brl-28500 and Sepsis

Efficacy of timentin was studied in the treatment of 19 patients with peritonitis of various etiology and clinical and laboratory signs of systemic inflammatory reaction characteristic of abdominal sepsis. The clinical and bacteriological effects were recorded in 84.2 and 87.5 per cent of the cases respectively. The drug was administered intravenously dropwise for 30 minutes in a dose of 3.1 g every 4 hours. The treatment course was 4-11 days. The treatment failed in 3 patients. One of them had general peritonitis of gynecological etiology. In the other no significant regression of abdominal sepsis was observed, Pseudomonas aeruginosa strains were isolated from the abdominal cavity, the antibiotic was changed, still incurable polyorganic insufficiency developed and the patient died. The third patient had perforation of the large intestine due to tumor. No adverse reactions to the use of timentin in any of the cases was observed.

Topics: Adult; Aged; APACHE; Clavulanic Acids; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Peritonitis; Sepsis; Ticarcillin; Time Factors

Current antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is not standardized and may be inadequate. We aimed to evaluate the efficacy of 3 days of additional oral antibiotics in the prevention of ERCP-related sepsis. One hundred and fifty-six patients were randomized prospectively to receive either intravenous ticarcillin and clavulinic acid (Timentin; SmithKline Beecham, Dandenong, Victoria, Australia), pre-ERCP (group I) or Timentin and 3 days of oral amoxycillin and clavulinic acid (Augmentin; SmithKline Beecham, Dandenong, Victoria, Australia), group II). Blood cultures were taken 30 min after the procedure. The occurrence of sepsis, defined as a temperature over 38 degrees C, occurring in the first 7 days was recorded and the risk factors for the development of sepsis were evaluated. Four patients had significant positive blood cultures despite the prior administration of Timentin. Sepsis occurred in 10% of group I patients, but only 3% of group II patients (relative risk 3.30; 95% confidence intervals 0.74-14.8). The performance of sphincterotomy and the presence of common bile duct stones were significant risk factors for the development of sepsis. We would recommend 3 days of additional oral Augmentin after a single dose of intravenous antibiotics in patients at increased risk of sepsis, which would include those with bile duct stones and/or those undergoing a therapeutic procedure.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Antibiotic Prophylaxis; beta-Lactamase Inhibitors; Case-Control Studies; Cholangiopancreatography, Endoscopic Retrograde; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sepsis; Ticarcillin; Time Factors

The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Body Fluid Compartments; Clavulanic Acid; Clavulanic Acids; Drug Administration Schedule; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infusions, Intravenous; Male; Models, Biological; Sepsis; Ticarcillin

In four prospective randomized clinical trials between November 1983 and March 1988, we studied 270 patients with severe bacterial infections, mainly lower respiratory tract ones. We compared ciprofloxacin and imipenem/cilastatin in the first study, ciprofloxacin and ofloxacin in the second study, ciprofloxacin and ticarcillin/clavulanic acid in the third study, and ofloxacin and cefpirome in the fourth study. A total of 90 pneumonias, 139 LRTIs, 22 septicaemias and 19 other bacterial infections were treated; the dominant pathogens were Pseudomonas aeruginosa and enterobacteria. Clinical success rates were high; cure or improvement was registered in 89% of the patients on ciprofloxacin, 89% on ofloxacin and 85% on beta-lactams. Treatment failures occurred mainly in ICU patients with terminal underlying diseases. Bacteriologically, eradication rates were high for enterobacteria and Staphylococcus aureus, but a relatively high persistence rate was seen for P. aeruginosa due to increased resistance and/or specific type and location of the infections. The incidence of side-effects was relatively high (23%-29%) which was related to careful monitoring. Adverse effects were group-specific (CNS reactions with quinolones, diarrhoea with beta-lactam antibiotics).

Topics: Cilastatin; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Clavulanic Acids; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Ofloxacin; Pneumonia; Prospective Studies; Remission Induction; Respiratory Tract Infections; Sepsis; Ticarcillin

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; beta-Lactamase Inhibitors; Child; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Netilmicin; Neutropenia; Penicillins; Retrospective Studies; Sepsis; Ticarcillin; Tobramycin

Timentin (ticarcillin + clavulanic acid) and cefamandole were compared in 484 patients undergoing elective thoracic or vascular surgery. Two hundred and forty eight patients received three 3 g/200 mg injections of Timentin and 236 patients received three 0.75 g injections of cefamandole. The patients were evaluated at discharge. Among the 248 patients given Timentin, only six (2.4%) had a post-operative infection, while nine (3.8%) of the 236 patients given cefamandole had a post-operative infection. There was no statistically significant difference between the two treatment regimes. This comparative study shows that Timentin may be used for antibiotic prophylaxis of clean vascular or thoracic surgery.

