brl-28500 and Bacterial-Infections

Broad-spectrum beta-lactam antibiotics have several advantages in the treatment of intra-abdominal infections. These agents are effective against gram-negative rods and anaerobes, reach therapeutic levels rapidly after parenteral administration, and, in the absence of penicillin allergy, generally exhibit low toxicity. The second-generation cephalosporins (e.g., cefoxitin, cefotetan) are used widely in surgical prophylaxis, trauma, and treatment of mild-to-moderate community-acquired infections, but limitations in their spectra and microbial resistance restrict their utility in more serious infections. Extended-spectrum penicillin/beta-lactamase-inhibitor combinations are effective in the treatment of intra-abdominal infections and include enterococci in their spectrum. Gram-negative aerobe resistance has developed to ampicillin/sulbactam. Piperacillin/tazobactam, a ureidopenicillin with increased gram-negative coverage and enhanced antipseudomonal activity, has proved to be effective in clinical trial therapy for intra-abdominal infections. The very broad spectrum carbapenems--imipenem/cilastatin and meropenem--are effective for serious infections or resistant organisms and are often used in the intensive care unit or for nosocomial intra-abdominal infection. These classes of beta-lactams comprise a range of antimicrobials that can be targeted effectively as single agents to both prevention and treatment of intra-abdominal infection.

Topics: Abdomen; Abdominal Abscess; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactamase Inhibitors; Carbapenems; Cephalosporins; Clavulanic Acids; Drug Resistance, Bacterial; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Surgical Wound Infection; Ticarcillin

Topics: Adolescent; Adult; Age Factors; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Infant; Infant, Newborn; Male; Pediatrics; Ticarcillin; Treatment Outcome

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the beta-lactamases in the Richmond and Sykes classes II-VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some beta-lactamase-producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I beta-lactamases frequently produced by Pseudomonas aeruginosa, Enterobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.

Topics: Ampicillin; Arthritis, Infectious; Bacterial Infections; Bacteroides fragilis; beta-Lactamase Inhibitors; Clavulanic Acids; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis; Pelvic Inflammatory Disease; Respiratory Tract Infections; Sulbactam; Ticarcillin

Ertapenem, a group I carbapenem antibiotic, has been shown to be safe and effective in treating adults with complicated intra-abdominal (cIAI) or acute pelvic infection (API). This study evaluated ertapenem for treating these infections in children.. In an open-label study, children aged 2 to 17 years with cIAI or API were randomized 3:1 to receive ertapenem or ticarcillin/clavulanate. Children 13 to 17 years of age received 1 g parenterally daily, and those 2 to 12 years of age received 15 mg/kg twice daily. Patients < 60 kg received ticarcillin/clavulanate 50 mg/kg 4 to 6 times daily and 3.1 g 4 to 6 times daily for those > or = 60 kg. Patients were assessed for safety and tolerability throughout the study and for efficacy after the completion of therapy.. One hundred five patients, 72 (69%) with cIAI, received > or = 1 dose of study drug and were included in the safety analysis. Eighty-one patients were treated with ertapenem. Infusion site pain was the most common drug-related adverse event in both groups. In the modified intent-to-treat analysis, the age-adjusted posttreatment clinical response rates were 87% (43/50 patients) and 100% (25/25 patients) in the cIAI and API patients, respectively, for ertapenem and 73% (11/15 evaluable patients) and 100% (8/8 evaluable patients), respectively, for ticarcillin/clavulanate. Overall age-adjusted response rates were 91% (68/75 evaluable patients) for ertapenem and 83% (19/23 evaluable patients) for the comparator.. This study suggests that ertapenem is generally safe and efficacious for treating cIAI or API in pediatric patients.

Topics: Abdominal Cavity; Acute Disease; Adolescent; Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Child; Child, Preschool; Clavulanic Acids; Ertapenem; Female; Humans; Male; Pelvis; Prospective Studies; Ticarcillin

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Clavulanic Acids; Female; Home Infusion Therapy; Humans; Male; Middle Aged; Ticarcillin; Treatment Outcome

Patients with diabetes mellitus, particularly those with poor glucose control, commonly experience various medical complications related to the disease (eg, renal impairment, decreased peripheral vascular circulation, suppressed immune function). Infections of the lower extremities can range from superficial cellulitis to ulcerative, deep soft-tissue infections to osteomyelitis that necessitates some degree of amputation.. This study compared the efficacy, tolerability, and cost differences associated with the use of metronidazole plus ceftriaxone (MTZ/CTX) given once daily with those of ticarcillin/clavulanate potassium (T/C) given every 6 hours in hospitalized older males with diabetic lower-extremity infections.. This prospective, open-label study was conducted at a Veterans Affairs Medical Center. Male patients with diabetes and a lower-extremity infection were randomized to receive MTZ/CTX 1 g once daily or T/C 3.1 g every 6 hours. Treatment success was determined at 96 hours or on discontinuation of antibiotic. Success was measured in terms of body temperature <38.3 degrees C (100.6 degrees F), normalization of the finger-stick blood sugar concentration, improvement in wound staging, or a white blood cell count <10,000 cells/mm3. Medication acquisition costs per treatment arm were calculated and compared.. Seventy patients were enrolled in the study (36 MTZ/CTX, 34 T/C). The study population had a mean (SD) age of 63.8 (10.8) years, a duration of diabetes of 12.4 (9.1) years, 0.5 (0.7) diabetes-related comorbidities, and an initial creatinine clearance of 67.1 (26.0) mL/min. There were no significant differences between groups at randomization. At 96 hours, treatment success was achieved in 31 (86%) patients in the MTZ/CTX group, compared with 28 (82%) patients in the T/C group (P=NS). Twenty-six patients were considered successfully treated on the final day of therapy in both the MTZ/CTX group (72%) and the T/C group (76%) (P=NS). There were no significant differences in primary or secondary measures of success between the 2 groups. No single or multiple baseline factors predicted treatment success or failure. No patient experienced adverse events considered related to study medication. MTZ/CTX was associated with savings of $61.06 per hospital admission, or $2198.05 for all patients who received this combination.. In this population of older males, once-daily MTZ/CTX was as well tolerated and effective as T/C in the treatment of diabetic lower-extremity infections and was associated with reduced institutional costs.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Clavulanic Acids; Cost Savings; Diabetic Foot; Drug Administration Schedule; Drug Combinations; Drug Costs; Drug Therapy, Combination; Hospital Costs; Hospitalization; Humans; Male; Metronidazole; Prospective Studies; Ticarcillin; Treatment Outcome

