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PubMed2006

[Interstitial nephritis attributed to treatment with piperacillin-tazobactam and with ciprofloxacin].

A 26-year-old man was treated with piperacillin-tazobactam because of suspected cholangitis and a 77-year-old man was given ciprofloxacin because of an infected knee-prosthesis. They both developed symptoms of an interstitial nephritis: malaise and laboratory deviations. The symptoms disappeared after the antibiotics were withdrawn. No other explanation for the renal function disorders could be found in either patient. Piperacillin-tazobactam and ciprofloxacin are considered to be relatively safe and serious adverse effects are rare. Acute interstitial nephritis may, however, occur and its clinical presentation may not be very informative. Withdrawal of the culprit usually leads to recovery.

Adult↗
PubMed2005

Simultaneous analysis of piperacillin and tazobactam in rabbits: application to pharmacokinetic study.

A simple and rapid assay is developed for the simultaneous analysis of piperacillin and tazobactam in rabbit serum and tissue cage fluid (TCF). To eliminate endogenous interferences, a wavelength switch technique was applied, in which the programmable UV detector changed the monitoring wavelength from 218 to 254 nm at 10 min. After liquid-liquid extraction, sample analyses were performed on a C(18) column by gradient elution; the mobile phase consisted of acetonitrile and phosphate buffer (0.014 m, pH 2.4). Owing to the limited amount of rabbit TCF available, a cross-validation of a proxy matrix was evaluated. The relative standard deviation of the between- and within-batch precision of both compounds was less than 5.1%; the relative error of the between- and within-batch accuracy was less than 7.3%. The recoveries of both compounds in serum and TCF were larger than 80%. This assay was successfully applied to simultaneously analyze piperacillin and tazobactam in rabbit serum and TCF samples.

Animals↗
PubMed1987

A comparative trial of moxalactam plus ticarcillin and clavulanic acid or piperacillin as empiric antibiotic therapy for febrile cancer patients.

Resistance of bacteria to beta-lactam antibiotics remains a difficult clinical problem that can be compounded in infected patients with serious underlying illness, especially those who are immunocompromised. In a prospective randomized safety and efficacy trial, febrile cancer patients received either ticarcillin disodium combined with the beta-lactamase inhibitor clavulante potassium (Timentin, Beecham Laboratories, Bristol, TN) plus moxalactam (T+M), or piperacillin plus moxalactam (P+M) as initial empiric antimicrobial therapy. Sixty-six febrile episodes in 53 patients were studied. In the T+M group, 14 (78%) of 18 clinically evaluable infections in patients with profound granulocytopenia improved as did all 14 (100%) such infections in the P+M group. In the T+M group 17 of 21 (81%) similarly evaluable infections improved irrespective of granulocyte count, as did 14 (88%) of 16 of such infections in the P+M group. These results are not statistically significantly different. Serious side effects were infrequent and comparable with both regimens. There was one antibiotic related hemorrhage in the P+M group and a serious episode of nephrotoxicity in a patient who died without recovering renal function in the T+M group. These results suggest that the overall safety and efficacy of Timentin plus moxalactam, and piperacillin plus moxalactam are comparable and similar to previous empiric antibiotic trials.

Bacterial Infections↗
PubMed1983

Pharmacokinetics of piperacillin and gentamicin following intravenous administration to dogs.

Piperacillin sodium was administered intravenously to dogs, alone or in combination with gentamicin, twice a day (approximately 5 hr apart) for 36-37 days. The pharmacokinetics of neither drug changed in the presence of the other; however, the percentage of the gentamicin dose recovered in the urine decreased significantly when coadministered with piperacillin. The data demonstrate that interaction between the two drugs in urine is feasible.

Animals↗
PubMed1984

Effects of cefotaxime, clindamycin, mezlocillin, and piperacillin on mouse sarcoma L-1 tumor.

For the study described in the paper, the effects of 10 days' chemotherapy with cefotaxime, clindamycin, mezlocillin, and piperacillin on local tumor growth and on spontaneous or artificial metastatic spread into the lungs were studied. For the animal tumor model Balb/c mice and the mouse sarcoma L-1 tumor were used. Chemotherapy was administered before, immediately after, or some time after the injection of tumor cells. The antibiotic dosage given to mice was calculated on a body weight basis from the doses recommended for humans. Cefotaxime and clindamycin did not influence the animal tumor model, whereas mezlocillin and piperacillin showed positive or negative effects depending on the chemotherapy schedule. In vitro none of the four antibiotics caused cytotoxic activity in cell cultures of mouse sarcoma L-1, human lung cancer E-14, or human malignant melanoma MEW.

Animals↗
PubMed1986

Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits.

