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PubMed2002

New and rapid fully automated method for determination of tazobactam and piperacillin in fatty tissue and serum by column-switching liquid chromatography.

A sensitive and rapid HPLC assay for determining tazobactam and piperacillin in fatty tissue and serum is described. While the common methods need liquid-liquid extraction before the injection in a automated column switching HPLC, the new method works by direct injection of the filtered tissue extract or diluted serum in a automated column switching HPLC without any other pre-treatment. This was performed by the use of a NH2-precolumn and enrichment/transfer at different pH-level. During the analyses, the NH2-precolumn was automatically regenerated with acetonitrile-water. The chromatogram peaks for piperacillin and tazobactam were identified by the retention time and quantified by peak area. The calibration curve was linear between 1 and 16 microg/ml. The quantification limit of tazobactam was about 1 microg/ml in fatty tissue extracts and in diluted serum (calculated for pure serum 2 microg/ml), respectively. For piperacillin it was less. The described procedure allows sample clean-up and determination of the antibiotic within 35 min. The chromatograms with this easy sample treatment had the same quantity of matrix peaks and in contrast to liquid-liquid extraction no loss of piperacillin. Because of the automatically rinsing of the NH2-precolumn during the chromatographic separation, more than 50 different biological samples could be measured with one NH2-precolumn without loss of performance.

Adipose Tissue↗
PubMed1996

Determination of free extracellular concentrations of piperacillin by microdialysis.

The tissue penetration and distribution of antibiotics is of great importance, since most of the infections occur in the tissue. At the infection site, the free, unbound fraction of the antibiotic is responsible for the antiinfective effect. These free extracellular concentrations can be measured by microdialysis. It was the aim of the study to correlate free levels of the beta-lactam antibiotic piperacillin in blood with those in tissue. In vivo microdialysis sampling was used to study the tissue distribution patterns of piperacillin in anesthetized rats after single dose iv administration of the drug. The pharmacokinetics of piperacillin in plasma were consistent with a two-compartment body model. Comparisons between calculated free concentrations in the peripheral compartment and measured free extracellular concentrations revealed excellent agreement. Microdialysis is a suitable method to evaluate unbound drug concentrations in the tissues. In case of piperacillin, predictions of the concentration time profiles of free drug in the peripheral compartment can be made on the basis of plasma data.

Animals↗
PubMed2000

Effect of pentaglobin and piperacillin on survival in a rat model of faecal peritonitis: importance of intervention timings.

BACKGROUND: Faecal peritonitis is a progressive pathophysiological condition which may lead to multiple organ failure and death. The reason for the associated morbidity and mortality could be attributed to the fact that some of the subtle alterations in cellular function that occur during the early stage of peritonitis are unidentified and consequently missed, leading to inadequate or delayed intervention. Recent studies have shown that early treatment with antibiotic and antisera containing antibodies to lipopolysaccharide (immunoglobulin) improve the survival rate in these patients. The present investigation was undertaken to study the effect of pentaglobin and piperacillin with particular attention to time lag of drug intervention on animal survival following experimental peritonitis. METHODS: Experimental peritonitis was produced by inoculating 1 ml/kg of faecal suspension (2:1 w/v in saline) into the peritoneal cavity. Two groups of animals were treated with pentaglobin (4 ml/kg) or piperacillin (1000 mg/kg) respectively, whereas rats in another group received both drugs simultaneously. The first dose of each drug was given at 4 h, 6 h, 8 h and 12 h after faecal inoculation followed by 3 additional doses at 8-h intervals. For biochemical studies, separate groups of animals were used in which the treatment was started 4 h after faecal inoculation and the animals were killed at 12 h after the treatment. RESULTS: Both piperacillin and pentaglobin prolonged survival time of animals which received the treatment within 6 h of faecal insult. The combination of pentaglobin plus piperacillin produced better results as compared to the individual effect. There was a significant decrease in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase in catalase following faeces-induced septicaemia, suggesting a significant increase in oxidative stress. The changes in enzyme levels were significantly attenuated by both the drugs. CONCLUSION: The findings suggest that intervention with a combination of pentaglobin and antibiotics within 6 h of peritonitis might significantly improve survival rate in rat.

Animals↗
PubMed1980

In-vitro inactivation of aminoglycoside antibiotics by piperacillin and carbenicillin.

