ro13-9904 and Cholangitis

The use of prophylactic antibiotics before endoscopic retrograde cholangiopancreatography (ERCP) is recommended by all major international gastroenterological societies, especially in the presence of an obstructed biliary system. This study compared the occurrence rate of post-procedural complications, including cholangitis and septicemia, between prophylactic intravenous moxifloxacin and ceftriaxone in patients with bile duct obstruction scheduled for therapeutic ERCP.. From November 2013 to July 2015, 86 consecutive patients with biliary obstruction with one or more factors predicting benefits of antibiotic prophylaxis prior to ERCP were included in the current randomized open-label non-inferiority trial (ClinicalTrial.gov identifier NCT02098486). Intravenous moxifloxacin (400 mg/day) or ceftriaxone (2 g/day) were given 90 minutes before ERCP, and were administered for more than 3 days if the patient developed symptoms and signs of cholangitis or septicemia. Recalcitrant cholangitis was defined as persistence of cholangitis for more than 5 days after ERCP or recurrence of cholangitis within 30 days after ERCP.. Recalcitrant cholangitis occurred in 1 (2.3%) and 2 (4.8%) patients receiving intravenous moxifloxacin and ceftriaxone group, respectively (P=0.612). Septicemia was noted in 1 (2.3%) and 1 (2.4%) patient in intravenous moxifloxacin and ceftriaxone group, respectively (P=1.0). The mean hospital stay was also not significantly different between the moxifloxacin and ceftriaxone groups (8.8±7.2 vs 9.1±9.4 days, P=0.867). Antibiotic resistance of the isolated pathogens by in vitro activity assay was noted in 1 (2.3%) and 2 (4.8%) patients in the moxifloxacin and ceftriaxone group, respectively (P=0.612).. Intravenous moxifloxacin is not inferior to intravenous ceftriaxone for the prophylactic treatment of post-ERCP cholangitis and cholangitis-associated morbidity.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Ceftriaxone; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Cholestasis; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Prospective Studies

To compare the efficacy of ceftriaxone and that of cefoperazone plus sulbactam (sulperazon) in controlling infection, in scavenging bacteria from bile, and in their costs when treating acute suppurative cholangitis with choledochostomy.. Patients were randomly assigned to two groups: the ceftriaxone group (R-group, n=95) and sulperazon group (S-group, n=95). Before choledochostomy, both groups received one intravenous dose of the corresponding antibiotics: and 2 g ceftriaxnoe for the R-group, 2 g sulperazon, containing 1 g cefoperazone and 1 g sulbactam, for the S-group. After the operation, the patients in the R-group received ceftriaxone 2 g i.v. q.d.; the patients in the S-group received sulperazon 2 g i.v. b.i.d.. In addition, all patients in both groups received metronidazole 0.5 g daily before and after the operation. The efficacy was evaluated by efficiency in controlling infection and the persisting days of symptoms due to infection, fever and leukocytosis; the persisting days was compared using the life table method to calculate the "cumulative probability of persistence of symptoms (CPPS)". The two groups were also compared in regards to their biliary bacterial clearance rates and the costs directly attributable to the antibiotics.. The efficiency in controlling infection was 98.9% (94/95) in both groups. However, the CPPS of the R-group decreased more rapidly than that of the S-group, Log-Rankchi2=6.7901, P=0.0092. Biliary bacterial clearance rate on post-operative day 3 was 72.0% (36/50) for the R-group, 41.3% (19/46) for the S-group, P=0.0037. Cost directly attributable to the antibiotics were (1788.29 +/- 518.46) yuan (RMB) for the R-group, and (3768.74 +/- 820.55) yuan for the S-group, F=395.51, P=0.0000.. Both ceftriaxone and sulperazon are effective in treating acute suppurative cholangitis when used before and after choledochostomy. Ceftriaxone is superior in expediting symptom relief and bacterial clearance from bile, and is more cost-effective.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Bacterial Agents; Cefoperazone; Ceftriaxone; Cholangitis; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Perioperative Care; Postoperative Period; Prospective Studies; Sulbactam; Suppuration

