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PubMed1981

Piperacillin in surgical infections: a clinical trial.

Piperacillin was administered in eighteen patients with mixed infections. Three had osteomyelitis, two had peritonitis, two had gangrenous toes, one had bronchopneumonia, and the other ten had leg ulcers of various types accompanies by cellulitis. In eleven patients one of the infecting organisms was Pseudomonas aeruginosa, and another had Pseudomonas maltophilia. All had appropriate surgical treatment, which in nine patients included skin grafting in the presence of Pseudomonas aeruginosa. All the patients were clinically cured except for one with osteomyelitis who relapsed and was found to have a residual sequestrum. None of the skin grafts failed. In other patient who underwent grafting, cloxacillin was also given because she had a beta-lactamase-producing staphylococcus. The only adverse reaction was thrombophlebitis of the vein used for drug administration in 15 out of 18 patients. One hundred and five other isolates of Pseudomonas aeruginosa were tested in the laboratory against piperacillin and resistance to the drug was found to be rare. It was concluded that piperacillin is a safe drug to use, is effective against a wide range of organisms, and is particularly effective in preventing the destruction of skin grafts by Pseudomonas aeruginosa. It is likely to be ineffective against beta-lactamase-producing staphylococci, and when these are present also, it would be wise to use another drug such as cloxacillin in addition.

Clinical Trials as Topic↗
PubMed1995

A piperacillin-tazobactam resistant Escherichia coli strain isolated from a faecal sample of a healthy volunteer.

As part of a surveillance programme of the prevalence of antibiotic resistance, the faecal bacteria of healthy people (n = 1348) were examined, and the antibiotic resistance of the Escherichia coli strains determined. One strain out of 142 amoxycillin-resistant isolates, E. coli strain 1662, was also resistant to piperacillin-tazobactam but susceptible to amoxycillin-clavulanic acid. The piperacillin-tazobactam resistance determinant was transferable to standard E. coli strains by conjugation. However, the strain produced a beta-lactamase with several characteristics very similar to those of the TEM-1 beta-lactamase, i.e. pI of 5.4, an M(r) value of 22,000 and a comparable substrate profile. The enzyme was as efficiently inhibited by clavulanic acid and tazobactam as the TEM-1 and TEM-2 beta-lactamases but more than the amoxycillin-clavulanic acid-resistant TRC-1 enzyme. The transferable resistance to piperacillin-tazobactam appears to be mediated by a novel resistance mechanism that has previously not been described.

Anti-Bacterial Agents↗
PubMed1980

Influence of inoculum size on activity of cefoperazone, cefotaxime, moxalactam, piperacillin, and N-formimidoyl thienamycin (MK0787) against Pseudomonas aeruginosa.

Forty clinical isolates of Pseudomonas aeruginosa were tested for their susceptibility to cefoperazone, cefotaxime, moxalactam, piperacillin, N-formimidoyl thienamycin (MK0787), and gentamicin at three different inocula. At an inoculum of 5 x 10(3) colony-forming units (CFU) per ml, the minimum inhibitory concentrations (in micrograms per milliliter) for 90% of isolates (MIC90) were as follows: gentamicin, 1; N-formimidoyl thienamycin, 2; cefoperazone, 4; piperacillin, 8; moxalactam, 16; and cefotaxime, 16. When the inoculum was increased to 5 x 10(5) CFU/ml, the MIC90 for all drugs tested increased. Among the beta-lactam antibiotics, N-formimidoyl thienamycin and cefoperazone had the lowest MIC90 (8 micrograms/ml) at this inoculum. When the inoculum was increased further to 5 x 10(7) CFU/ml, an MIC90 could be determined only for gentamicin and N-formimidoyl thienamycin (4 and 8 micrograms/ml, respectively). Indeed, the MIC50 for moxalactam, cefotaxime, cefoperazone, and piperacillin was 128 micrograms/ml or more at this inoculum. The minimum bactericidal concentration for 90% of isolates (MBC90) at an inoculum of 5 x 10(5) CFU/ml ranged from 8 micrograms/ml for gentamicin and N-formimidoyl thienamycin to 128 micrograms/ml for cefotaxime. At the highest inoculum, however, whereas the MBC90 for gentamicin and N-formimidoyl thienamycin remained at 8 micrograms/ml, the MBC90 for each of the other drugs was greater than 128 micrograms/ml. N-Formimidoyl thienamycin was the only drug tested for which an MIC100 and MBC100 (MIC and MBC for 100% of isolates) could be determined, and these were not significantly different from the MIC90 and MCB90.

Anti-Bacterial Agents↗
PubMed1981

Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis.

