Conferences and Medical Updates

General GI

 

 

 

 

Complicated intra abdominal infection

Saturday, December 19, 2015

12:25

 

 

start treatment in a critically ill patient with piperacillin/tazobactam, meropenem, or imipenem

Dr Solomkin: Would you discuss the recent STOP IT trial, which is the first solid randomized trial of stopping antibiotic therapy early?

Dr Mazuski: In this National Institutes of Health – sponsored trial, patients were randomized either to limited antimicrobial therapy (4 days) after appropriate source control or longer antimicrobial therapy (8 days) based on resolution of signs and symptoms and resumption of gastrointestinal function, and they were continued on therapy for 2 days after that.

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The failure rate in both groups was the same, approximately 20%. This study provides good data showing that we do not need to give prolonged antimicrobial therapy for most patients with cIAIs, with the caveat that they have early and appropriate source contro

Dr Solomkin: Would you discuss the recent STOP IT trial, which is the first solid randomized trial of stopping antibiotic therapy early?

Dr Mazuski: In this National Institutes of Health – sponsored trial, patients were randomized either to limited antimicrobial therapy (4 days) after appropriate source control or longer antimicrobial therapy (8 days) based on resolution of signs and symptoms and resumption of gastrointestinal function, and they were continued on therapy for 2 days after that.

(Enlarge Slide)
The failure rate in both groups was the same, approximately 20%. This study provides good data showing that we do not need to give prolonged antimicrobial therapy for most patients with cIAIs, with the caveat that they have early and appropriate source control.

Dr Solomkin: Is it definitive? In other words, has it changed your practice?

Dr Mazuski: We were already practicing that way. Yes, I would say it is definitive. The study provides very good data showing that prolonged antimicrobial therapy provides no benefit in adult patients who have adequate source control.

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use: cefoxitin, ertapenem, moxifloxacin, or tigecycline. Ticarcillin and clavulanate are no longer available. We would typically use a first- or second-generation cephalosporin, or even ceftriaxone with metronidazole for a lot of the mild-to-moderate infections, such as a perforated appendicitis.

We recommended using carbapenem (piperacillin-tazobactam, and then combination regimens with ceftazidime or cefepime) for very ill patients with cIAI and high severity scores. Typically these are people who go to the ICU. In this group we recommend ceftazidime with metronidazole or clindamycin. Ceftazidime does not have good gram-positive activity and given the importance of streptococci, that is an issue. Cefepime is much better against gram-positive organisms. Ciprofloxacin and levofloxacin are crossed out, because in most hospitals in the United States, the susceptibility of these organisms, particularly E coli, is so low that it is not a concern.

 

RECLAIM trial were recently presented at the 25th European Congress of the European Society of Clinical Microbiology and Infectious Diseases (ECCMID 2015), April 25-28, 2015, in Copenhagen, Denmark. In this trial, patients were randomized to receive ceftazidime/avibactam or meropenem for the treatment of cIAIs. Avibactam covers a large number of the ESBLs. It does not cover the metallo-beta-lactamases, but it does has activity against most of the carbapenemase-producing Klebsiella pneumoniae. The real role of this agent is probably going to be in therapy directed against carbapenemases. It has the potential for carbapenem-sparing therapy because it covers most of the ESBLs, but in the interest of antimicrobial co
nservation I would use it to target the carbapenemase producers (Carbapenem-resistant Enterobacteriaceae), even though there are not a lot of data about its efficacy in that group of patients.
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Linzess

Saturday, December 12, 2015

14:37

 

Use bottled water or  teaspoon of apple sauce

Open capsule.  Drug is coating beads.  So if beads remain it’s ok !

 

 

Relamorelin: Gastroparesis

Saturday, December 12, 2015

8:18 AM

 

Phase 2.  Ghrelin agonist drug

 

 

Viberzi – IBS

Saturday, December 12, 2015

9:18 AM

 

VIberzi is contraindicated with SOD spasm, alcoholism or drink more than 3 drinks a day or pancreatitis or cirrhosis Child’s C or severe constipation or mechanical obstruction

It is the first and only mixed opioid receptor modulator.  It binds to kappa, mu and delta.  It stimulates kappa and mu and blocks delta which is antagonistic.

Overall, it then modifies GI motility and slows down contraction of smooth muscle.It also decreases the activity of afferent neuron of the gut.

This causes decreased visceral hypersensitivity.

It does not get absorbed and only binds to mucosal receptors in the gut.  Give with food?

Bristol stool scale : Pain scale was 6.1 and stool consistency was 6.2 (max is 7 diarrhea)

The trial was 52 weeks and more than 1200 patients and the primary end point was improvement in pain, diarrhea at 12 weeks.

Composite responder ( improved pain and diarrhea )

Benefit was 30 and 33% in the 12 and 24 months compared to 16 and 20% in placebo

SOD occurs in patients with s/p chole. SOD occurs in 0.2% of s/p lap chole.

Pancreatitis occurred in 6 out of 3000 patients.

Side effect profile otherwise similar to placebo (except constipation 1-2% had to stop it). 1 % at 75 mg and 2% at 100 mg

It can cause euphoria (0.2%)and feeling drunk (0.1%).  Since it can activate mu receptor it is labeled as Schedule IV.

75 mg dose for patients with child’s A or B cirrhosis, s/p chole patients, those unable to tolerate 100 mg bid dose or they are on gemfibrozil or cyclosporine. (Similar to lomotil)

OATP1B1 receptor ((drugs are Rifampicin, Rifamycin SV, Clarithromycin, erythromycin, roxithromycin, telithromycin indinavir, saquinavir, ritonavir, Cyclosporine, gemfibrozil) (organic anion transporting polypeptide)

It increases absorption of Viberzi.

