a b s t r a c t

A nonsurgical approach using antimicrobial agents has been advocated as the initial treatment of uncomplicated appendicitis. Several studies and meta-analyses explored this approach. Because many of these studies included individuals with resolving appendicitis, their results were biased. Antimicrobials, however, are warranted and needed for the management of surgical high-risk patients with Perforated appendicitis and those with localized abscess or phlegmon. Randomized placebo-controlled trials that focus on early identification of complicated acute appendicitis patients needing surgery and that prospectively evaluate the optimal use of antibiotic treatment in patients with uncomplicated acute appendicitis are warranted.

(C) 2015

Surgical removal of the inflamed appendix has been the standard of care for more than 120 years [1]. More than 300,000 appendectomies are performed annually in the United States [2]. Because of the difficulty in the early identification of those who would progress to serious and sometimes lethal form of the infection, early appendectomy had be- come the norm [3]. Although appendectomy is generally well tolerated, it is a major surgical procedure and can be associated with postopera- tive morbidity. A nonsurgical option for the treatment of uncomplicated appendicitis using antimicrobial agents has been considered and studied for more than 60 years [4-14]. This approach was suggested as a substitute for surgery where the procedure is not available (ie, no surgeon available, remote areas, submarines) or the patient is not able to undergo surgery.

This review presents recent studies that evaluated nonsurgical treat- ment using antimicrobial agents for uncomplicated appendicitis.

Antimicrobial agents for the treatment of complicated appendicitis (perforated appendicitis with localized abscess or phlegmon)

Antibiotics are indicated for the treatment of perforated appendicitis with localized abscess or phlegmon and in selected surgical high-risk patients. This is supported by Andersson and Petzold’s [15] review and meta-analysis of 61 mainly retrospective studies published between 1964 and 2005 of nonsurgical treatment of appendiceal abscess or phlegmon. The authors concluded that nonsurgical treatment of appendicitis phlegmon or appendiceal abscess with antibiotics is efficient and associated with shorter hospital stay and lower morbidity compared with open appendectomy.

Simillis et al [16] performed meta-analysis on 17 (16 nonrandomized retrospective) studies of appendiceal abscess and phlegmon. The authors

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also concluded that conservative management of complicated appendici- tis is associated with a decrease in complications and reoperation rate compared with acute appendectomy, and patients had a similar duration of hospital stay.

Antimicrobial agents for the treatment uncomplicated appendicitis

Several recent randomized trials compared appendectomy to non- surgical treatment with antibiotics as a primary treatment for suspected uncomplicated appendicitis [7-9,14].

Styrud et al [7] studied 252 patients from 6 hospitals admitted for appendicitis between 1996 and 1999. Complications occurred in 14% in the surgery group. In the antibiotic group, 86% improved without surgery; and the rest were operated on within 24 hours. The rate of recurrence of symptoms of appendicitis among the patients treated with antibiotics was 14% during the 1-year follow-up.

Vons et al [9] evaluated 239 patients from 6 centers between 2004 and 2007 who were randomized to surgical or nonsurgical treatment of appendicitis. Incidence of 30-day postintervention peritonitis was significantly higher in the antibiotic-treatment group (8%) than in the appendectomy group (2%). In the antibiotic group, 12% underwent appendectomy during the first 30 days; and 29% had appendectomy between 1 and 12 months, 26 of whom had acute appendicitis (recur- rence rate, 26%).