The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative.. We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A).. Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm(3) (T) and 201cells/mm(3) (C+A). The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A). Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23). Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T) and 93% (C+A). Adverse events that occurred in group T were not related to the drugs used in this study.. In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.

Topics: Adolescent; Amikacin; Bacterial Infections; Brazil; Ceftriaxone; Child; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Epidemiologic Methods; Female; Fever; Humans; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neutropenia; Ticarcillin; Treatment Outcome

To describe the microbiologic etiology of post-cesarean endometritis developing after perioperative cephalosporin prophylaxis, endometrial samples were obtained from 27 women with a triple-lumen catheter. The women were assigned in a double-blind, randomized fashion to receive either ticarcillin/clavulanate, 3.1 g, or cefoxitin, 2 g, administered every six hours, until the clinical signs of infection resolved. A total of 149 microorganisms (84 facultative and 65 obligate anaerobes) were recovered from 26 women, for a mean of 5.5 isolates per specimen. One endometrial specimen was sterile. Bacteroides and Peptostreptococcus species were the most frequent isolates, followed by Gardnerella vaginalis, Enterococcus, facultative gram-negative rods and Mycoplasma hominis. Each of the isolates was tested for beta-lactamase activity. At least one beta-lactamase-producing isolate was recovered from 56% of the specimens. Susceptibility testing of endometrial isolates demonstrated that 96% of 118 potential pathogens (Gardnerella, Bacteroides, Peptostreptococcus, enterococci and streptococci) were susceptible to ticarcillin/clavulanate. By comparison, 86% of these isolates were susceptible to cefoxitin in vitro. Women who were treated with ticarcillin/clavulanate were less likely to have a temperature greater than 38 degrees C for two or more days (8% vs. 57%, P = .01). Also, there was a trend toward a decreased duration of uterine tenderness in the ticarcillin/clavulanate group, but it did not attain statistical significance (60% vs. 86%, P = .4). However, the overall clinical success rate with these single-agent treatments was not different for the two groups (77% vs. 79%, P = 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Bacteroides; Cefoxitin; Cephalosporins; Cesarean Section; Clavulanic Acids; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Endometritis; Female; Humans; Penicillins; Peptostreptococcus; Postoperative Complications; Pregnancy; Randomized Controlled Trials as Topic; Ticarcillin

One hundred and twelve patients with proven or suspected serious intra-abdominal infections were randomized for treatment with either ticarcillin/clavulanate (3.1 g every 4 h) or gentamicin (dosage schedule adjusted according to serum concentrations) plus clindamycin (in most cases 900 mg every 8 h). Positive intraperitoneal and/or blood cultures were available in 47 cases. Considering only fully evaluable cases, 15/20 (75%) were clinically cured or improved in the ticarcillin/clavulanate group and 16/25 (64%) in the gentamicin/clindamycin group, the difference not being significant (P greater than 0.05). Bacteraemia was documented in nine of 45 fully evaluable cases. During the course of the study, the serum creatinine concentration increased by more than 5 mg/l in only one patient (ticarcillin/clavulanate group). Two patients (one in each group) had apparent allergic reactions. No other drug-related adverse effects were noted. In-vitro sensitivity testing of anaerobic isolates revealed that, of those tested, 5/38, 1/38 and 2/37 were resistant to ticarcillin, ticarcillin/clavulanate and clindamycin, respectively. Among aerobic Gram-negative isolates, 34/78, 6/78 and 4/78 were resistant to ticarcillin, ticarcillin/clavulanate, and gentamicin, respectively. Among aerobic Gram-positive isolates, 2/32, 2/32, and 5/14 were resistant to ticarcillin, ticarcillin/clavulanate, and clindamycin, respectively. We conclude that ticarcillin/clavulanate is a safe and efficacious preparation for treating serious intra-abdominal infections.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Child; Clavulanic Acids; Clindamycin; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Penicillins; Randomized Controlled Trials as Topic; Ticarcillin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Penicillins; Ticarcillin; United Kingdom

