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PubMed1988

Cefotaxime plus metronidazole appears more effective than piperacillin in the prevention of postappendicectomy wound sepsis. Preliminary results of a comparative trial.

Metronidazole suppositories have previously been shown to be superior to povidone iodine intraoperative wound spray in reducing postappendicectomy wound sepsis. In subsequent studies metronidazole suppositories and cefotaxime injections reduced the sepsis rate to 9.3%, while the same combination produced a wound sepsis rate of 7.6% compared with 17.2% for cefotaxime alone. In an ongoing study, metronidazole and cefotaxime are now being compared with piperacillin in a single-blind trial. Adult patients undergoing emergency appendicectomy in Nottingham have been included in this study, which has ethical committee approval. When the decision to perform emergency appendicectomy was made, the patient was randomly allocated a numbered pack. This contained either 3 x 1g injections of cefotaxime and 6 x 1g metronidazole suppositories or 3 x 2g injections of piperacillin and 6 placebos. 40 minutes before operation the patient received the first suppository and the remainder every 8 hours. The patient received the first injection of antibiotic by intravenous or intramuscular injection and the remaining doses 8 and 16 hours later. A wound was regarded as infected if pus discharged either spontaneously or on incision. 175 patients have been studied to date. The treatment groups were well matched for age and sex. Seven of the 77 patients in the cefotaxime/metronidazole group (9.1%) compared with 12 of the 76 in the piperacillin group (15.8%) have developed wound infections. This study confirms that the combination of cefotaxime and metronidazole seems to be more effective than piperacillin alone in the reduction of postappendicectomy wound sepsis. Currently cefotaxime plus metronidazole is the therapy of choice.

Administration, Rectal↗
PubMed1994

Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group.

OBJECTIVE: To compare piperacillin and tobramycin with ceftazidime alone for the empiric treatment of fever in the neutropenic patient without evidence of skin infections or anaerobic infections. DESIGN: A multicenter, randomized, controlled trial. PATIENTS: 876 febrile, neutropenic episodes in 696 patients (83% acute leukemia or bone marrow transplantation); 92 episodes were excluded from analysis because of protocol violation. INTERVENTIONS: Patients received either intravenous ceftazidime (2 g every 8 h) or piperacillin (12 to 18 g/d in 4 to 6 divided doses plus tobramycin (1.7 to 2.0 mg/kg body weight every 8 h). Treatment could be modified at any time at the discretion of the investigator. MEASUREMENTS: Percentage of satisfactory response, eradication of the infecting organism, development of superinfections, and occurrence of adverse events. RESULTS: As a single agent, ceftazidime was as effective as the combination of piperacillin and tobramycin (62.7% satisfactory responses compared with 61.1%; odds ratio, 1.07%; 95% Cl, 0.79 to 1.44; P > 0.2). Equivalent responses were also obtained in episodes of profound neutropenia (odds ratio, 0.76; Cl, 0.43 to 1.33; P > 0.2). Infectious mortality was 6% for ceftazidime and 8% for the combination therapy. Eradication of the infecting organisms was achieved in 79% of bacteremic episodes treated with ceftazidime compared with 68% of the episodes treated with the combination therapy (odds ratio, 1.76; Cl, 0.92 to 3.38; P = 0.08), and rates for gram-negative rod bacteremia were also similar (95% compared with 77%; odds ratio, 5.25; Cl, 1.0 to 27.5; P = 0.03). Superinfections developed in 38 episodes in each group. An adverse event occurred in 8% of episodes treated with ceftazidime compared with 20% of episodes treated with combination therapy (P < 0.001). CONCLUSION: Ceftazidime alone was as effective but safer than the combination of piperacillin and tobramycin for the empiric treatment of febrile, neutropenic patients, even those with profound and prolonged granulocytopenia.

Adult↗
PubMed2002

Influence of piperacillin on pharmacokinetics of etimicin in healthy volunteers.

