Pharmacotherapy for primary biliary cholangitis: an assessment of medication candidacy and rates of treatment.

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.

D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease.

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

Changing Patterns of Causative Pathogens over Time and Efficacy of Empirical Antibiotic Therapies in Acute Cholangitis with Bacteremia.

Background/Aims: To select appropriate empirical antibiotics, updates on the changes in pathogens are essential. We aimed to investigate the changes in pathogens and their antibiotic susceptibility in acute cholangitis (AC) with bacteremia over a period of 15 years. Furthermore, the efficacy of empirical antibiotic therapies and the risk factors predicting antibiotic-resistant pathogens (ARPs) were analyzed. Methods: A total of 568 patients with AC and bacteremia who were admitted to Daegu Catholic University Medical Center from January 2006 to December 2020 were included. Their medical records were retrospectively reviewed. In addition, the data were grouped and analyzed at 3-year intervals under the criteria of Tokyo Guideline 2018. Results: During the study period, 596 pathogens were isolated from blood cultures of 568 patients. The three most common pathogens were Escherichia coli (50.5%), Klebsiella species (24.5%), and Enterococcus species (8.1%). The proportion of vancomycin-resistant Enterococci (VRE) has increased since the mid-2010 (0.0% to 4.3%, p=0.007). There was emergence of carbapenem-resistant Enterobacteriaceae (CRE) in 2018 to 2020, albeit not statistically significant (1.3%, p=0.096). Risk factors predicting ARP were healthcare-associated infection, history of previous biliary intervention, and the severity of AC. For patients with these aforementioned risk factors, imipenem was the most effective antibiotic and piperacillin-tazobactam was also effective but to a lesser degree (susceptibility rates of 92.1% and 75.0%, respectively). Conclusions: The proportion of VRE has increased and CRE has emerged in AC. In addition, healthcare-associated infection, history of previous biliary intervention, and the severity of AC were independent risk factors predicting ARP. For patients with these risk factors, the administration of imipenem or piperacillin-tazobactam should be considered.

Therapeutic drug monitoring guided fluconazole therapy in a patient with cholangitis sepsis.

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

Lay abstract A successful fluconazole treatment of Candida cholangitis based on therapeutic drug monitoring, is described in our case study. Unlike other azole antimycotic agents, fluconazole is not considered a desirable candidate for therapeutic drug monitoring. However, as shown in our case study, a fixed dosage regimen might not lead to adequate fluconazole exposure in every patient and a personalized dosing regimen might be useful in the achievement of adequate fluconazole exposure and the successful treatment of Candida infection.

A Network Pharmacology Study of the Molecular Mechanisms of Hypericum japonicum in the Treatment of Cholestatic Hepatitis with Validation in an Alpha-Naphthylisothiocyanate (ANIT) Hepatotoxicity Rat Model.

BACKGROUND This network pharmacology study aimed to identify the active compounds and molecular mechanisms involved in the effects of Hypericum japonicum on cholestatic hepatitis. We validated the findings in an alpha-naphthylisothiocyanate (ANIT) rat model of hepatotoxicity. MATERIAL AND METHODS The chemical constituents and targets of H. japonicum and target genes previously associated with cholestatic hepatitis were retrieved from public databases. A network was constructed using Cytoscape 3.7.2 software and the STRING database and potential protein functions were analyzed based on the public platform of bioinformatics. ANIT was used to induce cholestatic hepatitis in a rat model using 36 Sprague-Dawley rats, and this model was used to investigate intervention with 3 doses of quercetin (low-dose, 50 mg/kg; medium-dose, 100 mg/kg; and high-dose, 200 mg/kg), the main active component of H. japonicum. Levels of serum biochemical indexes were measured by commercial kits, and the messenger RNA (mRNA) levels of markers of liver and mitochondrial function and oxidative stress were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS The main active ingredients of H. japonicum were quercetin, kaempferol, and tetramethoxyluteolin, and their key targets included prostaglandin G/H synthase 2 (PTGS2), B-cell lymphoma-2 (BCL2), cholesterol 7-alpha hydroxylase (CYP7A1), and farnesoid X receptor (FXR). Quercetin intervention promoted recovery from cholestatic hepatitis. CONCLUSIONS The findings from this research provide support for future research on the roles of quercetin, kaempferol, and tetramethoxyluteolin in human liver disease and the roles of the PTGS2, BCL2, CYP7A1, and FXR genes in cholestatic hepatitis.

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.

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.

[Effect of ursodeoxycholic acid with traditional Chinese medicine on biochemical response in patients with primary biliary cholangitis: a real-world cohort study].

