Bile Culture May Guide Antibiotic Stewardship in Acute Bacterial Cholangitis.

BACKGROUND: Bile cultures are often sent with blood cultures in patients with acute bacterial cholangitis. AIMS: To assess the yield of blood and bile cultures in patients with cholangitis and the clinical utility of bile cultures in guiding therapy. METHODS: All patients diagnosed with cholangitis, based on the Tokyo 2013/2018 guidelines were recruited retrospectively over ten years. The clinical and investigation details were recorded. The results of bile and blood cultures including antibiotic sensitivity patterns were noted. The concordance of microorganisms grown in blood and bile cultures and their sensitivity pattern were assessed. RESULTS: A total of 1063 patients with cholangitis were included. Their mean age was 52.7 ± 14 years and 65.4% were males. Blood cultures were positive in 372 (35%) patients. Bile culture was performed in 384 patients with 84.4% being positive, which was significantly higher than the yield of blood culture (p < 0.001). Polymicrobial growth was more in bile (59.3%) than in blood cultures (13.5%, p < 0.001). E.coli, Klebsiella, Enterococcus and Pseudomonas were the four most common organisms isolated from both blood and bile. Extended spectrum betalactamase producing organisms were isolated in 57.7% and 58.8% of positive blood and bile cultures, respectively. Among 127 patients with both blood and bile cultures positive, complete or partial concordance of organisms was noted in about 90%. CONCLUSION: Bile and blood cultures have a similar microbial profile in most patients with cholangitis. As bile cultures have a significantly higher yield than blood cultures, they could effectively guide antimicrobial therapy, especially in those with negative blood cultures.

Endoscopic retrograde cholangiopancreatography-obtained bile culture in acute cholangitis: retrospective analysis of bile cultures and risk factors in a tertiary care center.

BACKGROUND: Collection of bile aspirate during endoscopic retrograde cholangiopancreatography (ERCP) is essential to identify pathogens responsible for acute cholangitis. Limited data are available on the risk factors for the presence of multidrug-resistant organisms (MDRO) in bile. METHODS: We conducted this retrospective, single-center study to assess the prevalence and susceptibility rates of bacteria in bile cultures, and the risk factors for the presence of pathogens, MDRO, and fungi in bile. All consecutive patients who underwent biliary drainage for acute cholangitis from January 2017 to December 2019 were included. RESULTS: 443/1610 ERCPs were performed for acute cholangitis. Bile culture was collected in 91.4% (405/443), of which 86.7% were positive. Most common isolates were Enterococcus faecalis (37.6%) and Escherichia coli (32.8%). Vancomycin resistance was found in 9.9% of Enterococcus species (spp.); extended-spectrum beta-lactamases (ESBL) and carbapenemases in 11.2% and 0.9% of Enterobacteriaceae, respectively. The empiric antimicrobial therapy was changed in 26.4% (n = 107) of cases, with a clinical response in 90.7%. In multivariate analysis, biliary stenting was an independent risk factor for positive bile culture (odds ratio [OR] 9.43; P < 0.01). Independent risk factors for MDRO in bile were patient age>60 years (OR 2.51; P = 0.03), previous sphincterotomy (OR 2.57; P = 0.02), and biliary stenting (OR 2.80; P < 0.01). Previous sphincterotomy was the only risk factor for isolation of fungi in bile (OR 1.61; P = 0.04). CONCLUSIONS: Our study showed an increasing prevalence of Enterococcus spp. and MDRO. Bile cultures should be routinely collected in cholangitis and in patients with repeated ERCPs to allow more efficient antimicrobial treatment.

Quick detection of causative bacteria in cases of acute cholangitis and cholecystitis using a multichannel gene autoanalyzer.

