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PubMed1988

Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients.

The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.

Adolescent↗
PubMed1993

Double-blind; placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture.

OBJECTIVE: We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection. STUDY DESIGN: Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress. RESULTS: Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37). There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 +/- 3 vs 30.3 +/- 2.9 weeks). However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1% vs 10.8% p = 0.005) and the mean latency period was significantly prolonged (11.4 +/- 18.8 vs 6.1 +/- 13.6 days, p = 0.001) in the piperacillin group compared with the control groups. CONCLUSIONS: Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery.

Adult↗
PubMedDate not supplied

Studies to optimize the in vitro testing of piperacillin combined with tazobactam (YTR 830).

The combination of piperacillin and the beta-lactamase inhibitor tazobactam (formerly YTR 830) was studied to determine optimal disk concentrations and dilution testing conditions. In addition, the potency of the combination was compared to that of piperacillin alone. The spectrum of piperacillin was greatly expanded by the addition to tazobactam principally against beta-lactamase producing strains of Haemophilus influenzae, Escherichia coli, Morganella morganii, Proteus vulgaris, Providencia stuartii, Shigella spp., Neisseria gonorrhoeae, and Staphylococcus spp. Tazobactam was active alone against Branhamella catarrhalis (minimum inhibitory concentration [MIC] 50, less than or equal to 1 microgram/ml), gonococci (MIC 50, 0.5-4 micrograms/ml), and N. meningitidis (MIC 50, less than or equal to 1 microgram/ml). Studies with beta-lactamase-producing type strains showed tazobactam to have high affinity for plasmid-mediated enzymes (TEM-1 and 2, SHV-1, HMS-1, and some CARB or OXA types) and not chromosomal beta-lactamases. Piperacillin/tazobactam inhibited 93% of fluoro-quinolone resistant strains at less than or equal to 64/8 micrograms/ml but failed to suppress the growth of 15 strains producing stably depressed cephalosporinases. Comparisons of piperacillin/tazobactam results determined with 100/10-, 100/20-, and 100/30-micrograms disks established the 100/10-micrograms disk as most usable. Among five different MIC combinations the ratio of eight parts piperacillin to one part tazobactam or fixed concentration tests at greater than or equal to 4 micrograms tazobactam/ml were preferred, each producing very low occurrences (less than or equal to 1.6%) of false-resistance or -susceptibility when compared to disk test results. MICs determined by agar and broth microdilution methods were essentially the same. The recommended breakpoints for piperacillin/tazobactam MICs were identical to those now found in the NCCLS susceptibility testing standards with the following exceptions: (1) for tests with H. influenzae and Staphylococcus spp.--susceptible at greater than or equal to 21 mm (MIC less than or equal to 16/2 micrograms/ml) and resistant less than or equal to 20 mm (MIC less or equal to 32/4 micrograms/ml); and (2) all remaining nonspeudomonas isolates would be interpreted by the NCCLS piperacillin enteric bacilli susceptibility criteria. This newer beta-lactamase inhibitor combination appears to be worthy of further in vivo trials guided by these or similar tentative in vitro susceptibility testing parameters.

4-Quinolones↗
PubMed1996

Pharmacokinetic-pharmacodynamic modeling of the antibiotic effect of piperacillin in vitro.

PURPOSE: It was the aim of the present study to investigate the in vitro antimicrobial effects of the beta-lactam antibiotic piperacillin on Escherichia coli using concentration-time profiles similar to those encountered in vivo. METHODS: An in vitro dilution model was used to expose E. coli to various piperacillin concentration profiles. The antimicrobial effect was evaluated by determination of the number of bacteria over time. RESULTS: A modified Emax-model was found appropriate to describe the pharmacodynamic effect. This model was linked with the respective piperacillin concentrations to provide a suitable pharmacokinetic-pharmacodynamic (PK-PD) model. The average growth half-life in absence of piperacillin was 28 min and the maximum kill half-life was 25 min. The EC50 for the various dosing regimens averaged 5.2 micrograms/mL and was independent of dose. These parameters were used the simulate the bacterial effects of commonly administered doses or dosing regimens in humans. CONCLUSIONS: Based on the in vitro data a more frequent administration of piperacillin will be more efficacious. The proposed PK-PD-model allows a more detailed evaluation of dosing regimens than the use of minimum inhibitory concentrations.

Computer Simulation↗
PubMed1993

Piperacillin versus cefotetan as single-dose prophylaxis in abdominal hysterectomy: a prospective, randomized, multicenter study.

