(From the November 2015 Issue of PediatricsOnline)
The cheap and widely available antibiotic amoxicillin strengthens duodenal contractions in rat models, suggesting the drug may be a candidate for treating dysmotility in people, researchers at Nationwide Children's Hospital have found.
The work helps define an earlier Nationwide Children's study that showed children suffering from gastrointestinal motility issues had improved small bowel function after taking the drug Augmentin, which is a combination of amoxicillin and clavulanic acid.
The new research found clavulanic acid alone had no effect on rat duodenal contractions. Instead, tests indicate that amoxicillin starts working when it reaches the surface of the intestine and acts on the nerves that stimulate the muscles rather than the muscles themselves.
"If people benefitted from the use of the combined form, Augmentin, the work suggests they may benefit from amoxicillin alone," says Steven Ciciora, MD, a gastroenterologist at Nationwide Children's and lead author of the study. The work is published in the Journal of Pediatric Gastroenterology and Nutrition.
Carlo Di Lorenzo, MD, chief of Gastroenterology, Hepatology and Nutrition at Nationwide Children's, suspected that Augmentin may be beneficial for dysmotility patients a few years ago. Dr. Di Lorenzo noticed that children suffering from dysmotility felt better when they were taking the antibiotic. He then led a study in children that found the drug appears to promote duodenal phase III contractions—what gastroenterologists call the "intestinal housekeeper."
"The vast majority of people take that for granted, but for patients with motility problems, lack of these contractions can lead to a lot of problems," explains Dr. Ciciora, also an assistant professor of Pediatrics at The Ohio State University College of Medicine.The problems include bloating, vomiting and abdominal pain.
While diagnosis of motility issues has improved, available treatments are plagued with unwanted side effects and high costs.
Dr. Ciciora’s team found amoxicillin alone increased the strength of contractions by an average of 26 percent in duodenal segments of juvenile rat models. But no effect was seen when neuronal activity was suppressed, suggesting the antibiotic acts on the nerves.
Dr. Di Lorenzo's study found amoxicillin was effective 10 to 12 minutes after administration, indicating the drug becomes active when it reaches the intestinal surface. The new study confirms this and shows that absorption and circulation in the blood is unnecessary.
While Augmentin appears to treat small intestine dysmotility in people, its use has not been widely embraced due to concerns about changing the microbiome of the gut, inducing antibiotic resistance and increasing the risk of Clostridium difficile colitis. The researchers say that amoxicillin alone affects a narrower spectrum of bacteria and should lessen those concerns.
Dr. Ciciora and colleagues have begun studying the effect of amoxicillin alone on motility in children. They expect to finish the research in about a year.
Ciciora SL, Williams KC, Gariepy CE. Effects of amoxicillin and clavulanic acid on the spontaneous mechanical activity of juvenile rat duodenum. Journal of Pediatric Gastroenterology and Nutrition.2015 Sept; 61(3) 340-345.
Gomez R, Fernandez S, Aspirot A, Punati J, Skaggs B, Mousa H, Di Lorenzo C. Effect of amoxicillin/clavulanate on gastrointestinal motility in children. Journal of Pediatric Gastroenterology and Nutrition. 2012 Jun;54(6):780-4.