Alimentary Pharmacology and Therapeutics Letters to the Editors
Letter: treatment for small intestinal bacterial overgrowth – where are we now? M. Furnari*, V. Savarino* & E. Savarino† *Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. † Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. E-mail: [email protected] doi:10.1111/apt.12585
SIRS, We read with great interest the study by Shah et al.1 who performed a meta-analysis on antibiotic therapy for small intestinal bacterial overgrowth (SIBO). The effort the authors made to find data should be acknowledged. Recently, studies on the pathophysiology of intestinal microbiota have grown exponentially. However, focusing on therapy, of 1356 articles initially found, only 10 fitted the authors’ criteria due to marked differences existing among them in terms of study design. To limit treatment heterogeneity, the authors analysed separately rifaximin vs. placebo studies, highlighting that there was no statistically significant difference in terms of effectiveness between these arms. This worrisome report is clearly in conflict with the daily worldwide use of rifaximin in case of symptoms, suggestive of SIBO and it is likely due to the limited number of patients enrolled. Moreover, the low number of randomised trials available forced the authors to include in their analysis studies assessing antibiotic effectiveness in patients with concomitant SIBO and functional or organic diseases. However, these latter conditions deeply impact the eradication rate and determine false-positive results on breath testing (BT). Indeed, in our study,2 we excluded such influencing variables (motility disorders, mucosal injuries, anatomical
changes, therapies) that should be carefully considered in trials evaluating drug effectiveness for SIBO eradication. Finally, we have some concerns regarding the association of lactulose- with glucose-BT. To date, important data have been published against the reliability of LBT in detecting SIBO,3–5 whose diagnostic accuracy should be reconsidered by applying new restrictive criteria for SIBO positivity or combining LBT with radiological investigations.6 In conclusion, we believe that the findings of this meta-analysis should be interpreted in relation to the above criticisms. Nevertheless, this work clearly underlines the need of further RCTs on SIBO treatment with uniform methodology and including both placebo and probiotics arms.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2013; 38: 925–34. 2. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2010; 32: 1000–6. 3. Yu D, Cheeseman F, Vanner S. Combined oro-cecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testis detects oro-cecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut 2010; 60: 334–40. 4. Bratten JR, Spanier J, Jones MP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol 2008; 103: 958–63. 5. Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using lactulose H2 breath test: comparison with 14C-D-xylose and healthy controls. Am J Gastroenterol 2005; 100: 1566–70. 6. Savarino E, Sconfienza L, Gemignani L, et al. Can we estimate orocecal transit time using MRI? A comparison with hydrogen breath test (hbt) in healthy volunteers. Preliminary results. Gut 2010; 59(sIII): A360.
†
Letter: treatment for small intestinal bacterial overgrowth – where are we now? Authors’ reply J. L. Sewell*,† & S. C. Shah‡ *Department of Medicine, Center for Innovation in Access and Quality, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
442
GI Health, Outcomes, Policy and Economics (GI-HOPE) Program, Division of Gastroenterology, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA. ‡ Department of Medicine, University of California, San Francisco, CA, USA. E-mail: [email protected] doi:10.1111/apt.12591
Aliment Pharmacol Ther 2014; 39: 440-445 ª 2014 John Wiley & Sons Ltd
Letters to the Editors SIRS, We appreciate the response to our article1 offered by Furnari et al., including their recognition of our efforts to summarise the effectiveness of antibiotic therapy for small intestinal bacterial overgrowth (SIBO).2 We agree that the lack of statistical significance in the meta-analysis of rifaximin vs. placebo is likely due to the small number of included studies and subjects. Their points regarding lactulose vs. glucose breath testing, and the inclusion of patients with coexisting functional and organic gastrointestinal disorders are also well made. The motivation to perform our study was a pragmatic one. Our clinical experience was that many of our patients reported symptoms suggestive of SIBO; yet, the ideal antibiotic regimen remained unclear. As such, we felt that a summary of the evidence for antibiotic therapy in SIBO would be useful to ourselves and to others. Although our study could not identify the ‘ideal’ antibiotic regimen for SIBO, we believe that it does summa-
Letter: pitavastatin supplementation of PEG-IFN/ribavirin improves sustained virological response against HCV S. Yokoyama, Y. Kawakami & K. Chayama Department of Gastroenterology and Metabolism, Applied Life Sciences, Institution of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. E-mail: [email protected] doi:10.1111/apt.12605
