Tag Archives: Clostridium difficile

No Habla Appendicitis

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Before today’s blog, I wanted to state that our physicians now can treat Clostridium difficile with fecal microbiota transplant (would have been more relevant to yesterday’s blog: “Gut Microbiome”) :

GI Care for Kids is one of the few places in the region to offer this capability for children (thanks to Jeff Lewis for working to navigate the logistics/regulatory burdens).

Today’s blog: Though physicians make efforts to combat language barriers with translators, the personal connection between physicians and patients is undoubtedly weakened in those with limited English proficiency LEP).  Recently, one of my emergency room colleagues explained that he had ordered a CT scan on a young man in part due to his hispanic ethnicity and concern that this would lead him to overlook a diagnosis of appendicitis.  According to a recent study, my emergency room colleague was right –hispanic ethnicity and language barriers increased the risk for appendiceal perforation (J Pediatr 2014; 164: 1286-91).

The researchers performed a secondary analysis of a prospective, cross-sectional, multi center study of children aged 3-18 years who presented with abdominal pain/possible appendicitis (2009-2010) at 10 tertiary care pediatric emergency departments in the U.S.

Results:

  • Of the 2590 patients enrolled, 1001 (38%) had appendicitis.
  • Hispanics with LEP had an odds ratio of 1.44 of having appendiceal perforation.  In addition, these patients were less likely to undergo advanced imaging (OR 0.64)

Bottomline: Patients/families who speak English are more likely to communicate the severity of their medical problem.  Those with limited English proficiency are at increased risk for complications and this extends beyond perforation with appendicitis.

Related blog post: How much radiation from your CT scanner? | gutsandgrowth

Diarrhea -a Universal Experience

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To be clear, by the term “universal” I am in no way referring to a theme park.  A recent review in the NEJM (N Engl J Med 2014; 370:1532-1540) discusses acute diarrhea, http://nej.md/1l2bAIn .

“In the United States, there are approximately 179 million cases of acute diarrhea per year. This update on the diagnosis and management of acute diarrhea in immunocompetent adults gives particular attention to the roles of noroviruses and Clostridium difficile.”

This post is mainly to provide an up-to-date useful reference.

OpenBiome -Nation’s 1st Human Stool Bank

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From NY Times: http://t.co/LIIk4JNMfl

An excerpt:
Around noon on a recent Friday, Donor Five, a healthy 31-year-old, walked across M.I.T.’s frigid, wind-swept campus to a third-floor restroom to make a contribution to public health.

Less than two hours later, a technician blended the donor’s stool into preparations that looked like chocolate milk. The material was separated and stored in freezers at an M.I.T. microbiology lab, awaiting shipment to hospitals around the country. Each container was carefully labeled: Fecal Microbiota Preparation.

Nearly a year ago, Mark Smith, a 27-year-old doctoral candidate, and three colleagues launched OpenBiome, the nation’s first human stool bank. Its mission: to provide doctors with safe, inexpensive fecal material from screened donors to treat patients with Clostridium difficile, a gastrointestinal infection that kills at least 14,000 Americans a year.

“People are dying, and it’s crazy because we know what the solution is,” Mr. Smith said. “People are doing fecal transplants in their basements and may not be doing any of the right screening or sterile preparation. We need an intermediate solution until there are commercial products on the market.”…

The bacteria are increasingly resistant to conventional treatments. But researchers have discovered an alternative: A donor’s stool can be transplanted in the intestine or colon of a sick patient via an enema, colonoscopy or nasogastric tube. The healthy bacteria fight off C. diff and re-establish a normal community in the gut.

A study published last year in The New England Journal of Medicine found that fecal transplants were nearly twice as effective as antibiotics in treating patients with recurring C. difficile.

But where to get healthy donor stool? For doctors, it’s a tedious, time-consuming process, and some patients turn awkwardly to relatives or friends. Since September, OpenBiome has delivered more than 135 frozen, ready-to-use preparations to 13 hospitals. The nonprofit project fields dozens of requests from doctors, hospitals and patients every week. (The preparations are not sent directly to patients.) 

Carol Capps, 75, a retired nurse in Clemmons, N.C., had been in and out of hospitals for months with a C. diff infection that was not going away despite multiple courses of antibiotics. After a recurrence, her doctor suggested OpenBiome, and she received a fecal transplant. By that afternoon, Ms. Capps said, she felt like a new person and has been healthy since…

Because of the legal ambiguity, some researchers are not preparing fecal microbiota for sale (usually at cost) …

At the same time, Mr. Smith and Eric J. Alm, an M.I.T. microbiologist and adviser to OpenBiome, said the F.D.A.’s classification of fecal transplants as drugs hinders research into their possible uses to treat inflammatory bowel diseases and obesity.

Related blog posts:

Clostridium difficile: Colonization vs. Symptomatic Infection

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A recent study provides another way to distinguish individuals colonized with Clostridium difficile from those with symptomatic infection (J Pediatr 2013; 163: 1697-704).