Topics: Bacterial Infections; Clavulanic Acids; Clinical Trials as Topic; Drug Therapy, Combination; Female; Floxacillin; Gentamicins; Humans; Infant, Newborn; Male; Penicillins; Piperacillin; Ticarcillin

Clinical studies have been conducted on BRL 28500 (a formulation containing 15 parts ticarcillin (TIPC) plus 1 part clavulanic acid (CVA]. BRL 28500 was administered at doses of 1.6 g or 3.2 g b.i.d., generally for 10 days by drip infusion to patients with intraperitoneal infections or biliary tract infections. Drug concentrations in the ascites were determined. A total of 76 cases was treated with BRL 28500. These cases included 49 intraperitoneal infections (suppurative peritonitis 29, postoperative peritonitis 20) and 18 biliary tract infections (cholecystitis 5, cholangitis 13). Nine cases were excluded from evaluation according to the committee's assessment. The clinical improvement as assessed by surgeons in charge increased with the duration of continued treatment and efficacies were assessed as 57.1% on day 5, 63.1% on day 7 and 77.8% on day 10 in intraperitoneal infections. Corresponding results in biliary tract infections were 38.9%, 40.0% and 42.9%, respectively. From these results, it is clear that the degree of improvement is related to the duration of treatment. The clinical usefulness as assessed by surgeons in charge of the study was 63.8% in intraperitoneal infections (suppurative peritonitis 75.0%, postoperative peritonitis 47.4%) and 58.8% in biliary tract infections (cholecystitis 100%, cholangitis 41.7%). The overall rate of usefulness was 62.5%. The clinical efficacy rates as assessed by the committee were 81.6% in intraperitoneal infections (suppurative peritonitis 93.1%, postoperative peritonitis 65.0%) and 66.7% in biliary tract infections (cholecystitis 100%, cholangitis 53.8%). In cases where causative organisms were isolated, the efficacies were 92.9% in suppurative peritonitis, 58.8% in postoperative peritonitis, 50.0% in cholangitis and overall, 69.2%. In cases from which TIPC-resistant organisms were isolated, the overall efficacy rate was 65.4% (suppurative peritonitis 88.9%, postoperative peritonitis 58.3% and cholangitis 40.0%). Regarding bacteriological effect as assessed by the committee, the eradication rate was 76.9% in intraperitoneal infections and 40.0% in biliary tract infections (71.0% overall). In cases from whom ticarcillin-resistant organisms were isolated the corresponding rates were 68.4% and 33.3% respectively, (63.6% overall). In 4 patients with peritonitis drug levels in the ascites were determined following administration of BRL 28500 by drip infusion. Good levels of both TIPC and CVA were detected 1 to

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cholangitis; Cholecystitis; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillins; Peritonitis; 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

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

Topics: Bacterial Infections; Clavulanic Acids; Clinical Trials as Topic; Drug Combinations; Humans; Kinetics; Microbial Sensitivity Tests; Penicillins; Ticarcillin

Topics: Adult; Aged; Bacteria; Bacterial Infections; Cellulitis; Clavulanic Acids; Drug Combinations; Female; Humans; Male; Middle Aged; Moxalactam; Penicillins; Skin Diseases, Infectious; Ticarcillin

In a comparative study, 47 patients received Timentin, a combination of ticarcillin plus clavulanic acid, or piperacillin to treat serious urinary tract infections. Thirty-nine infections in 38 patients were clinically evaluable (21 in the Timentin-treated group and 18 in the piperacillin-treated group). These included pyelonephritis (10 in the Timentin-treated group and five in the piperacillin-treated group), bladder infections with sepsis (11 in the Timentin-treated group and 11 in the piperacillin-treated group) and bladder infections without fever (two in the piperacillin-treated group). The addition of clavulanic acid to ticarcillin greatly enhanced the susceptibility of five of the 28 evaluable pathogens in the Timentin-treated group (two Escherichia coli isolates, two Staphylococcus aureus isolates, and one Klebsiella pneumoniae isolate). The minimal inhibitory concentrations at which 50 and 90 percent of the bacterial growth was inhibited were 4 and 64 micrograms/ml, respectively, for Timentin, and 4 and 32 micrograms/ml, respectively, for piperacillin. All evaluable patients had a satisfactory symptomatic response at the end of the trial. Of 28 evaluable pathogens treated with Timentin, 18 were eradicated up through the one-week post-therapy evaluation period; of 27 evaluable pathogens treated with piperacillin, 18 were eradicated up through the same time period. Eradicated pathogens included E. coli (six of 13 in the Timentin-treated group and six of 11 in the piperacillin-treated group), other Enterobacteriaceae (three of three in the Timentin-treated group and eight of 10 in the piperacillin-treated group), Pseudomonas aeruginosa (two of four in the piperacillin-treated group), enterococcus (two of three in the Timentin-treated group and two of two in the piperacillin-treated group), staphylococcal species (four of five in the Timentin-treated group), and other organisms (three of four in the Timentin-treated group). Resistance did not develop in any of the persisting pathogens. Adverse effects thought possibly to be related to the study drugs were minimal and included rash in one Timentin-treated patient and diarrhea in another.

