Distribution Characteristics, Antimicrobial Resistance, and Variation Trends of Biliary Microbiome in Acute Cholangitis patients : A 7-Year Retrospective Study in a Tertiary Hospital in Northwest China

Distribution Characteristics, Antimicrobial Resistance, and Variation Trends of Biliary Microbiome in Acute Cholangitis patients : A 7-Year Retrospective Study in a Tertiary Hospital in Northwest China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Distribution Characteristics, Antimicrobial Resistance, and Variation Trends of Biliary Microbiome in Acute Cholangitis patients : A 7-Year Retrospective Study in a Tertiary Hospital in Northwest China Yuqi Hao, Wenting Du, Jinshuai Lu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4162226/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background With the increase in bacterial resistance worldwide, the bacterial characteristics of the biliary tract may have changed. Bile specimens for microbiological analysis are obtained primarily during endoscopic retrograde cholangiopancreatography, with a few from percutaneous transhepatic cholangial drainage. However, in some regions of China, patients still undergo laparoscopic T-tube drainage. The lack of data from this subset may lead to an incomplete understanding of the characteristics of the biliary microbiome. Method 1094 hospitalized patients diagnosed acute cholangitis from January 1, 2017 to December 31, 2023, who underwent biliary drainage procedures with bile specimen collection in our hospital were selected.Collect and analyse their general information, results of biliary culture, antimicrobial susceptibility and potential reasons for changes over 7 years. Results Among the 1,094 patients with acute cholangitis, 875 specimens (79.91%) yielded positive bile cultures, facilitating the detection of 1,026 strains belonging to 24 genera and 75 species of pathogens..Gram-negative bacteria were predominant,accounting for 63.65%(653/1,026) of the isolates, followed by gram-positive bacteria at 31.97%(328/1,026) and fungi at 4.39%(45/1,026). The main genera were Escherichia (249, 24.27%), Enterococcus (197, 19.20%), Klebsiella (170, 16.57%). Over the years, there has been a fluctuating upward trend in the diversity of pathogens. From 2017 to 2021, the proportion of gram-negative bacilli gradually decreased while gram-positive cocci increased, although the difference was not statistically significant. However, from 2022 to 2023, the proportion of gram-negative bacilli significantly increased compared to the previous five years.There was an increasing trend in the resistance rates of Escherichia coli and Klebsiella pneumoniae to various antibiotics.They were more sensitive to piperacillin/sulbactam sodium than to cefoperazone/sulbactam sodium. Conclusion The proportion of gram-positive bacteria increased annually in patients without differences in the history of Oddi sphincter incision. Incision of the Oddi sphincter increased the proportion of gram-negative bacteria but did not increase the proportion of major bacterial species and had no significant effect on the distribution of Enterococcus. The detection rates of resistant bacteria increased significantly. The resistance rates of Escherichia coli and Klebsiella pneumoniae to antibiotics showed an overall increasing trend. bacteria fungi antimicrobial༛trends༛cholangitis༛Oddi sphincter incision Figures Figure 1 Figure 2 Figure 3 1. Introduction Acute cholangitis is primarily caused by cholelithiasis and biliary obstruction. In severe cases, it can progress to sepsis, infective shock, or multiple organ failure, posing a life-threatening risk [1]. Treatment for acute cholangitis includes administering antimicrobial drugs, biliary drainage, and addressing the underlying causes [2] . Timely and effective biliary drainage can reduce mortality rates by 2.8% [3,4] . Current clinical approaches for biliary drainage encompass endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangial drainage (PTCD), and surgical drainage. ERCP is the primary drainage method for acute cholangitis [2,5] , while PTCD is a salvage option if endoscopic drainage fails [6] . PTCD is preferred for acute cholangitis resulting from biliary obstruction at and above the hilum hepatis. For severe biliary obstructions with no significant improvement in symptoms post-ERCP or PTCD, laparoscopic biliary drainage becomes the last resort [7] . Early use of antibiotics plays a crucial role in treating acute cholangitis. Alongside relieving biliary obstruction, routine bile culture should be routinely performed to adjust antibiotic application [8] . Clinical experience has shown that despite thorough biliary drainage, some patients show inadequate control of biliary infections with antibiotics recommended by existing guidelines. This could be attributed to widespread antibiotic use, increased biliary-related surgeries, and other factors altering the bacterial spectrum of biliary infections [9,10] . Therefore, identifying the biliary microbiological characteristics and trends and determining the resistance patterns of resistant strains can help shift from the empirical use of broad-spectrum antibiotics to targeted therapy, improving efficacy [2,11-13] . This study aimed to describe the microbiological patterns of bile in patients with acute cholangitis.These bile specimens obtained by through appropriate biliary drainage.Specifically, we aimed to define the distribution and trends of the biliary microbiome over seven years, identify factors influencing the microbiological patterns, include the presence/absence of a history of gallbladder removal, sphincterotomy, or cholangiotomy, and describe the antibiotic resistance profiles and variation trends of detected pathogenic microorganisms. The insights found herein will help diagnose and treat patients with acute cholangitis, improving clinical efficacy and patient outcomes. 2. Methods This is a single-center retrospective study from a large, comprehensive Class A tertiary teaching hospital. The procedures of biliary drainage, bile bacterial culture, and drug sensitivity tests were all completed in our hospital, with complete electronic medical records, imaging data, and laboratory reports retained. This study was approved by the Ethics Committee of the People’s Hospital of Xinjiang Uygur Autonomous Region(KY2022072217).Data was collected from inpatients in our hospital from July 1, 2017, to December 31, 2023. The inclusion criteria were as follows: (1) The patients met the diagnostic criteria for acute cholangitis in the 2018 Tokyo Guidelines[2]; (2) The patients underwent ERCP, PTCD, or surgical biliary drainage; (3) The bile samples were collected for examination during surgery; (4) For repeated bacterial culture results in the same patient, only the data of the first strain were collected; (5) Before surgery, the patient and his family were explained the bile extraction operation and the informed consent for research was signed. Patients with a preoperative history of antibiotic use over three days or with incomplete clinical data (missing medical records and specimen contamination) were excluded from this study. The surgeon decided on the biliary drainage method based on the patient’s age, general condition, comorbidities and decided after departmental case discussions. Some patients switched to PTCD after failing ERCP. 2.1. Data analysis Statistical analysis was performed using SPSS 29.0 software. Basic clinical data, including gender, age, etiology, and history of biliary surgery of patients with acute cholangitis from 2017 to 2023, were collected and compared. The distribution and change trends of microorganisms in positive bile culture specimens, the change trends of major pathogens (accounting for > 50%), and the drug resistance of Escherichia coli , Klebsiella pneumoniae, Enterococcus faecium , and Candida albicans were analyzed. Normally distributed measurement data were expressed as ͞X±s. Count data were expressed as numbers and percentages. The chi-square test or Fisher’s exact test was used to compare different years。When comparing between the two groups, the difference was statistically significant with P<0.05.Compare the difference for each year over a 7-year period，the P-value was adjusted to 0.002 according to the Bonferroni method. 3. Results 3.1. General Information and Clinical Data of Patients Among the 1,094 patients included in this study, 595 were males, and 498 were females, with an average age of 61.96 ± 1.63 years. Benign lesions were the primary cause of acute cholangitis, accounting for 79.71% (872/1,094) of the cases. Some patients had concurrent benign and malignant lesions; however, this study categorized them according to malignant lesions. Among the 207 malignant cases, cholangiocarcinoma accounted for the majority at 52.17% (108/207), followed by pancreatic carcinoma (38/207), gallbladder carcinoma (30/207), duodenal and ampullary cancer (19/207) combined, and liver cancer (13/207). Additionally, gastric cancer was found in four cases and esophageal cancer in one case (1/207) (table 1). Chi-square tests were conducted yearly to measure the composition ratio of benign and malignant causes, history of cholecystectomy, history of Oddi sphincterotomy, and history of cholangiotomy for patients. The composition ratio of benign and malignant causes was similar among acute cholangitis patients over seven years (P = 0.570). The difference in the history of cholecystectomy was not statistically significant (P = 0.027). However, there was a significant difference in the history of Oddi sphincterotomy (P < 0.001). Further analysis showed no significant difference in the history of Oddi sphincterotomy from 2017 to 2021 (P = 0.990). There was also no significant difference in the history of Oddi sphincterotomy between 2022 and 2023 (P = 0.278). However, the proportions of patients with a history of Oddi sphincterotomy in 2022 and 2023 were significantly higher than in the previous five years (P < 0.001). Additionally, the history of cholangiotomy varied among different years (P < 0.001), with 2018 and 2020 having a significantly higher proportion of cholangiotomy history compared to other years (P = 0.003).。