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PubMed2002

New onset of multiple organ dysfunction after receiving long-term high-dose piperacillin for outpatient treatment of osteomyelitis.

Toxic side effects of piperacillin occur in many organ systems and may be cumulative dose related. We report a patient receiving long-term high-dose piperacillin to accommodate convenient outpatient intravenous therapy of osteomyelitis. He developed life-threatening multiorgan dysfunction on day 20 of piperacillin administration after 49 days of antibiotics, suggesting a likely adverse drug reaction. Piperacillin should be administered according to the manufacturer's recommendations of dosage, frequency and duration, and suggested monitoring. Unorthodox treatment regimens are discouraged.

Journal Article↗
PubMed1978

Piperacillin: in vitro evaluation.

The in vitro activity of a new semisynthetic penicillin, piperacillin, was determined against 577 clinical isolates of gram-positive cocci and gram-negative bacilli. A concentration of 12.5 mug/ml inhibited 92% of isolates of Pseudomonas aeruginosa, 82% of Serratia marcescens, 73% of Escherichia coli, 61% of Klebsiella spp., and 42% of Enterobacter spp. Most Proteus spp. were extremely susceptible; over 85% were inhibited by 0.10 mug/ml. Piperacillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. The type of media and pH had variable effects on the activity of piperacillin, depending upon the organism. Piperacillin was generally less active than PC-904 against gram-negative bacilli, but was consistently more active than carbenicillin and ticarcillin.

Bacteria↗
PubMed1978

Comparison of the in vitro activity of Bay k 4999 and piperacillin, two new antipseudomonal broad-spectrum penicillins, with other beta-lactam drugs.

Bay k 4999 and piperacillin, two new substituted ampicillins, were compared with other beta-lactam antibiotics, including carbenicillin, azlocillin, mezlocillin, benzylpenicillin, ampicillin, and cefoxitin, against a wide range of gram-positive and -negative organisms. Bay k 4999 and piperacillin were extremely active against Pseudomonas aeruginosa (50% inhibited by 2 mug/ml), being about 16-fold more active than carbenicillin. Bay k 4999 was the most active drug against Escherichia coli (50% inhibited by 0.5 mug/ml) and Klebsiella spp. (50% inhibited by 2 mug/ml). Piperacillin and Bay k 4999 were equally active against Proteus spp., and piperacillin had high activity against Bacteroides fragilis (50% inhibited by between 1 and 2 mug/ml).

Azlocillin↗
PubMed1978

Comparative evaluation of piperacillin in vitro.

The minimal inhibitory concentrations of piperacillin and seven other betalactam antibiotics were determined against 407 bacterial isolates. Piperacillin was found to be more active than ampicillin against susceptible gram-negative bacilli and more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa and streptococci. Although piperacillin was active against Klebsiella pneumoniae, this activity was less than that of the cephalosporins. Piperacillin was not active against penicillin-resistant Staphylococcus aureus and Enterobacteriaceae that were resistant to the other test antibiotics.

Bacteria↗
PubMed1979

In vitro activity of piperacillin compared with that of carbenicillin, ticarcillin, ampicillin, cephalothin, and cefamandole against Pseudomonas aeruginosa and Enterobacteriaceae.

Piperacillin (T-1220), a semisynthetic derivative of aminobenzylpenicillin, was more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa; over 60% of isolates were inhibited at a concentration of 6.3 mug/ml. Piperacillin was bactericidal for 84% of Pseudomonas strains at 100 mug/ml, carbenicillin killed 60%, and ticarcillin killed 68% at that concentration. Piperacillin was also more active than the other penicillins against isolates of Escherichia coli, Enterobacter, and Proteus mirabilis. The combination of piperacillin and tobramycin, demonstrating synergistic inhibition of 87% of strains of P. aeruginosa, was the most active of the penicillin-aminoglycoside combinations tested for synergism.

Ampicillin↗
PubMed1984

Piperacillin versus clindamycin plus gentamicin for pelvic infections.

