Table 2 Summary of the included studies

Study design

Randomized, controlled, open-label, clinical trial

Double-blinded, placebo-controlled, randomized study

Double-blinded,

placebo-controlled,

randomized study

Randomized

controlled

trial

Randomized controlled, open, parallel-group,

noninferiority trial

Open-label, noninferiority, randomized clinical trial

Single-center, randomized, controlled, double-blinded trial

Country

The Netherlands

Sweden

South Korea

South Korea

The Netherlands

France

Argentina

Duration

From March 2016 to February 2020

From 14 December 2009 to 4 April 2017

From March 2019 to October 2021

From August 2015 to April 2016

From April 2012 to October 2014

From May 2010 to August 2012

From February 2014 to March 2017

Inclusion criteria

All adult patients presenting with ACC, in whom the intention was to perform immediate LC, were assessed for eligibility

Clinical and radiological signs of AC grades I and II suitable for acute LC and age ≥ 18 years

AC grade I and IIa patients, according to Tokyo Guidelines 2018

Patients with mild or

moderate ACC

undergoing laparoscopic

cholecystectomy

Adult patients suffering from mild ACC with an Acute Physiology and Chronic Health

Evaluation (APACHE) II score of 6 or lower

Patients aged 18 years or older with mild (grade I) or moderate (grade II) ACC (as defined by the Tokyo consensus meeting)

Diagnosis of mild or moderate ACC men and nonpregnant, nonlactating women between 18 and 85 years of age who undergo early LC

Exclusion criteria

Patients who presented with severe cholecystitis, received antibiotics, acalculous cholecystitis, already receiving or needing antibiotic treatment for a concomitant infection or

sepsis, proven allergy to cefazolin, pregnancy, or an indication for ERCP on admission

Ongoing septicemia, pregnancy,

bile duct obstruction, contraindication to LC,

treatment with antibiotic drugs within 24 h, and symptom duration longer than 5 days

Immunodeficiency, concurrent operation on other organs, suspicion of malignancy, history of previous

upper abdominal surgery, suspicion of a hollow organ injury, exploration of the common bile duct or conversion to laparotomy during the operation

If the boundary of the GB was already dissolved owing to severe inflammatory changes in the wall structure, as in the case of GB perforation. Any evidence of bile peritonitis during the operation. Immunodeficiency, concurrent operation on other organs, suspicion of malignancy, history

of previous upper abdominal surgery, suspicion of hollow

organ injury, or exploration of the common bile duct or conversion to laparotomy during the operation

Age < 18 years, antibiotics before diagnosis of cholecystitis, known allergy to cefuroxime or metronidazole, pregnancy, indication for ERCP on admission, abnormal liver test results with suspicion of acute cholangitis

Grade III severe ACC (with an indication of percutaneous transhepatic biliary drainage or required emergency cholecystectomy for septic shock, complaints lasting form or more than 5 days, common bile duct stones discovered at the time of surgery, cholangitis, biliary peritonitis, acute pancreatitis, cirrhosis, suspected biliary cancer, β-lactam allergy, and pregnant or breastfeeding

Hypersensitivity to amoxicillin or clavulanic acid or lactose (used in placebo); severe ACC; moderate ACC associated with liver and/or gallbladder abscesses, cholangitis, or bile peritonitis, intraoperative findings such as liver cancer, liver metastases, common bile duct stones, or gallbladder carcinoma, conversion to laparotomy, previous treatment with antibiotics for > five days, active oncologic diseases, AIDS, and transplant patients

Antibiotic

Name

First-generation

cephalosporin (cefazolin)

Piperacillin/tazobactam

First-generation cephalosporin (cefazolin)

Second-generation cephalosporin (cefoxitin sodium)

Cefuroxime and metronidazole

Amoxicillin/clavulanic acid

Amoxicillin/clavulanic acid

Route of administration

Intravenously

Intravenously

Intravenously

Intravenously

Intravenously

Intravenously

Orally

Dosage

Single dose, 2 g, 15–30 min before surgery

4 g. As the time between inclusion and the procedure varied, infusions were given over periods varying from less than an hour to 72 h

Empirical antibiotics, 1 g of

first-generation cephalosporin (cefazolin)

All patients received preoperative antibiotics with 1.0 g of second-generation cephalosporin (cefoxitin sodium) three times a day intravenously from the time of diagnosis of AC and received a single dose of antibiotics 30 min before surgery. The same antibiotic was routinely given once more during the operation. After surgery, patients were given either the placebo (group A) or postoperative antibiotics (cefoxitin) (group B). In group B, all patients received 1.0 g of cefoxitin three times a day postoperatively and then switched to oral pills (cefaclor, 250 mg

per pill, two times a day)

Once included, patients received a single prophylactic dose of antibiotics 15–30 min before surgery (cefazolin 2000 mg intravenously). The antibiotic group was admitted for 3 days after

surgery to receive intravenous cefuroxime 750 mg and metronidazole 500 mg three times daily

The treatment group received the same antibiotic regimen three times daily for 5 days. Patients who were not yet eating received 2 flasks of 1 g/200 mg intravenously, and those who could eat received 2 pills of 1 g each. Patients discharged within 5 days of surgery completed oral antibiotic treatment at home

1000 mg orally every 8 h for 5 days immediately after surgery

Follow-up

30 days after cholecystectomy

30 days postoperatively

4 weeks postoperatively

30 days

postoperatively

30 days after cholecystectomy

Four weeks postoperatively

30 postoperative days

Diagnosis of acute cholecystitis

The diagnosis AC was established according to the Tokyo Guidelines 07

Clinical and radiological signs of acute cholecystitis grades I and II

The diagnosis of AC was based on the Tokyo Guidelines 13

AC was defined according to the Tokyo Guidelines

AC was defined according to the Tokyo Guidelines

Diagnosis of mild or moderate ACC according to the Revised Tokyo Guidelines

Description of cholecystectomy

LC using the four-trocar technique according to the guidelines of the Dutch Society of Surgery, which included establishing the critical view of safety

LC, but four patients were included based on the primary intent to perform laparoscopic cholecystectomy,

but the surgeon responsible for the procedure decided to do an open procedure for technical reasons

In most cases, LC was performed by the three-trocar technique. A fourth trocar was additionally inserted in special cases. All the operations were performed by LC-specialized surgeons who had performed more than 1000 cases

In most cases, LC was done using the standard technique with three trocars. A fourth trocar was additionally inserted in special cases

LC was performed by the

four-trocar technique, with transection of the cystic duct and artery after reaching the critical view of safety as described by Strasberg

The surgical approach (laparoscopic or open cholecystectomy), intraoperative cholangiography, and abdominal drainage were performed according to each surgeon’s preferences and standard practice

The American technique for LC was used, and intraoperative cholangiography was used as a routine in all patients after having achieved the “critical view of safety”