In rabbits methotrexate (MTX) plasma concentrations showed a triexponential decline after short-term infusion (12 mg/kg in 10 min). Probenecid (50 mg/kg PO 1 h before MTX) and piperacillin (100 mg/kg SC 10 min before MTX plus 50 mg/kg SC 4 h later) increased the plasma concentrations of MTX and its metabolite 7-hydroxy-methotrexate (7-OH-MTX) 40 min to 6 h after the end of MTX infusion. The total body clearance of MTX was reduced, while the elimination half-life and the drug distribution to the peripheral body compartments were unchanged. Doxycycline (5 mg/kg PO 30 min before MTX) had no influence on the pharmacokinetics of MTX. Tobramycin was ineffective when given either only on the day of MTX infusion (2 mg/kg SC, 5 min before MTX and 2 mg/kg SC 4 h later) or as a 5-day pretreatment (2 X 2 mg/kg SC daily). The influence of probenecid and piperacillin can be explained by a reduction of the renal elimination of MTX via the tubular transport mechanism for organic acids. This interaction occurred with therapeutic drug concentrations and thus may be clinically relevant.

Animals↗
PubMed1988

Microbial pharmacodynamics of piperacillin in neutropenic mice of systematic infection due to Pseudomonas aeruginosa.

Mathematical solutions for two possible pharmacodynamic interactions (linear nonsaturable and nonlinear saturable) between antibiotics and microorganisms derived from the incorporation of clinically relevant antibiotic dosage regimens such as single bolus dosing, multiple doses, and constant infusion at steady state have been obtained. It is concluded that the saturable nonlinear interaction model between the tested antibiotic and microorganism appears appropriate. The model and its derived equations are capable of describing in vivo bacterial growth of P. aeruginosa after single bolus dosing and multiple doses of piperacillin as described by a linear one-compartment pharmacokinetic model. The activity of piperacillin against P. aeruginosa in the neutropenic mouse systemic infection model can be described by an equation with three dynamic parameters: the bacterial growth rate constant kapp, 0.02345 min-1, the bacterial killing rate constant k'kill, 0.02623 min-1, and the Michaelis-Menten type saturation constant Km, 0.05467 microgram/ml. The concept and derived equations for the optimal dosing interval and minimum critical concentration are of clinical importance for the proper selection of antibiotic dosage regimens.

Agranulocytosis↗
PubMed2001

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients.

The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

Adolescent↗
PubMed1985

A controlled study of ticarcillin plus clavulanic acid versus piperacillin as empiric therapy for fever in the immunocompromised host.

Clavulanic acid, a potent beta-lactamase inhibitor, was studied in fixed combination with ticarcillin and used with tobramycin as empiric therapy for fever in the immunocompromised host. Fifty febrile episodes were evaluated in patients with hematologic malignancy and/or neutropenia. Eighty-one percent of evaluable infections treated with the study regimen of ticarcillin, clavulanic acid, and tobramycin responded. Seventy-four percent of evaluable infections treated with the control regimen of piperacillin, tobramycin, and vancomycin responded (p = 0.4). Resistance to piperacillin and ticarcillin were noted in 23.8 percent of 21 isolated organisms. Resistance to ticarcillin and clavulanic acid was noted in only one (4.7 percent) of the isolated organisms (p = 0.092). Untoward reactions, including rash, nephrotoxicity, and superinfection, were unusual and occurred with equal frequency in the study and control groups. Clavulanic acid in combination with ticarcillin was effective and safe in treating fever in the immunocompromised host.

Bacterial Infections↗
PubMed1990

Placental transfer of cefazolin and piperacillin in pregnancies remote from term complicated by Rh isoimmunization.

Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 +/- 3.37 micrograms/ml, and in nonhydropic fetuses the concentration was 21.02 +/- 17.8 micrograms/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 +/- 12 micrograms/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.

Blood Transfusion, Intrauterine↗
PubMed1987

Single-dose piperacillin versus cefoxitin combined with 10 percent mannitol bowel preparation as prophylaxis in elective colorectal operations.

A prospective, randomized study was utilized to compare the effectiveness of a single dose of preoperative piperacillin versus triple-dose cefoxitin in prophylaxis for elective colorectal operations. All patients received a simple 1 day mechanical bowel preparation using 10 percent mannitol preparation administered orally. Ninety-four patients were entered into the study. Septic complications occurred in 9 percent of the piperacillin patients and in 12 percent of the cefoxitin patients.

Cathartics↗
PubMed1983

Clinical and microbiological evaluation of piperacillin in elective biliary surgery.

Fifty patients undergoing electric biliary surgery were given piperacillin 2 g i.m. 2 h preoperatively followed by 2 g i.v. at the beginning of the operation. Venous blood and bile from the gall bladder and common bile duct were assayed for piperacillin. Blood levels exceeded 100 mg 1(-1) in all instances unless the protocol was not followed. Both gallbladder and common bile duct bile levels exceeded 50 mg 1(-1), and the only exceptions were due to poor penetration into three obstructed gallbladders. Common bile duct levels exceeded 50 mg 1(-1) even in the presence of obstructive jaundice. Only one patient developed a minor postoperative wound infection.

Bacteria↗
PubMed1988

A multicentre study to compare piperacillin with the combination of netilmicin and metronidazole for prophylaxis in elective colorectal surgery undertaken in district general hospitals.

