Biliary Tract Excretion of Cefazolin, Cephalothin, and Cephaloridine in the Presence of Biliary Tract Disease

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 mug/ml, respectively) than either cephaloridine (7 and 9 mug/ml) or cephalothin (1 and 4 mug/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 mug/ml after intravenous and 26 mug/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 mug/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.     

Cefamandole bile levels in patients with hepatobiliary disease.

Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic dose of 1 g administered by intravenous drip showed therapeutically effective concentrations of cefamandole in 84% (11 of 13) of gall bladder samples with a median of 220 micrograms/ml (range, 1.6 to 1,400), and in 100% (13 of 13) of common bile duct samples with a median of 1,100 micrograms/ml (range, 9.0 to greater than 2,000). Only with complete aseptic cystic duct obstruction was cefamandole undetectable in gall bladder bile.     

Cefoperazone concentrations in bile and gall bladder wall after intravenous administration.

Cefoperazone concentrations in the common duct bile, gall bladder bile, and gall bladder wall were determined in four patients with cholelithiasis and one patient with carcinoma of the head of the pancreas, all of whom had normal renal functions. Within 65 min after a 1-g intravenous administration, maximum concentrations ranged from 373.4 to 3,100 micrograms/ml in common duct bile and from 6.8 to 680 micrograms/ml in gall bladder bile. Cefoperazone concentrations per gram of the gall bladder wall ranged from 16.8 to 48.0 micrograms.     

Latamoxef (moxalactam) in acute exacerbations of chronic bronchitis

Forty-three patients admitted to the hospital with acute exacerbations of chronic bronchitis were treated with latamoxef (moxalactam) twice daily intramuscularly for 10 days. Five patients received 0.5 g injections, 23 patients 1 g and 15 patients were given 2 g. Three patients dropped out of the study; one died suddenly, one was treated with another antibiotic because of suspected Gram-negative pneumonia and one developed pneumococcal septicaemia after the active treatment course. Most strains of Haemophilus influenzae, H. parainfluenzae and Branhamella catarrhalis were successfully eradicated but, by day 17, there were 7 patients with reinfections with Streptococcus pneumoniae. Latamoxef MIC values for Str. pneumoniae varied from 0.03 to 2 g mg/1, but most were in the region of 1 mg/1. Sputum concentrations reached approximately 1.5 mg/1 on the highest dosage but only 0.25 to 1 mg/1 on the lower doses. Peak Serum concentrations with the increasing doses averaged 14, 27 and 45 mg/1 respectively. The role and dosage of latamoxef in respiratory infections in the possible presence of streptococci are discussed.     

Impact of single dose as compared to three dose prophylaxis with latamoxef (moxalactam) on the colonic microflora in patients undergoing colorectal surgery

Twenty patients undergoing colorectal surgery were given an initial dose of 2 g latamoxef (moxalactam) parenterally at the induction of anaesthesia. Ten of the patients received two subsequent doses at 8 h intervals. A series of serum and faecal specimens were taken for analysis of latamoxef concentrations. Tissue samples from intestinal mucosa and peritoneal fat were also taken at surgery. The mean serum peak level was 119.8 +/- 10.7 mg/l. The mean half life was 2.8 h and the mean area under the serum concentration curve was 345.0 +/- 25.7 mg h/l. The concentrations in intestinal mucosa were high when the tissue was removed within 4 h after the administration of latamoxef (22.6 +/- 1.7 micrograms/g, mean +/- S.E.). The concentrations declined when the tissues were removed later (7.8 +/- 0.7 micrograms/g). The content of latamoxef in peritoneal fat varied, range 0.8-23.4, mean 8.5 +/- 1.4 micrograms/g. Measureable levels of latamoxef in faeces were found in all patients except one. The values varied between 0.2 to 23.0, mean 8.9 +/- 1.5 micrograms/g. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria-streptococci, enterococci and enterobacteria--were suppressed significantly during the prophylaxis period. Among the anaerobic bacteria--cocci, lactobacilli, bifidobacteria, clostridia, bacteroides and fusobacteria--decreased markedly during the same period. After two weeks the microflora was normalized in all patients. There were no differences between the patients receiving one dose of latamoxef and those receiving three doses. No postoperative infections occurred.     