The study showed that antibiotic treatment (with amoxicillin plus clavulanic acid) was not noninferior to emergency appendectomy for treatment of acute uncomplicated appendicitis. Another important observation was that, in the appendectomy group, despite computed tomography (CT) scan assessment suggesting a noncomplicated appen- dicitis, 21 of 119 (18%) patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. This illustrated that the distinction between uncomplicated and complicated appendicitis remains difficult even with the utilization of diagnostic CT scans [17].

http://dx.doi.org/10.1016/j.ajem.2015.11.063

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Hansson et al [8] performed a randomized trial that included 558 pa- tients; 79% received antibiotics as first-line therapy, and 20% had surgery. Seventy-seven percent of patients that received antibiotics re- covered, and 23% had subsequent appendectomy due to failed initial treatment with antibiotics. Thirty-eight patients (11%) of those treated with antibiotics experienced recurrent appendicitis at 1-year follow- up. Primary antibiotic treatment had fewer complications compared with primary surgery. The study was difficult to evaluate because of 48% crossovers from nonsurgical to surgical treatment and 13% from surgical to nonsurgical treatment. These occurred because of patients’ preference or because of surgeons’ decision.

A study by Salminen et al [14] randomly assigned 273 patients with acute appendicitis to appendectomy and 256 to a 10-day course of antibiotics. Appendectomies were successful in all but 1 of 273 (0.4%) patients. Among 256 patients treated with antibiotics and followed for a year, 186 (73%) did not require surgery. However, 70 (27%) of the patients treated with antibiotics had to have their appendix removed within a year. No patient in the antibiotic group developed a serious infection (ie, intraAbdominal abscesses) resulting from delayed appendectomy, suggesting that a delay in appendectomy for uncomplicated acute appendicitis can be made with low likelihood of major complications.

The authors concluded [14] that emergency appendectomy is only indicated in those with CT-proven complicated appendicitis that can cause the appendix to rupture, which occurs only in about 20% of the pa- tients. In contrast, those with CT-proven uncomplicated appendicitis can be treated with antibiotics.

Discussion

Recent studies [7-9,14] explored the use of antimicrobials as a first line of treatment for patients with uncomplicated appendicitis. Because patients with complicated appendicitis, those with appendicoliths, children, and pregnant women were excluded from these studies, the results do not apply to these groups [18].

One of the major limitations of these studies is the inability to differ- entiate between patients with uncomplicated and complicated appen- dicitis, as well as those with nonspecific abdominal pain. The criteria used for selection for nonsurgical treatment of presumed uncomplicat- ed appendicitis are not described in these randomized trials [7-9,14], thus weakening their validity. Furthermore, CT scan used to differenti- ate between uncomplicated and complicated appendicitis missed 18% of patients with complicated appendicitis who had peritonitis [9].

The frequent occurrence of spontaneous resolution of appendicitis also complicates the assessment of the effects of nonsurgical management using antimicrobial therapy [19]. The results of studies can be biased by the inclusion of patients who would not need any treatment, and the assumed effect of treatment can be attributed to spontaneous resolution. The routine utilization of antimicrobials is expected to decrease the number of explorations, for both uninflamed appendices and uncompli- cated appendicitis, either because of the effect of the antimicrobials or because of spontaneous resolution. However, this approach may increase the risk for the emergence of Antimicrobial resistance, allergic reactions, untoward adverse effects, and Clostridium Difficile colitis [20]. Furthermore, a delay in the surgical treatment for those who will respond only partly to this treatment may increase hospital stay, as

well as morbidity and mortality [21].

Another risk of nonsurgical approach is the inability to detect malignancy as the underlying condition for the suspected appendicitis. Although this condition is diagnosed in a small number of cases, colonic examination is advisable in older individuals [22].

Although antibiotics treatment is indicated for the treatment of perforated appendicitis with localized abscess or phlegmon and in selected surgical high-risk patients [23], future studies are warranted that would explore the nonsurgical option in treating appendicitis. These studies should both focus on early identification of complicated acute appendicitis patients needing surgery and prospectively evaluate the optimal use of antibiotic treatment in patients with uncomplicated acute appendicitis.

The pitfalls of antibiotic treatment should also be addressed in future studies. broad-spectrum antibiotics can promote the emergence of resistant organisms [23] as well as C difficile infections [20]. These potential adverse effects may tilt the balance toward performing appendectomy. Furthermore, inclusion of greater number of patients is required in future studies to evaluate the ability of antibiotics to prevent Pelvic abscesses as effectively as surgery.

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