Topics: Bacteria; Cefamandole; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Humans; Penicillin Resistance; Penicillins; Premedication; Prospective Studies; Random Allocation; Sepsis; Surgical Wound Infection; Thoracic Surgery; Ticarcillin; Vascular Surgical Procedures

The efficacy of ticarcillin and clavulanic acid (Timentin) was assessed in a regimen combined with tobramycin in febrile episodes in neutropenic patients. After randomization, 151 patients were assessable following treatment with either Timentin and tobramycin or piperacillin and tobramycin. The overall success rate was 70% in the Timentin and tobramycin group and 71% when piperacillin and tobramycin were given: when no infection could be demonstrated efficacy was 73% in the Timentin group, 65% when only clinical or radiological evidence of infection was present and 63% with conclusive microbiology. The figures in the groups treated with the piperacillin-containing regimen were 83%, 79%, and 50% respectively. There was no significant difference between the treatment groups. In septicaemic patients, the Timentin regimen was effective in 55% of cases, while the piperacillin group was successful in 40%. Timentin is a useful addition to the agents suitable for the treatment of febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Penicillin Resistance; Penicillins; Piperacillin; Random Allocation; Sepsis; Ticarcillin; Tobramycin

One hundred febrile episodes in neutropenic (PMN less than 500/mm3) patients were treated with Timentin alone or in combination with amikacin. The overall response rate in 87 episodes was 82.9% with Timentin alone and 84.5% with the combination. Eleven out of 15 patients with septicaemia were cured by Timentin alone and 12 out of 13 by the combination, a response rate of 73.3% and 92.4% respectively (not-statistically significant P = 1.307). The rates of superinfection were low. Few side effects occurred. Timentin is a useful antibiotic in the treatment of febrile neutropenic patients and was, in this study, as effective alone as in combination with an aminoglycoside in the initial therapy.

Topics: Adolescent; Adult; Aged; Amikacin; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Kanamycin; Male; Middle Aged; Penicillin Resistance; Penicillins; Prospective Studies; Random Allocation; Sepsis; Ticarcillin

The efficacy and safety of Timentin (ticarcillin plus potassium clavulanate) and piperacillin were compared in a clinical trial of 78 hospitalized patients with urinary tract infections. There were 37 evaluable patients in the Timentin-treated group and 39 in the piperacillin-treated group. The 43 infection sites in each group were primarily complicated pyelonephritis or complicated cystitis; six patients in the Timentin-treated group and four in the piperacillin-treated group also had septicaemia. Both ticarcillin (3 g) plus potassium clavulanate (200 mg) and piperacillin (125-200 mg/kg per day) were administered intravenously. The 43 most common pathogens in each treatment group were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa from the urinary tract and E. coli from the blood. Nine pathogens in the Timentin-treated group and 11 in the piperacillin-treated group were resistant to ticarcillin in vitro. Eradication was achieved for 39 of the 43 (91%) pathogens in the Timentin group, including all six organisms isolated from the blood, and eight (89%) of the ticarcillin-resistant pathogens. In the piperacillin-treated group, 33 of the 43 (77%) pathogens were eradicated, including three of the four blood isolates, but only eight (73%) of the ticarcillin-resistant pathogens. Clinical cure or improvement occurred in 97% of the patients in each group. Mild and transient increases in levels of liver enzymes or eosinophils were reported for 11 patients in the Timentin group and seven in the piperacillin group. In one patient in the Timentin group, a drug-related rash and nausea developed, and treatment was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Cross Infection; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Penicillin Resistance; Penicillins; Piperacillin; Sepsis; Ticarcillin; Urinary Tract Infections

In a randomized comparative study, 116 patients with acute bacterial infections were treated with timentin (ticarcillin plus clavulanic acid) or a comparative agent (piperacillin for respiratory or urinary tract infections, and moxalactam for soft tissue infections). There were 91 clinically evaluated infections (timentin, 46; piperacillin, 29; moxalactam, 16). Twelve patients were bacteremic. A satisfactory clinical response occurred in all 46 patients treated with timentin and in 42 of the 45 treated with a comparative agent. Two clinical failures were due to superinfection (a Staphylococcus aureus pneumonia in the piperacillin group and an enterococcal skin infection in the moxalactam group), and one clinical failure was due to a primary S. aureus skin infection (moxalactam group). One wound isolate of Pseudomonas aeruginosa developed resistance to timentin during therapy (despite clinical improvement). Adverse reactions were uncommon but did include one patient treated with timentin who developed unexplained hallucinations.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Bacterial Infections; Clavulanic Acids; Drug Combinations; Female; Hallucinations; Humans; Male; Middle Aged; Moxalactam; Penicillins; Piperacillin; Sepsis; Ticarcillin