Objective: To examine the effects of ursodeoxycholic acid combined with Traditional Chinese Medicine on biochemical response in patients with primary biliary cholangitis. Methods: According to the method of receiving treatment, 197 patients with primary biliary cholangitis were divided into Traditional Chinese Medicine plus Western medicine group (93 cases, 47.2%) and Western medicine group (104 cases, 52.8%). From the baseline date, the combined group was treated with ursodeoxycholic acid plus traditional Chinese medicine decoction or Chinese patent medicine for at least one month and the Western medicine group simply took ursodeoxycholic acid . Additionally, Traditional Chinese medicine decoction prescriptions were mainly Xiaoyaosan and Yinchenhao. Chinese patent medicine were restricted to Biejia Ruangan tablets, Fuzheng Huayu capsules, Jiuweigantai capsules and Yinzhihuang capsules, which were used to treat liver fibrosis and cholestasis. The primary efficacy endpoint was defined as ALP level < 1.67 × ULN and ≥ 15% decrease in ALP with baseline level and TBIL≤ULN after 12 months of treatment. Results: The overall biochemical response rate of patients was 35.0% (69/197). The response rate of TCM+ Western medicine group was 43.0% (40/93), and that of Western medicine group was 27.9% (29/104). The difference between the two groups was statistically significant (χ(2) = 4.936, P < 0.05). Further analysis showed that the Chinese and Western medicine group was superior to the Western medicine group alone in reducing γ-glutamyltransferase (GGT) and TBiL [the median decline were GGT: 160.1 U/L and 111.3 U/L (Z = -2.474, P < 0.05), TBiL: 5.2 umol/l and 3.1 umol/l (Z = -2.125, P < 0.05)]. Conclusion: UDCA combined with TCM therapy can remarkably improve the biochemical response rate in patients with PBC and distinctly decrease the TBIL and GGT levels than UDCA monotherapy.

Prospective comparison of prophylactic antibiotic use between intravenous moxifloxacin and ceftriaxone for high-risk patients with post-ERCP cholangitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Intravenous moxifloxacin is not inferior to intravenous ceftriaxone for the prophylactic treatment of post-ERCP cholangitis and cholangitis-associated morbidity.

Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A systematic review.

BACKGROUND: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA. METHODS: We performed a systematic literature search on MEDLINE and the Cochrane Database of Systematic Reviews of the published literature. A total of 23 articles fulfilling our inclusion criteria were found. RESULTS: Several studies have shown an improvement in liver biochemistries with the use of obeticholic acid in conjunction with UDCA. Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit in this population but need more robust studies to confirm these observational results. Neither obeticholic acid nor fibrates have shown to increase transplant free survival. While there may be some benefit with methotrexate, colchicine, budesonide, mycophenolate mofetil and azathioprine, these findings were not consistent and the benefits were marginal. Further investigation is needed. CONCLUSION: In patients with PBC refractory to UDCA, obeticholic acid or a fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further investigation with randomized controlled trials is needed to provide high quality evidence to formulate standardized therapies in this difficult to treat population.

Obeticholic acid for the treatment of primary biliary cholangitis.

INTRODUCTION: Primary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destruction and inflammation of the intrahepatic bile ducts. The disease affects mainly women. The disease is often discovered through abnormal alkaline phosphatase (ALP) activity, and is confirmed when anti-mitochondrial antibodies (AMA) are present. The etiology of PBC is poorly understood. Cigarette smoking, immune dysregulation, nail polish, urinary tract infections, and low socioeconomic status have been implicated but none have been confirmed. Genome wide association studies (GWAS) have disclosed strong associations between certain human leukocyte antigen (HLA) alleles and PBC. PBC can progress to cirrhosis and end-stage liver disease. Hepatocellular carcinoma (HCC) develops in up to 3.5% of PBC patients. Ursodeoxycholic acid (UDCA) is the only medication approved for the treatment of PBC. The use of UDCA in PBC delays histological progression and extends the transplant-free survival. 40% of PBC patients do not respond adequately to UDCA, and these patients are at high risk for serious complications. Therefore, there is a critical need for more effective therapies for this problematic disease. Multiple other agents have either been or are currently being studied as therapeutic options in UDCA non-responder PBC patients. Six-ethyl chenodeoxycholic acid (6-ECDCA), a potent farnesoid X receptor (FXR) agonist, has shown anti-cholestatic activity in rodent models of cholestasis. Obeticholic acid (OCA, 6-ECDCA, or INT-747), a first-in-class FXR agonist, has been examined in PBC patients with inadequate response to UDCA, and shown promising results. Particularly, initial clinical trials have demonstrated that the use of OCA (in addition to UDCA) in PBC patients with inadequate response to UDCA led to significant reduction of serum alkaline phosphatase (ALP, an important prognostic marker in PBC). More recently, the results of a randomized clinical trial of OCA monotherapy in PBC reported significant reduction of ALP in the treatment group compared to placebo. AREAS COVERED: This review covers the preclinical and clinical studies of OCA in PBC. In addition, other alternative therapies that are currently being examined in PBC patients will also be discussed in this review. A literature search was carried out using the PubMed database. EXPERT OPINION: If approved by the U.S. FDA, OCA will likely be an important alternative add-on therapy in PBC patients who have inadequate response to UDCA.