The pharmacokinetics of piperacillin administered intravenously were studied in five patients with stable mild to moderate renal impairment and in five patients undergoing hemodialysis. Patients with stable renal failure given 1 g of piperacillin intravenously had peak serum concentrations within 30 min ranging from 78 to 280 micrograms/ml. The mean serum half-life was 3.57 +/- 1.36 h; the mean apparent volume of distribution was 28.6 +/- 13.5 liters/100 kg; and the plasma clearance was 4.10 +/- 1.46 liters/h per 1.73 m2. Neither serum half-life nor clearance correlated with serum creatinine, implying significant nonrenal elimination. Patients undergoing hemodialysis had peak serum concentrations within 30 min of 66 to 138 micrograms/ml after 1 g of piperacillin infused intravenously. During hemodialysis, the serum half-life was 3.6 +/- 2.5 h; the mean apparent volume of distribution was 26.7 +/- 16.7 liters/100 kg; and the plasma clearance was 3.28 +/- 0.76 layers/h per 1.73 m2. Mean hemodialysis clearance was 0.484 +/- 0.282 liters/h per 1.73 m2, and only 10.0 +/- 5.3% of the total dose could be recovered in the dialysate.

Adult↗
PubMed1981

Comparative efficacy of piperacillin and penicillin G in treatment of gonococcal urethritis.

The comparative efficacy of 2 g of piperacillin and 4.8 X 10(6) U of penicillin G in the treatment of uncomplicated gonococcal urethritis was assessed in a randomized prospective study. Sixty-five evaluable patients received piperacillin, and 55 received penicillin G. All patients received either therapy were cured of gonorrhea. We conclude that piperacillin is as efficacious as aqueous procaine penicillin G in the therapy of uncomplicated gonococcal urethritis.

Gonorrhea↗
PubMed1982

Clinical evaluation of the therapeutic efficacy and tolerability of piperacillin.

The efficacy and tolerance of parenterally administered piperacillin were evaluated in 50 adult patients hospitalized with systemic and urinary tract infections. Dosage for 46 patients was 4 to 12 g daily and for 4 patients, 16 to 24 g daily; in each case divided doses were given every 4 to 6 h. The duration of treatment for most patients was 5 to 10 days. Of the 50 patients, 45 (90%) were considered cured, and 57 (89%) of the 64 pathogens isolated were eradicated by piperacillin treatment. Side effects, reported by 12 patients, were mild to moderate in degree and consisted of vein irritation, thrombophlebitis, pain at the injection site, and diarrhea, Piperacillin appears to be a highly effective antibiotic for treating infections caused by susceptible gram-positive and gram-negative microorganisms.

Adolescent↗
PubMed1982

Piperacillin pharmacokinetics in pediatric patients.

The pharmacokinetics of piperacillin were studied in 15 pediatric patients (age range, 3.3 to 14.3 years). Piperacillin was administered in a dosage of 1.5 +/- 0.4 g/m2 (mean +/- standard deviation) every 4 to 6 h. Peak serum concentrations ranged from 69 to 354 micrograms/ml. The mean elimination half-life was 37.0 +/- 13.3 min, which is shorter than that observed in most adults with normal renal function. The mean elimination half-life in three patients with renal impairment was 60.1 +/- 12.4 min, and the mean ratio of renal clearance to total clearance was 0.57. These results suggest a significant nonrenal elimination of piperacillin. Based on these data, a dosage of 1.5 g/m2 given as a 30-min infusion every 4 h is suggested for children with normal renal function. For patients with renal impairment, the daily dosage could be calculated as follows: corrected dose = normal dose x (0.35 + [0.65 x (ClCr/0.06)]), where ClCr is the creatinine clearance expressed as liters per minute per square meter.

Adolescent↗
PubMed1983

Effect of piperacillin on tobramycin pharmacokinetics in patients with normal renal function.

Aminoglycosides are inactivated by extended-spectrum penicillins in vitro and in patients with end-stage renal failure. In this prospective controlled study, we determined the effect of piperacillin on tobramycin pharmacokinetics. In 10 clinically stable male patients with calculated creatinine clearances of greater than or equal to 60 ml/min, serial levels in serum of tobramycin alone and after single 4-g intravenous doses of piperacillin were determined. No statistically significant changes in the concentration of drug in serum, the half-life (t1/2), the elimination rate constant (Ke), the volume of distribution (Vd), or the area under the serum concentration-time curve (AUC0-oo) occurred when tobramycin was used concurrently with piperacillin. Therefore, this antibiotic combination will not result in a clinically significant interaction in patients with normal renal function.

Adult↗
PubMed1984

Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients.

Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients. The response rate in 95 episodes of documented infection was 72%. The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively. The response in infections caused by gram-negative organisms was 73%. Only 6 of 10 Pseudomonas aeruginosa infections responded to therapy, although the organisms were sensitive in vitro to piperacillin. Of 14 infections caused by gram-positive organisms, 12 responded to this combination. No major side effects were observed with this regimen. Although the overall response rate with this antibiotic combination was comparable with other regimens used for neutropenic patients, superior results might be obtained by combining piperacillin with an extended-spectrum cephalosporin or an aminoglycoside.

Bacterial Infections↗
PubMed1984

Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections.

In a randomized comparative study, 116 patients with acute bacterial infections were treated with timentin (ticarcillin plus clavulanic acid) or a comparative agent (piperacillin for respiratory or urinary tract infections, and moxalactam for soft tissue infections). There were 91 clinically evaluated infections (timentin, 46; piperacillin, 29; moxalactam, 16). Twelve patients were bacteremic. A satisfactory clinical response occurred in all 46 patients treated with timentin and in 42 of the 45 treated with a comparative agent. Two clinical failures were due to superinfection (a Staphylococcus aureus pneumonia in the piperacillin group and an enterococcal skin infection in the moxalactam group), and one clinical failure was due to a primary S. aureus skin infection (moxalactam group). One wound isolate of Pseudomonas aeruginosa developed resistance to timentin during therapy (despite clinical improvement). Adverse reactions were uncommon but did include one patient treated with timentin who developed unexplained hallucinations.

Acute Disease↗
PubMed1985

Comparative activities of piperacillin, ceftazidime, and amikacin, alone and in all possible combinations, against experimental Pseudomonas aeruginosa infections in neutropenic rats.

This study compared the efficacy of therapy with the double beta-lactam combination of ceftazidime plus piperacillin with that of single-agent therapy with ceftazidime, piperacillin, or amikacin alone and with that of two aminoglycoside-beta-lactam combinations against Pseudomonas aeruginosa peritonitis and bacteremia in neutropenic rats. Rats made severely granulocytopenic with cyclophosphamide became bacteremic secondary to peritonitis which was induced by intraperitoneal challenge with P. aeruginosa. Antibiotic therapy with single agents (amikacin, 20 mg/kg of body weight, intramuscularly; ceftazidime, 20 mg/kg of body weight, subcutaneously; piperacillin, 200 mg/kg of body weight, intramuscularly) or with the various combinations of agents was begun 2 h after bacterial challenge and was continued every 6 to 8 h for 62 h. Therapeutic efficacy was judged on the basis of survival 72 h after bacterial challenge, rate of mortality, incidence of bacteremia, and the emergence of resistant organisms. Based on these criteria, therapy with the double beta-lactam combination had no advantage over single-agent therapy and was in all cases clearly inferior to beta-lactam-aminoglycoside combinations.

Amikacin↗
PubMed1985

Correlation between growth curve and killing curve of Escherichia coli after a brief exposure to suprainhibitory concentrations of ampicillin and piperacillin.

Escherichia coli strains that were susceptible to multiple antibiotics were exposed to suprainhibitory concentrations of ampicillin and piperacillin. As with the majority of beta-lactam antibiotics, the growth curves showed an increase in optical density (OD) before lysis during the first hours. This increase in OD depended on the concentration of ampicillin and was independent of 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 per milliliter remained constant. The decrease in the number of CFU per milliliter depended on the concentration of ampicillin and was independent of the concentration of piperacillin. pH variations gave rise to similar effects on growth curves and killing curves.

Ampicillin↗
PubMed1987

Pharmacokinetics of the acyclureidopenicillins piperacillin and mezlocillin in the postpartum patient.

The postpartum patient experiences numerous physiologic alterations, which may affect the pharmacokinetics of certain drugs. Six patients received either piperacillin or mezlocillin intravenously immediately after delivery. Serum half-life and clearance were, respectively, 82.4 min and 202 +/- 105 ml/min for mezlocillin and 32.9 min and 456 +/- 88 ml/min for piperacillin. The data revealed that mezlocillin and piperacillin have significantly different pharmacokinetic reactions in the postpartum patient at the doses used.

Chromatography, High Pressure Liquid↗
PubMed1992

Comparison of two antibiotic regimens (piperacillin plus amikacin versus ceftazidime plus amikacin) as empiric therapy for febrile neutropenic patients with cancer.

