IBD & Intestinal Disorders

CHICAGO – Observation, compared with elective resection, was associated with significantly increased recurrence rates in a single-center randomized, controlled trial of patients who had successfully recovered via nonoperative management from their first episode of acute sigmoid diverticulitis with extraluminal air/abscess.

Recurrence rates in 111 patients randomized to observation or elective resection were 31% in the observation group and 7% in the resection group, at 15 and 18 months, respectively, Dr. Ryan Bendl of State University of New York, Stony Brook reported at the annual meeting of the American Surgical Association.

Patients in the two groups were comparable with respect to age, sex, body mass index, Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM), and comorbidities, he noted.

Subjects included in the single-center study were adults admitted for a first episode of acute diverticulitis with abscess or extraluminal air who were managed nonoperatively with intravenous antibiotics, a period of nothing by mouth, drainage, and total parenteral nutrition followed by colonoscopy. They were randomized 3:1 to observation or resection, and 68% of the elective resection patients underwent minimally invasive surgery. The study’s primary endpoint was recurrent diverticulitis defined as an acute episode confirmed by computed tomography and requiring hospitalization with intravenous antibiotics.

Diverticulitis accounted for more than 300,000 hospital admissions in 2010 in the United States alone, and 10%-20% of patients had abscess formation. At one time, most patients were managed with immediate operative intervention, but medical and radiologic advances have led to a shift toward nonoperative management, Dr. Bendl said.

Some prior studies have suggested that recurrence rates are higher with nonoperative management, and the current study supports those data.

However, despite the significant increase in the recurrence rate with observation vs. resection, most patients in the observation group did not experience recurrence, and of those who did, none had peritonitis.

“All those with recurrences were successfully treated again using nonoperative management,” he said.

This study was supported in part by grants from Merck and Covidien. Dr. Bendl reported having no relevant financial disclosures.

CHICAGO – Observation, compared with elective resection, was associated with significantly increased recurrence rates in a single-center randomized, controlled trial of patients who had successfully recovered via nonoperative management from their first episode of acute sigmoid diverticulitis with extraluminal air/abscess.

Recurrence rates in 111 patients randomized to observation or elective resection were 31% in the observation group and 7% in the resection group, at 15 and 18 months, respectively, Dr. Ryan Bendl of State University of New York, Stony Brook reported at the annual meeting of the American Surgical Association.

Patients in the two groups were comparable with respect to age, sex, body mass index, Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM), and comorbidities, he noted.

Subjects included in the single-center study were adults admitted for a first episode of acute diverticulitis with abscess or extraluminal air who were managed nonoperatively with intravenous antibiotics, a period of nothing by mouth, drainage, and total parenteral nutrition followed by colonoscopy. They were randomized 3:1 to observation or resection, and 68% of the elective resection patients underwent minimally invasive surgery. The study’s primary endpoint was recurrent diverticulitis defined as an acute episode confirmed by computed tomography and requiring hospitalization with intravenous antibiotics.

Diverticulitis accounted for more than 300,000 hospital admissions in 2010 in the United States alone, and 10%-20% of patients had abscess formation. At one time, most patients were managed with immediate operative intervention, but medical and radiologic advances have led to a shift toward nonoperative management, Dr. Bendl said.

Some prior studies have suggested that recurrence rates are higher with nonoperative management, and the current study supports those data.

However, despite the significant increase in the recurrence rate with observation vs. resection, most patients in the observation group did not experience recurrence, and of those who did, none had peritonitis.

“All those with recurrences were successfully treated again using nonoperative management,” he said.

This study was supported in part by grants from Merck and Covidien. Dr. Bendl reported having no relevant financial disclosures.

CHICAGO – Observation, compared with elective resection, was associated with significantly increased recurrence rates in a single-center randomized, controlled trial of patients who had successfully recovered via nonoperative management from their first episode of acute sigmoid diverticulitis with extraluminal air/abscess.

