Oral antibiotics for appendicitis

Contents

Treating Appendicitis With Antibiotics

Antibiotics, when combined with surgery, are a standard part of treatment. But can antibiotics alone reliably treat appendicitis?

Intravenous (IV) antibiotics are often given to fight infection following an appendectomy for a ruptured appendix. Supachok Pichetkul/Getty Images

Your appendix — a small pouch connected to your large intestine — can become inflamed and filled with bacteria and pus, resulting in a painful condition called appendicitis. If appendicitis isn’t treated promptly, your infected appendix will rupture, releasing its bacteria into the rest of your abdomen and leading to a potentially life-threatening infection.

Surgery to Treat Appendicitis: Appendectomy

Appendectomy, a surgical procedure to remove the appendix, is the standard treatment for appendicitis. But antibiotics are often used in conjunction with an appendectomy and sometimes instead of the surgery if the case is uncomplicated.

Doctors have been treating appendicitis with appendectomies for more than 100 years. (1)

If you undergo either an open or laparoscopic appendectomy, you can expect to leave the hospital one or two days after surgery (an open appendectomy requires one two- to four-inch incision, while a laparoscopic appendectomy requires three small incisions). Some laparoscopic appendectomies are even performed on an outpatient basis. (2) Full recovery is relatively quick (several weeks), and few postoperative complications occur. Most patients don’t need to make lifestyle or diet changes after the operation. (3)

Before conducting an appendectomy, surgeons usually give their patients prophylactic broad-spectrum antibiotics, which work against a wide range of bacteria. (4)

Antibiotics Used for Treating Appendicitis

The antibiotics used for appendicitis, particularly Cefotan cefotetan and cefotaxime (Claforan, Mefotoxin), help prevent wound infections after surgery.

Other antibiotics used for appendicitis include:

  • Zosyn (piperacillin and tazobactam)
  • Unasyn (ampicillin and sulbactam)
  • Timentin (ticarcillin and clavulanate)
  • Rocephin (ceftriaxone)
  • Maxipime (cefepime)
  • Gentamicin Gentacidin, Garamycin
  • Merrem (meropenem)
  • Invanz (ertapenem)
  • Flagyl (metronidazole)
  • Cleocin (clindamycin)
  • Levaquin (levofloxacin)

In the case of a ruptured appendix, doctors will prescribe an intravenous (IV) antibiotic to treat abdominal infection — such as peritonitis, a serious infection of the peritoneum membrane that lines your abdominal cavity — after removing your appendix.

Your doctor may decide to follow that up with several weeks of an oral antibiotic that you take at home, but research suggests that three to five days of IV antibiotics are enough, according to a March 2014 report in the Scandinavian Journal of Surgery. (4)

Doctors often opt for a so-called interval appendectomy if a patient has a ruptured appendix. In this case, you will be treated with several days of IV antibiotics and then may be sent home with an oral antibiotic. Some research has suggested that IV treatment alone in the hospital is sufficient. After an interval of six to eight weeks, if your infection has cleared up, you will undergo an appendectomy.

Are Antibiotics Alone Enough for Appendicitis?

In recent years, some research has suggested that appendectomies aren’t necessary to treat uncomplicated appendicitis, which is appendicitis without a ruptured appendix, pus-filled abscesses, or peritonitis. Instead, an antibiotic-only treatment can do the trick. In clinical trials, patients with uncomplicated appendicitis who were treated only with antibiotics required fewer doses of narcotics, returned to work quicker, and did not have a higher perforation rate than those who underwent an immediate appendectomy. (5)

Although there’s increasing evidence to support this approach in uncomplicated appendicitis, there are nevertheless concerns. Uncomplicated appendicitis can be hard to reliably distinguish from complicated appendicitis, and sometimes the complexity of a case isn’t determined until the time of surgery. (5) And as the American College of Surgeons notes, there’s a higher chance of recurrence with antibiotic-only treatment. (6)

Up to 63 percent of patients who receive antibiotic-only treatment for acute uncomplicated appendicitis, which comes on quickly, need no additional treatment for at least a year, according to a 2012 study in BMJ, which consisted of a meta-analysis of four controlled trials involving 900 patients. Additionally, antibiotic-only treatment is cheaper than surgery and results in 31 percent fewer complications (though appendectomies already have low complication rates), according to the study. (7)

A report published in May 2015 in The New England Journal of Medicine also found that an “antibiotics first” option may be useful for people who have had complications from prior surgery. However, the NEJM report also found that “as many as half the patients so treated will have early treatment failures, and all have a risk of recurrent appendicitis that may ultimately require appendectomy.” (8)

Additionally, about 20 percent of patients who receive antibiotic-only treatment suffer from appendicitis again within a year, according to BMJ. What’s more, 20 percent of those people with recurrences (another case of appendicitis) require treatment for a ruptured appendix and its associated complications. (7)

A study published in June 2015 in The Journal of the American Medical Association (JAMA) found a similar failure rate of antibiotic treatment. In patients with uncomplicated appendicitis (as proved by a CT scan), 27 percent required surgical intervention within a year. Still, most patients receiving antibiotic treatment did not require an appendectomy during the one-year follow-up period, and those who required an appendectomy did not experience significant complications. (9)

A review of studies published in October 2017 in the World Journal of Emergency Surgery considered whether nonoperative treatment should replace appendectomy as first-line treatment based on an analysis of the current evidence. The researchers determined that while nonoperative treatment is “definitely a feasible and effective alternative for uncomplicated appendicitis,” appendectomy remains the “gold standard of treatment” for uncomplicated appendicitis due to its higher rate of treatment efficacy. (10)

Additional reporting by Deborah Shapiro

Surgery, not antibiotics, should remain first-line treatment for appendicitis: study

Credit: CC0 Public Domain

Treating appendicitis with antibiotics as an alternative to surgical removal of the inflamed organ was found to be more costly in the long term and result in higher rates of hospital readmissions, according to a study by researchers at the Stanford University School of Medicine.

“People treated with antibiotics alone have a higher chance of coming back needing further treatment for appendicitis-related problems, such as abdominal abscesses,” said Lindsay Sceats, MD, a surgical resident and lead author of the study. “They also have a higher risk of having a reoccurrence, and the cost is no lower.”

The study will be published Nov. 14 in JAMA Surgery. Kristan Staudenmayer, MD, associate professor of surgery, is the senior author.

Appendicitis is an inflammation of the appendix, a finger-shaped pouch that projects from the colon on the lower right side of the abdomen. Acute appendicitis, if left untreated, can result in a ruptured appendix that can spread infection throughout the abdomen and be life-threatening. It occurs in about 5 percent of the United States population, according to the National Institutes of Health, and is most common before the age of 30.