For the therapy of acute cholangitis complete biliary drainage and antibiotic therapy is needed. The aim of the current study was to compare intravenous therapy of acute cholangitis with Ceftriaxone or Levofloxacin in a prospective and randomized fashion.. Patients with biliary obstruction and clinical signs of infection received in addition to 1.5 g Metronidazole either 500 mg Levofloxacin/die or 2 g Ceftriaxone/die. Early on during ERCP, bile was aspirated via the cannulation catheter and cultured for bacteria under aerobic and anaerobic conditions. Minimal inhibitory concentrations of the respective antibiotics were determinate for each isolate. The clinical course was followed for at least 6 days with clinical and laboratory data.. 60 patients with clinical signs of acute cholangitis were randomised. In 40 patients (66 %) biliary colonization with bacteria could be identified. In all bacterial species Levofloxacin showed significantly lower rates of in-vitro resistance as compared to Ceftriaxone. However, the percentage of patients with a clinical cure or significant improvement was the same in the two groups.. The clinical effect of Levofloxacin and Ceftriaxone in patients with acute cholangitis showed no significant differences. Because of improved in-vitro efficiency, a calculated therapy with Levofloxacin might be advantageous.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacteriological Techniques; Bile; Ceftriaxone; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Data Interpretation, Statistical; Drug Resistance, Bacterial; Humans; Infusions, Intravenous; Levofloxacin; Metronidazole; Middle Aged; Ofloxacin; Prospective Studies; Time Factors

The combination of penicillin with an aminoglycoside has been recommended as an initial treatment of choice for patients with acute infections of the biliary tract. However, many patients have incidence of renal problems and for this reason aminoglycosides must be avoided. Newer antimicrobial agents with lesser nephrotoxic effects will be tried. We, therefore, performed a prospective, randomized trial of ofloxacin, a new quinolone and ceftriaxone in patients with acute biliary tract infections. Fifty-two patients with severe biliary tract infections (cholecystitis and cholangitis) were randomly assigned to receive either ofloxacin (n = 28) or ceftriaxone (n = 24). The 2 groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. Bacteria were documented in 48% of patients in the ofloxacin group and in 46% in the ceftriaxone group. The percentage of patients with a clinical cure or significant improvement was the same in the 2 groups. No significant difference was noted between the 2 treatment groups with respect to drug toxicity. These data suggest that intravenous ofloxacin followed by oral administration is an effective and safe single drug for the therapy of patients with acute biliary tract infections.

Topics: Anti-Infective Agents; Bacteremia; Ceftriaxone; Cephalosporins; Cholangitis; Cholecystitis; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Ofloxacin; Phlebitis

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Female; Gallstones; Humans; Kidney; Kidney Transplantation; Pneumonia, Bacterial; Risk Assessment; Stents

Ceftriaxone (CTRX) is a third-generation cephalosporin commonly used to treat infections such as community-acquired pneumonia and urinary tract infections caused by mainly Gram-negative bacteria and some Gram-positive bacteria. Here, we report a case of a patient on hemodialysis who had chorea-like symptoms with high blood concentration of CTRX. A 74-year-old Japanese woman receiving hemodialysis was admitted with obstructive cholangitis and was started on CTRX therapy at a dose of 2 g every 24 hours. On the 6th day after starting administration of CTRX, chorea-like symptoms appeared. We suspected that her symptoms were caused by a high blood concentration of CTRX. We performed a series of blood sampling to determine the concentration of CTRX at different time points before and after discontinuing CTRX administration. CTRX concentrations were higher than those expected in healthy adults, and her chorea-like symptoms had disappeared from the second day of discontinuation of CTRX. The association between CTRX blood concentration and chorea-like symptoms is unclear. However, measuring a series of plasma or serum concentrations from symptom onset to disappearance suggested that chorea-like symptoms appeared when the concentration exceeded approximately 450 μg/mL. Care should be taken when administering CTRX to patients with cholestasis undergoing hemodialysis, as blood CTRX levels may rise unexpectedly and result in complications.