Recurrence rates in 111 patients randomized to observation or elective resection were 31% in the observation group and 7% in the resection group, at 15 and 18 months, respectively, Dr. Ryan Bendl of State University of New York, Stony Brook reported at the annual meeting of the American Surgical Association.

Patients in the two groups were comparable with respect to age, sex, body mass index, Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM), and comorbidities, he noted.

Subjects included in the single-center study were adults admitted for a first episode of acute diverticulitis with abscess or extraluminal air who were managed nonoperatively with intravenous antibiotics, a period of nothing by mouth, drainage, and total parenteral nutrition followed by colonoscopy. They were randomized 3:1 to observation or resection, and 68% of the elective resection patients underwent minimally invasive surgery. The study’s primary endpoint was recurrent diverticulitis defined as an acute episode confirmed by computed tomography and requiring hospitalization with intravenous antibiotics.

Diverticulitis accounted for more than 300,000 hospital admissions in 2010 in the United States alone, and 10%-20% of patients had abscess formation. At one time, most patients were managed with immediate operative intervention, but medical and radiologic advances have led to a shift toward nonoperative management, Dr. Bendl said.

Some prior studies have suggested that recurrence rates are higher with nonoperative management, and the current study supports those data.

However, despite the significant increase in the recurrence rate with observation vs. resection, most patients in the observation group did not experience recurrence, and of those who did, none had peritonitis.

“All those with recurrences were successfully treated again using nonoperative management,” he said.

This study was supported in part by grants from Merck and Covidien. Dr. Bendl reported having no relevant financial disclosures.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Treatment at the nanomolecular level may become an alternative for various types of constipation, in particular for the opioid-induced constipation that is common after surgery, based on data from a proof of concept study involving mice and a small-molecule activator.

“Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the primary pathway that drives fluid secretion in the intestine, which maintains lubrication of luminal contents,” wrote Dr. Onur Cil of the University of California, San Francisco, and colleagues. The researchers examined whether direct activation of the CFTR would prompt fluid secretion and reverse stool dehydration when applied to constipated mice. The findings were published online in the May issue of the journal Cellular and Molecular Gastroenterology and Hepatology (2016. doi: 10.1016/j.jcmgh.2015.12.010).

The researchers identified a promising activator, the phenylquinoxalinone CFTRact-J027. Mice received up to 10 mg/kg CFTRact-J027 either orally or intraperitoneally (IP), with doses including 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.

Overall, IP doses of CFTRact-J027 at 10 mg/kg normalized stool in the constipated mice, and dose-response studies showed a 50% effective dose of 2 mg/kg in these mice.

When given orally, CFTRact-J027 “normalized stool output and water content in a loperamide-induced mouse model of constipation with a 50% effective dose of approximately 0.5 mg/kg,” that was significantly lower than the IP administration, the researchers noted. An oral dose of 10 mg/kg CFTRact-J027 1 hour before inducing constipation also was effective in normalizing stool output and water content in loperamide-treated mice, with no effect in control nonconstipated mice.

The activator was not effective against constipation in cystic fibrosis mice that were missing a functional CFTR, they added.

The researchers used an in vivo closed loop model to specifically test the effects of CFTRact-J027 on intestinal fluid secretion and absorption and found that CFTRact-J027 caused “a 140% increase in loop weight/length ratio, indicating fluid secretion into the intestinal lumen in wild-type mice.” However, there was no effect in cystic fibrosis mice, further supporting the CFTR-selective mechanism of action, the researchers said.

As for potential toxic effects of the treatment, CFTRact-J027 showed no impact on the major serum chemistry and blood parameters of the mice after 7 days, and had no apparent impact on body weight. No accumulation of fluid (the most significant potential adverse effect) was noted in the airway or lungs of the treated mice.