Piperacillin, a new semisynthetic penicillin, has broad spectrum activity against most clinically important aerobic and anaerobic bacteria. In the present study, piperacillin was compared with a combination of clindamycin and gentamicin for the treatment of 83 women with pelvic infection (42 with endometritis, 29 with posthysterectomy cuff infections, 11 with acute salpingitis, and one with a wound infection). There were 179 bacterial isolates, 98 (53%) aerobic and 81 (45%) anaerobic. Of the 42 patients treated with piperacillin, there were three (7.1%) clinical failures compared with one (2.4%) in the 41 patients treated with clindamycin-gentamicin. A single drug, piperacillin, was shown to be as safe and effective as the combined clindamycin plus gentamicin therapy for pelvic infections.

Adult↗
PubMed2004

Efficacy of piperacillin-tazobactam in the treatment of surgical wound infection after clean-contaminated head and neck oncologic surgery.

BACKGROUND: Although perioperative antibiotic prophylaxis has significantly reduced surgical wound infection rates, this complication is still a frequent complication of head and neck cancer surgery. Because these infections are typically polymicrobial, our study evaluated the safety and efficacy of piperacillin-tazobactam in the treatment of surgical wound infection after clean-contaminated head and neck oncologic surgery. METHODS: In this multicenter, prospective clinical trial, 70 patients with surgical wound infection received piperacillin-tazobactam. RESULTS: Of patients who were evaluable, 92.4% were also clinically cured or improved, and the bacteriologic eradication rate was 80.3%. Of the 70 patients enrolled in the study, six (8.5%) experienced six adverse events: two cases of moderate diarrhea, one allergic skin reaction, and three cases of phlebitis. No deaths were attributable to the study drug. CONCLUSIONS: Piperacillin-tazobactam is a good choice of treatment as monotherapy for surgical wound infection after clean-contaminated head and neck oncologic surgery.

Adult↗
PubMed2005

The clinical and economic benefits of administering piperacillin-tazobactam by continuous infusion.

Beta-lactam antibiotics, such as piperacillin-tazobactam, are commonly administered frequently throughout the day as intermittent infusions over a period of 30-60 min. However, increasing knowledge of how these antibiotics kill bacteria has made continuous infusion a valuable option to achieve maximal clinical outcomes while consuming the least amount of institutional resources. Continuous infusion of piperacillin-tazobactam is currently used at our hospital because of its clinical and economic benefits when compared with intermittent infusion. This article will review our experience with the administration of piperacillin-tazobactam by continuous infusion and the numerous advantages we have documented. Additionally, advantages related to a reduction in nursing resource consumption will be a focus of discussion.

Anti-Bacterial Agents↗
PubMed2004

Efficacy of ertapenem against methicillin-susceptible Staphylococcus aureus in complicated skin/skin structure infections: results of a double-blind clinical trial versus piperacillin-tazobactam.

Staphylococcus aureus is the predominant pathogen in complicated skin/skin structure infections. In this analysis of a subgroup of data from a randomised, double-blind trial, the efficacy of ertapenem 1 g daily was compared with piperacillin-tazobactam 3.375 g Q6H for treatment of complicated skin/skin structure infections caused by methicillin-susceptible S. aureus (MSSA). Of the 529 treated patients in this trial, 185 (35.0%) had MSSA as a baseline pathogen. At the test of cure assessment 10-21 days post-therapy, 54 of 67 (80.6%) protocol evaluable patients in the ertapenem group and 55 of 68 (80.9%) in the piperacillin-tazobactam group were cured (odds ratio: 1.0 (95% confidence interval (CI): 0.4-2.4), P = 0.99). In both treatment groups, cure rates were higher in patients with monomicrobial than polymicrobial infections, but the difference was not significant. In this subgroup analysis of patients with MSSA complicated skin/skin structure infections, therapy with ertapenem 1 g daily was as effective as piperacillin-tazobactam 13.5 g divided in four daily doses.

Adolescent↗
PubMed2005

[Treatment of febrile neutropenia episodes in children, with a piperacillin-tazobactam and netilmicin combination].

