Oral Administration of Nanoiron Sulfide Supernatant for the Treatment of Gallbladder Stones with Chronic Cholecystitis.

Cholelithiasis with chronic cholecystitis is prevalent and threatens human health. Most cholecystitis caused by bacterial infection or biofilms is accompanied by gallstones in the clinic, making gallbladder removal the only effective solution. Here, we provide a strategy to eliminate gallstone biofilms and dissolve gallstones by oral administration of a supernatant derived from nanoscale iron sulfide (nFeS supernatant). First, by using gallstones obtained from the clinic, we simulated biofilm formation on gallstones and tested the antibacterial activity of a nFeS supernatant in vitro. We found that the supernatant kills bacteria with a 5-log reduction in viability and destroys the biofilm structure. Smashed gallstones coincubated with E. coli biofilms promote gallstone formation, while nFeS supernatant can inhibit this process. Second, by using a murine (C57BL/6) model of cholelithiasis and cholecystitis, we tested the antibacterial efficacy and therapeutic effects of nFeS supernatant on cholelithiasis in vivo. Animal experimental data show that oral administration of nFeS supernatant can reduce 60% of bacteria in the gallbladder and, remarkably, remove gallstones with 2 days of treatment compared with clinical drug combinations (chenodeoxycholid acid and ciprofloxacin). Third, by performing protein abundance analysis of L02 cells and mouse livers, we observed the changes in CYP7a1, HMGCR, and SCP2 expression, indicating that the nFeS supernatant can also regulate cholesterol metabolism to prevent gallstone formation. Finally, hematologic biochemistry analysis and high-throughput sequencing technology show that the nFeS supernatant possesses high biocompatibility. Therefore, our work demonstrates that the nFeS supernatant may be a potential regimen for the treatment of cholelithiasis and cholecystitis by oral administration.

[Biliary microbiote in cholecystectomized patients: Review of empirical antibiotherapy]. / Microbiota biliar en pacientes colecistectomizados: Revisión de la antibioterapia empírica.

OBJECTIVE: Cholecystitis is an important cause of hospital admission. In moderate or severe cholecystitis, the delay in treatment can lead to serious complications. Our objective is to analyze the microorganisms isolated in bile from cholecystectomized patients and their sensitivity pattern, to evaluate the empirical treatment in those cases in which the surgical removal of the gallbladder should be delayed. METHODS: Prospective descriptive study of biliary cultures of patients undergoing cholecystectomy from May 2013 to February 2015, in the Surgery Department of the Hospital General Universitari de Castelló. RESULTS: We studied 196 patients, 83 women (42.3%) and 113 men (57.7%), with an average age of 61.5 years. The most used antibiotics as empiric treatment were piperacillin/tazobactam (77.8%) and amoxicillin/clavulanic (14.8%). In 46.4% of patients (91/196) bile cultures were positive. 165 microorganisms were isolated. The majority were Gram-negative bacilli (60.5%), mainly of the Enterobacterales order (91/54.5%), with Escherichia coli being the most frequent microorganism (24%) followed by Klebsiella spp. (12.5%). 3 E. coli with extended-spectrum beta-lactamase (ESBL) and 1 K. pneumoniae with ESBL were isolated. Microorganisms producing carbapenemase and methicillin-resistant Staphylococcus aureus were not isolated. CONCLUSIONS: The bile microbiota, with a predominance of Enterobacterales is similar to that found in european studies..

Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.

Evaluation of Lysimachia christinae Hance extracts as anticholecystitis and cholagogic agents in animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Lysimachia christinae Hance is one of the herbs commonly used in traditional Chinese medicine for the treatment of cholecystitis and cholagogic efficiency. AIMS OF THE STUDY: The water extract of Lysimachia christinae Hance was investigated to see if it possesses cholecystitis and cholagogic effects through traditional pathways. MATERIALS AND METHODS: Lithocholic acid (LCA) and Escherichia coli were used to induce cholecystitis in adult guinea pigs. The present study evaluated the cholagogic effects of LCHE treatment on bile secretion and bile emptying in Sprague-Dawley rats and male Kunming mice. RESULTS: The results showed that LCHE not only produced excellent anticholecystitis effects but also improved lesion severity in gallbladders induced by LCA. Similarly, LCHE administered to animals in the high-dose group exhibited an antibacterial effect in acute cholecystitis, and treatment with a mid-range or a high dose of LCHE resulted in an antipyretic effect, however, three doses of LCHE treatment groups had no effect on pathological change induced by Escherichia coli in gallbladder. Treatment with a high dose of LCHE significantly promoted bile secretion (0-90min, P<0.01), and treatment with a mid-range dose also significantly promoted bile secretion (30-60min P<0.05). Furthermore, treatment with a high dose of LCHE significantly promoted bile emptying (P<0.01). CONCLUSIONS: Our results demonstrate that LCHE exhibits a marked anticholecystitis and cholagogic activity in animals, which supports previous claims of its use in traditional Chinese medicine.