Further comparison of cholangiotomy history between 2018 and 2020 showed no significant difference (P=0.421). Together, these data show that there was no significant difference between the patients included in this study in the composition of benign and malignant causes and the history of cholecystectomy by year. 3.2. Distribution of Pathogenic Bacterial Genera in Bile Cultures Among the 875 bile samples yielding positive bile culture results, 1,026 pathogenic bacterial strains were identified, representing 24 genera and 75 species. Escherichia accounted for 24.27% (249/1,026) of the isolates, followed by Enterococcus at 16.76% (172/1,026), Klebsiella at 16.57% (170/1,026), Enterobacter at 7.89% (81/1,026), Staphylococcus at 7.11% (73/1,026), Candida at 4.39% (45/1,026), Pseudomonadaceae at 3.80% (39/1,026), Streptococcus at 3.61% (37/1,026), Citrobacter at 3.61% (37/1,026), Acinetobacter at 2.92% (30/1,026), Aeromonas at 1.17% (12/1,026), Xanthomonas at 1.07% (11/1,026), and other less frequently detected strains which accounted for <1% each. These frequently detected strains included Salmonella (9/1,026), Micrococcus (7/1,026), Morganella (5/1,026), Proteus (4/1,026),Bacillus (3/1,026), Corynebacterium (3/1,026),Raoultella (2/1,026), Leukonostoc (2/1,026), Lactobacillus (2/1,026), Providencia (1/1,026), Shewanella (1/1,026), and Burkholderia (1/1,026) (table 2). Throughout the study period, the primary pathogens consistently identified each year were Escherichia, Klebsiella , Enterococcus , and Enterobacter species. As the years progressed, an increasing trend towards an expanding diversity of bacterial species was detected, with 17, 27, 24, 33, 39, 28, and 39 species identified year on year, respectively. 3.3. Trends in the Distribution and Variation of Gram-negative, Gram-positive, and Fungal Microorganisms The detection of gram-negative bacteria revealed 15 genera and 32 species, totaling 653 cases, accounting for 63.65% (653/1,026) of the cases assessed. The annual proportions were 65.45% (36/55), 65.32% (81/124), 62.81% (76/121), 62.14% (87/140), 58.70% (135/230), 68.12% (94/138), and 66.06% (144/218) from 2017 to 2021. Over the five years, gram-negative bacteria exhibited a statistically insignificant decreasing trend (P = 0.743). From 2022 to 2023, there was a significant increase in the proportion of gram-negative bacteria compared to the previous five years (Fisher exact test, P = 0.014). Nevertheless, no statistically significant variance was observed between 2022 and 2023 (P = 0.687). Gram-positive bacteria comprised 8 genera and 37 species, totaling 328 cases, representing 31.97% (328/1,026). From 2017 to 2021, gram-positive bacteria exhibited a consistent upward trend, with annual proportions of 30.90% (17/55), 32.25% (40/124), 33.88% (41/121), 35.00% (49/140), and 37.83% (87/230), respectively, although these changes lacked statistical significance (P = 0.793). Conversely, in 2022 and 2023, the proportion of gram-positive bacteria decreased substantially to 26.09% (36/138) and 26.61% (58/218), respectively, representing a significant decline compared to the preceding five years (P = 0.005). Fungi, represented by one genus and five species, accounted for 4.39% (45/1,026) of the total cases. From 2017 to 2023, fungal detection exhibited fluctuating upward trends, with annual proportions of 3.63% (2/55), 2.41% (3/124), 3.31% (4/121), 2.86% (4/140), 3.48% (8/230), 5.80% (8/138), and 7.34% (16/218). The chi-square test showed no statistical difference in the overall fungal proportion over the seven years (P = 0.240). Further examination revealed no statistical difference in fungal proportions from 2017 to 2022 (P = 0.748), but a significant increase was observed in 2023 compared to the previous six years (P = 0.016).（Figure 1） Among the 875 specimens, 57 cases exhibited mixed infections of gram-positive and gram-negative bacteria, with Escherichia coli/Enterococcus faecium being the predominant combination, accounting for 17.54% (10/57) of cases. Furthermore, 12 cases showed fungal-bacterial co-infections, primarily with gram-negative bacteria, constituting 61.54% (8/13) of the cases. 3.4. Analysis of Gram-negative Bacteria, Gram-positive Bacteria, Fungal Types, and their Composition 3.4.1. Gram-negative Bacteria: The predominant gram-negative bacteria were Escherichia coli (24.27%, 249/1,026), Klebsiella pneumoniae (13.16%, 135/1,026), Enterobacter cloacae (6.04%, 62/1,026), Pseudomonas aeruginosa (3.41%, 35/1,026), Klebsiella oxytoca (3.22%, 33/1,026), and Acinetobacter baumannii (2.83%, 29/1,026). Other species included Citrobacter freundii (26 strains), Enterobacter asburiae (12 strains), Stenotrophomonas maltophilia (11 strains), Citrobacter braakii (9 strains), Aeromonas hydrophila (5 strains), Aeromonas caviae (7 strains), Enterobacter aerogenes (6 strains), Serratia marcescens (6 strains), Morganella morganii (5 strains),, Raoulia ornitholytica (2 strains), Niornithine klebber (2 strains), Citrobacter amalonaticua (2 strains), Proteus mirabilis (2 strains), and others were detected as 1 strain(14 strains), with 2 strains of undifferentiated species. The variety of gram-negative pathogens fluctuated upward over the years, with species counts of 10, 15, 10, 14, 16, 14, and 17 for each year, respectively. 3.4.2. Gram-positive Bacteria Enterococcus faecium (11.89%, 122/1,026), Enterococcus faecalis (5.07%, 52/1,026), Staphylococcus epidermidis (2.53%, 26/1,026), Staphylococcus hominis (1.85%, 19/1,026), and Staphylococcus aureus (1.46%, 15/1,026) were the major gram-positive bacteria identified. Other gram-positive bacteria accounted for less than 1.00% of the cases, including Enterococcus avium (10 strains), Streptococcus salivarius (10 strains), Streptococcus oralis (7 strains), Streptococcus anginosus (7 strains), Enterococcus casselifavus (7 strains), Streptococcus mitis (5 strains), Staphylococcus haemolyticus (4 strains), Micrococcus luteus (3 strains), Staphylococcus cohnii (2 strains), Enterococcus hirae (2 strains), Streptococcus intermadius (2 strains), Staphylococcus warneri (2 strains), Enterococcus gallinarum (2 strains), Corynebacterium striatum (2 strains), Streptococcus pneumoniae (2 strains), Streptococcus bovis (2 strains), and others were detected as 1 strain(17 strains), with 4 strains of undifferentiated micrococcus、 2 strains of undifferentiated bacillus and 1undifferentiated staphylococcus.The variety of gram-positive pathogens fluctuated upward over the years, with species counts of 5, 10, 12, 16, 21, 11, and 18 for each year, respectively. 3.4.3. Fungi All detected fungi belonged to the Candida genus, with four species, including Candida albicans (2.73%, 28/1,026), Candida glabrata (7 strains), Candida tropicalis (5 strains), Candida krusei (3 strains), and Candida parapsilosis (2 strains). From 2017 to 2023, the annual species counts were 2, 2, 2, 3, 2, 3, and 4 for each year.（Figure 2). 3.4.4. Trends in the Proportions of Major Pathogens and Fungi Based on the proportion of species, the top five species, whose cumulative proportion exceeded 50%, were selected for trend analysis: Escherichia coli (24.34%), Klebsiella pneumoniae (13.20%), Enterococcus faecium (11.93%), Enterobacter cloacae (6.04%), and Enterococcus faecalis (5.07%). Our data indicate that from 2017 to 2023, the proportions of Escherichia coli , Enterococcus faecium , Enterobacter cloacae , and Enterococcus faecalis remained relatively stable, with P-values of 0.393, 0.171, 0.508, and 0.051 respectively. Klebsiella pneumoniae had a higher proportion in 2019 and 2022 (31.6%, 28.7%) and a smaller proportion in 2023 (9.7%), with statistically significant differences compared to other years (P < 0.001). There were no significant differences between 2017, 2018, 2020, and 2021 (P = 0.276). The fungus with the highest proportion was Candida albicans, representing 62.22% (28/45) of the cases. Fisher’s exact test was used to examine its proportions for each year, yielding a P-value of 0.399, indicating no significant differences.