While appendectomy, the surgery to remove the appendix, has long been the standard treatment, some physicians have begun offering drug therapy as an alternative, primarily to patients who are poor candidates for surgery, following the publication of several European studies showing positive outcomes.

“More and more patients in the Stanford emergency room have been asking about whether they can just take antibiotics when they come in with appendicitis instead of having surgery,” Sceats said. This study was designed, in part, to help answer those questions.

Analyzing claims data

To conduct the study, researchers used claims data from a private insurance database to compare patients admitted with appendicitis from 2008 through 2014. Of the 58,329 patients with appendicitis, 55,790, or 95.5 percent, underwent appendectomy. The remaining 4.5 percent were treated with drug therapy alone.

Results showed that, surprisingly, overall costs were 5.5 percent higher for patients who didn’t have the surgery. The average cost of care was $14,932 for these patients. For patients who underwent the surgery, the average cost of care was $14,186.

“Even if the initial hospitalization is cheaper, when you look at long-term cost, which our study did, it ends up being more expensive,” Sceats said. The study collected medical care data for patients after treatment for up to an average of three years.

“People treated with antibiotics are more likely to come back and be hospitalized for any sort of belly pain,” Sceats said. “Doctors may also be more cautious when the appendix isn’t removed. This extra caution can be expensive.”

The study also found slightly higher rates of abdominal abscess post-treatment for those who didn’t have surgery.

Low reoccurrence rate

The study did show that the reoccurrence of appendicitis is only 3.9 percent among those treated with antibiotics alone and pointed out that surgery comes with its own risks of postoperative complications, but the authors concluded that overall results suggest appendectomy should remain the first-line treatment for most people with appendicitis

“These results tell us that, in most cases, surgery is still the best strategy,” Sceats said. “For your average, healthy 30-year-old, the alternative treatment is no cheaper, and it’s easier to have the surgery. You also no longer have an appendix, so you’re no longer at risk of having appendicitis again.”

Explore further

Antibiotics for appendicitis? Surgery often not needed Journal information: JAMA Surgery Provided by Stanford University Medical Center Citation: Surgery, not antibiotics, should remain first-line treatment for appendicitis: study (2018, November 14) retrieved 2 February 2020 from https://medicalxpress.com/news/2018-11-surgery-antibiotics-first-line-treatment-appendicitis.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

I Chose Antibiotics to Treat Appendicitis and Lived to Tell

I did my best to make small talk with the Uber driver even though the pain made it difficult. It occurred to me it might be a bit rude to task a stranger with getting me to the hospital, and I’d better be polite just in case I expired in his back seat.

A dull pain

My gastrointestinal distress had started mildly 12 hours earlier. I thought the odd, uncomfortable feeling around my diaphragm was just gas from my attempt at healthier eating—carrot noodles—at dinner. Too much fiber, I guessed.

An hour later, I blamed gluten. It is often the cause of troubles in the bathroom, thanks to living with celiac disease. Stomach issues are a part of my life and typically no cause for alarm. A hot water bottle and a good night’s sleep were what I thought would help, so I went to bed.

Followed by vomiting

Then the odd uncomfortable feeling became agonizing. I needed to vomit, but not because I felt nauseated. It just hurt so much that throwing up felt like the right thing to do.

I started Googling around 4 a.m. as my body refused to sleep. The usual suspects (food poisoning, gallstones, pancreatitis and appendicitis) appeared. In denial, I continued to blame gluten and thought about visiting urgent care in the morning—just in case.

I spent the next several hours curled in the fetal position. My attempts at vomiting the pain away weren’t effective. Morning arrived; I felt optimistic and tried to take the dog for a walk before I headed to urgent care. I was sure they’d tell me it was my celiac disease.

Sharp pain, lower right side

I made it across the street before I realized a walk was a bad idea. I was reminded of my former boss who tried to go for a run before being rushed to the hospital with appendicitis. This memory coupled with the increasing pain on my right side made me realize I should probably bypass urgent care and go straight to the emergency room.

By the time I made it to University of Washington Medical Center (thank you, Uber driver), it was hard to keep it together (i.e. not cry in public). I work for UW Medicine, so I felt a duty to behave as I would at the office. (This went out the window when I attempted to navigate wearing a hospital gown on pain medication.)

A diagnosis

I would end up being in the emergency department for nearly 11 hours having diagnostic tests and being treated. I had all of the typical symptoms of appendicitis: pain in the right lower side, high white blood cell count and fever. But my appendix was hard to visualize on the ultrasounds. Was a possible ovarian cyst shown in the CT scan the actual culprit? Could it be a dilated fallopian tube instead of a dilated appendix? I learned appendicitis can be difficult to diagnose.

After a bonus pelvic ultrasound to rule out cyst and fallopian tube troubles, I was diagnosed with appendicitis and it was time for a surgical consult.

Then a choice

I was expecting to be wheeled away, “Grey’s Anatomy”-style, into the operating room. Instead, I was offered the choice of trying antibiotics first and avoiding surgery.

If I chose the antibiotics-first approach, I’d receive intravenous antibiotics in the ED and be sent home with a course of oral antibiotics. My best case scenario was being out of pain the next day (Sunday) and back to work on Monday. Worst case scenario, I wouldn’t get better and would have to undergo an appendectomy anyway. I might also have “unpleasant” side effects from the drugs.

Choosing surgery meant a longer recovery time, but by removing my appendix, I wouldn’t have to worry about another episode of appendicitis. However, even a simple, minimally invasive surgery like an appendectomy comes with the risk of complications—from skin infection to abdominal abscess to scar tissue causing a bowel obstruction (yikes!) sometime down the road.

Vanity for the win

I’d like to say I intelligently weighed the pros and cons and made my decision based on facts alone, but it was vanity that won out. I wanted to continue going to my boot camp exercise classes and didn’t want stomach stiches and scars during summer swimsuit season.

After I finished my IV antibiotic treatment, I was released and sent home with pain medication and a weeklong course of heavy duty antibiotics used to treat a range of intestinal and bacterial infections. I still had pain the next morning, but it was more soreness than a “total takeover of my gut” pain. The antibiotics appeared to be working.

There may be some side effects

In the end, I landed somewhere in between the best and worst case scenarios. The antibiotics made me feel awful. I did indeed develop some “unpleasant” side effects, including insomnia and a disgusting metallic taste that took a few days to go away after I finished the medication. I missed three days of work and an outing with friends.

But, it worked and I’m still OK. I avoided the scalpel, the scars and likely a larger hospital bill. I can be considered a positive statistic in the antibiotics-first approach.

Can you treat appendicitis with antibiotics instead of surgery?

