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PubMed1986

Clinical comparison of piperacillin and cefoxitin in patients with bacteriologically confirmed infections.

The objective of this double-blind study was to compare the efficacy and safety of piperacillin with that of cefoxitin in patients with bacterial infections. Seventy hospitalized patients were treated with intravenous piperacillin (18 g/day) or cefoxitin (12 g/day) for a mean period of 11.5 days. Multiple serious underlying conditions were present in 91% of the patients in both treatment groups. The infection sites were the respiratory, urinary, and gastrointestinal tracts, the skin and skin structures, and the bones. Among the patients with evaluated courses of therapy, 87% (20 of 23) of the patients in the piperacillin-treated group and 90% (19 of 21) of the cefoxitin-treated patients were cured or improved. Multiple sites of infection were present in 6 patients given piperacillin and in 11 patients given cefoxitin. Gram-negative aerobic bacteria were the most frequently isolated organisms (56% of isolates). In each treatment group, 91% of the pathogens were eradicated. Three piperacillin-treated patients (9%) and four cefoxitin-treated patients (11%) had adverse clinical effects related to therapy; most of the effects were moderate in intensity. In conclusion, both piperacillin and cefoxitin were clinically safe and effective antibiotics for the treatment of these patients, most of whom had severe underlying conditions.

Adult↗
PubMed1992

Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin.

The dynamic interaction of planktonic and biofilm cells of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin was investigated in a chemostat system. The results indicated that planktonic and young biofilm cells of the 2-day-old chemostat culture of P. aeruginosa were susceptible to killing by chemostat-controlled doses of either 250 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml or 500 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml. Complete eradication of the planktonic and young biofilm cells was observed after exposure of the cells to six chemostat-controlled doses of these antibiotic at 8-h intervals for 7 days. Regrowth of the organism was not observed after the termination of antibiotic therapy on day 7. A different picture was observed when antibiotic treatment was initiated on day 10 after inoculation. Viable old biofilm cells were reduced to approximately 20% after exposure to the chemostat-controlled doses of 500 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml. Complete eradication of old biofilm cells could not be achieved, and regrowth of the organism occurred after the termination of antibiotic therapy. These data suggest that young biofilm cells of mucoid P. aeruginosa can be effectively eradicated with the combination of piperacillin and tobramycin, while old biofilm cells are very resistant to these antibiotics and eradication of old biofilm cells is not achievable with the chemostat-controlled doses of piperacillin and tobramycin used in this study.

Culture Media↗
PubMed1994

Penetration of piperacillin-tazobactam into bronchial secretions after multiple doses to intensive care patients.

The penetration of piperacillin-tazobactam in eight mechanically ventilated intensive care patients (age, 56.0 +/- 12.2 years, and weight, 76.5 +/- 15.2 kg [means +/- standard deviations]) with bacterial pneumonia was investigated. They were given intravenous doses of piperacillin (4 g) and tazobactam (0.5 g) as 30-min infusions every 6 h. The kinetic study was performed after the fourth dose on day 2 of treatment. Samples of blood and bronchial secretions (BS) were collected before the fourth dosing and 0.5, 1, 2, 4, and 6 h after the end of infusion. Drug concentrations in both sera and BS were measured by high-performance liquid chromatography. Concentrations (in micrograms per milliliter) in serum were 184.80 +/- 63.03 and 40.03 +/- 30.79 for piperacillin and 23.05 +/- 7.53 and 4.86 +/- 4.54 for tazobactam at 0.5 and 6 h, respectively, after the end of infusion. The corresponding concentrations (in micrograms per milliliter) in BS were 29.33 +/- 25.08 and 20.25 +/- 19.11 for piperacillin and 6.86 +/- 4.25 and 4.25 +/- 2.78 for tazobactam. The percentages for the extent of penetration of piperacillin and tazobactam, as defined by the BS/serum area under the curve ratio, were 35.70 and 78.42%, respectively. These data indicate good penetration of both piperacillin and tazobactam into BS. The concentrations of tazobactam in BS are persistent and high enough to exceed the values found to be effective in vitro against the tazobactam-susceptible beta-lactamases produced by the most important pathogens responsible for nosocomial pneumonia.

Adult↗
PubMed2004

Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and Monte Carlo simulation.