（Figure 3） 3.4.5. Drug Resistance Status In accordance with the drug usage recommendations from the Chinese Medical Association and our hospital’s routine susceptibility test results, this study focused on the drug resistance analysis of gram-negative bacteria to third- and fourth-generation cephalosporins (cefuroxime, ceftriaxone, ceftazidime, cefepime), β-lactamase inhibitor combinations (cefoperazone/sulbactam, piperacillin/tazobactam), and carbapenems (imipenem, meropenem). Additionally, gram-positive bacteria were analyzed for resistance to vancomycin, teicoplanin, and linezolid. A total of 1,002 strains were included in the susceptibility tests (98.04%), with 35 strains (3.49%) showing resistance. Among them, 22 strains of carbapenem-resistant Enterobacteriaceae (CRE) were identified, predominantly represented by Klebsiella pneumoniae (40.91%, 9/22), Acinetobacter baumannii (31.82%, 7/22), and Escherichia coli (18.18%, 4/22), with one strain each of Enterobacter cloacae and Enterobacter asburiae . The frequency of multidrug-resistant bacteria was similar over the experiment period (P = 0.532). Additionally, when explicitly analyzing CRE, no statistical difference was found in the detection rate of CRE from 2017 to 2022 (Fisher’s exact test, P = 0.851); however, the detection rate in 2023 significantly increased compared to the previous six years (Fisher’s exact test, P = 0.014). Acinetobacter baumannii demonstrated multidrug resistance in 10 strains, constituting 58.62% of this species (17/29). From 2017 to 2023, among the 122 Enterococcus faecium strains subjected to susceptibility testing, only one strain resistant to vancomycin was found in 2020, with no significant differences between years (P = 0.467). For drug susceptibility analysis, strains that collectively accounted for over 50% of gram-negative, gram-positive, and fungal categories were selected. This included 233 strains of Escherichia coli (93.57%), 116 strains of Klebsiella pneumoniae (85.93%), 122 strains of Enterococcus faecium (100%), 50 strains of Enterococcus faecalis (96.15%), and 17 strains of Candida albicans (60.71%). Gram-negative bacilli: Escherichia coli exhibited noticeable resistance to third-generation cephalosporins, with sensitivity rates below 50% for ceftriaxone and cefuroxime. Additionally, Escherichia coli showed sensitivity to fourth-generation cephalosporins at around 55%, while β-lactamase inhibitor combinations exhibited sensitivity of 80% of the Escherichia coli strain assessed. Moreover, Escherichia coli showed a higher sensitivity to piperacillin/sulbactam sodium than cefoperazone/sulbactam sodium. Klebsiella pneumoniae had the lowest sensitivity to cefuroxime sodium, while the effective rate of other cephalosporin antibiotics was measured at 75%. Klebsiella pneumoniae’s sensitivity to piperacillin/sulbactam sodium was slightly higher than to cefoperazone/sulbactam sodium. Additionally, both Klebsiella pneumoniae and Escherichia coli had sensitivity above 90% to carbapenems The Both Klebsiella pneumoniae and Escherichia coli showed a fluctuated downward trend in sensitivity to cefuroxime sodium, cefoperazone/sulbactam sodium, and piperacillin/sulbactam sodium. Klebsiella pneumoniae showed a fluctuating decrease in the sensitivity to imipenem and meropenem, while resistance appeared in Escherichia coli only in 2023. The specific results are shown below（table 3）. Gram-positive cocci: The sensitivity of Enterococcus faecium and Enterococcus faecalis to teicoplanin and linezolid was 100%, and vancomycin was 99.42%. Fungi: Candida albicans showed 100% sensitivity to voriconazole and fluconazole, while itraconazole and flucytosine both had sensitivities of 94.12%. 4. Discussion Among the 1,094 bile specimens collected, 875 were culture-positive, with a positivity rate of 79.98%. From these samples, 1,026 microorganisms were detected, of which gram-negative bacteria accounted for 63.65% (653/1,026), lower than the 70% reported in bile bacterial surveillance in China from 2014 to 2019 [14] . This difference may be attributed to the vast territory of China and the variation in bile bacterial spectra among different regions and populations. It may also suggest a decline in gram-negative rods in recent years in biliary tract infections. From 2017 to 2021, the proportion of gram-negative rods gradually decreased, while the proportion of gram-positive cocci increased, consistent with some domestic and international research results [15,16] . In 2022-2023, there was a significant increase in the proportion of gram-negative rods and a noticeable decrease in the proportion of gram-positive cocci. Considering the patients’ general information, the history of Oddi sphincterotomy in 2022-2023 was higher than in the previous five years, suggesting that Oddi sphincterotomy may disrupt the barrier between the duodenal lumen and the biliary tract, increasing the invasion of gram-negative bacteria. In the absence of Oddi sphincterotomy, gram-positive bacterial infections increased yearly, consistent with some relevant reports [15,16] . However, analysis of the proportions of major gram-negative species each year found that the proportions of Escherichia coli , Klebsiella pneumoniae , Enterobacter cloacae , and Enterococcus species ( Enterococcus faecalis , Enterococcus faecium ) did not change over the seven years, indicating that Oddi sphincterotomy does not increase the proportions of these bacteria or affect the distribution of Enterococcus species, which differs from some domestic and international research results [10,16,17,18] . We found that the proportion of fungi has continuously increased over the past seven years, with a significant rise observed in 2023 compared to the previous six years. Recent reports suggest that the incision of the Oddi sphincter is an independent risk factor for fungal detection [17] . In our study, there was no difference in the history of Oddi sphincter incisions between 2022 and 2023; however, there was a difference in detection rates, leading to inconclusive results, possibly related to fewer cases in our hospital in 2022. The increasing trend observed in the diversity of gram-negative, gram-positive, and fungal species over the years underscores the dynamic nature of microbial populations within the studied samples. Notably, in 2020, Enterococcus species detected included Enterococcus hirae , Enterococcus raffinosa , Enterococcus intestinalis , and Enterococcus gallinarum . In 2021, Morganella, Raoultella and Leuconostoc were detected. In 2022, Bacillus species were detected, indicating a change in the types of biliary bacteria. Possible reasons for this include: first, the widespread use of antibiotics in recent years, which has led to changes in intestinal microbiota, indirectly affecting the types of biliary bacteria through the gut-liver axis [19,20,21,22] . Second, environmental pollutants such as microplastics and mercury can affect the stability of the adult microbiota [23,24] . Third, the intake of ultra-processed foods and food additives has been shown to affect intestinal health [25,26] , affecting biliary flora. Lastly, using antibiotics in livestock and aquaculture can directly or indirectly affect human intestinal flora, thereby altering biliary flora [27] . According to data from the Bacterial Drug Resistance Monitoring Network in China, the top three bile-resistant bacteria from 2014 to 2019 were Escherichia coli (30.9%), Klebsiella pneumoniae (12.7%), and Enterococcus faecium (10.1%) [14] . In this study, from 2017 to 2023, the top three pathogens in bile culture were Escherichia coli at 24.27% (249/1,026), Klebsiella pneumoniae at 13.16% (135/1,026), and Enterococcus faecium at 11.89% (122/1,026), consistent with the monitoring results. The detection of CRE in 2023 increased significantly compared to the previous six years. The longitudinal comparison revealed a rising trend in overall resistance of Escherichia coli and Klebsiella pneumoniae , particularly against third-generation cephalosporins. Among β-lactamase inhibitor combinations, sensitivity to piperacillin/sulbactam sodium was higher. This antibiotic resistance is globally documented [28,29] , indicating an increasing trend in bile pathogen resistance on a global scale, emphasizing the necessity to identify resistance patterns. Our antimicrobial sensitivity tests recommend piperacillin/sulbactam sodium as the first choice for empirical treatment in suspected cases of acute cholangitis. Considering the lower prevalence of Enterococcus species, early antibiotic treatment need not specifically target this group. Our data indicate that adjustments to antibiotic use can be made based on bile culture results. Additionally, current guidelines suggest collecting bile samples before using antimicrobial drugs whenever possible to avoid false-negative results [6] . Patients using antibiotics for over three days or over three days of antibiotic exposure before admission were excluded from this study. Since the majority of patients were referred from external hospitals, we could not gather detailed information on their antibiotic usage before admission, potentially introducing selection bias. We observed a small number of patients diagnosed with acute suppurative cholangitis who underwent emergency surgery (with intraoperative bile described as white), yet their bile cultures yielded negative results. This observation suggests that these patients might have received antibiotic treatment before admission, lowering the positivity rate of the cultures. The impact of the 2022 pneumonia epidemic in our region led to decreased patient volume, which may affect the results. Additionally, variations in microbial frequency and antibiotic resistance among different regions and populations may limit the generalizability of this study. 5. Conclusion In conclusion, from 2017 to 2023, Escherichia coli remained the predominant organism in bile cultures of acute cholangitis patients; however, there were changes in the types, biological characteristics, and resistance patterns of bile microorganisms. The proportion of gram-positive bacteria increased annually in cases without differences in Oddi sphincterotomy history. Additionally, Oddi sphincterotomy increased the proportion of gram-negative bacteria but did not affect the major species ( Escherichia coli , Klebsiella pneumoniae , and Enterobacter cloacae ) or Enterococcus species. Over time, there was an increase in pathogen diversity, with higher detections of fungi and drug-resistant strains, indicating a changing microbial community in the biliary tract with worsening resistance. The resistance rates of Escherichia coli and Klebsiella pneumoniae were on the rise, with sensitivity to third-generation cephalosporins below 50% and being more sensitive to piperacillin/ sulbactam sodium than to cefoperazone/sulbactam sodium. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Xinjiang Uiger Municipal People’s Hospital (KY2022072217). Consent for publication All authors read and approved the final manuscript. Availability of data and materials The datasets used or analyzed for the study were provided within the manuscript and additional data can be requested from the corresponding author. Competing interests The authors declare no competing interests. Funding No funding was provided for data collection or the creation of this manuscript. Authors' contributions YH: Study concept and design; execution of the study; data interpretation; writing and revisions of manuscript. WD：Data interpretatio.JL: Study concept and design;critical revision of manuscript.study supervision. Acknowledgements We would like to thank the cooperative and supportive staff of the Gastroenterology and Hepatobiliary surgery Department. References Mohammad A, Cholangitis AH. Diagnosis, Treatment and Prognosis. J Clin Transl Hepatol. 2017;5:404–13. Miura F, Okamoto K, Takada T, et al. Tokyo guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. 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Gastroenterol Rep (Oxf). 2024. 10.1093/gastro/goae010 . 12 Gastroenterol Rep (Oxf). Stathopoulos P, Lerner P, Astheimer P, et al. Endoscopic retrograde cholangiopancreatography-obtained bile culture in acute cholangitis: retrospective analysis of bile cultures and risk factors in a tertiary care center. J Gastroen Hepatol. 2024. 10.1111/jgh.16492 . Miutescu B, Vuletici D, Burciu C, et al. Comparative Analysis of Antibiotic Resistance in Acute Cholangitis Patients with Stent Placement and Sphincterotomy Interventions. Life (Basel). 2023;13(11). 10.3390/life13112205 . Maier L, Goemans CV, Wirbel J, et al. Unravelling the collateral damage of antibiotics on gut bacteria. Nature. 2021;599(7883):120–4. 10.1038/s41586-021-03986-2 . Zhao JW, Hou YC, Yang ZY, et al. Genome-wide Mendelian randomization study of the pathogenic role of gut microbiota in benign biliary tract diseases. Zhonghua Wai Ke Za Zhi. 2024;62(3):217–23. 10.3760/cma.j.cn112139-20230714-00008 . Huang X, Yang Y, Li X, et al. The gut microbiota: A new perspective for tertiary prevention of hepatobiliary and gallbladder diseases. Front Nutr. 2023;10:1089909. 10.3389/fnut.2023.1089909 . Milosevic I, Vujovic A, Barac A, et al. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int J Mol Sci. 2019;20(2). 10.3390/ijms20020395 . Wang X, Deng K, Zhang P et al. Microplastic-mediated new mechanism of liver damage: From the perspective of the gut-liver axis. SCI TOTAL ENVIRON. 2024; 919 170962. 10.1016/j.scitotenv.2024.170962 . Lin X, Zhang W, He L et al. Understanding the hepatoxicity of inorganic mercury through guts: Perturbance to gut microbiota, alteration of gut-liver axis related metabolites and damage to gut integrity. ECOTOX ENVIRON SAFE. 2021; 225 112791. 10.1016/j.ecoenv.2021.112791 . Song Z, Song R, Liu Y, et al. Effects of ultra-processed foods on the microbiota-gut-brain axis: The bread-and-butter issue. FOOD RES INT. 2023;167:112730. 10.1016/j.foodres.2023.112730 . Whelan K, Bancil AS, Lindsay JO, et al. Ultra-processed foods and food additives in gut health and disease. NAT REV GASTRO HEPAT. 2024. 10.1038/s41575-024-00893-5 . Patel J, Shah D, Ahmad U, UNDERSTANDING THE ADAPTATION AND SENSITIVITY OF THE MICROBIOME: MICROBIAL RESILIENT AND HUMAN WELL-BEING. N,. Georgian Med News. 2023; (343): 134–8. PMID: 38096530. Gromski MA, Gutta A, Lehman GA, et al. Microbiology of bile aspirates obtained at ERCP in patients with suspected acute cholangitis. ENDOSCOPY. 2022;54(11):1045–52. 10.1055/a-1790-1314 . Chandra S, Klair JS, Soota K, et al. Endoscopic retrograde cholangio pancreatography-obtained bile culture can guide antibiotic therapy in acute cholangitis. Dig Dis. 2019;37:155–60. Tables Table1 General information and clinical data of patients Year cases gender age symptom cause History of cholecystectomy History of biliary surgery Bile collection method male female fever bellyache jaundice benign malignant Oddi sphincterotomy PTCD cholangiotomy ERCP PTCD cholangiotomy 2017 49 29 20 58.93±3.12 22 33 14 41 8 17 3 3 7 4 18 27 2018 129 73 56 59.69±1.81 32 87 27 98 31 46 8 2 20 42 53 34 2019 137 67 70 58.28±1.94 31 100 34 109 28 45 10 7 12 37 58 42 2020 171 69 102 64.15±1.31 48 110 47 137 34 58 13 14 21 10 80 81 2021 243 147 96 66.41±0.93 65 157 69 202 41 65 17 5 18 31 106 106 2022 146 81 64 61.08±1.36 25 99 36 118 28 37 27 15 8 32 64 50 2023 220 129 90 65.19±0.98 38 166 69 183 37 45 33 22 7 87 89 43 Tables 2-3 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table2.docx table3.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4162226","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":283934820,"identity":"4e3ed18d-d611-4962-811a-aa157f12e81a","order_by":0,"name":"Yuqi Hao","email":"","orcid":"","institution":"People’s Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Yuqi","middleName":"","lastName":"Hao","suffix":""},{"id":283934821,"identity":"b81401f3-a973-4cd6-aaa8-0574a3b66bce","order_by":1,"name":"Wenting Du","email":"","orcid":"","institution":"People’s Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Wenting","middleName":"","lastName":"Du","suffix":""},{"id":283934823,"identity":"c083d056-97cb-4a12-b6d9-8045485085c2","order_by":2,"name":"Jinshuai Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIie3RsQrCMBCA4ZNCXFJdAyK+QiGTk/gmCa4OPkJBqJuuuqiPUBGcHAI3OLoKOrQKnQXBqYPXRbc2boL5yZAhH7kQAJfrB2sAKANAy/MMCBvCPoQpa1JEBHhgNxgTKsVRftGzCX+K7n6nY+Ol11M5UbiIMj1HfxuI7EyESTmsIn6IOkR/kwhTEM5alYTnqFfIE/MFYahj5DXLW3hCg0UoN8hkQEQusOItzfpw8KDB2ssjZi0i7elhnN7KCH2Hem89+sr+GkuPF9XNe1u7A/Q6YSVxuVyuP+sFF+JX2nA3F5AAAAAASUVORK5CYII=","orcid":"","institution":"People’s Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":true,"prefix":"","firstName":"Jinshuai","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2024-03-25 09:35:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4162226/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4162226/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53875849,"identity":"af599a9c-f6a5-4851-b888-5488e8670b74","added_by":"auto","created_at":"2024-04-01 16:37:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106612,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends of gram-negative, gram-positive, and fungi bacteria（%）\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/1ac2e75a22473738172692e5.jpg"},{"id":53875852,"identity":"b5d39009-dbe3-409f-aad5-c48d695fc632","added_by":"auto","created_at":"2024-04-01 16:37:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":115602,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends in the species of gram-negative bacteria, gram-positive bacteria and fungi\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/8c1db3ba1d88dd88b039708a.jpg"},{"id":53875854,"identity":"3b13cc9f-7707-4a62-873f-8d2bd79b7048","added_by":"auto","created_at":"2024-04-01 16:37:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":143156,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends in the Proportions of Major Pathogens and Fungi（%）\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/6f232890bef0ea78d9f82321.jpg"},{"id":53877849,"identity":"f0442ab3-238b-441f-a02d-41b9f89dcdc0","added_by":"auto","created_at":"2024-04-01 16:53:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":408431,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/bbdba1a3-f019-4bb9-b8bb-741eaf2ec055.pdf"},{"id":53875853,"identity":"44576467-c31a-4561-af6a-417264db5ed5","added_by":"auto","created_at":"2024-04-01 16:37:02","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18351,"visible":true,"origin":"","legend":"","description":"","filename":"table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/a3c40efc9f0e4af028d50391.docx"},{"id":53875851,"identity":"61ae358a-81c7-4152-8ff6-cd4f6b25aac6","added_by":"auto","created_at":"2024-04-01 16:37:02","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15035,"visible":true,"origin":"","legend":"","description":"","filename":"table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4162226/v1/c981409ca10a576d7adecbce.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Distribution Characteristics, Antimicrobial Resistance, and Variation Trends of Biliary Microbiome in Acute Cholangitis patients : A 7-Year Retrospective Study in a Tertiary Hospital in Northwest China","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAcute cholangitis is primarily caused by cholelithiasis and biliary obstruction. In severe cases, it can progress to sepsis, infective shock, or multiple organ failure, posing a life-threatening risk\u003csup\u003e[1].