brl-28500 and Cross-Infection

Efficacy of ticarcillin/clavulanate was studied in the treatment of 11 patients with severe community- and hospital-acquired pneumonia in an open controlled trial. The drug was administered in a dose of 3.1 g every 4 or 6 hours depending on the infection severity. When pneumonia was due to Pseudomonas aeruginosa, amikacin was additionally used. The positive clinical effect of ticarcillin/clavulanate was stated in 73 per cent of the patients. The pathogen eradication was stated in all the patients. However, in 2 cases superinfection due to P.aeruginosa developed. Mild adverse effects were observed in 2 cases. It is concluded that ticarcillin/clavulanate is highly efficient in the treatment of patients with severe or complicated pneumonia. In cases with ventilator-associated pneumonia it is advisable to use ticarcillin/clavulanate in combination with an aminoglycoside.

Topics: Acute Disease; Adolescent; Adult; Clavulanic Acids; Community-Acquired Infections; Cross Infection; Drug Therapy, Combination; Humans; Lung Abscess; Middle Aged; Pneumonia, Bacterial; Ticarcillin; Time Factors

Topics: Bacteremia; Child; Child, Preschool; Clavulanic Acids; Cross Infection; Drug Therapy, Combination; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Prognosis; Severity of Illness Index; Ticarcillin; Treatment Outcome

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

Currently, the use of beta-lactamase inhibitors in combination with beta-lactam antibiotics represents an effective measure to combat a specific resistance mechanism of beta-lactamase producing organisms. Knowledge about the susceptibility profile of bacteria to different combination agents available is essential to guide appropriate treatment of severe infections in hospitalized patients. The present study compares the in vitro activity of three commercially available beta-lactam/beta-lactamase inhibitor combinations (piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanic acid) against beta-lactamase producing gram negative bacteria in a tertiary care hospital in north India.. A total of 9004 consecutively isolated extended spectrum beta-lactamase (ESBL) producing gram negative bacteria isolated from various clinical samples from patients admitted to the All India Institute of Medical Sciences, New Delhi, from September 2003 to August 2004 were included in the study. These isolates were screened for ESBL production by the inhibitor based test recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Antibiotic susceptibility testing was carried out by disc diffusion method as per NCCLS guidelines.. Of the 9004 isolates tested, 3232 (35.89%) were sensitive and 568 (6.31%) were resistant to all three combination agents, and rest 5204 (57.80%) were resistant to at least one of the combinations. Susceptibility to piperacillin/tazobactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid was 81.37, 76.06 and 45.48 per cent respectively. Piperacillin/tazobactam exhibited significantly (P<0.05) greater antimicrobial activity against Pseudomonas spp., Escherichia coli and Klebsiella spp. compared to cefoperazone/sulbactam.. Overall piperacillin/tazobactam was observed to be the best combination agent followed by cefoperazone/sulbactam in our setting. This difference in activities of these combination agents needs to be evaluated further by ascertaining their efficacy in clinical studies.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Cefoperazone; Clavulanic Acids; Cross Infection; Gram-Negative Bacteria; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Ticarcillin

The prevalence of vancomycin-resistant enterococci (VRE) is increasing, despite infection control measures. Limited data link ticarcillin-clavulanate to higher VRE prevalence.. Active surveillance for VRE was conducted before and after a formulary switch from ticarcillin-clavulanate to piperacillin-tazobactam. Rectal swabs were obtained serially in 863 adult patients admitted to intensive care units (ICUs) between November 1, 2000 and September 30, 2004.. In the postswitch period, 38 of 497 (7.6%) patients acquired VRE versus 42 of 366 (11.5%) patients in the preswitch period. Survival analysis showed an overall hazard ratio (HR) of .68 postswitch versus preswitch ( P = .07), with the greatest change in the surgical ICU (HR = .17, P = .006). Multivariate analysis showed an overall HR = .51 ( P = .004). Hospital-wide, nonstool VRE clinical cultures fell from 39 (.58/1000 patient days) in the 10-month preswitch period to 27 (.33/1000 patient days) in the 12-month postswitch period. Infection control practices and use of other antibiotics remained stable.. VRE acquisition appeared to decrease in association with a formulary change from ticarcillin-clavulanate to piperacillin-tazobactam.

Topics: Anti-Bacterial Agents; Carrier State; Clavulanic Acids; Cross Infection; Enterococcus faecium; Female; Formularies, Hospital as Topic; Gastrointestinal Tract; Humans; Intensive Care Units; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Risk Factors; Ticarcillin; Time Factors; Vancomycin Resistance

The aim of the study was to determine the activity of four beta-lactam antibiotics against nosocomial strains of Gram-positive bacteria. Two antibiotics combined with beta-lactamase inhibitors: timentin (TIC/CLAV) and tazocin (PIP/TZB) and two carbapenems: imipenem and meropenem were applied. The clinical strains were isolated from patients hospitalized in surgical ward of the National Clinical Hospital No 1 in Warsaw. The strains were identified in the automatic ATB system using ID 32 STAPH, API STREP, API CORYNE and API 20 A strips. The susceptibility of isolates to antibacterial agents was determined in the automatic ATB system using ATB STAPH, ATB STREP and ATB ANA strips. The susceptibility of strains to timentin, tazocin, imipenem and meropenem was tested with disc diffusion method. 111 strains of Gram-positive bacteria were cultured. Staphylococci (49) and enterococci (44) dominated among isolated strains. 33 Staphylococcus spp. strains were identified as methicillin-resistant. The obtained results indicate a significant role of Gram-positive cocci (staphylococci and enterococci) in the aetiology of nosocomial infections. Antibiotics combined with beta-lactamase inhibitors and carbapenems demonstrate broad antibacterial spectrum against clinical strains of Gram-positive bacteria except E. faecium strains.

Topics: Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acids; Cross Infection; Drug Resistance, Microbial; Drug Therapy, Combination; Gram-Positive Bacteria; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Species Specificity; Thienamycins; 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

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

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

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

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