SIRS, Hwang et al.1 reported a retrospective analysis of rapid virological responses (RVR) for hepatitis C virus (HCV) patients with PEG-IFN/ribavirin. RVR rates were lower in patients with lower platelet counts, total cholesterol levels and low-density lipoprotein levels. RVR rates of genotype-1 patients were independent of statins. We performed a retrospective analysis of PEG-IFN/ ribavirin therapy in the presence or absence of pitavastatin. Duration of treatment was determined by patient response: patients with undetectable HCV RNA at week 12 continued treatment until week 48; patients with detectable HCV RNA at week 12 continued treatment until week 72. Thirty-seven pitavastatin-treated patients and seventy-one controls were evaluated by
Aliment Pharmacol Ther 2014; 39: 440-445 ª 2014 John Wiley & Sons Ltd
rise the existing data, and, importantly, highlights the shortcomings of the current literature – which Furnari et al. also nicely summarise. Like Furnari et al. we hope that future studies of SIBO therapy will conform to a more uniform and comparable standard so that management of SIBO can be optimised.
ACKNOWLEDGEMENT The author’s declarations of personal and financial interests are unchanged from those in the original article.1 REFERENCES 1. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2013; 38: 925–34. 2. Furnari M, Savarino V, Savarino E. Letter: treatment for small intestinal bacterial overgrowth – where are we now? Aliment Pharmacol Ther 2014; 39: 442.
per-protocol (PP) analysis. Of 37 patients completing pitavastatin treatment, 23 underwent treatment for 48 weeks and 14 for 72 weeks. Of 71 controls completing treatment, 61 underwent treatment for 48 weeks and 10 for 72 weeks. There was no significant difference in sustained viral response (SVR) rate by PP analysis: 56.8% pitavastatin group vs. 36.6% control, P = 0.21. Pitavastatin patients with serum total cholesterol
Letter: treatment for small intestinal bacterial overgrowth – where are we now? M. Furnari*, V. Savarino* & E. Savarino† *Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy. † Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. E-mail: [email protected] doi:10.1111/apt.12585
SIRS, We read with great interest the study by Shah et al.1 who performed a meta-analysis on antibiotic therapy for small intestinal bacterial overgrowth (SIBO). The effort the authors made to find data should be acknowledged. Recently, studies on the pathophysiology of intestinal microbiota have grown exponentially. However, focusing on therapy, of 1356 articles initially found, only 10 fitted the authors’ criteria due to marked differences existing among them in terms of study design. To limit treatment heterogeneity, the authors analysed separately rifaximin vs. placebo studies, highlighting that there was no statistically significant difference in terms of effectiveness between these arms. This worrisome report is clearly in conflict with the daily worldwide use of rifaximin in case of symptoms, suggestive of SIBO and it is likely due to the limited number of patients enrolled. Moreover, the low number of randomised trials available forced the authors to include in their analysis studies assessing antibiotic effectiveness in patients with concomitant SIBO and functional or organic diseases. However, these latter conditions deeply impact the eradication rate and determine false-positive results on breath testing (BT). Indeed, in our study,2 we excluded such influencing variables (motility disorders, mucosal injuries, anatomical
changes, therapies) that should be carefully considered in trials evaluating drug effectiveness for SIBO eradication. Finally, we have some concerns regarding the association of lactulose- with glucose-BT. To date, important data have been published against the reliability of LBT in detecting SIBO,3–5 whose diagnostic accuracy should be reconsidered by applying new restrictive criteria for SIBO positivity or combining LBT with radiological investigations.6 In conclusion, we believe that the findings of this meta-analysis should be interpreted in relation to the above criticisms. Nevertheless, this work clearly underlines the need of further RCTs on SIBO treatment with uniform methodology and including both placebo and probiotics arms.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2013; 38: 925–34. 2. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2010; 32: 1000–6. 3. Yu D, Cheeseman F, Vanner S. Combined oro-cecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testis detects oro-cecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut 2010; 60: 334–40. 4. Bratten JR, Spanier J, Jones MP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol 2008; 103: 958–63. 5. Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using lactulose H2 breath test: comparison with 14C-D-xylose and healthy controls. Am J Gastroenterol 2005; 100: 1566–70. 6. Savarino E, Sconfienza L, Gemignani L, et al. Can we estimate orocecal transit time using MRI? A comparison with hydrogen breath test (hbt) in healthy volunteers. Preliminary results. Gut 2010; 59(sIII): A360.