\u003c/sup\u003e Treatment for acute cholangitis includes administering antimicrobial drugs, biliary drainage, and addressing the underlying causes\u003csup\u003e[2]\u003c/sup\u003e. Timely and effective biliary drainage can reduce mortality rates by 2.8%\u003csup\u003e[3,4]\u003c/sup\u003e. Current clinical approaches for biliary drainage encompass endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangial drainage (PTCD), and surgical drainage. ERCP is the primary drainage method for acute cholangitis\u003csup\u003e[2,5]\u003c/sup\u003e, while PTCD is a salvage option if endoscopic drainage fails\u003csup\u003e[6]\u003c/sup\u003e. PTCD is preferred for acute cholangitis resulting from biliary obstruction at and above the hilum hepatis. For severe biliary obstructions with no significant improvement in symptoms post-ERCP or PTCD, laparoscopic biliary drainage becomes the last resort\u003csup\u003e[7]\u003c/sup\u003e. Early use of antibiotics plays a crucial role in treating acute cholangitis. Alongside relieving biliary obstruction, routine bile culture should be routinely performed to adjust antibiotic application\u003csup\u003e[8]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eClinical experience has shown that despite thorough biliary drainage, some patients show inadequate control of biliary infections with antibiotics recommended by existing guidelines. This could be attributed to widespread antibiotic use, increased biliary-related surgeries, and other factors altering the bacterial spectrum of biliary infections\u003csup\u003e[9,10]\u003c/sup\u003e. Therefore, identifying the biliary microbiological characteristics and trends and determining the resistance patterns of resistant strains can help shift from the empirical use of broad-spectrum antibiotics to targeted therapy, improving efficacy\u003csup\u003e[2,11-13]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThis study aimed to describe the microbiological patterns of bile in patients with acute cholangitis.These bile specimens obtained by through appropriate biliary drainage.Specifically, we aimed to define the distribution and trends of the biliary microbiome over seven years, identify factors influencing the microbiological patterns, include the presence/absence of a history of gallbladder removal, sphincterotomy, or cholangiotomy, and describe the antibiotic resistance profiles and variation trends of detected pathogenic microorganisms. The insights found herein will help diagnose and treat patients with acute cholangitis, improving clinical efficacy and patient outcomes.\u0026nbsp;\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis is a single-center retrospective study from a large, comprehensive Class A tertiary teaching hospital. The procedures of biliary drainage, bile bacterial culture, and drug sensitivity tests were all completed in our hospital, with complete electronic medical records, imaging data, and laboratory reports retained. This study was approved by the Ethics Committee of the\u0026nbsp;People\u0026rsquo;s Hospital of Xinjiang Uygur Autonomous Region(KY2022072217).Data was collected from inpatients in our hospital from July 1, 2017, to December 31, 2023. The inclusion criteria were as follows:\u0026nbsp;(1)\u0026nbsp;The patients met the diagnostic criteria for acute cholangitis in the 2018 Tokyo Guidelines[2];\u0026nbsp;(2)\u0026nbsp;The patients underwent ERCP, PTCD, or surgical biliary drainage;\u0026nbsp;(3)\u0026nbsp;The bile samples were collected for examination during surgery;\u0026nbsp;(4)\u0026nbsp;For repeated bacterial culture results in the same patient, only the data of the first strain were collected; (5) Before surgery, the patient and his family were explained the bile extraction operation and the informed consent for research was signed. Patients with a preoperative history of antibiotic use over three days or with incomplete clinical data (missing medical records and specimen contamination) were excluded from this study. The surgeon decided on the biliary drainage method based on the patient\u0026rsquo;s age, general condition, comorbidities and decided after departmental case discussions. Some patients switched to PTCD after failing ERCP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e Data analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS 29.0 software. Basic clinical data, including gender, age, etiology, and history of biliary surgery of patients with acute cholangitis from 2017 to 2023, were collected and compared. The distribution and change trends of microorganisms in positive bile culture specimens, the change trends of major pathogens (accounting for \u0026gt; 50%), and the drug resistance of\u0026nbsp;\u003cem\u003eEscherichia coli\u003c/em\u003e,\u0026nbsp;\u003cem\u003eKlebsiella pneumoniae,\u003c/em\u003e \u003cem\u003eEnterococcus faecium\u003c/em\u003e, and\u0026nbsp;\u003cem\u003eCandida albicans\u003c/em\u003e were analyzed. Normally distributed measurement data were expressed as ͞X\u0026plusmn;s. Count data were expressed as numbers and percentages. The chi-square test or Fisher\u0026rsquo;s exact test was used to compare different years。When comparing between the two groups, the difference was statistically significant with P\u0026lt;0.05.Compare the difference for each year over a 7-year period，the P-value was adjusted to 0.002 according to the Bonferroni method.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e3.1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; General Information and Clinical Data of Patients\u003c/p\u003e\n\u003cp\u003eAmong the 1,094 patients included in this study, 595 were males, and 498 were females, with an average age of 61.96 \u0026plusmn; 1.63 years. Benign lesions were the primary cause of acute cholangitis, accounting for 79.71% (872/1,094) of the cases. Some patients had concurrent benign and malignant lesions; however, this study categorized them according to malignant lesions. Among the 207 malignant cases, cholangiocarcinoma accounted for the majority at 52.17% (108/207), followed by pancreatic carcinoma (38/207), gallbladder carcinoma (30/207), duodenal and ampullary cancer (19/207) combined, and liver cancer (13/207). Additionally, gastric cancer was found in four cases and esophageal cancer in one case (1/207) (table 1).\u003c/p\u003e\n\u003cp\u003eChi-square tests were conducted yearly to measure the composition ratio of benign and malignant causes, history of cholecystectomy, history of Oddi sphincterotomy, and history of cholangiotomy for patients. The composition ratio of benign and malignant causes was similar among acute cholangitis patients over seven years (P = 0.570). The difference in the history of cholecystectomy was not statistically significant (P = 0.027). However, there was a significant difference in the history of Oddi sphincterotomy (P \u0026lt; 0.001). Further analysis showed no significant difference in the history of Oddi sphincterotomy from 2017 to 2021 (P = 0.990). There was also no significant difference in the history of Oddi sphincterotomy between 2022 and 2023 (P = 0.278). However, the proportions of patients with a history of Oddi sphincterotomy in 2022 and 2023 were significantly higher than in the previous five years (P \u0026lt; 0.001). Additionally, the history of cholangiotomy varied among different years (P \u0026lt; 0.001), with 2018 and 2020 having a significantly higher proportion of cholangiotomy history compared to other years (P = 0.003).。Further comparison of cholangiotomy history between 2018 and 2020 showed no significant difference (P=0.421).\u003c/p\u003e\n\u003cp\u003eTogether, these data show that there was no significant difference between the patients included in this study in the composition of benign and malignant causes and the history of cholecystectomy by year.\u003c/p\u003e\n\u003cp\u003e3.2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Distribution of Pathogenic Bacterial Genera in Bile Cultures\u003c/p\u003e\n\u003cp\u003eAmong the 875 bile samples yielding positive bile culture results, 1,026 pathogenic bacterial strains were identified, representing 24 genera and 75 species. Escherichia accounted for 24.27% (249/1,026) of the isolates, followed by Enterococcus at 16.76% (172/1,026), Klebsiella at 16.57% (170/1,026), Enterobacter at 7.89% (81/1,026), Staphylococcus at 7.11% (73/1,026), Candida at 4.39% (45/1,026), Pseudomonadaceae at 3.80% (39/1,026), Streptococcus at 3.61% (37/1,026), Citrobacter at 3.61% (37/1,026), Acinetobacter at 2.92% (30/1,026), Aeromonas at 1.17% (12/1,026), Xanthomonas at 1.07% (11/1,026), and other less frequently detected strains which accounted for \u0026lt;1% each. These frequently detected strains included Salmonella (9/1,026), Micrococcus (7/1,026), Morganella (5/1,026), Proteus (4/1,026),Bacillus (3/1,026), Corynebacterium (3/1,026),Raoultella (2/1,026), \u0026nbsp; Leukonostoc (2/1,026), Lactobacillus (2/1,026), \u0026nbsp;Providencia (1/1,026), Shewanella (1/1,026), and Burkholderia (1/1,026) (table 2).\u003c/p\u003e\n\u003cp\u003eThroughout the study period, the primary pathogens consistently identified each year were \u003cem\u003eEscherichia, Klebsiella\u003c/em\u003e, \u003cem\u003eEnterococcus\u003c/em\u003e, and \u003cem\u003eEnterobacter\u003c/em\u003e species. As the years progressed, an increasing trend towards an expanding diversity of bacterial species was detected, with 17, 27, 24, 33, 39, 28, and 39 species identified year on year, respectively.\u003c/p\u003e\n\u003cp\u003e3.3. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Trends in the Distribution and Variation of Gram-negative, Gram-positive, and Fungal Microorganisms\u003c/p\u003e\n\u003cp\u003eThe detection of gram-negative bacteria revealed 15 genera and 32 species, totaling 653 cases, accounting for 63.65% (653/1,026) of the cases assessed. The annual proportions were 65.45% (36/55), 65.32% (81/124), 62.81% (76/121), 62.14% (87/140), 58.70% (135/230), 68.12% (94/138), and 66.06% (144/218) from 2017 to 2021. Over the five years, gram-negative bacteria exhibited a statistically insignificant decreasing trend (P = 0.743). From 2022 to 2023, there was a significant increase in the proportion of gram-negative bacteria compared to the previous five years (Fisher exact test, P = 0.014). Nevertheless, no statistically significant variance was observed between 2022 and 2023 (P = 0.687).\u003c/p\u003e\n\u003cp\u003eGram-positive bacteria comprised 8 genera and 37 species, totaling 328 cases, representing 31.97% (328/1,026). From 2017 to 2021, gram-positive bacteria exhibited a consistent upward trend, with annual proportions of 30.90% (17/55), 32.25% (40/124), 33.88% (41/121), 35.00% (49/140), and 37.83% (87/230), respectively, although these changes lacked statistical significance (P = 0.793). Conversely, in 2022 and 2023, the proportion of gram-positive bacteria decreased substantially to 26.09% (36/138) and 26.61% (58/218), respectively, representing a significant decline compared to the preceding five years (P = 0.005).