Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Updates

Posted on March 9, 2017 by gutsandgrowth

A recent clinical practice update (S Khanna et al. Clin Gastroenterol Hepatol; 2017; 15: 166-74) provides some succinct recommendations regarding Clostridium difficile infection (CDI) in Inflammatory Bowel Disease (IBD).

Background: In 2011, the authors note that CDI was associated with 29,000 deaths and is now the most lethal enteric pathogen in the U.S.

Differences in pathogenesis of C diff in IBD compared to those without IBD:

Younger age
Less frequent antibiotic exposure
More often community onset (rather than hospital onset)
Higher recurrence (may be related to dysbiosis)

Key recommendations:

In patients with IBD flare, test for CDI
In patients with CDI and IBD, clinicians should consider “using vancomycin instead of metronidazole.”
In patients with recurrent CDI and IBD, consider fecal microbiota transplantation

Figure 4 proposes a management algorithm (for adults). If uncomplicated CDI, recommended dose of vancomycin was 125 mg q6h. If no improvement in 3-4 days, then “consider escalation of immunosuppression.” For complicated CDI, consider oral vancomycin at 500 mg q6h and IV metronidazole 500 mg q8. In addition, consider rectal vancomycin and surgery consult.

Complicated CDI includes ICU admission, hypotension, T >38.5, ileus/megacolon, mental status changes, leukocyte count >35,000 or < 2000, or lactate >2.2 mmol/L

Another review article (Y Chen et al. Inflamm Bowel Dis 2017; 23: 200-07) is a meta-analysis that identified six studies. One of these studies was a case-control study with nearly 400,000 patients (and about 7000 cases of C diff). Key finding: CDI results in nearly a doubling of the risk of colectomy (OR 1.90), mainly in patients with ulcerative colitis.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Rare Tragic Reaction to Infliximab

Posted on March 8, 2017 by gutsandgrowth

A recent post on the pediatric GI Listserv pointed out a troubling case report: “Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease,” FM. Baumer et al; Pediatric Neurology 2016; 57: 91-94.

“A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded…Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage…Within four days he met criteria for brain death.”

The authors note that “the close temporal association between our patient’s presentation and the infliximab infusion raises concern for a drug-related cause for his cerebral injury.” While this case report is terribly sad, severe and fatal reactions can unfortunately be encountered with a wide range of medications, including commonly used antibiotics.

My take: Thus, while the vast majority of pediatric patients with inflammatory bowel disease will benefit from infliximab therapy, there are rare tragic outcomes.

Gastrojejunostomy Complications Frequent

Posted on March 7, 2017 by gutsandgrowth

Gastrojejnostomy (GJ) placement allows enteral feeds to bypass the stomach. When a gastrostomy is already in place, GJ placement may allow patients to avoid surgery (eg. fundoplication). Most practitioners would consider the risk of GJ placement to be low, but a recent report (J Moorse et al. JPS 2017; http://dx.doi.org/10.1016/j.jpedsurg.2017.01.026) suggests that it is higher than expected. The abstract and link are below.

Link: Gastrojejunostomy tube complications — A single center experience and systematic review

Abstract

Purpose

Gastrojejunostomy tubes (GJTs) enable enteral nutrition in infants/children with feeding intolerance. However, complications may be increased in small infants. We evaluated our single-institution GJT complication rate and systematically reviewed existing literature.

Methods

With REB approval, a retrospective single-institution analysis of GJT placements between 2009 and 2015 was performed. For the systematic review, MOOSE guidelines were followed.

Results

At our institution, 48 children underwent 154/159 successful insertions primarily for gastroesophageal reflux (n = 27; 55%) and aspiration (n = 11; 23%). Median age at first GJT insertion was 2.2 years (0.2–18). Thirty-five (73%) had an index insertion when ≤10 kg. GJTs caused 2 perforations and 1 death. The systematic review assessed 48 articles representing 2726 procedures. Overall perforation rate was estimated as 2.1% (n = 36 studies, 23/1092, 95% CI: 1.0–3.2). Perforation rates in children <10 kg versus ≥10 kg were estimated as 3.1%/procedure (95% CI: 1.1%–5.0%) and 0.1%/procedure (95% CI: 0%–0.3%), respectively. The relative risk of perforation was 9.4 (95% CI: 2.8–31.3). Overall mortality was estimated as 0.9%/patient (n = 39 studies; 95% CI: 0.2–1.6%). Most perforations (19/23; 83%) occurred ≤30 days of attempted tube placement.

Conclusion

Gastrojejunostomy tubes are associated with significant complications and frequently require revision/replacement. Insertion in patients <10 kg is associated with increased perforation risk. Caution is warranted in this subgroup.