Additional toxicity data are needed to continue preclinical development, the researchers said. However, “our data provide evidence for the prosecretory action of a CFTR activator in mouse intestine and proof of concept for its use in the treatment of various types of constipation, which could include opioid-induced constipation, chronic idiopathic constipation, and irritable bowel syndrome with constipation predominance,” they wrote. In addition, a CFTR activator similar to that used in this study may have clinical applications for other conditions including asthma, dry eye, cholestatic liver disease, chronic obstructive pulmonary disease and bronchitis, and cigarette smoke–induced lung dysfunction, they added.

Dr. Cil and two coauthors are inventors on a provisional patent filing, with rights owned by the University of California, San Francisco. The study was funded in part by several grants from organizations including the National Institutes of Health and the Cystic Fibrosis Foundation.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

Among a large cohort of patients referred for endoscopy for suspected celiac disease as well as all upper gastrointestinal symptoms, a single additional D1 biopsy specimen from any site significantly increased the diagnostic yield for celiac disease, according to researchers.

Of 1,378 patients who had D2 and D1 biopsy specimens taken, 268 were newly diagnosed with celiac disease, and 26 had villous atrophy confined to D1, defined as ultrashort celiac disease (USCD). Compared with a standard D2 biopsy, an additional D1 biopsy increased the diagnostic yield by 9.7% (P less than .0001). Among the 26 diagnosed with USCD, 7 had normal D2 biopsy specimens, and 4 others had negative tests for endomysial antibodies (EMAs), totaling 11 patients for whom celiac disease would have been missed in the absence of a D1 biopsy.

“The addition of a D1 biopsy specimen to diagnose celiac disease may reduce the known delay in diagnosis that many patients with celiac disease experience. This may allow earlier institution of a gluten-free diet, potentially prevent nutritional deficiencies, and reduce the symptomatic burden of celiac disease,” wrote Dr. Peter Mooney of Royal Hallamshire Hospital, Sheffield, England, and his colleagues. (Gastroenterology 2016 April 7. doi: 10.1053/j-gastro.2016.01.029).

The prospective study recruited 1,378 consecutive patients referred to a single teaching hospital for endoscopy from 2008 to 2014. In total, 268 were newly diagnosed with celiac disease, and 26 were diagnosed with USCD.

To investigate the optimal site for targeted D1 sampling, 171 patients underwent quadrantic D1 biopsy, 61 of whom were diagnosed with celiac disease. Biopsy specimens from any topographical area resulted in high sensitivity, a fact that increases the feasibility of a D1 biopsy policy, since no specific target area is required, according to the researchers. Nonceliac abnormalities such as peptic duodenitis or gastric heterotopia have been suggested to impede interpretation of D1 biopsies, but these were rare in the study and did not interfere with the analysis.

USCD may be an early form of conventional celiac disease, an idea supported by the findings. Compared with patients diagnosed with conventional celiac disease, patients diagnosed with USCD were younger and had a much lower rate of diarrhea, which by decision-tree analysis was the single factor discriminating between the two groups. Compared with healthy controls, individuals with conventional celiac disease, but not USCD, were more likely to present with anemia, diarrhea, a family history of celiac disease, lethargy, and osteoporosis. Patients with USCD and conventional disease had similar rates of IgA tissue transglutaminase antibodies (tTG), but USCD patients had lower titers (P less than .001). The USCD group also had fewer ferritin and folate deficiencies.

The researchers suggested that clinical phenotypic differences may be due to minimal loss of absorptive capacity associated with a short segment of villous atrophy. Given the younger average age at diagnosis of USCD and lower tTG titers, USCD may represent an early stage of celiac disease, resulting in fewer nutritional deficiencies observed because of a shorter lead time to diagnosis.

Although USCD patients had a milder clinical phenotype, which has raised concerns that a strict gluten-free diet may be unnecessary, follow-up data demonstrated that a gluten-free diet produced improvement in symptoms and a significant decrease in the tTG titer. These results may indicate that the immune cascade was switched off, according to the researchers, and that early diagnosis may present a unique opportunity to prevent further micronutrient deficiency.