Topics: Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; 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

To evaluate the efficacy and cost of treatment with two beta-lactam/beta-lactamase-inhibitor combinations.. Retrospective, open-label multicenter study.. Fifty-four hospitals across the United States.. Eight hundred ninety patients with skin and soft tissue, intraabdominal, gynecologic, respiratory, urinary tract, or other infections that required parenteral antibiotic therapy.. Patients were administered either ampicillin-sulbactam 1.5 or 3.0 g every 6 hours or ticarcillin-clavulanate 3.1 g every 6 hours.. The agents did not differ significantly in efficacy for most infections; although, ampicillin-sulbactam was bacteriologically superior to ticarcillin-clavulanate in the treatment of intraabdominal infections (p=0.0011). Costs of ampicillin-sulbactam, particularly the 1.5-g dose, were lower than those of ticarcillin-clavulanate for skin and soft tissue (p<0.001), intraabdominal (p=0.005), and respiratory tract (p<0.001) infections.. Ampicillin-sulbactam provides effective coverage for patients with the above infections and is as effective as the broader-spectrum agent.

Topics: Adult; Aged; Ampicillin; Analysis of Variance; Bacterial Infections; Clavulanic Acids; Drug Costs; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Middle Aged; Retrospective Studies; Sulbactam; Ticarcillin; Treatment Outcome; United States

We report a case of Alcaligenes xylosoxidans keratitis following penetrating keratoplasty in a rigid gas permeable (RGP) lens wearer.. A 61 year old RGP lens wearer with a history of nonresponsive keratitis of the right eye which involved the graft margin was referred to us for treatment. Corneal cultures revealed growth of a gram-negative rod on the fifth day and the organism was subsequently identified as Alcaligenes xylosoxidans, which was resistant to most antibiotics and sensitive only to Bactrim, Timentin, and imipenem.. Clinical improvement was observed within 24 hours after treatment with the use of topical i.v. Bactrim and topical i.v. Timentin 2% alternating every 30 minutes. Complete resolution of the infection with mild scarring was observed 6 weeks after treatment.. Alcaligenes xylosoxidans is a potential cause of bacterial keratitis which should be considered in cases of nonresponsive gram-negative keratitis. The addition of topical Bactrim or Timentin may need to be considered in such cases.

Topics: Administration, Topical; Alcaligenes; Anti-Bacterial Agents; Bacterial Infections; Clavulanic Acids; Contact Lenses; Cornea; Drug Therapy, Combination; Gases; Humans; Keratitis; Keratoplasty, Penetrating; Male; Middle Aged; Permeability; Postoperative Complications; Ticarcillin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Male; Ticarcillin

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Retrospective Studies; Ticarcillin; Treatment Outcome

The therapeutic efficacy of ticarcillin/clavulanate was assessed in 71 patients with severe infections: 38 acute pyelonephritis, 16 septicaemia and 19 miscellaneous infections. The patients were classified according to their renal function in: Group A, normal (16 cases); B, mild renal impairment (RI) with creatinine clearance (Clcr) between 80 and 40 ml/min (18 cases); C, moderate RI with Clcr between 40 and 15 ml/min (12 cases); D, severe RI with (Clcr) between 15 and 5 ml/min (13 cases) and E, terminal with (Clcr) less than 5 ml/min (12 cases). A total of 105 microorganisms (48.6% resistant to ticarcillin): 31 Pseudomonas aeruginosa, 18 Escherichia coli, 21 other Enterobacteriaceae, 2 Haemophilus influenzae, 10 Bacteroides spp., 14 enterococci, 8 staphylococci and 1 streptococcus, were isolated. All except six Ps. aeruginosa were sensitive to ticarcillin/clavulanate, using 75:10 microgram discs. Bacteriological eradication was obtained in 97% of the cases on the third day and at the end of treatment, and in 82% of the cases after one month. In all the assessable cases, the clinical symptoms disappeared on the third day except in one patient who developed a resistant strain (Klebsiella oxytoca). The wide range of bacteria assessed and the clinical-bacteriological success rates demonstrated that the ticarcillin/clavulanate combination had an efficacy/safety profile that could be considered excellent. Tolerance was good and side effects were not observed. This study confirms the practical efficacy of the recommended dosages derived from our previous kinetic studies in RI.

Topics: Adult; Aged; Aged, 80 and over; Bacteria; Bacterial Infections; Body Temperature; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Ticarcillin

In a prospective study, 46 episodes of serious infection with ticarcillin-resistant microorganisms were treated with the combination ticarcillin disodium and clavulanate potassium (Timentin). Clinical cure was achieved in 35 of the 46 episodes (76%), and microbiologic eradication was achieved in 30 (65%). We found no development of resistance to ticarcillin-clavulanate and observed no serious side effects.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Clavulanic Acids; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Humans; Male; Middle Aged; Penicillin Resistance; Penicillins; Prospective Studies; Ticarcillin

Topics: Bacterial Infections; beta-Lactamase Inhibitors; Clavulanic Acids; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Penicillins; Ticarcillin

The efficacy of a single antibiotic--Timentin (ticarcillin with clavulanic acid)--was compared with a standard two antibiotic regimen (clindamycin and gentamicin) for the treatment of endomyometritis after cesarean delivery. The regimens were 3 grams of ticarcillin plus 100 milligrams of clavulanic acid given intravenously every four hours, or 600 milligrams of clindamycin given intravenously every six hours plus 3 to 5 milligrams per kilogram per day of gentamicin given intramuscularly. The diagnosis of endomyometritis was based upon an oral temperature of 100.4 degrees F. or higher on any two occasions, excluding the first 24 hours post partum, uterine tenderness and the absence of another focus of infection. Ninety-one patients were treated. Treatment failure rates were three of 49 in the clindamycin and gentamicin group and four of 42 of the ticarcillin plus clavulanic acid group. Treatment failures did not appear to be different from successes demographically or in risk factors for endomyometritis. The results of this study suggest that ticarcillin with clavulanic acid is as effective in the treatment of postcesarean endomyometritis as the standard regimen of clindamycin and gentamicin.

