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PubMed1997

Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa.

Owing to the broad spectrum of activity afforded by beta-lactam-beta-lactamase inhibitor preparations, these agents are frequently selected as empiric therapy for the treatment of mixed infections such as intra-abdominal and diabetic foot infections, either alone or in combination with an aminoglycoside. Twelve healthy volunteers were enrolled in a randomized, open-label, four-way crossover trial comparing the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against microorganisms commonly isolated from mixed infections. Subjects received the following regimes: (i) 3.375 g of piperacillin-tazobactam intravenously (i.v.) every 6 h (q6h) (ii) 4.5 g of piperacillin-tazobactam i.v. q8h, (iii) 3.1 g of ticarcillin-clavulanate i.v. q6h, and (iv) 3.0 g of ampicillin-sulbactam i.v. q6h. Serum bactericidal titers were determined and used to calculate the duration of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. The percentage of the dosing interval over which drug concentrations in serum remained above the MIC for each organism was determined and compared with the observed duration of bactericidal activity was noted (r = 0.78; P < 0.001). All of the regimens demonstrated good activity against B. fragilis and E. coli. Against E. faecalis and P. aeruginosa, however, all of the regimens provided bactericidal activity for less than 50% of the respective dosing intervals. These data suggest that use of shorter dosing intervals or continuous-infusion regimens should be considered in combination with an aminoglycoside to improve the bactericidal profiles of these agents for E. faecalis and P. aeruginosa.

Adult↗
PubMed1999

Comparative in vitro activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime in combination with tobramycin, rifampin, or ciprofloxacin against Burkholderia cepacia isolates from patients with cystic fibrosis.

We evaluated the activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime by determination of the MICs for 66 genotypically characterized Burkholderia cepacia isolates obtained from the sputum of cystic fibrosis patients. In vitro synergy assays, as performed by the time-kill methodology, of two- and three-drug combinations of the beta-lactams with tobramycin, rifampin, and/or ciprofloxacin were also performed with 10 strains susceptible, intermediate, or resistant to fluoroquinolones. On the basis of the MICs, meropenem and temocillin were the most active beta-lactam agents, with MICs at which 90% of isolates are inhibited of 8 and 32 micrograms/ml, respectively. The addition of ciprofloxacin significantly enhanced the killing activities of piperacillin, imipenem, and meropenem against the 10 strains tested (P < 0.05). The best killing activity was obtained with the combination of meropenem and ciprofloxacin, with bactericidal activity of 3.31 +/- 0.36 log10 CFU/ml (P < 0.05). Compared to the activity of the two-drug beta-lactam-ciprofloxacin combination, the addition of rifampin or tobramycin did not significantly increase the killing activity (P > 0.05). The three-drug combinations (with or without ciprofloxacin) significantly enhanced the killing activities of piperacillin, imipenem, and meropenem relative to the activities of the beta-lactams used alone (P < 0.05). The combination beta-lactam-ciprofloxacin-tobramycin was the combination with the most consistently synergistic effect.

Burkholderia Infections↗
PubMed2003

Population pharmacokinetic analysis of nonlinear behavior of piperacillin during intermittent or continuous infusion in patients with cystic fibrosis.

The purpose of this study was to describe the nonlinear pharmacokinetics of piperacillin observed during intermittent infusion and continuous infusion by using a nonparametric population modeling approach. Data were 120 serum piperacillin concentration measurements from eight adult cystic fibrosis (CF) patients. Individual pharmacokinetic parameter estimates during intermittent infusion or continuous infusion were calculated by noncompartmental analysis and with a maximum iterative two-stage Bayesian estimator. To simultaneously describe concentration-time data during intermittent infusion and continuous infusion, nonlinear models were parameterized as two-compartment Michaelis-Menten models. Models were fit to the data with the nonparametric expectation maximization algorithm. The calculations were executed on a remote supercomputer. Nonlinear models were evaluated by log-likelihood estimates, residual plots, and R(2) values, and predictive performance was based on bias (mean weighted error [MWE]) and precision (mean weighted square error [MWSE]). A linear pharmacokinetic model could not describe combined intermittent infusion and continuous infusion data well. A good population model fit to the intermittent infusion and continuous infusion data was obtained with the constructed nonlinear models. Maximum a posteriori probability (MAP) Bayesian R(2) values for the nonlinear models were 0.96 to 0.97. Median parameter estimates for the best nonlinear model were as follows: K(m), 58 +/- 75 mg/liter (mean and standard deviation); V(max), 1,904 +/- 1,009 mg/h; volume of distribution of the central compartment, 14.1 +/- 3.0 liters; k(12), 0.63 +/- 0.41 h(-1); and k(21), 0.37 +/- 0.19 h(-1). The median bias (MWE) and precision (MWSE) values for MAP Bayesian estimation with the Michaelis-Menten model were 0.05 and 4.6 mg/liters, respectively. The developed nonlinear pharmacokinetic models can be used to optimize piperacillin therapy administered via continuous infusion in patients with CF and have distinct advantages over conventional linear models.

