Treatment Of Biliary Tract Infections Research Articles

Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion meropenem/vaborbactam in a case series of orthotopic liver transplant recipients.

To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization. Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (fCss) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM fCss/MIC ratio >4 coupled with VBM free area under time-concentration curve (fAUC)/threshold concentration (CT) ratio >24. Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21-0.79) and 0.40 for VBM (range 0.20-0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one. The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L.

Addition of anaerobic coverage for treatment of biliary tract infections: a propensity score-matched cohort study.

To evaluate whether additional antibiotics that target anaerobes, including Bacteroides spp., are associated with improved clinical outcomes in patients with biliary tract infections (BTIs). This was a retrospective propensity score-matched cohort of adults aged ≥18 years with BTIs, admitted to hospital between 1 April 2015 and 30 March 2021. Eligible patients treated with antibiotics that provided coverage of anaerobes were compared with those treated with comparable regimens without anaerobic coverage. The primary outcome was a composite of mortality within 30 days or relapse within 90 days of source control or completion of antibiotics. Secondary outcomes included length of stay (LOS), duration of antibiotic therapy and adverse drug reactions. ORs were calculated using a weighted generalized linear regression model with propensity-score matching. Among 398 patients included, 209 were treated without anaerobic coverage and 189 with anaerobic coverage. After propensity-score matching, there was no significant difference in primary outcome between propensity-matched patients who received additional anaerobic coverage and those who did not [adjusted OR (aOR) 1.23; 95% CI 0.69-2.22)]. Those with anti-anaerobic coverage had longer LOS (aOR 4.85; 95% CI 1.68-13.98) and longer duration of antibiotic treatment (aOR 4.14; 95% CI 2.61-6.57) than those who did not receive additional anaerobic therapy, but not more adverse drug reactions (aOR 1.01; 95% CI 0.97-1.05). Omitting anti-anaerobic antibiotics may be a safe antimicrobial stewardship intervention. However, a randomized controlled trial may be warranted to definitively conclude whether additional anaerobic coverage in BTI treatment is necessary.

Comparison of Drug Resistance of Bile Isolated Bacteria in Nanjing from 2017 to 2020

Background: Analyzed pathogenic bacteria isolated from bile samples of patients with biliary tract infection and their drug resistance in the first Affiliated Hospital of Nanjing Medical University from 2017 to 2020, so as to provide evidence for the treatment of biliary tract infection. Methods: Clinical strains isolated from bile specimens of patients suspected of biliary infection in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020 were collected, The drug susceptibility criteria are based on the standards published by the National Standardization Committee of the US Clinical Laboratories. WHONET 5.6 software was used to analyze the distribution of pathogens and drug resistance. Results: From January 2017 to December 2020, a total of 2006 strains of bile pathogenic bacteria were cultured and identified. There were 1253 cases of gram-negative bacilli, 638 cases of gram-positive cocci, 98 cases of fungi, and 17 cases of Gram-positive bacilli. The top five pathogens of Gram negative bacilli were Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii. The top five pathogens of gram positive cocci were Enterococcus faecium, Enterococcus faecalis, Enterococcus gallinarum, Enterococcus faecalis and Staphylococcus epidermidis. the resistance rate of Escherichia coli to ampicillin, ampicillin / sulbactam, cefotetan, ceftazidime, ceftriaxone,cefepime, itronam, compound trimethoprim decreased, the resistance rate of Klebsiella pneumoniae to gentamicin, levofloxacin decreased, the resistance rate of Enterobacter cloacae to ciprofloxacin, levofloxacin decreased. the resistance rate of Pseudomonas aeruginosa to ceftazidime, cefepime, gentamicin decreased. the resistance rate of Acinetobacter baumannii to ceftazidime, ciprofloxacin decreased. the resistance rate of Enterococcus faecium to penicillin G, high concentration streptomycin, erythromycin decreased. Conclusions: Enterogenic pathogens were the main pathogens in China. Such as Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis and Enterococcus faecalis; Nosocomial infection pathogens. For example, Pseudomonas aeruginosa and Acinetobacter also need to be paid attention to. Clinicians should improve their awareness of microbiological examination and provide more reliable pathogenic evidence for the selection of clinical antibiotic.

Antibiotics in the Biliary Tract: A Review of the Pharmacokinetics and Clinical Outcomes of Antibiotics Penetrating the Bile and Gallbladder Wall.