OBJECTIVES: The authors had for aim to assess the effectiveness and toxicity of a piperacillin-tazobactam-netilmicin combination, and the possibility of avoiding using glycopeptide, in children with febrile neutropenic episodes induced by chemotherapy. METHODS: A retrospective study was made, including children treated for a febrile neutropenic episode (absolute neutrophile count < 0.5 x 10(9)/l) by a piperacillin-tazobactam-netilmicin combination. If fever persisted 48 hours after the beginning of antibiotic therapy, a glycopeptide could be added. The responses to the treatment were defined as follows: 1) total success (no fever or documented infection) at 48 hours and at 72 hours following the beginning of treatment; 2) partial success (apyrexia beyond 72 hours without any therapeutic change); 3) failure (persistent infectious signs 48 hours after the introduction of glycopeptide). RESULTS: Sixty-nine episodes were assessable, corresponding to 41 patients, treated for a solid tumour (29), an acute leukaemia in remission (11), or a metabolic disease (1). The febrile episodes were divided into fever of unknown origin (71%), microbiologically documented fever (12%), and clinically documented fever (17%). No death occurred, no toxicity was reported. With this antibiotic therapy, total success at 72 hours was observed in 72% in case of fever of unknown origin and 45% in case of documented infections. The success rate reached 84% when a glycopeptide was added (30% of the cases). CONCLUSION: The piperacillin-tazobactam-netilmicin combination is very effective and well tolerated in probabilistic treatment of febrile neutropenia induced by chemotherapy, but does not allow to decreasing the frequency of glycopeptide administration.

Adolescent↗
PubMed2004

Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies.

We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 through June 2003, 42 (19.3%) had > or =1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay.

Adolescent↗
PubMed2006

Knowledge, attitudes, and behaviors regarding piperacillin-tazobactam prescribing practices: results from a multicenter study.

We investigated knowledge, attitudes, and behaviors of prescribers concerning piperacillin-tazobactam use at 4 Emory University-affiliated hospitals. Discussions during focus groups indicated that the participants' perceived knowledge of clinical criteria for appropriate piperacillin-tazobactam use was inadequate. Retrospective review of medical records identified inappropriate practices. These findings have influenced ongoing interventions aimed at optimizing piperacillin-tazobactam use.

Anti-Bacterial Agents↗
PubMed2003

Cost analysis of continuous versus intermittent infusion of piperacillin-tazobactam: a time-motion study.

The time and associated costs (drug, labor, supply) of administering a continuous versus an intermittent i.v. infusion of piperacillin-tazobactam were compared. The total labor cost was calculated for each regimen based on the time required for nurses, pharmacists, and pharmacy technicians to either prepare or administer the drug, according to their standard responsibilities. Thirty timed observations were made for each of the dosing formulations. Observations were conducted on separate occasions for at least four different nurses, pharmacists, and pharmacy technicians per formulation. Labor costs were calculated by multiplying the mean times recorded by the average U.S. hourly wages and local wages for these health professionals and extrapolated to encompass a 24-hour period of drug administration. The average wholesale price and hospital contract price of piperacillin-tazobactam were used to calculate the costs of both intermittent and continuous infusions. The costs for all items used in drug preparation and administration were also calculated for supplies. Basic descriptive statistics were used to evaluate the costs of the time needed to prepare and administer the different regimens. Drug acquisition costs accounted for the largest percentage of the total cost for all regimens. Analysis of labor costs revealed that nursing time accounted for the majority of the labor costs, with continuous infusion regimens being the least time-consuming and least costly administration method. Continuous-infusion regimens were more cost-efficient when evaluated on a daily basis and for the total cost of 5- and 10-day treatments. The use of continuous infusion as a means of administering piperacillin-tazobactam maximized the drug's pharmacodynamics and was more cost-efficient than intermittent infusion of the drug.

Costs and Cost Analysis↗
PubMed2001

Pharmacokinetic and pharmacodynamic profile of high dose extended interval piperacillin-tazobactam.