Combined endoscopic and laparoscopic treatment of common bile duct stones

In a consecutive series of 228 patients reterred to Kalundborg Sygehus, Surgical Department, for treatment of gall bladder disease, 17 patients had common bile duct (CBD) stones. Nine were found pre-operatively and treated with endoscopic retrograde cholangiography (ERC), papillotomy and stone extraction. In two cases, however, the ERC procedure failed and the patients were treated successfully using laparoscopic therapy. Six CBD stones were found during laparoscopic surgery. Four of these patients were treated with laparoscopic stone extraction. In two patients laparoscopic stone extraction was not possible and they were treated post-operatively with ERC and stone extraction. Two CBD stones were discovered after laparoscopic cholecystectomy. One was treated with ERC and stone extraction, the other with open surgery. By combining endoscopic and laparoscopic procedures, it is possible in most cases to avoid open surgery for the treatment of CBD stones.     

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.     

Influence of three modes of administration on the penetration of latamoxef into interstitial fluid and fibrin clots and its in-vivo activity against Haemophilus influenzae

The extravascular penetration and bactericidal activity of latamoxef against beta-lactamase positive Haemophilus influenzae were studied in a rabbit model. All groups of animals received over 24 h an identical dose of 100 mg/kg of latamoxef given by three different intravenous modes of administration including a single large injection of 100 mg/kg, four 25 mg/kg intermittent injections every 6 h, and a continuous infusion of 100 mg/kg over 24 h. A single large injection resulted in significantly higher peak levels and higher initial area under the curve of concentrations of drug in serum, interstitial fluid, and fibrin clots than other modes of administration. Continuous infusion resulted in an accumulation of drug in clots which rose from 1.0 microgram/g at 4 h to 4.9 micrograms/g at 24 h (P value less than 0.01). The rate of killing of H. influenzae imbedded in fibrin clots was greatly influenced by the different modes of therapy. Even though all regimens resulted in peak concentrations which were more than 80 times the MIC (0.03 mg/l) in the fibrin clots, rapid killing (from 10(7) to less than 10(2) micro-organisms per g of clots in less than 6 h) was only observed with a single bolus. Continuous infusion and intermittent injections of latamoxef resulted in limited in-vivo bactericidal activity. Large doses of latamoxef given at long intervals may be more effective than intermittent dosing or continuous infusion.     

Influence of surgical biliary pathology on the diffusion of ceftriaxone in the biliary tract

Ceftriaxone is a third generation cephalosporin remarkable for its wide distribution in the biliary tract. The purpose of this study was to determine whether biliary tract pathology, as observed during surgery, had an influence on this distribution. 52 patients about to be operated upon and presenting with a high risk of bile infection received a single 1 or 2 g dose of ceftriaxone administered intravenously over 20 min during the hour that preceded surgery. Samples of blood and of bile from the gallbladder (GB) and the common bile duct (CBD), as well as specimens of the GB wall were taken during the operation. In patients whose GB was normal at laparotomy (apart from stones) ceftriaxone concentrations in bile and GB wall were 10-25 and 2 times respectively higher than in plasma. In patients with a grossly distended but not infected GB (hydrocholecystis) ceftriaxone levels were high in CBD bile but null in GB bile and only one-quarter to one-half of plasma levels in GB wall. In patients with stones in the CBD or inflamed GB wall ceftriaxone levels were high in bile (although lower than in cases with normal GB) and similar to plasma levels in GB wall. When malignant pancreatic lesions were present ceftriaxone concentrations could not be measured in both GB and CBD bile but reached 50% of plasma concentrations in GB wall.(ABSTRACT TRUNCATED AT 250 WORDS)     

The physicochemical basis of cholesterol gallstone formation in man

The concentrations of bile salt, lecithin, and cholesterol were determined on each of 66 samples of gall bladder bile from patients with cholesterol gallstones and 25 samples of normal gall bladder bile. When these three constituents were plotted simultaneously on triangular coordinates, a complete separation of the normal and “abnormal” bile was achieved. This separation was the result of an increase in the quantity of cholesterol relative to the amounts of bile salts and lecithin contained in the bile from patients with cholesterol gallstones.     