PURPOSES: Acute cholangitis and cholecystitis can become severe conditions as a result of inappropriate therapeutic administration and thereafter become increasingly resistant to antimicrobial treatment. The simultaneous detection of the bacterial nucleic acid and antimicrobial resistance gene is covered by the national health insurance program in Japan for sepsis. In this study, we evaluate the use of a multichannel gene autoanalyzer (Verigene system) for the quick detection of causative bacteria in cases of acute cholangitis and cholecystitis. METHODS: This study included 108 patients diagnosed with acute cholangitis or cholecystitis between June 2015 and November 2018. A bacterial culture test and Verigene assay were used to evaluate the bile samples. RESULTS: The most commonly isolated bacteria were Escherichia coli, which includes six extended-spectrum beta-lactamase (ESBL)-producing E. coli. Among the patients with positive bile cultures, bacteria were detected in 35.7% of cases via the Verigene system. The detection rates of the Verigene system significantly increased when the number of bacterial colonies was ≥ 106 colony-forming unit (CFU)/mL (58.1%). Cases with a maximum colony quantity of ≥ 106 CFU/mL exhibited higher inflammation, suggesting the presence of a bacterial infection. CONCLUSIONS: The Verigene system might be a new method for the quick detection of causative bacteria in patients with infectious acute cholangitis and cholecystitis.

Managing Contamination and Diverse Bacterial Loads in 16S rRNA Deep Sequencing of Clinical Samples: Implications of the Law of Small Numbers.

In this article, we investigate patterns of microbial DNA contamination in targeted 16S rRNA amplicon sequencing (16S deep sequencing) and demonstrate how this can be used to filter background bacterial DNA in diagnostic microbiology. We also investigate the importance of sequencing depth. We first determined the patterns of contamination by performing repeat 16S deep sequencing of negative and positive extraction controls. This process identified a few bacterial species dominating across all replicates but also a high intersample variability among low abundance contaminant species in replicates split before PCR amplification. Replicates split after PCR amplification yielded almost identical sequencing results. On the basis of these observations, we suggest using the abundance of the most dominant contaminant species to define a threshold in each clinical sample from where identifications with lower abundances possibly represent contamination. We evaluated this approach by sequencing of a diluted, staggered mock community and of bile samples from 41 patients with acute cholangitis and noninfectious bile duct stenosis. All clinical samples were sequenced twice using different sequencing depths. We were able to demonstrate the following: (i) The high intersample variability between sequencing replicates is caused by events occurring before or during the PCR amplification step. (ii) Knowledge about the most dominant contaminant species can be used to establish sample-specific cutoffs for reliable identifications. (iii) Below the level of the most abundant contaminant, it rapidly becomes very demanding to reliably discriminate between background and true findings. (iv) Adequate sequencing depth can be claimed only when the analysis also picks up background contamination. IMPORTANCE There has been a gradual increase in 16S deep sequencing studies on infectious disease materials. Management of bacterial DNA contamination is a major challenge in such diagnostics, particularly in low biomass samples. Reporting a contaminant species as a relevant pathogen may cause unnecessary antibiotic treatment or even falsely classify a noninfectious condition as a bacterial infection. Yet, there are few studies on how to filter contamination in clinical microbiology. Here, we demonstrate that sequencing of extraction controls will not reveal the full spectrum of contaminants that could occur in the associated clinical samples. Only the most abundant contaminant species were consistently detected, and we present how this can be used to set sample specific thresholds for reliable identifications. We believe this work can facilitate the implementation of 16S deep sequencing in diagnostic laboratories. The new data we provide on the patterns of microbial DNA contamination is also important for microbiome research.

First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

A case report on death from acute bacterial cholangitis accompanied by von Meyenburg complexes: Use of 16S rRNA gene sequencing to identify pathogenic microbes from postmortem formalin-fixed, paraffin-embedded tissue.

RATIONALE: In some cases, autopsy is the first opportunity to find a previously unrecognized critical infection. Pathogens are identified by various methods, such as microscopic examination, special stains, culture tests, and immunohistochemistry. Here, we report a case of 16S ribosomal RNA (rRNA) gene sequencing using a postmortem formalin-fixed, paraffin-embedded (FFPE) tissue, which was useful for identifying pathogenic microbes. PATIENT CONCERNS: Autopsy was performed on an 87-year-old man who had chronic renal failure and had developed sepsis from a central venous catheter infection 10 days before his death. Prior to these events, von Meyenburg complexes (VMCs) were also found during regular checkups. DIAGNOSIS: Postmortem microscopic examination revealed acute purulent cholangitis with numerous microabscesses, accompanied by VMCs. Gram-negative rods were observed in some microabscesses, which were considered causative pathogens. INTERVENTIONS: 16S rRNA gene sequencing using postmortem FFPE tissue. OUTCOMES: Pseudomonas aeruginosa was identified, different from the one detected in the central venous catheter culture while alive. LESSONS: 16S rRNA gene sequencing is a useful tool for identifying pathogenic microbes in postmortem FFPE tissues. This technique may be useful for amplicon sizes of approximately 100 bp or less.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Temocillin as an alternative treatment for acute bacterial cholangitis: a retrospective microbiology susceptibility-based study of 140 episodes.