A total of 170 febrile episodes in neutropenic patients with cancer were randomly assigned to be treated with piperacillin-amikacin or ceftazidime-amikacin. The overall response rates were similar in both groups (68 and 65%, respectively). Response rates for clinically or microbiologically documented episodes were 54.5% for piperacillin-amikacin and 58.8% for ceftazidime-amikacin. Response rates for gram-negative bacillary infections were 65 and 73%, respectively. There was also no difference for gram-positive infections (31 and 50%, respectively). The toxicities were also comparable and consisted of skin rashes, hypokalemia, and diarrhea. Vancomycin was added if the fever persisted 72 h after the beginning of therapy; it increased the response rates to 94% when used with piperacillin-amikacin and 92% when used with ceftazidime plus amikacin. Our results suggest that the combinations show similar global efficacies in the treatment of febrile episodes in cancer patients.

Adult↗
PubMed1992

Simulation of human serum pharmacokinetics of cefazolin, piperacillin, and BRL 42715 in rats and efficacy against experimental intraperitoneal infections.

Studies were performed to determine the effects of BRL 42715, a potent beta-lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats. Compounds were administered to rats as a continuous infusion of an exponentially diluted solution to simulate in rat plasma the concentration-versus-time curves obtained for humans following intravenous bolus administration. A simulated 1-g dose of cefazolin was ineffective in reducing the bacterial counts in blood and peritoneal fluid samples of animals infected with S. marcescens US20, which produced class Ia beta-lactamase, and as a result, mortality was similar to that of infected controls. Similarly, a simulated 2-g dose of piperacillin was ineffective in reducing bacterial numbers and mortality in animals infected with E. coli 41548, producing a TEM-1 beta-lactamase. However, when the antibiotics were coadministered with BRL 42715, bacterial numbers were reduced significantly and all animals survived at least 16 h after infection. These data demonstrate the ability of BRL 42715 to potentiate the activity of cefazolin and piperacillin against beta-lactamase-producing bacteria that would otherwise be resistant to these antibiotics and illustrate the application of a model to simulate human serum concentrations in conscious rats.

Animals↗
PubMed1994

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase.

We evaluated the pharmacokinetics and therapeutic efficacies of piperacillin and tazobactam, a beta-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase. Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20% of the total dose. The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 +/- 0.34 and -0.73 +/- 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 +/- 0.35 log CFU/ml/h). The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various beta-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum beta-lactamases.

Animals↗
PubMed1996

Biliary excretion of ciprofloxacin and piperacillin in the obstructed biliary tract.

Biliary excretion of ciprofloxacin and piperacillin was determined in cholestatic patients who had undergone endoscopic cholangiography. The median concentration of ciprofloxacin (n = 9) was 2.36 micrograms/ml (range, 0.29 to 19.8 micrograms/ml) in bile compared with 1.66 micrograms/ml (range, 0.73 to 2.69 micrograms/ml) in serum. The median concentration of piperacillin (n = 7) was < 5 micrograms/ml (range, < 5 to 26) in bile compared with 14.3 micrograms/ml (range, 5.3 to 80) in serum. Ciprofloxacin, but not piperacillin, can be actively excreted into bile in the presence of a biliary tract obstruction.

Adult↗
PubMed1997

Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens.

The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam (3.375 g every 6 h and 4.5 g every 8 h) were evaluated at steady state for 12 healthy adult volunteers. Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection (ATCC) organisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis). The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated. Areas under the inhibitory (AUIC0-24) and bactericidal activity (AUBC0-24) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen. In order to assess the validity of predicted measures of bactericidal (AUC0-24/MBC) and inhibitory (AUC0-24/MIC) activity to determine bacteriological response to beta-lactam antimicrobial agents, AUC0-24/MBC and AUC0-24/MIC values were compared with measured AUBC0-24 and AUIC0-24 values. Total body clearance values were equivalent for piperacillin (183.96 +/- 22.66 versus 181.72 +/- 19.54 ml/min/1.73 m2, P > 0.05) and tazobactam (184.71 +/- 19.89 versus 184.87 +/- 18.35 ml/min/1.73 m2, P > 0.05) following the administration of the 3.375-g-every-6-h and 4.5-g-every-8-h dosages, respectively. Comparison of area under the plasma concentration-time curve (AUC0-24) for piperacillin (967.74 +/- 135.56 microg x h/ml versus 978.88 +/- 140.96 microg x h/ml) and tazobactam (120.14 +/- 15.78 microg x h/ml versus 120.01 +/- 16.22 microg x h/ml) revealed no significant differences (P > 0.05) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens, respectively. Both regimens provided T > MIC values of > 60% for all organisms tested. Measured values of bactericidal (AUBC) and inhibitory (AUIC) activity were significantly different (P < 0.05) from predicted values (AUC0-24/MBC and AUC0-24/MIC) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus. Additionally, ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC0-24 and AUIC0-24 values. Reasons for this difference may be inherent differences in organism specific susceptibility.

Adult↗