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PubMed2006

Mutant prevention concentrations of levofloxacin alone and in combination with azithromycin, ceftazidime, colistin (Polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin against Pseudomonas aeruginosa.

The mutant prevention concentrations (MPCs) of levofloxacin alone and in combination with ceftazidime, colistin (polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin were established against Pseudomonas aeruginosa. Antibiotic combinations using levofloxacin with any antibiotic with individual activity against P. aeruginosa resulted in synergistic lowering (an at-least-fourfold reduction) of the isolate's MPC.

Anti-Bacterial Agents↗
PubMed1989

Treatment of Pseudomonas lung infection in cystic fibrosis with piperacillin plus tobramycin versus ceftazidime monotherapy: preliminary communication.

Twenty-one patients with cystic fibrosis and chronic Pseudomonas lung infection were treated at random with ceftazidime, 150 mg/kg/day, or with piperacillin, 300 mg/kg/day, and tobramycin, 10 and more mg/kg/day for 14 days. On admission and at discharge, body weight, erythrocyte sedimentation rate, white blood cell count, and differential were determined. Pulmonary function analysis and chest X-rays were also obtained on both occasions as was sputum bacteriology. After hospitalization, the patients were followed in the outpatient department for 14-26 months. Both treatments were associated with significant improvement in most of the parameters that were studied, but neither treatment was superior.

Ceftazidime↗
PubMed1982

Antibacterial activity of N-formimidoyl thienamycin in comparison with cefotaxime, lamoxactam, cefoperazone, piperacillin gentamicin.

The in vitro activity of N-formimidoyl thienamycin (MK 0787), a new stable derivative of thienamycin was compared with that of lamoxactam, cefotaxime, cefoperazone, piperacillin and gentamicin against 410 clinical isolates of common bacteria. In comparison with the other agents, MK 0787 was more or equally active against Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Citrobacter spp., Klebsiella spp., and Serratia spp. It inhibited all isolates at a concentration of 0.5 mg/l, but was less active than cefotaxime and lamoxactam against Proteus mirabilis and less active than cefotaxime, lamoxactam and cefoperazone against Beta-lactamase positive Haemophilus influenzae. Strains of Pseudomonas aeruginosa were more susceptible to N-formimidoyl thienamycin than to other antibiotics.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparative efficacies of ticarcillin, ticarcillin/clavulanic acid, piperacillin and cefoxitin against polymicrobial infections in mice caused by Escherichia coli and Bacteroides fragilis.

A model of localised abscess formation was used to establish mixed infections caused by Escherichia coli and Bacteroides fragilis. The beta-lactamase producing, ticarcillin-resistant strains E. coli E96 and B. fragilis VPI 8708 were used to produce one infection, and in another infection, a beta-lactamase hyperproducing strain E. coli 41548 was combined with a ticarcillin-susceptible strain, B. fragilis B3. Treatment, at doses producing clinically achievable concentrations in mouse serum, began 1 h after inoculation, and continued three times daily for four days. Bacterial numbers in infected tissue were measured at intervals. Against both infections, ticarcillin was ineffective in preventing bacterial growth and abscess formation in all mice. Piperacillin prevented abscess formation in 60% of the mice infected with E. coli E96/B. fragilis VPI 8708, and in 40% of those in the E. coli 41548/B. fragilis B3 group. Therapy with ticarcillin/clavulanic acid or cefoxitin reduced the number of both organisms at the site of infection, and thus prevented abscess formation in 100% treated animals.

Abscess↗
PubMed1989

Randomized trial using piperacillin versus ampicillin and amikacin for treatment of premature neonates with risk factors for sepsis.