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Cholangitis; Chorea; Female; Humans; Renal Dialysis

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; C-Reactive Protein; Ceftriaxone; Cholangitis; Dose-Response Relationship, Drug; Drainage; Drug Administration Schedule; Endoscopy, Digestive System; Female; Humans; Leukocyte Count; Male; Microbial Sensitivity Tests; Middle Aged; Prognosis; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Cholangiopancreatography, Magnetic Resonance; Cholangitis; Cholelithiasis; Female; Humans; Pressure Ulcer; Tomography, X-Ray Computed

The objective of this study was to evaluate the serum and bile concentrations of cefazolin and ceftriaxone at the third and sixth hours in an experimental obstructive jaundice model and to identify the rate of excretion of these antibiotics into the bile.. Thirty-two Wistar albino rats were used in this study. The bile and serum levels of cefazolin were measured at the third hour in the A1 group and at the sixth hour in the A2 group, with cefazolin administered as 5 mg/rat; while the bile and serum levels of ceftriaxone were studied at the third hour in the B1 group and at the sixth hour in the B2 group, with ceftriaxone administered as 5 mg/rat.. After 3 hr of cefazolin administration, the serum concentration in the A1 group reached a mean of 1.8 μg/ml, while the bile concentration was 90% of the serum concentration, with a mean of 1.6 μg/ml; whereas in the B1 group, the third-hour serum concentration of ceftriaxone was 18.6 μg/ml, while the bile concentration was found to be as high as 330% of this level, i.e., 56 μg/ml. The serum value of cefazolin decreased to 1.4 μg/ml in the A2 group and ceftriaxone decreased to 3.7 μg/ml in the B2 group at the sixth hour.. Although the excretory level of cefazolin and ceftriaxone into the bile reaches therapeutic doses, the duration for which these levels are above those required for bactericidal activity is short. Ceftriaxone is better concentrated in the serum and bile than cefazolin.

Topics: Animals; Anti-Bacterial Agents; Bacterial Translocation; Bile; Cefazolin; Ceftriaxone; Cholangitis; Cholestasis, Extrahepatic; Drug Evaluation, Preclinical; Female; Ligation; Male; Microbial Sensitivity Tests; Rats; Rats, Wistar; Serum

Topics: Acute Disease; Anti-Bacterial Agents; Bile; Ceftriaxone; Cholangitis; Humans; Male; Middle Aged; Tomography, X-Ray Computed

Antimicrobial agents should be administered to all patients with suspected acute cholangitis as a priority as soon as possible. Bile cultures should be performed at the earliest opportunity. The important factors which should be considered in selecting antimicrobial therapy include the agent's activity against potentially infecting bacteria, the severity of the cholangitis, the presence or absence of renal and hepatic diseases, the patient's recent history of antimicrobial therapy, and any recent culture results, if available. Biliary penetration of the microbial agents should also be considered in the selection of antimicrobials, but activity against the infecting isolates is of greatest importance. If the causative organisms are identified, empirically chosen antimicrobial drugs should be replaced by narrower-spectrum antimicrobial agents, the most appropriate for the species and the site of the infection.

Topics: Acute Disease; Anti-Bacterial Agents; Bile; Ceftriaxone; Cholangitis; Humans

In 12 patients with inoperable malignant obstructive jaundice, percutaneous transhepatic biliary drainage was performed to decompensate the bile ducts. For a period of 7 days, the patients received a single daily i.v. dose of 1 g CFTX, and the serum and bile concentrations were measured at defined intervals.. The dose sufficed to kill about 85% of the expected organisms. Although an accumulation of the substance as documented under conditions of normal bile flow was not demonstrable under cholestatic conditions, effective levels were nevertheless found in the bile and showed a tendency to increase with increasing bile flow.

Topics: Aged; Aged, 80 and over; Bile; Biliary Tract Neoplasms; Bilirubin; Ceftriaxone; Cholangitis; Cholestasis, Extrahepatic; Female; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged

The risk of cholangitis after ERCP has been reported to occur in up to 50% of patients with obstructive jaundice. Prophylactic antibiotics have therefore been advocated to reduce the risk. Here we report on the results of 46 patients with obstructive jaundice who were given 1 g of Ceftriaxone i.v. 30 to 60 min. prior to the procedure. Only one patient developed cholangitis with septicemia, which was treated conservatively. No side effects were observed in this group of patients. It is suggested that Ceftriaxone is an adequate prophylactic method to prevent cholangitis and septicemia in patients with obstructive jaundice.

Topics: Adult; Aged; Aged, 80 and over; Ceftriaxone; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Cholestasis; Female; Humans; Male; Middle Aged; Premedication

Topics: Abscess; Bacteria; Ceftriaxone; Cholangitis; Female; Humans; Liver Abscess; Male; Middle Aged; Pancreatic Diseases; Pancreatitis; Peritonitis