Dr. Mooney and his coauthors reported having no relevant financial disclosures.

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Intravenous tigecycline was significantly more effective than standard therapy at curing refractory Clostridium difficile infections, according to a case-control study presented at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Tigecycline effected a 76% clinical cure rate, compared with 53% for the combination regimen of intravenous metronidazole and oral vancomycin, Dr. Baltin Gergely Szabo reported. And despite the fact that those who took tigecycline had more clinically severe disease, no colectomies were required in that group, while two patients in the standard treatment arm did need the procedure.

However, tigecycline didn’t significantly improve relapse rates or mortality, noted Dr. Szabo of the St. Stephan and St. Ladislaus Hospital-Clinic, Budapest, Hungary.

He presented the results of a matched case-control study of 90 patients with severe C. difficile infections, who were treated with either of the protocols. Patients who took tigecycline were more likely to have a recurrent infection (38% vs. 29%). Thus, they were also more likely to have previously been treated with metronidazole (38% vs. 24%) and vancomycin (24% vs. 7%). Prior tigecycline use was very rare in both groups (2% vs. 0%).

Those who took tigecycline were significantly younger as well (72 vs. 78 years), and more often men (56% vs. 30%). They were more likely to be hypertensive, have chronic obstructive pulmonary disease, have cancers, be immunosuppressed, and be chronic users of corticosteroids.

However, the Charlson comorbidity index was similar between the tigecycline and standard therapy groups (4.6 vs. 5). They were also matched for ATLAS scores (mean 7.8 in each group).

Significantly more patients taking tigecycline had acquired their infections during hospitalization (64% vs. 30%). They also had a longer duration of symptoms (17 vs. 10 days).

Imaging showed more severe disease in the tigecycline group with significantly more colonic distension, mural thickening, and ascites. Tigecycline patients had also undergone significantly more colonoscopies and blood cultures.

Tigecycline was given in the hospital for 7-10 days, with a 100-mg loading dose and subsequent 50-mg daily doses. The main duration of therapy was 10 days, but that varied widely, from 2 to 22 days. It was given only as first-line treatment to 15% of patients; the rest received tigecycline as an alternative treatment, often after the combination of metronidazole/vancomycin had failed. No adverse drug reactions occurred in the group.

Clinical cure was achieved in 76% of the tigecycline group and 53% of the standard protocol group – a significant difference. The drug was associated with a decreased rate of complicated disease course (29% vs. 53%) and significantly fewer colectomies (0 vs. 2).

Rates of toxic megacolon were equal (7% each group); ileus was more frequent in the tigecycline group (11% vs. 9%), but this difference was not statistically significant.

However, tigecycline had no impact on either in-hospital or 90-day relapse, or on in-hospital mortality (15 vs. 16 deaths). At 90 days, fewer patients taking the drug had died (17 vs. 21), but that difference was not statistically significant (P = 0.52).

A multivariate analysis identified several characteristics associated with a beneficial response to tigecycline:

• Male sex.

• Being immunosuppressed.

• Chronic steroid treatment.

• Malignancy.

• Longer duration of symptoms.

• Prior C. difficile infections.

• Nosocomial onset.

• Signs of severe infection on imaging.

Dr. Szabo said these characteristics can be used to create a profile of patients who might be good candidates for the drug.

He had no relevant financial declarations.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

Screening asymptomatic patients admitted through the emergency department for occult Clostridium difficile infection, then isolating those found to be carriers throughout their hospital stay, substantially reduced the incidence of hospital-acquired C. difficile infection in a tertiary acute-care hospital, according to a report published online April 25 in JAMA Internal Medicine.