A multiple-dose, open-labelled, randomized, two period crossover human volunteer study was performed (i) to describe the pharmacokinetic profile and safety profile of piperacillin and tazobactam (P/T) administered 6.0/0.75 g and 8.0/1.0 g q12h and (ii) to characterize the pharmacodynamic profile of these regimens against a variety of common targeted pathogens. Blood samples were collected after the third dose and concentrations of P/T were determined by a validated high-performance liquid chromatography assay. Pharmacokinetic profiles of P/T were determined by non-compartment analysis. Percentage time above the MIC (%T > MIC) of piperacillin was calculated for a range of MICs. In this study, no adverse events were attributed after multiple administrations of either 6.0/0.75 g or 8.0/1.0 g dose regimens. The peak concentration, half-life and area under the curve (AUC0-(0-tau)) of piperacillin were significantly different by a paired t-test (P < 0.05) between the two study regimens. The trough concentration, half-life and area under the curve (AUC0-(0-tau)) of tazobactam were substantially different from parameters reported previously for conventional regimens. The 8.0/1.0 g regimen provided 50% T > MIC for MICs < or =32 mg/L, while a similar value for the 6.0/0.75 g regimen was < or = 16 mg/L. High-dose P/T regimens with extended interval were well tolerated and provide adequate dynamic exposure for a variety of susceptible pathogens.

Adult↗
PubMed2004

Treatment of polymicrobial infections: post hoc analysis of three trials comparing ertapenem and piperacillin-tazobactam.

The efficacy of ertapenem 1 g once a day for the treatment of polymicrobial complicated intra-abdominal, complicated skin/skin-structure and acute pelvic infections was compared with piperacillin-tazobactam 3.375 g every 6 h in a post hoc analysis of data from three large randomized double-blind trials. Of the 1,558 treated patients in the three trials, no pathogen was identified in 345 (22.1%), 423 (27.2%) had a monomicrobial infection and 790 (50.7%) had a polymicrobial infection. At the test-of-cure assessment, there were no significant differences in outcome between the two treatment groups for any of the three infections. Cure rates (clinical and microbiological for intra-abdominal infection, clinical for skin/skin-structure and pelvic infections) in microbiologically evaluable patients for ertapenem and piperacillin-tazobactam, respectively, were 85.6% (154/180 evaluable patients) and 82.5% (127/154) for polymicrobial intra-abdominal infection, 80.3% (53/66) and 78.7% (48/61) for polymicrobial skin/skin-structure infection, and 95.7% (88/92) and 92.6% (88/95) for polymicrobial pelvic infection. Respective cure rates for all evaluable patients in the original trials were: 83.6% and 80.4% for intra-abdominal, 83.9% and 85.3% for skin/skin-structure, and 93.9% and 91.5% for pelvic infections. These data show that in the three trials, ertapenem 1 g once a day was highly effective for the treatment of polymicrobial infections and as effective as piperacillin-tazobactam 3.375 g every 6 h.

Abdomen↗
PubMed2006

Prospective drug utilization evaluation of three broad-spectrum antimicrobials: cefepime, piperacillin-tazobactam and meropenem.

BACKGROUND: Cefepime, piperacillin-tazobactam and meropenem are among the broadest-spectrum and most expensive antimicrobials. AIM: To evaluate guidelines for appropriate use of these drugs. METHODS: We developed guidelines for use of these antibiotics, and conducted a two-phase drug utilization evaluation. We included all patients who received one of the study drugs during two 3-month periods, with an educational intervention in the intervening period. Appropriateness was determined for initiation of treatment, and for adaptation or continuation of established treatment. RESULTS: Overall, 205 patients received 271 courses with one of these antibiotics, for a total of 709 defined daily doses (DDD) of cefepime, 543 of piperacillin-tazobactam, and 680 of meropenem (8.3, 6.3 and 7.9 DDD/1000 admission days, respectively). Of these 271 courses, 234 were appropriate (86%). Treatment was continued for > or =5 days in 60%, of which 88% were appropriate (NS). Of the 271 courses, 210 (77%) were empirical (83% appropriate), while 61 (23%) were based on a relevant culture result (97% appropriate) (p < 0.001). Appropriateness differed significantly between departments (p < 0.001), and between the two phases (p < 0.001). The major difference between the two surveys was a decrease in meropenem usage (p < 0.05). DISCUSSION: The vast majority of courses with cefepime, piperacillin-tazobactam and meropenem are empirically selected and continued, underlying the importance of an optimal initial choice. Antibiotic guidelines, in conjunction with formal infectious disease consultation, can contribute to more appropriate use of these drugs.