Biliary tract infections (BTIs), including cholangitis and cholecystitis, are common causes of bacteremia. Bacteremic BTIs are associated with a mortality rate of 9-12%. The extent to which antibiotics are excreted in the bile and the ratio of their exposure to the minimum inhibitory concentration of the infecting organism are among the important factors for the treatment of BTIs. This review updates health care professionals on the distribution of antibiotics in the common bile duct, gallbladder, and gallbladder wall. Antibiotic efficacy in treating BTIs based on the latest available clinical studies is also discussed. The efficacy and pharmacokinetics of 50 antibiotics are discussed. Overall, most antibiotic classes exhibit biliary penetration that translates into clinical efficacy. Only seven antibiotics (amoxicillin, cefadroxil, cefoxitin, ertapenem, gentamicin, amikacin, and trimethoprim/sulfamethoxazole) had poor biliary penetration profiles. Three antibiotics (ceftibuten, ceftolozane/tazobactam, and doripenem) had positive clinical outcomes despite the lack of pharmacokinetic studies on their penetration into the biliary tract. Conflicting efficacy data were reported for ampicillin despite adequate biliary penetration, whereas conflicting pharmacokinetic data were reported with cefaclor and moxifloxacin. Even in the absence of supportive clinical studies, antibiotics with good biliary penetration profiles may have a place in the treatment of BTIs.

Antibacterial-Agent-Immobilized Gelatin Hydrogel as a 3D Scaffold for Natural and Bioengineered Tissues.

Hydrogels and their medical applications in tissue engineering have been widely studied due to their three-dimensional network structure, biocompatibility, and cell adhesion. However, the development of an artificial bile duct to replace the recipient’s tissue is still desired. Some challenges remain in the tissue engineering field, such as infection due to residual artifacts. In other words, at present, there are no established technologies for bile duct reconstruction as strength and biocompatibility problems. Therefore, this study investigated hydrogel as an artificial bile duct base material that can replace tissue without any risk of infectious diseases. First, an antibacterial agent (ABA), Finibax (an ABA used for the clinical treatment of biliary tract infection), was immobilized in gelatin using a crosslinking agent, and the antibacterial properties of the gel and its sustainability were tested. Furthermore, the immobilized amount and the improvement of the proliferation of the human umbilical vein endothelial cells (HUVECs) were cultured as the ABA-Gelatin hydrogel was introduced to prepare a 3D scaffold. Finally, we performed hematoxylin and eosin (H&E) staining after subcutaneous implantation in the rat. Overall, the ABA-Gelatin hydrogel was found to be viable for use in hydrogel applications for tissue engineering due to its good bactericidal ability, cell adhesion, and proliferation, as well as having no cytotoxicity to cells.

Changes in Microbial Profiles and Antibiotic Resistance Patterns in Patients with Biliary Tract Infection over a Six-Year Period.

Background: Biliary tract infection (BTI) is a common complication in patients with biliary obstruction caused by various biliary tract disorders. To improve the management of patients with BTI, microbial profiles from bile cultures and antibiotic resistance patterns were evaluated in this six-year retrospective study. Methods: A total of 709 patients with various biliary tract disorders from January 2012 to December 2017 were enrolled in this study. Bile specimens were taken from intra-operative puncture or post-operative drainage for microbial culture under sterile conditions. Microbial culture, identification, and antibiotic resistance test were performed according to a standard routine. Results: Cultures were positive in 574 of 789 bile specimens (73%). Of all isolates, 386 were gram-negative bacilli (67%), 170 were gram-positive cocci (30%), and 18 were fungi (3%). The two most common micro-organisms were Escherichia coli (29%) and Klebsiella pneumoniae (16%), the extended-spectrum β-lactamases (ESBL) positivity rates of which were 52% and 21%, respectively. Both bacteria were highly resistant to commonly used antibiotic agents (penicillins, cephalosporins, and quinolones), and highly susceptible to carbapenems, amikacin, and piperacillin-tazobactam. Enterococcus (19%) was the next most common bacteria isolated from bile samples, mainly including Enterococcus faecium (8%) and Enterococcus faecalis (6%). These two bacteria were resistant to cefazolin and clindamycin but sensitive to teicoplanin, tigecycline, and vancomycin. Enterococcus faecium was more resistant than Enterococcus faecalis to most of the tested antibiotic agents. Annual statistical analysis showed that the frequency of gram-negative enteric bacteria was decreasing slowly, but that of gram-positive enterococci was increasing slowly. Moreover, the overall antibiotic resistance rates of the most common strains have been decreasing slowly over the past six years. Conclusions: Enterobacteriaceae (Enterococcus coli and Klebsiella pneumoniae) and Enterococcus (Enterococcus faecium and Enterococcus faecalis) were the common pathogenic bacteria causing BTI, which exhibited high resistance to routinely used antibiotic agents and were highly sensitive to piperacillin-tazobactam, carbapenem, amikacin, and vancomycin. The microbial profiles from bile and its antibiotic resistance patterns have changed, which will help in the empirical treatment of BTI.