In what investigators described as the first study to assess the benefit of such an intervention, the Quebec Heart and Lung Institute (QHLI) in Quebec City went from being endemic for C. difficile infection to having the lowest incidence among 22 academic hospitals across the province of Quebec. “If confirmed in subsequent studies, isolating asymptomatic carriers could potentially prevent thousands of cases of hospital-acquired C. difficile infection every year in North America,” said Dr. Yves Longtin of the infection prevention and control unit at Jewish General Hospital, Montreal, and his associates.

CDC/D. Holdeman

The QHLI implemented the screen-and-isolate program because, despite robust infection-control efforts, it continued to exceed the government-imposed target level of 9.0 C. difficile infections per 10,000 patient-days. The program, which involved 7,599 patients admitted to the facility through its ED during a 17-month period, called for rectal sampling with a sterile swab, using a polymerase chain reaction (PCR) assay to detect the tcdB gene, obtaining the results within 24 hours, and isolating any carriers for the remainder of their stay. A total of 368 asymptomatic patients (4.8%) were found to be carriers.

Before the intervention, the hospital’s monthly incidence averaged 8.2 cases per 10,000 patient-days, with a high of 28.6 cases per 10,000 patient-days during an epidemic. After the intervention was implemented, the monthly incidence dropped to 3.0 per 10,000 patient-days. The hospital exceeded target levels of cases in 24.4% of the months preceding the intervention, compared with none of the months afterward. The investigators calculated that only 121 patients needed to be screened and 6 asymptomatic carriers needed to be isolated to prevent 1 case of hospital-acquired C. difficile infection.

During the same time period, rates of C. difficile infection remained stable at other hospitals across the province, Dr. Longtin and his associates said (JAMA Intern Med. 2016 Apr 25. doi: 10.1001/jamainternmed.2016.0177).

“The intervention may be effective not only by preventing direct patient-to-patient transmission but also by limiting contamination of the hospital environment,” they noted.

The study was supported by the Quebec Heart and Lung Institute, the Quebec Ministry of Health and Social Services, and the Quebec Foundation for Health Research. Dr. Longtin reported being a coapplicant on a patent for methods, reagents, and kits for the assessment of bacterial infections. His associates reported ties to Sanofi Pasteur, Merck, and Otsuka.

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.

However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Michele G. Sullivan/Frontline Medical News

Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.

The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.

They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.

Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.

The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.

The mean follow-up was 21 months, also with a wide range (3-68 months).

A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.

Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.

Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.

There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.

The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”

She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.

Of the other four patients with transplant complications:

• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.

• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.

• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.

• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.

During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.

• Colonoscopic administration is mandatory for any patient with a swallowing disorder.

• A smaller volume of feces is now infused.

• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.

• There is no eating or drinking for at least 1 hour after the transplant.

• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

A 10-mg dose of tofacitinib twice daily significantly improved remission, mucosal healing, and clinical response in adults with active ulcerative colitis (UC), based on data from a pair of identical phase III studies including nearly 900 patients. The findings were presented at the European Crohn’s and Colitis Organisation conference in Amsterdam.

“In up to one-third of patients with UC, treatment is not completely successful or complications arise,” study coauthor Dr. Geert D’Haens of the University of Amsterdam said in an interview. The goal of the studies was to evaluate the safety and efficacy of a 10-mg dose of oral tofacitinib twice daily in inducing remission in UC patients, he added. The OCTAVE (Oral Clinical Trials for Tofacitinib in Ulcerative Colitis) Induction 1 study included 476 patients taking tofacitinib and 122 patients taking placebo; the OCTAVE Induction 2 study included 429 patients on tofacitinib and 112 patients on placebo.