AIM: To investigate the influence of piperacillin on the pharmacokinetics of etimicin. METHODS: Ten healthy male volunteers subjects were administered randomly with 200 mg of etimicin alone or in combination with 2000 mg of piperacillin. After two weeks washout period, the subjects were crossed over to the second regimen. Blood and urinary samples were collected at specified time intervals. Etimicin concentration was analyzed using micro-bioassay method with Bacillus pumillus as the tested strain. Pharmacokinetic para-meters were determined from serum concentration-time data with the 3p87-software package. RESULTS: Maximum serum concentrations of etimicin alone was (21 +/- 5) mg/L compared with (19 +/- 4) mg/L for the combination. The elimination half-lives were (1.9 +/- 0.4) h and (1.9 +/- 0.2) h for etimicin alone and in combination, respectively. The area under the concentration-time curve of etimicin alone was (38 +/- 7) mg . h . L-1 as opposed to (41 +/- 8) mg . h . L-1 in combination. Twelve hours after administration, urinary recovery rates of etimicin were (56 +/- 8) % and (56 +/- 6) % for etimicin alone and with piperacillin, respectively. CONCLUSION: The results indicated that the pharmacokinetics of etimicin was not affected by concurrent administration of piperacillin in healthy male volunteers. No modification in dosing regimen is necessary when two drugs were co-administered.

Adult↗
PubMed2002

[Clinical case of the month. Cholestatic hepatitis after administration of piperacillin].

We describe a patient suffering from infection of the upper respiratory tract, who was treated with a dose of 4 x 4 g of piperacillin over 10 days. Two days after the end of the treatment, she developed jaundice and had elevated alkaline phosphatase, gammaglutamyltransferase and transaminases. After exclusion of viral hepatitis, a vascular problem, and gall stone disease, the possibility of piperacillin-induced hepatitis was discussed. Lymphocyte transformation test for piperacillin was positive, suggesting an immunological mechanism for the observed hepatopathy. The patient was discharged a few days after in good clinical condition and with reduced liver values. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 2 months. We conclude that short-term therapy with piperacillin can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Positive lymphocyte transformation is compatible with an immunological mechanism.

Chemical and Drug Induced Liver Injury↗
PubMed1991

Piperacillin compared with cefuroxime plus metronidazole in diffuse peritonitis.

Eighty-five patients were randomly allocated to receive either piperacillin (n = 38) or cefuroxime plus metronidazole (n = 45) after surgical treatment of diffuse peritonitis; 78 were evaluable. A mean of 1.5 (piperacillin group) and 1.7 (cefuroxime/metronidazole group) pathogens/patient were identified. Twenty-seven patients (71%) were successfully treated in the piperacillin group compared with 29 (64%) in the cefuroxime/metronidazole group. These data suggest that piperacillin was neither better nor worse than cefuroxime/metronidazole in diffuse, secondary peritonitis.

Acute Disease↗
PubMed1991

[Diffusion of piperacillin into the sinuses of patients with nosocomial sinusitis].

Six mechanically ventilated patients with nosocomial sinusitis received an intravenous infusion of 4 g of piperacillin. Piperacillin concentrations were measured in the serum and in drained sinusal fluid 1, 2, 3, 4, 6 and 8 hours after the beginning of the infusion. A peak piperacillin level of 33 mg/l was obtained 30 minutes after the end of administration, and concentrations of 14 mg/l or more persisted for up to 8 hours. It is concluded that piperacillin can be used to treat patients with nosocomial sinusitis.

Adult↗
PubMed1991

[Changes in resistance of Pseudomonas aeruginosa to beta-lactams in a general intensive care unit over a three-year period. Role of piperacillin].