Five hundred and sixty-six women, consecutively admitted to nine different hospitals for elective abdominal hysterectomy, were randomized to receive a single 2 g i.v. dose of either cefotetan or piperacillin at induction of anesthesia. Five patients were excluded and 561 (287 given cefotetan and 274 given piperacillin) could be evaluated. In 10 patients (5 for each drug) the concentrations of either cefotetan or piperacillin in serum and subcutaneous tissue at the beginning and at the end of surgery and in uterus, salpinx and ovary samples, were microbiologically assessed. No significant differences could be found between cefotetan and piperacillin groups for any of the considered infectious complications (bacteremia, wound or vaginal cuff infection, pelvic cellulitis and febrile morbidity) nor for the pooled data (cefotetan group: 4.9%, piperacillin group: 5.8%, p:NS). As for the concentrations of prophylactic drugs, serum levels throughout surgery were found to be adequate.

Adult↗
PubMed2003

Oral administration of beta-lactamase preserves colonization resistance of piperacillin-treated mice.

We hypothesized that orally administered, recombinant class A beta-lactamase would inactivate the portion of parenteral piperacillin excreted into the intestinal tract, preserving colonization resistance of mice against nosocomial pathogens. Subcutaneous piperacillin or piperacillin plus oral beta-lactamase were administered 24 and 12 h before orogastric inoculation of piperacillin-resistant pathogens. Oral administration of beta-lactamase reduced piperacillin-associated alteration of the indigenous microflora and prevented overgrowth of pathogens.

Animals↗
PubMed1983

Piperacillin and tobramycin in the treatment of Pseudomonas lung infections in cystic fibrosis.

Fourteen children with cystic fibrosis and pulmonary lung infection due to Pseudomonas aeruginosa were treated with piperacillin (300 mg/kg/day) alone or piperacillin and tobramycin (7 mg/kg/day) iv. The outcome with respect to clinical state, chest X-ray and lung function tests was better with combination therapy than with piperacillin alone. Bacteriological response was the same with both regimens: leucocyte content of the sputum decreased, non-mucoid Ps. aeruginosa strains were eliminated, but mucoid strains were only suppressed (11 children). Peak serum levels of piperacillin averaged 102 mg/l, the overall serum elimination was 0.75 h and the mean sputum concentrations ranged from 1.07 to 2.2 mg/l. Peak serum levels of tobramycin averaged 5.15 mg/l, the half life was 1.25 h and the mean sputum concentrations ranged from 0.57 to 0.68 mg/l. The clearance of piperacillin and tobramycin was increased significantly. Drug-resistance did not develop during therapy.

Adolescent↗
PubMed1985

The influence of prophylactic piperacillin on the postoperative course of transurethral prostatectomy.

Forty patients undergoing transurethral prostatectomy were randomized prospectively into a controlled study to determine the influence of prophylactic piperacillin (4 X 2 g for 48 h) on the postoperative course. Samples of urine, prostate, urethral swabs and faeces were cultured to determine the origin of infection and to record the development of resistance and selection of the intestinal flora. Piperacillin lowered the incidence of early postoperative urinary tract infection (UTI) (P less than 0.01), of fever (P less than 0.05) and the occurrence of reinfection within three weeks postoperatively (P less than 0.01). The organisms causing early UTIs and reinfections originated mainly from the prostate and urethra in the immediate perioperative period and were both Gram-positive (40%) and Gram-negative (60%); those causing late UTIs in previously uninfected patients originated from faecal flora and were mainly Gram-negative (92%). Prostatic levels of piperacillin were 30.3 +/- 29.2 mg/g; the ratio serum: prostate was 1;0.27. There was no development of resistance to piperacillin or selection of resistant strains in intestinal or urogenital flora. Except for a significant increase of Candida albicans, piperacillin did not influence numbers or composition of aerobic and anaerobic bacteria in the intestinal flora.

Aged↗
PubMed1988

Use of a continuous culture system for susceptibility testing of gram-negative bacterial isolates to piperacillin.

Fifteen (15.2%) of 99 Gram-negative bacteria isolated from patients during episodes of fever and neutropenia had minimum inhibitory concentrations ranging from less than 2 to 32 mg/l but were not fully sensitive to piperacillin by disc diffusion testing. These 15 isolates were further examined using a chemostat system, in which susceptible isolates were rapidly killed by piperacillin. Only three of the 15 isolates were susceptible to piperacillin when compared to sensitive control strains using the chemostat system. The results of this study suggest that an increase in the MIC to piperacillin is a less sensitive indicator of resistance to piperacillin amongst Gram-negative isolates than a reduction in the zone of inhibition in disc diffusion testing.

Bacterial Infections↗
PubMed1991

Pharmacokinetics of piperacillin during pregnancy.