Anaerobic coverage as definitive therapy does not affect clinical outcomes in community-onset bacteremic biliary tract infection without anaerobic bacteremia

BackgroundAntibiotics with anaerobic coverage are widely used for the treatment of biliary tract infection (BTI), even in the absence of isolated anaerobes. The current study aimed to investigate the differences in clinical outcomes in patients with community-onset bacteremic BTIs without anaerobic bacteremia, treated with vs. without anti-anaerobic coverage.MethodsA retrospective analysis was conducted at a medical center in Taiwan from September 2014 to March 2016. Patients with community-onset bacteremic BTIs without anaerobic bacteremia and who were treated with appropriate antibiotics were analyzed. The clinical outcomes were compared between patients treated with and without anti-anaerobic coverage as definitive therapy after the blood culture reports were available. Multivariable and propensity score-adjusted analysis were used to identify the risk factors associated with treatment failure.ResultsAmong the enrolled 87 patients, 63 and 24 patients were treated with and without anaerobic coverage, respectively. Escherichia coli (55.2%) and Klebsiella pneumoniae (23.0%) were the most common organisms isolated from the blood cultures. The rate of treatment failure (relapse and 28-day mortality) was similar between the groups with and without anaerobic coverage (20.6% vs. 16.7%, p = 0.677). Propensity score-adjusted multivariable analysis revealed that definitive therapy without anaerobic coverage was not a predisposing factor for treatment failure (OR = 0.92, 95% CI 0.18–4.67, p = 0.916).ConclusionsDefinitive therapy without anaerobic coverage does not affect the outcomes of patients with community-onset bacteremic BTIs without anaerobes isolated from blood. Our results might provide a possible target for antibiotic stewardship interventions in BTIs.

Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections

Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication. Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC. Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33. The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

Liver tissue concentrations of levofloxacin after single intravenous administration of 500 mg for antibiotic prophylaxis in liver surgery

High concentrations of levofloxacin in soft tissues and body fluids, including gallbladder and bile, have been repeatedly reported, but no study on its penetration into human liver tissue after single-shot application has yet been published. Levofloxacin 500 mg was administered intravenously to 28 patients scheduled for liver resection. Blood samples were taken after the end of infusion and at the time of liver resection; concomitantly, a tissue specimen was also obtained. Serum concentrations (mean ± standard deviation) 10 min after the end of infusion were 6.59 ± 1.72 μg/mL and decreased only slightly throughout the operation. At the time of liver resection, levofloxacin concentrations in liver tissue were 18.14 ± 5.44 μg/g with corresponding serum concentrations of 4.84 ± 1.37 μg/mL. The tissue/serum ratio (3.72 ± 0.73 at the time of resection) was nearly constant over the sampling period ranging from 0.4 h to 3.8 h after the end of infusion, indicating a fast distribution of levofloxacin into the liver tissue. The tissue concentrations showed a significant correlation with serum concentrations and an inverse correlation with the grade of steatosis but not cirrhosis. Infectious post-operative complications were not observed. Levofloxacin penetrates into liver tissue exceptionally well and fast and is therefore a good candidate for antibiotic prophylaxis before invasive hepatobiliary procedures such as liver surgery as well as for treatment of biliary tract infections caused by levofloxacin-susceptible microorganisms.

Estudio comparativo, prospectivo y aleatorizado de piperacilina/tazobactam frente a ceftriaxona y ornidazol en el tratamiento de las infecciones de las vías biliares