Adult↗
PubMed1988

Comparative killing activity and postantibiotic effect of streptomycin combined with ampicillin, ciprofloxacin, imipenem, piperacillin or vancomycin against strains of Streptococcus faecalis and Streptococcus faecium.

Nine strains of Streptococcus faecalis and Streptococcus faecium were studied with respect to ampicillin, ciprofloxacin, imipenem, piperacillin, vancomycin and streptomycin. Two strains were highly resistant (MIC greater than or equal to 2,000 micrograms/ml) to streptomycin. Evaluation and comparison of the killing activity with killing curves, and duration of the postantibiotic effect (PAE) after exposure for 1 h with regrowth curves was done with combinations of antibiotics or alone. The overall killing effect of ciprofloxacin with streptomycin was antagonistic, whereas synergism (greater than or equal to one log10 decrease in viable counts) was observed in streptomycin-susceptible strains with combinations of streptomycin and ampicillin, imipenem, piperacillin or vancomycin. In addition, prolongation of PAE (greater than or equal to 0.5 h) was seen only in streptomycin-susceptible strains. Thus, seven (100%) strains showed a synergistic increase in PAE to combinations with ampicillin and vancomycin, three (43%) to imipenem, four (57%) to piperacillin, but none to the combination of streptomycin and ciprofloxacin. A significant correlation was observed between the magnitude of increased killing and the extent of increase in recovery period with combinations of streptomycin with either ampicillin or vancomycin.

Ampicillin↗
PubMed1989

Correlation between the growth and killing curves of Escherichia coli in the presence of cefotetan or piperacillin.

Escherichia coli strains that were susceptible to multiple antibiotics were exposed to cefotetan and piperacillin. As with the majority of beta-lactam antibiotics, the growth curves showed an increase in optical density (OD) due to an increasing volume of cell-wall-deficient bacteria during the first hours before lysis. This increase in OD depended on the concentration of cefotetan and was less dependent on the concentration of piperacillin. A good correlation was found between the prelytic increase in OD and the killing curve. During the prelytic increase in OD, the number of CFU/ml remained more or less constant. The decrease in the number of CFU/ml depended on the concentration of cefotetan and was less dependent on the concentration of piperacillin.

Cefotetan↗
PubMed1985

Pharmacokinetics of piperacillin in the postpartum patient.

Six women were given 1 g of piperacillin on the 2nd postpartum day and serum concentrations of the drug were measured at 0.5, 1, 2, and 4 h after infusion. The same women returned for an identical test 6 months later and hence served as their own controls. A second group of 6 women were treated identically except that they received the first dose of piperacillin on the 3rd postpartum day. The serum levels of antibiotic were consistently lower during the puerperium than at 6 months. The levels obtained at 2 compared to 3 days post partum were similar, but were about one half the levels obtained at 6 months post partum. These results indicate that antibiotic therapy for postpartum endomyometritis may need to take account of the fact that the altered pharmacokinetics of pregnancy persists into the puerperium. If used in this setting, the dose of piperacillin may need to be increased by 50% over the normal adult dose.

Adult↗
PubMed1986

Developmental pharmacology and therapeutics of piperacillin in gram-negative infections.

Twenty children ranging in age from 1 week to 19 years with documented or suspected bacterial infections arising outside the central nervous system were studied. Pharmacokinetic analysis was possible in 15 children; 8 after the first dose, 6 during steady-state conditions, and 4 on both occasions. Data were obtained utilizing noncompartmental pharmacokinetic methods. Peak piperacillin serum concentrations ranged from 51 to 232 mg/l and correlated directly (r = 0.75) with the dose administered. In children with normal renal function, there was an age-dependent decrease in elimination half-life and apparent steady-state volume of distribution, whereas plasma clearance increased logarithmically. All but 1 child responded favorably to piperacillin therapy, and 1 child with a urinary tract infection relapsed 10 days after discontinuation of the therapy. Although improved clinically, piperacillin monotherapy failed to eradicate pathogens in 2 children. No adverse clinical or biochemical effects were observed in any child.

Adolescent↗
PubMed1981

Clinical evaluation of piperacillin in bronchopulmonary infection.