Nosocomial infections by Pseudomonas aeruginosa seen in a general intensive care unit from January 1987 through December 1989 were studied. Use of piperacillin, ticarcillin, cefsulodine, ceftazidime, and imipenem over the same period were recorded. Rate of infection by P. aeruginosa among the 1,844 patients admitted during the study period was 3.2%; 32% of all nosocomial infections during this period were due to P. aeruginosa. The proportion of P. aeruginosa strains exhibiting in vitro susceptibility to ticarcillin rose from 45.5% in 1987 to 59% in 1988 and 86% in 1989. Concomitantly, the proportion of P. aeruginosa strains simultaneously resistant to ticarcillin, piperacillin, cefsulodine and ceftazidime fell from 32% to 18.5% then 0%. A statistically significant correlation was found between the decrease in piperacillin use and the fall in penicillinase-producing ticarcillin-resistant strains of P. aeruginosa. Because piperacillin has undesirable effects on the intestinal flora and promotes the emergence of resistant strains of P. aeruginosa, the authors now use narrow spectrum antimicrobial agents as first line treatment of nocosomial infections.

Cefsulodin↗
PubMed1990

[Biliary elimination and hepatic disposition of piperacillin: experimental evaluation].

The rate of biliary elimination and the hepatic disposition of piperacillin were studied by using an experimental model of a three hours perfusion of five isolated rabbit liver preparations. After addition of 10 mg of the antibiotic to the circulating blood, a mean biliary peak of 1,013 +/- 305 micrograms/ml was obtained between the 30th and 60th minute. The cumulated biliary elimination (0-3 hr) amounted to 5,665 +/- 389 micrograms (56.7% of the dose given). The hepatobiliary clearance was calculated to 134.2 ml/hr and the biliary elimination rate constant to 0.5 545 (h-1). After the procedure, 7.2 +/- 2.7% of the dose of piperacillin was still present in the circulating blood and 0.4 +/- 0.1% in the liver. The degradation of the antibiotic in the perfusion device concerned 24.9% of the dose. The percentage of piperacillin undergoing hepatic biotransformation, calculated by subtraction, was 10.8%. Under these conditions, the biliary elimination of piperacillin is much higher than that of the twenty other beta-lactams studied in our laboratory by the same experimental procedure.

Animals↗
PubMed1986

[Evaluation of bile diffusion of piperacillin].

In 10 patients undergoing cholecystectomy peroperative samples of serum, bile and gall bladder tissue were obtained one hour after intravenous injection of 2 g of piperacillin. Measurements were made by high performance liquid chromatography. Mean concentrations of piperacillin were 81.7 +/- 13.6 micrograms/ml in serum (S), 382 +/- 110 micrograms/ml in choledochal bile (CB), 30.8 +/- 8.5 micrograms/ml in gall bladder bile and 10.5 +/- 2.6 micrograms/g of gall bladder tissue. With a CB/S ratio of 4.7, piperacillin may be classified among beta-lactams showing good distribution in the biliary tract. This property would make piperacillin useful against the pathogens usually responsible for biliary tract infections.

Adult↗
PubMed1986

[Effectiveness and tolerance of piperacillin in 333 patients].

In a French multicentric trial the effectiveness and safety of piperacillin were evaluated in 333 patients with severe infections. Piperacillin was administered alone in 212 cases. The overall results show that the drug was clinically effective in 85% of the patients. The results of this French study are similar to those of other studies previously published. They demonstrate an increase in the number of failures against ampicillin-resistant and carbenicillin-resistant strains, even when these strains were sensitive to piperacillin in vitro. Piperacillin was tolerated as well as the other beta-lactam antibiotics, the main side-effects being hypersensitivity reactions.

Anti-Bacterial Agents↗
PubMed1987

[Cefmenoxime or piperacillin plus amikacin. A prospective randomized comparison of empiric antibiotic therapy of febrile granulocytopenic cancer patients].

Cefmenoxime plus amikacin was compared in a prospective randomized trial with our standard regimen of piperacillin plus amikacin as an empiric therapy for fever in patients with granulocytopenia. Initial profound granulocytopenia (fewer than 100/mm3 mature granulocytes) was present in approximately 45% of the patients in trial of both treatment groups. Of 53 microbiologically and clinically documented infections treated with piperacillin plus amikacin, 36 (68%) showed improvement. Of 48 microbiologically and clinically documented infections treated with cefmenoxime plus amikacin, 23 (48%) showed improvement. The response rate for gram-negative infections treated with cefmenoxime plus amikacin was lower than that for infections treated with piperacillin plus amikacin. Toxicity was minimal, with an equivalent incidence of skin rash, diarrhea and hepatic dysfunction. Although clinical efficacy of the combination of piperacillin plus amikacin may be superior to cefmenoxime plus amikacin therapy, this study demonstrated no statistically significant differences.