With regard to the methodology

~90% of the procedures were performed by interventional radiology and the interventionist had a median of 6.6 years of experience
Most GJs were 16 French in width and most were either 15 cm or 22 cm in length

My take: This report highlights the significant risks associated with GJ placement, particularly in smaller patients (<10 kg). Despite these risks, GJ placement is often the safest option.

Costa Maya, Mexico

PICC versus Broviac for TPN in Intestinal Failure

Posted on March 6, 2017 by gutsandgrowth

Link: A comparison of Broviac^® and peripherally inserted central catheters in children with intestinal failure

Abstract:

Central venous catheters (CVCs) are a source of morbidity for children with intestinal failure (IF). Complications include infection, breakage, occlusion, and venous thrombosis. Broviacs® have traditionally been preferred, but peripherally inserted central catheters (PICCs) are gaining popularity. This study compares complications between Broviacs® and PICCs in children with IF.

Methods

After IRB approval, children with IF receiving parenteral nutrition (2012–2016) were reviewed. Complications were compared between Broviacs® and PICCs using the generalized estimation equation population-averaged Poisson regression model. P values <0.05 were considered significant.

Results

36 children (0.1–16 years) with IF were reviewed, accounting for 27,331 catheter days, 108 Broviacs® (3F–9F), and 54 PICCs (2-11F). Broviacs® had a significantly higher infection rate (4.2 vs. 2.6/1000 catheter days, p = 0.011), but PICCs were more likely to break (1.56 vs. 0.26/1000 catheter days, p = 0.002). When comparing same size catheters (3F), there were no significant differences in infection, breakage, or occlusion. Twelve children (33%) had central venous thrombosis, all after Broviac® placement. Three children (8%) had basilic vein thrombosis after PICC placement.

Conclusion

Although Broviacs® and PICCs had similar complication rates, there were fewer central venous thromboses associated with PICCs. This should be considered when choosing catheters for children with IF.

My take: Despite some possible advantages of PICC in this study, a prospective randomized study is needed if one is to make a compelling argument regarding better outcomes. Given the retrospective nature of this study, it could be that the sicker patients may have been more likely to receive a Broviac® and this could have skewed the results.

Chronic Diarrhea Recommendations

Posted on March 5, 2017 by gutsandgrowth

Recent guidelines for adults with chronic diarrhea (>4 weeks):

Full text link: LR Schiller, DS Pardi, JH Sellin. Clin Gastroenterol Hepatol 2017; 15: 182-193.

A few key points:

The authors advocate treatment, not testing, for adults who meet Rome criteria for irritable bowel syndrome (IBS) without alarm symptoms.
Dietary history is essential.
“True food allergies are rare causes of chronic diarrhea in adults”

One of my colleagues questioned whether this product could be part of an effective cleanout

Expert Advice on Clostridium difficile and Inflammatory Bowel Disease

Posted on March 4, 2017 by gutsandgrowth

Clinical Gastroenterology and Hepatology Volume 15, Issue 2, February 2017, Pages 166–174.

Link: Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute

Abstract: The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence.

Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection.

Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection.

Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole.

Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis.

Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations.

Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.

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Heartfelt Apologies

Posted on March 3, 2017 by gutsandgrowth

“Resentment is like drinking poison and then hoping it will kill your enemies.”

–Nelson Mandela

A recent NY Times article explains how the right type of apology can be good medicine: The Right Way to Say ‘I’m Sorry’

An excerpt:

I admit to a lifetime of challenges when it comes to apologizing, especially when I thought I was right or misunderstood or that the offended party was being overly sensitive. But I recently discovered that the need for an apology is less about me than the person who, for whatever reason, is offended by something I said or did or failed to do, regardless of my intentions…

Nor should a request for forgiveness be part of an apology. The offended party may accept a sincere apology but still be unready to forgive the transgression. Forgiveness, should it come, may depend on a demonstration going forward that the offense will not be repeated…

Offering an apology is an admission of guilt that admittedly leaves people vulnerable. There’s no guarantee as to how it will be received. It is the prerogative of the injured party to reject an apology, even when sincerely offered…

“Apology has the power to repair harm, mend relationships, soothe wounds and heal broken hearts. An apology actually affects the bodily functions of the person receiving it — blood pressure decreases, heart rate slows and breathing becomes steadier.”

Related blog posts:

Safe Sleep (AAP 2017)

Posted on March 2, 2017 by gutsandgrowth

Behind the scenes, there is a core group of pediatricians and staff at the American Academy of Pediatrics working to improve the health of children and the ability of pediatricians to be effective.

