Appendicitis: Up-Front Antibiotics OK in Select Patients

Pam Harrison

December 14, 2021

Appendectomy is still the first-line treatment for most patients with acute appendicitis, but treatment with up-front antibiotics rather than having patients proceed to laparoscopic surgery can be done in appropriately selected patients with uncomplicated appendicitis, a comprehensive review of the literature suggests.

We think it's going to be 60% to 70% of patients who are good candidates for consideration of antibiotics. Dr Theodore Pappas and colleagues

"I think this is a wonderful thing that we have for our patients now, because think about the patient who had a heart attack yesterday and has appendicitis today — you don't want to operate on that patient — so this gives us a wonderful option in an environment where sometimes surgery is just bad timing," Theodore Pappas, MD, professor of surgery, Duke University School of Medicine, Durham, North Carolina, told Medscape Medical News.

"It's not that every 25-year-old who comes in should get antibiotics instead of surgery. It's really better to say that this gives us flexibility for patients who we may not want to operate on immediately, and now we have a great option," he stressed.

The study was published December 14 in JAMA.

Acute appendicitis is the most common abdominal surgical emergency in the world, as the authors point out.

"We think it's going to be 60% to 70% of patients who are good candidates for consideration of antibiotics," they speculate.

Current Evidence

The review summarizes current evidence regarding the diagnosis and management of acute appendicitis based on a total of 71 articles including 10 systematic reviews, nine meta-analyses, and 11 practice guidelines. "Appendicitis is classified as uncomplicated or complicated," the authors explain. Uncomplicated appendicitis is acute appendicitis in the absence of clinical or radiographic signs of perforation.

In contrast, complicated appendicitis is when there is appendiceal rupture with subsequent abscess of phlegmon formation, the definitive diagnosis of which can be confirmed by CT scan. "In cases of diagnostic uncertainty imaging should be performed," investigators caution — usually with ultrasound and CT scans.

If uncomplicated appendicitis is confirmed, three different guidelines now support the role of an antibiotics-first approach, including guidelines from the American Association for Surgery of Trauma. For this group of patients, empirical broad-spectrum antibiotic coverage that can be transitioned to outpatient treatment is commonly used. For example, patients may be initially treated with intravenous (IV) ertapenem monotherapy or IV cephalosporin plus metronidazole, then on discharge put on oral fluoroquinolones plus metronidazole.

Antibiotics that cover streptococci, nonresistant Enterobacteriaceae, and the anaerobes are usually adequate, they add. "The recommended duration of antibiotics is 10 days," they note. In most of the clinical trials comparing antibiotics-first to surgery, the primary endpoint was treatment failure at 1 year, in other words, recurrence of symptoms during that year-long period. Across a number of clinical trials, that recurrence rate ranged from a low of 15% to a high of 41%.

In contrast, recurrence rarely occurs after surgical appendectomy. Early treatment failure, defined as clinical deterioration or lack of clinical improvement within 24 to 72 hours following initiation of antibiotics, is much less likely to occur, with a reported rate of between 8% to 12% of patients. The only long-term follow-up of an antibiotics-first approach in uncomplicated appendicitis was done in the Appendicitis Acuta (APPAC) trial, where at 5 years, the recurrence rate of acute appendicitis was 39% (95% CI, 33.1% – 45.3%) in patients initially treated with antibiotics alone.

Typically, there have been no differences in the length of hospital stay in most of the clinical trials reviewed. As Pappas explained, following a standard appendectomy, patients are typically sent home within 24 hours of undergoing surgery. On the other hand, if treated with IV antibiotics first, patients are usually admitted overnight then switched to oral antibiotics on discharge — suggesting that there is little difference in the time spent in hospital between the two groups.

However, there are groups of patients who predictably will not do well on antibiotics first, he cautioned. For example, patients who present with a high fever, shaking and chills, and severe abdominal pain do not have a mild case of appendicitis. Neither do patients who may not look sick but on CT scan, they have a hard piece of stool jammed into the end of the appendix that's causing the blockage: these patients are also more likely to fail antibiotics, Pappas added.

"There is also a group of patients who have a much more dilated appendix with some fluid around it," he noted, "and these patients are less likely to be managed with antibiotics successfully as well," he said. Lastly, though not part of this review and for whom an antibiotics-first protocol has long been in place, there is a subset of patients who have a perforated appendix, and that perforation has been walled off in a pocket of pus.

"These patients are treated with an antibiotic first because if you operate on them, it's a mess, whereas if patients are reasonably stable, you can drain the abscess and then put them on antibiotics, and then you can decide 6 to 8 weeks later if you are going to take the appendix out," Pappas said, adding: "Most of the time, what should be happening is the surgeon should consult with the patient and then they can weigh in — here are the options and here's what I recommend," he said.

"But patients will pick what they pick, and surgery is a very compelling argument: it's laparoscopic surgery, patients are home in 24 hours, and the complication rate [and the recurrence rate] are incredibly low, so you have to think through all sorts of issues and when you come to a certain conclusion, it has to make a lot of sense to the patient," Pappas emphasized.

Asked to comment on the findings, Ram Nirula, MD, D. Rees and Eleanor T. Jensen Presidential Chair in Surgery, University of Utah, Salt Lake City, Utah, noted that as with all things in medicine, nothing is 100%.

"There are times where antibiotics for uncomplicated appendicitis may be appropriate, and times where appendectomy is most appropriate," he told Medscape Medical News in an email. Most of the evidence now shows that the risk of treatment failure following nonoperative management for uncomplicated appendicitis is significant, ranging from 15% to 40%, as Nirula reaffirmed.

A more recent randomized controlled trial from the CODA collaborative found that quality of life was similar for patients who got up-front antibiotics as for those who got surgery at 30 days, but the failure rate was high, particularly for those with appendicolith (what review authors would have classified as complicated appendicitis).

Moreover, when looking at this subset of patients, quality of life and patient satisfaction in the antibiotic treatment group were lower than it was for surgical controls, as Nirula also pointed out. While length of hospital stay was similar, overall healthcare resource utilization was higher in the antibiotic group, he added. "So, if it were me, I would want my appendix removed at this stage in my life, however, for those who are poor surgical candidates, I would favor antibiotics," he stressed. He added that the presence of an appendicolith makes the argument for surgery more compelling, although he would still try antibiotics in patients with an appendicolith who are poor surgical candidates.

Pappas reported serving as a paid consultant for Transenterix Corp. Nirula has disclosed no relevant financial relationships.

JAMA. Published online December 14, 2021. Abstract

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