Growing evidence supports antibiotics-first strategy in uncomplicated appendicitis

Last Updated: 2016-01-01

By Will Boggs MD

NEW YORK (Reuters Health) - Mounting evidence supports the strategy of antibiotics-first for treating adults with acute uncomplicated appendicitis (AUA), but several questions remain to be answered, according to a systematic review.

"Currently, a vast majority of US surgeons treat AUA with appendectomy even following six randomized controlled trials studying antibiotics compared to surgery," said Dr. Anne P. Ehlers from the University of Washington, Seattle.

"Although change in practice takes a long time following new studies, the lack of evolution in surgical practice for appendicitis is in large part because of the major evidence gaps that remain. We wanted to identify these evidence gaps so that they could be addressed in a future study," she told Reuters Health by email.

In their systematic review, Dr. Ehlers and colleagues examined six randomized controlled trials including more than 1,700 patients. The appendectomy rates ranged from 24% to 35% with the exception of one study where 60% of patients eventually underwent appendectomy, primarily due to high crossover from the antibiotics-only group.

Length of hospital stay was about the same - around three days - in the surgery and antibiotics-first groups, but days of pain and days away from work were lower and complications were less common in the antibiotics-first group.

Selection bias was a common theme across all studies, and most studies failed to describe standardized diagnostic criteria for study eligibility (suggesting that the study population does not necessarily reflect the real population of patients with AUA), Dr. Ehlers' team reports in the Journal of the American College of Surgeons, online December 16.

Treatment strategies varied across studies, with at least one employing antibiotics that provided inadequate coverage for typical causative agents. Only one study had a laparoscopy rate above 50%, thereby limiting the generalizability of findings to patients in the U.S., where the vast majority of appendectomies are performed laparoscopically.

Finally, many of the primary outcomes were vague or not clinically meaningful, and most studies had follow-up periods of one year, which may be insufficient to demonstrate the long-term effectiveness of antibiotic treatment or to detect such events as appendiceal cancer or recurrent appendicitis.

All five meta-analyses reviewed by the authors concluded that antibiotics-first is probably safe, but that definitive conclusions about its effectiveness compared to appendectomy cannot be made.

"Physicians should use this as a guide when considering antibiotics-first for treatment of AUA," Dr. Ehlers said. "If possible, physicians should make use of publicly available registries such as that available at http://www.becertain.org/AppyRegistry so that we can continue to learn about this strategy to inform decision making in the future."

"Patients should be informed of the available treatment options, including the option of antibiotics-first for AUA," she said. "It is important to make sure that they understand the potential risks, as well as benefits, of surgery versus antibiotics-first. We should tell patients that we think either strategy is safe, but that there are unanswered questions about the antibiotics-first approach, particularly regarding patient reported outcomes following treatment."

She added, "Surgeons and emergency medicine physicians in Washington and California are planning the first U.S. based study in adults, the Comparing Outcomes of Drugs and Appendectomy (CODA) Study, funded by the Patient Centered Outcomes Research Institute (PCORI) to help address many of these evidence gaps. We plan to begin enrolling patients in early 2016."

Dr. Peter C. Minneci from The Research Institute at Nationwide Children's Hospital in Columbus, Ohio, who was not involved in the review, has studied nonoperative options for managing AUA in children.

He told Reuters Health by email, "The use of antibiotics first as a primary treatment for uncomplicated appendicitis is just starting to gain traction as a treatment option in the U.S. because appendectomy is considered a safe, effective, and routine operation. There has been no impetus to change until the available studies have suggested that (the antibiotics-first strategy) is safe and reasonable and may lead to lower costs and fewer complications."

"Unfortunately, most of the available adult data is from international studies using different inclusion criteria and performed in health systems that are very different than the U.S.," he explained. "These variations and differences make their results hard to interpret or apply in practice."

"There is reasonably good evidence that antibiotics first is safe and has a reasonable success rate at one year; the question really is whether it is worth doing," Dr. Minneci said. "That should be explained to the patients and the decision about whether to offer antibiotics first as a treatment option needs to be made jointly based on the surgeon's and patient's comfort with the risks and benefits associated with each treatment option."

Dr. Chad G. Ball from the University of Calgary in Canada, who also was not involved in the new analysis, recently compared outcomes of laparoscopic versus open appendectomy.

"Until we have a well-constructed, multicenter, (randomized controlled trial) that I would postulate encompasses at least 10,000 patients, I would argue that laparoscopic appendectomy remains the standard of care," he told Reuters Health by email. "It is clear that this trial (and size) is very 'doable' given the extraordinarily large RCTs recently completed by our orthopedic surgery colleagues. Furthermore, these trials need to include countries such as India and China to achieve their denominator, as well as to be globally relevant."

"There is no doubt that a subset of these patients exist who could avoid an operative intervention and be treated with antimicrobials alone," Dr. Ball said. "Our issue on Acute Care Surgery services is a lack of specific and safe targeting of these patients."

SOURCE: http://bit.ly/1YPZSyE

J Am Coll Surg 2015.