One of the options for managing mild to moderately severe appendicitis that is unlikely to be associated with major perforation of the appendix or complications is treatment with antibiotics but no surgery. Patients often resolve their inflammation with antibiotics alone, but it has not been clear how many respond to antibiotics alone and what happens to them in the longer term, that is, over the ensuing weeks, months, or years. Specifically, does appendicitis recur and/or is surgery ultimately required?

A Swedish study looked specifically at these questions. The study randomized 252 men ages 15-50, to surgery or antibiotic treatment alone, excluding patients with a high suspicion of major perforation or complications. The antibiotic-treated patients received intravenous antibiotics for two days and then were switched to oral antibiotics for 10 days. Antibiotic-treated patients who did not respond within 24 hours to the antibiotics went to surgery immediately.

How effective are antibiotics in treating appedicitis?

Fifteen antibiotic-treated patients did not respond to antibiotics alone (12% of patients) and went to surgery after 24 hours. The number of patients who experienced a major perforation identified at the time of surgery were the same in the surgery-treated group and the antibiotic treated group, namely 5%, suggesting that waiting 24 hours to see if antibiotics alone would work did not result in more perforations. Most of the antibiotic-treated patients (88%) recovered without surgery, demonstrating that antibiotics are very effective for treating mild to moderate appendicitis. Within the following five years, almost one-quarter (24%) of the patients who responded to antibiotics alone developed a second episode of appendicitis with most of the recurrences during the first year. (All of the recurrences were treated with surgery.)

What is the recurrence rate of appendicitis treated with antibiotics?

A rate of recurrence of 24% is not high, but it also is not negligible. How can the findings of this study be used? First, the findings suggest that if there are reasons to postpone surgery, antibiotics alone are a satisfactory way to treat mild to moderate appendicitis without complications. Whether or not a 24% rate of recurrence is enough reason to undergo elective surgery–after the appendicitis has resolved with antibiotics alone and before it has a chance to recur–probably will be a choice made by individual patients. For some, the risk of recurrence will be acceptable and they will not opt for elective surgery. For others the risk will be too great not to undergo elective surgery. It is important to remember that the results of this study apply only to younger patients (ages 15-50) with mild to moderate, uncomplicated appendicitis. Although the study was limited to men, there is no reason to believe that the results would be different in women.

CONTINUE SCROLLING FOR RELATED SLIDESHOW

US Pharm. 2013;38(12):HS14-HS20.

ABSTRACT: Appendicitis is an inflammation of an obstructed appendix that may become infected, gangrenous, and perforated. Classically, it presents as abdominal pain that is often accompanied by nausea and vomiting. Appendicitis is the most common cause of abdominal surgery in children, with the highest incidence during the second decade of life. A ruptured appendix, however, is more common in younger children. There is no one diagnostic measure that is specific for appendicitis, and in many cases, a wrong diagnosis may be made, particularly in children. The condition can be managed with antibiotics as well as an appendectomy, if necessary.

Appendicitis is the most common cause of abdominal pain requiring surgical intervention, and the most common reason for emergent abdominal surgery in children.1-3 An individual’s lifetime risk for developing appendicitis is about 7%, and out of all the children who present to the emergency department with abdominal pain, 1% to 8% have appendicitis.1,3 In the United States, the current incidence of appendicitis is 86 per 100,000 patients per year, with 80,000 hospitalizations and more than one-third of hospital days for abdominal pain annually in patients under the age of 18 years.2,4 While appendicitis can affect all ages, including infants, the incidence is higher in the second decade of life.1 Moreover, the condition is slightly more common in males than females.1

Appendicitis with rupture (perforated appendicitis) is associated with a more severe clinical illness, higher morbidity, and longer hospital stays than non-perforated appendicitis.2 A ruptured appendix is common in young children, with rates as high as 100% for children under 1 year, reducing to about 82% for children between the ages of 1 and 5 years.5 The mortality rates for appendicitis ranges between 1% and 5% for young and elderly patients.6 This is partly due to the fact the younger children are unable to express themselves, and it is often assumed that they are suffering from gastroenteritis.

PATHOPHYSIOLOGY

The appendix is a long, thin diverticulum located on the posteromedial surface of the cecum, approximately 3 cm below the ileocecal valve.1,3 Its length varies from 8 to 13 cm in adults, and in children it averages around 4.5 cm.1,3 There is no known function of the appendix to date.1

Appendicitis occurs when the lumen of the appendix between the cecal base and the tip is occluded by fecaliths, adhesions, lymph node hyperplasia, foreign bodies, parasites, or, in rare cases, tumors.7,8 This obstruction causes the intraluminal pressure within the appendix to increase as mucosal secretions accumulate, leading to appendiceal distension and inhibiting lymphatic and venous drainage.1 The visceral afferent nerves that enter the spinal cord at T8 and T10 level are stimulated as a result of the distension, leading to a dull epigastric or periumbilical pain.1 A progressive condition causes overgrowth and translocation of bowel flora and leads to an acute inflammatory infiltrate in the wall of the appendix.1,2 As inflammation within the appendiceal serosa continues, it irritates the local somatic fibers on the parietal peritoneum, which leads to more localized pain. Within 24 to 36 hours of symptom onset, the appendix becomes gangrenous and is at risk for perforation, abscess formation, and peritonitis.9-11

ETIOLOGY AND RISK FACTORS

The organisms most commonly isolated from perforated appendicitis include Escherichia coli, alpha-hemolytic streptococci, Bacteroides species (e.g., Bacteroides fragilis), Bilophila wadsworthia, and Peptostreptococcus species.2 Various factors may increase or decrease a patient’s risk of developing appendicitis or perforation, which are detailed in TABLE 1.1-3

PRESENTATION

Classical appendicitis is characterized by constant pain that is poorly localized to the periumbilical or epigastric region.1 The pain is often accompanied by anorexia, nausea, and vomiting.1 As the condition progresses, the pain migrates towards the right quadrant at the area of the McBurney point and may be accompanied by low-grade fever.1 The McBurney point is one-third of the distance between the right anterior superior iliac spine to the umbilicus.2 Initially, the patient’s body temperature is normal or slightly increased, but fever develops as disease progresses.1

The clinical presentation may vary depending upon the location of the appendix, the host response to infection, and the age of the patient. Patients complaining of pain in the right flank, pelvis, testicle, suprapubic region, or even left lower quadrant (if the appendix crosses the midline) should be investigated for appendicitis.1 Furthermore, symptoms such as dysuria, increased urinary frequency, diarrhea, and tenesmus may be the result of appendicitis in patients whose appendix is in a slightly different location.12

A positive Rovsing sign (pain in the right lower quadrant when the left lower quadrant is pressed) is often a sign of appendicitis.1 However, the sensitivity and specificity of the Rovsing sign, psoas sign (abdominal pain that results when the patient flexes the thigh at the hip), and obturator sign (pain upon flexion and internal rotation of the hip), which are useful for diagnosis in adults, are not well established in children.1,2 Furthermore, patients suffering from appendicitis often display rebound tenderness or guarding as a result of the inflamed parietal peritoneum.1