Clinical microbiology laboratory experiences wherein aminoglycoside serum assay results appeared inconsistent with the amount of the compound given when administered in combination with a semisynthetic penicillin led us to compare the interaction of three currently available aminoglycoside antibiotics with carbenicillin, as a representative semisynthetic penicillin given in large doses, and with piperacillin, a new broad-spectrum semisynthetic penicillin. Amikacin, gentamicin, and tobramycin were incubated in serum in vitro with various concentrations of carbenicillin and piperacillin. In the presence of very high concentrations of the two penicillins, tobramycin was the most rapidly inactivated aminoglycoside, gentamicin was next, and amikacin was only slightly inactivated. With low concentrations of the two penicillins, the rates of aminoglycoside inactivation were negligible. Carbenicillin, in high concentration, inactivated the aminoglycosides more rapidly than piperacillin. In patients experiencing renal failure, the maintenance of moderate serum levels of carbenicillin and piperacillin may be important in attempting to maintain adequate aminoglycoside serum levels.

Amikacin↗
PubMed1985

Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin.

We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins--ticarcillin, mezlocillin and piperacillin alone and in combination with 80 mg gentamicin in normal volunteers. Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin. Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350 mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l. Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin-gentamicin combination. However, except for the mezlocillin-gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin-gentamicin regimes were greater than 1:8 at zero and 2 h after the infusion against the organisms tested. It is unlikely that these differences in the three penicillin-gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.

Adult↗
PubMed1986

A randomized trial of Timentin and tobramycin versus piperacillin and tobramycin in febrile neutropenic patients.

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.

Adolescent↗
PubMed1988

Selection of resistance by piperacillin during Pseudomonas aeruginosa endocarditis.

The mechanisms responsible for emergence of resistance during antimicrobial therapy were investigated in isolates obtained from a patient suffering from Pseudomonas aeruginosa endocarditis. The strain was first isolated from blood cultures obtained upon admission of the patient. It was sensitive to piperacillin, ticarcillin and tobramycin. Piperacillin-tobramycin therapy was therefore instituted and led to a rapid improvement of the patient's condition. Unfortunately, the patient subsequently became febrile again and blood cultures continued to yield P. aeruginosa. However, the organism isolated was now resistant to piperacillin and other penicillins tested. Cell-free extracts of the pre- and post-therapy isolates were analyzed for their beta-lactamase activity. The susceptible pre-therapy strain did not produce significant levels of beta-lactamase. In contrast, the post-therapy strain produced high levels of the enzyme. Induction experiments indicated that the production of beta-lactamase was constitutive in the post-therapy isolate. Thus, piperacillin therapy has led to the selection of resistant mutants which produced high levels of beta-lactamase constitutively. This was associated with relapse of the infection and therapeutic failure.

Endocarditis, Bacterial↗
PubMed1990

A comparative study of intravenous ciprofloxacin and benzylpenicillin versus netilmicin and piperacillin for the empirical treatment of fever in neutropenic patients.

We examined the efficacy of ciprofloxacin as an empirical treatment for fever in 97 neutropenic patients in a randomized study of ciprofloxacin and benzylpenicillin versus netilmicin and piperacillin. Benzylpenicillin was included because of evidence of in-vitro resistance to ciprofloxacin in some streptococci. Clinical response rate was similar in the two groups (46% resolution for ciprofloxacin/benzylpenicillin and 52% for netilmicin/piperacillin). Microbiological assessment revealed more pathogens eradicated by ciprofloxacin and benzylpenicillin (66%) and fewer persisting (3%) than in patients receiving netilmicin and piperacillin (52% and 13% respectively). Staphylococcus epidermidis was the commonest pathogen, accounting for 38% of all isolates and 30% of all treatment failures. There were no treatment failures or superinfections due to streptococci. More therapy-related adverse reactions were seen in patients on netilmicin and piperacillin (28%) compared with those on ciprofloxacin and benzylpenicillin (10%). The combination of ciprofloxacin and benzylpenicillin is as effective as a standard regimen of netilmicin and piperacillin, with fewer adverse effects, and is highly attractive as empirical therapy for the febrile, neutropenic host. The inclusion of benzylpenicillin prevents streptococcal-associated treatment failure.

Adult↗
PubMed1990

Comparison of i.v. ofloxacin and piperacillin in the treatment of complicated urinary tract infections.

Sixty consecutive hospitalized patients with complicated urinary tract infections were randomly assigned in a ratio of two patients to 200 mg i.v. ofloxacin per day and one patient to 3 x 4000 mg piperacillin. The duration of treatment was seven days. Ten patients were excluded from the study because of primary resistance of the pathogens to the respective drug (6 of the 40 ofloxacin patients and four of the 20 piperacillin patients). Gram-negative bacteria were isolated in 64% and Staphylococcus species in 21%. A complete eradication of the organisms was found three to four days after the end of therapy in 75% of the ofloxacin group and in 73% of the piperacillin patients. At the three to four weeks follow-up reinfections were observed in three patients of each group. There were no statistical differences in the results. Therapy was discontinued because of adverse reactions (nausea, vomiting) in one patient from each group. The study shows that it is possible to treat complicated urinary tract infections just as successfully with 200 mg i.v. ofloxacin per day as with 3 x 4000 mg piperacillin per day.