The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was performed to estimate the probability of attaining a target free-piperacillin concentration greater than the MIC for 50% of the dosing interval for 3.375 g every 6 h or every 4 h given as a 0.5-h infusion at each MIC between 0.25 and 32 microg/ml. In the population pharmacokinetic analysis, measurements of bias and precision, observed-predicted plots, and r2 values were highly acceptable for all three models and all three models were appropriate candidates for the Monte Carlo simulation evaluation. Visual comparison of the distribution of the piperacillin concentrations at the pharmacodynamic endpoint--h 3 concentrations of a 6-h dosing interval--between the simulated populations and raw data revealed that the linear model was most reflective of the raw data at the pharmacodynamic endpoint, and the linear model was therefore selected for the target attainment analysis. In the target attainment analysis, administration of 3 g of piperacillin every 6 h resulted in a robust target attainment rate that exceeded 95% for MICs of < or =8 mg/liter. The 4-h piperacillin administration interval had a superior pharmacodynamic profile and provided target attainment rates exceeding 95% for MICs of < or =16 mg/liter. This study indicates that piperacillin-tazobactam should have utility for empirical therapy of hospital-onset infections.

Algorithms↗
PubMed2003

Ertapenem once a day versus piperacillin-tazobactam every 6 hours for treatment of acute pelvic infections: a prospective, multicenter, randomized, double-blind study.

OBJECTIVE: To compare ertapenem therapy with piperacillin-tazobactam therapy for the management of acute pelvic infections. METHODS: In a multicenter, double-blind study, 412 women with acute pelvic infection were assigned to one of two strata, namely obstetric/postpartum infection or gynecologic/postoperative infection, and were then randomized to ertapenem, 1 g once a day, or piperacillin-tazobactam, 3.375 g every 6 hours, both administered intravenously. RESULTS: In total, 163 patients in the ertapenem group and 153 patients in the piperacillin-tazobactam group were clinically evaluable. The median duration of therapy was 4.0 days in both treatment groups. The most common single pathogen was Escherichia coli. At the primary efficacy endpoint 2-4 weeks post therapy, 93.9% of patients who received ertapenem and 91.5% of those who received piperacillin-tazobactam were cured (95% confidence interval for the difference, adjusting for strata, -4% to 8.8%), indicating that cure rates for both treatment groups were equivalent. Cure rates for both treatment groups were also similar when compared by stratum and severity of infection. The frequency and severity of drug-related adverse events were generally similar in both groups. CONCLUSIONS: In this study, ertapenem was as effective as piperacillin-tazobactam for the treatment of acute pelvic infection, was generally well tolerated, and had an overall safety profile similar to that of piperacillin-tazobactam.

Acute Disease↗
PubMed1990

Antibacterial activity of piperacillin and tazobactam against beta-lactamase-producing clinical isolates.

The effectiveness of a combination of the recently developed penam sulphone tazobactam with piperacillin was studied in clinical isolates with defined beta-lactamase production. The combination was highly effective against piperacillin-resistant beta-lactamase-producing Staphylococcus aureus, TEM-1-producing Escherichia coli and Proteus vulgaris isolates. It was less effective against E. coli isolates producing the OXA-1 enzyme and marginally active against TEM-1-producing Klebsiella spp. isolates. The presence of tazobactam at a concentration of 10 mg/l markedly reduced the minimal inhibitory concentrations for piperacillin in most of the beta-lactamase-derepressed Enterobacter cloacae, Serratia marcescens and Citrobacter freundii isolates; however, this synergism was much less pronounced in beta-lactamase-derepressed Klebsiella spp. isolates. The selection frequency of resistant clones from clinical E. cloacae and C. freundii isolates could be markedly reduced by the addition of 10 mg/l tazobactam to the piperacillin-containing selective medium. Resistant clones could be obtained only from part of the wild-type strains at 2 or 4 times the MIC of piperacillin in the presence of tazobactam, whereas resistant clones could be selected up to 64 times the MIC of piperacillin without the addition of tazobactam. This aspect deserves attention with respect to the rapid selection of beta-lactamase-derepressed clones from nosocomial pathogens.