The treatment of biliary tract infections requires antibiotics and an appropriate surgical procedure. The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of biliary tract infections. This was a randomized, prospective and comparative clinical trial of two antibiotic regimens in the treatment of biliary tract infection. One hundred and fifty three patients were randomly allocated into two groups; three patients were excluded after randomization. One group (n = 75) received piperacillin/tazobactam (4 g/8 h iv) and the other group (n = 75) was administered a combination of ceftriaxone (2 g/24 h iv) plus ornidazole (1 g/24 h iv). In both groups, protocolized surgical or endoscopic procedures were carried out. Clinical efficacy and safety were assessed at the end of treatment. Demographic data and severity of disease were similar in both groups. Three patients were excluded of the study by deviations from the protocol. Sixty-seven patients (89.3%) out of the piperacillin/tazobactam group and sixty-six patients (88%) out of the ceftriaxone plus ornidazole group were clinically cured (OR = 0.87 [95% CI, 0.31-2.4]). Twelve patients died, seven in the piperacillin/tazobactam group and five in the ceftriaxone plus ornidazole group. Adverse events were similar in both groups (OR = 1.18 [95% CI, 0.37-3.7]). This study suggests that piperacillin/tazobactam is as efficacious and safe as ceftriaxone plus ornidazole in the treatment of biliary tract infections.

Surgical Treatment of Biliary Tract Infections

Despite major advances in surgical and nonsurgical therapy, biliary tract infections remain a significant cause of morbidity and mortality. The two classic biliary tract infections most commonly encountered are acute cholecystitis (either calculous or acalculous) and acute cholangitis. In addition, bile leakage associated with bile duct injuries during laparoscopic cholecystectomy has become a problem not infrequently encountered by surgeons. Acute calculous cholecystitis results from a combination of mechanical, biochemical, and infectious mechanisms, initiated by stone impaction in the cystic duct. After instituting empiric antibiotics, early laparoscopic cholecystectomy should be performed. Although conversion to open cholecystectomy is more common than in chronic cholecystitis, there appears to be no increased morbidity or mortality in that setting. Acute acalculous cholecystitis usually occurs in critically ill patients and may present both a diagnostic and therapeutic dilemma. Aggressive management, however, is warranted, both because of the critical nature of illness in these patients and the high incidence of perforation. Percutaneous cholecystostomy is indicated, particularly in high-risk patients both for diagnosis and treatment. Acute cholangitis results from a combination of bactibilia and biliary obstruction. The majority of patients can be successfully managed with intravenous antibiotics and fluid resuscitation. In those patients in whom initial management is not successful, biliary drainage, which is best accomplished nonoperatively, should be instituted. There is a very limited role for early surgical intervention in acute suppurative cholangitis. Biliary leaks resulting in bile "peritonitis" or bilomas are common sequelae of laparoscopic bile duct injury. Although surgeons may feel it is necessary to operate urgently, delineation of the proximal biliary anatomy via percutaneous transhepatic cholangiography and biliary stent placement is the appropriate first step in management. This procedure will usually control the bile leak and allow delineation of the anatomy and opportune timing of definitive reconstruction.

Biliary excretion of rufloxacin in humans.

Rufloxacin is a new once-daily antibacterial fluoroquinolone with a long half-life. The aim of the present study was to evaluate the plasma and biliary kinetics and biliary and urinary excretion of rufloxacin in patients with extrahepatic cholestasis. Twelve patients with total external percutaneous transhepatic biliary drainage were given a single oral dose of 400 mg of rufloxacin. Plasma, bile, and urine samples and fractions were collected over 72 h after drug administration. Rufloxacin and its major metabolite, the N-desmethyl derivative, were measured by high-performance liquid chromatography. Maximum rufloxacin concentrations in plasma and bile (means +/- standard deviations) were 4.05 +/- 1.38 micrograms/ml and 8.24 +/- 7.16 micrograms/ml, respectively, and were reached in 4.2 +/- 3.0 h and 4.2 +/- 3.5 h, respectively. The terminal elimination half-life of rufloxacin in plasma was 45.1 +/- 13.5 h. Apparent plasma clearance was 31.3 +/- 10.5 ml/min, while biliary clearance was 0.4 +/- 0.2 ml/min and renal clearance was 12.7 +/- 6.0 ml/min. In 72 h, 0.9% +/- 0.8% of the dose given was recovered in bile and 27.2% +/- 12.0% was recovered in urine. Biliary concentrations exceeded the MICs of most common biliary tract pathogens for at least 24 h after administration. The broad antibacterial spectrum of rufloxacin and its high and prolonged biliary concentrations suggest that this drug may be useful for treatment of biliary tract infections.