Premature infants with risk factors for early onset sepsis who were less than seven days of age were blindly randomized to receive either piperacillin and placebo (200 infants) or ampicillin and amikacin (196 infants). One of 30 treated infants developed positive blood cultures. The overall mortality in the two groups was 8.5% for piperacillin/placebo and 13.8% for ampicillin/amikacin (p = 0.11). Serum creatinine elevation above 100 mumol/l (1.131 mg/dl) during treatment was similar in the two groups. The effectiveness of piperacillin/placebo is similar to that of ampicillin/amikacin for empiric treatment of premature newborns with risk factors for early onset sepsis.

Amikacin↗
PubMed1983

Comparative synergistic activity of ceftriaxone-piperacillin versus ceftriaxone-netilmicin.

The effect of combination of ceftriaxone with piperacillin or netilmicin was studied in a total of 119 clinical isolates using the checkerboard titration technique. The isolates included Pseudomonas aeruginosa, Staphylococcus aureus, enterococci and various Enterobacteriaceae. Synergy was observed in all Streptococcus faecalis strains with both combinations. Whereas the ceftriaxone/netilmicin combination showed a higher rate of synergy against Pseudomonas aeruginosa, the rate of synergy against Enterobacteriaceae was the same for the two combinations. In no instance was antagonism encountered.

Cefotaxime↗
PubMed1997

Pharmacokinetics of piperacillin and tazobactam in critically ill patients with renal failure, treated with continuous veno-venous hemofiltration (CVVH).

OBJECTIVE: Kinetics of piperacillin (pip), in combination with the beta-lactamase inhibitor tazobactam (taz) have been studied in volunteers and patients in relatively stable conditions. The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired, but no data are available for critically ill patients in anuric renal failure. This study should provide such data. PATIENTS, DESIGN: We studied the pharmacokinetics in nine patients with multiple organ failure, including anuric renal failure, treated with continuous veno-venous hemofiltration (CVVH). Patients received a standard schedule of 4 g pip and 0.5 g taz administered over 0.5 h intravenously, 8 hourly. During 2 consecutive days, the serum levels of both compounds were determined, and total clearance (CIT) was calculated from serum concentrations. RESULTS: All nine patients completed day 1, and 8 completed day 2 of the protocol. On day 1, single-dose kinetics showed considerable spread, but pip/taz serum levels followed the pattern as expected, with a pip/taz concentration ratio of 20:1. On day 2, however, taz serum concentrations showed a relative increase as compared to pip, resulting in a change in the serum pip/taz concentration ratio to 10:1 on day 2. The CIT of pip was 2.52 +/- 1.38 l/h (t 1/2: 5.9 +/- 2.9 h), and CIT of taz 4.44 +/- 2.28 l/h (t 1/2: 8.1 +/- 3.7 h). The CIT and t 1/2 of pip and taz correlated highly significantly with clearance by CVVH. Despite a higher CIT, taz has a longer half-life, because of a higher volume of distribution. CONCLUSION: In CVVH dependent patients, pip/taz fixed drug preparations can be used initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compared to the active antimicrobial agent pip.

Adult↗
PubMed2000

Thrombotic thrombocytopenia purpura caused by piperacillin successfully treated with plasma infusion.

An 81-year-old man was admitted to the hospital with a fever and loss of appetite. After treatment with piperacillin sodium (PIPC), the patient exhibited thrombocytopenia, hemorrhagic colitis, and drug-induced skin eruption. On the fifth day after PIPC induction, he further experienced neurological abnormalities, such as disorientation and confusion, renal dysfunction, and microangiopathic hemolytic anemia (MAHA). The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) on the basis of thrombocytopenia, MAHA, renal dysfunction, fever, and neurological abnormalities. Infusion of fresh-frozen plasma was initiated for treatment. His condition improved markedly after this treatment. It is rare for TTP to be accompanied with hemorrhagic colitis and skin eruption. These symptoms were induced by PIPC and were successfully treated with plasma infusion.

Aged↗
PubMed1998

Influence of piperacillin on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate.