Topics: Adult; Bacterial Infections; beta-Lactamase Inhibitors; Cesarean Section; Clavulanic Acids; Clindamycin; Drug Administration Schedule; Drug Combinations; Endometritis; Female; Gentamicins; Humans; Penicillins; Ticarcillin

Clavulanic acid/ticarcillin (BRL 28500) was administered to 36 patients with severe infections accompanying various hematological diseases. The rate of efficacy was 52% on the whole. Adverse reactions were minimal.

Topics: Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Hematologic Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Penicillins; Ticarcillin

16 patients admitted to a MICU were treated with timentin (ticarcillin + clavulanic acid) for bacterial infections: 11 cases of pulmonary infection, 3 cases of urinary tract infection, 2 septic shocks, 3 septicemias and 1 case of multifocal infection. The pathogens considered as a firmly established cause of infection were: 5 Acinetobacter, 12 Pseudomonas, 3 Serratia, 4 Klebsiella, 1 E. coli, 2 Proteus, 1 Providencia, 1 Staphylococcus aureus, 1 Staphylococcus epidermidis, 1 Streptococcus D and 1 Flavobacterium meningosepticum. The susceptibility of these pathogens to ticarcillin and timentin is reported. Timentin was prescribed alone in 9 cases and associated (with an aminoglycoside) in 7, in a daily dose of 9 to 18 g, for 6 to 45 days. 3 patients died. The value of timentin in infections due to multiresistant MICU pathogens is stressed.

Topics: Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Critical Care; Drug Combinations; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Penicillins; Ticarcillin

A clinical trial with Timentin (ticarcillin plus clavulanic acid) was undertaken in patients with hospital-acquired lower respiratory tract infections. Two formulations, 3.2 and 5.2 g consisting of 200 mg clavulanic acid and 3 or 5 g ticarcillin, respectively were usually given three times daily. Eighty-one patients were evaluable for clinical efficacy and 89 for tolerance. The clinical cure rate was 96% of the assessable cases even though all patients had severe concurrent or underlying diseases. The pronounced synergism between ticarcillin and clavulanic acid resulted in a bacteriological elimination rate of 94%. Adverse effects were very rare and of a mild nature, and restricted to those usually seen with the well-tolerated penicillins. No toxicological abnormalities could be detected in extensive laboratory screening. Timentin is a highly effective broad-spectrum antibiotic with good tolerance. Its potentiated action in comparison to other penicillins against beta-lactamase-producing strains, could reduce the usage of aminoglycosides in the future.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bronchitis; Clavulanic Acids; Critical Care; Cross Infection; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Metronidazole; Middle Aged; Penicillin Resistance; Penicillins; Pneumonia; 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

Sixty-four severe infections in hospitalized patients were treated with intravenous Timentin. Most patients (mean age: 50.5 years, range 18-85) had serious underlying conditions such as agranulocytosis, heart failure, cancer, diabetes mellitus, chronic alcoholism or other functional or anatomical abnormalities. Forty-three episodes were bacteriologically proved, and bacteraemia was diagnosed in 18. The sites of infection were: lower respiratory tract (10), upper respiratory tract (10), soft tissues (9), urinary tract (7), bones (6), peritoneal cavity (3), meninges (1) and pelvis (1). In addition, 13 episodes of fever and four of septicaemia in patients with agranulocytosis were treated with Timentin plus amikacin. Overall, 59% of the episodes were cured, 14% improved and 17% failed to respond. In 9% of cases the efficacy of the Timentin was unassessable mainly because of concurrent administration of other antimicrobials. Failure appeared to be more frequent in soft tissue and intra-abdominal infections, in patients infected with bacteria susceptible to Timentin but resistant to ticarcillin and in patients superinfected with Timentin-resistant strains. Major side effects were haemorrhagic diathesis with platelet dysfunction (1), severe water sodium overload (1), and possibly pancreatitis (1). Other side effects were mild: catheter-related phlebitis, and abnormal but clinically insignificant laboratory test results. Timentin appears to be an effective and safe broad-spectrum combination which compares favourably with third-generation cephalosporins in the treatment of severe hospital infections. More experience is needed to decide whether the somewhat lower response rate in patients infected with ticarcillin-resistant strains is significant.