A couple items from this year’s Georgia board of directors meeting:

Increasing Safe Sleep practices
Working with legislators to improve access to health care
Establishing strategic goals for the next few years

The emphasis on Safe Sleep follows recent AAP guidelines –see previous posts:

Right now, in Georgia, it is estimated that there are 3 infant deaths per week associated with sleep practices. In Tennessee, following widespread adoption and promotion of safe sleep practices, this resulted in a 50% reduction in these types of infant deaths within two years. In Georgia, the department of public health has been working on distributing inexpensive portable bassinets to Medicaid population, along with educational material. There is a lot more to do. In hospital nurseries infants are often NOT placed on their backs to go to sleep until shortly before discharge.

Useful website: Charlieskids.org This website has a book called “Sleep Baby Safe and Snug” which incorporates updated recommendations on safe sleep practices. Interestingly, the fact that the book has a picture of a pacifier has slowed distribution of this book (even when free) because this runs counter to another program (“Baby Friendly” hospital designation) to promote breastfeeding.

Here are some of the slides from Dr. Freed’s presentation on safe sleep practices:

Word of Caution with New Hepatitis C Medications

Posted on March 1, 2017 by gutsandgrowth

From NY Times: Are New Drugs for Hepatitis C Safe? A Report Raises Concerns

An excerpt:

Drugs approved in recent years that can cure hepatitis C may have severe side effects, including liver failure, a new report suggests. The number of adverse events appears relatively small, and the findings are not conclusive. But experts said the report was a warning that should not be ignored…

The report will be published online on Wednesday [1/25/17] by the Institute for Safe Medication Practices, a nonprofit in Horsham, Pa., that studies drug safety. Its findings are based on the group’s analysis of the Food and Drug Administration’s database of reports from doctors around the world of adverse events that might be related to medications.

In October, the F.D.A. identified the first major safety problem caused by the nine antiviral drugs. In 24 patients, the drugs wiped out hepatitis C — but also reactivated hepatitis B infections that had been dormant. Two of those patients died, and one needed a liver transplant. The agency said there were probably additional cases that had not been reported.

As a result, the agency required that a boxed warning, its most prominent advisory, be added to the labeling of the newer antivirals, telling doctors to screen and monitor for hepatitis B in all patients taking the drugs for hepatitis C. Infection with both viruses is not common, and how the reactivation occurs is not known. The problem was not detected during premarket testing of the drugs because patients who currently had hepatitis B or who had a history of it were not allowed into the studies…

The other cases of liver failure are a separate problem. He said it was important for doctors prescribing the newer drugs to test patients’ liver function thoroughly first, because liver disease can be deceptive

My take: Overall, these newer Hepatitis C medications represent a tremendous achievement. However, as with most medications, rare serious problems can occur and in some cases may be preventable.

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February Briefs

Posted on February 28, 2017 by gutsandgrowth

JM Powers et al. J Pediatr 2017; 180: 212-6. This retrospective study details a protocol for using intravenous ferric carboxymaltose (FCM) (Injectafer) in children. This product has become available for adults in U.S. since June 2013; it had been available in Europe since 2009. In this retrospective study, 72 pediatric patients received FCM for iron deficiency anemia (off-label); there was a good safety profile and a good response with hemoglobin increasing from 9.1 to 12.3 (4-12 weeks post infusion). FCM is a relatively costly IV iron formulation, but can be given over 15 minutes.

L Peyrin-Biroulet et al. Clin Gastroenterol Hepatol 2017; 15: 25-36. This systemic review with more than 2800 patients showed that TNF antagonists were effective for extraintestinal manifestations of inflammatory bowel disease, including cutaneous disorders (eg.. pyoderma gangrenosum, erythema nodosum), hematologic problems (eg anemia), ocular disorders, and rheumatologic symptoms( eg. arthralgias/arthritis).

AE Mikolajczyk et al. Clin Gastroenterol Hepatol 2017; 15: 17-24. Useful review of the GI/Liver manifestations of autosomal-dominant polycystic kidney disease. “There is not a role for therapy [for the liver] in asymptomatic patients.” Other problems reviewed included pancreatic cysts, hernias, and diverticular disease. Related posts:

T Rajalahti et al. JPGN 2017; 64: e1-6. Among 455 patients <18 with Celiac disease, anemia was noted in 18%. This resolved in 92% after one year of a gluten-free diet. Anemia is associated with more severe histological and serological presentation. Related posts:

FL Cameron et al. JPGN 2017; 64: 47-55. This retrospective review of 93 children treated with infliximab and 28 children with adalimumab provides data on growth after anti-TNF therapy. This study shows that anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty.

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Chattahoochee River