Adolescent↗
PubMed1986

Genetic toxicology evaluation of the novel semi-synthetic antibiotic piperacillin.

Piperacillin (T-1220, Pipracil) a semi-synthetic antibiotic was evaluated in a battery of genetic toxicology assays. The assays employed were: the microbial assay, the host mediated assay, the microbial assay incorporating urine samples from mice dosed with piperacillin, the in vivo cytogenetic assay, and the dominant lethal assay. In all assays, piperacillin produced consistent negative results indicating that piperacillin does not have mutagenic potential.

Animals↗
PubMed1986

[In vitro bacteriostatic activity of piperacillin sodium against Pseudomonas].

One hundred and twenty-two strains of Pseudomonas isolated from diverse pathological processes were typified. In vitro activity of Piperacillin (antibiogram and MIC) was studied and compared with another two semisynthetic penicillins, Carbenicillin and Mezlocillin, and two aminoglycosides, Amikacin and Gentamicin. The strains isolated corresponded to: Pseudomonas aeruginosa (116), Pseudomonas cepacia (3), Pseudomonas fluorescens (1) and Pseudomonas putida (1). It was found that 110 Pseudomonas aeruginosa, one Pseudomonas cepacia and one Pseudomonas fluorescens were susceptible to Piperacillin. The susceptibility to this drug was quite higher than to the other penicillins tested. The MIC50 and MIC90 of Piperacillin were lower than those of semisynthetic penicillins and the minimum susceptibility value. In comparison with aminoglycosides it was found that, although Amikacin and Gentamicin did not reach the minimum value, Piperacillin exhibited higher MICs.

Humans↗
PubMed1985

Role of piperacillin in surgical prophylaxis of genitourinary infections.

One hundred sixty-five men and women undergoing open or transurethral urologic surgery participated in a study designed to compare the prophylactic efficacy and safety of piperacillin with those of cefotaxime when administered perioperatively. The piperacillin-treated group received 2 Gm one hour before surgery and 2 Gm three hours later, and the cefotaxime-treated group was administered 1 Gm on the same schedule. In 9 per cent of the piperacillin-treated patients and in 11 per cent of the cefotaxime-treated patients postoperative urinary tract infections developed, although no patient in either group had sepsis. The most frequently isolated pathogens were Escherichia coli and Enterococcus sp. As expected, the females in both surgical groups had a greater incidence of postoperative infections than did the males. No significant drug-related clinical reactions or changes in the results of the laboratory tests were encountered in either treatment group. Thus, a two-dose perioperative prophylactic regimen of piperacillin was as safe and as effective as a two-dose regimen of cefotaxime in preventing postoperative urinary tract infections or sepsis in these patients.

Bacterial Infections↗
PubMed1985

[Comparative antibacterial activity of piperacillin against Pseudomonas aeruginosa, Escherichia coli and Streptococcus faecalis in cultures and human serum].

The in vitro activity of piperacillin at 1/4, 1 and 4 X MHK against 5 strains each of Pseudomonas aeruginosa, Escherichia coli and Streptococcus faecalis was compared in Mueller-Hinton-bouillon and human serum. Serum without piperacillin was bacteriostatic against P. aeruginosa for 8 hrs., against E. coli for 24 hrs. Subinhibitory piperacillin concentrations were bacteriostatic against E. coli, but had no effect against P. aeruginosa and S. faecalis. Bactericidal activity against E. coli was achieved at 1 X MHK against P. aeruginosa and S. faecalis at 4 X MHK. Except for P. aeruginosa in concentrations of 1/4 and 1 X MHK the piperacillin activity in bouillon and serum was almost identical.

