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PubMed1998

Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration.

OBJECTIVE: Continuous hemofiltration is now widely used in the intensive care unit. Our study aimed to assess the removal of piperacillin under continuous hemofiltration and to define a suitable dosage regimen of administration. DESIGN: Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic. SETTING: The medical intensive care unit of a teaching hospital. PATIENTS: Ten patients were included in the study. Six patients were receiving their first dose of piperacillin (group 1) and four had already been treated for 2 to 6 days (group 2). The mean Simplified Acute Physiology II score was 74 +/- 6 (SEM), and the number of organ failures was 3.6 +/- 0.3 (range 3 to 5). Renal failure was related to septic shock in seven patients and to cardiogenic shock in three patients. Seven patients were anuric. Hepatic dysfunction was present in four of the ten patients. INTERVENTIONS: Patients were treated with continuous venovenous hemofiltration using a hollow polysulfone capillary fiber. Piperacillin (4 g) was injected intravenously over 20 mins. Arterial blood and ultrafiltrate were sampled immediately before the injection and then every hour until 8 hrs after injection time. Piperacillin concentrations were assayed using high performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: In group 1, the mean serum peak concentration of piperacillin was in the normal range (125 +/- 21 mg/L), but trough values were higher (48 +/- 8 mg/L) than in normal subjects. In group 2, trough values before the injection were increased in all patients (188 +/- 71 mg/L). At T1, blood peak concentration reached 470 +/- 127 mg/L. A small amount of piperacillin was retrieved from the ultrafiltrate. The elimination half-life was 5.1 +/- 1.4 and 4.8 +/- 1.4 hrs in groups 1 and 2, respectively. CONCLUSIONS: Piperacillin was not removed to a significant extent during continuous hemofiltration. Further, in the intensive care unit, patients in shock with multiple organ failure such as liver failure might behave differently from patients with stable end-stage renal disease. A 4-g dose of piperacillin twice a day is recommended in such patients.

Aged↗
PubMed1988

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals.

The protective effect of piperacillin against the nephrotoxicity of cephaloridine and gentamicin was examined in experimental animals. In rabbits, piperacillin was infused at a dose of 1 mg/kg (body weight) per min over 225 min and cephaloridine (300 mg/kg) was intravenously administered as a bolus 45 min after the start of a drip infusion. Blood urea nitrogen, serum creatinine, and N-acetyl-beta-D-glucosaminidase (NAG) in urine were measured as the renal toxicological parameters before and 24 h after cephaloridine dosing. Although the single administration of cephaloridine significantly elevated these parameters, the elevation was prevented by the concomitant administration of piperacillin. The protective effect of piperacillin was superior to those of cephalothin and fosfomycin. In rats, piperacillin (1,000 mg/kg) was intravenously administered and immediately followed by the intramuscular administration of gentamicin (100 mg/kg) every 24 h for 5 days. When piperacillin was concomitantly administered with gentamicin, the elevations of blood urea nitrogen, serum creatinine, and urinary NAG were significantly lower than when gentamicin was given alone. The concomitant administration of piperacillin resulted in a significant protective effect against the nephrotoxicity of cephaloridine in rabbits and of gentamicin in rats. Histopathological observation also supported the protective effect of piperacillin. The protective mechanism of piperacillin might be the inhibition of transport from the peritubular side to tubular cells for cephaloridine and from both the peritubular and luminal sides for gentamicin.

Animals↗
PubMed1990

Enhanced activity of combination of tobramycin and piperacillin for eradication of sessile biofilm cells of Pseudomonas aeruginosa.

An in vitro chemostat system in which Pseudomonas aeruginosa can be cultivated at a slow growth rate and under iron limitation conditions was used to study the susceptibilities of sessile bacteria of mucoid and nonmucoid P. aeruginosa strains to tobramycin and piperacillin. Planktonic cells of both mucoid and nonmucoid P. aeruginosa strains were susceptible to tobramycin and piperacillin. None of the cells was found to be viable after 2 h of exposure to 200 micrograms of piperacillin plus 10 micrograms of tobramycin per ml. Young sessile bacteria were slightly more resistant to piperacillin or tobramycin than the planktonic cells were. However, eradication of young sessile bacteria could be achieved with a combination of piperacillin and tobramycin. None of these young biofilm bacteria were found to be viable after a 2-h exposure to 200 micrograms of piperacillin plus 10 micrograms of tobramycin per ml. Old sessile bacteria were very resistant to these antibiotics. Eradication of old sessile bacteria could not be achieved with either tobramycin (200 micrograms/ml) or piperacillin (200 micrograms/ml) alone. Combination of higher concentrations of tobramycin with piperacillin resulted in an enhancement of killing of the old sessile bacteria. Exposure of old sessile bacteria to 200 micrograms of piperacillin plus 100 micrograms of tobramycin per ml resulted in the reduction of the viable count to approximately 0.02%. The data suggest that the eradication of biofilm-associated infections is best carried out as early as possible. Enhanced activities against the sessile bacteria were achieved when higher concentrations of aminoglycosides were combined with beta-lactam antibiotics.