Role of intrahepatic protein binding in the hepatobiliary extraction profile of cefixime in humans

The hepatobiliary extraction profile of cefixime, a dianionic cephalosporin antibiotic, was studied in 10 patients, each of whom was provided with T-tube drainage of his or her common bile duct after cholecystectomy. After a single 200 mg oral dose, cefixime biliary clearance proved to be nonlinear, mostly in its initial phase, which is consistent with a concentrative uptake and intracellular protein binding for the drug. The latter process appears to be saturable and to operate at a rate that correlates with the total amount of cefixime recovered in the 24-hour bile drainage. Such findings seem to confirm the significant role played in vivo by hepatic ligandin in the hepatobiliary extraction of organic anions. The data also show that a single 200 mg oral dose of cefixime yields drug levels in bile substantially higher than the minimal inhibitory concentrations for the most frequent Enterobacteriaceae in biliary tract infections. Accordingly, this cephalosporin could be an interesting alternative in both prophylaxis and treatment of biliary tract infections.

Biliary excretion of cefixime: assessment in patients provided with T-tube drainage

The biliary excretion profile of cefixime was studied in 10 patients provided with T-tube drainage of the common bile duct after cholecystectomy. Following a single 200-mg oral dose, the peak concentration of cefixime in bile reached 56.9 +/- 70 mg/liter, approximately 20 times as high as the peak concentration in serum, 2.3 +/- 0.85 mg/liter. Cefixime levels in bile proved relatively sustained, since a concentration of 4.3 +/- 3.7 mg/liter was still found 20 h after dosing. The cumulative amount of cefixime recovered in the 24-h bile drainage averaged 10.0 +/- 12.3 mg, which is 5% of the administered dose and positions this beta-lactam antibiotic among the most highly bile-excreted cephalosporins. The presented results show that a single 200-mg oral dose of cefixime provided drug levels in bile consistently higher than the MICs for the most frequently recovered members of the family Enterobacteriaceae in biliary tract infections and maintained these levels for over 20 h after dosing. Accordingly, this cephalosporin deserves further clinical trials to assess its usefulness in both prophylaxis and treatment of biliary tract infections.

Pharmacokinetics and biliary elimination of temafloxacin in pigs.

The purpose of the present work was to investigate the 48 h pharmacokinetic and biliary elimination of temafloxacin, administered intraduodenally at a single dose of 10 mg/kg to six conscious pigs provided with a double terminal choledocal fistula allowing the collection and the reinstillation of bile. The concentrations of temafloxacin in biological fluids were measured by both HPLC and bioassay. The mean serum half-life of temafloxacin was 11.45 +/- 4.4 h and the apparent oral clearance (assuming a 95% bioavailability) was 171 +/- 66 mL/min. The penetration of temafloxacin into bile is significant as indicated by a bile/serum AUC ratio of 9.1 +/- 2.2. The 0-45 h biliary excretion amounted to 2.002 +/- 0.8 mg, representing 0.9 +/- 0.3% of the administered dose. Biliary peak concentrations ranged from 8.0 to 37.5 mg/L and the 24 h mean biliary concentration was 3.7 +/- 2.4 mg/L. No statistically significant differences between HPLC and bioassay concentrations or AUCs could be observed in bile, indicating that temafloxacin is not extensively biotransformed into active metabolites in this model. These data, together with data in man, suggest that temafloxacin could be a useful agent for the treatment of biliary tract infections.

High hepatic excretion in humans of cefpiramide, a new cephalosporin

After intravenous administration of 1 g of cefpiramide, the biliary elimination of the drug was studied by using high-performance liquid chromatography. In five healthy volunteers, a mean peak concentration of 339 +/- 107 (standard error of the mean) micrograms/ml was measured in aspirated duodenal fluid during h 2 after administration, and 1.2% of the dose given was recovered over a 4-h period. A maximal concentration of 1,161 +/- 392 micrograms/ml was reached during h 2 in T-tube bile from 10 recently cholecystectomized patients, with a 24-h biliary recovery of 23.1%; urinary recovery over the same period averaged 49.4%. In 10 patients undergoing cholecystectomy, the concentrations in serum, choledochal bile, gallbladder bile, and gallbladder wall 1 h after cefpiramide administration were 157 +/- 21, 1,726 +/- 501, and 84 +/- 33 micrograms/ml and 23 +/- 4 micrograms/g, respectively. These figures represent the highest biliary concentrations attained so far with a beta-lactam antibiotic and are therefore a good prerequisite for treatment of biliary tract infections with cefpiramide.

Biliary tract excretion of ofloxacin in man.

