What was the aim of this review?
This Cochrane Review aimed to determine whether antibiotics are useful and safe for people with ulcerative colitis (UC) in achieving or maintaining remission.
Key messages
We found that antibiotics, when added to standard therapies, are similar to placebo in how often they fail to achieve remission or disease improvement for people with UC, measured up to three months from taking them.
We found that antibiotics when compared to placebo may be useful in achieving remission or some improvement of UC symptoms, measured at 12 months from taking them.
In terms of safety, the evidence is of low certainty, but antibiotics may be as safe as placebo.
We have confidence in the findings up to three months, but have less confidence in the evidence at 12 months due to low numbers of study participants.
What is ulcerative colitis?
UC is a chronic (long term) inflammatory disease that affects the large bowel. The most common symptoms include bloody diarrhoea, abdominal pain, and a sudden almost uncontrollable urge to pass stool. Some people have other symptoms including sore joints, mouth sores, and inflammation in their eyes. When someone is experiencing symptoms of UC, they are said to have 'active' disease. When symptoms improve with treatment, the disease is said to be responding to therapy. When symptoms stop, the disease is said to be in 'remission'. People with UC in remission are often given therapy with medicines to try and prolong (maintain) their remission or response to therapy.
What did the review study?
This review studied the use of antibiotics in the treatment of UC. Eleven studies considered antibiotics as a therapy for achieving remission and one study as therapy for maintaining remission.
Antibiotics could theoretically be helpful as they might be able to fight harmful bacteria in the gut that are thought to be a partial cause for the presence of UC symptoms.
Currently, most doctors do not recommend the use of antibiotics unless the patient has an infection.
What were the main results of the review?
We searched for randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) comparing antibiotics with another treatment or dummy treatment. We found 12 RCTs including 847 participants. The trials looked at people of all ages; using different types and doses of antibiotics; and at antibiotics taken as tablets, injections, or any other way. The main results from our review are as follows.
1. Antibiotics, when added to standard therapies, are no different from placebo in failing to achieve remission or improve disease symptoms for people with UC when measured up to three months from taking them.
2. Antibiotics probably fail less than placebo in achieving remission or some improvement of UC symptoms measured at 12 months from taking them.
3. In terms of safety, antibiotics may be similar to placebo, but the evidence is of low certainty.
4. We are uncertain about how antibiotics compare to other treatments because there is not enough good evidence to make a judgement.
Conclusion
There is no difference between antibiotics and placebo when added to standard therapies to achieve remission or improvement of symptoms in the short term. However, they may help to lessen the number of people who do not achieve remission, and they probably lead to fewer numbers of people who have not achieved improvement of symptoms at 12 months.
No conclusions can be drawn on other treatments or safety due to lack of evidence, even though there may be a possibility that antibiotics are as safe as placebo. Further research would be needed to clarify the usefulness of antibiotics in the treatment of UC; however, such studies should focus on longer-term outcomes given the findings of this review.
How up-to-date is this review?
This review is up-to-date as of December 2021.
There is high certainty evidence that there is no difference between antibiotics and placebo in the proportion of people who achieve clinical remission at the end of the intervention period. However, there is evidence that there may be a greater proportion of people who achieve clinical remission and probably a greater proportion who achieve clinical response with antibiotics when compared with placebo at 12 months. There may be no difference in serious adverse events or withdrawals due to adverse events between antibiotics and placebo.
No clear conclusions can be drawn for any other comparisons.
A clear direction for future research appears to be comparisons of antibiotics and placebo (in addition to standard therapies) with longer-term measurement of outcomes. Additionally. As there were single studies of other head-to-head comparisons, there may be scope for future studies in this area.
Antibiotics have been considered to treat ulcerative colitis (UC) due to their antimicrobial properties against intestinal bacteria linked to inflammation. However, there are concerns about their efficacy and safety.
To determine whether antibiotic therapy is safe and effective for the induction and maintenance of remission in people with UC.
We searched five electronic databases on 10 December 2021 for randomised controlled trials (RCTs) comparing antibiotic therapy to placebo or an active comparator.
We considered people with UC of all ages, treated with antibiotics of any type, dose, and route of administration for inclusion. Induction studies required a minimum duration of two weeks for inclusion. Maintenance studies required a minimum duration of three months to be considered for inclusion.
We used standard methodological procedures expected by Cochrane. Our primary outcome for induction studies was failure to achieve remission and for maintenance studies was relapse, as defined by the primary studies.
We included 12 RCTs (847 participants). One maintenance of remission study used sole antibiotic therapy compared with 5-aminosalicylic acid (5-ASA). All other trials used concurrent medications or standard care regimens and antibiotics as an adjunct therapy or compared antibiotics with other adjunct therapies to examine the effect on induction of remission.
There is high certainty evidence that antibiotics (154/304 participants) compared to placebo (175/304 participants) result in no difference in failure to achieve clinical remission (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06). A subgroup analysis found no differences when steroids, steroids plus 5-ASA, or steroids plus 5-ASA plus probiotics were used as additional therapies to antibiotics and placebo.
There is low certainty evidence that antibiotics (102/168 participants) compared to placebo (121/175 participants) may result in no difference in failure to achieve clinical response (RR 0.75, 95% CI 0.47 to 1.22). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were used as additional therapies to antibiotics and placebo.
There is low certainty evidence that antibiotics (6/342 participants) compared to placebo (5/349 participants) may result in no difference in serious adverse events (RR 1.19, 95% CI 0.38 to 3.71). A subgroup analysis found no differences when steroids were additional therapies to antibiotics and placebo.
There is low certainty evidence that antibiotics (3/342 participants) compared to placebo (1/349 participants) may result in no difference in withdrawals due to adverse events (RR 2.06, 95% CI 0.27 to 15.72). A subgroup analysis found no differences when steroids or steroids plus 5-ASA were additional therapies to antibiotics and placebo.
It is unclear if there is any difference between antibiotics in combination with probiotics compared to no treatment or placebo for failure to achieve clinical remission (RR 0.68, 95% CI 0.39 to 1.19), serious adverse events (RR 1.00, 95% CI 0.07 to 15.08), or withdrawals due to adverse events (RR 1.00, 95% CI 0.07 to 15.08). The certainty of the evidence is very low.
It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to achieve clinical remission (RR 2.20, 95% CI 1.17 to 4.14). The certainty of the evidence is very low.
It is unclear if there is any difference between antibiotics compared to probiotics for failure to achieve clinical remission (RR 0.47, 95% CI 0.23 to 0.94). The certainty of the evidence is very low.
It is unclear if there is any difference between antibiotics compared to 5-ASA for failure to maintain clinical remission (RR 0.71, 95% CI 0.47 to 1.06). The certainty of the evidence is very low.
It is unclear if there is any difference between antibiotics compared to no treatment for failure to achieve clinical remission in a mixed population of people with active and inactive disease (RR 0.56, 95% CI 0.29 to 1.07). The certainty of the evidence is very low.
For all other outcomes, no effects could be estimated due to a lack of data.