Bacterial Adhesion↗
PubMed1998

Pharmacodynamic interactions of ciprofloxacin, piperacillin, and piperacillin/tazobactam in healthy volunteers.

Mathematical modeling methods were used to study pharmacokinetic and pharmacodynamic interactions of the antimicrobial combinations piperacillin plus ciprofloxacin and piperacillin plus tazobactam. Twelve healthy volunteers received the following treatments: piperacillin (4 g), ciprofloxacin (400 mg), piperacillin (4 g) plus ciprofloxacin (400 mg), and piperacillin (4 g) plus tazobactam (0.5 g), via intravenous infusion in a four-period crossover design. Serum drug concentrations were analyzed by means of high-performance liquid chromatography (HPLC), and inhibitory titers were performed against eight organisms. The pharmacodynamic response (growth or no growth) was modeled for each of the monotherapy courses using a Hill-type model where Emax was 1 (100% probability of no growth [P(NG)]), and EC50 was the concentration associated with a 50% P(NG). For piperacillin plus ciprofloxacin, P(NG) was a function of 1) plasma concentrations for both drugs; 2) EC50 values from the monotherapy courses; and 3) theta, an interaction term that accommodates synergy, additivity, or antagonism. For piperacillin/tazobactam, the serum ultrafiltrate area under the inhibitory curve was compared with that of piperacillin alone to determine the benefit of tazobactam. The interaction between piperacillin and ciprofloxacin was additive. The addition of tazobactam to piperacillin was beneficial against certain organisms. The model developed can be used to evaluate the activity of combination regimens against representative pathogens.

Adolescent↗
PubMedDate not supplied

Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients.

BACKGROUND: Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (i.v.) piperacillin in automated PD patients. PATIENTS AND METHODS: Eight patients (3 males, 5 females) were recruited and received a single i.v. dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on cycler), and end of dwells 4-5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. RESULTS: The patients were 49.5 +/- 10.1 years of age (mean +/- SD) and had been receiving PD for a median of 3 months (range 2-66 months). Dwell times were 2.25 +/- 0.06 hours on cycler and 7.26 +/- 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 +/- 0.39 hr, off cycler 4.39 +/- 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 +/- 0.41 hr, off cycler 2.54 +/- 1.48 hr; p = 0.19). Piperacillin total CL (CL(T)) was 31.29 +/- 6.02 mL/minute. Renal CL (CL(R)) and PD CL (CL(PD)) accounted for 8.8% and 16.8% of CL(T); CL(R) correlated well with GFR (CL(R) = 0.86 GFR + 0.1; p < 0.00003). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 microg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that i.v. piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. CONCLUSION: The current i.v. piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.

Adult↗
PubMed1993

Piperacillin versus cefazolin given perioperatively to high-risk patients who undergo open cholecystectomy: a double-blind, randomized trial.

OBJECTIVE: To study the efficacy, microbiologic features and toxicity of prophylactic cefazolin versus prophylactic piperacillin in high-risk patients who undergo open cholecystectomy. DESIGN: Double-blind randomized trial with follow-up for 6 weeks postoperatively. SETTING: An 850-bed community hospital, located in a major Canadian city. Patients admitted to hospital who satisfied published criteria for being at high-risk for infection after open cholecystectomy were entered into the protocol, and those who satisfied the criteria and provided consent were entered into the study. Eighty-one patients were randomly assigned by computer to receive either piperacillin or cefazolin as the prophylactic agent. INTERVENTIONS: Open cholecystectomy. MAIN OUTCOME: Provides detailed information on the organisms found in the biliary tree in patients with acute cholecystitis, assesses the in-vitro activity of cefazolin versus piperacillin against the isolated organisms, expecting that piperacillin would be much more active against isolated anaerobes and gram-negative bacteria. RESULTS: Bactobilia was documented in 42% of patients in the cefazolin group and 29% of patients in the piperacillin group. Piperacillin was active in vitro against 94% of all isolates versus 56% for cefazolin (p < 0.005, McNemar's test). Adverse effects and toxicities in both the piperacillin and cefazolin group were low and were not serious. CONCLUSIONS: Both piperacillin and cefazolin are safe and effective prophylactic antimicrobials for high-risk patients who undergo open cholecystectomy. However, piperacillin had a much wider spectrum of in-vitro activity against the isolated pathogens, especially Enterococcus sp., Enterobacter cloacae and the anaerobes.