†
Letter: treatment for small intestinal bacterial overgrowth – where are we now? Authors’ reply J. L. Sewell*,† & S. C. Shah‡ *Department of Medicine, Center for Innovation in Access and Quality, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA.
442
GI Health, Outcomes, Policy and Economics (GI-HOPE) Program, Division of Gastroenterology, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA. ‡ Department of Medicine, University of California, San Francisco, CA, USA. E-mail: [email protected] doi:10.1111/apt.12591
Aliment Pharmacol Ther 2014; 39: 440-445 ª 2014 John Wiley & Sons Ltd
Letters to the Editors SIRS, We appreciate the response to our article1 offered by Furnari et al., including their recognition of our efforts to summarise the effectiveness of antibiotic therapy for small intestinal bacterial overgrowth (SIBO).2 We agree that the lack of statistical significance in the meta-analysis of rifaximin vs. placebo is likely due to the small number of included studies and subjects. Their points regarding lactulose vs. glucose breath testing, and the inclusion of patients with coexisting functional and organic gastrointestinal disorders are also well made. The motivation to perform our study was a pragmatic one. Our clinical experience was that many of our patients reported symptoms suggestive of SIBO; yet, the ideal antibiotic regimen remained unclear. As such, we felt that a summary of the evidence for antibiotic therapy in SIBO would be useful to ourselves and to others. Although our study could not identify the ‘ideal’ antibiotic regimen for SIBO, we believe that it does summa-
Letter: pitavastatin supplementation of PEG-IFN/ribavirin improves sustained virological response against HCV S. Yokoyama, Y. Kawakami & K. Chayama Department of Gastroenterology and Metabolism, Applied Life Sciences, Institution of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. E-mail: [email protected] doi:10.1111/apt.12605
SIRS, Hwang et al.1 reported a retrospective analysis of rapid virological responses (RVR) for hepatitis C virus (HCV) patients with PEG-IFN/ribavirin. RVR rates were lower in patients with lower platelet counts, total cholesterol levels and low-density lipoprotein levels. RVR rates of genotype-1 patients were independent of statins. We performed a retrospective analysis of PEG-IFN/ ribavirin therapy in the presence or absence of pitavastatin. Duration of treatment was determined by patient response: patients with undetectable HCV RNA at week 12 continued treatment until week 48; patients with detectable HCV RNA at week 12 continued treatment until week 72. Thirty-seven pitavastatin-treated patients and seventy-one controls were evaluated by
Aliment Pharmacol Ther 2014; 39: 440-445 ª 2014 John Wiley & Sons Ltd
rise the existing data, and, importantly, highlights the shortcomings of the current literature – which Furnari et al. also nicely summarise. Like Furnari et al. we hope that future studies of SIBO therapy will conform to a more uniform and comparable standard so that management of SIBO can be optimised.
ACKNOWLEDGEMENT The author’s declarations of personal and financial interests are unchanged from those in the original article.1 REFERENCES 1. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2013; 38: 925–34. 2. Furnari M, Savarino V, Savarino E. Letter: treatment for small intestinal bacterial overgrowth – where are we now? Aliment Pharmacol Ther 2014; 39: 442.
per-protocol (PP) analysis. Of 37 patients completing pitavastatin treatment, 23 underwent treatment for 48 weeks and 14 for 72 weeks. Of 71 controls completing treatment, 61 underwent treatment for 48 weeks and 10 for 72 weeks. There was no significant difference in sustained viral response (SVR) rate by PP analysis: 56.8% pitavastatin group vs. 36.6% control, P = 0.21. Pitavastatin patients with serum total cholesterol