Topics: Acute Disease; Adolescent; Adult; Aged; Amikacin; Bacteria; Bacterial Infections; Clavulanic Acids; Cross Infection; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Pancreatitis; Penicillin Resistance; Penicillins; Ticarcillin

The combination of ticarcillin and clavulanic acid (Timentin) was used in a nonrandomized open study in 28 patients with severe nosocomial infections. The infections were polymicrobial in 19 cases. Ten patients were bacteraemic and all were severely ill, receiving mechanical ventilation and with at least one organ system failure. Seventeen patients were treated with Timentin alone, 11 with a combination of Timentin and aminoglycosides. Timentin was used empirically, before identification of the bacteria in 14 patients (group I) and after identification of all the micro-organisms in 14 patients (group II). In group I, the empirical choice of Timentin was wrong in four cases, because at least one micro-organism was resistant to this drug. In the remaining 24 evaluable patients 12 patients were definitively cured. A relapse of the infection occurred in two cases. Five patients were initially improved but a secondary failure occurred due to a residual abscess in one case and to the underlying disease in four cases. Five initial failures due to the underlying disease in three cases were noted. The antimicrobial spectrum of Timentin is valuable in the management of nosocomial and polymicrobial infection, especially intra-abdominal infections and this study confirms a good clinical efficacy. However, combination with aminoglycosides seems mandatory, at least until the identification of all the micro-organisms involved in the infection.

Topics: Aminoglycosides; Bacteria; Bacterial Infections; Clavulanic Acids; Cross Infection; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Humans; Penicillin Resistance; Penicillins; Recurrence; Ticarcillin

Fifty patients were treated for suspected serious bacterial infection with Timentin 3.2 g 6-8-hourly. Three patients did not complete a minimum of 48 h treatment. Pathogens were isolated from 28 of the remaining 47 patients; 13 were resistant to ticarcillin but fully sensitive to Timentin; six of these isolates were Staphylococcus aureus. Five of the patients with Timentin-sensitive organisms or no significant growth failed to respond or relapsed after Timentin but also failed on subsequent therapy. An additional patient relapsed because of inadequate duration of treatment and one patient, with salmonella enteritis, became an asymptomatic carrier. The Timentin-resistant organisms were a Pseudomonas aeruginosa which responded to ceftazidime, a Klebsiella pneumoniae which was of doubtful clinical significance and an Escherichia coli which caused a relapse of pyelonephritis 16 days after apparently successful treatment with Timentin. No serious adverse reactions were seen. Timentin was effective against ticarcillin-resistant organisms but its final role will depend on the prevalence and significance of in-vitro resistance to the combination amongst Enterobacteriaceae and pseudomonads.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Hemorrhagic Disorders; Humans; Liver Function Tests; Middle Aged; Penicillin Resistance; Penicillins; Ticarcillin

In an open, non-comparative study 40 patients with severe, often life-threatening infections, were treated with Timentin 5.2 g (5 g ticarcillin plus 200 mg potassium clavulanate) by iv infusion every 6 or 8 h. They were suffering from septicaemia (9), obstructed UTI (8), non-obstructed urinary tract infection (10), respiratory tract infection (6), infected burns (4) or malignant otitis externa (3). Many patients had important aggravating factors such as renal transplantation, peritoneal or haemodialysis, leukaemia, extensive burns, renal stones, tracheostomy and diabetes. Pathogens included Pseudomonas aeruginosa (21), Escherichia coli (7), and other Enterobacteriaceae (6). Twenty-four pathogens (13 P. aeruginosa) were ticarcillin-resistant. Thirty-six patients were clinically cured including all cases of malignant otitis externa, infected burns and non-obstructed urinary tract infection. Three patients improved and one patient with obstructed urinary tract infection failed. In 32 patients the pathogen was eradicated, in one patient it persisted and in seven it reappeared. In particular, 11 of 13 patients with infections due to ticarcillin-resistant P. aeruginosa were cured and two improved. There was, however, bacteriological relapse in five. There were no side-effects or evidence of toxicity in any of the patients. In an in-vitro study a synergistic effect between ticarcillin and clavulanate was noted against Enterobacteriaceae but only a slight synergistic effect against P. aeruginosa. Studies in patients with normal liver and kidney function showed pharmacokinetic compatibility of the two agents. Timentin can be recommended for the initial treatment of serious infections.

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

In an open study 50 patients were treated for a variety of infections with 3.2 g Timentin 6, 8- or 12-hourly for a mean period of six days. Timentin was clinically successful in 87% of patients assessed at the end of treatment of whom 95% remained cured or improved at a later follow-up. Bacteriologically Timentin was successful against 92% of organisms, including all 11 which were ticarcillin or ampicillin resistant. Side effects were reported in seven patients, the majority of which were minor local reactions at the site of infusion. This open study shows Timentin to be a safe and effective antibiotic for the treatment of infection.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Humans; Kinetics; Male; Middle Aged; Penicillin Resistance; Penicillins; Postoperative Complications; Ticarcillin

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

Timentin (5.2 g tds) and tobramycin (40 mg tds) were administered to 51 patients (22 male, 29 female, age range 17-72, mean age 40.4) with acute leukaemia, chronic myeloid leukaemia in blastic crisis, severe aplastic anaemia and acute agranulocytopenia. All patients had neutropenia (PMN less than 1000/mm3) and fever (greater than 38 degrees C). Febrile episodes consisted of 22 proved septicaemias due to Gram-positive organisms (Staphylococcus aureus, S. epidermidis, enterococcus) in 11 cases and to Gram-negative organisms (Escherichia coli, Pseudomonas aeruginosa, Alkaligenes faecalis, Serratia marcescens, Klebsiella pneumoniae) in 10 cases. One patient had a polymicrobial infection (P. aeruginosa, S. aureus, non-haemolytic streptococcus). Twenty-nine infections were diagnosed only clinically. The mean duration of treatment was 11.1 days (range 4-20 days). Eighty-seven per cent of evaluable febrile episodes improved. Among 11 infections due to Gram-positive cocci, eight (72%) resolved, and in nine (90%) of ten cases due to Gram-negative bacilli success was obtained. The polymicrobial infection also resolved. In only four patients were mild side effects seen, e.g. exanthema, pruritus, phlebitis: renal toxicity was not observed. These data suggest that the combination of Timentin and tobramycin is an effective and safe empirical antibiotic regimen in febrile neutropenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Anemia, Aplastic; Bacteria; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Male; Middle Aged; Neutropenia; Penicillin Resistance; Penicillins; Ticarcillin; Tobramycin

