Table 1 Brief information of the included studies

Ceresoli [14]

RCT, single center, 45 patients

Participants aged 18–65 years were diagnosed by AIR score and adjunctive abdominal ultrasound in selected participants

Participants with intermediate probability of acute appendicitis from AIR score were examined with abdominal

ultrasound and were included in the study if ultrasound findings confirmed the clinical suspicion of acute appendicitis

Participants with high probability of acute appendicitis from AIR score without signs of perforation and with WCC of less

than 15 000/µl and CRP less than 5 mg/l were included for the randomization

Days 1–3: IV ertapenem (1 g, q24h)

Days 4–8: PO amoxicillin plus clavulanic acid (1 g TID)"

Primary outcome: resolution of symptoms and inflammatory markers (WCC < 10 000/µl and CRP < 1 mg/l) within 2 weeks

after surgery in the surgical group or from the third dose of ertapenem without other treatments in the antibiotic group

Secondary outcomes: complications, negative appendicectomy, duration of hospital stay, work absence, long-term

negative outcomes within 1 year, including: bowel occlusion/intraperitoneal abscess leading to surgical re-operation,

bowel occlusion longer than 48 h, intraperitoneal abscess, incisional hernia or wound dehiscence in the surgical group

and recurrence of acute appendicitis in the antibiotic group

Eriksson [4]

RCT, single center, 40 patients

typical history and clinical signs, positive findings at ultrasound and either increased WCC and CRP

values or high CRP or WCC on two occasions within a 4 h interval

Days 1–2: IV cefotaxime (2 g, q12h) plus tinidazole (800 mg, q24h) Days 3–10: PO ofloxacin (200 mg BID) plus tinidazole (500 mg BID)

Pain scores (every 6 h using a visual analogue scale), morphine consumption, WCC and temperature, positive diagnosis at

surgery, duration of hospital stay, wound infection and recurrent appendicitis

6, 10, and 30 days AD

Hansson [15]

RCT, multicenter, 369 patients

Participants with positive history, clinical signs, laboratory tests and in some cases, ultrasonography, CT and

gynecological examination

Day 1: IV cefotaxime (1 g × 2 doses) plus metronidazole (1.5 g × 1 dose)

Days 2–11: PO ciprofloxacin (500 mg BID) plus Metronidazole (400 mg TID)

Treatment efficacy, complications, recurrences and reoperations, duration of antibiotic therapy, abdominal pain after

discharge from hospital, duration of hospital stay and sick leave. The total costs for the primary hospital stay were

analyzed for each patient

1 month and 1 year

AD

Khan [16]

RCT, single center, 130 patients

Participants aged 15–45 years old with positive history, clinical signs, laboratory tests and in some cases, ultrasonography, CT

Days 1–5: ciprofloxacin (250 mg TID) plus metronidazole (500 mg TID), route of administration not specified

O'Leary [17]

RCT, single center, 186 patients

Participants aged 16 years and older admitted to the emergency department with right iliac fossae pain, raised WCC/CRP,

fluent in English (and negative β-HCG in females) were screened for inclusion

Participants without exclusion criteria would then proceed to radiological investigation with abdominal ultrasound with/without magnetic resonance imaging performed in those under 45 years; CT in participants above 45 years of age

was performed

Participants were randomized if acute uncomplicated appendicitis was evidenced from radiological investigation

Intravenous (IV) antibiotic (co-amoxiclav,1.2 g, 3 times daily). IV antibiotics were continued until there was a clinical improvement followed by 5 days of oral co-amoxiclav(625 mg 3 times a day orally for 5 days)

Primary endpoint: success rate of antibiotic treatment at 1-year follow-up for the antibiotic group; successful

appendicectomy for the surgical group

Secondary endpoints: quality of life, cost and duration of hospital stay

Salminen [18]