Possibilities of laparoscopic decompression of the gallbladder in middle-aged and elderly patients with diseases of the biliary tract]

It is established that laparoscopic cholecystostomy presents the most acceptable method of gall bladder decompression in acute cholecystitis patients of advanced age comprising a high-risk group for surgery. Cholecystostomy efficiency reaches 97.2%. In case the procedure is not feasible in acute cholecystitis patients with intrahepatic position of the gall bladder or perivesicular adhesions the preference should be given to transhepatic drainage of the gall bladder whose effectiveness is 88.5%. An expedient method of laparoscopic decompression of the biliary tracts in mechanical jaundice due to tumor obstruction of the terminal part of the common bile duct is the formation of an external biliary fistula and "continuous" direct drainage of the gall bladder warranting satisfactory results in 93.3 and 100% of cases, respectively. Patients with a 1.5-week history of mechanical jaundice are not recommended transhepatic drainage, in longer duration of the jaundice (more than 1 month) it becomes contraindicated.     

右美托嘧啶影响黄疸患者全身麻醉苏醒质量的研究

目的探讨右美托嘧啶对黄疸患者全身麻醉苏醒质量的影响。方法。选取肝胆外科需做胆道探查手术的黄疸患者40例,采用双盲研究随机分为右美托嘧啶组（D组）和对照组（C组）各20例,所有患者均采用静吸复合麻醉,其中D组在麻醉诱导前15min开始以0．5μg/kg负荷量泵注右美托嘧啶,术中以0．008μg／（kg·min）至缝皮前10min结束,C组注等量生理盐水。记录两组肌松药总量、拮抗剂用量、停药后麻醉苏醒时间以及拔管期间的血压、心率的变化幅度,并比较苏醒期并发症的发生率。记录麻醉诱导前未给予右美托嘧啶或生理盐水时（M1）、插管后5min（M2）、切皮后10min（M3）、拔管后10min（M4）各时点去甲肾上腺素的血浆浓度。结果两组呼吸恢复时间、拔管时间、定向力恢复时间比较差异均无统计学意义（P〉0．05）;D组患者苏醒过程中血压变化幅度明显小于C组患者,差异有统计学意义（P〈0．05）。C组M3和M4时点的去甲肾上腺素水平较M1时增高,差异有统计学意义（P〈0．05）;D组以上指标相应时点与M1比较无明显变化。与C组比较,D组寒战和烦躁发生率较低,但心率变缓（〈60次／分钟）的发生率较高（P〈0．05）。结论右美托嘧啶用于黄疸患者的麻醉不仅不影响苏醒时间,还使血流动力学更加稳定,降低了术后烦躁和寒战的发生率。     

Latamoxef: single agent prophylaxis in colorectal surgery

To assess the suitability of latamoxef (moxalactam) as single agent chemoprophylaxis in elective colorectal surgery, 120 consecutive patients were randomized to receive latamoxef (L) 1 g or cephazolin 1 g and metronidazole 500 mg (CM) administered intravenously at induction of anaesthesia and 6 and 12 h postoperatively. The groups were well matched for age, sex, pathology and procedures. Serum and tissue levels of latamoxef were well above the MIC90 for most bowel organisms. Inpatient stay was similar for both groups. Pyrexia was seen in 44 patients (11 L, 23 CM) and eight developed a wound infection (3 L, 5 CM). Major intra-abdominal sepsis occurred in seven patients (2 L, 5 CM), secondary to anastomotic leakage in four (1 L, 3 CM). Twenty patients developed a chest infection (5 L, 15 CM) and eight urinary sepsis (2 L, 6 CM). No bleeding complication occurred, and there was no difference in clotting function between the two groups. Six patients died prior to follow-up at six weeks (1 L, 5 CM), two from anastomotic dehiscence. All but three wounds had healed (1 L, 2 CM) and one further patient had an incisional hernia (CM). These results suggest that latamoxef is an efficient chemoprophylactic agent in elective colorectal surgery, and is marginally better than cephazolin plus metronidazole.     

Assessment of biliary excretion of piperacillin-tazobactam in humans.