\u003c/p\u003e\n\u003cp\u003eFungi, represented by one genus and five species, accounted for 4.39% (45/1,026) of the total cases. From 2017 to 2023, fungal detection exhibited fluctuating upward trends, with annual proportions of 3.63% (2/55), 2.41% (3/124), 3.31% (4/121), 2.86% (4/140), 3.48% (8/230), 5.80% (8/138), and 7.34% (16/218). The chi-square test showed no statistical difference in the overall fungal proportion over the seven years (P = 0.240). Further examination revealed no statistical difference in fungal proportions from 2017 to 2022 (P = 0.748), but a significant increase was observed in 2023 compared to the previous six years (P = 0.016).（Figure 1）\u003c/p\u003e\n\u003cp\u003eAmong the 875 specimens, 57 cases exhibited mixed infections of gram-positive and gram-negative bacteria, with Escherichia coli/Enterococcus\u0026nbsp;faecium\u0026nbsp;being the predominant combination, accounting for 17.54% (10/57) of cases. Furthermore, 12 cases showed fungal-bacterial co-infections, primarily with gram-negative bacteria, constituting 61.54% (8/13) of the cases.\u003c/p\u003e\n\u003cp\u003e3.4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Analysis of Gram-negative Bacteria, Gram-positive Bacteria, Fungal Types, and their Composition\u003c/p\u003e\n\u003cp\u003e3.4.1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gram-negative Bacteria:\u003c/p\u003e\n\u003cp\u003eThe predominant gram-negative bacteria were \u003cem\u003eEscherichia coli\u003c/em\u003e (24.27%, 249/1,026), \u003cem\u003eKlebsiella pneumoniae\u0026nbsp;\u003c/em\u003e(13.16%, 135/1,026), \u003cem\u003eEnterobacter cloacae\u003c/em\u003e (6.04%, 62/1,026), \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (3.41%, 35/1,026), \u003cem\u003eKlebsiella oxytoca\u003c/em\u003e (3.22%, 33/1,026), and \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e (2.83%, 29/1,026). Other species included \u003cem\u003eCitrobacter freundii\u003c/em\u003e (26 strains), \u003cem\u003eEnterobacter asburiae\u003c/em\u003e (12 strains), \u003cem\u003eStenotrophomonas maltophilia\u003c/em\u003e (11 strains), \u003cem\u003eCitrobacter braakii\u003c/em\u003e (9 strains), \u003cem\u003eAeromonas hydrophila\u003c/em\u003e (5 strains), \u003cem\u003eAeromonas caviae\u003c/em\u003e (7 strains), \u003cem\u003eEnterobacter aerogenes\u003c/em\u003e (6 strains), \u003cem\u003eSerratia marcescens\u0026nbsp;\u003c/em\u003e(6 strains), \u003cem\u003eMorganella morganii\u003c/em\u003e (5 strains),, Raoulia ornitholytica (2 strains), Niornithine klebber (2 strains), \u003cem\u003eCitrobacter amalonaticua\u003c/em\u003e (2 strains), \u003cem\u003eProteus mirabilis\u003c/em\u003e (2 strains), and others were detected as 1 strain(14 strains), with 2 strains of undifferentiated species. The variety of gram-negative pathogens fluctuated upward over the years, with species counts of 10, 15, 10, 14, 16, 14, and 17 for each year, respectively.\u003c/p\u003e\n\u003cp\u003e3.4.2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gram-positive Bacteria\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEnterococcus faecium\u003c/em\u003e (11.89%, 122/1,026), \u003cem\u003eEnterococcus faecalis\u003c/em\u003e (5.07%, 52/1,026), \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e (2.53%, 26/1,026), \u003cem\u003eStaphylococcus\u0026nbsp;\u003c/em\u003ehominis (1.85%, 19/1,026), and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (1.46%, 15/1,026) were the major gram-positive bacteria identified. Other gram-positive bacteria accounted for less than 1.00% of the cases, including \u003cem\u003eEnterococcus avium\u003c/em\u003e (10 strains), \u003cem\u003eStreptococcus salivarius\u003c/em\u003e (10 strains), \u003cem\u003eStreptococcus oralis\u003c/em\u003e (7 strains), \u003cem\u003eStreptococcus anginosus\u003c/em\u003e (7 strains), \u003cem\u003eEnterococcus casselifavus\u003c/em\u003e (7 strains), \u003cem\u003eStreptococcus mitis\u003c/em\u003e (5 strains), \u003cem\u003eStaphylococcus haemolyticus\u003c/em\u003e (4 strains), \u003cem\u003eMicrococcus luteus\u003c/em\u003e (3 strains), \u003cem\u003eStaphylococcus cohnii\u003c/em\u003e (2 strains), \u003cem\u003eEnterococcus hirae\u003c/em\u003e (2 strains), \u003cem\u003eStreptococcus intermadius\u003c/em\u003e (2 strains), Staphylococcus warneri (2 strains), \u003cem\u003eEnterococcus gallinarum\u003c/em\u003e (2 strains), \u003cem\u003eCorynebacterium striatum\u003c/em\u003e (2 strains), \u003cem\u003eStreptococcus pneumoniae\u0026nbsp;\u003c/em\u003e(2 strains), \u003cem\u003eStreptococcus bovis\u003c/em\u003e (2 strains), and others \u0026nbsp;were detected as 1 strain(17 strains), with 4 strains of undifferentiated micrococcus、 2 strains of undifferentiated bacillus and 1undifferentiated staphylococcus.The variety of gram-positive pathogens fluctuated upward over the years, with species counts of 5, 10, 12, 16, 21, 11, and 18 for each year, respectively.\u003c/p\u003e\n\u003cp\u003e3.4.3. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Fungi\u003c/p\u003e\n\u003cp\u003eAll detected fungi belonged to the Candida genus, with four species, including \u003cem\u003eCandida albicans\u003c/em\u003e (2.73%, 28/1,026), \u003cem\u003eCandida glabrata\u003c/em\u003e (7 strains), \u003cem\u003eCandida tropicalis\u003c/em\u003e (5 strains), \u003cem\u003eCandida krusei\u003c/em\u003e (3 strains), and \u003cem\u003eCandida parapsilosis\u003c/em\u003e (2 strains). From 2017 to 2023, the annual species counts were 2, 2, 2, 3, 2, 3, and 4 for each year.（Figure 2).\u003c/p\u003e\n\u003cp\u003e3.4.4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Trends in the Proportions of Major Pathogens and Fungi\u003c/p\u003e\n\u003cp\u003eBased on the proportion of species, the top five species, whose cumulative proportion exceeded 50%, were selected for trend analysis: \u003cem\u003eEscherichia coli\u003c/em\u003e (24.34%), \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (13.20%), \u003cem\u003eEnterococcus faecium\u003c/em\u003e (11.93%), \u003cem\u003eEnterobacter cloacae\u003c/em\u003e (6.04%), and \u003cem\u003eEnterococcus faecalis\u003c/em\u003e (5.07%). Our data indicate that from 2017 to 2023, the proportions of \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eEnterococcus faecium\u003c/em\u003e, \u003cem\u003eEnterobacter cloacae\u003c/em\u003e, and \u003cem\u003eEnterococcus faecalis\u003c/em\u003e remained relatively stable, with P-values of 0.393, 0.171, 0.508, and 0.051 respectively. \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e had a higher proportion in 2019 and 2022 (31.6%, 28.7%) and a smaller proportion in 2023 (9.7%), with statistically significant differences compared to other years (P \u0026lt; 0.001). There were no significant differences between 2017, 2018, 2020, and 2021 (P = 0.276). The fungus with the highest proportion was \u003cem\u003eCandida albicans,\u003c/em\u003e representing 62.22% (28/45) of the cases. Fisher\u0026rsquo;s exact test was used to examine its proportions for each year, yielding a P-value of 0.399, indicating no significant differences.（Figure 3）\u003c/p\u003e\n\u003cp\u003e3.4.5. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Drug Resistance Status\u003c/p\u003e\n\u003cp\u003eIn accordance with the drug usage recommendations from the Chinese Medical Association and our hospital\u0026rsquo;s routine susceptibility test results, this study focused on the drug resistance analysis of gram-negative bacteria to third- and fourth-generation cephalosporins (cefuroxime, ceftriaxone, ceftazidime, cefepime), \u0026beta;-lactamase inhibitor combinations (cefoperazone/sulbactam, piperacillin/tazobactam), and carbapenems (imipenem, meropenem). Additionally, gram-positive bacteria were analyzed for resistance to vancomycin, teicoplanin, and linezolid.\u003c/p\u003e\n\u003cp\u003eA total of 1,002 strains were included in the susceptibility tests (98.04%), with 35 strains (3.49%) showing resistance. Among them, 22 strains of carbapenem-resistant Enterobacteriaceae (CRE) were identified, predominantly represented by \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (40.91%, 9/22), \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e (31.82%, 7/22), and \u003cem\u003eEscherichia coli\u003c/em\u003e (18.18%, 4/22), with one strain each of \u003cem\u003eEnterobacter cloacae\u003c/em\u003e and \u003cem\u003eEnterobacter asburiae\u003c/em\u003e. The frequency of multidrug-resistant bacteria was similar over the experiment period (P = 0.532). Additionally, when explicitly analyzing CRE, no statistical difference was found in the detection rate of CRE from 2017 to 2022 (Fisher\u0026rsquo;s exact test, P = 0.851); however, the detection rate in 2023 significantly increased compared to the previous six years (Fisher\u0026rsquo;s exact test, P = 0.014). \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e demonstrated multidrug resistance in 10 strains, constituting 58.62% of this species (17/29). From 2017 to 2023, among the 122 \u003cem\u003eEnterococcus faecium\u003c/em\u003e strains subjected to susceptibility testing, only one strain resistant to vancomycin was found in 2020, with no significant differences between years (P = 0.467).\u003c/p\u003e\n\u003cp\u003eFor drug susceptibility analysis, strains that collectively accounted for over 50% of gram-negative, gram-positive, and fungal categories were selected. This included 233 strains of \u003cem\u003eEscherichia coli\u003c/em\u003e (93.57%), 116 strains of \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (85.93%), 122 strains of \u003cem\u003eEnterococcus faecium\u003c/em\u003e (100%), 50 strains of \u003cem\u003eEnterococcus faecalis\u003c/em\u003e (96.15%), and 17 strains of \u003cem\u003eCandida albicans\u003c/em\u003e (60.71%).