With rising antibiotic resistance, alternatives to carbapenems are needed for acute cholangitis (AC). Temocillin reaches high biliary concentrations with limited impact on microbiota. We retrospectively included 140 AC episodes and assessed the efficacy of temocillin using microbiology susceptibility testing from blood cultures. Considering all bacteria collected by episode, resistance to temocillin, PIP/TAZ and 3GC occurred in 27/140 (26%), 32 (22.8%) and 31 (22%) episodes, respectively (p = 0.7). After documentation, temocillin could have spared PIP/TAZ or carbapenems in 14/26 and 4/11 episodes. Temocillin may constitute an alternative treatment after microbiological documentation by sparing carbapenems and/or PIP/TAZ, but not as an empirical therapeutic option.

[Pathogens' distribution and changes of antimicrobial resistance in the bile of acute biliary tract infection patients].

Objective: To investigate the pathogens' distribution and antimicrobial resistance in the bile of acute biliary tract infection patients. Methods: The data of bile bacterial culture and drug sensitivity test of 223 acute biliary tract infection patients who underwent gallbladder puncture or endoscopic retrograde cholangiopancreatography drainage from July 2009 to July 2019 were analyzed retrospectively at Department of General Surgery,Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine.There were 141 males and 82 females with age of 67.3 years(range:28 to 93 years).Three to five milliliter of bile was extracted from each patient and sent to the laboratory for bacterial culture,identification and drug sensitivity test.The patients were divided into two groups according to the visiting time: the former group (n=124) was admitted from July 2009 to July 2014,and the latter group(n=99) was admitted from August 2014 to July 2019.The distribution of pathogenic bacteria and the changing trend of drug resistance rate of common bacteria in the two groups were compared.The results of drug sensitivity test were analyzed by WHONET software provided by WHO bacterial surveillance network.The drug resistance rates in different time periods were compared by χ2 test. Results: In this study,there were 147 cases of acute cholangitis and 76 cases of acute cholecystitis.A total of 376 strains of pathogenic bacteria were cultured.Among them,98 strains(26.1%) were gram-positive bacteria,269 strains(71.5%) were gram-negative bacteria and 9 strains(2.4%) were fungi.The top three gram-positive bacteria were Enterococcus faecium (49.0%,48/98),Enterococcus faecalis(20.4%,20/98),and Enterococcus luteus(7.1%,7/98).The top 5 gram-negative bacteria were Escherichia coli(33.5%,90/269),Klebsiella pneumoniae(13.8%,37/269),Pseudomonas aeruginosa(13.0%,35/269),Acinetobacter baumannii (12.6%,34/269),and Enterobacter cloacae(4.8%,13/269).From 2009 to 2019,there was no significant change in the proportion of gram-positive bacteria (former group vs. latter group: 25.3% vs. 28.2%) and gram-negative bacteria(former group vs.latter group: 74.7% vs. 71.8%) in the bile of patients with acute biliary tract infection.Gram-positive bacteria were mainly Enterococci(85.7%,84/98) and gram-negative bacteria were Escherichia coli(33.5%,90/269).Acinetobacter baumannii accounted for 7.8%(11/142) of gram-negative bacteria in the former group and 18.1%(23/127) in the latter group,an increase of 10.3% over previous five years.Pseudomonas aeruginosa had a downward trend,16.9% in the former group(24/142) and 8.7% in the latter group (11/127),the proportion decreased by 8.2%,and the other changes were not significant.The drug resistance rates of common gram-positive bacteria were relatively stable,and the drug resistance rates of Enterococcus faecium to many antibiotics were higher than those of Enterococcus faecalis.The resistance rates of gram-negative bacteria to most antibiotics showed an upward trend,among which Klebsiella pneumoniae showed an upward trend to most of antibiotics(former group: 0/15－4/13, latter group: 55.0%－70.0%; χ2=3.996－16.942, P=0.000－0.046).The drug resistance rates of Acinetobacter baumannii was generally higher,but there were no significant changes in the drug resistance rates of Acinetobacter baumannii between the two groups.The drug resistance rates of Pseudomonas aeruginosa to most antibiotics increased,and the overall drug resistance rates of Escherichia coli were stable and showed a slight upward trend. Conclusions: The main pathogens in bile of patients with acute biliary tract infection are gram-negative bacteria.The constituent ratio of various gram-negative bacteria had no significant change from 2009 to 2019,but the drug resistance rates shows an upward trend.Among the gram-negative bacteria, Escherichia coli is the most important pathogen,and the proportion has no significant change.The proportion of Acinetobacter baumannii in the former group was significantly higher than that in the former group.And the proportion of Pseudomonas aeruginosa has a decreased trend.

