For the Next Upper GI Bleed, Azithromycin?

Earlier this week, I was tasked with helping a teenager with an upper GI bleed.  I was surprised to learn that our hospital did not have IV erythromycin available due to a shortage.  A potential alternative is azithromycin.

The following is a 2017 ACG abstract (D Issa et al): A Comparison of Azithromycin to Erythromycin Infusions in Improving Visualization of Endoscopy for Upper Gastrointestinal Bleeding

Introduction: Several studies show the use of intravenous erythromycin prior to upper endoscopy for upper gastrointestinal bleeding (GIB) improves visualization and decreases the need for second look endoscopy. Erythromycin requires reconstitution delaying administration in emergency procedures. Azithromycin is more readily available as it is part of pneumonia treatment protocols and does not require reconstitution. Physiologic studies show azithromycin produces motility effects similar to that of erythromycin.

Aim: To assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin.

Methods: We performed a retrospective analysis of patients admitted with acute upper GIB who underwent emergent endoscopy and were ordered either erythromycin or azithromycin before procedure. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8 with a maximum of 2 points assigned to each of the fundus, body, antrum and bulb. Secondary outcomes included time elapsed between administering the infusion and starting the procedure, length of hospital stay, blood transfusions, and procedure-related complications.

Results: The study included 31 patients in the erythromycin group and 18 patients in the azithromycin group. Mean age was 57 years and 68% were male. The overall median visualization score was significantly higher in the azithromycin group compared to that of the erythromycin group {7.0 (1.5) vs. 6.0 (3.0), respectively; P=0.02}. Time between administration of azithromycin and starting the procedure was longer than that of erythromycin but did not meet statistical significance (67 vs 48.5 minutes, respectively; P = 0.92). Length of hospital stay was comparable between the two groups after adjusting for the admission primary diagnosis (6.0 days for azithromycin vs. 7.0 days for erythromycin; P=0.48). Four patients were ordered erythromycin but this was not administered on time whereas all patient who were ordered azithromycin started the infusion prior to the procedure. Procedure immediate complications, need for second look endoscopy and number of transfused blood units did not differ between the groups.

Discussion: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin, the current standard of care. Randomized trials are needed to validate these findings.

Here is a link to a summary from Gastro and Endoscopy News: Azithromycin Appears Worthy Stand-In For Erythromycin in Upper GI Bleeding

There have been prior publications showing that azithromycin, like erythromycin, has prokinetic properties: Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycinBr J Pharmacol. 2013 Apr;168(8):1859-67.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Macrolide Antibiotics and Pyloric Stenosis

It is well-recognized that infants who receive macrolide antibiotics are at increased risk of pyloric stenosis. A recent study (BMJ 2014;348:g1908) indicates that maternal macrolide intake can also increase the risk of pyloric stenosis in their infants.

Link to article from NASPGHAN twitter feed: http://t.co/CnkbdZoRVf

Conclusions Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk. Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS. A possible association was also found with use during late pregnancy.

What to do with delayed gastric emptying/gastroparesis

More information for pediatric patients with the perplexing problem of poor gastric emptying is available in three articles:

JPGN 2012; 55: 166-72, 185-90, & 194-199.

The first study by Waseem et al describes the “Spectrum of Gastroparesis:”

  • Retrospective chart review included 239 eligible children with mean age of 7.9 years.  Nearly equal numbers of males and females. .
  • Time to empty half of solid or liquid considered abnormal if more than 45-90 minutes for solid and more than 60 minutes for liquid (labelled pediasure)
  • Etiology: idiopathic 70%, drug-induced 18%, postsurgical 12%
  • Treatment in 74% diet and erythromycin (74%)
  • Over 24 months, 60% had significant improvement regardless of treatment

The second study by Rodriguez et al is titled “Clinical Presentation, Response to Therapy, and Outcome of Gastroparesis in Children.”