Piperacillin-tazobactam concentrations in serum and bile were measured intraoperatively in 10 patients undergoing cholecystectomy (group 1) and 5 cholecystectomized patients provided with external bile duct drainage (group 2). Each patient received a single intravenous dose of piperacillin at 4 g plus tazobactam at 0.5 g over 30 min. Drug concentrations in both serum and bile were measured by high-performance liquid chromatography. In group 1 patients, serum and bile specimens and gallbladder wall fragments were collected at mean times of 70 and 83 min postinfusion, respectively. The mean concentrations of piperacillin and tazobactam were, respectively, 69.1 +/- 41.5 (standard deviation) and 9.9 +/- 5.1 microg/ml in serum, 630.4 microg/ml (range, 24.8 to 1,194 microg/ml) and 11.8 microg/ml (range, 3.6 to 22 microg/ml) in choledochal bile, 342.3 microg/ml (range, 1.1 to 1,149 microg/ml) and 7.7 microg/ml, (range, 0.2 to 23.1 microg/ml) in gallbladder bile, and 49.3 microg/g (range, 9.7 to 223 microg/g) and 2.9 microg/g (range, 0.1 to 5.9 microg/g) in the gallbladder wall. In group 2 patients, the amounts of drugs recovered in bile drainage obtained over 12 h were 28.4 +/- 18.0 and 1.0 +/- 0.5 mg for piperacillin and tazobactam, respectively. Peak piperacillin and tazobactam concentrations in bile reached 358 +/- 242 and 10.8 +/- 4.2 microg/ml, respectively. Comparison of drug levels in serum and bile suggests an underlying active secretion process for piperacillin elimination into the bile, unlike that of tazobactam. From a therapeutic viewpoint, given the concentrations of tazobactam recorded in bile fluid and tissue, the addition of this beta-lactamase inhibitor to piperacillin therapy might be of interest in the management of biliary tract infections, mostly in patients at risk of mixed aerobic-anaerobic infections due to beta-lactamase-producing organisms.     

Immediate and long-term effects of endoscopic papillosphincterotomy in patients with cholelithiasis

The subjects of the study were 164 patients, divided into two groups. Group I included 76 patients at the physicochemical stage of cholelithiasis, and 38 patients after cholecystectomy, who underwent endoscopic papillosphincterotomy (EPST). Group II (control) included 30 patients at the physicochemical stage of cholelithiasis, and 20 patients after cholecystectomy, who did not undergo EPST. Endoscopic retrograde pancreatocholangiography revealed type II Oddi's sphincter dysfunction in all the patients. Evaluation of the chemical composition of bile in Group I, performed 6, 12, 18, and 24 months after EPST, revealed its graduate stabilization. In Group II the dynamics of bile composition was negative--in 8 patients bile became more lithogenic. Long-term observations showed that 6 years after EPST bile was lithogenic only in 4 Group I patients, while at the same moment in 25 Group I patients bile lithogenicity did not disappear, but even worsened. Biliferous tract ultrasonography, performed long after EPST, found biliary sludge in 4 Group I patients. 6-year observation of Group Il patients, including ultrasonography, demonstrated that during the 4th year of observation biliary sludge occurred in as many as 28 patients, in 15 of whom small concrements on the bottom of the gall bladder were found during the 5-6th year of observation, and in 3 of whom a solitary concrement of 4 to 5 mm in diameter was found in the choledoch. The results demonstrate that it is appropriate to perform EPST as early as at the physicochemical stage of cholelithiasis, because this procedure results in stabilization of biliary colloid balance and thus prevents biliary sludge and forming of gall bladder concrements. At the same time, 36% of patients with cholelithiasis at various stages who did not undergo EPST, formed gall bladder concrements. EPST is also appropriate in some patients after cholecystectomy, in order to prevent repeating gall bladder concrement formation.     

THE REACTION OF HUMAN BILE AND ITS RELATION TO GALL STONE FORMATION

1. The human gall bladder acidifies the bile. In this respect its action is similar to that of the gall bladders of lower animals, previously described by other workers. 2. The hydrogen ion concentration of gall bladder bile is increased considerably in cases of obstruction of the common or cystic ducts. The highest values were found following complete obstruction. 3. The occurrence of gall stones was not associated with a consistent change in the hydrogen ion concentration of the gall bladder bile.     