The Intestinal Flora at Kasai Procedure in Children with Biliary Atresia Appears Not to Affect Postoperative Cholangitis.

INTRODUCTION: Evidence supports long-term oral antibiotic prophylaxis to prevent cholangitis after Kasai procedure. Data regarding perioperative intravenous prophylaxis are lacking. Ascending pathogens from the intestine are made responsible for recurrent cholangitis. Therefore, we analyzed the flora in the upper jejunum during the Kasai procedure and their potential impact on postoperative cholangitis. MATERIALS AND METHODS: In 26 patients, swabs were taken at the bowel prepared for the Roux-en-Y-loop. Our postoperative protocol includes intravenous third-generation cephalosporins for 2 weeks and rectal steroids starting at day 4. Cholangitis was defined as the postoperative reappearance of acholic stools or increase of serum bilirubin in combination with fevers or increase of inflammatory parameters. In this scenario, Tazocin was administered for another 2 weeks. RESULTS: Swabs remained sterile in nine patients (34.6%). In 17 patients (65.4%), gram-positive and gram-negative pathogens were identified; all belonging to physiological intestinal flora. A total of 96.2% pathogens were covered by the antibiotic prophylaxis. The cholangitis incidence was 55.6% in the sterile cohort, and 23.5% in the gram-positive and gram-negative cohort (p = 0.06). In the cholangitis cohort, no significant differences were detected for the age at Kasai and the pre- and postoperative total bilirubin. CONCLUSION: We found that our antibiotic regiment covered bacteria in the upper gastrointestinal (GI) tract in the majority of our patients at the time of Kasai. Nonetheless, a significant proportion of patients developed signs of cholangitis. There was no higher rate of cholangitis in patients with resistant bacteria. Thus, our data do not support the hypothesis of extended postoperative intravenous antibiotics to prevent ascending cholangitis.

Aspergillus fumigatus cholangitis in a patient with cholangiocarcinoma: case report and review of the literature.

Aspergillus spp. cholangitis is an uncommon presentation of invasive aspergillosis. Only few cases are described in the literature affecting severely immunocompromised patients or patients following biliary surgery. Especially, invasive aspergillosis in non-haematological patients is associated with high mortality rates, caused by atypical presentations, which is associated with a delay in diagnosis and therapy. We report a 72-year-old man with primary diagnosis of cholangiocarcinoma and stent implantation by endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression who developed severe cholangitis with invasive aspergillosis. The patient had no history of prior hospitalisation, no immunosuppressive therapy and no preceding biliary surgery. Furthermore, in this exceptional case of extrapulmonary aspergillosis, there were no signs of pulmonary involvement. From the literature review, only three cases of Aspergillus cholangitis could be identified. Clinical manifestations of invasive aspergillosis can be variable and classical risk factors such as immunosuppression are not mandatorily present. Clinical awareness of these rare cases is of vital importance for initiation of correct therapy.

Shewanella: an important, emerging and lethal pathogen in a patient with recurrent presentations of cholangitis.

We present a case of recurrent cholangitis caused by Shewanella algae, a lethal, emerging pathogen that clinicians should be made aware of. An 86-year-old man with a history of gastrectomy for peptic ulcer disease and a cerebrovascular accident with known choledocholithiasis presented with recurrent episodes of cholangitis that failed conservative antibiotic treatment regimens. Shewanella has been described to have increasing resistance to piperacillin and tazobactam. Both S. algae and multidrug-resistant Escherichia coli were co-isolated in this patient, which required broader spectrum antibiotics for successful treatment and management. A high index of suspicion is required if the history is suggestive of marine or aquatic exposure, which could expose the patient to this lethal pathogen. Re-thinking and re-taking the history are important cornerstones in refining the diagnosis when faced with recurrent presentations of the same problem.