We have conducted a multicentre randomized study to compare piperacillin with the combination of netilmicin and metronidazole in patients undergoing elective colorectal surgery. There was no significant difference in the incidence of operation-related infection, chest or urinary tract infection. Major life-threatening sepsis occurred in 6% and the overall incidence of operation-related infection was 24%. Organisms which normally inhabit the bowel lumen were cultured from most of the postoperative infections; however, Staphylococcus aureus was isolated as a causative organism in nine patients in the piperacillin group compared with none in the netilmicin and metronidazole group. We are concerned at the high incidence of infection in both groups, and we believe that other factors in addition to prophylactic antibiotics need to be evaluated if the incidence of infection is to be reduced further.

Adult↗
PubMed1991

Micro-method for the determination of piperacillin in plasma by high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method for the determination of piperacillin in plasma is described. A C8 reversed-phase column was used with a mobile phase consisting of methanol-water-triethylamine (550:450:4, v/v/v) adjusted to pH = 3 with orthophosphoric acid and UV detection at 270 nm. Cephalothin was used as internal standard. The method involves a plasma protein precipitation with acetonitrile followed by extraction of endogenous compound with chloroform and injection of the upper aqueous phase into the chromatograph. Within-day and between-day assays give relative standard deviations less than or equal to 5.7%. The detection limit is 0.2 microgram ml-1. Stability studies show that piperacillin degradation starts at -4 degrees C. Therefore, samples have to be processed promptly and stored at -20 degrees C. The method described is convenient for clinical monitoring and for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Comparative in vitro activity of piperacillin combined with the beta-lactamase inhibitor tazobactam (YTR 830).

Combination with tazobactam substantially enhanced the activity of piperacillin against routine isolates of staphylococci, various Enterobacteriaceae, Acinetobacter anitratus, and Bacteroides fragilis. Tazobactam enhanced the activity of piperacillin more than fourfold against Pseudomonas aeruginosa spp. harboring eight of 12 plasmid-mediated beta-lactamases.

Acinetobacter↗
PubMed1992

Antimicrobial prophylaxis for major head and neck cancer surgery with piperacillin and ornidazole.

A prospective study in 53 eligible patients, undergoing major head and neck cancer surgery was carried out to assess the combination of an ureido penicillin, piperacillin with a nitro imidazole agent, ornidazole, in order to prevent post-operative general and wound infections. Both antibiotics were administered for five days. Each patient had piperacillin 4 gm every eight hours and ornidazole 1 gm every 24 hours. The overall rate of infections was 13.2 per cent (n = 7), with 3.8 per cent (n = 2) wound infections and 11.3 per cent (n = 6) general infections (one patient presented both complications). There was no wound infection in the total surgery group (n = 12). General infections who only consisted of pneumonias were respectively 12.2 per cent (n = 5) in the group with partial procedures (n = 41) and 8.3 per cent (n = 1) in the total surgery group. This antibioprophylaxis can be recommended in major oncological neck surgery, specially in the case of partial procedures.

Adult↗
PubMed1989

A prospective evaluation of optimal sampling theory in the determination of the steady-state pharmacokinetics of piperacillin in febrile neutropenic cancer patients.

We examined the use of optimal sampling theory in the determination of the pharmacokinetics of piperacillin in febrile, neutropenic cancer patients. Patients were studied prospectively as part of a randomized, double-blind clinical trial of piperacillin and amikacin versus imipenem and placebo. The results from the analysis of 5 optimal samples were compared with those derived from 15 concentration determinations (10 samples, with the 5 optimal samples assayed in duplicate). The use of a standard least-squares estimator as opposed to a bayesian estimator, with normal prior distributions placed on beta and serum clearance, was also examined. Finally, the use of duplicate determinations in improving the precision of parameter estimation was studied. Plasma concentrations obtained at time points determined by optimal sampling theory, when analyzed with a bayesian estimator, produced estimates of pharmacokinetic parameter values that were in good agreement with those derived from the 15-determination set. Duplicate assay did not improve the precision of parameter estimation. Estimation of plasma clearance was quite robust, irrespective of the estimator used, probably because this evaluation was performed at steady state. Optimal sampling theory is a promising technique that can be employed to determine patient-specific estimates of pharmacokinetic parameter values in target populations.

Adolescent↗
PubMed1987

[Piperacillin dosage and elimination in premature infants].

In 19 premature newborns (mean birth weight 1600 g, range 800-2430 g), receiving a daily dose of 100-150 mg piperacillin/kg body weight in four divided doses, serum concentration of the drug at the end of its interval of administration was a mean of 32.6 +/- 25.0 mg/l. In six mature newborns it was lower at 12.5 +/- 9.0 mg/l. The mean serum drug level on days 1, 5 and 10 in ten premature newborns at the end of the respective interval of administration was reduced to about 69% of the initial level. Elimination of piperacillin (half-life and clearance) was determined in the middle of their first week of treatment in 11 prematures. Compared with values in adults, mean half-life was increased fourfold. In individual cases it was increased tenfold. Compared with a control group of mature newborns, clearance was markedly reduced. Because of the danger of underdosage as a result of increasing maturation of elimination during the period of treatment, piperacillin should be given in slightly higher doses, 200-300 mg/kg in premature and mature newborns. However, the clearly prolonged half-life makes it possible to divide daily dosage into two doses.

Birth Weight↗