Adolescent↗
PubMed1992

Post-antibiotic effect of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin for Pseudomonas cepacia.

The post-antibiotic effects (PAE) of ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin were studied for ten strains of Pseudomonas cepacia isolated from patients with cystic fibrosis. Antibiotic concentrations used for exposure were either the MIC of each agent for the sensitive isolates or the recommended sensitivity breakpoint concentrations for the resistant isolates. After 2 h of exposure, cultures were rapidly diluted 1000-fold to eliminate the antibiotic. Out of the ten isolates, there were eight sensitive to ceftazidime, six to ciprofloxacin, six to imipenem, nine to piperacillin and five to tobramycin. All antibiotics tested demonstrated PAE for some isolates of P. cepacia, however, each antibiotic failed to produce a PAE for at least one isolate. The mean PAE was 1.35 h for ceftazidime, 2.38 h for ciprofloxacin, 2.39 h for imipenem, 2.16 h for piperacillin and 1.77 h for tobramycin. Imipenem demonstrated PAE of > or = 0.5 h for all sensitive isolates tested; ceftazidime, piperacillin, ciprofloxacin and tobramycin demonstrated PAE of > or = 0.5 h for 6/8, 8/9, 5/6 and 2/5 sensitive isolates, respectively. These data indicate that several antibiotics have significant (> or = 0.5 h) PAE for isolates of P. cepacia.

Burkholderia cepacia↗
PubMed1994

Aspoxicillin versus piperacillin in severe abdominal infections--a comparative phase III study.

We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection. Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess. Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing. The efficacy rates were similar in the two study groups. Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS). The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs. Both drugs were generally well tolerated and no serious drug-related adverse events were noted. However, five patients died because of their illness and one patient had a fatal myocardial infarction. In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.

Abdominal Abscess↗
PubMed2005

Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis.

OBJECTIVES: Pharmacokinetic (PK)/pharmacodynamic (PD) models have become increasingly important in optimizing antimicrobial therapy. This approach is highly recommended by regulatory authorities intending to force the evaluation of antimicrobial action at the site of infection. METHODS: Clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus with MICs of 4, 8 and 16 mg/L for piperacillin were used in an in vivo PK/in vitro PD model. Bacteria were exposed in vitro to the concentration-versus-time profiles of piperacillin in plasma and subcutaneous adipose tissue measured in vivo in septic patients. Samples were withdrawn at defined intervals and the numbers of bacteria per mL were counted and plotted against time. RESULTS: Piperacillin levels determined in plasma were able to effectively inhibit bacterial growth of all bacterial strains used in the present study (MIC ranged from 4-16 mg/L). In contrast, concentration-versus-time profiles of subcutaneous adipose tissue were effective in killing isolates with MICs of 4 and 8 mg/L only, while bacterial growth of S. aureus and P. aeruginosa with MICs of 16 mg/L was not inhibited. CONCLUSIONS: Bacteria with MICs < 16 mg/L were effectively inhibited in subcutaneous adipose tissue in patients with sepsis. The prediction of microbiological outcome based on concentrations of piperacillin in plasma resulted in a marked overestimation of antimicrobial activity at the site of infection.

Aged↗
PubMedDate not supplied

Comparison of piperacillin vs. ticarcillin plus tobramycin in the treatment of acute pulmonary exacerbations of cystic fibrosis.

During a 22-month period 35 children with cystic fibrosis received 52 courses of antibiotic therapy for acute pulmonary exacerbations, including 26 cases of therapy with piperacillin and 26 courses with ticarcillin plus tobramycin. Groups were similar in age (5 vs. 5.4 years), disease severity based on Schwachman scores and presenting symptoms. Pseudomonas aeruginosa was the most common organism isolated in 90% of sputum cultures. Mean minimal inhibitory concentrations for piperacillin, ticarcillin and tobramycin were 8, 64 and 1 microgram/ml, respectively. Piperacillin pharmacokinetic data revealed an average half-life in serum of 36 minutes. Peak serum concentrations averaged 144 micrograms/ml, and after 4 hours serum concentrations continued to exceed the P. aeruginosa 90% minimal inhibitory concentration in 50% of children. The dosage requirement for tobramycin was quite variable, necessitated monitoring of aminoglycoside serum concentrations and in most cases resulted in at least one dosage adjustment. Emergence of resistant bacteria was not seen in 26 courses of piperacillin therapy. Both regimens were effective and well-tolerated. Single agent therapy has the advantage of providing reliable serum concentrations and, in contrast to the standard therapy, does not necessitate monitoring of serum drug concentrations.