First case report of Solobacterium moorei bacteremia due to acute cholangitis in South Korea.

Solobacterium moorei is an anaerobic gram-positive bacillus that rarely causes bacteremia. Herein, we report a case of S. moorei bacteremia associated with acute cholangitis in a patient without malignancy. The patient had a history of chronic pancreatitis with pancreaticogastrostomy and presented with fever and abdominal pain. Computed tomography scans showed acute cholangitis and S. moorei identified in blood cultures were confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and 16S rRNA sequencing. The patient was successfully treated with endoscopic retrograde biliary drainage and antibiotics including meropenem and piperacillin-tazobactam.

Molecular characterization of a carbon dioxide-dependent Escherichia coli small-colony variant isolated from blood cultures.

A carbon dioxide-dependent small-colony variant of Escherichia coli SH4888 was isolated from blood cultures of a patient with cholangitis. To date, little is known regarding the molecular mechanisms leading to formation of carbon dioxide-dependent phenotypes in clinical isolates, but abnormalities in the carbonic anhydrase are thought to cause carbon dioxide autotrophy. In this study DNA sequence analysis of the carbonic anhydrase-encoding can locus in the carbon dioxide-dependent E. coli SH4888 revealed that the isolate had a 325-bp deletion spanning from the 3'-terminal region of can to the 3'-terminal region of hpt, which encodes a hypoxanthine phosphoribosyltransferase. To confirm that the carbon dioxide-dependent SCV phenotype of E. coli SH4888 was due to the can mutation, we performed a complementation test with a plasmid carrying an intact can that restored the normal phenotype. However, E. coli SH4888 had increased virulence compared to the can-complemented E. coli SH4888 in a murine infection model. In conclusion, these data confirm that impaired carbonic anhydrase function can cause a carbon dioxide-dependent SCV phenotype in E. coli SH4888 and provides a fitness advantage in terms of infection.

Microbiology and risk factors for gram-positive Cocci bacteremia in biliary infections.

BACKGROUND: The rapid antibiotics treatment targeted to a specific pathogen can improve clinical outcomes of septicemia. We aimed to evaluate the clinical characteristics and outcomes of biliary septicemia caused by cholangitis or cholecystitis according to causative organisms. METHODS: We performed a retrospective cohort study in 151 patients diagnosed with cholangitis or cholecystitis with bacterial septicemia from January 2013 to December 2015. All patients showed clinical evidence of biliary tract infection and had blood isolates that demonstrated septicemia. RESULTS: Gram-negative, gram-positive, and both types of bacteria caused 84.1% (127/151), 13.2% (20/151), and 2.6% (4/151) episodes of septicemia, respectively. The most common infecting organisms were Escherichia coli among gram-negative bacteria and Enterococcus species (Enterococcus casseliflavus and Enterococcus faecalis) among gram-positive bacteria. There were no differences in mortality, re-admission rate, and need for emergency decompression procedures between the gram-positive and gram-negative septicemia groups. In univariate analysis, previous gastrectomy history was associated with gram-positive bacteremia. Multivariate analysis also showed that previous gastrectomy history was strongly associated with gram-positive septicemia (Odds ratio = 5.47, 95% CI: 1.19-25.23; P = 0.029). CONCLUSIONS: Previous gastrectomy history was related to biliary septicemia induced by gram-positive organisms. This information would aid the choice of empirical antibiotics.

Microbiology and clinical characteristics of acute cholangitis with their impact on mortality; a retrospective cross sectional study.

