Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

doi:10.5867/medwave.2016.6375

Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)

Medwave 2016;16(Suppl 1):e6375 doi: 10.5867/medwave.2016.6375

Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

Felipe Moraga, Vanessa Ahumada, Fernando Crovari

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Abstract

Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified nine systematic reviews including five pertinent randomized trials overall. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy.

Problem

Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery, with an estimated lifetime incidence between 7 and 14% [1],[2]. Since the 1890s, when McBurney described early appendectomy as the therapy of choice for acute appendicitis [3],[4], surgery has remained the mainstay of treatment of this disease, drastically reducing its mortality rate [5].

Treatment of acute appendicitis with antibiotics as initial strategy was historically reserved for patients with several days of evolution of the inflammatory process who developed appendicular plastron or abscess, in an attempt to avoid major surgery [2]. In 1953, Harrison reported 42 of 47 cases of acute appendicitis treated successfully with antibiotics. Meanwhile, Coldrey published an article in 1959 with 471 cases of acute appendicitis treated conservatively, with only 1 death, 9 patients who required drainage of abscess and only 48 cases requiring a subsequent appendectomy [6].

In the past two decades, growing evidence has been published on the use of antibiotics as the sole treatment of acute appendicitis.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

The use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy.
The use of antibiotics to treat acute uncomplicated appendicitis probably increases major complications compared with appendectomy.
The conclusions of this summary are consistent with existing systematic reviews and the recommendations of the main guidelines.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found nine systematic reviews [5],[6],[7],[8],[9],[10],[11],[12],[13] including seven primary studies [14],[15],[16],[17],[18],[19],[20], from which five correspond to randomized controlled trials [14],[15],[18],[19],[20]. This table and the summary in general are based on the latter.
What types of patients were included	All studies included adult patients with suspected acute appendicitis. All studies excluded pediatric patients and one study also excluded women [15]. One study established the suspected acute appendicitis based on clinical and laboratory parameters [15], one study on clinical criteria and images [20] and three studies on clinical criteria, laboratory parameters and images [14],[18],[19].
What types of interventions were included	Four of the studies used intravenous antibiotics for 48 hours [14],[15],[18],[19]. Of these, two studies used a combination of cefotaxime with tinidazole [14],[15], another study used ciprofloxacin plus metronidazole [18] and one used associated ampicillin with gentamicin and metronidazole [19]. The remaining study [20] used a combination of amoxicillin with clavulanic acid intravenously only if the patient had nausea or vomiting and for a time not specified. All studies continued oral antibiotic therapy. One study completed 7 days of treatment [18], another study completed eight days of treatment [20] and three studies completed 10 days [14],[15],[19]. To complete oral treatment, two studies used a combination of ofloxacin with tinidazole [14],[15], another a combination of ciprofloxacin with tinidazole [18], one used amoxicillin with clavulanic acid [20] and one study did not specify the antibiotic used orally [19]. All of the studies compared antibiotic treatment versus appendectomy.
What types of outcomes were measured	Treatment efficacy, defined as absence of symptoms within two weeks, without major complications (including recurrence) within one year. Major complications defined as the need of further invasive treatment or prolonged admission (e.g. abscesses, ileus, deep wound infection, recurrence, re-operation, secondary perforation). Minor complications (e.g. negative appendectomy, diarrhea, and superficial wound infection). Duration of hospital stay. Period of sick leave. Cost effectiveness.

We found three systematic reviews [5], [6], [7], including 14 studies reported in 21 references [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. Eight studies correspond to randomized controlled trials (15 references [9], [10], [11], [12], [13], [14], [16], [17], [19], [21], [22], [23], [24], [26], [27]). This table and the summary in general are based on the latter. One study [15] did not contribute data to any of the outcomes of interest.

Summary of findings

Information on the effects of antibiotic treatment versus appendectomy is based on five randomized trials [14],[15],[18],[19],[20] including 901 patients, of whom 415 were initially treated with antibiotic and 486 with appendectomy.

All studies reported the outcomes effectiveness of treatment and major complications.

The use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy. The certainty of the evidence is low.
The use of antibiotics to treat acute uncomplicated appendicitis probably increases major complications compared with appendectomy. The certainty of the evidence is moderate.

Other considerations for decision-making

To whom this evidence does and does not apply

The evidence included in this summary is applicable to adult patients with acute uncomplicated appendicitis, independent of sex and age.
It does not apply to patients presenting complications of acute appendicitis (such as drilling, appendicular mass, peritonitis, gangrene or other), since they have a clinical course and treatment indication different than acute uncomplicated appendicitis.
Studies in pediatric patients were not included in this summary, so this evidence cannot be extrapolated to that population.

About the outcomes included in this summary

Effectiveness of treatment and presence of major complications were selected as critical outcomes for decision-making.
Other outcomes such as length of hospital stay or time to return to work, were considered less important when choosing a treatment over the other.

Balance between benefits and risks, and certainty of the evidence

While the certainty of the evidence is low or moderate for major outcomes, it is an intervention which benefits are likely to outweigh the low risk associated with appendectomy.
In patients with a high surgical risk, this balance could eventually favor antibiotic treatment [2],[21].

What would patients and their doctors think about this intervention

It is highly likely that patients and their carers would be inclined to surgery, since it is the established treatment for both clinicians and patients, which is reinforced by the evidence.

Resource considerations

Although surgery has a higher cost, it is likely that the costs of complications and low effectiveness of antibiotic treatment make surgery the most cost-effective intervention

Differences between this summary and other sources

The conclusions of this summary are consistent with those of the systematic reviews identified and existing overviews of reviews [1],[21].
The main guideline on the subject [22] recommends appendectomy as the treatment of choice for acute appendicitis. It states antibiotic therapy as primary treatment is safe for patients with acute uncomplicated appendicitis, but less effective in the long-term because of higher rate of recurrence.

Could this evidence change in the future?

The probability that future studies change what we know is low, because of the certainty of the evidence.
However, there is at least one randomized controlled trial that is not included in any of the identified systematic reviews [23] and at least one ongoing study, which will provide new evidence in this regard [24].

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Antibiotics versus appendectomy for acute uncomplicated appendicitis

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

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