Piperacillin sodium, a new semi-synthetic penicillin, was administered to eleven patients with acute bronchial infection and to fourteen patients with pneumonia. Piperacillin dosage was either 8 g/day (twenty-one patients) or 16 g/day (four patients) intravenously for periods of between 5 and 15 days. Clinical assessment was determined by diminution of sputum purulence, eradication of pathogen from sputum, clinical and radiological progress. There was a beneficial response in all but six patients, two of whom had severe chronic infective bronchial disease and four had underlying pulmonary malignancy. The low toxicity of piperacillin was confirmed, although one patient with chronic renal failure had a significant decline in renal function. Dosage should be reduced in patients with renal impairment.

Aged↗
PubMed1995

Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker.

A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma. He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics. Symptoms disappeared after being transferred to the packaging section. When the subject was admitted to our department he was asymptomatic. Basal lung function tests were in the normal range. Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative. Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration. Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash. A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative. We conclude that piperacillin sodium is an agent that can cause occupational asthma.

Adult↗
PubMed1986

Decreased baseline beta-lactamase production and inducibility associated with increased piperacillin susceptibility of Pseudomonas cepacia isolated from children with cystic fibrosis.

The incidence of pulmonary infections in children with cystic fibrosis caused by Pseudomonas cepacia, an organism which may possess an inducible beta-lactamase, has increased since 1978. Seven of 13 sputum isolates of P. cepacia from children with cystic fibrosis were classified as inducible by quantitative enzyme production following preincubation with 100, 200, or 400 micrograms/ml of cefoxitin. The recovery of inducible strains tended to be associated with recent ceftazidime therapy. Susceptibility to aztreonam, ceftazidime, and piperacillin alone or combined with the beta-lactamase inhibitors. YTR 830 or sulbactam, and isoelectric focusing for beta-lactamase were performed. Inducible isolates produced significantly more beta-lactamase than noninducible strains with or without the addition of cefoxitin. Noninducible isolates were more susceptible than inducible isolates to 8 micrograms/ml of piperacillin, a difference that was eliminated with the addition of either beta-lactamase inhibitor. Twelve of 13 strains produced a beta-lactamase band in the pH range of 7.9-8.1; no differences in satellite patterns were noted between the two groups of organisms. Increased production of beta-lactamase in the absence of an inducer may account for piperacillin resistance in P. cepacia in children with cystic fibrosis.

Analysis of Variance↗
PubMed1992

A pilot study of piperacillin and ciprofloxacin as initial therapy for fever in severely neutropenic leukemia patients.

We studied the efficacy of piperacillin and ciprofloxacin as initial parenteral therapy in 41 adult patients with leukemia who developed 47 febrile episodes during severe neutropenia following chemotherapy. 40 patients (98%) survived their febrile episode(s), whereas 1 patient died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 24/47 episodes (51%) had been successfully treated. These 24 favourable responses were seen in 15/24 (63%) microbiologically documented infections and 9/19 (47%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 46 episodes were evaluable, and 28 (61%) had responded successfully to piperacillin and ciprofloxacin. Successful treatment was most frequently observed in microbiologically defined infections, 18/23 (78%). Three of 5 (60%) Gram-positive, 11/12 (92%) Gram-negative and 1 of 2 mixed bacteremias were successfully treated. In contrast, only 10/19 (53%) FUO and none of 4 clinically defined infections had responded. Thus, this pilot study indicates that piperacillin and ciprofloxacin may be a safe and effective combination for the treatment of febrile episodes in severely neutropenic leukemia patients, which merits further investigation in randomized trials.

Adult↗
PubMed1986

Enhancement of 5-fluorouracil uptake into the bacterial cell by piperacillin.

The antibacterial activity of 5-fluorouracil, an antineoplastic agent, was found to be enhanced by piperacillin, a beta-lactam antibiotic, resulting in a synergism. It was considered that the synergism was caused by an increase of 5-fluorouracil uptake into the bacterial cell. On the other hand, amount of piperacillin bound to penicillin binding protein (PBP) did not change when 5-fluorouracil was added. The morphological change of the cell was due to the 5-fluorouracil when synergism appeared between 5-fluorouracil and piperacillin.

Bacteria↗
PubMed1982

Azlocillin, mezlocillin, and piperacillin: new broad-spectrum penicillins.