Anti-Bacterial Agents↗
PubMed2006

Randomized controlled trial of moxifloxacin compared with piperacillin-tazobactam and amoxicillin-clavulanate for the treatment of complicated intra-abdominal infections.

OBJECTIVE: To compare the safety and efficacy of sequential intravenous (IV) to oral (PO) moxifloxacin treatment against a standard antimicrobial regimen of IV piperacillin-tazobactam followed by PO amoxicillin-clavulanate for the treatment of adults with complicated intra-abdominal infection (cIAI). SUMMARY BACKGROUND DATA: cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy. METHODS: A prospective, double-blind, randomized, phase III comparative trial. Patients with cIAI were stratified by disease severity (APACHE II score) and randomized to either IV/PO moxifloxacin (400 mg q24 hours) or comparator (IV piperacillin-tazobactam [3.0/0.375 g q6 hours] +/- PO amoxicillin-clavulanate [800 mg/114 mg q12 hours]), each for 5 to 14 days. The primary efficacy variable was clinical cure rate at the test-of-cure visit (days 25-50). Bacteriologic outcomes were also determined. RESULTS: : Of 656 intent-to-treat patients, 379 (58%) were valid to assess efficacy (183 moxifloxacin, 196 comparator). Demographic and baseline medical characteristics were similar between the 2 groups. Clinical cure rates at test-of-cure were 80% (146 of 183) for moxifloxacin versus 78% (153 of 196) for comparator (95% confidence interval, -7.4%, 9.3%). The clinical cure rate at test-of-cure for hospital-acquired cIAI was higher with moxifloxacin (82%, 22 of 27) versus comparator (55%, 17 of 31; P = 0.05); rates were similar for community-acquired infections (80% [124 of 156] versus 82% [136 of 165], respectively). Bacterial eradication rates were 78% (117 of 150) with moxifloxacin versus 77% (126 of 163) in the comparator group (95% confidence interval, -9.9%, 8.7%). CONCLUSIONS: Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs.

Abdominal Abscess↗
PubMed2003

Pharmacokinetics-pharmacodynamics of cefepime and piperacillin-tazobactam against Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: report from the ARREST program.

The frequency of resistance to beta-lactams among nosocomial isolates has been increasing due to extended-spectrum beta-lactamase (ESBL)-producing enteric bacilli. Although clinical outcome data are desirable, assessment of clinical efficacy has been limited due to the lack of a statistically meaningful number of well-documented cases. Since time above the MIC (T>MIC) is the pharmacokinetic-pharmacodynamic (PK-PD) measure that best correlates with in vivo activity of beta-lactams, a stochastic model was used to predict the probability of PK-PD target attainment ranging from 30 (P30) to 70% (P70) T>MIC, for standard dosing regimens of both piperacillin-tazobactam and cefepime against Escherichia coli and Klebsiella pneumoniae ESBL phenotypes. The P70/30 T>MIC for cefepime at 2 g every 12 h against E. coli and K. pneumoniae was 0.99/1.0 and 0.96/1.0 and for a regimen of 1 g every 12 h was 0.96/1.0 and 0.93/0.99, respectively. For piperacillin-tazobactam at 3.375 g every 4 h against E. coli and K. pneumoniae, the P70/30 T>MIC was 0.77/0.96 and 0.48/0.77 and for a regimen of 3.375 g every 6 h was 0.28/0.91 and 0.16/0.69, respectively. These data suggest that the probability of achieving T>MIC target attainment rates is generally higher with cefepime than with piperacillin-tazobactam for present-day ESBL-producing strains when one uses contemporary dosing regimens.

Cefepime↗