  • Restrospective study with 230 children, mean age 9 years.  In adolescents, female gender was more common (77%) whereas in infants (n=36), male gender was more common (61%).  Most common causes were postviral in 42%, mitochondrial in 18%, and diabetes in 5%.
  • Delayed gastric emptying was defined as having solids or liquids emptying <40% of the meal at one hour.
  • Resolution occurred in 22% at 6 months, 53% at 18 months, and 61% at 36 months.  Median time to resolution was 14 months; though among resolvers, 84% did so by 12 months.
  • Presence of longer duration of symptoms and mitochondrial disorder was associated with lower rates of resolution.
  • Younger age and response to promotility agents increased likelihood of resolution
  •  Treatment with proton pump inhibitors (PPIs) were used in 79% as first-line agents; only 3% reported resolution of symptoms with PPIs.
  • Prokinetics: Domperidone (0.1-0.2mg/kg/dose qid to max of 10mg) in 33 patients. Tegaserod in 20 patients.  Metoclopropramide in 142 patients. Erythromycin (EES) in 40 patients (3-10 mg/kg/dose qid).  Of these agents, metoclopropramide was inferior with an 80% failure rate.  In contrast, EES was associated with symptom resolution in 5% and symptom improvement in 46%.  Domperidone was associated with symptom resolution in 26% and symptom improvement in 48%.

The third study by Bhardwaj et al highlights “Impaired Gastric Emptying and Small Bowel Transit in Children with Mitochondrial Disorders.”

  • Prospective study enrolled 26 subjects from mitochondrial clinic.  58 patients were screened but the majority were not eligible; the most common reasons included the following: 14 were receiving enteral feedings, 1 was receiving parenteral nutrition, 6 had no GI symptoms.
  • Delayed gastric emptying was considered if >50% at 90 minutes of a solid meal was present, at 60 minutes for semisolid, and at 40 minutes for liquid meal. For small bowel transit, delayed transit was considered if radiotracer had not reached cecum within 4 hours.  Severely prolonged transit was diagnosed if transit time exceeded 6 hours.
  • In this cohort, 18 (69%) had delayed gastric emptying and 12 (46%) had prolonged small bowel transit.  Common symptoms included abdominal pain and vomiting.
  • In the small numbers of patients who received prokinetics,there was a poor response.  One of three patients with bethanecol and two of five patients with metoclopropramide had normalized GE time; one patient treated with azithromycin continued with abnormal GE time

Additional references:

  • -Gastroenterol 2011; 140: 101.  Clinical features -mostly females, often incr BMI.  Defined as severe gastroparesis if >35% at 4hrs, moderate if 20-35%, and mild if <20%.
  • -Clincal Gastro & Hep 2011; 9: 5.  Review of diabetic gastroparesis & mgt.
  • -Clin Gastro & Hep 2009; 7: 823. Radiation from gastric emptying is ~10mrad, CXR is 12mrad, yearly background is 300mrad.
    Norms:
    1 hr 37-90%
    2 hr 30-60%
    4 hr 0-10%
  • -Gastroenterol 2009; 136: 1526.  Tests of gastric emptying -review.
  • -Clin Gastro & Hep 2008; 6: 1309. algorithm for nausea & delayed GE.  REC;
    1. small meals, low fiber/fat
    2. prokinetic: reglan, EES, ?domperidone
    3. Antiemetics: zofran, prochloroperazine
    4. TCA
    5. ?Botox injection
    6. jejunal feeds
  • -Gastroenterol 2009; 136: 1526.  Tests of gastric emptying -review.  Consider domperidone, reglan, ?gastric stimulation, ?surgery, discusses novel Rxs.
  • -Gastroenterol 2009; 136: 1225.  Review of prevalence and outcomes in Olmsted County.
  • -Am J Gastro 2008; 103: 416-23.  Botox is NOT effective for gastroparesis/delayed GE.
  • Need to distinguish delayed gastric emptying from rumination. Treatment for rumination and belching