OBJECTIVE: To evaluate microbiological and clinical characteristics of acute cholangitis along with their impact on mortality, and to compare the role of early versus late biliary drainage in the management of cholangitis. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital Research Centre, Lahore, Pakistan, and comprised records of all patients presenting with acute cholangitis from June, 2012, to June, 2017. The risk factors, presence of bacteremia, resistance pattern of microbial pathogens and severity were assessed according to Tokyo guidelines in addition to associated mortality and recurrence at 3 months. Data was analysed using SPSS 20. RESULTS: Of the 230 patients, 137(59.6%) were male. The overall mean age was 56±13 years. The most common isolated organism was Escherichia coli 54(70.1%). Clinical severity (p=0.001), late biliary drainage (p=0.001) and use of multiple stents (p=0.03) were associated with increased mortality. However, in multivariable analysis, only high body mass index (p=0.01) and Tokyo severity grades II (p=0.04) and III (p=0.001) were significant factors associated with mortality. CONCLUSIONS: Early identification of risk factors, administration of appropriate antibiotics and establishing early biliary drainage were found to be the key management steps to reduce cholangitis-related mortality.

Postoperative infectious complications caused by multidrug-resistant pathogens in patients undergoing major hepatectomy with extrahepatic bile duct resection.

BACKGROUND: Few reports have addressed postoperative infectious complications caused by multidrug-resistant pathogens. The aim of this study was to review the surgical outcomes of patients undergoing major hepatectomy with extrahepatic bile duct resection and to clarify the incidence of and the risk factors for postoperative infectious complications caused by multidrug-resistant pathogens. METHODS: Medical records of consecutive patients who underwent major hepatectomy with extrahepatic bile duct resection between 2006 and 2017 were retrospectively reviewed. RESULTS: Among 620 study patients, 219 had postoperative infectious complications, including 62 (10.0%) with postoperative infectious complications caused by multidrug-resistant pathogens. The mortality of the 62 patients with postoperative infectious complications caused by multidrug-resistant pathogens was higher (n = 8, 12.9%) than that in the 157 patients with postoperative infectious complications caused by non-multidrug-resistant pathogens(n = 2, 1.3%) (P < .001). With multivariate analysis, the presence of preoperative cholangitis, the extent of liver resection more than 50%, operative time longer than 600 minutes, the amount of blood loss more than 1500 mL, and the presence of postoperative infectious complications caused by multidrug-resistant pathogens were identified as independent risk factors for postoperative death. The presence of multidrug-resistant pathogens in preoperative bile culture, the amount of blood loss greater than 1500 mL, the presence of bile leakage, and pancreatic fistula were identified as independent risk factors for postoperative infectious complications caused by multidrug-resistant pathogens. CONCLUSION: The incidence of postoperative infectious complications caused by multidrug-resistant pathogens in patients undergoing major hepatectomy with extrahepatic bile duct resection is high, approximately 10%. This troublesome complication is closely associated with postoperative death. Thus, preventing postoperative infectious complications caused by multidrug-resistant pathogens is an urgent task to improve surgical outcome after major hepatectomy with extrahepatic bile duct resection.

Use of microbiological and patient data for choice of empirical antibiotic therapy in acute cholangitis.

BACKGROUND: Ineffective antibiotic therapy increases mortality of acute cholangitis. The choice of antibiotics should reflect local resistance patterns and avoid the overuse of broad-spectrum agents. In this study, we analysed how results of bile and blood cultures and patient data can be used for selection of empirical antibiotic therapy in acute cholangits. METHODS: Pathogen frequencies and susceptibility rates were determined in 423 positive bile duct cultures and 197 corresponding blood cultures obtained from 348 consecutive patients with acute cholangitis. Patient data were retrieved from the medical records. Associations of patient and microbiological data were assessed using the Chi-2 test and multivariate binary logistic regression. RESULTS: In bile cultures, enterobacterales and enterococci were isolated with equal frequencies of approximately 30% whereas in blood cultures, enterobacterales predominated (56% compared to 21% enterococci). Antibiotic resistance rates of enterobacterales were > 20% for fluorochinolones, cephalosporines and acylureidopenicillins but not for carbapenems (< 2%). The efficacy of empirical therapy was poor with a coverage of bacterial bile and blood culture isolates in 51 and 69%, respectively. By multivariate analysis, predictors for pathogen species, antibiotic susceptibility and expected antibiotic coverage were identified. CONCLUSIONS: In unselected patients treated for acute cholangitis in a large tertiary refferential center, use of carbapenems seems necessary to achieve a high antibiotic coverage. However, by analysis of patient and microbiological data, subgroups for highly effective carbapenem-sparing therapy can be defined. For patients with community-acquired cholangitis without biliary prosthesis who do not need intensive care, piperacillin/tazobactam represents a regimen with an expected excellent antibiotic coverage.