Surgical infections of the hepatobiliary system generally refer to infectious diseases requiring surgical treatment and infections occurring after trauma or surgery, such as cholangitis caused by various types of intra- and extrahepatic bile duct stones and liver abscesses, etc. The appropriate use of antimicrobial drugs is essential. The application of antimicrobial drugs not only greatly improves the prevention and treatment of surgical infectious diseases, but also plays a great role in increasing surgical safety, reducing surgical complications and expanding the scope of surgery. Hepatobiliary diseases often have hepatic and renal insufficiency, and the incidence of such patients is now significantly higher in elderly patients, which makes the rational application of antimicrobial drugs particularly important. In this paper, we will discuss the rational application of antibiotics in hepatobiliary surgical diseases based on a review of the literature and the authors’ clinical experience. Firstly, the pathogenic diagnosis should be established as early as possible. Bacterial culture should be routinely performed, and preoperative culture can suggest the dominant flora and help the selection of antibiotics; intraoperative and postoperative culture can help the adjustment of antibiotics, and the bile culture results obtained from the common bile duct are the most valuable. Statistics show that the causative organisms of biliary tract infection mainly come from the intestine, and the most common bacteria in positive bile culture are Gram-staining negative Escherichia coli, E. coli, E. parapsilosis, E. variegatus, Enterococcus, Streptococcus faecalis, Pseudomonas aeruginosa and anaerobic bacteria and Gram-positive cocci (such as Staphylococcus, Streptococcus haemolyticus, etc.), of which the detection rate of E. coli is about 50%. The culture positivity rate of anaerobic bacteria in the biliary tract reaches 3.5 to 45%, and its positivity rate can reach 80% in acute obstructive septic cholangitis. In biliary tract infections, about 50-70% are mixed infections of multiple bacteria (including anaerobic and aerobic bacteria). The application of antibacterial drugs should be strictly controlled by the indications and the correct combination application. The most likely pathogenic bacteria can be empirically treated based on clinical diagnosis, combined with the antibacterial activity of the drugs, taking into account pharmacokinetic properties, pharmacodynamics, adverse reactions, as well as drug sources and prices, and then decide whether to make adjustments based on the results of drug sensitivity and the clinical effects of empirical use of drugs. For serious infections and mixed infections caused by multiple bacteria, the combination of multiple antibiotics can be considered. The combination of drugs should pay attention to the synergistic effect, the dose should be adjusted accordingly to avoid increasing the adverse reactions and toxic side effects of drugs. The ideal antibiotic is the one that is most effective against the biliary pathogenic flora and can maintain a higher blood concentration for a longer period of time and may have a larger concentration in the bile or a combination of antibiotics. Based on the phenomenon that biliary tract infections are mostly Gram-negative bacilli and anaerobic bacteria, antibiotics that target these types of bacteria should be selected clinically. The commonly used antibacterial drugs for the treatment of biliary tract infections are: penicillin family, cephalosporin family, aminoglycosides, quinolones, nitroimidazole derivatives and peptide antibiotics. Among the penicillin family, piperacillin (oxypiperazine penicillin) and piperacillin tazobactam (Contrave) are among the more ideal drugs against biliary anaerobic infections, which have higher concentrations in bile, 15 times higher than the blood concentration, and have a strong killing effect on Bacteroides fragilis. Cephalosporins are currently the most widely used drugs in clinical practice. It is divided into four generations: the first generation includes cefalexin, cefalexin and cefradin, which mainly act on gram-positive bacteria, stronger than the second and third generation, and poorly act on gram-negative bacteria, and have certain toxicity to kidney. The second generation includes cefuroxime, cefotiam, etc., with effects between the first generation and the third generation and less nephrotoxic. The third generation includes ceftriaxone, cefoperazone (sulbactam), cefotaxime, cefotaxime, etc. They have less effect on Gram-positive bacteria than the first and second generation, but have powerful anti-Gram-negative effect, and also have different degrees of antibacterial effect on Pseudomonas aeruginosa and anaerobic bacteria, and almost no toxicity to kidney. Ceftriaxone (Bacteroides) has a half-life of 8 hours, and the effective concentration in serum can be maintained for 24 hours after a single dose, which is one of the third generation cephalosporins with the longest sustained effective antibacterial effect after a single dose. Aminoglycosides mainly include gentamicin and butamycin, which are no longer preferred because of their nephrotoxicity and ototoxicity. The quinolones include ofloxacin and ciprofloxacin, which are mainly metabolized by the liver and excreted from urine and bile, and are suitable for urinary tract and biliary tract infections and serious systemic infections. Nitroimidazole derivatives mainly include metronidazole (methotrexate), tinidazole and ornidazole, which can selectively act on anaerobic strains of bacteria. In addition, the peptide antibiotics are represented by vancomycin, which is not a broad antibacterial spectrum, but has strong antibacterial effect and more obvious toxicity, especially nephrotoxicity. It is only used clinically for serious infections caused by sensitive bacteria, and the indications are more strict. Our experience in choosing antibiotics for different biliary tract diseases is: quinolones plus metronidazole or second-generation cephalosporins plus tinidazole, and those with moderate to severe infections or those who have applied antibiotics several times are switched to third-generation cephalosporins plus tinidazole/ornidazole. The above medications will be adjusted according to the specific situation after the bacterial culture and drug sensitivity results are reported. The liver is the main organ of drug metabolism. Drugs with high concentration of intrahepatic distribution or inactivated mainly by hepatic metabolism, such as tetracycline, chloramphenicol, erythromycin, lincomycin, rifampicin and diphenhydramine, should be avoided in case of hepatic insufficiency or decompensation. In case of renal insufficiency, the excretion of drugs is slowed down, which may lead to accumulation of poisoning. The following characteristics should be noted: ① The total water in the body of the elderly is reduced, the renal function is low, and the conventional dose of drugs can sometimes easily cause high blood concentration and toxic reactions; ② The plasma protein in the body of the elderly is reduced, and the plasma concentration after the use of conventional dose of antibiotics is higher than that of young people; ③ In vitro drug sensitivity is effective, but the actual efficacy is uncertain; ③ The drug is not effective. The actual efficacy of in vitro drug sensitivity is uncertain; ④ The application of broad-spectrum antibiotics is likely to cause intestinal flora dysbiosis and cause secondary infection. In addition, the current clinically used once daily drip administration method is not desirable, because the bacteria have a long time every day without contact with drugs, can continue to be able to reproduce, daily intravenous injection method is significantly better than continuous intravenous drip, it can make the drug in the body often maintain a high blood concentration and tissue concentration, better antibacterial efficacy. The course of antibacterial drugs varies with different infections, and it is generally advisable to stop using them until the temperature drops to normal and the symptoms subside 3 to 4 days later. In severe infections or sepsis, the drug should be stopped 1 to 2 weeks after the condition is stabilized.