Adult↗
PubMed1998

Single or triple dose piperacillin prophylaxis in elective cesarean section.

OBJECTIVE: To evaluate the efficacy and safety of piperacillin in the prevention of perioperative febrile morbidity in elective cesarean sections, a combination of cephradine plus metronidazole vs. a control group which did not receive any antibiotic prophylaxis. METHOD: 198 women undergoing elective cesarean section were included in a randomized control study to compare the prophylactic efficacy and safety of a single dose (4 g) or three doses (2 g) of piperacillin, three doses of cephradine plus metronidazole combination, when administered peri-operatively and a control group which did not receive prophylactic antibiotics. RESULT: 198 women were randomized to the study, but 14 had to be excluded leaving 184 for analysis. Statistically significant difference was reached when comparing the piperacillin groups (group A and group C) with control (group D) in the prevention of postoperative febrile morbidity inclusive of wound infection and endomyometritis (single-dose piperacillin group A: Relative Risk = 0.14, 95% CI 0.03-0.58). Multi-dose piperacillin therapy group C: R.R. = 0.27, 95% CI 0.10-0.77). The combination of cephradine and metronidazole (group B) when compared with the control group did not show any statistical significant difference in prevention of postoperative febrile morbidity (R.R.= 0.49, 95% CI 0.22-1.10). Single-dose piperacillin when compared to multi-dose piperacillin regimen appears to be more effective at reducing postoperative infective morbidity but this is not statistically significant (R.R. = 0.51, 95% CI 0.10-2.65). When febrile morbidity is separated into wound infection and myometritis, the reduction rates in either of them in each antibiotic study group A, B and C compared to the control group D are not significant except when study groups A and C are combined and compared to control group D (R.R. = 0.21, 95% CI 0.76-0.06). CONCLUSION: Piperacillin single agent therapy, either as a single dose of 4 g or a triple dose of 2 g, is effective and safe in the prevention of postoperative infection when given as prophylaxis in elective cesarean cases.

Anti-Infective Agents↗
PubMed1982

Preliminary report comparing piperacillin and carbenicillin for complicated urinary tract infections.

Piperacillin is a new semisynthetic penicillin with a broad spectrum of in vitro activity against common gram-negative urinary tract pathogens. We compared the efficacy and safety of piperacillin versus carbenicillin in patients with complicated urinary tract infection. A total of 56 adult patients (mean age 55 years) in stable medical condition with 1 or more structural genitourinary abnormalities entered the study. Of these patients 27 were evaluated for antibiotic efficacy. There were 20 lower tract and 7 upper tract infections, of which 17 were acute and 10 were chronic. Patients were randomized into 2 groups: 17 patients with 18 organisms received single agent treatment with 181 mg. per kg. intravenous piperacillin daily for 6 days and 10 patients with 11 organisms received 270 mg. per kg. intravenous carbenicillin daily for 6 days. Infecting organisms were Escherichia coli 45 per cent, Proteus mirabilis 14 per cent, Klebsiella pneumoniae 14 per cent. Enterobacter species 10 per cent, Pseudomonas aeruginosa 7 per cent and so forth. Antimicrobial susceptibility assessed by measurement of minimal inhibitory concentration and disk diffusion zone size demonstrated superior activity of piperacillin over carbenicillin for most micro-organisms tested. All patients responded clinically. The bacteriologic cure rate was 72 per cent at 5 to 9 days after therapy in both groups. Three patients who received piperacillin had urosepsis and were cured. No resistance emerged during therapy. Superinfections developed in 5 patients on carbenicillin (50 per cent) and in 4 patients on piperacillin (24 per cent), and none was resistant to piperacillin. Superinfections were attributed to catheterization and structural genitourinary abnormalities. The over-all incidence of adverse effects in patients on piperacillin was less than that of those on carbenicillin, 31 and 51 per cent respectively. Side effects in both groups were mild and did not require discontinuation of therapy. There were no significant alterations in fluid and electrolyte balance, or hematologic or renal function.