It is important to note that while the classic presentation is fairly well established in adults, the signs and symptoms of appendicitis in children deviate greatly from the classical description.5 Furthermore, the child’s clinical condition varies in severity and clinical presentation.5 Anatomical and developmental differences contribute to age-based differences in pediatric appendicitis.2 Children’s appendices are less likely to be attached to the cecum, the ascending colon, or the abdominal wall, and, therefore, the appendix tends to be more mobile.2

In children under the age of 2 years, vomiting, abdominal pain, fever, abdominal distension, diarrhea, irritability, right hip pain, and limp are the most common symptoms.3 Physical findings include diffuse tenderness and fever.3 In children between the age of 2 and 5 years, abdominal pain precedes vomiting and is usually associated with fever and anorexia as well as right lower quadrant tenderness, fever, and involuntary guarding.2

Infants and toddlers commonly experience tenesmus that may be misdiagnosed for diarrhea.13 School-aged children describe abdominal pain that is constant and worsens with movement or coughing as well as nausea, vomiting, anorexia, tenesmus, and dysuria.3 They tend to have localized right lower quadrant tenderness or diffuse guarding and rebound tenderness.

The incidence of appendicitis peaks in adolescence and the late teen years.3 In females of childbearing age, pelvic pathology is easily confused with appendicitis. Appendicitis in older children may present as the feeling of hunger.3

DIAGNOSIS

Acute abdominal pain can be the result of many disorders including appendicitis, so it is useful to rule out the following diagnoses: infectious gastroenteritis, cholecystitis, right hip septic arthritis, pneumonia, urinary tract infection (UTI), mesenteric adenitis, intussusception, inflammatory bowel disease, Meckel’s diverticulum, hernia, primary peritonitis, orchitis, testicular torsion, blunt abdominal trauma, and ovarian cysts (females).2

A delay in diagnosis and treatment, possibly due to a difficulty in establishing a diagnosis or lack of access to healthcare services, substantially increases morbidity, length of hospital stay, and cost.3,14 Children are at a particularly higher risk of delayed diagnosis of appendicitis and its complications.1 This population may initially be misdiagnosed with gastroenteritis, UTIs, otitis media, or respiratory tract infections, resulting in increased perforation rates and hence longer hospital stays.15-17 A high index of suspicion is necessary during evaluation, and appendicitis should be considered as a differential diagnosis of abdominal pain.1 It is important to note that there is no single test specific for appendicitis.

Laboratory Tests

It has been shown that either the white blood cell (WBC) or neutrophil percentage is elevated in 90% to 96% of children with appendicitis.3 However, WBC counts are a useful but poor predictor of appendicitis on their own since elevations are also noted in nearly half of all patients with gastroenteritis, mesenteric adenitis, pelvic inflammatory disease, and other infectious disease.3 Furthermore, WBC or neutrophil counts do not discriminate between perforated and nonperforated appendicitis.3

The C-reactive protein (CRP) count has a low (43%-92%) sensitivity and low specificity (33%-95%) in children with acute abdominal pain.1,3 The combination of the WBC and CRP counts is a fairly accurate test for appendicitis in adults, but not in children.1,2 A urinalysis may be conducted to test for pyuria and hematuria, UTI, or nephrolithiasis.2

Imaging Studies

While newer modalities are increasingly used over the traditional WBC and CRP tests, some healthcare professionals feel that these tests increase costs but not accuracy.3 Plain film or radiography has limited use in the detection of appendicitis and is misleading in about 82% of children.3 Radioisotope-labeled WBC scanning in children shows sensitivity of about 27% to 97% and specificity of 38% to 94%. This procedure is lengthy and prone to poor interpretation agreement. Moreover, many emergency centers are unfamiliar with this technique.3

An ultrasound is particularly useful in children in whom harmful ionizing radiation is to be avoided.1 It is sensitive and specific for appendicitis (90%-95%) but may give a false negative if the appendix is perforated.18 In some cases, the appendix may not be visible at all on an ultrasound even if the sonographer is highly experienced.1

CT scans are widely available and can detect other abdominal disorders.1 A CT scan has a sensitivity (92%-97%) and specificity (98.6%-99%) that are higher than ultrasound in both adults and children.2,3 However, a CT scan exposes patients to radiation and delays diagnosis.1 MRI techniques are also useful since they avoid the use of radiation and contrast.3

Clinical Scores

The Alvarado or MANTRELS score (Migration to the right iliac fossa, Anorexia, Nausea/vomiting, Tenderness in the right iliac fossa, Rebound pain, Elevated temperature, Leukocytosis, and Shift of leukocytes to the left) has been adapted for use in children and named the Pediatric Appendicitis Score (PAS). It is used to determine the likelihood that a child has appendicitis (TABLE 2).19

TREATMENT

The choice of treatment depends upon the severity of the condition as well as the patient’s general condition. Children with appendicitis are frequently dehydrated and may be febrile, acidotic, and septic.5 If appendicitis is suspected, the child should receive nothing by mouth and be started on IV volume replacement.3 Adequate hydration is important for patients with suspected appendicitis, and in many cases IV fluids may be required even after an appendectomy.20 Broad-spectrum IV antibiotics effective against enteric aerobes and anaerobes should be administered immediately to all children with obvious perforation.3 Appendectomy is performed in nonperforated appendicitis and in some cases on perforated appendicitis.21 Analgesics may be administered for symptomatic relief and antiemetics for vomiting.1

Appendectomy

An appendectomy is a definitive treatment for appendicitis that can be performed using either laparoscopy or open technique. It is indicated in all patients that have early, nonperforated appendicitis. However, in cases where the appendix is perforated, an appendectomy may provide no further benefit and may be avoided altogether.5 Percutaneous drainage may be required in patients who develop an intra-abdominal abcess.22

Antibiotic Therapy

Antibiotic therapy is an important aspect of the management of ruptured (perforated) appendicitis.20 IV antibiotics that are effective against enteric gram-negative organisms and anaerobes including E coli and Bacteroides species should be initiated as soon as the diagnosis of appendicitis is established.1,20 If an appendectomy is required, preoperative antibiotics therapy may be continued to prevent postoperative infections. These can be stopped postoperatively if the appendix is not found to be gangrenous or perforated during the operation.20 In cases where the appendix is gangrenous, postoperative antibiotic therapy should be continued for 24 to 72 hours and for a minimum of 7 to 10 days if the appendix is ruptured. Postoperative antibiotics can be administered orally if the patient is otherwise well enough to be discharged.20