The influence of concomitant administration of piperacillin (PIP) on the pharmacokinetic parameters of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) was studied in rabbits. Six rabbits received an initial i.v. bolus (0.21 mg kg(-1)) followed by a constant-rate i.v. infusion of the drug (5 microg min(-1) kg(-1)) for 240 min. The PIP dose (30 mg kg(-1)) was repeated every 30 min until the end of the infusion period. The control group consisted of four rabbits treated the same way except for the addition of PIP. There were significant increases in the mean residence times found for MTX (MRTinf) and 7-OH-MTX (MRTm,inf) following PIP administration. Concomitant administration of PIP with MTX also produced significant 1.5- and 2.8-fold increases in the area under the curve of MTX and 7-OH-MTX, respectively. The total body clearance of MTX and the operative total body clearance of 7-OH-MTX significantly decreased, but in a less than proportional manner. The study demonstrates that the interaction between MTX and PIP is mainly due to the reduced clearance of both MTX and 7-OH-MTX combined with a slight increase in the formation clearance of the metabolite.

Animals↗
PubMed1986

A randomized, double-blind trial of single dose piperacillin versus multidose cefoxitin in alimentary tract operations.

For elective alimentary tract operations in which contamination is moderate, single dose prophylaxis with piperacillin is equivalent to triple dose cefoxitin, a well established and effective regimen. Both methods failed to control infection arising in the perineal wound after abdominoperineal resection. Just as is the case with drain site infection, such infection often evolves from postoperative contamination and, indeed, is in theory and in fact unlikely to be controlled by perioperative prophylaxis. This study is among the first of several examining the issue of single dose prophylaxis and will be the harbinger of other studies from other groups examining whether or not the course of therapeutic antibiotics can be safely shortened in patients with peritoneal contamination.

Adult↗
PubMedDate not supplied

Single-dose prophylaxis with broad-spectrum penicillins (piperacillin and mezlocillin) in gynecologic oncological surgery, with observation on serum and tissue concentrations.

Serum, fat and pelvic tissue levels of piperacillin or mezlocillin (patients randomly selected to receive one of both) were measured during surgery of 48 patients (mean age 55 years) with gynecologic cancer and related to the minimal inhibitory concentrations (MIC). Only during the first 3 hours the fat and pelvic tissue levels of these antibiotics were above the MIC levels (3 to 5 mg/l), while the serum reached marginal levels after 4 to 5 hours. Excessive blood loss (more than 1.500 ml) decreases the serum and fat levels; however, during the first 3 hours not below the MIC values. Single-dose prophylaxis with both antibiotics appeared fully effective in debulking surgery, total abdominal hysterectomy and radical hysterectomy. However, out of a group of 12 patients who underwent radical vulvectomy, 8 patients had postoperative infections.

Adipose Tissue↗
PubMed1998

Determination of piperacillin and mezlocillin in human serum and urine by high-performance liquid chromatography after derivatisation with 1,2,4-triazole.

High-performance liquid chromatographic methods have been developed for the determination of piperacillin and mezlocillin in human serum and urine samples. The methods involve ultrafiltration of samples followed by reaction with 1.5 M 1, 2, 4-triazole and 0.5 x 10(-3) M mercury (II) chloride in solution (pH 8.50) at 50 degrees C for 15 min. The resulting products were separated on a C18 column following stabilisation in an eluent containing sodium thiosulphate. They were detected at 323 nm for both penicillins. The methods have been applied to assays applied to assays of these penicillins in human serum and urine samples. The procedures, which permit the determination of penicillin concentration down to 0.1 microgram m1-1 in serum and 1 microgram m1-1 in urine samples, are specific to intact penicillins without interference from corresponding penicilloates [see J. Haginaka et al., Anal. Sci. 1 (1985) 73]. At concentrations of 1-500 micrograms ml-1 for each compound, the within- and between-day precisions were 1.8-4.8 and 3.7-6.9, respectively. The accuracy was ca. 100% for all samples assayed.

Calibration↗
PubMed1986

Hemorrhagic complications of piperacillin therapy.