Acute Disease↗
PubMed2006

Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients.

Combination therapy with a beta-lactam plus an aminoglycoside has been the standard approach for treating febrile neutropenia for many years. More recently, beta-lactam monotherapy has also been shown to be a reliable and safe approach. In the present study, 763 eligible patients with fever and neutropenia received piperacillin-tazobactam monotherapy. On day 3, according to the study protocol, 165 patients with persistent fever who fulfilled the study entry criteria were randomised to receive vancomycin or a placebo. The success rate was 51% in the intention-to-treat analysis and 62% in the per-protocol analysis. The overall mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the initial or subsequent infection. Randomisation had no influence on the study endpoints. The adverse event rate was evaluated only in the patient population not included in the randomised part of the study. Among these patients, adverse events probably or definitely related to piperacillin-tazobactam therapy were uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It was concluded that piperacillin-tazobactam could be considered as monotherapy for patients with high-risk febrile neutropenia.

Adolescent↗
PubMed1991

Pharmacokinetics and ascitic fluid penetration of piperacillin in cirrhosis.

The pharmacokinetics of piperacillin were evaluated in seven healthy volunteers, eight cirrhotic patients without ascites and 11 cirrhotic patients with sterile ascites after a single 15-min intravenous infusion of 4 g of the drug. In ascitic patients, piperacillin rapidly entered the peritoneal fluid. Peritoneal concentrations were higher than 10 mg/l from 0.5 to 8 h after the infusion. Disappearance rate of piperacillin was slower in the ascitic fluid than in plasma. The plasma half life of piperacillin was more prolonged in cirrhotic patients that in control subjects. This difference was more marked in ascitic patients for whom half life was twice as high as in volunteers (1.95 versus 0.91 h; P less than 0.01).

Adult↗
PubMed1988

Stability of ampicillin, piperacillin, cefotaxime, netilmicin and amikacin in an L-amino acid solution prepared for total parenteral nutrition of newborn infants.

The stability of ampicillin, piperacillin and cefotaxime, alone or in combination with either netilmicin or amikacin, was tested by microbiological methods at 29 degrees C (ampicillin, also at 22 degrees C) in an L-amino acid solution specially prepared for newborn infants. In the case of ampicillin, the mean concentration had dropped to 84% of the initial value after 24 hours. This fall is acceptable. Piperacillin and cefotaxime were stable. Admixture of netilmicin or amikacin did not affect the activity of ampicillin, piperacillin and cefotaxime. The concentrations of netilmicin and amikacin were stable for 24 hours. Combination with ampicillin, piperacillin or cefotaxime did not affect the activity of either aminoglycoside. The antibiotics investigated could therefore be used in our TPN infusion system.

Amikacin↗
PubMed1980

Comparative study of piperacillin, ticarcillin, and carbenicillin pharmacokinetics.

Piperacillin, ticarcillin, and carbenicillin were administered intravenously to 10 healthy volunteers in a three-way, crossover study. The pharmacokinetics of the three drugs were in general quite similar. The peak serum concentration of piperacillin achieved at the end of a 30-min intravenous infusion was 63.5 +/- 27.6 microgram/ml. During the first 8 h, 67.5% of the dose of piperacillin was excreted in the urine, and the urinary concentration was extremely high. All three penicillins had high volumes of distribution. The serum half-life of the beta elimination phase of carbenicillin was lower than that of either piperacillin or ticarcillin. The volunteers experienced no adverse reactions from the administration of the drugs.

Adult↗
PubMed1980

Clinical trial of piperacillin with acquisition of resistance by Pseudomonas and clinical relapse.

A total of 20 serious infections were treated with piperacillin. These infections included bacteremias (5), pneumonias (5), urinary tract infections (5), soft tissue infections (3), septic arthritis (1), and osteomyelitis (1). The most common bacterial pathogen was Pseudomonas aeruginosa, accounting for eight infections. The clinical and bacteriological response rates were 75 and 70%, respectively. Four of the five patients who failed to respond to piperacillin therapy were infected with Pseudomonas. In two patients with Pseudomonas infections clinical relapse was accompanied by the development of piperacillin-resistant P. aeruginosa. The findings suggest that the use of piperacillin as a single agent for the treatment of serious gram-negative infections may be ill-advised, especially if P. aeruginosa is the offending pathogen.

Adolescent↗