Methods: This study comprised two designs. “The first is a case-control study comparing children with a positive C difficile test (cases), children with diarrhea but no C difficile (symptomatic controls), and asymptomatic controls, some of whom were colonized with C difficile.  The second is a prospective-cohort study where we followed our cases for the duration of their illness.”

Results: Fecal cytokines (CXCL-5 and IL-8 mRNA) were elevated in samples from symptomatic children, whether cases or controls.

Bottomline: Inflammatory cytokines can help distinguish C difficile colonization from disease.  Of course, this may have limited utility in patients with underlying inflammatory bowel disease.

Recent posts regarding C difficile:

Consensus Guidelines on FMT

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Recent links from AGA for FMT (fecal microbiota transplantation) for Clostridium difficile –excellent resource:

Also, summary of recent abstracts from ACG regarding FMT for C difficile, IBS, and IBD: http://t.co/7LFnDYq5V5

Some previous blog posts on this topic:

IBD Update 2014 (part 1)

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A number of recent articles that may be helpful for clinicians who help patients with inflammatory bowel disease.

1. Inflamm Bowel Dis 2013; 19: 2778-86.  “The Incidence and Predictors of Lupus-Like Reaction in Patients with IBD treated with Anti-TNF therapies.”  Key result: 20 of 289 (6.9%) developed lupus-like reactions (LLRs).  Female gender and IBD-unclassified were more prevalent in this group.  Clinical features included arthropathy (100%); fatigue and dermatitis were common.  All tested positive for ANA, 16 of 20 also had anti-dsDNA.  LLRs resolved with cessation of culprit agent and steroids.  Only one patient had recurrence who had switched to an alternative anti-TNF.

2. Inflamm Bowel Dis 2013; 19: 2753-62. This phase 3, randomized open-label multicenter study enrolled 60 children and provided data regarding infliximab pharmacokinetics in patients with moderate-to-severe ulcerative colitis.  The findings indicate that infliximab exposure-response is similar to adult patients.  At week 8, those with higher serum infliximab levels (≥41.1 mcg/mL) had higher efficacy (response 92.9%, remission 64.3%) compared with those with a lower levels <18.1 mcg/mL (response 53.9%, remission 30.8%).  Trough levels (at week 30) for q8 week-dosing was 1.9 mcg/mL compared with 0.8 mcg/mL for q12 week-dosing.

3. Inflamm Bowel Dis 2013; 19: 2744-52. A lot of pediatric IBD patients are colonized with Clostridium difficile.  In this prospective study of 85 outpatient IBD pediatric patients and 78 age-matched controls, asymptomatic C difficile carriage was noted in 17% of IBD patients compared with 3% of controls.  Use of proton pump inhibitors was associated with an increased carriage rate.

4. Inflamm Bowel Dis 2013; 19: 2937-48.  Excellent review article regarding fertility and pregnancy for women with IBD.  This review includes a discussion about the timing of pregnancy with regard to remission, effects of surgery and medications, acceptable radiology testing in pregnant patients, and issues regarding delivery.

Something New with FMT

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

A brief review on Fecal Microbiota Transplantation (FMT) (Gastroenterol 2013; 145: 946-53) made a few points that I was not familiar with and reiterated many other important aspects.

  • With regard to preparation of FMT, early data suggests that using water rather than saline may result in better resolution of Clostridium difficile infection (CDI)
  • Adequate volumes of FMT material are needed, with rates as high as 97% CDI resolution with infusions >500 mL
  • While preliminary data suggested higher CDI resolution with colonoscopy infusion, a recent randomized controlled trial indicated that duodenal infusion was as effective as colonoscopic administration
  • Short-term data indicate very low adverse effect rates
  • While the only accepted role for FMT outside of clinical trials is for CDI, the review examined the potential benefit for inflammatory bowel disease (IBD), irritable bowel syndrome, chronic fatigue syndrome, and metabolic/cardiovascular disorders.
  • With IBD, there are currently 6 registered trials testing FMT for patients with IBD.  Preliminary data have been more evident in small studies with ulcerative colitis.
  • The rationale for FMT in IBD is that IBD patients have reduced diversity and altered microbial flora.  “However, it is not clear whether these differences are a cause or a consequence of the development of IBD.”

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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.

Predicting Severe Clostridium Difficile

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According to a recent publication (Clin Gastroenterol Hepatol 2013; 11: 1466-71), the most important risk factors for severe Clostridium difficile infection (CDI) are the following:

  • Peripheral leukocytosis (WBC >15,000)
  • Elevated serum creatinine >1.5 times baseline
  • Narcotic use
  • Acid-blocking medications
  • Older age

This study reviewed the records of inpatient cases at the Mayo clinic between 2007-2010. In total, 487 of 1446 patients had severe CDI, defined as ICU admssion (26.7%), colectomy (2.7%) or death (8.9%) within 30 days of diagnosis.