Isolated bacteria and susceptibilities to antimicrobial agents in biliary infections.

BACKGROUND/AIMS: A total of 209 bacterial strains were isolated from patients with biliary infection in our department between January 1982 and December 2000. METHODOLOGY: Antimicrobial susceptibility tests were conducted to ascertain the presence of drug-resistant bacteria. RESULTS: The breakdown of the 109 strains from the patients with primary biliary infections was as follows: 70 strains of gram-negative aerobic bacteria; 27 strains of gram-positive aerobic bacteria; 6 strains of gram-negative anaerobic bacteria; and 6 strains of gram-positive anaerobic bacteria. Among the 100 strains isolated from the patients with postoperative infection, the frequency of anaerobic bacteria was similar, but the frequency of gram-negative aerobic bacteria was lower at 55 strains, whereas frequency of gram-positive aerobic bacteria was higher at 36 strains. Of the 70 strains of gram-negative aerobic bacteria isolated from patients with primary biliary infection, the following four bacteria accounted for 75% of the total: Klebsiella pneumoniae, Escherichia coli, Enterobacter spp., and Pseudomonas aeruginosa. CONCLUSIONS: The frequencies of gram-negative aerobic bacteria were high among patients with primary biliary infection, while those of gram-positive aerobic bacteria were high among patients with postoperative biliary infection. Although VRE was not isolated, the frequency of MRSA was extremely high.

Analysis of etiology and drug resistance of biliary infections / 华中科技大学学报（医学）（英德文版）

The bile was collected from fro patients with biliary infections, with the bacterium isolated to study the sensitivity of each kind of the bacterium to several antibiotics in common use. Except G- bacterium, we also found some kinds of G+ bacterium in infection bile. G- bacterium were not sensitive to Clindamycin, G+ bacterium were sensitive to Ciprofloxacin. Escherichia coli, Xanthomonas maltophilia, Enterobacter cloacae, Pseudomonas aeruginosa were sensitive to Ampicillin. G+ bacterium were not sensitive to Azactam. Enterococcus faecalis, Enterococcus faecium, Enterobacter cloacae were not sensitive to Ceftazidime. Enterococcus faecalis, Staphylococcus coagulase negative, Staphylococcus epidermidis, Pseudomonas aeruginosa were not sensitive to Ceftriaxone Sodium. We didn't found any bacterium resistance Imipenem. The possibility of the existence of G+ bacterium as well as drug resistance should be considered n patients with biliary infections. The value of susceptibility test should be respected to avoid drug abuse of antibiotics.

[Relationship between endotoxemia and APACHE-III scoring and integrated therapy of Chinese and Western medicine].

OBJECTIVE: To explore the relationship between endotoxemia and the severity of disease condition and therapeutic effect. METHODS: According to randomized controlled principle, the 153 acute infectious patients were divided into simple antibiotics treated group and antibiotics plus Chinese drugs combined treated group, and patients in each group were subdivided into 3 types according to acute physiology and chronic health evaluation (APACHE-III) scoring: type A (APACHE-III scoring < or = 20 points), type B (APACHE-III scoring 21-40 points) and type C (APACHE-III scoring > 40 points). The 77 cases in the simple treated group were 40 males and 37 females, aging 18-76 years, mean 46.5 +/- 27.5 years, 41 cases of type A, 28 of type B and 8 of type C, treatment course 10-14 days, mean 11.5 +/- 2.5 days. The 76 cases in the combined treated group were 39 males and 37 females, aging 18-70 years, mean 44.5 +/- 25.5 years, 37 of type A, 30 of type B and 9 of type C, treatment course 10-14 days, mean 10.5 +/- 2.5 days. Limulus test was used to determine the endotoxin content in peripheral blood of patients, and further analysis on the relationship between endotoxemia and APACHE-III scoring was conducted. RESULTS: Acute severe infectious patients whose APACHE-III scoring > 20 points occurred endotoxemia (P < 0.05), and the condition of disease was positively related to the APACHE-III scoring (r = 0.718, P < 0.05). Chinese drugs plus antibiotics can obviously alleviate endotoxemia (P < 0.05) and improve the prognosis of patients. CONCLUSION: Endotoxemia can serve as a referential parameter for predicting the severity of disease. Integrated therapy of Chinese and western medicine in treating bacterial infection revealed better results than that of antibiotics solely.

Acalculous nontyphoidal salmonellal cholecystitis requiring surgical intervention despite ciprofloxacin therapy: report of three cases.