The pharmacokinetics of piperacillin during pregnancy were investigated. Eight pregnant women received 4 g of piperacillin intravenously before caesarean section. Likewise, five non-pregnant subjects of child bearing age received the same dose before a gynaecological operation. The mean peak plasma concentrations of piperacillin were 87.5 and 172.2 mg/L for the pregnant and non-pregnant patients, respectively. The mean umbilical vein concentration was 9.7 mg/L; the mean umbilical artery concentration was 7.4 mg/L and the amniotic fluid concentration 6.8 mg/L. The feto-maternal ratio at the time of caesarean section was 0.27. Pharmacokinetic parameters of piperacillin indicate larger volumes of distribution and higher clearance rates during pregnancy compared with the non-pregnant state. The altered pharmacokinetics of piperacillin during pregnancy suggest that higher doses may be required for effective treatment of serious infections in pregnant women near term.

Adult↗
PubMed1990

Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in 11 critically ill surgical patients who had no evidence of pre-existing renal and hepatic disease. Interpatient variations were demonstrated in the drug's half-life, distribution volume, and clearance, with values of 1.50 +/- 2.05 (SD) h, 25.0 +/- 17.2 L, and 23.8 +/- 17.2 L/h, respectively. Variations in piperacillin disposition were best explained by serum concentrations of albumin, total protein, and bilirubin, and the amount of urea nitrogen excreted daily in urine. Age and renal function were moderately associated with piperacillin elimination rate and clearance. Altered piperacillin disposition thus appeared to occur as secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid/colloid therapy. These alterations may necessitate dosage modifications to achieve optimal patient response when treating patients with piperacillin as well as with other similar drugs eliminated via renal and nonrenal routes.

Adult↗
PubMed1990

A randomized study of teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin for the empirical treatment of fever in neutropenic patients.

We compared the combination of teicoplanin plus ciprofloxacin with gentamicin plus piperacillin for the empirical treatment of fever in 80 neutropenic patients. A favourable clinical response rate was achieved in 28/38 (74%) patients receiving teicoplanin plus ciprofloxacin and in 17/35 (49%) of those receiving gentamicin plus piperacillin (P = 0.05). Microbiologically documented infections accounted for 55% of febrile events. When these episodes were analysed separately, response to teicoplanin plus ciprofloxacin remained unchanged at 74% whereas only 35% patients responded to gentamicin and pieracilin (P = 0.034). Gram-positive organisms accounted for 78% bacterial isolates with Staphylococcus epidermidis the most common pathogen. Ten out of 12 (83%) Staph. epidermidis infections resolved when treated with teicoplanin and ciprofloxacin as compared with a response rate of only two out of eight (25%) with gentamicin and piperacillin (P = 0.032). The combination of teicoplanin and ciprofloxacin was associated with no severe drug-related adverse events; by contrast, two patients receiving gentamicin plus piperacilin were withdrawn owing to adverse drug reactions, one with acute renal failure and one following a severe allergic reaction to piperacillin. We conclude that teicoplanin with ciprofloxacin is more effective than gentamicin plus piperacillin for the empirical treatment of febrile neutropenic patients. The high incidence of Gram-positive infection in our unit probably justifies the use of a specific anti-Gram-positive agent in the first-line antibiotic regimen.

Anti-Bacterial Agents↗
PubMed1981

Biliary concentrations of piperacillin in patients undergoing cholecystectomy.

Piperacillin is a new semisynthetic, expanded-spectrum penicillin with marked activity against Pseudomonas aeruginosa. The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy. Concentrations of piperacillin in common duct bile at 35 to 90 min postinfusion of 1-g doses ranged from 31 to 920 micrograms/ml, with a mean (+/- standard deviation) of 467 +/- 363 micrograms/ml. Gallbladder piperacillin levels at 30 to 75 min postinfusion ranged from 2.2 to 80 micrograms/ml, with a mean of 27 +/- 31 micrograms/ml. No correlation occurred with peak serum level of antibiotic, creatinine, bilirubin, or alkaline phosphatase. Significant amounts of piperacillin were excreted via the biliary system.

Bile↗
PubMed1983

Tobramycin inactivation by carbenicillin, ticarcillin, and piperacillin.

