Current opinions on the use of prophylactic antibiotics in patients undergoing laparoscopic cholecystectomy

Abstract

Inappropriate use of antibiotics leads to microbial resistance. Single-dose antibiotic prophylaxis prior to laparoscopic cholecystectomy is well known for reducing the risk of postoperative infection in high-risk patients despite some conflicting aspects. High-risk patients are those who are older than 70 years, have diabetes mellitus, whose operation time exceeded 120 minutes, have acute cholecystitis, experienced iatrogenic intraoperative gallbladder perforation resulting in bile or gallstone spillage, suffered from obstructive jaundice, or were deemed immunocompromised. For gallbladder perforation, one dose of antibiotic prophylaxis is sufficient. Therefore, guidelines are needed and must be strictly followed. Prophylactic treatment is not needed for patients at low risk of developing sepsis following elective laparoscopic cholecystectomy, although the opposite is supported. Similarly, superficial surgical infections are related to low morbidity. Patients without risk factors have a very low risk of infection. Thus, the routine use of antibiotic prophylaxis in elective laparoscopic cholecystectomy is not recommended.

Key Words: Prophylactic antibiotics; Gallstone disease; Laparoscopic cholecystectomy; Acute cholecystitis; Skin incision infection; Septic complications

Core Tip: In the most cases of elective laparoscopic cholecystectomy, there is a low possibility of septic complication development and no need for prophylactic antibiotics. In few patients with some well-defined risk factors for infection, including acute cholecystitis, the antibiotic prophylaxis before skin incision is necessary to minimize such complications.

TO THE EDITOR

Clinicians must be careful in deciding to administer antibiotics for prophylaxis, as there is a risk of microbial resistance in the event of excessive use or abuse. Microbial resistance has become a source of major concern worldwide, as new, more powerful, antibiotics are being discovered to treat severe infections refractory to previously effective treatment methods. Perioperative antibiotic prophylaxis has been used in patients scheduled for elective and emergency operative procedures[1]. Laparoscopic simple cholecystectomy for uncomplicated cholelithiasis is related to a very low risk of infection[2,3], since the bile entering the biliary tree is typically aseptic; however, impeded flow of bile is known to promote the growth of microbes, especially in patients of an advanced age[4,5]. Wang[6] recently published a retrospective study in the World Journal of Gastrointestinal Surgery evaluating the risk factors for surgical site infections and the effectiveness of prophylactic antibiotics in patients undergoing laparoscopic cholecystectomy and reported very interesting outcomes.

Single-dose intravenous antibiotic prophylaxis at the beginning of laparoscopic cholecystectomy is well known for preventing the risks of skin incision infections or other septic complications in high-risk patients[6,7-10], despite the existence of some conflicting aspects and the opposite supporting no antibiotic prophylaxis at all[11-15]. High-risk patients are those who are older than 70 years, have diabetes mellitus, whose surgery duration exceeded 120 minutes, were diagnosed with acute cholecystitis, suffered from iatrogenic intraoperative gallbladder perforation resulting in bile or gallstone spillage, experienced obstructive jaundice, and were deemed immunocompromised[6,7,15,16]. The timing, selection, and duration of perioperative antibiotic prophylaxis for skin wound infections are the determining factors[11,12]. However, guidelines are needed and strict adherence is required for all medical and nursing staff[17].

Antibiotic prophylaxis is not required for patients at low risk of developing sepsis after elective laparoscopic cholecystectomy; however, in addition to the most appropriate surgical technique, meticulous application of alternative infection prevention measures with antiseptic protocols and thorough preoperative preparation, is needed for such patients[18-22]. However, the opposite has been supported. The argument for the latter opinion is based on a meta-analysis that revealed a reduction in the incidence of surgical site infections and distant or overall infections after antibiotic prophylaxis[23].

In addition, superficial surgical infections such as skin incision infections are unlikely to lead to morbidity[24]. Therefore, patients without risk factors have a very low risk of infection and do not need prophylactic antibiotics[1,25,26].