Drug Synergism↗
PubMed1984

Piperacillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Piperacillin is one of the new generation of semisynthetic penicillins which can be administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Although piperacillin has shown greater activity against beta-lactamase-producing organisms than the other penicillins, it is hydrolysed by the plasmid-mediated beta-lactamases (TEM-1). Activity against Pseudomonas aeruginosa is better than that of ticarcillin, carbenicillin and mezlocillin. Although only limited controlled studies have been reported, in those which have been conducted and in a larger number of open studies piperacillin was effective in the treatment of complicated urinary tract infections and lower respiratory tract infections, particularly pneumonia, caused by Gram-negative bacilli. Favourable clinical results have been obtained in patients with infections caused by mixed aerobic/anaerobic organisms (such as intra-abdominal infections) but the relatively average in vitro activity of piperacillin against Bacteroides fragilis may not indicate its usage in situations where this organism is the suspected or proven pathogen. Piperacillin in combination with an aminoglycoside or a 'third generation' cephalosporin gave encouraging results in the treatment of infections in immunocompromised patients, whilst its penetration into the diseased central nervous system and lack of toxicity indicate a potential value in the treatment of neonatal Gram-negative bacillary meningitis, particularly where the causative organism is Pseudomonas aeruginosa. Whether piperacillin alone is appropriate therapy for conditions usually treated with aminoglycosides (other than pseudomonal infections) needs additional clarification, but if established as equally effective in such conditions it has the advantages of its apparent lack of serious adverse effects and freedom from the need to undertake plasma concentration monitoring. These advantages would not, however, apply when considering one of the new (third generation) cephalosporins as alternative therapy in non-pseudomonal infections. Generally, however, it is still considered necessary to treat serious and complicated infections with combination therapy, either a cephalosporin, or in cases of resistance to P. aeruginosa an aminoglycoside.

Animals↗
PubMed1980

Piperacillin: evaluation against inpatient and gentamicin-resistant bacteria.

When species-matched collections, each consisting of 128 bacterial strains, were compared, inpatient organisms were found to be significantly more resistant to piperacillin than outpatient organisms. A collection of 143 gentamicin-resistant gram-negative bacilli was significantly more resistant to piperacillin than a species-matched collection of gentamicin-sensitive organisms. Piperacillin resistance was transferred by conjugation from isolates of 8 different Enterobacteriaceae species to a recipient Escherichia coli strain. In each of 67 mating experiments in which transfer of carbenicillin resistance by conjugation occurred, resistance to ticarcillin, azlocillin and piperacillin was also transferred. As in previous studies, piperacillin was found to be markedly more active against non-fastidious gram-negative bacilli than carbenicillin, ticarcillin or azlocillin. Nevertheless, piperacillin resistance, apparently plasmid mediated, was detected in multiple species.

Bacteria↗
PubMed1999

[Piperacillin: use at a general hospital].

AIM: To analyze the use of piperacillin in a general hospital in 1996 and 1997. MATERIAL AND METHODS: The data from 338 patients who were treated with piperacillin between January 1996 and December 1997 were collected retrospectively. RESULTS: We analyzed 385 infectious episodes in 338 patients with a mean age of 63.1 years. The therapeutic indications included nosocomial infection, infection in neutropenic patients and other diagnoses such as respiratory, intraabdominal and osteoarticular infections. In most episodes, there were infections in neutropenic patients, representing 39.2% of all cases. In 86.2% of the episodes the combination of piperacillin and aminoglycoside was established. The mean duration of the treatment with piperacillin was 8.9 days. Positive cultures were presented in 39.7% of the episodes. The microorganisms most frequently isolated were the Gram-negative bacilli, such as Pseudomonas aeruginosa and Escherichia coli. The isolations were obtained from sputum (24.6%), blood (22.1%), urine (19.8) and exudate (8.8%). The activity of piperacillin and aminoglycoside was 93% and 90% respectively against P. aeruginosa. The global mortality of the series was 25.5% with 18.9% being related to the infectious episode. CONCLUSIONS: From the above analyses we can deduce that piperacillin maintains its indications in a general hospital, these being, basically, neutropenic infection and nosocomial pneumonia. Another indication is infection by Pseudomonas, against which it continues to show good activity.

Adult↗
PubMed1992

[Diffusion of piperacillin in the eye].

Intraocular diffusion of piperacillin was studied in 42 patients scheduled for cataract surgery (n = 35) or vitrectomy (n = 7). Piperacillin was administered intravenously (4 g/injection). Thirty-four patients were given a single dose and 8 were given two doses 12 hours apart. Peak piperacillin levels in the aqueous (7.3 mg/l) occurred one hour after the injection; levels in the vitreous were low (less than 0.6 mg/l). Intraocular diffusion of piperacillin was also studied in rabbits with an experimental Staphylococcus epidermidis infection of one eye; the other eye served as the control. In pigmented rabbits (6 Fauve de Bourgogne animals), increased diffusion and decreased elimination of piperacillin were seen in the aqueous, iris and cornea of the infected eyes, as compared with uninfected control eyes. In albino rabbits (6 New Zealand animals), results were less conclusive, with a difference between the infected and healthy eyes appearing only during the second hour following the injection. The good diffusion of piperacillin in the aqueous, especially in infected eyes (at least in rabbits), suggests that this drug may be useful for the treatment of ocular infections provided it is initiated early and given in combination with another antimicrobial exhibiting good intraocular diffusion.

