Shorter Post-Op Antibiotic Course Non-Inferior for Complex Appendicitis

Two days of postoperative intravenous antibiotics for complex appendicitis was non-inferior to 5 days in terms of complications and mortality, according to results of an open-label randomized trial.

In 1,005 patients, the vast majority of whom underwent laparoscopic appendectomy, that composite endpoint occurred in 10% of the 2-day group and 8% of the 5-day group, for an adjusted absolute risk difference of 2% (95% CI -1.6 to 5.6), reported Ann van den Boom, MD, of Erasmus MC-University Medical Centre in Rotterdam, The Netherlands, and colleagues.

As shown in their study in The Lancet, patients in the 5-day group had fewer Clavien-Dindo class 2 complications, visits to the emergency department, and hospital readmissions. Patients in the 2-day group had fewer adverse effects from antibiotics, and their overall hospital stay was shorter, even when including readmissions.

The majority of patients in the trial (95%) underwent laparoscopic appendectomy. In the small number of patients whose laparoscopy was converted to open appendectomy, those in the 5-day group had fewer infectious complications than the 2-day group did (4% vs 27%).

"To our knowledge, this is the first adequately powered level I randomized controlled trial that evaluates the safety and efficacy of postoperative antibiotics restricted to 2 days," the researchers wrote. "The optimum duration of treatment has been a topic of debate, while the increasing global threat of antimicrobial resistance calls for antibiotic stewardship."

"This study indicates that more than 2 days of postoperative antibiotics for complex appendicitis is not needed after adequate source control," the team continued, adding that adopting this strategy for patients with complex appendicitis could reduce the adverse effects of antibiotics and relieve pressure on hospital bed capacity.

The researchers cautioned, however, that the recommendations are valid for laparoscopic appendectomy in a "well-resourced" healthcare setting. "After open appendectomy, patients might benefit from an extended regimen of antibiotics. Whether 2 days of antibiotics is safe for patients who are immunocompromised or pregnant is unknown," van den Boom and co-authors wrote.

The trial included patients ages 8 and older from 15 hospitals in the Netherlands. These patients had acute appendicitis, an American Society of Anesthesiologists classification of I–III, and a diagnosis of complex appendicitis, defined as the presence of necrosis, perforation, or abscess. Pregnant and immunocompromised patients were excluded. The majority of patients were ages 18 to 64 years, and 57% were male.

Patients were randomized 1:1 to either course of antibiotics. However, there was no placebo, and neither physicians nor patients were blinded to treatment. The primary endpoint was a composite of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7.5%. Outcomes were assessed with electronic records and a telephone consultation 90 days after appendectomy.

There were no treatment-related deaths, the authors noted. One patient in the 2-day group died of metastatic esophageal cancer on postoperative day 84.

In an accompanying editorial, Aneel Bhangu, MD, PhD, of the University of Birmingham in England, and colleagues agreed with the study authors' conclusions. "Taken together, the findings suggest that giving shorter courses of antibiotics is safe and should be adopted in patients who have laparoscopic appendectomy," the editorialists wrote.

"Subgroup analysis suggested that the small number of patients who had open surgery, including laparoscopic surgery that was converted to an open operation, had more infections if they received shorter antibiotic courses. For such patients, more caution might be needed as longer courses could be protective," Bhangu and co-authors suggested.

The researchers speculated that the higher rate of hospital readmissions in the 2-day group (12% vs 6%, HR 2.1, 95% CI 1.3-3.34) might have been due to caution on the part of physicians. "Physicians could have had a low threshold for readmitting patients and restarting antibiotics for patients in the 2-day group, as this was experimental when the study started," van den Boom and co-authors noted.

"It can be concluded that the benefit of reduced antibiotic use and shorter hospital stay outweighs an increased risk of readmission or complications that do not need surgical or radiological interventions," the researchers added.

A key limitation of the study, they said, was that just 28% of eligible patients agreed to participate. While the reasons for non-participation were not known, this could have introduced some form of selection bias. The lack of a placebo and masking were other obvious limitations. Such methods, however, would not have been practical or feasible, the researchers explained, as it would have required placebo patients to stay additional days in the hospital receiving intravenous saline.

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