The World Health Organization has general guidelines for the prevention of surgical site infections in patients undergoing any surgical procedure, particularly cardiothoracic and orthopedic procedures, mainly for Staphylococcus aureus, where beta-lactam antibiotics play a dominant role as well as other prophylactic measures[27]. Elective laparoscopic cholecystectomy has a low risk for such infection.

Strong evidence-based guidelines for laparoscopic cholecystectomy do not exist, and there is ongoing debate. The United States of America Surgical Infection Society recognizes the need for better evidence in guidelines focusing on the appropriate use of antibiotics in patients undergoing laparoscopic cholecystectomy. They recommend the following: (1) No routine perioperative prophylactic antibiotic use in patients undergoing elective operations, only selective use in high-risk cases; (2) No use for symptomatic cholelithiasis; (3) No use for mild or even moderate acute cholecystitis; and (4) Use only for severe inflammation according to the Tokyo classification for a maximum of 4 days[28].

Identifying any risk factor for infection is the first step in diagnosis[6]. Liver function tests (transaminases, bilirubin, alkaline phosphatase, and gamma-glutamyl transferase) are necessary before every cholecystectomy. Elevations in such markers indicate cholestasis, and gallstone disease found on biliary ultrasound warrant magnetic resonance cholangiopancreatography (MRCP)[29].

Gallbladder bile samples for culture obtained via paracentesis under imaging guidance can be helpful in the event that inflammation markers (white blood cell count, polymorphonuclear cell count, and c-reactive protein level) are elevated or that imaging is not possible, indicating acute gallbladder inflammation; however, there are practical challenges and limitations in routine clinical practice[4,5].

Elderly patients, patients with symptoms, and patients who undergo preoperative endoscopic retrograde cholangiopancreatography (ERCP) are more likely to have a positive bile culture[5].

In the case of concomitant common bile duct stones on MRCP, the recommendation is ERCP-endoscopic sphincterotomy and stone removal, followed by laparoscopic cholecystectomy[29], at which time antibiotic prophylaxis is necessary[5]. Bile culture-based antibiotics are more effective than empiric antibiotics after ERCP and in cases of acute cholecystitis[5,13].

Researchers have previously postulated that because antibiotic prophylaxis does not provide extra benefit for reducing the risk of postoperative infections and is not cost-effective, its use is not justified, even more so for patients with mild-to-moderate acute cholecystitis undergoing emergency laparoscopic cholecystectomy[12,17,30].

A comparative study revealed that cefazolin (2 g) before anesthesia for elective laparoscopic cholecystectomy in low-risk cases had no impact on the incidence of surgical site infection, with a ratio of 2% in both groups[31]. However, in patients with acute cholecystitis, a recent multicenter randomized controlled trial showed that 2 g of cefazolin before incision was associated with fewer postoperative infections (7.1%) than no antibiotic prophylaxis (12.6%), leading to its undeniable recommendation[17,32].

Prophylactic antibiotics is required for older patients in any case[4]. Additionally, if the operation time is expected to be prolonged, a single dose of 2 g of cefazolin intravenously must be applied before the skin is incised[7].

The most preferred antibiotic for prophylaxis is cefazolin[3,4,18,20,32], a first-generation cephalosporin, but cefuroxime[33], a second-generation cephalosporin or even third-generation ceftriaxone, has also been used in cases of acute cholecystitis[8].

For iatrogenic intraoperative gallbladder perforation and spillage of bile or stones, a single dose of an antibiotic is sufficient, especially in combination with proper cleaning and local irrigation of the operative field[34-36].

Alternatives for patients with beta-lactam allergies or for those undergoing prolonged surgeries who are at risk of gram-negative infections constitute beta-lactamase inhibitors, i.e., mainly among tazobactam (piperacillin with clavulanic acid), ampicillin with sulbactam, third-generation cephalosporins or carbapenems[37].

The routine use of antibiotic prophylaxis in patients scheduled to undergo elective laparoscopic cholecystectomy is not recommended, except in select patients at high risk of infection, including those scheduled for emergency laparoscopic cholecystectomy for mild to moderate acute cholecystitis.