Aged↗
PubMed1990

Prospective comparative study of cefotetan with piperacillin for prophylaxis against infection in elective colorectal surgery.

This study compared one dose of cefotetan with three doses of piperacillin as prophylaxis against wound infection in 153 patients undergoing elective colorectal surgery. The patients were randomized into two groups: the first received 2 g cefotetan intravenously with induction of anaesthesia (n = 75), and the second received three doses of 2 g piperacillin (n = 78). Wound infection was defined as the presence of an abscess or discharging pus from the wound. In the cefotetan group there were 14 (19%) wound infections and 13 (17%) in the piperacillin group. There were three septic deaths, one in the cefotetan group and two in the piperacillin group. Both groups were comparable with regard to age, sex, nature of pathology and pre- and perioperative risk factors. No significant haematological or biochemical abnormalities were detected. The only adverse reaction was one patient who had an allergic reaction (rash) to piperacillin. These data suggest that single-dose cefotetan is as effective as triple-dose piperacillin in prophylaxis against infection in elective colorectal surgery.

Cefotetan↗
PubMed1989

Intravitreal injection of piperacillin.

Piperacillin was injected into the vitreous body of rabbit eyes to evaluate its suitability for intraocular injection and its toxicity on intraocular tissues. Doses ranged from 50 micrograms to 3,000 micrograms. Toxicity was determined through histology and electroretinograms by comparing the piperacillin-injected eyes with eyes injected with balanced saline solution. Retinal toxicity was noted in the outer layer of the retina when 3,000 micrograms was injected intravitreally. No toxicity was noted by histology with 1,500 micrograms of piperacillin. The minimal inhibitory concentration of piperacillin is 800 micrograms/cc for both gram negative and gram positive organisms. The large dose of intravitreal piperacillin tolerated by rabbit eyes makes piperacillin a potentially safe and effective broad spectrum antibiotic for the treatment of bacterial endophthalmitis in human eyes.

Animals↗
PubMed1986

[Comparative pharmacokinetics of piperacillin in young and elderly subjects].

One single 4 g dose of piperacillin was administered by intravenous infusion over 30 min to 15 patients aged from 66 to 90 years (mean +/- s.e.m.: 79.8 +/- 2.0 years); the patients mean weight was 53 +/- 4 kg. Fifteen samples of blood were withdrawn from each subject. Plasma piperacillin levels were measured by high performance liquid chromatography with detection in ultraviolet light at 214 nm. Mean plasma piperacillin concentrations in elderly subjects, measured 0.5, 2 and 12 h after dosing, were 168.5 +/- 15.7, 79.9 +/- 11.5 and 1.72 +/- 0.69 microgram.ml-1, as against 146.8 +/- 10.6, 35.5 +/- 3.9 and 0.212 +/- 0.040 microgram.ml-1 in healthy young adults. Plasma piperacillin concentrations versus time curves obtained after the infusion was discontinued were bi-exponential, with half-lives T1/2 (lambda 1) and T1/2 (lambda 2) of 0.65 +/- 0.11 and 1.72 +/- 0.09 h respectively; the corresponding figures in young adults were 0.59 +/- 0.03 and 1.81 +/- 0.13 h respectively). In elderly subjects the mean total clearance of piperacillin (ClT = 2.90 +/- 0.25 ml.min-1.kg-1) was reduced by 15% (NS) and the volume of distribution during steady state (Vdss = 0.337 +/- 0.027 L.kg-1) was increased by 43% (P less than 0.001). As a result, the mean time of piperacillin stay in the body (MRS = Vdss/Cl) was practically doubled in elderly subjects (2.09 +/- 0.15 h as against 1.15 +/- 0.04 h in young adults (P less than 0.01).

Adult↗
PubMed1988

[Pharmacokinetics of piperacillin during continuous ambulatory peritoneal dialysis].

We studied the kinetics of piperacillin in patients under continuous ambulatory peritoneal dialysis. Piperacillin 2 g was injected intravenously in 6 patients whereas 1 g was given intraperitoneally either a single dose in 3 patients without infection or the same dose every six-hours in 4 patients with peritonitis. Piperacillin was assayed by HPLC. After intravenous administration, the mean plasma piperacillin concentration was 3.1 +/- 5.6 mg/l at 12 h, the mean plasma t1/2 at 2.43 +/- 0.84 h, the volume of distribution at 20.4 +/- 6.3 l and the peritoneal clearance at 0.19 +/- 0.04 ml/min. After iterative intraperitoneal administration, serum and dialysate concentrations of piperacillin were above the minimum inhibitory concentration for susceptible pathogens without antibiotic accumulation. Peritoneal absorption was higher during peritonitis (83.4 +/- 4.8%) than without peritonitis (67.8 +/- 8.5%). Piperacillin 2 g IV every 8 hours or 1 g IP every 6 hours seemed to be the appropriate regimen in patients with chronic renal failure on CAPD.