\u003c/p\u003e\n\u003cp\u003eGram-negative bacilli: \u003cem\u003eEscherichia coli\u003c/em\u003e exhibited noticeable resistance to third-generation cephalosporins, with sensitivity rates below 50% for ceftriaxone and cefuroxime. Additionally, \u003cem\u003eEscherichia coli\u003c/em\u003e showed sensitivity to fourth-generation cephalosporins at around 55%, while \u0026beta;-lactamase inhibitor combinations exhibited sensitivity of 80% of the \u003cem\u003eEscherichia coli\u0026nbsp;\u003c/em\u003estrain assessed. Moreover, \u003cem\u003eEscherichia coli\u003c/em\u003e showed a higher sensitivity to piperacillin/sulbactam sodium than cefoperazone/sulbactam sodium. \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e had the lowest sensitivity to cefuroxime sodium, while the effective rate of other cephalosporin antibiotics was measured at 75%. \u003cem\u003eKlebsiella pneumoniae\u0026rsquo;s\u003c/em\u003e sensitivity to piperacillin/sulbactam sodium was slightly higher than to cefoperazone/sulbactam sodium. Additionally, both \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e and \u003cem\u003eEscherichia coli\u003c/em\u003e had sensitivity above 90% to carbapenems The Both \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e and \u003cem\u003eEscherichia coli\u003c/em\u003e showed a fluctuated downward trend in sensitivity to cefuroxime sodium, cefoperazone/sulbactam sodium, and piperacillin/sulbactam sodium. \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e showed a fluctuating decrease in the sensitivity to imipenem and meropenem, while resistance appeared in \u003cem\u003eEscherichia coli\u003c/em\u003e only in 2023. The specific results are shown below（table 3）.\u003c/p\u003e\n\u003cp\u003eGram-positive cocci: The sensitivity of \u003cem\u003eEnterococcus faecium\u003c/em\u003e and \u003cem\u003eEnterococcus faecalis\u003c/em\u003e to teicoplanin and linezolid was 100%, and vancomycin was 99.42%.\u003c/p\u003e\n\u003cp\u003eFungi: \u003cem\u003eCandida albicans\u003c/em\u003e showed 100% sensitivity to voriconazole and fluconazole, while itraconazole and flucytosine both had sensitivities of 94.12%.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAmong the 1,094 bile specimens\u0026nbsp;collected, 875 were culture-positive, with a positivity rate of 79.98%.\u0026nbsp;From these samples,\u0026nbsp;1,026 microorganisms were detected, of which\u0026nbsp;gram-negative bacteria accounted for 63.65% (653/1,026), lower than the 70% reported in bile bacterial surveillance in China from 2014 to 2019 \u003csup\u003e[14]\u003c/sup\u003e. This difference may be attributed to the vast territory of China and the variation in bile bacterial spectra among different regions and populations. It may also suggest a decline in\u0026nbsp;gram-negative rods in recent years in biliary tract infections. From 2017 to 2021, the proportion of\u0026nbsp;gram-negative rods gradually decreased, while the proportion of\u0026nbsp;gram-positive cocci increased, consistent with some domestic and international research results\u0026nbsp;\u003csup\u003e[15,16]\u003c/sup\u003e.\u0026nbsp;In 2022-2023, there was a significant increase in the proportion of\u0026nbsp;gram-negative rods and a noticeable decrease in the proportion of\u0026nbsp;gram-positive cocci.\u0026nbsp;Considering the\u0026nbsp;patients\u0026rsquo;\u0026nbsp;general information, the history of\u0026nbsp;Oddi\u0026nbsp;sphincterotomy in 2022-2023 was higher than in the previous five years, suggesting that\u0026nbsp;Oddi\u0026nbsp;sphincterotomy\u0026nbsp;may disrupt\u0026nbsp;the barrier between the duodenal lumen and the biliary tract, increasing the invasion of\u0026nbsp;gram-negative bacteria. In the absence of\u0026nbsp;Oddi\u0026nbsp;sphincterotomy,\u0026nbsp;gram-positive bacterial infections increased\u0026nbsp;yearly, consistent with some relevant reports\u003csup\u003e[15,16]\u003c/sup\u003e. However, analysis\u0026nbsp;of\u0026nbsp;the proportions of major\u0026nbsp;gram-negative species each year found that the proportions of \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, \u003cem\u003eEnterobacter cloacae\u003c/em\u003e, and Enterococcus\u0026nbsp;species\u0026nbsp;(\u003cem\u003eEnterococcus faecalis\u003c/em\u003e, \u003cem\u003eEnterococcus faecium\u003c/em\u003e) did not change over the seven years, indicating that\u0026nbsp;Oddi\u0026nbsp;sphincterotomy does not increase the proportions of these bacteria or affect the distribution of Enterococcus\u0026nbsp;species, which differs from some domestic and international research results\u003csup\u003e[10,16,17,18]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWe found that the proportion of fungi has continuously increased over the past seven years, with a significant rise observed in 2023 compared to the previous six years. Recent reports suggest that the incision of the Oddi sphincter is an independent risk factor for fungal detection\u003csup\u003e\u0026nbsp;[17]\u003c/sup\u003e. In our study, there was no difference in the history of Oddi sphincter incisions between 2022 and 2023; however, there was a difference in detection rates, leading to inconclusive results, possibly related to fewer cases in our hospital in 2022.\u003c/p\u003e\n\u003cp\u003eThe increasing trend observed\u0026nbsp;in the\u0026nbsp;diversity\u0026nbsp;of\u0026nbsp;gram-negative, gram-positive, and\u0026nbsp;fungal species over the years underscores the dynamic nature of microbial populations within the studied samples. Notably, in\u0026nbsp;2020, Enterococcus species detected included \u003cem\u003eEnterococcus hirae\u003c/em\u003e, \u003cem\u003eEnterococcus raffinosa\u003c/em\u003e, \u003cem\u003eEnterococcus intestinalis\u003c/em\u003e, and \u003cem\u003eEnterococcus gallinarum\u003c/em\u003e. In 2021, Morganella, Raoultella and Leuconostoc were detected. In 2022, Bacillus species were detected, indicating a change in the types of biliary bacteria. Possible reasons for this include:\u0026nbsp;first, the\u0026nbsp;widespread use of antibiotics in recent years, which\u0026nbsp;has led to changes in intestinal microbiota, indirectly affecting the types of biliary bacteria through the gut-liver axis \u003csup\u003e[19,20,21,22]\u003c/sup\u003e.\u0026nbsp;Second, environmental\u0026nbsp;pollutants such as microplastics and mercury can affect the stability of the adult microbiota \u003csup\u003e[23,24]\u003c/sup\u003e.\u0026nbsp;Third, the\u0026nbsp;intake of ultra-processed foods and food additives has been shown to affect intestinal health \u003csup\u003e[25,26]\u003c/sup\u003e, affecting biliary flora.\u0026nbsp;Lastly, using\u0026nbsp;antibiotics in livestock and aquaculture can directly or indirectly affect human intestinal flora, thereby altering biliary flora \u003csup\u003e[27]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAccording to data from the Bacterial Drug Resistance Monitoring Network in China, the top three bile-resistant bacteria from 2014 to 2019 were \u003cem\u003eEscherichia coli\u003c/em\u003e (30.9%), \u003cem\u003eKlebsiella pneumoniae\u0026nbsp;\u003c/em\u003e(12.7%), and \u003cem\u003eEnterococcus faecium\u003c/em\u003e (10.1%) \u003csup\u003e[14]\u003c/sup\u003e. In this study, from 2017 to 2023, the top three pathogens in bile culture were \u003cem\u003eEscherichia coli\u003c/em\u003e at 24.27% (249/1,026), \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e at 13.16% (135/1,026), and \u003cem\u003eEnterococcus faecium\u003c/em\u003e at 11.89% (122/1,026), consistent with the monitoring results. The detection of CRE in 2023 increased significantly compared to the previous six years.\u0026nbsp;The longitudinal\u0026nbsp;comparison revealed a rising trend in overall resistance of \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, particularly against third-generation cephalosporins. Among \u0026beta;-lactamase inhibitor combinations, sensitivity to piperacillin/sulbactam sodium was higher. This antibiotic resistance is globally documented\u003csup\u003e[28,29]\u003c/sup\u003e, indicating an increasing trend in bile pathogen resistance on a global scale, emphasizing the necessity to identify resistance patterns.\u0026nbsp;Our\u0026nbsp;antimicrobial sensitivity tests recommend piperacillin/sulbactam sodium as the first choice for empirical treatment in suspected\u0026nbsp;cases of\u0026nbsp;acute cholangitis. Considering the lower prevalence of Enterococcus species, early antibiotic treatment need not specifically target this group.\u0026nbsp;Our data indicate that adjustments\u0026nbsp;to antibiotic use can be made based on bile culture results.\u0026nbsp;Additionally, current\u0026nbsp;guidelines suggest collecting bile samples before using antimicrobial drugs whenever possible to avoid false-negative results\u003csup\u003e[6]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients using antibiotics for over three days or over three days of antibiotic exposure before admission were excluded from this study. Since the majority of patients were referred from external hospitals, we could not gather detailed information on their antibiotic usage before admission, potentially introducing selection bias. We observed a small number of patients diagnosed with acute suppurative cholangitis who underwent emergency surgery (with intraoperative bile described as white), yet their bile cultures yielded negative results. This observation suggests that these patients might have received antibiotic treatment before admission, lowering the positivity rate of the cultures. The impact of the 2022 pneumonia epidemic in our region led to decreased patient volume, which may affect the results. Additionally, variations in microbial frequency and antibiotic resistance among different regions and populations may limit the generalizability of this study.