©selvanegra/thinkstockphotos.com

Overall, significantly more patients receiving tofacitinib 10 mg twice daily achieved remission, mucosal healing, and clinical response in both studies, compared with the placebo, at 8 weeks. In the OCTAVE Induction 1 and Induction 2 studies, remission at 8 weeks for tofacitinib compared with placebo was 19% vs. 8% and 17% vs. 4%, respectively. Mucosal healing rates in the Induction 1 and 2 studies for tofacitinib compared with placebo were 31% vs. 16% and 28% vs. 12%, respectively, and clinical response rates were 60% vs. 33% and 55% vs. 29%, respectively. Efficacy was similar for patients previously treated with tumor necrosis factor inhibitors and those who were not.

The incidence of adverse events and serious adverse events was not significantly different between treatment and placebo groups in either study. However, tofacitinib treatment was associated with increases in serum lipid (total cholesterol, low-density and high-density lipoprotein), and creatine kinase levels.

“The clinical trial data confirm our blinded observations,” Dr. D’Haens said. “Even when all other drugs have failed, tofacitinib can be effective. Since Janus kinase inhibitors reduce the production of many proinflammatory cytokines, the clinical findings are in line with what we expected. Fortunately, adverse events were limited and allowed prolonged treatment with this agent,” he noted.

Research on tofacitinib and UC is ongoing, said Dr. D’Haens. The two studies reported here, OCTAVE Induction 1 and 2, are part of the global OCTAVE program, he said. Other related studies include a third phase III study, OCTAVE Sustain, and a long-term extension trial called OCTAVE Open. “OCTAVE Sustain is a phase III placebo-controlled study evaluating oral tofacitinib 10 mg and 5 mg b.i.d. as maintenance therapy in adult patients with moderately to severely active UC. Top-line results for this study are anticipated at the end of this year,” he said. “OCTAVE Open is an ongoing open-label extension study designed to assess the safety and tolerability of tofacitinib 10 mg and 5 mg b.i.d. in patients who have completed or who have had treatment failure in OCTAVE Sustain or who were nonresponders upon completing OCTAVE Induction 1 or 2,” he added.

The study was supported in part by Pfizer. Dr. D’Haens disclosed financial relationships with multiple companies, including Pfizer.

A 10-mg dose of tofacitinib twice daily significantly improved remission, mucosal healing, and clinical response in adults with active ulcerative colitis (UC), based on data from a pair of identical phase III studies including nearly 900 patients. The findings were presented at the European Crohn’s and Colitis Organisation conference in Amsterdam.

“In up to one-third of patients with UC, treatment is not completely successful or complications arise,” study coauthor Dr. Geert D’Haens of the University of Amsterdam said in an interview. The goal of the studies was to evaluate the safety and efficacy of a 10-mg dose of oral tofacitinib twice daily in inducing remission in UC patients, he added. The OCTAVE (Oral Clinical Trials for Tofacitinib in Ulcerative Colitis) Induction 1 study included 476 patients taking tofacitinib and 122 patients taking placebo; the OCTAVE Induction 2 study included 429 patients on tofacitinib and 112 patients on placebo.

©selvanegra/thinkstockphotos.com

Overall, significantly more patients receiving tofacitinib 10 mg twice daily achieved remission, mucosal healing, and clinical response in both studies, compared with the placebo, at 8 weeks. In the OCTAVE Induction 1 and Induction 2 studies, remission at 8 weeks for tofacitinib compared with placebo was 19% vs. 8% and 17% vs. 4%, respectively. Mucosal healing rates in the Induction 1 and 2 studies for tofacitinib compared with placebo were 31% vs. 16% and 28% vs. 12%, respectively, and clinical response rates were 60% vs. 33% and 55% vs. 29%, respectively. Efficacy was similar for patients previously treated with tumor necrosis factor inhibitors and those who were not.

The incidence of adverse events and serious adverse events was not significantly different between treatment and placebo groups in either study. However, tofacitinib treatment was associated with increases in serum lipid (total cholesterol, low-density and high-density lipoprotein), and creatine kinase levels.

