In healthy people, bile is sterile. Bacteria entering the gallbladder retrograde through the bile duct, bloodstream, and lymphatic pathways and proliferating abnormally cause acute cholecystitis when bile duct obstruction, bile duct injury, and bile stasis cause poor bile excretion[10–12]. Bacteria and toxins enter into capillaries and lymphatic vessels and invade the blood circulation leading to bacteremia and even sepsis When the mucosa of the gallbladder is damaged and the pressure in the bile duct rises above 25 cm H2O[13, 14].
The results of this study showed that the positivity rate of bile culture was 65.5% and blood culture was 35.3%, which is higher than that reported in the literature. Because most of the cases enrolled in this study were patients with severe acute cholecystitis, the rate of positive bacterial culture was higher than that of patients with acute cholecystitis who underwent laparoscopic cholecystectomy[15, 16]. The latter are mostly mild or moderate acute cholecystitis. The Gram-negative bacteria among the isolated strains were mainly Escherichia coli and Klebsiella pneumoniae, and the Gram-positive bacteria were mainly Enterococcus faecium and Enterococcus faecalis, which were consistent with the composition of the intestinal flora. It indicates that the causative organisms of acute cholecystitis originate from the intestinal tract. The positive rate of bile culture was significantly higher than that of blood culture (p < 0.05), considering that the patient received early PTGBD drainage and decompression to reduce the risk of bacterial entry into the blood.
Among the causative organisms of acute cholecystitis, the resistance rates of Gram-negative bacteria were on the rise, which was in line with the trend reported in the Chinese bacterial drug resistance surveillance study[17]. The resistance rate of Gram-positive bacteria is stable, probably due to the relatively low use of anti-Gram-positive antibiotics in the clinic, which is why it maintains a high sensitivity to antibiotics[18]. The rate of mixed infections with multiple bacteria was (26.8%), and the most common type was Escherichia coli mixed with Enterococcus faecium. The actual proportion of mixed infections is presumed to be higher, ranging from 15–90%, because the bile was not cultured for anaerobic bacteria in this study. The proportion of mixed infections with multiple bacteria is higher in severe cases and should be taken seriously[19, 20].
Drug sensitivity testing revealed that the pathogenic bacteria had low susceptibility to quinolone antibiotics and a high proportion of ESBL-producing strains. Quinolone antibiotics are widely used in clinical practice because of their broad antibacterial spectrum, ease of application, and high biliary concentration. In this study, the sensitivity rate of Escherichia coli to quinolones was around 65%, and many studies found that the resistance rate of bacteria to quinolone antibiotics is increasing, and there is a strong cross-resistance between such drugs[21]. Therefore, it is not recommended to use these drugs alone for the treatment of severe acute cholecystitis. Escherichia coli is the main causative agent of biliary sepsis, and ESBL production is the principal mechanism of its resistance to β-lactam antibacterial drugs[22]. Studies showed that the prevalence of ESBL-producing Escherichia coli in biliary tract infections was 23.8%, and the morbidity and mortality rate of these patients was higher than ESBL-negative population[23]. Long-term nursing home stays were found to be a high-risk factor for multi-drug-resistant bacterial infections. It is presumed to be associated with repeated antibiotic exposure in such patients.
Third-generation cephalosporins are selected as empirical antibiotics for the treatment of severe acute cholecystitis, with a greater likelihood of requiring escalating antibiotics thereafter[11]. If anti-Gram-negative antibiotics alone are not very effective clinically, a Gram-positive infection or mixed Gram-positive bacterial infections need to be considered. A combination of anti-Gram-positive antibiotics may be used. The prevalence of fungal infections is low in patients without underlying diseases. In some specific populations, such as immunosuppressed patients, the rate of fungal infections has increased. PTGBD should be given more attention as an emergency treatment option. It not only decompresses the gallbladder and reduces the risk of bacterial entry into the bloodstream, but also provides the opportunity to obtain bile specimens to refine bacterial culture and drug sensitivity for later antibiotic use[9, 24, 25].