Cholagenic diarrhea

AIM: To characterize cholagenic diarrhea as a nosological entity with its specific features of etiology, pathogenesis, clinical picture and treatment. MATERIAL AND METHODS: A total of 167 patients with chronic diarrhea (CD) participated in the trial. Of them, 25 patients have undergone resection of the small intestine, 98--cholecystectomy for cholelithiasis, 44 had concurrent hypokinesia of the gall bladder caused by celiac disease (n = 30) or biliary dyskinesia (n = 14). The examination included estimation of cholic acid in the duodenal content (40% glucose solution or cholecystokinin were used as stimulators); 24-h fecal mass; fecal mass for 24 hours, fat, potassium and sodium content in the feces; electromotor activity (EMA) of the gall bladder, small intestine and colon. RESULTS: Duodenal intubation with 40% glucose in patients with extensive resection of the small intes- tine detected a fall in cholic acid content in vesical bile to 408 +/- 58.39 mg compared to normal (910 +/- 97.29 mg%). In intravenous administration of cholecystokinin cholic acid concentration rose insignificantly (547.0 +/- 94.7 mg%) and was accompanied with bile loss with feces, polyfecalia, steatorrhea and high sodium concentration in feces. In celiac disease patients bile with high cholic acid concentration was secreted only in administration of cholecystokinin (1673 +/- 175.9 mg/%, normal 1701 +/- 140.6 mg/%). In patients after cholecystectomy colon EMA was primarily slow-wave and middle-amplitude, typical for hypermotor dyskinesia. CONCLUSION: CD develops after extensive resection and in inflammatory ileac diseases, suppression of contractile function of the gall bladder and after cholecystectomy. CD after cholecystectomy can be considered as a variant of postcholecystectomy syndrome. The treatment of CD should include drugs binding excessive bile acids in the colon, in hypokinesia of the gall bladder the treatment should include stimulators of its contractile function.     

Comparison of intravenous teicoplanin with intramuscular amoxycillin for the prophylaxis of streptococcal bacteraemia in dental patients

Teicoplanin 400 mg, given as an intravenous bolus dose after induction of general anaesthesia, was highly effective in reducing the prevalence of streptococcal bacteraemia following dental extraction. Pulse rate and blood pressure monitoring did not show any adverse cardiovascular reactions after this dose which was extremely well tolerated. Blood samples were collected from adult patients for culture and antibiotic assay about two minutes after the dental procedure. Viridans streptococci were isolated from one of 40 patients receiving teicoplanin (2.5%) compared with 13 of 40 (32.5%) control patients. Another group of patients investigated received amoxycillin 1.0 g, intramuscularly shortly before anaesthesia, and viridans streptococci were isolated from 10 of 40 (25%) patients in this group. The mean serum teicoplanin and amoxycillin concentrations at the time of extraction were 37 and 10 mg/l respectively. Although amoxycillin was administered with lignocaine patients occasionally complained of pain following intramuscular injection. The results of this study suggest that the 400 mg intravenous bolus dose of teicoplanin is more suitable than 1.0 g intramuscular amoxycillin for the parenteral prophylaxis of streptococcal endocarditis in patients with cardiac lesions who require a dental procedure. Also as the teicoplanin dose is easy to administer and free of cardiovascular reactions or 'red man' syndrome it is probably more suitable than vancomycin for providing prophylaxis in patients allergic to penicillin.     

Absorption of Bile Pigments by the Gall Bladder

A technique is described for preparation in the guinea pig of an in situ, isolated, vascularized gall bladder that exhibits normal absorptive functions. Absorption of labeled bile pigments from the gall bladder was determined by the subsequent excretion of radioactivity in hepatic bile.     

无钛夹腹腔镜胆囊切除术625例经验

目的探讨无钛夹法处理胆囊管及胆管动脉在腹腔镜胆囊切除术中的应用。方法回顾性分析腹腔镜无钛夹法胆囊切除625例，术中应用超声刀或单极电刀封闭切断胆囊动脉，丝线结扎、套扎器结扎或可吸收夹结扎疸囊管。结果术后无1例病人出现腹腔感染、胆漏和出血等并发症。术后随访1-12个月。未见有腹痛、肩背部疼痛、黄疸及发热等症状。结论腹腔镜胆囊切除术中无钛夹法处理胆囊管及胆管动脉安全、可靠。能避免使用钛夹所致的并发症。