Microbiological Assessment of Bile and Corresponding Antibiotic Treatment: A Strobe-Compliant Observational Study of 1401 Endoscopic Retrograde Cholangiographies.

The aim of this study was to determine the antibiotic susceptibility profiles of bacteria in bile samples and to analyze the clinical relevance of the findings as only limited information about risk factors for elevated frequence of bacterial and fungal strains in routinely collected bile samples has been described so far.A prospective cohort study at a tertiary care center was conducted. Seven hundred forty-four patients underwent 1401 endoscopic retrograde cholangiographies (ERCs) as indicated by liver transplantation (427/1401), primary sclerosing cholangitis (222/1401), choledocholithiasis only (153/1401), obstruction due to malignancy (366/1401), or other conditions (233/1401). Bile samples for microbiological analysis were obtained in all patients.The 71.6% (823/1150) samples had a positive microbiological finding, and 57% (840/1491) of the bacterial isolates were gram-positive. The main species were Enterococcus spp (33%; 494/1491) and Escherichia coli (12%; 179/1491). Of the samples, 53.8% had enteric bacteria and 24.7% had Candida spp; both were associated with clinical and laboratory signs of cholangitis (C-reactive proteins 35.0 ±â€Š50.1 vs 44.8 ±â€Š57.6; 34.5 ±â€Š51.2 vs 52.9 ±â€Š59.7; P < 0.001), age, previous endoscopic intervention, and immunosuppression. Multi-resistant (MR) strains were found in 11.3% of all samples and were associated with clinical and laboratory signs of cholangitis, previous intervention, and immunocompromised status. In subgroup analysis, strain-specific antibiotic therapy based on bile sampling was achieved in 56.3% (89/158) of the patients. In cases with a positive bile culture and available blood culture, blood cultures were positive in 29% of cases (36/124), and 94% (34/36) of blood cultures had microbial species identical to the bile cultures.Bactobilia and fungobilia can usually be detected by routine microbiological sampling, allowing optimized, strain-specific antibiotic treatment. Previous endoscopic intervention, clinical and laboratory signs of cholangitis, and age are independent risk factors. MR bacteria and fungi are an evolving problem in cholangitis, especially in immunocompromised patients.

PPARγ ligand attenuates portal inflammation in the MRL-lpr mouse: a new strategy to restrain cholangiopathy in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is characterized by chronic destructive cholangitis, which is associated with the reduced expression of an anti-inflammatory molecule, peroxisome proliferator-activated receptor-γ (PPARγ), in intrahepatic bile ducts. We previously demonstrated the anti-inflammatory effects of PPARγ ligands using cultured human biliary epithelial cells. In this study, we evaluated the effectiveness of PPARγ ligand against peribiliary inflammation in vivo. As an animal model of PBC, we used MRL/lpr mice in which a PBC-like cholangitis occurs naturally. Anti-inflammatory effects of the intraperitoneal administration of a PPARγ ligand, the prostaglandin D metabolite 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), were evaluated. In untreated mice, portal inflammation including cholangitis was found to some degree in the majority of portal tracts. In mice given a high-dose group, the degree of portal inflammation was significantly reduced and mice mostly lacking portal inflammation and cholangitis were also found. T cell numbers in portal tracts were markedly decreased in the high-dose group, compared with controls, whereas there was no significant difference in terms of B cells and macrophages. This study is the first to assess the therapeutic potential of a PPARγ ligand against portal inflammation including cholangitis. Anti-inflammatory effects of PPARγ ligands may prevent the progression of cholangiopathy in PBC patients.

Superiority of ceftriaxon to cefazolin in a rat model of obstructive jaundice: an experimental study.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Microbial profile and antibiotic sensitivity pattern in acute bacterial cholangitis.