“The clinical trial data confirm our blinded observations,” Dr. D’Haens said. “Even when all other drugs have failed, tofacitinib can be effective. Since Janus kinase inhibitors reduce the production of many proinflammatory cytokines, the clinical findings are in line with what we expected. Fortunately, adverse events were limited and allowed prolonged treatment with this agent,” he noted.

Research on tofacitinib and UC is ongoing, said Dr. D’Haens. The two studies reported here, OCTAVE Induction 1 and 2, are part of the global OCTAVE program, he said. Other related studies include a third phase III study, OCTAVE Sustain, and a long-term extension trial called OCTAVE Open. “OCTAVE Sustain is a phase III placebo-controlled study evaluating oral tofacitinib 10 mg and 5 mg b.i.d. as maintenance therapy in adult patients with moderately to severely active UC. Top-line results for this study are anticipated at the end of this year,” he said. “OCTAVE Open is an ongoing open-label extension study designed to assess the safety and tolerability of tofacitinib 10 mg and 5 mg b.i.d. in patients who have completed or who have had treatment failure in OCTAVE Sustain or who were nonresponders upon completing OCTAVE Induction 1 or 2,” he added.

The study was supported in part by Pfizer. Dr. D’Haens disclosed financial relationships with multiple companies, including Pfizer.

A 10-mg dose of tofacitinib twice daily significantly improved remission, mucosal healing, and clinical response in adults with active ulcerative colitis (UC), based on data from a pair of identical phase III studies including nearly 900 patients. The findings were presented at the European Crohn’s and Colitis Organisation conference in Amsterdam.

“In up to one-third of patients with UC, treatment is not completely successful or complications arise,” study coauthor Dr. Geert D’Haens of the University of Amsterdam said in an interview. The goal of the studies was to evaluate the safety and efficacy of a 10-mg dose of oral tofacitinib twice daily in inducing remission in UC patients, he added. The OCTAVE (Oral Clinical Trials for Tofacitinib in Ulcerative Colitis) Induction 1 study included 476 patients taking tofacitinib and 122 patients taking placebo; the OCTAVE Induction 2 study included 429 patients on tofacitinib and 112 patients on placebo.

©selvanegra/thinkstockphotos.com

Overall, significantly more patients receiving tofacitinib 10 mg twice daily achieved remission, mucosal healing, and clinical response in both studies, compared with the placebo, at 8 weeks. In the OCTAVE Induction 1 and Induction 2 studies, remission at 8 weeks for tofacitinib compared with placebo was 19% vs. 8% and 17% vs. 4%, respectively. Mucosal healing rates in the Induction 1 and 2 studies for tofacitinib compared with placebo were 31% vs. 16% and 28% vs. 12%, respectively, and clinical response rates were 60% vs. 33% and 55% vs. 29%, respectively. Efficacy was similar for patients previously treated with tumor necrosis factor inhibitors and those who were not.

The incidence of adverse events and serious adverse events was not significantly different between treatment and placebo groups in either study. However, tofacitinib treatment was associated with increases in serum lipid (total cholesterol, low-density and high-density lipoprotein), and creatine kinase levels.

“The clinical trial data confirm our blinded observations,” Dr. D’Haens said. “Even when all other drugs have failed, tofacitinib can be effective. Since Janus kinase inhibitors reduce the production of many proinflammatory cytokines, the clinical findings are in line with what we expected. Fortunately, adverse events were limited and allowed prolonged treatment with this agent,” he noted.

Research on tofacitinib and UC is ongoing, said Dr. D’Haens. The two studies reported here, OCTAVE Induction 1 and 2, are part of the global OCTAVE program, he said. Other related studies include a third phase III study, OCTAVE Sustain, and a long-term extension trial called OCTAVE Open. “OCTAVE Sustain is a phase III placebo-controlled study evaluating oral tofacitinib 10 mg and 5 mg b.i.d. as maintenance therapy in adult patients with moderately to severely active UC. Top-line results for this study are anticipated at the end of this year,” he said. “OCTAVE Open is an ongoing open-label extension study designed to assess the safety and tolerability of tofacitinib 10 mg and 5 mg b.i.d. in patients who have completed or who have had treatment failure in OCTAVE Sustain or who were nonresponders upon completing OCTAVE Induction 1 or 2,” he added.