40% increase in Crestor level

Developed by same scientist from J and J that developed loperamide.

10%  delta (compared to placebo) of patients who did not respond to loperamide responded to Viberzi.

Agonist for mu, antagonist to delta and unknown to kappa.  Passes BBB.  Eat it with meal to decrease absorption

Avoid in lap chole : because they may have SOD.

Child’s A and B, use reduced dose and Child’s C contraindicated.

Most of the events of constipation occurred in first 2 weeks (50%)

P value for primary endpoint.  Confidence interval for secondary endpoint.

SOD issues occurred in 0.2% at 75 mg dose and 0.8% in 100 mg dose.  All resolved after stopping medication.

1 pt with SOD got abnormal LFT, one got pancreatitis. The other 5 pancreatitis had sludge or had alcohol.

 

 

Discontinuation rate of Viberzi is 8%

 

 

Diverticulitis

Friday, December 11, 2015

06:38

 

The American Gastroenterological Association (AGA) has announced new guidelines for the management of acute diverticulitis, the first practice guidelines for the disease since 1999, and they appear in the December issue of Gastroenterology.

“The management of acute diverticulitis has undergone meaningful change over the past decade, including a more judicious use of antibiotics and surgery, as well as preliminary and ongoing investigations into medical therapies to decrease symptoms and reduce recurrences,” the AGA noted. “The majority of the evidence currently, however, is of poor quality, and most of our recommendations are therefore conditional.”

Courtesy Wikimedia Commons/Hellerhoff/Creative Commons

The guidelines strongly recommend that patients not use mesalamine after acute uncomplicated diverticulitis, citing “moderate” evidence to this effect and saying that currently available evidence regarding the anti-inflammatory agent often used for ulcerative colitis “does not suggest efficacy in reducing recurrence risk, pain resolution, or need for surgery in this specific population.” All other recommendations, however, are conditional and offer either “low-” or “very low-quality” evidence to support them.

These additional recommendations include the following:

  • Antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis.
  • Colonoscopy should be performed after resolution of acute uncomplicated diverticulitis in appropriate candidates to exclude the misdiagnosis of a colonic neoplasm, if a high-quality exam of the colon has not been recently performed.
  • Patients with a history of diverticulitis should consume a fiber-rich diet or consider fiber supplementation.
  • Patients with diverticular disease should consider vigorous physical activity.

The AGA recommendations also advise against certain practices, all with conditional application and either “low-” or “very low-quality” supportive evidence. These are as follows:

  • Elective colonic resection should not be done in patients with an initial episode of acute, uncomplicated diverticulitis; the decision to perform elective prophylactic colonic resection in this setting should be individualized.
  • Patients with a history of diverticulitis should not be advised to avoid consumption of seeds, nuts, and popcorn.
  • Patients with a history of diverticulitis should not be advised to avoid the use of aspirin.
  • Patients with a history of diverticulitis should not be advised to avoid the use of nonselective nonsteroidal anti-inflammatory drugs.
  • Do not advise the use of mesalamine after acute uncomplicated diverticulitis.
  • Do not advise the use of rifaximin after acute uncomplicated diverticulitis.
  • Do not advise the use of probiotics after acute uncomplicated diverticulitis.

“Acute diverticulitis is the third most common inpatient gastrointestinal diagnosis in the United States, costing over $2 billion annually, and is a common outpatient and emergency department diagnosis as well,” stated the AGA recommendations, which were developed by the AGA’s Clinical Guidelines Committee and approved by the AGA Institute Governing Board.

The statement notes that the condition “occurs in approximately 4% of patients with diverticulosis, roughly 15% of whom will have complicated disease, defined as an abscess, perforation, fistula or colon obstruction, and 15%-30% will experience recurrence.”

The new guidelines do not address other forms of diverticular disease, including symptomatic uncomplicated diverticular disease, diverticular bleeding, and segmental colitis associated with diverticulosis. It does not address the prevention of incident diverticulitis or the management of complicated disease.

Areas of further research, advises the AGA, should be in identifying patients who will benefit the most from antibiotics, identifying those in whom antibiotics can be withheld safely, identifying risk factors for recurrent diverticulitis, examining the risks of colonoscopy following acute diverticulitis, and taking a closer looks at anti-inflammatory drugs, antibiotics, probiotics, and dietary interventions as viable therapies.

 

 

 

PPI

Friday, November 27, 2015

06:58

 

esophagus patients. There are case reports of proton pump inhibitor induced gastric neuroendocrine tumours and adenocarcinomas as consequences of these effects. In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric neuroendocrine tumour development with chronic proton pump inhibitor use in these patients. Eradication status of Helicobacter pylori prior to commencing long term proton pump inhibitor therapy should be established to reduce the risk of severe atrophic gastritis and development of gastric dysplasia.

Nausea medicine

Thursday, September 3, 2015

21:45

 

The U.S. Food and Drug Administration approved Tesaro Inc’s oral drug rolapitant (Varubi) for treatment for chemotherapy-induced nausea and vomiting in adults, the company said on Wednesday.

 

Naloxegol – 25 mg

GFR > 60, cyp34a, can cross bbb

Contraindicated with biaxin, ketoconazole

 

Lynch syndrome

Wednesday, September 30, 2015

12:05 PM

MLH1, MSH2, MSH6, PMS2 testing – 95% sensitive

If MLH1 def, BRAF and MLH1 promoter sequence hypermethylation studies.  If either is positive no further studies needed

If PMS2, MSH2, MSH6 def pt or MLH1 def patients with neg BRAF and hypermethylation, germline genetic testing is done.

 

Gastroparesis

Wednesday, November 4, 2015

 

Sarcina ventriculi gastroparesis