A single antibiotic is sufficient for a nonperforated appendicitis. Second- or third-generation cephalosporins such as cefoxitin or cefotetan are used in uncomplicated cases.1 Broader-spectrum coverage is obtained with piperacillin-tazobactam, ampicillin-sulbactam, ticarcillin-clavulanate, or imipenem-cilastatin.23 For perforated appendicitis, the most common combination is ampicillin, clindamycin (or metronidazole), and gentamicin.20 Alternatives include ceftriaxone-metronidazole or ticarcillin-clavulanate plus gentamicin. Antibiotic dosing is provided in TABLE 3.24-32

Penicillins: Bactericidal antibiotics inhibit the biosynthesis of cell wall mucopeptide. They are used in combination with beta-lactamase inhibitors in the management of appendicitis for extended coverage. These agents include:

  • Ampicillin-sulbactam (beta-lactamase inhibitor), which demonstrates activity against some gram-positive, gram-negative, and anaerobic bacteria.24 It is available as a combination in a ratio of 2:1 (ampicillin:sulbactam)
  • Piperacillin-tazobactam, which is useful against gram-positive, gram-negative, and anaerobic bacteria25
  • Ticarcillin-clavulanate, which is effective against most gram-positive and gram-negative bacteria and most anaerobes26
  • Imipenem-cilastatin, which can be used for the treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of the potential for toxicity.27

The most common side effects seen with penicillins are hypersensitivity reactions, which can give rise to a number of clinical syndromes including anaphylaxis, angioedema, and urticarial and maculopapular rashes in the early stages and serum sickness–like reactions and hemolytic anemia in later stages.22

Large IV doses of penicillins may be associated with hemolytic anemia and neutropenia.22 Gastrointestinal (GI) effects are common with oral administration. Patients receiving high doses or long courses of beta-lactams are at risk of neutropenia. Healthcare professionals should watch out for fever, rash, and eosinophilia.22

Aminoglycosides: These antibiotics are employed primarily to treat gram-negative infections. They bind to the 30S and 50S subunits of bacterial ribosomes and achieve their bacteriostatic effects by interfering with bacterial protein synthesis.

Gentamicin is effective against gram-negative bacteria including pseudomonads, and works synergistically with beta-lactams against enterococci.28 The dose of gentamicin needs to be adjusted based on the creatinine clearance and changes in volume of distribution. This drug may be administered intravenously or intramuscularly.28

Aminoglycosides can produce irreversible, cumulative ototoxicity that can affect both the cochlea and the vestibular system, resulting in hearing loss and dizziness, respectively.22 Other side effects include reversible nephrotoxicity, acute renal failure, respiratory depression, muscular paralysis, and hypersensitivity reactions. Concurrent use of nephrotoxic drugs as well as those that can cause neuromuscular blockage should be avoided.22

Metronidazole: This synthetic nitroimidazole derivative antibacterial and antiprotozoal agent is often used in combination with aminoglycosides and provides broad gram-negative and anaerobic coverage.29 Metronidazole in combination with aminoglycosides may be given orally or intravenously.

Metronidazole is associated with dose-related GI disturbances, including nausea, unpleasant taste in the mouth, vomiting, and diarrhea.22 Weakness, dizziness, ataxia, headache, drowsiness, insomnia, and changes in mood or mental state may occur. Some patients experience peripheral neuropathy and complain of tingling or numbness in the extremities.22

Clindamycin: This lincosamide is effective against gram-positive aerobic and anaerobic bacteria, except enterococci.30 The drug inhibits bacterial growth by binding to the 50S subunit of the bacterial ribosome and halting protein synthesis.

Clindamycin can cause GI side effects including diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal pain, cramps, and an unpleasant or metalling taste in the mouth following the IV administration of high doses. Hypersensitivity reactions, leukopenia, and agranulocytosis have all been reported in patients taking clindamycin.30

Cephalosporins: Cefoxitin is a second-generation cephalosporin with activity against some gram-positive, gram-negative (non-Pseudomonas species), and anaerobic bacteria.31 Cefotetan is also a second-generation cephalosporin effective against gram-positive and gram-negative cocci.32 The side effects associated with cephalosporins are very similar to those with penicillins. Furthermore, patients who are hypersensitive to one group of antibacterials are highly likely to react to a drug from the other group, particularly penicillins and cephalosporins.

CONCLUSION

Despite the availability of effective therapies for the management of appendicitis, pediatric mortality rates remain high. This is mainly due to poorly developed diagnostic tools, particularly for young children. There is no one test that is specific for the diagnosis of appendicitis. Further investigation of diagnostic techniques as well as the development of guidelines for the management of this condition may assist in reducing complications in children.

To comment on this article, contact [email protected]uspharmacist.com.

Signs of a Ruptured Appendix and What to Expect After Treatment

The symptoms of appendicitis can be similar to those of other conditions that affect the abdomen, such a stomach flu or ovarian cyst. For this reason, it can be hard to tell if you have appendicitis.

If you have these symptoms and think you have appendicitis, get evaluated by a doctor as soon as possible. Prompt treatment is essential to avoid rupture. Rupture can occur within 36 hours of the onset of symptoms.

The classic symptoms of appendicitis are pain starting around the belly button followed by vomiting. Several hours later, the pain moves to the lower abdomen on the right side.

One study found only about half of the people who get appendicitis have these classic symptoms.

Other symptoms of appendicitis include:

  • fever
  • nausea and vomiting
  • abdominal pain that may start in the upper or middle abdomen but usually settles in the lower abdomen on the right side
  • abdominal pain that increases with walking, standing, jumping, coughing, or sneezing
  • decreased appetite
  • constipation or diarrhea
  • inability to pass gas
  • bloated or swollen abdomen
  • abdominal tenderness when you push on it that may worsen when you quickly stop pressing on it

The pain is often spread out all over the abdomen in babies and children. In pregnant and older people, the abdomen may be less tender and pain may be less severe.

Once your appendix ruptures, symptoms vary depending on what happens. At first, you may actually feel better for a few hours because the high pressure in your appendix is gone along with your original symptoms.