The study was supported in part by Pfizer. Dr. D’Haens disclosed financial relationships with multiple companies, including Pfizer.

PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Do you have patients with undiagnosed celiac disease or legitimate gluten sensitivity, or are they self-diagnosing with the need to steer clear of gluten, only to find themselves in danger of nutritional deficiencies and other health concerns?

Of the roughly 1% of Americans who have celiac disease, only about 17% ever receive a diagnosis, leaving the remainder at risk for serious health complications, according to Dr. Peter H.R. Green, director of the Celiac Disease Center at Columbia University, New York.

Meanwhile, many people choose to go gluten free, which Dr. Green calls the most popular “fad” diet in the country. Aside from this trend being more expensive, and often inconvenient, it’s also a health risk. “It’s ironic that so many people who should be on a gluten-free diet aren’t, and those who are don’t need to be, and might even be harming their health,” he said in an interview.

In this video, Dr. Green discusses how to determine whether patients have celiac disease or another diagnosis, and how to counsel those who do have the disease and those who don’t.

The video was recorded at this year’s Digestive Diseases: New Advances, held by Global Academy for Medical Education and Rutgers, the State University of New Jersey. Global Academy and this news organization are owned by the same company.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

jevans@frontlinemedcom.com

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

jevans@frontlinemedcom.com

A biosimilar version of the anti–tumor necrosis factor–alpha agent Remicade has been approved by the Food and Drug Administration, making it the first biosimilar drug approved by the agency for inflammatory diseases and just the second biosimilar it has approved.

The agency said in its April 5 announcement that the biosimilar drug, to be marketed as Inflectra, will have the same indications as Remicade: moderately to severely active Crohn’s disease in patients aged 6 years and older who have had an inadequate response to conventional therapy; moderately to severely active ulcerative colitis that has inadequately responded to conventional therapy; moderately to severely active rheumatoid arthritis in combination with methotrexate; active ankylosing spondylitis; active psoriatic arthritis; and chronic, severe plaque psoriasis.

Courtesy Wikimedia Commons/ FitzColinGerald/Creative Commons License

The drug, given the generic name of infliximab-dyyb under the agency’s nomenclature for biosimilar products, earned its approval as a biosimilar by showing it has no clinically meaningful differences in terms of safety and effectiveness from Remicade. According to FDA regulations, biosimilar products can have only minor differences in clinically inactive components and must have the same mechanism(s) of action (to the extent that it is known) and route(s) of administration, dosage form(s), and strength(s) as the reference product; and can be approved only for the indication(s) and condition(s) of use that have been approved for the reference product.

Inflectra’s approval is only as a biosimilar, not as an interchangeable product. The agency has yet to define the regulatory requirements for interchangeability that are necessary to meet the requirements of the Biologics Price Competition and Innovation Act of 2009. That Act states that an approved biosimilar “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” A statement about implementation of the Act on the FDA website explains that for interchangeability, “a sponsor must demonstrate that the biosimilar product can be expected to produce the same clinical result as the reference product in any given patient and, for a biological product that is administered more than once, that the risk of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of maintaining the patient on the reference product.”

Like Remicade, Inflectra will come with a boxed warning and a Medication Guide that describes important information about its uses and risks, which include serious infections (tuberculosis, bacterial sepsis, invasive fungal infections, and others), lymphoma and other malignancies, liver injury, blood problems, lupuslike syndrome, psoriasis, and in rare cases, nervous system disorders.

Inflectra is manufactured by Celltrion, based in South Korea, for Illinois-based Hospira. Inflectra’s label can be found here.

jevans@frontlinemedcom.com