Adolescent↗
PubMed2002

Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat.

1. The effects of the administration piperacillin on bile flow and biliary lipid secretion were studied in male Wistar rats. 2. Intravenous injection of piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an increase in its biliary concentration and excretion rate. Maximal biliary excretion was reached at a dose of 2.0 mmol/kg piperacillin. 3. Excretion of the antibiotic into bile was associated with a marked choleresis. A linear relationship was observed between bile flow and piperacillin excretion, 5.7 micro L bile being produced per micro mol piperacillin excreted into the bile. 4. Continuous i.v. infusion of piperacillin at 2.0 mmol/100 g per min did not result in significant changes in bile acid or cholesterol secretion, but biliary phospholipid secretion was markedly reduced. The inhibitory effect on phospholipid secretion was also present when biliary lipid output had been previously increased by an infusion of taurocholate (200 nmol/100 g per min). Addition of taurocholate did not reverse the impairment of phospholipid secretion induced by piperacillin. 5. These results indicate that acute administration of piperacillin in the rat induces a marked choleresis by stimulating bile acid-independent bile flow. The significant impairment in phospholipid secretion suggests a specific effect on intracellular supply and/or translocation across the canalicular membrane.

Animals↗
PubMed1988

Interaction between piperacillin and pefloxacin or amikacin on the selection of resistant mutants of Pseudomonas aeruginosa.

Pseudomonas aeruginosa mutants were selected with piperacillin, pefloxacin, amikacin and the combinations pefloxacin-piperacillin and amikacin-piperacillin. With amikacin and the piperacillin-amikacin combination no mutants were selected. With piperacillin (1-32 x MIC) mutants resistant to carboxypenicillins, ureidopenicillins, monobactam and cephalosporins were selected. With pefloxacin, three different types of mutant were observed which showed different patterns of cross-resistance to pefloxacin, sulphonamides, imipenem, piperacillin and other beta-lactam antibiotics. With the pefloxacin-piperacillin association, mutants similar to one of the types selected by pefloxacin alone and resistant to both of the selective antibiotic were predominantly obtained. No mutants were selected with this combination if one of the antibiotics was used at a concentration equal to its MIC for the wild type strain and the other at concentrations above 4 x MIC. Since the association of piperacillin and pefloxacin was only moderately bactericidal against the predominantly cross-resistant mutant selected, the concentration of these antibiotics may have to be carefully controlled to prevent the emergence of such mutants.

Amikacin↗
PubMed1994

Inhibition of the renal excretion of tazobactam by piperacillin.

A 1:4 by weight of combination of tazobactam, a new beta-lactamase inhibitor, and piperacillin, is now under development in Japan. After bolus iv administration of the combination to beagle dogs, piperacillin both significantly raised the area under plasma concentration time curve (AUC0 approximately infinity) and significantly decreased the total body clearance (Cltot) of tazobactam. The percentage binding of tazobactam and piperacillin to dog and human serum protein was the same for the combination as for the individual compounds. Piperacillin significantly decreased the renal clearance (Clr) and the clearance ratio (Cr) of tazobactam in dogs. Further, probenecid significantly decreased Clr of both tazobactam and piperacillin, and the Cr of tazobactam and piperacillin approximately reached unity. These results indicate that piperacillin inhibits the renal excretion of tazobactam. Both tazobactam and piperacillin are secreted by a tubular anion transport system which is identical to the probenecid secretion system.

Animals↗
PubMed1987

Experimental studies of biliary excretion of piperacillin.