When bacteria leave the intestine and enter the abdominal cavity, the lining on the inside of your abdomen and outside of abdominal organs become inflamed. This condition is called peritonitis. It’s a very serious condition that can be very painful and requires immediate treatment. The symptoms will be similar to those for appendicitis, except:

  • the pain is in your entire abdomen
  • the pain is constant and more severe
  • fever is often higher
  • your breathing and heart rate may be fast in response to the severe pain
  • you may have other symptoms including chills, weakness, and confusion

When there’s an infection in your abdomen, the surrounding tissues sometimes try to wall it off from the rest of the abdominal cavity. When this is successful, it forms an abscess. This is a closed off collection of bacteria and pus. Symptoms of an abscess are also similar to those for appendicitis, except:

  • the pain may be in one area, but not necessarily the lower right abdomen, or it may be in your entire abdomen
  • the pain can be either a dull ache or sharp and stabbing
  • fever is usually persistent, even when you take antibiotics
  • you may have other symptoms, like chills and weakness

When left untreated, the bacteria from a ruptured appendix can get into your bloodstream, causing a serious condition called sepsis. This is inflammation that occurs throughout your entire body. Some of the symptoms of sepsis are:

  • fever or a low temperature
  • fast heartbeat and breathing
  • chills
  • weakness
  • confusion
  • low blood pressure

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial

Trial design

The Antibiotics following aPPendectomy In Complex appendicitis (APPIC) trial is a phase IV, prospective, multicenter, non-blinded, randomized controlled trial powered for non-inferiority. Patients are randomly allocated to a short course of 48 h (intervention arm), or the standard course of 5 days (control arm) of IV antibiotics following appendectomy for complex appendicitis. An overview of enrollment, interventions, and follow-up of participants in the APPIC trial is shown in Fig. 1. Figure 2 shows the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) Figure. The SPIRIT Checklist is shown in Additional file 1.

Fig. 1

APPIC flowchart of inclusion and randomization. Legend: * All except intraoperative criteria regarding type of appendicitis; ** If the patient has not been able to give informed consent prior to appendectomy, this may still be acquired postoperatively, as long as inclusion and randomization takes place within 24 h; *** Intravenously administered antibiotic treatment continues for three more days to complete 5 days in total

Fig. 2

APPIC schedule of enrollment, interventions, and assessments

Trial setting

The trial will run in at least 14 hospitals in the Netherlands. This includes one academic hospital and 13 teaching hospitals. The participating hospitals are listed on the trial webpage (www.appictrial.nl). In all participating hospitals appendectomy is mostly performed laparoscopically.

Eligibility criteria

Patients of at least 8 years of age who are scheduled to undergo surgery for suspected acute appendicitis will be approached for participation in the study. If a complex appendicitis is diagnosed intraoperatively, patients are eligible for inclusion. A complex appendicitis is defined as a gangrenous and/or perforated appendicitis or any appendicitis in presence of an IAA . Written informed consent is preferably obtained before surgery, but may be obtained postoperatively as long as inclusion and randomization is performed within 24 h after surgery. Exclusion criteria are:

  • Unable to give informed consent (language barrier, legally incapable)

  • Interval appendectomy

  • Clinical suspicion of severe sepsis*

  • Conservative treatment of acute appendicitis

  • American Society of Anesthesiologists (ASA) score IV or not able to undergo surgery

  • Known allergy or other contraindication to study medication*

  • Immunocompromised patients*

  • Pregnancy

  • Concurrent use of antibiotics for other indication*

  • Simple acute appendicitis*

  • Appendicular infiltrate not amendable for appendectomy

  • Inadequate source control in opinion of the surgeon*

* more elaborate definitions are given in the full study protocol.

Interventions

Postoperative antibiotic treatment

Participants will be randomized (1:1) to receive either: (1) a short course of 48 h or (2) a standard 5-day course of postoperative antibiotic treatment. All patients receive IV antibiotics during the first 48 h after appendectomy: cefuroxime/metronidazole (three times a day, 1500/500 mg), or alternatively ceftriaxone/metronidazole (once a day, 2000 mg/three times a day, 500 mg) according to local antibiotic policy. In the control group the IV antibiotics are continued for three more days (a switch to an oral formula is not allowed). A daily dose of gentamicin as co-intervention is optional. No other antibiotics are permitted.

Criteria for modifying the allocated treatment

Antibiotic treatment may be prolonged or restarted only in case of a proven source of infection (a decision algorithm is provided in the full protocol). A switch to a different antibiotic regimen is allowed only if necessary due to an adverse reaction to the antibiotics or if indicated by culture results (if a micro-organism resistant to cefuroxime (or ceftriaxone) is cultured a switch should be made to ensure effective antibiotic treatment).

Discharge and follow-up

Laboratory tests, imaging studies, and blood cultures will be performed only when clinically indicated. The following clinical parameters will be registered on a daily basis: body temperature < 38° Celsius, able to tolerate oral intake, able to mobilize independently; Visual Analog Scale (VAS) < 4 requiring only orally administered analgesia. However, these criteria are not mandatory for discharge and ultimately the responsible physician decides when a patient is able to go home. After discharge a standard outpatient visit is planned at 2 to 4 weeks according to local hospital policy. Four weeks after appendectomy, patients are asked to complete a productivity-cost questionnaire. At 90 days after appendectomy a standardized follow-up by telephone will be conducted.

Outcome measures

All outcome measures will be registered directly from the electronic patient files. Outcome assessors will not be blinded for the treatment allocation. The telephone follow-up is introduced to check missing data on the primary endpoint; e.g., visits to hospitals or medical facilities other than the center where the patient was treated and included into the trial.

Primary outcome measure

The primary endpoint of this trial is a composite endpoint of infectious complications related to appendectomy, including IAA and surgical site infection (SSI), and mortality within 90 days after appendectomy. An IAA is defined as an infection that involves the abdominal part of the body deeper than the fascial/muscle layers that is opened or manipulated during the operative procedure. IAA can be diagnosed through imaging or during reintervention, through purulent drainage from a drain placed into the IAA, or isolation of organisms from a culture of the IAA . An SSI can be either deep or superficial, involving the skin, subcutaneous tissue and/or deep soft tissues of the incision. IAA and SSI are defined in more detail according to the Center for Disease Control (CDC) criteria in the full study protocol .

Secondary outcome measures

Secondary endpoints are separate rates of IAA, SSI and mortality; duration of antibiotic treatment; the antibiotic regimen; proportion of patients that restarted antibiotics; length of hospital stay (LOS); time to fulfill discharge criteria; postoperative complications; reoperation; percutaneous drainage; number of visits to the general practitioner (GP), emergency room (ER) and outpatient clinic; readmission rate; adverse events on antibiotics; and cost-effectiveness. Complications will be classified according to the Clavien-Dindo classification of surgical complications as well as the Comprehensive Complication Index (CCI). To analyze cost-effectiveness, the validated Institute for Medical Technological Assessment – Productivity Cost Questionnaire (iMTA-PCQ) (version October 2012) will be used, enhanced with a section concerning school absence.

Sample size calculation

A power analysis was performed based on a one-sided 97.5% confidence interval for the effect of study arm (intervention or control), an expected 15% primary endpoint rate and a 7.5% non-inferiority margin. To obtain a power of 90%, 960 patients are needed (480 per treatment arm). To account for possible effects of dropout and missing data (10%) we will recruit 1066 patients. This sample size should also yield sufficient power for the analysis of secondary endpoints.