Humans↗
PubMed1988

Treatment of febrile episodes in neutropenic leukemic patients with the antibiotic combinations piperacillin or ceftazidime plus amikacin: results of a randomized study.

Seventy-six consecutive neutropenic patients with hematologic malignancies, admitted to the "Department of Hematology" of Rome between March and September 1986, were randomly assigned to receive either piperacillin (300 mg/kg in four divided doses) or ceftazidime (100 mg/kg in four divided doses) plus amikacin (15 mg/kg in two divided doses) whenever they developed a febrile episode (temperature greater than 38 degrees C thrice over 12 hours, not related to drugs or transfusions, or else temperature greater than 38.5 degrees C). After 72 hours of antibiotic therapy, in case of persistent fever, piperacillin or ceftazidime was added to the ceftazidime + amikacin or piperacillin + amikacin combination, respectively. The antibiotic treatment was, however, modified according to in vitro susceptibility if a positive culture was present. Success without regimen modification was observed in both antibiotic combinations in 52.6% of cases. Considering the empiric cross of antibiotics, the response rate reached 78%. Neither toxicity nor side effects were observed in the reported groups. Considering blood isolates, we observed a greater incidence of gram-positive organisms compared with gram-negatives (28 cases vs 5 cases, 84.7% vs 15.3% respectively). Fungal infections were documented in four cases, two in each group. Even though no statistical difference was found between the two groups as far as patients not responding to the first antibiotic combination are concerned, piperacillin seems to have had more efficacy (twelve patients responding to the addition of piperacillin vs seven patients responding to the addition of ceftazidime). Piperacillin + amikacin seems to be as effective as ceftazidime + amikacin in the empirical therapy of febrile episodes in neutropenic patients.

Adolescent↗
PubMed1986

The effect of hemodialysis on piperacillin pharmacokinetics.

The disposition of piperacillin given as a 4 gm i.v. infusion was assessed during an interdialytic period and during hemodialysis in 12 chronic hemodialysis patients. Piperacillin concentrations in serum and dialysate were determined by HPLC. The half-life decreased from 2.84 +/- 2.04 h (mean +/- SD) during the interdialytic period to 1.30 +/- 0.43 h during the hemodialysis period (p = 0.008). Piperacillin total body clearance was 74.9 +/- 34.0 ml/min during the interdialytic period and the hemodialysis clearance was 92.4 +/- 30.0 ml/min. A significant change in the volume of distribution was observed from the interdialytic to dialytic period (0.21 +/- 0.06 vs 0.26 +/- 0.07 l/kg) (p = 0.026). A significant correlation between the hemodialysis clearance of piperacillin and hemodialysis clearance of creatinine and blood flow rate was also noted. No significant rebound in serum piperacillin concentrations was observed after cessation of hemodialysis. Approximately 46% of the amount of piperacillin in the body was removed by dialysis.

Adult↗
PubMed1982

Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.

In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.

Adolescent↗
PubMed1995

[In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin].

The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmicin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae. These strains were selected for their resistance pattern to beta-lactam antibiotics and their beta-lactamases were characterized by the mean of isoelectric focusing in comparison with reference strains. A comparison of the MICs of piperacillin, alone and in combination, assessed the efficacy of tazobactam as beta-lactamase inhibitor, particularly when a TEM-1 beta-lactamase was produced. When the strains were sensitive to the aminoglycosides (111 netilmicin-sensitive ones and 131 amikacin-sensitive ones), we observed 55% of synergistic effects and 45% of additions with the combinations piperacillin-tazobactam-netilmicin or amikacin. A synergistic effect was usually encountered with P. mirabilis, P. vulgaris, M. morganii and with the strains of E. coli, E. cloacae and S. marcescens which produced a cephalosporinase only. Among the 51 strains that were intermediate or resistant to netilmicin, 8 ones were inhibited by piperacillin-tazobactam-netilmicin at therapeutic levels (3 synergisms, 5 additions). Among the 31 strains that were intermediate or resistant to amikacin, 24 ones (18 synergisms, 6 additions) were inhibited by piperacillin-tazobactam-amikacin at therapeutic concentrations. In most of the cases, the combination of piperacillin-tazobactam with an aminoglycoside enhanced the antibacterial activity of these agents by decreasing the concentrations necessary to inhibit the strains.

Amikacin↗