Nontyphoidal salmonellal cholecystitis is a rare complication of nontyphoidal salmonellal enterocolitis. We describe three patients with this complication who were hospitalized in a regional infectious disease unit at Ruchill Hospital, Glasgow, Scotland, over a period of 12 months. All three patients were receiving ciprofloxacin therapy before the episodes of cholecystitis became clinically evident, and all required surgical intervention.

Biliary tract infections treated with ciprofloxacin.

Thirty-two patients with severe biliary tract infections (cholecystitis and cholangitis) were treated with ciprofloxacin intravenously followed by oral ciprofloxacin. Complete clinical and bacteriological cure has been observed in 28 out of 32 patients and therapy failure occurred in four patients. Overall, no major adverse effects were encountered. These data suggest that intravenous ciprofloxacin followed by oral administration is an effective and safe agent for the therapy of severe biliary tract infections.

A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.

[Use of antibiotics and nitrofurans in treating acute and chronic cholecystitis]. / Primenenie antibiotikov i nitrofuranov v lechenii ostrogo i khronicheskogo kholetsistita.

Sixty-two patients with acute cholecystitis and 108 patients with chronic calculous cholecystitis were examined. High levels of contamination of the bile, gallbladder mucosa and gallstones were shown. E. coli, Staphylococcus and Streptococcus were most frequent among 20 species of aerobic and anaerobic bacteria. Preoperative sanation of the hepatoduodenal area with antibiotics did not result in complete elimination of the bacteria in the bile, gallbladder mucosa and gallstones. The use of nitrofurans and especially furazolidone and furagin in the preoperative period prevented the microbial growth in the specimens collected during the operations. The data of the study allow recommending the use of furazolidone and furagin for preoperative sanation of the biliferous tract.

Antibiotics in acute cholecystitis.

In 460 cholecystectomies performed for acute cholecystitis 215 (47%) positive gallbladder bile cultures were obtained. In 73% of emergency operations bacteria were recovered, in 48% of early operations (p less than 0.001) and in 29% of late operations (p less than 0.001). In vitro concentrations of 8-16 mcg/ml of ampicillin or cephalothin inhibited in most cases the growth of E. coli, Klebsiella and Enterococci, which comprised 75% of all strains isolated. One hour after intravenous infusion of 1 g ampicillin the mean serum level was 21 mcg/ml, the mean common duct level 16 mcg/ml and the mean gallbladder bile level 4.4 mcg/ml. In acute cholecystitis 2 g cephalothin gave mean concentrations of 14, 8, and 1.2 mcg/ml. Most of these patients had cystic duct obstruction both on intravenous cholegraphy and during operation. Control patients with patent cystic ducts who received ampicillin had mean gallbladder and common duct bile levels of 47 and 56 mcg/ml, and those receiving cephalothin 23 and 28 mcg/ml. It appears that adequate gallbladder bile concentrations of antibiotics are not attainable in acute cholecystitis because of the obstruction to the bile flow. The favourable results of prophylactic antibiotic treatment in reducing septic complications seem to depend more on adequate serum and tissue concentrations than on the concentration of antibiotics in the bile.

Biliary tract surgery.

Postoperative wound infection rates after biliary tract surgery vary tremendously from 2% after uncomplicated cholecystectomy to 20% in series including many jaundiced patients. Almost all such infections arise from organisms growing in the diseased biliary tract, since infection rate of 1% are achieved when the bile is sterile. A history of cholangitis identifies only one third of the patients with infected bile, but four easily recognized clinical factors point to positive bile cultures in 60% to 75% of patients: (1) age over 70, (2) obstructive jaundice, (3) common duct stones without jaundice, and (4) emergent acute cholecystitis. These selected high-risk patients have postoperative infection rates of 20% to 27%. Preoperative administration of cephaloridine reduced this high rate of infection to 5% in a prospective randomized but not blinded trial. The initially reported experience of 84 patients has been extended to 140 and continues to confirm the efficacy of prophylactic antibiotics in selected high-risk patients. In contrast, there is no present evidence supporting the use of antibiotic prophylaxis in low-risk patients under 70 years of age undergoing uncomplicated cholecystectomy.

Rifamide in acute cholecystitis and biliary surgery.

Determination of the minimum inhibitory concentrations of rifamide necessary to inhibit organisms isolated from the biliary tract showed that the organisms were almost invariably sensitive to concentrations which are readily attainable in the biliary tract. Three cases of severe acute inflammation of the biliary tract were treated and this led to rapid clinical improvement. In 61 patients undergoing biliary surgery a random group was given rifamide 150 mg twice daily, beginning 24 hours before operation and continuing for three days afterwards. In the untreated group eight patients had infected bile at operation and five subsequently developed a wound infection. In the rifamide group three had infected bile at operation and only one developed a wound infection. A similar number of postoperative chest infections occurred in each group of patients. There is some evidence of reduction in length of hospital stay in the treated patients.