Twenty-four children, ten of whom had an infection due to ticarcillin-resistant, Timentin-sensitive bacteria, were treated with Timentin. A full clinical success was obtained in sixteen cases (13 pyelonephritis, nine of them due to ticarcillin-resistant, Timentin-sensitive Escherichia coli, two neonatal infections and one pneumonia). Four children were improved (1 bronchiectasis, 3 leukaemias), three were unassessable and one failure occurred with a staphylococcal urinary tract infection. A pharmacokinetic study was performed in three newborns (under three months) and ten children (mean age 3 years). Timentin was administered as four daily 30-min iv infusions. The mean dosage used in patients under three months was 225 mg/kg/d ticarcillin and 9 mg/kg/d clavulanic acid. In infants older than three months of age the mean dosage was 250 mg/kg/d ticarcillin and 16 mg/kg/d clavulanic acid. The pharmacokinetic results demonstrated similar serum concentrations of ticarcillin to those in earlier studies, and serum concentrations of clavulanic acid of 3.1 +/- 0.63 mg/l and 2.18 +/- 0.17 mg/l at 1 h and 2 h respectively after infusion in newborns. For children, at the same times, the serum levels were respectively 2.3 +/- 0.9 mg/l and 1.4 +/- 0.9 mg/l. The peak serum concentrations of clavulanic acid were the same in the two groups of dosages (4.7 mg/l), but the half-lives of clavulanic acid were 1.1 h in children older than three months and 1.8 h in infants younger than 3 months. The tolerance was good. Timentin may be useful as a first line antibiotic in infections in hospitalized children in the dosage described, as three or four injections daily, according to the age and the severity of the disease.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Cross Infection; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Kinetics; Male; Penicillin Resistance; Penicillins; Pyelonephritis; Ticarcillin

Timentin proved to be highly effective in the treatment of 70 urological patients suffering from complicated urinary tract infections. There were few adverse effects, and development of resistance was not observed. Surgical treatment was possible in each case, without any septic complications. The results show that Timentin is a very useful drug for the urologist who often treats complicated urinary tract infections, especially because of its low re- and super-infection rate and the absence of development of resistance.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Penicillin Resistance; Penicillins; Premedication; Recurrence; Ticarcillin; Urinary Tract Infections; Urologic Diseases

Topics: Animals; Bacterial Infections; Clavulanic Acids; Drug Combinations; Humans; Penicillins; Ticarcillin

The efficacy and tolerance of Timentin was studied in 41 patients with various infections of the ears, nose and throat. The pharmacokinetics of Timentin were determined in pus, mucosa and polyps of the nose and paranasal sinuses, the tonsils and submandibular gland as well as in the interstitial fluid collected in Redon vacuum drainage. Experimental pharmacokinetic studies in the guinea pig were performed in the inner ear and eye fluids and in serum. Ticarcillin and clavulanic acid concentrations were determined by a microbiological micromethod. The clinical studies demonstrated that Timentin was very effective and well tolerated. The clinical and experimental pharmacokinetic studies provide a good explanation of this high degree of effectiveness.

Topics: Adolescent; Adult; Aged; Animals; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Guinea Pigs; Humans; Kinetics; Liver Function Tests; Male; Middle Aged; Otorhinolaryngologic Diseases; Penicillins; Ticarcillin

Timentin (ticarcillin + clavulanic acid) combined with an aminoglycoside usually netilmicin, was given to 33 children with neutropenic haematological malignancies. The combination of Timentin and aminoglycoside was effective treatment in 27 (87%) of 31 febrile episodes. There were four failures and three results which could not be interpreted. Bacteriological investigations were positive in 13 patients, three strains were resistant to ticarcillin but all were sensitive to Timentin. Clinical success, based upon reduction of fever within 48 h of treatment, was identical whether an organism was isolated or not. The combination of Timentin plus aminoglycoside was very successful and represents one of the best combinations available for empirical treatment for febrile neutropenic children.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Infant; Leukemia; Male; Neoplasms; Neutropenia; Penicillins; 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