Recruitment

Recruitment of participants started on 12 April 2017 and is ongoing. Additional participating hospitals may be recruited to ensure feasibility of the trial. The target of 1066 patients is expected to be completed in early 2020.

Allocation

Computerized block randomization (stratified for center) will take place within 24 h after surgery through ALEA, a web-based application managed by the Clinical Trial Center (CTC) of the Erasmus MC. Random blocks of different lengths are used. Eligible patients will be randomized in a 1:1 ratio to arm A (short course) or arm B (standard course). Each patient will be given a unique study number. An independent data manager from the CTC who is not involved with the clinical practice or patient recruiting created the randomization sequence. The result of the randomization and the patient study number will immediately be provided through ALEA per email to all parties predefined in the system who should receive such notifications.

Implementation

Before the start of the trial, each center is visited by the research team to inform and instruct the involved personnel on study-specific procedures. Surgeons and residents are trained how to assess the type of appendicitis to decide whether patients are eligible for study participation by means of recorded examples of all types of appendicitis.

Blinding

Blinding for treatment allocation in this study would not only be difficult to achieve, but is also undesirable because good clinical decision-making during the postoperative course requires specific knowledge of antibiotics that have or have not been given to the patient. Therefore, this is an non-blinded trial.

Data collection and management

A data manager from each participating hospital will carry out the data collection in collaboration with the trial coordinator. Baseline demographics, as well as preoperative, intraoperative and postoperative variables, will be collected from the electronic medical records. The validated iMTA-PCQ will be used for cost analysis. A list of all variables is provided in the full study protocol. All data will be entered into the secure online ALEA database, a system validated and supported by the Erasmus University Medical Centre. Data will be handled confidentially and anonymously. A short intraoperative video or static picture(s) should be recorded for quality assurance of the diagnosis complex appendicitis. Quality control will involve collecting data on adherence to the intervention, patient inclusion and follow-up, as well as monitoring the quality of the data entry. Qualified data managers of the CTC of the Erasmus MC will perform quality control and assurance. Checks and queries will be performed to ensure quality, consistency, and completeness. Missing data and inconsistencies will be reported back to the centers to be clarified by the local responsible investigator.

Statistical analysis

We anticipate a 15% rate of infectious complications and mortality in this study population. A 7.5% difference (non-inferiority margin) in the primary endpoint rate is deemed acceptable between the intervention group and control group. This margin is considered acceptable since mortality is expected to account for a negligible proportion within the primary endpoint and infectious complications after appendectomy can be well treated with minimum morbidity and long-term consequences.

Primary endpoint

The study hypothesis will be tested by a one-sided 97.5% confidence interval for the effect of study group (absolute risk difference). This confidence interval will be adjusted for effects of type of appendicitis and age (as a single categorical covariate: < 16 years old/non-perforated, < 16 years old/perforated, ≥16 years old/non-perforated, ≥16 years old/perforated) using the method proposed by Klingenberg . Non-inferiority will be established if the upper limit of the confidence interval is lower than 7.5%. Both per-protocol and intention-to-treat analyses will be performed. In a secondary analysis, logistic regression analysis will be performed to identify predictors of the composite primary endpoint. Independent variables in this model will include treatment group and also age, sex, surgical approach, type of appendicitis, ASA score, and center, as well as significant interaction effects of these independent variables with treatment group.

Secondary endpoints

General patient characteristics and other clinically relevant parameters will be compared between the intervention group and the control group with the independent samples Student’s t test or the Mann-Whitney test in case of continuous outcome variables and the chi-square or Fisher’s exact test in case of categorical outcome variables where appropriate. All secondary endpoints will be compared between the trial arms using linear regression for continuous outcomes and logistic regression for dichotomous outcomes, with adjustment for age, sex, surgical approach (open versus laparoscopic), type of appendicitis, ASA score, and center. In case of non-normally distributed continuous outcomes, appropriate transformation of these outcomes will be applied. A two-sided significance level of 0.05 will be used for all secondary analyses. Uncertainty with respect to cost-effectiveness will be analyzed by bootstrapping results for incremental costs and health effects. The results will be shown in an acceptability curve that indicates the probability that the intervention meets several cost-effectiveness thresholds.

Data monitoring and safety

An independent safety committee (DSMB) is assembled to monitor trial safety and progress, with special focus on imbalance between the two trial arms in 90-day mortality and serious postoperative complications. The DSMB is composed of a statistician, two surgeons and a microbiologist, all of whom are unrelated to the study and have no conflict of interest with the coordinating investigator of the study. There will be two planned formal safety analyses: after the first 266 included patients have completed follow-up and after 666 patients have completed follow-up. Safety stopping rules will be applied using the alpha spending approach of O’Brien and Fleming, described into more detail in the full study protocol. The DSMB will notify the coordinating and principal investigators if conditions of the stopping rules have been reached. The Steering Committee will decide on continuation of the trial. The DSMB roles, responsibilities, meetings and logistics are outlined in the APPIC trial DSMB Charter.

Independent monitors of the CTC of Erasmus MC will visit participating centers intervals at regular intervals to verify adherence to the protocol and legal requirements and perform source data verification. A first site monitoring visit will take place at each participating hospital after the first three randomized patients have completed follow-up. Subsequent monitoring visits will be planned according to the predefined monitoring plan.

Rationale for the chosen study design

A non-inferiority design is chosen as the objective of this trial is to show that a short course of antibiotics is no less effective than a standard course, in terms of preventing infectious complications. This is relevant in light of several potential advantages of reduced use of antibiotics, such as fewer adverse reactions to antibiotics, shorter length of hospital stay, lower medical care costs and less antimicrobial resistance. In the academic literature, postoperative infectious complications are reported in 15–20% of patients . Furthermore, a similar study by Sawyer et al. was aimed at detecting a 10% difference in complication rates after a shorter course of postoperative antibiotic treatment in complicated intra-abdominal infections . Based on these findings and the fact that a reduction in antibiotic consumption will lead to a significant reduction in costs and antimicrobial resistance, we accept a 7.5% difference (non-inferiority margin) in the primary endpoint rate. A non-inferiority trial with this margin is acceptable based on the assumption that infectious complications after an appendectomy for a complex appendicitis are in general not associated with severe morbidity and/or mortality. Since it is known that treatment with IV antibiotics for 48 h ensures adequate tissue concentrations (to eliminate the relevant micro-organisms such as E. coli) , we have chosen 48 h of IV antibiotics as our intervention. For the individual patient advancing from the regular (3 to) 5 days of antibiotics towards 48 h may not seem an enormous step forward. However, extrapolating this to all patients with complex appendicitis could have a major impact on healthcare. From a methodological perspective, we choose to administrate antibiotics completely intravenously for both the intervention and the control group. Some studies found no support for use of orally administered antibiotics after the initial postoperative intravenous administration . In addition, it is questioned if adequate tissue concentrations can be met by orally administered antibiotics for bacteria commonly isolated in complex appendicitis . Complete intravenous courses will ensure homogenous treatment in both study arms, without patients’ compliance or effectiveness of orally administered antibiotics as uncertainties.