This study examined the biliary tract excretion of ofloxacin in 6 post-cholecystectomy patients with a T-tube inserted into the common duct (group A) and 6 patients during cholecystectomy (group B). The patients were given 7 oral doses of ofloxacin 200mg with a 12-hour interval between each dose. Blood and common duct bile samples were collected in group A at various time intervals after the first and the seventh dose. Blood, gallbladder wall, and gallbladder and common duct bile were collected in group B during operation, 6 hours after the seventh dose. Assays were performed by use of high performance liquid chromatography (HPLC). In group A, mean serum Cmax and half-life were 2.6 mg/L and 7.6 hours after the first dose, and 5.3 mg/L and 8 hours after the seventh dose, respectively. Mean common duct bile Cmax and half-life were 6.5 mg/L and 7.5 hours after the first dose, and 12.0 mg/L and 14 hours after the seventh dose, respectively. In group B, mean concentrations (mg/L) were 2.6 in blood, 5.3 in gallbladder wall, 24.6 in gallbladder bile and 10.1 in common duct bile, 6 hours after the seventh dose. These data suggest that ofloxacin may be suitable for the treatment of biliary tract infections.

Biliary elimination of cefotiam, an experimental and clinical study.

Five isolated rabbit livers were in vitro perfused over a 3-hour period. After addition of 10 mg of cefotiam to the circulating blood, a biliary peak concentration of 76.2 +/- 14.2 micrograms/ml (mean +/- SEM) was reached between the 90th and 120th min; 3.1 +/- 0.4% of the dose given was excreted in the bile during the 3-hour period. In 10 recently cholecystectomized patients provided with a T-tube drain, 1 g of cefotiam was given intravenously. A biliary peak concentration of 340 +/- 81 micrograms/ml was observed 2 h later. 1.8 +/- 0.7% of the administered dose was recovered in the bile during the 12-hour period. In 5 clinically normal subjects given intravenously 1 g of cefotiam, 0.5 +/- 0.2% of the administered dose was found in the duodenal fluid aspirated over a 4-hour period. Cefotiam concentrations measured in choledochal and gallbladder bile collected simultaneously during operation 1 h after intravenous administration of 1 g of the drug to 10 patients were 502 +/- 102 micrograms/ml and 143 +/- 39 micrograms/ml, respectively; they exceeded significantly the concentration determined in the serum sampled at the same time (17.9 +/- 2.6 micrograms/ml). The biliary parameters of cefotiam were compared with those of 14 other beta-lactam antibiotics previously studied by the same procedure. The results of the present study are consistent with a possible beneficial effect of cefotiam in the treatment of biliary tract infections.

Biliary excretion and pharmacokinetics of ceftriaxone after cholecystectomy.

Three groups of patients with biliary tract disease treated by cholecystectomy were given ceftriaxone. In Group 1 single doses of 150 mg and 1500 mg were given on Days 1 and 5 after cholecystectomy. In Group 2 2 g was given daily for 6 days and the cholecystectomy was on Day 2. Patients in Group 3 received 2 g every 12 h for 3 to 5 doses before cholecystectomy. Plasma samples, urine and T-drain bile were collected at various times from Groups 1 and 2 patients. Gallbladder bile and plasma were collected from Group 3 patients at the time of cholecystectomy. The mean (+/- SEM) T-drain bile-to-plasma concentration ratio of ceftriaxone in Groups 1 and 2 was 6.7 +/- 0.92. The mean (+/- SEM) gallbladder bile-to-plasma concentration ratio was 33 +/- 4.2. No clinically significant differences were detected between the kinetics of ceftriaxone in the cholecystectomy patients compared to normal volunteers. The usual dosage of ceftriaxone appeared adequate for prophylaxis or treatment of biliary tract infection by susceptible organisms.

Biliary excretion of ceftizoxime in humans.

Biliary concentrations of a new cephalosporin, ceftizoxime, were measured in bile collected in 8 cholecystectomized patients provided with T-tube drainage and in 14 patients where bile was obtained by puncture of the gall bladder and choledochus during cholecystectomy. In patients with external biliary drainage, a mean biliary peak of 150.3 +/- SEM 49.8 micrograms/ml has been observed 2 h after intravenous injection of 2 g of ceftizoxime; the antibiotic activity amounted still to 17.3 +/- 6.0 micrograms/ml after 6 h. Assays performed during operation showed the following simultaneous concentrations 1 h after 2 g of ceftizoxime given intravenously: serum: 85.3 +/- 8.1 micrograms/ml; main duct bile: 279.8 +/- 40.0 micrograms/ml; gallbladder bile: 119.9 +/- 19.4 micrograms/ml. These findings were compared with the biliary excretion of 8 other cephalosporins studied previously under the same conditions. The results of the present study suggest that administration of ceftizoxime may be effective in the treatment of biliary tract infections.