RCT, multicenter, 530 patients

Participants aged 18–60 years admitted to the emergency department with clinical suspicion of acute uncomplicated

appendicitis confirmed by CT were considered. Acute appendicitis was considered present when the appendiceal

diameter exceeded 6 mm with wall thickening and at least one of the following: abnormal contrast enhancement of the

appendiceal wall, inflammatory oedema, or fluid collections around the appendix. Participants with complicated

appendicitis, defined as the presence of an appendicolith, perforation, abscess or suspicion of a tumor on the scan, were

excluded

Days 1–3: IV ertapenem (1 g/day)

Days 4–10: PO levofloxacin (500 mg QD) and metronidazole (500 mg TID)

The primary outcome measure in the antibiotic group was resolution of acute appendicitis, with discharge from

hospital without the requirement for surgical intervention and no recurrent appendicitis during the 1-year follow-up

Treatment success in the appendicectomy group was defined as the patient successfully undergoing an

appendicectomy

Secondary outcomes: post-intervention complications, late recurrence of appendicitis (more than 1 year), duration of

hospital stay, sick leave taken, pain scores on a visual analogue scale, and the use of analgesics

1 week, 2 months, and

1 year after

intervention

Styrud [19]

RCT, multicenter, 252 patients

Men, 18–50 years of age, admitted to six different hospitals between 1996 and 1999. Participants with suspected

appendicitis with a CRP concentration above 10 mg/l and with no clinical signs of perforation

Days 1–2: V cefotaxime (2 g, q12h) plus tinidazole (800 mg, q24h) Days 3–12: PO ofloxacin (200 mg BID) plus tinidazole (500 mg BID)

Duration of hospital stay, sick leave, diagnosis at operation, recurrences and complications

1 week, 6 weeks, and

1 year AD

Talan [20]

RCT, single center, 30 patients

Days 1–2: IV ertapenem (1 g/day)

Days 3–10: PO cefdinir and metronidazole

Dosing is dependent on age

Cefdinir: 13 + years, 300 mg BID; 5–12 years, 7 mg/kg BID, max 300 mg

Metronidazole: 13 + years, 500 mg tablets TID; 5–12 years, 10 mg/kg TID, max. 500 mg

The CODA Collaborative [21]

RCT, multicenter, 1552 patients

Consecutive English-speaking or Spanish-speaking participants above 18 years of age were approached by the research

coordinator if imaging confirmed they had appendicitis. All participants with evidence of appendicolith from imaging

results were included in a prespecified subgroup before randomization. Evidence of perforation from the imaging result

was not an exclusion criterion

Day 1: IV metronidazole (+ ceftriaxone or levofloxacin), ertapenem, cefoxitin Days 2–10: PO metronidazole + ciprofloxacin or cefdinir

Primary outcome: 30-day health status, assessed with EQ-5D™ questionnaires

Secondary outcomes: appendicectomy in the antibiotics group, patient-reported resolution of symptoms, and National

Surgical Quality Improvement Program-defined complications at the time of index treatment or during follow-up, visits

to the emergency department or hospital related to appendicitis symptoms, appendiceal neoplasms, treatment-related

complications, days of missed work for the participants and their career

Vons [22]

RCT, multicenter, 239 patients

All adults 18 years and older with suspected acute appendicitis. Eligible participants had CT diagnosis of uncomplicated

appendicitis, using defined radiological criteria and were randomized to appendicectomy or antibiotic therapy

IV amoxicillin plus clavulanic acid (3 g/day)

Primary endpoint: occurrence of peritonitis within 30 days of initial treatment, diagnosed either at appendicectomy or

postoperatively by CT

Secondary endpoints: number of days with a post-intervention visual analogue scale pain score of 4 or higher, duration of

hospital stay and absence from work, incidence of complications other than peritonitis within 1 year and recurrence of

appendicitis after antibiotic treatment (appendicectomy performed between 30 days and 1 year follow-up, with a

confirmed diagnosis of appendicitis)

15, 30, 90, 180, and

360 days AD