Animals↗
PubMed1985

Pharmacokinetics of piperacillin in hospitalized patients.

Piperacillin is an extended-spectrum penicillin active against Pseudomonas. It has been documented to be effective in the treatment of complicated urinary tract infections and urosepsis. Much of the pharmacokinetic information available is obtained from normal subjects. The purpose of this study is to evaluate piperacillin pharmacokinetics in hospitalized patients. Ten clinically stable hospitalized urology patients were given 4 grams of piperacillin intravenously in a single dose. Serial blood samples were then obtained and serum piperacillin concentrations were determined by high performance liquid chromatography. The following pharmacokinetic parameters (mean +/- SD) were determined: half-life = 1.09 +/- 0.31 h, elimination rate constant = 0.69 +/- 0.22 h-1, volume of distribution = 0.36 +/- 0.13 l/kg, total body clearance = 0.230 +/- 0.054 l/h/kg. These parameters are comparable to those obtained in normal subjects except for the volume of distribution which is slightly higher than that reported in healthy volunteers. Pharmacokinetic information obtained in healthy subjects may, therefore, be applied to the clinically stable hospitalized urology patient. However, changes in pharmacokinetic characteristics may be found in the critically ill patient with compromise in hemodynamics and significant third spacing of fluid.

Adult↗
PubMed1982

Chemotherapy against Pseudomonas aeruginosa in cystic fibrosis. A study of carbenicillin, azlocillin or piperacillin in combination with tobramycin.

A comparative study was made on tobramycin combined with either carbenicillin (500 mg/kg/day) or one of the new penicillins: azlocillin or piperacillin (both 300 mg/kg/day) in 50 cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Average 2-h levels of penicillins in serum were 46 micrograms/ml (piperacillin), 88 micrograms/ml (azlocillin) and 66 micrograms/ml (carbenicillin). The Pseudomonas strains were significantly more sensitive to piperacillin and azlocillin than to carbenicillin (minimal inhibitory concentrations 1.9, 2.3 and 4.2 micrograms/ml). In 21 of 54 treatment course temporary eradication of Pseudomonas was achieved. Improved ventilatory capacity and diminished proteolytic activity in sputum were seen in most patients with or without bacteriological treatment success. Resistant strains - often belonging to other types - appeared in the patients with treatment failure. With increased number of precipitating antibodies against Pseudomonas and with increased minimal inhibitory concentrations, the chance of eradication was smaller. Seven out of 20 treated with azlocillin and 14 out of 30 treated with piperacillin developed fever and exanthema by the end of treatment. Our experience suggests caution in the use of the new penicillins.

Anti-Bacterial Agents↗
PubMed1995

Interaction of vecuronium with piperacillin or cefoxitin evaluated in a prospective, randomized, double-blind clinical trial.

Interactions between beta-lactam antibiotics, particularly acylaminopenicillins, and vecuronium, a widely used muscle relaxant, leading to prolonged neuromuscular blockade have been reported in studies of experimental animals and in a few clinical case reports. In the clinical reports, however, confounding factors always existed. A clinical trial to evaluate interactions between vecuronium and cefoxitin or piperacillin was conducted. Patients having major operations requiring both muscle relaxants as part of general anesthesia and prophylactic antibiotics were entered into the trial and randomly assigned to receive either cefoxitin or piperacillin. The electromyographic twitch response was measured before and after administration of the antibiotic. Five of 27 evaluable patients had minor prolongation of the time to recovery of baseline twitch. No prolonged neuromuscular blockade was observed. There were no differences in responses between the two antibiotic treatment groups. Cefoxitin and piperacillin administered pre- or intra-operatively are not associated with clinically important prolongation of muscle relaxation induced by vecuronium. The potential for prolongation of neuromuscular blockade induced by vecuronium through concomitant administration of piperacillin or cefoxitin as antibiotic prophylaxis was investigated in a clinical trial of 30 patients having major abdominal operations. Quantitative measurement of neuromuscular blockade was done using the electromyographic twitch response to a supramaximal current stimulus.

Abdomen↗