Three new broad-spectrum penicillins--azlocillin, mezlocillin, and piperacillin--will soon be available for clinical use. Azlocillin and piperacillin are more active than carbenicillin or ticarcillin against Pseudomonas aeruginosa. Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective. All three new drugs show substantial activity against anaerobes and ampicillin-susceptible gonococci and Haemophilus influenzae. Because these agents are inactivated by various beta-lactamases, most Staphylococcus aureus isolates and a number of gram-negative organisms, including some important nosocomial pathogens, will be resistant to these antibiotics. The new penicillins appear to be relatively safe and have been used successfully to treat patients with various infections; however, comparative trials have not yet established the superiority of these drugs over conventional therapeutic agents.

Azlocillin↗
PubMedDate not supplied

Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.

The purpose of this study was to compare meropenem monotherapy with combination therapy for empirical treatment of neutropenic fever in children with lymphoma and solid tumors. Ninety episodes of neutropenic fever in children (0.7-16.0; mean age 7.7 years) with solid tumors in a single center were randomized to receive either meropenem (50 mg/kg/dose-maximum 1 g, every 8 hours) or piperacillin (200 mg/kg/dose, every 6 hours) plus amikacin (15 mg/kg daily). Failure was defined as treatment modification. Non-Hodgkin's lymphoma (NHL) accounted for 62.2 percent of all episodes, and solid tumors (37.8%) for the rest. Blood cultures were positive in 23 percent of all episodes. Sixty-seven percent of all isolated microorganisms stained Gram-positive. Overall success was 70.0 percent (63/90). The success with meropenem was comparable to that seen with piperacillin plus amikacin: 76.6 versus 64.6 percent (p = 0.25). The failure rate was 33 percent with Gram-positive culture and 78 percent with Gram-negative or mixed cultures. The solid tumor group had significantly less bacteremia (4/34 versus 17/56; p < 0.05) and treatment failure (3/34 versus 24/56; p < 0.001) than the NHL group. No serious drug-related adverse event was noticed. Meropenem monotherapy was as effective as piperacillin plus amikacin combination in the empirical treatment of neutropenic fever in children with lymphoma and solid tumors.

Adolescent↗
PubMed1979

[In vitro studies with piperacillin. Effectiveness against enterobacteriaceae and pseudomonas aeruginosa compared to other antibiotics (author's transl)].

The in vitro activity of piperacillin, a new semisynthetic penicillin was compared with the inhibitory effect of other broad-spectrum penicillins and beta-lactamase stable cephalosporins. The examination was carried out by agar diffusion test with 1699 gram-negative strains. The antibacterial activity of piperacillin was generally superior to that of the other penicillins. Less than one per cent. of pseudomonas aeruginosa strains tested was resistant against piperacillin. Only klebsiella spp. showed a higher sensitivity against cefoxitin and cefuroxime.

Cefoxitin↗
PubMed1992

[Value of the combination of piperacillin and pefloxacin possibly followed by vancomycin in the treatment of febrile neutropenia in nephrotoxic chemotherapy].

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

Adolescent↗
PubMed1992

Stability of ranitidine hydrochloride with aztreonam, ceftazidime, or piperacillin sodium during simulated Y-site administration.

The stability of ranitidine hydrochloride after being mixed with commonly used i.v. beta-lactam antibiotics and administered by simulated Y-site injection was studied. Solutions of ranitidine 1 mg/mL (as the hydrochloride salt), aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), and piperacillin 30 mg/mL (as the sodium salt) were prepared by reconstitution in i.v. mini-bags. To simulate Y-site injection, 2 mL of ranitidine hydrochloride was mixed with 2 mL of each antibiotic in glass test tubes. These admixtures were prepared in triplicate and stored at room temperature under fluorescent light. Concentrations of each drug in each admixture were determined by stability-indicating high-performance liquid chromatography immediately and after one, two, and four hours. Aztreonam, ceftazidime, and piperacillin each retained more than 95% of the original concentration for at least four hours when mixed 1:1 with ranitidine. Ranitidine retained more than 90% of its original concentration for at least four hours when combined with each of the other drugs. Ranitidine 1 mg/mL (as the hydrochloride salt) and aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), or piperacillin 30 mg/mL (as the sodium salt) were stable for at least four hours during simulated Y-site administration.

Anti-Bacterial Agents↗
PubMed1992

[Piperacillin: comparison of antibacterial activity in vitro during the triennium 1986-88 versus the biennium 1981-82].

The antibacterial activity in vitro of piperacillin on strains commonly isolated in hospital practice in 1986-88 was compared with that obtained for piperacillin from 1981 to 1982 and with the activity of other antibiotics usually employed. Piperacillin showed a good antibacterial activity on Gram-positive and Gram-negative strains, while few resistant strains were found.

Anti-Bacterial Agents↗