The in vitro and in vivo inactivation of tobramycin by carbenicillin, ticarcillin, or piperacillin was investigated by the enzyme immunoassay method in clinically employed dosages. After the addition of an 80-mg dose of tobramycin to 4- to 5-g doses of a penicillin in 100 ml of 0.9% saline or distilled water, the degradation profile of tobramycin appeared to follow a biexponential pattern of decay. Remarkable losses (30 to 40%) of tobramycin combined with carbenicillin or ticarcillin were observed within 1 h, as compared with the later decline. The combination of tobramycin with piperacillin was least inactivating. When the admixture of tobramycin with carbenicillin or piperacillin used in the in vitro study was infused to six volunteers over 1 h, the observed maximum concentrations of tobramycin were on the average 66 and 74% for carbenicillin and piperacillin, respectively, of that observed after tobramycin alone was given. In contrast, the value obtained for tobramycin in combination with piperacillin was close to 90% of the control value. The elimination half-lives of tobramycin combined with the penicillins were slightly shorter than those of tobramycin alone, indicating that the interaction occurs even in patients with normal renal function.

Adult↗
PubMed1990

Evaluation of piperacillin-tazobactam in experimental meningitis caused by a beta-lactamase-producing strain of K1-positive Escherichia coli.

We evaluated the pharmacokinetics and therapeutic efficacy of piperacillin combined with tazobactam, a novel beta-lactamase inhibitor, in experimental meningitis due to a beta-lactamase-producing strain of K1-positive Escherichia coli. Different doses of piperacillin and tazobactam, as single agents and combined (8:1 ratio; dosage range, 40/5 to 200/25 mg/kg per h), and of ceftriaxone were given to experimentally infected rabbits by intravenous bolus injection followed by a 5-h constant infusion. The mean (+/- standard deviation) rates for penetration into the cerebrospinal fluid of infected animals after coadministration of both drugs were 16.6 +/- 8.4% for piperacillin and 32.5 +/- 12.6% for tazobactam. Compared with either agent alone, combination treatment resulted in significantly better bactericidal activity in the cerebrospinal fluid. The bactericidal activity of piperacillin-tazobactam was dose dependent: cerebrospinal fluid bacterial titers were reduced by 0.37 +/- 0.19 log10 CFU/ml per h with the lowest dose versus 0.96 +/- 0.25 log10 CFU/ml per h with the highest dose (P less than 0.001). At the relatively high doses of 160/20 and 200/25 mg of piperacillin-tazobactam per kg per h, the bactericidal activity of the combination was comparable to that of 10 and 25 mg of ceftriaxone per kg per h, respectively.

Animals↗
PubMed1990

Comparative in vitro activities of a new quinolone, WIN 57273, and piperacillin plus tazobactam against anaerobic bacteria.

The in vitro activities of a new quinolone, WIN 57273, and the combination of piperacillin and tazobactam, a beta-lactamase inhibitor, were compared with those of cefoxitin, ceftizoxime, chloramphenicol, clindamycin, imipenem, metronidazole, and piperacillin for 123 clinical anaerobic isolates. Ceftizoxime and cefoxitin had equivalent activities, while metronidazole was active against gram-negative isolates. In the Bacteroides fragilis group, species other than B. fragilis were the most resistant. The combination of piperacillin with tazobactam in a ratio of 8 to 1 was more effective than piperacillin against B. fragilis group organisms when the MIC of piperacillin was greater than or equal to 64 micrograms/ml. Overall, WIN 57273 (i) and imipenem (ii) were the most active agents, with MICs for 50 and 90% of strains of (i) 0.25 and 0.5 and (ii) 0.125 and 2 microgram/ml, respectively.

4-Quinolones↗
PubMed1993

Use of a predictor panel to evaluate susceptibility test methods proposed for piperacillin-tazobactam.

A predictor panel of clinical isolates that produce a variety of types and amounts of beta-lactamases was used to assess the accuracy of dilution and disk diffusion susceptibility tests for piperacillin-tazobactam. Combinations of piperacillin-tazobactam with a fixed ratio of 8:1 and with tazobactam held constant at 4 micrograms/ml were examined in dilution tests performed in agar. In addition, disks containing 100 and 10 micrograms of piperacillin and tazobactam, respectively, were examined in diffusion tests. Three very major discrepancies between MICs determined with an 8:1 ratio and MICs determined with tazobactam held constant at 4 micrograms/ml were noted. These involved strains that appeared to be susceptible in tests with the 8:1 ratio but resistant when tazobactam was held constant at 4 micrograms/ml. However, the differences were only twofold. Error rate-bounded analysis with the disk containing 100 and 10 micrograms of piperacillin and tazobactam, respectively, revealed low error rates, regardless of whether MICs were determined with an 8:1 ratio or tazobactam held constant at 4 micrograms/ml. Thus, a predictor panel was useful in the identification of accurate susceptibility test for piperacillin-tazobactam.

Drug Therapy, Combination↗
PubMed1994

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species.

The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml). Erythromycin (1 microgram/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.

Animals↗