INTRODUCTION: The changing antimicrobial sensitivity pattern of causative organisms poses a therapeutic challenge in treating patients with acute cholangitis. We therefore evaluated the microbial profile and sensitivity pattern to antibiotics in patients with acute bacterial cholangitis. METHODS: Data of patients above 18 years of age with acute bacterial cholangitis seen between January 2004 and March 2007 were retrospectively analyzed. The study was continued prospectively from April 2007 to December 2008. Data on clinical features, etiological and microbial profile and therapy, and patient outcomes were analyzed. In the prospective group, the antibiotic susceptibility patterns of organisms grown on bile and blood culture were also obtained. RESULTS: One hundred and eighty-five patients with acute cholangitis were studied. Choledocholithiasis (62.7%) and malignancy (29.2%) were the main predisposing factors. Bile culture was positive in 88 of 95 patients, and blood culture was positive in 47 of 178 (26.4%) patients. Bile cultures were predominantly polymicrobial (69.5%) in contrast to blood cultures (2.2%). E. coli was the predominant isolate in blood and bile. No growth was seen on anaerobic bile or blood cultures. The prospective group showed high resistance of E. coli to third generation cephalosporins and ciprofloxacin. CONCLUSIONS: Changing antimicrobial sensitivity patterns requires a revision of empiric antibiotic therapy policy in cholangitis.

Off-label drug use evaluation in paediatrics--applied to ciprofloxacin when used as treatment of cholangitis.

PURPOSE: To evaluate drug and indication specific off-label use in paediatrics, applied to ciprofloxacin (CPFX) in cholangitis. METHODS: We collected four different sets of data for an off-label drug use evaluation. (1) Literature review from medical journals, (2) the use and safety profile from the whole Swedish paediatric population by extracting data from national registers, (3) locally performed retrospective drug chart reviews, and (4) interviews regarding paediatric patients with CPFX treated cholangitis. RESULTS: The literature reviews show a lack of information for paediatric use of CPFX in cholangitis. The prescribing of CPFX to Swedish children has grown over the last decade and generated a small number of reports for adverse drug reactions. In our local biliary atresia population 32 patients had suffered from at least one episode of cholangitis and 13 patients had been prescribed CPFX. The dosing strategy had an empirical prescribing approach, since monitoring of bacterial resistance and efficacy is difficult in the biliary ducts. No clear relationship was seen between dosing and age/weight. Reports of suspected side effects could not be found in the retrospective chart reviews. The interviews show that the existing dosage forms are well accepted. CONCLUSIONS: This drug use evaluation creates awareness of the off-label situation. The international and national data are sparse for the paediatric use of CPFX in cholangitis. Locally we have highlighted a heterogeneous dosing strategy of CPFX, drug/drug interactions, and the need to monitor and report the risk of short- and long-term adverse drug reactions.

Un caso de QT largo y torsades de pointes por ciprofloxacino / No disponible

No disponible

[Cholangitis with hepatic microabscesses caused by Salmonella enterica serovar choleraesuis]. / Cholangitis mit hepatischen Mikroabszessen durch Salmonella enterica Serovar Choleraesuis.

HISTORY AND ADMISSION FINDINGS: A 71-year-old man was admitted to the emergency unit of another hospital with a mild gastroenteritis and high fever. On admission g-GT and C-reactive protein (CRP) levels were markedly elevated. Under nonspecific antibiotic therapy with ampicillin/sulbactam the fever persisted and for the first time, on day 5, the patient complained of right-sided abdominal pain. An increase in the laboratory values indicated cholestasis. After changing the antibiotics to ceftriaxon and metronidazole, acute cholangitis being suspected, the fever subsided immediately and the CRP level decreased. The patient was discharged after seven days of antibiotic treatment. But he was once more admitted after four weeks to another hospital because of severely reduced general condition and mild fever. He was transferred to our unit after two weeks. INVESTIGATIONS AND DIAGNOSIS: The test values indicated cholestasis and CRP was markedly elevated, while aminotransferase activity was slightly increased and normocytic normochromic anemia developed. Viral hepatitis, autoimmune and metabolic liver diseases, toxic liver damage, extrahepatic cholestasis and an endocarditis were excluded. Bile was aspirated by endoscopic retrograde cholangiopancreatography and added to blood culture bottles. Salmonella enterica serovar choleraesuis var. Kunzendorf was isolated. TREATMENT AND FURTHER COURSE: The patient was treated with ciprofloxacin, 2 x 250 mg by mouth for a total of five weeks. After 17 days of treatment no Salmonella bacteria were grown from a newly aspirated bile sample and the patient became free of fever. CONCLUSION: Salmonella infections do not always present as gastroenteritis. Bacteremia should be considered in the differential diagnosis of such infections. If cholangitis persists, the aspiration of bile for microbiological tests can be a rational diagnostic step and facilitates treatment. Prolonged administration of antibiotics is necessary to avoid relapse. and follow-up is very important when treatment is finished.

[Characteristics of immune homeostasis in patients with cholelithiasis complicated by hepatitis and cholangitis].

The most distinctive and typical complications of cholelithiasis are cholangitis and hepatitis. The article presents an analysis of peculiarities of immune homeostasis in 41 patients with cholelithiasis complicated by hepatitis and cholangitis before and after surgical treatment and with the use of antihomotoxicologic and homeopathic medications.