Clinically significant hemorrhage associated with extended spectrum anti-Pseudomonas penicillins is uncommon. We describe 2 patients with bleeding complications owing to piperacillin. In addition, we review the incidence and mechanism of this adverse reaction, and make suggestions for the management of these patients.

Blood Coagulation Tests↗
PubMed1989

Determination of tazobactam and piperacillin in human plasma, serum, bile and urine by gradient elution reversed-phase high-performance liquid chromatography.

A gradient elution high-performance liquid chromatographic method is described for the analysis of the beta-lactamase inhibitor tazobactam (YTR-830H) and a semi-synthetic parenteral penicillin, piperacillin, in human plasma, serum, bile and urine. The assay for plasma, serum and bile involves deproteinization with acetonitrile and the removal of lipids with dichloromethane; urine is diluted with buffer. Separation and quantitation are achieved using a mobile phase based on ion-suppression chromatography on a C18 reversed-phase column with ultraviolet detection at 220 nm. The limit of quantitation for both compounds is 1.0 microgram/ml in plasma, serum and bile using a 0.2-ml sample and 50.0 micrograms/ml in urine using a 0.1-ml sample. The method has been validated by preparing and analyzing a series of fortified samples (range 1.0-200 micrograms/ml for each compound in plasma, serum and bile and 50.0-10,000 micrograms/ml for each compound in urine). Excellent linearity, accuracy, precision and recovery were obtained. The method was not interfered with by other endogenous components, nor by other commonly administered antibiotics such as amoxicillin, mezlocillin, cefometazole and cefotaxime. The assay has been successfully applied to the analysis of samples from pharmacokinetic studies in man and animals.

Anti-Bacterial Agents↗
PubMed2002

In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas aeruginosa.

The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and ciprofloxacin demonstrated similar in vitro activity, with ofloxacin demonstrating less activity compared to the other agents. Predominantly additive effects were seen with all combinations, with no significant differences detected between the fluoroquinolone agents.

Anti-Infective Agents↗
PubMed2002

In vitro bactericidal activity of piperacillin, gentamicin, and metronidazole in a mixed model containing Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis.

An anaerobic, mixed model assay was used to study the bactericidal activities of piperacillin, gentamicin, and metronidazole, alone and in double- and triple-antibiotic combinations against a polymicrobial suspension of E. coli, E. faecalis, and B. fragilis. Only slight differences were noted with the agents when tested against single (10(5) cfu/mL inoculum) versus polymicrobic suspensions (10(6) cfu/mL final inoculum) of susceptible and resistant organisms. Contrary to previous reports in the literature, metronidazole was not active against E. coli in an anaerobic environment (even in the presence of B. fragilis) nor was the activity of metronidazole reduced against B. fragilis in the presence of E. faecalis. Gentamicin demonstrated excellent activity against E. coli when tested in a Bactron anaerobic chamber (5% hydrogen, 5% CO(2,) 90% nitrogen). The pH of the media was only reduced to 6.3-6.7, considerably higher than the pH range of 5-6 needed to significantly reduce the activity of aminoglycosides.

Air↗
PubMed1998

Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin-tazobactam.

BACKGROUND: Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk. AIM: To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin-tazobactam (PT). METHODS: A prospective, ward-based, crossover study was carried out on two well-matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad-spectrum antibiotic treatment. RESULTS: There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P=0.001) and diarrhoea (18/34 vs. 1/14, P=0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment. CONCLUSIONS: Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.

Aged↗
PubMed1982

Piperacillin in paediatric surgery.

23 infants and children, aged 1 month - 15 years, were treated with piperacillin, a new semi-synthetic penicillin with a broad spectrum of activity. The indications were perforated appendicitis with peritonitis or abscess formation (12 patients), urinary tract infection due to congenital anomalies (3 patients), miscellaneous infections (3 patients) and peroperative prophylactic treatment (5 patients). The clinical response was good. Few adverse reactions were noted. The drug seems to be effective and safe.

Abscess↗