\u0026nbsp;\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, from 2017 to 2023, \u003cem\u003eEscherichia coli\u003c/em\u003e remained the predominant organism in bile cultures of acute cholangitis patients; however,\u0026nbsp;there were changes in the types, biological characteristics, and resistance patterns of bile microorganisms. The proportion of\u0026nbsp;gram-positive bacteria\u0026nbsp;increased\u0026nbsp;annually in cases without differences in Oddi sphincterotomy history.\u0026nbsp;Additionally,\u0026nbsp;Oddi sphincterotomy increased the proportion of\u0026nbsp;gram-negative bacteria but did not affect the major species (\u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e,\u0026nbsp;and\u0026nbsp;\u003cem\u003eEnterobacter cloacae\u003c/em\u003e) or Enterococcus species. Over time, there was an increase in pathogen diversity, with higher detections of fungi and drug-resistant strains, indicating a changing microbial community in the biliary tract with worsening resistance. The resistance rates of \u003cem\u003eEscherichia coli\u003c/em\u003e and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e were on the rise, with sensitivity to third-generation cephalosporins below 50% and being more sensitive to piperacillin/ sulbactam sodium than to cefoperazone/sulbactam sodium. \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Xinjiang Uiger Municipal People\u0026rsquo;s Hospital (KY2022072217).\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used or analyzed for the study were provided within the manuscript and additional data can be requested from the corresponding author.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNo funding was provided for data collection or the creation of this manuscript.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eYH: Study concept and design; execution of the study; data interpretation; writing and revisions of manuscript. WD：Data interpretatio.JL: Study concept and design;critical revision of manuscript.study supervision.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe would like to thank the cooperative and supportive staff of the Gastroenterology and Hepatobiliary surgery Department.\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMohammad A, Cholangitis AH. Diagnosis, Treatment and Prognosis. J Clin Transl Hepatol. 2017;5:404\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiura F, Okamoto K, Takada T, et al. Tokyo guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. 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Dig Dis. 2019;37:155\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable1\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eGeneral information and clinical data of patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"3.225806451612903%\" rowspan=\"2\"\u003e\n \u003cp\u003eYear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.225806451612903%\" rowspan=\"2\"\u003e\n \u003cp\u003ecases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.526881720430108%\" colspan=\"2\"\u003e\n \u003cp\u003egender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.451612903225806%\" rowspan=\"2\"\u003e\n \u003cp\u003eage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" colspan=\"3\"\u003e\n \u003cp\u003esymptom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.827956989247312%\" colspan=\"2\"\u003e\n \u003cp\u003ecause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.602150537634408%\" rowspan=\"2\"\u003e\n \u003cp\u003eHistory of cholecystectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.731182795698924%\" colspan=\"3\"\u003e\n \u003cp\u003eHistory of biliary surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.27956989247312%\" colspan=\"3\"\u003e\n \u003cp\u003eBile collection method\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.555555555555555%\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.166666666666667%\"\u003e\n \u003cp\u003efever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003ebellyache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003ejaundice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.555555555555555%\"\u003e\n \u003cp\u003ebenign\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\"\u003e\n \u003cp\u003emalignant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.88888888888889%\"\u003e\n \u003cp\u003eOddi sphincterotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.555555555555555%\"\u003e\n \u003cp\u003ePTCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003echolangiotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.555555555555555%\"\u003e\n \u003cp\u003eERCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.555555555555555%\"\u003e\n \u003cp\u003ePTCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003echolangiotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e58.93\u0026plusmn;3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.695652173913043%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.869565217391305%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.782608695652174%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.782608695652174%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n 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width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.782608695652174%\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e65.19\u0026plusmn;0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.260869565217391%\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.521739130434782%\"\u003e\n \u003cp\u003e166\u003c/p\u003e\n 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\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTables 2-3 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"bacteria, fungi, antimicrobial༛trends༛cholangitis༛Oddi sphincter incision","lastPublishedDoi":"10.21203/rs.3.rs-4162226/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4162226/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWith the increase in bacterial resistance worldwide, the bacterial characteristics of the biliary tract may have changed. Bile specimens for microbiological analysis are obtained primarily during endoscopic retrograde cholangiopancreatography, with a few from percutaneous transhepatic cholangial drainage. However, in some regions of China, patients still undergo laparoscopic T-tube drainage. The lack of data from this subset may lead to an incomplete understanding of the characteristics of the biliary microbiome.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003e1094 hospitalized patients diagnosed acute cholangitis from January 1, 2017 to December 31, 2023, who underwent biliary drainage procedures with bile specimen collection in our hospital were selected.Collect and analyse their general information, results of biliary culture, antimicrobial susceptibility and potential reasons for changes over 7 years.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 1,094 patients with acute cholangitis, 875 specimens (79.91%) yielded positive bile cultures, facilitating the detection of 1,026 strains belonging to 24 genera and 75 species of pathogens..Gram-negative bacteria were predominant,accounting for 63.65%(653/1,026) of the isolates, followed by gram-positive bacteria at 31.97%(328/1,026) and fungi at 4.39%(45/1,026). The main genera were Escherichia (249, 24.27%), Enterococcus (197, 19.20%), Klebsiella (170, 16.57%). Over the years, there has been a fluctuating upward trend in the diversity of pathogens. From 2017 to 2021, the proportion of gram-negative bacilli gradually decreased while gram-positive cocci increased, although the difference was not statistically significant. However, from 2022 to 2023, the proportion of gram-negative bacilli significantly increased compared to the previous five years.There was an increasing trend in the resistance rates of Escherichia coli and Klebsiella pneumoniae to various antibiotics.They were more sensitive to piperacillin/sulbactam sodium than to cefoperazone/sulbactam sodium.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe proportion of gram-positive bacteria increased annually in patients without differences in the history of Oddi sphincter incision. Incision of the Oddi sphincter increased the proportion of gram-negative bacteria but did not increase the proportion of major bacterial species and had no significant effect on the distribution of Enterococcus. The detection rates of resistant bacteria increased significantly. The resistance rates of Escherichia coli and Klebsiella pneumoniae to antibiotics showed an overall increasing trend.\u003c/p\u003e","manuscriptTitle":"Distribution Characteristics, Antimicrobial Resistance, and Variation Trends of Biliary Microbiome in Acute Cholangitis patients : A 7-Year Retrospective Study in a Tertiary Hospital in Northwest China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-01 16:36:56","doi":"10.21203/rs.3.rs-4162226/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac0d268c-4616-4c9d-a7d7-40480c7a5a81","owner":[],"postedDate":"April 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-01T16:37:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-01 16:36:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4162226","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4162226","identity":"rs-4162226","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}