The nonrecirculating isolated perfused rat liver was used to study biliary antibiotic excretion by the liver in a steady-state, controlled environment in which bile flow, bile salt output, and antibiotic delivery were maintained under constant conditions. The effects of piperacillin, ampicillin, and gentamicin on bile flow and bile salt output were analyzed; none altered bile salt output, and only high concentrations of piperacillin (100 micrograms/mL) increased bile flow. The ratio of antibiotic concentration in bile and perfusate depended on the type of antibiotic and perfusate concentration. Piperacillin infusions at perfusate concentrations of 50 or 100 micrograms/mL (in the presence of 60 microM taurocholate) yielded bile to perfusate ratios of 112 +/- 10 versus 49 +/- 3, respectively. Using similar perfusate, the concentration ratios for ampicillin (20 micrograms/mL) and gentamicin (10 micrograms/mL) were only 3.4 +/- 0.5 and 0.5 +/- 0.1, respectively. By altering the perfusate to contain either 60 microM or 240 microM taurocholate, we found variance in bile salt output from 27 +/- 1 to 115 +/- 2 mumol/h, yet this alteration had little effect on the output of ampicillin (perfusate concentration of 20 micrograms/mL), 73 +/- 7 versus 74 +/- 12 micrograms/h, or piperacillin (perfusate concentration 100 micrograms/mL), 10 +/- 1 versus 11 +/- 2 mg/h. Thus, it appears ampicillin and piperacillin are excreted into bile at high concentrations by bile salt-independent pathways. Partial biliary obstruction (6 cm H2O) results in significant decreases in bile volume. Infusion of 50 micrograms/mL of piperacillin resulted in increased biliary flow that approached nonobstructed values. Obstruction resulted in significant decreases in bile piperacillin concentration. Whether the choleretic effect of high concentrations of piperacillin has any clinical significance in nonobstructed or obstructed conditions remains to be established.

Ampicillin↗
PubMed1980

Synergistic activity of piperacillin in combination with beta-lactamase inhibitors.

Clavulanic acid and a penicillanic acid sulfone, when combined individually with piperacillin, synergistically inhibited various Enterobacteriaceae, Staphylococcus aureus, and Bacteroides fragilis. Clavulanic acid and piperacillin synergistically inhibited 91 of 170 (55%) isolates tested. Synergy was most often found against piperacillin-resistant bacteria: 65 of 69 isolates (94%). Although the penicillanic acid sulfone acted synergistically with piperacillin, inhibiting 62 of 170 strains (33%), the concentration of clavulanic acid required for synergy generally was less than that of penicillanic acid sulfone. Combination of piperacillin and cefotaxime, an inhibitor of type 1 beta-lactamases, rarely was synergistic and was antagonistic for several species. The combination of piperacillin with potent beta-lactamase inhibitors made piperacillin active against those isolates of Escherichia coli and Klebsiella and Bacteroides species, as well as selected other species, that are resistant to piperacillin by virtue of their production of beta-lactamases.

Anti-Bacterial Agents↗
PubMed1984

Comparative in vitro activities of apalcillin and piperacillin against gram-negative bacilli.

The susceptibilities of 317 gram-negative bacilli to apalcillin and piperacillin were determined by standardized microdilution and disk diffusion tests. The respective percentages of strains susceptible to less than or equal to 64 micrograms of apalcillin and piperacillin per ml were as follows: members of the family Enterobacteriaceae, 90 and 88%; randomly selected Pseudomonas aeruginosa, 100 and 100%; multi-drug-resistant P. aeruginosa, 100 and 75%; and other nonfermenters and Aeromonas hydrophila, 99 and 97%. The drugs had equal activity against Enterobacteriaceae and A. hydrophila; apalcillin was more active against Pseudomonas species and Acinetobacter calcoaceticus, and piperacillin was more active against other nonfermenters. By using linear regression analysis, we found that the MICs of apalcillin and piperacillin were highly interrelated; the lines of best fit had slopes close to unity, and correlation coefficients (r) were greater than 0.90 for Enterobacteriaceae as a group and for other species individually. With disk diffusion testing, inhibition zone diameters around 100 micrograms apalcillin and 100 micrograms piperacillin disks correlated well with respective MICs for Enterobacteriaceae and P. aeruginosa (r = -0.93 to -0.96). Using an error rate-bound classification scheme, we determined breakpoints for apalcillin susceptibility and confirmed those previously established for piperacillin to be appropriate. The apalcillin disk, with modified breakpoints, could be used to predict piperacillin MICs for all organisms, but the piperacillin disk could not be used to predict apalcillin MICs for nonfermenters.

Ampicillin↗
PubMed1991

Pharmacokinetics and tissue penetration of tazobactam administered alone and with piperacillin.

