchitis, i.e. symptoms patients whose symptoms were in clinical remission, a quickly responded to antibiotic therapy but quickly Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 recurred after stopping antibiotics. If the probiotic agent previous study indicated, NSAID use is an independent were effective, we would expect that it would have at risk factor for pouchitis.20 Whether NSAID-induced least postponed the recurrence of symptoms. The mean pouchitis is a subset of antibiotic-dependent pouchitis duration of VSL #3 use by the patients in Group B was is not known. The description of NSAID use in this only 1.2 ± 1.2 months, and these patients stopped the study was intended to acknowledge potential differ- agent because of reported recurrence of symptoms or ence in patient populations between this and previous trials. In addition, antibiotic use for the induction of Previous randomized trials have demonstrated that remission was different. In our trial, we used a 2-week VSL #3 was highly effective in maintaining remission of course of ciprofloxacin, while the previous trials6–8 used pouchitis.6–8 The mechanism of action of probiotics in a 4-week course of combined ciprofloxacin and rifaxi- patients with pouchitis is not well understood. During min. Whether the number and/or type of antibiotics probiotic treatment, fecal concentrations of Lactobacillus, and the duration of treatment as an induction therapy Bifidobacterium and S. salivarius increased with no affect the outcome of VSL #3 as a maintenance therapy change in other commensal bacteria.6 It was speculated is not known. Another possibility is that the potency of that probiotics may help maintain remission in patients the agent purchased from the US may be different from with pouchitis by: (i) suppressing resident pathogenic that of the Europe. One final source of discrepancy could bacteria; (ii) stimulating mucin glycoprotein production be the methods used to obtain VSL #3. In this study, the by intestinal epithelial cells; (iii) preventing adhesion of patients were instructed to purchase the agent through pathogenic strains to epithelial cells; and (iv) inducing the Internet by themselves, which was the only way host immune responses.11 Being able to prevent relapse patients could obtain the agent in the US. In contrast, of pouchitis using non-toxic, physiologic bacterial the agent was given free of charge to the patients in the agents would be a significant clinical advance.
previous randomized trials. This would raise the con- The results of our current open-label study differ from cern about patients’ adherence in our trial.
that of the previous randomized trials.6–8 The open-label We chose a 2-week course of ciprofloxacin as an design of the current study was not intended to verify or induction therapy because of the excellent outcome in validate the randomized trials. The goal of this study our previous randomized trial of ciprofloxacin vs.
was done to determine whether VSL #3 was effective metronidazole in treating acute pouchitis.21 A 2-week when used in clinical practice. Unfortunately, only a single-agent antibiotic (ciprofloxacin or metronidazole) small number of patients remained in clinical response has also been shown to be effective in treating acute to VSL #3 for the 8-month duration of the trial. The pouchitis by other investigators.22, 23 In clinical practice, reported causes for discontinuation of VSL #3 were ciprofloxacin with a dose of 500–1500 mg/day is a recurrence of symptoms and the development of adverse commonly used therapy. In contrast, the European effects. The discrepancy between this study and the studies used a 4-week ciprofloxacin and rifaximin previous studies could be because of several possibilities.
regimen for induction therapy in relapsing pouchitis6, 7 Firstly, the diagnostic criteria and the classification used – the same regimen they used to treat patients with in the study populations, especially in distinguishing chronic, treatment resistant pouchitis.24 relapsing pouchitis (defined as >3 relapses per year) 6 This study was intended to test the efficacy of VSL #3 and antibiotic-dependent pouchitis, could differ. It is in antibiotic-dependent pouchitis in routine clinical best to acknowledge that the difference in results may practice. With this in mind, there are inherent limita- be related to the difference in patient population. It can tions to the study. Firstly, some patients in this series easily be argued that patients with relapsing pouchitis voiced the concern about cost, as VSL #3 is not have a different clinical disease from patients with considered a medicine, and it is rarely covered by antibiotic-dependent pouchitis. Secondly, the gut flora insurance polices. This would raise the question of may be different in European and in US patients because adherence to therapy. However, the patients were of differences in diet.17–19 Another discrepancy could be informed of the cost before entering the study, and they because of the fact that NSAID use was common in our were also aware of possible alternatives to probiotics, study population at the entry of the study, while NSAID including long-term antibiotic therapy. The majority of use was not mentioned in all the previous studies.6, 7 patients discontinued VSL #3 within 1–2 months after In this trial, NSAID use was not allowed. As our the initiation of the therapy because of reported relapse Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 P R O B I O T I C T H E R A P Y I N P O UC H I T I S of symptoms or adverse effects; none of the patients reported discontinuation of the agent because of the cost. Secondly, the study agent VSL #3 was self- administered by patients after they obtained the agent Gastroenterology 1994; 107: 1856–60.
over the Internet. Medicine counts and evaluation of 2 Zuccaro G, Fazio VW, Church JM, Lavery IC, Ruderman WB, prescription records were impossible. Unlike the previ- Farmer RG. Pouch ileitis. Dig Dis Sci 1989; 34: 1505–10.
3 Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal ous trials, fecal bacteriology was not conducted. This anastomosis complications and function in 1005 patients.
would further raise the issue about patients’ adherence.