The pharmacokinetics of ticarcillin and clavulanic acid were studied by blood and urine assay methods in 25 patients divided into five groups with varying degrees of renal insufficiency i.e. mild, moderate and severe renal insufficiency, almost anuric patients and those requiring haemodialysis (groups A to E). A single dose of 5.2 g Timentin (5.0 g ticarcillin and 200 mg clavulanic acid) was administered intravenously by infusion over 30 min. The average elimination half-life (T1/2) of ticarcillin increased from 0.95 h in patients with creatinine clearance (Clcr) of 80 ml/min to 1.8, 4.4, 6.9 and 11.2 h respectively in mild, moderate and severe renal insufficiency and in almost anuric patients. The T1/2 values for clavulanic acid were 0.75, 0.9, 2.0, 2.5 and 4.8 h in the same groups. The area under concentration-time curve (AUC) for ticarcillin increased from 787 to 2839 mg/l/h and for clavulanic acid from 12.8 to 29 mg/l/h when group mean values from patients with mild and severe renal insufficiency were compared. The plasma clearance (Clpl) of clavulanic acid was in all groups greater than that of ticarcillin i.e. 166 and 100 ml/min vs. 79.2 and 25.0 ml/min when comparing mean values from groups with mild and severe renal insufficiency respectively. The plasma clearance ratio clavulanic acid/ticarcillin increased proportionally to the degree of renal insufficiency from a value of 1.5 in normal subjects to between 3.3 and 3.8 in more advanced cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Kidney Injury; Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Penicillins; Renal Dialysis; Ticarcillin

The safety and effectiveness of Timentin were evaluated in 34 adult patients with symptomatic complicated urinary tract infections, principally due to multiply-drug-resistant bacteria. Although a wide variety of organisms, particularly gram-negative bacilli, were found, Escherichia coli was the most frequent, accounting for 14 of 45 (31 percent) pathogens isolated. Ten (22 percent) isolates were Pseudomonas aeruginosa; 11 (24 percent) were Proteus or Morganella species; three (7 percent) were Citrobacter; one (2 percent) was Klebsiella pneumoniae; two (4 percent) were Staphylococcus aureus; and two (4 percent) were enterococci. Ninety-three percent of all pathogens isolated produced a beta-lactamase. Eight (24 percent) infections were polymicrobial; seven (21 percent) were associated with bacteremia. Clinical improvement occurred in 30 of 34 (86 percent) patients. All bacteremias were cured. Although bacteriologic cure occurred in only 32 percent of patients, control of sepsis and temporary eradication of bacteria (bacteriologic improvement) occurred in 96 percent. Not surprisingly, the rates of relapses and reinfections were high. It was concluded that Timentin is a useful agent in the management of complicated urinary tract infection and offers clinicians an alternative to more toxic antibiotics, such as aminoglycosides.

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

Timentin is an exciting new antibiotic agent that is a combination of ticarcillin and clavulanic acid. Forty-seven patients with osteomyelitis received 3.1 g of Timentin intravenously every six hours. The mean duration of therapy was 32 days. The diagnosis was made by bone biopsy; bone biopsy was repeated at the completion of therapy. The bacterial etiology was predominately gram-positive organisms. Of the organisms isolated, Staphylococcus aureus was the most common isolate and represented 39 percent of the total isolates. Streptococcus species were isolated in 13 percent, Group D Enterococcus in 15 percent, Pseudomonas aeruginosa in 10 percent; 23 percent of the isolates were other gram-negative organisms. All but one organism were initially sensitive to Timentin. Three resistant organisms were isolated during therapy. Twenty-seven patients were classified as having a cure, based on no growth on repeat bone biopsy cultures and clinical signs of bone healing. Twenty-two patients returned for follow-up (one to nine months after therapy) and had no evidence of infection; however, because of the short follow-up period, these patients were classified as showing improvement. Six patients had adverse reactions to Timentin: two had mild allergic phenomena and two had prolonged bleeding times. In all four, therapy was discontinued. Two patients had a transient, mild elevation in the level of serum glutamic-pyruvic transaminase (less than twice normal levels). This new agent looks exciting for therapy of both gram-positive and gram-negative bacterial osteomyelitis.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Clavulanic Acids; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Osteomyelitis; Penicillins; Ticarcillin

Timentin, a combination of clavulanic acid (0.1 g) and ticarcillin (3.0 g), has proved effective in vitro against bacterial pathogens that produce beta-lactamases. The usual etiologic bacteria of osteochondritis of the foot (Pseudomonas species) and osteomyelitis/septic arthritis (Staphylococcus aureus) are commonly resistant to penicillins. To date, we have used Timentin to treat 30 children with bone, joint, and deep soft tissue infections. Timentin was administered intravenously at an average dosage of 207 mg/kg per day for mild to moderate infection and 310 mg/kg per day for bone and joint infections with systemic signs (sepsis). The lower dose was used in 24 patients and the other six patients, who had signs of sepsis, received the higher dose. All patients received Timentin intravenously over 30 minutes every four to six hours for a minimum of five days (mean 6.6 +/- 2.6 days, range five to 14 days). The mean time to defervescence and/or reduction in clinical symptoms was 1.6 +/- 1.3 days (range zero to four days). Osteochondritis due to P. aeruginosa was diagnosed in six patients, and septic bursitis, osteomyelitis, or septic arthritis due to S. aureus (13 patients) or Staphylococcus species and group A streptococci (four patients) was diagnosed in 17 patients. All isolates were susceptible to Timentin in vitro by disk-diffusion analysis. All patients showed a response to therapy with Timentin, with or without surgical intervention. All patients had clinical and microbiologic cures; no adverse reactions or side effects were observed. There have been no clinical or microbiologic relapses to date. Timentin may prove to be useful in specific bone and joint infections in children.

Topics: Arthritis, Infectious; Bacterial Infections; Bone Diseases; Cellulitis; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Female; Humans; Joint Diseases; Male; Osteochondritis; Osteomyelitis; Penicillins; Prospective Studies; Ticarcillin