The pharmacokinetics of tazobactam (500 mg) administered intravenously alone were compared with the pharmacokinetics of tazobactam coadministered with piperacillin (4 g), and the penetration into an inflammatory exudate in six healthy males was studied. Piperacillin influenced the pharmacokinetics of tazobactam. The mean levels of tazobactam in plasma at 4 h were 0.6 microgram/ml when it was given alone and 1.2 micrograms/ml when it was given with piperacillin (P = 0.0003). The mean total clearances of tazobactam were 203.5 and 134.2 ml/min (P = 0.035) when it was given alone and with piperacillin, respectively There were no significant differences in the elimination half lives, areas under the concentration-time curve from 0 h to infinity, or volumes of distribution. Inflammatory exudate penetration was rapid, and the mean maximum levels of tazobactam attained were 6.4 and 11.3 micrograms/ml when it was given alone or with piperacillin, respectively (P less than 0.06). The mean percent penetration of tazobactam and the area under the concentration-time curve from 0 h to infinity in inflammatory exudate were greater when tazobactam was given with piperacillin. The mean 24-h urinary recoveries of tazobactam were 63.7% +/- 7.9% when it was given alone and 56.8% +/- 2.7% when it was given with piperacillin. The explanation for the differences in the pharmacokinetics of tazobactam when it was administered alone compared with those when it was given with piperacillin was unclear.

Adult↗
PubMed1992

Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease.

Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by high-performance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. The total body clearance (3.79 +/- 0.71 versus 3.94 +/- 1.05 ml/min), the steady-state volume of distribution (0.19 +/- 0.04 versus 0.18 +/- 0.03 liter/kg), and the terminal elimination half-life (47.91 +/- 7.20 versus 45.08 +/- 10.34 h) were not significantly altered in the presence of piperacillin. In contrast, the terminal elimination half-life (47.68 +/- 20.58 versus 35.67 +/- 11.18 h) of gentamicin was significantly reduced when gentamicin was given with piperacillin. The total body clearance (4.26 +/- 3.07 versus 4.89 +/- 1.94 ml/min) and the steady-state volume of distribution (0.19 +/- 0.04 versus 0.20 +/- 0.04 liter/kg) of gentamicin were not significantly altered during combination therapy; however, the nonrenal clearance of gentamicin administered in combination with piperacillin (3.56 +/- 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 +/- 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients.

Adult↗
PubMed1983

Piperacillin in early neonatal infection.

Seventy infants with suspected bacterial infection in the first 48 hours of life were treated either with piperacillin and flucloxacillin or with penicillin and gentamicin. Infection was confirmed and successfully eradicated in 6 of the 35 infants receiving piperacillin and flucloxacillin. Four infants treated with penicillin and gentamicin had confirmed infection and one deteriorated initially but then recovered when treated with piperacillin. Serum piperacillin concentrations above 100 mg/l and cerebrospinal fluid piperacillin concentrations of 2.6-6 mg/l were noted for up to four hours and 7 hours respectively, even in the absence of inflamed meninges, after administration of piperacillin 100 mg/kg body weight intravenously. Median half life of piperacillin was 6.5 hours and was prolonged in renal impairment. Piperacillin is considered to be a safe and effective first line single agent treatment for early neonatal infection but because some Escherichia coli are resistant to it we recommend that a second agent be used in critically ill infants with neutropenia or meningitis.

Bacterial Infections↗
PubMedDate not supplied

Piperacillin with and without tazobactam against extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa in a rat thigh abscess model.

BACKGROUND: We compared the antibacterial effect of piperacillin, piperacillin-tazobactam and imipenem in a paired rat thigh abscess model. METHODS: Two abscesses were provoked in the thighs of rats, one on the right with an extended-spectrum beta-lactamase (OXA-14)-producing Pseudomonas aeruginosa (Ps-162) and the other on the left thigh with a control strain. RESULTS: The colony counts from the abscesses in log 10 colony-forming units per gram (mean +/- SD) in the imipenem group were 2.78 +/- 1.71 and 3.19 +/- 1.66, in the piperacillin-tazobactam group 4.36 +/- 0.23 and 2.44 +/- 1.97, and in the piperacillin group 4.44 +/- 0.21 and 3.71 +/- 0.99 for Ps-162 and the control strain, respectively. The mean colony counts were significantly different (p < 0.05) between Ps-162 and the control strain in the piperacillin and piperacillin-tazobactam groups. CONCLUSION: These data showed that piperacillin and piperacillin-tazobactam were significantly less effective against extended-spectrum beta-lactamase-producing P. aeruginosa, while imipenem was equally effective against both Ps-162 and the control strain in this abscess model.

Abscess↗