However, we have attempted to create the best possible 4 Mahadevan U, Sandborn WJ. Diagnosis and management of scenario for routine clinical practice, by providing out- pouchitis [Review]. Gastroenterology 2003; 124: 1636–50.
patient evaluation and keeping frequent contact with 5 Shen B. Diagnosis and management of patients with pouchitis. Drugs 2003; 65: 453–61.
6 Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy Another issue is that although all patients underwent as maintenance treatment in patients with chronic pouchitis: a baseline evaluation before the initiation of the a double-blind, placebo-controlled trial. Gastroenterology sequential antibiotic-probiotic therapy that included pouch endoscopy and biopsy, none of them had pouch 7 Mimura T, Rizzello F, Helwig U, et al. Once daily high dose endoscopy at the beginning of the VSL #3 trial to probiotic therapy (VSL 3) for maintaining remission inrecurrent or refractory pouchitis. Gut 2004; 53: 108–14.
document a complete resolution of endoscopic inflam- 8 Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of mation of the pouch. This would have missed residual pouchitis onset with probiotic therapy: a double-blind, pouch inflammation in some patients, although our placebo-controlled trial. Gastroenterology 2003; 124: 1202–9.
previous study showed that a 2-week course of ciprofl- 9 Shen B, Fazio VW, Remzi FH, et al. Comprehensive evaluation oxacin achieved remission rate of 100% in active of inflammatory and non-inflammatory sequelae of ileal pouchitis patients.21 A final limitation to the study is pouch-anal anastomosis. Am J Gastroenterol 2004; 100:93–101 the fact that the determination of patients’ response to 10 Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, the antibiotic or the probiotic was largely based on Phillips SF. Pouchitis after ileal pouch-anal anastomosis: a symptoms. It is important to acknowledge that the pouchitis disease activity index. Mayo Clin Proc 1994; 69: recurrence of symptoms on VSL #3 does not necessarily indicate the presence of pouchitis.25, 26 Symptoms may 11 Sartor RB. Probiotics in chronic pouchitis. Restoring luminal microbial balance. Gastroenterology 2000; 119: 584–5.
be related to irritable pouch syndrome, cuffitis, and 12 Shen B, Lashner BA. Can we immuogenotypically and proximal small bowel bacterial overgrowth. Despite the limitations, the results of this study reflect the reality of pouchitis? Am J Gastroenterol 2004; 99: 442–4.
the effects, which the sequential use of antibiotic- 13 Mowschenson PM, Critchlow JF, Peppercorn MA. Ileoanal probiotic therapy would have on our daily clinical pouch operation: long-term outcome with or without diverting ileostomy. Arch Surg 2000; 135: 463–5.
14 Hurst RD, Chung TP, Rubin M, Michelassi F. Implications of In conclusion, we demonstrated in the study that acute pouchitis on the long-term functional results after although symptomatic remission was achieved by a restorative proctocolectomy. Inflamm Bowel Dis 1998; 4: 2-week therapy with ciprofloxacin in all patients, the majority of patients were not able to continue the 15 Madiba TE, Bartolo DC. Pouchitis following restorative long-term maintenance probiotic therapy. More studies therapeutic outcome. J Royal Coll Surg Edinburgh 2001; are warranted to further evaluate the safety and efficacy of probiotic agents. Several hurdles need to be 16 Lohmuller JL, Perberton JH, Dozois RR, Dozois FF, Ilstrup D, overcome before we incorporate the routine use of van Heerden J. Pouchitis and extraintestinal manifestations of probiotics into our daily clinical practice for managing anastomosis. Ann Surg 1990; 211: 622–9.
17 Hill MJ. Diet and the human intestinal flora. Cancer Res 1981; 18 Hayashi H, Sakamoto M, Benno Y. Fecal microbial diversity in a strict vegetarian as determined by molecular analysis and No external funding was received for this study.
cultivation. Microbiol Immunol 2002; 46: 819–31.
Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728 19 Peltonen R, Nenonen M, Helve T, Hanninen O, Toivanen P, pouchitis in 104 consecutive patients after restorative Eerola E. Faecal microbial flora and disease activity in proctocolectomy. Arch Surg 1996; 131: 497–502.
rheumatoid arthritis during a vegan diet. Br J Rheumotol 24 Gionchetti P, Rizzello F, Venturi A, et al. Antibiotic combination therapy in patients with chronic, treatment 20 Achkar J-P, Al-Haddad M, Lashner BA, et al. Differentiating resistant pouchitis. Aliment Pharmacol Ther 1999; 13: 713– risk factors for acute and chronic pouchitis. Clin Gastroenterol 25 Shen B, Achkar J-P, Lashner BA, et al. Endoscopic and 21 Shen B, Achkar JP, Lashner BA, et al. A randomized trial of histologic evaluation together with symptom assessment are ciprofloxacin and metronidazole in treating acute pouchitis.
required to diagnose pouchitis. Gastroenterology 2001; 121: 22 Madden MV, McIntyre AS, Nicholls RJ. Double-blinded 26 Shen B, Achkar JP, Lashner BA, et al. Irritable pouch crossover trial of metronidazole versus placebo in chronic syndrome: a new category of diagnosis for symptomatic unremitting pouchitis. Dig Dis Sci 1994; 39: 1193–6.
23 Hurst RD, Molinari M, Chung TP, Rubin M, Michelassi F.
Prospective study of the incidence, timing, and treatment of Ó 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 22, 721–728

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