Topics: Anti-Bacterial Agents; Clavulanic Acids; Humans; Sepsis; Surgical Wound Infection; Ticarcillin; Treatment Outcome

Topics: Abdomen; Administration, Topical; Anti-Bacterial Agents; Antibiotic Prophylaxis; Clavulanic Acids; Digestive System Surgical Procedures; Humans; Injections, Intravenous; Sepsis; Surgical Wound Infection; Ticarcillin

Twenty-one patients with infected burns were treated with 5.2 g Timentin (ticarcillin 5 g + potassium clavulanate 200 mg) three times a day for an average of 8.3 days. Staphylococcus aureus was the commonest pathogen, there being ten cases of septicaemia with this organism and all were cured. Three patients with Pseudomonas aeruginosa septicaemia and infections with methicillin-resistant S. aureus failed. No drug related side effects were noted.

Topics: Adult; Bacteria; Bacterial Infections; Burns; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Humans; Male; Penicillin Resistance; Penicillins; Sepsis; Ticarcillin

Twenty-eight patients with bacteraemia were treated with Timentin, a combination of ticarcillin and clavulanic acid, and tobramycin. According to a simple physiological classification scheme 20 patients were moderately and eight severely ill. Clinical cure was achieved in 15 of 20 moderately ill and in four of eight severely ill patients. The nine therapeutic failures were due to non-removable foreign material (2 cases), abscesses that were not effectively evacuated (5 cases), urolithiasis (1 case), and decubitus ulcer (1 case). One of these cases was complicated by infection with a Klebsiella strain with Timentin and tobramycin MICs of 64 mg/l. Thirteen of 31 bacterial isolates from blood were resistant to greater than or equal to 128 mg/l of ticarcillin of which 11 were susceptible to less than or equal to 64 mg/l of Timentin. The addition of Timentin to tobramycin offered a better coverage in vitro than ticarcillin combined with tobramycin against the strains isolated from the blood of the patients included in this study.

Topics: Adult; Aged; Bacteria; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Penicillin Resistance; Penicillins; Sepsis; Ticarcillin; Tobramycin

Timentin (ticarcillin plus clavulanic acid) plus amikacin was administered as an empirical regimen to 52 febrile granulocytopenic patients with cancer and appeared as effective as the other commonly recommended combinations of antimicrobial agents. A favourable response was observed in 61% of episodes with bacteraemia and in 83% of the episodes without bacteraemia. However, the efficacy in Gram-positive bacteraemia was suboptimal and the emergence of superinfections caused by Gram-positive cocci may represent a clinical challenge.

Topics: Adult; Aged; Agranulocytosis; Amikacin; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Kanamycin; Male; Middle Aged; Neoplasms; Penicillin Resistance; Penicillins; Sepsis; Ticarcillin

The safety and tolerance of four intravenous formulations of Timentin (ticarcillin + clavulanic acid) have been evaluated in 1659 patients (1512 adults and 147 paediatric) included in clinical trials conducted in Europe and U.S.A. Timentin 3.2 and 5.2 g were administered respectively to 877 and 635 adults and Timentin 1.6 and 2.6 g to 117 and 30 paediatric patients three, four or six times daily for between 7.7 and 9.0 days in adults and 8.0 and 12.0 days in paediatric cases. Patients with septicaemia were 16%, 14% and 28% respectively of the Timentin 3.2, 5.2 g and paediatric groups, which together with respiratory tract and other serious miscellaneous infections accounted for the majority of cases treated within these three groups. Of the 1659 patients studied, 161 adverse reactions were reported from 151 patients (9.1%), 36 of which (2.2%) resulted in discontinuation of treatment. The reactions were at the injection site in 86 cases (5.2%), hypersensitivity in 35 (2.1%) and miscellaneous systemic symptoms in 40 cases (2.4%). Local reactions, i.e. phlebitis, pain and erythema, were self-limiting and did not necessitate early cessation of treatment. Hypersensitivity reactions occurred equally in all groups and necessitated cessation of treatment in about half of the patients. Gastro-intestinal disturbances were observed in eight, four and one patient within the Timentin 3.2, 5.2 g and paediatric groups. Changes in haemostatic status were reported in nine patients treated with Timentin. In all cases they were associated with contributory pathology and/or concurrent use of anticoagulants. Laboratory monitoring revealed transient variations in haemoglobin, blood cellular or plasma composition and plasma enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Cross Infection; Drug Combinations; Drug Evaluation; Drug Hypersensitivity; Female; Gastrointestinal Diseases; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Middle Aged; Penicillins; Phlebitis; Sepsis; Ticarcillin