Surgery, not antibiotics, should remain first-line treatment for appendicitis

Treating appendicitis with antibiotics as an alternative to surgical removal of the inflamed organ was found to be more costly in the long term and result in higher rates of hospital readmissions, according to a study by researchers at the Stanford University School of Medicine.

“People treated with antibiotics alone have a higher chance of coming back needing further treatment for appendicitis-related problems, such as abdominal abscesses,” said Lindsay Sceats, MD, a surgical resident and lead author of the study. “They also have a higher risk of having a reoccurrence, and the cost is no lower.”

The study was published Nov. 14 in JAMA Surgery. Kristan Staudenmayer, MD, associate professor of surgery, is the senior author.

Appendicitis is an inflammation of the appendix, a finger-shaped pouch that projects from the colon on the lower right side of the abdomen. Acute appendicitis, if left untreated, can result in a ruptured appendix that can spread infection throughout the abdomen and be life-threatening. It occurs in about 5 percent of the United States population, according to the National Institutes of Health, and is most common before the age of 30.

While appendectomy, the surgery to remove the appendix, has long been the standard treatment, some physicians have begun offering drug therapy as an alternative, primarily to patients who are poor candidates for surgery, following the publication of several European studies showing positive outcomes.

“More and more patients in the Stanford emergency room have been asking about whether they can just take antibiotics when they come in with appendicitis instead of having surgery,” Sceats said. This study was designed, in part, to help answer that question.

Analyzing claims data

To conduct the study, researchers used claims data from a private insurance database to compare patients admitted with appendicitis from 2008 through 2014. Of the 58,329 patients with appendicitis, 55,790, or 95.5 percent, underwent appendectomy. The remaining 4.5 percent were treated with drug therapy alone.

Results showed that, surprisingly, overall costs were 5.5 percent higher for patients who didn’t have the surgery. The average cost of care was $14,932 for these patients. For patients who underwent the surgery, the average cost of care was $14,186.

“Even if the initial hospitalization is cheaper, when you look at long-term cost, which our study did, it ends up being more expensive,” Sceats said. The study collected medical care data for patients after treatment for up to an average of three years.

“People treated with antibiotics are more likely to come back and be hospitalized for any sort of belly pain,” Sceats said. “Doctors may also be more cautious when the appendix isn’t removed. This extra caution can be expensive.”

The study also found slightly higher rates of abdominal abscess post-treatment for those who didn’t have surgery.

Low recurrence rate

The study did show that the recurrence rate of appendicitis is only 3.9 percent among those treated with antibiotics alone and pointed out that surgery comes with its own risks of postoperative complications, but the authors concluded that overall results suggest appendectomy should remain the first-line treatment for most people with appendicitis

“These results tell us that, in most cases, surgery is still the best strategy,” Sceats said.“For your average, healthy 30-year-old, the alternative treatment is no cheaper, and it’s easier to have the surgery. You also no longer have an appendix, so you’re no longer at risk of having appendicitis again.”

Other authors included biostatician Amber Trickey, PhD; Arden Morris, MD, professor of surgery; and Cindy Kin, MD, assistant professor of surgery.

The study was funded by the National Institutes of Health (grants UL1TROO1O85, KL2TROO1O83 and UL1TROO1O85).

Stanford’s Department of Surgery also supported the work.

Image

Antibiotics may be a good option for many cases of appendicitis.

Several randomized trials have shown that treating appendicitis with antibiotics rather than surgery may be safe and effective, but the long-term effects of avoiding an appendectomy have been unclear.

Now in a new study, published in JAMA, researchers did a five-year follow-up of 256 patients who had been randomized in a large trial to receive antibiotics instead of surgery for uncomplicated appendicitis — in which the appendix is not ruptured, there is a low white blood count and there is no fecal blockage.

About 60 percent of the patients never needed an appendectomy. Of the 100 who did eventually need surgery, 70 percent had it in the first year, and none of the 100 had any adverse outcomes related to the delay in performing the operation. The decision to perform surgery was left to the discretion of the treating surgeon, which could have resulted in more operations than necessary.

“If I have a CT scan, and I can see that the appendicitis is uncomplicated,” said the lead author, Dr. Paulina Salminen, a surgeon at the University of Turku in Finland, “I would discuss with the patient the possible results of antibiotic treatment alone or surgery. Then we would make a joint, unbiased decision about what would be best.”

Turku, Finland—Most patients—about 60%—who had uncomplicated acute appendicitis and were treated with antibiotics didn’t require appendectomy in a 5-year follow-up, a randomized clinical trial found.
A report in JAMA notes that the clinical trial included 273 patients who underwent an appendectomy and 257 patients who were initially treated with antibiotics for uncomplicated acute appendicitis. Just 100 of the patients initially treated with antibiotics underwent appendectomy during the 5-year study period, and 15 of those had surgery during an initial hospitalization.
According to Finnish researchers from the University of Turku, their findings indicate that antibiotics might be a feasible alternative to surgery for patients with uncomplicated acute appendicitis.
While short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, long-term outcomes have been unknown. To remedy that, the researchers sought to determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.
To do that, the study team conducted a 5-year observational follow-up of patients in the Appendicitis Acuta multicenter clinical trial comparing appendectomy with antibiotic therapy. For that study, 530 patients aged 18 to 60 years who had computed tomography–confirmed uncomplicated acute appendicitis were randomized to either undergo an appendectomy or receive antibiotic therapy.
The initial trial lasted until June 2012 in Finland, with follow-up in September 2017. The current analysis assessed 5-year outcomes only for the group of patients treated with antibiotics alone. Those patients had received antibiotic therapy with IV ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.
Results indicate that 70 patients who initially received antibiotics had to undergo appendectomy within the first year (27.3% ; 70/256), with 30 additional antibiotic-treated patients (16.1% ; 30/186) having appendectomy between 1 and 5 years later.
The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years, according to the report.
Researchers noted that, of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, two had complicated appendicitis, and seven did not have appendicitis.
By 5 years, the overall complication rate—surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms—was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in the group receiving only antibiotics—a 17.9% difference.
Length of hospital stay didn’t differ between the two groups, but surgical patients had to take an average of 22 more days of sick leave, the researchers wrote. “Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within five years was 39.1%,” the study authors concluded. “This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.”

About the author

Leave a Reply

Your email address will not be published. Required fields are marked *