Patients with these risk factors may need to be treated more aggressively.

Also, noted: Am J Gastroenterol 2013; 108: 1794-1801. (Thanks to Ben Gold). Using electronic medical records, the authors identified 894  adult inpatients with a first-time CDI (2009-2012).  Receipt of PPIs concurrent with CDI treatment was not associated with CDI recurrence.

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Trends in Clostridium difficile Infection

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Many recent reports have provided conflicting data with regard to Clostridium difficile infection (CDI) epidemiology.  Some of the newest data needs to be interpreted with caution due to the adoption of PCR technology.  Previously, CDI was difficult to culture and identify.  The problem now is proving causation when C diff is identified.

J Pediatr 2013; 163: 699-705.  This study, using an administrative database, analyzed 33,095 first pediatric hospitalizations for malignancy from 43 pediatric hospitals between 1999 and 2011.  A total of 1736 admissions with CDI were identified; 380 were considered hospital-acquired.  The authors noted an apparent decrease in CDI incidence between 2006-2010.  Exposure to chemotherapy, proton pump inhibitors and certain antibiotics were independent risk factors for hospital-acquired CDI.

JPGN 2013; 57: 487-88. New-onset patients with IBD cases were retrospectively reviewed from 2010-2012.  10 cases (8.1%) of 124 were positive for CDI within the first two months of diagnosis.  Only 42% of the total 290 new IBD cases had documented testing for CDI.  The prevalence of CDI without obvious preceding antibiotic exposure was 2.4%.

JPGN 2013; 57: 293-97. Between 2006-2012, stool samples were prospectively obtained from children with IBD (UC, n=76, Crohn, n=69) and controls with other noninflammatory GI conditions (n=51).

Key points:

  • The prevalence of positive PCR results were 11.6% in patients with Crohn disease, 18.4% in patients with UC, and 11.8% in controls.  No significant difference.
  • CDI as identified by PCR may be an incidental finding.
  • Only test diarrheal stools.  Testing for cure is not recommended.
  • Asymptomatic colonization with C diff is frequent in patients with and without IBD

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Precise Identification of C difficile Transmission

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A recent study uncovers some useful information about C difficile by using whole-genome sequencing on 1250 separate C difficile cases (NEJM 2013; 369: 1195-205).

Between 2007-2011, the authors used genetic sequencing to determine the similarity of C difficile cases.  They were able to successfully sequence 1223 (98%) of the identified cases.  Of these isolates, 71% were from inpatients, 25% from outpatients, and 4% from patients at other hospitals. To determine similarity, they compared single-nucleotide variants (SNVs) between the isolates.  If isolates were related, it was anticipated that there would be 0 to 2 SNVs between transmitted isolates (95% prediction if less than 124 days apart).

This study was from the Oxford University Hospitals which provide all acute care and 90% of hospital services in Oxfordshire, United Kingdom (~600,000 population).

Results:

  • Only 35% of cases were genetically related to at least one previous case.
  • Of the 333 (35%) with ≤2 SNVs (consistent with transmission), and 126 (38%) had close hospital contact with another patient, 120 (36%) had no hospital or community contact with another patient.
  • 13% of cases were genetically related (≤2 SNVs) but without any evidence of plausible contact.
  • 45% of C difficile cases were genetically distinct (>10 SNVs from any previous case) from all previous cases.  This indicates that the source of the infection was not from another symptomatic case; most likely these cases were acquired from asymptomatic persons or an environmental reservoir.
  • There were reductions in the rate of C difficile infection during the 4-year study.  The authors relate this to changes in antibiotic prescribing behavior, specifically the restriction of fluoroquinolones and cephalosporins.

Aspects of the setting may limit some of the conclusions.  For example, the study was conducted in a nonoutbreak setting and the hospitals had established measures to limit transmission from symptomatic patients.  These included the following:

  • isolation of patients with suspected C difficile
  • daily hypochlorite disinfection
  • monitoring of compliance

These measures will decrease nosocomial transmission.  However, at the same time, some of the genetically distinct cases could still have been acquired in the hospital setting from asymptomatic hospital sources. While the authors concede a number of limitations, this study is quite helpful in understanding the role of hospitals in controlling C difficile infection.

Take-home message: the fact that only 35% of cases were related to other symptomatic cases indicates that hospital control measures by themselves will not be effective.  The most important aspect in reducing C difficile infection will be optimizing antibiotic usage.

Related news media: On the same day of that I read this study, there was an article in the Atlanta Journal Constitution (“PLEASE wash your hands … Please.”) which describes a first-hand account of C difficile infection which contributed to a slow recovery from intestinal surgery.  The article contained some questionable assertions including that C difficile was “impossible to eradicate” and that her immune system trapped C difficile in peritoneal abscesses which required drainage (these abscesses were more likely related to the initial operation). However, the article is a stark reminder that many hospital staff do not follow basic hand washing recommendations.  The article is really bad PR for the named hospital.

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