Piperacillin-Tazobactam Infusion Methods for Infections in Obesity

Overseen By Benoît Crevier, PharmD., MSc., BCCCP

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: CR-CSSS Champlain-Charles-Le Moyne

Must be taking: Piperacillin-tazobactam

Must not be taking: Antiepileptic drugs

Disqualifiers: Renal therapy, Pregnancy, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 42 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of administering piperacillin-tazobactam, an antibiotic, to individuals with obesity who have infections. Researchers aim to determine if a slow infusion (over a few hours) is more effective than a quick one (over 30 minutes) in fighting infections. The trial seeks participants who are hospitalized, have a body mass index (BMI) of 30 or more, and began this medication within the last 24 hours. Eligible participants must not be on dialysis or allergic to penicillin. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment benefits a broader range of patients.

Do I need to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for seizures or epilepsy, you may not be eligible to participate.

What is the safety track record for piperacillin-tazobactam?

Research has shown that piperacillin-tazobactam is generally safe to use. Studies have found that administering it as a prolonged infusion (a slower, extended method of delivering the drug) can be beneficial. One study linked this method to a lower risk of death within 14 days and fewer cases of C. difficile infections, which are serious gut infections.

Previous studies have safely used even high doses of piperacillin-tazobactam in critically ill obese patients. Serious side effects were uncommon, indicating acceptable safety. However, the dose must be carefully adjusted in obese patients to avoid harmful levels of medication or treatment failure.

Overall, evidence supports that piperacillin-tazobactam, whether given quickly or slowly, is well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores different infusion methods of piperacillin-tazobactam, an antibiotic commonly used to treat infections, especially in people with obesity. Unlike the standard 30-minute infusion, this trial examines prolonged infusion over 3 to 4 hours, which could potentially enhance the drug's effectiveness by maintaining higher concentrations in the body for a longer period. This approach might optimize treatment outcomes and reduce the risk of antibiotic resistance, offering a promising alternative to current practices.

What evidence suggests that this trial's infusion methods for piperacillin-tazobactam could be effective for infections in obesity?

Research has shown that piperacillin-tazobactam effectively treats infections. For adults with anaerobic infections, about 85% of those treated with this antibiotic combination were cured. Studies indicate that it works equally well for both obese and non-obese patients. The treatment's effectiveness depends on how long the drug remains in the body, making dose timing crucial, especially for obese individuals. In this trial, one group will receive piperacillin-tazobactam through a prolonged infusion, which might optimize its effectiveness for these patients. Another group will receive the drug via a standard infusion, allowing for a comparison of the two methods. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with obesity who may have infections. It's designed to see if a longer infusion of the antibiotic piperacillin-tazobactam works better than the standard way it's given. Participants must meet certain health criteria, but specific inclusion and exclusion details are not provided.

Inclusion Criteria

My BMI is 30 or higher.

Patients hospitalized at Hôpital Charles-Le Moyne

I am scheduled for a treatment with piperacillin-tazobactam for at least 24 hours.

Exclusion Criteria

I am on dialysis or other kidney replacement therapy.

Pregnancy

Documented allergy to beta-lactams of the penicillin class

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 24 hours

Treatment

Participants receive piperacillin-tazobactam administered as either a prolonged intermittent infusion or a standard infusion

Up to 42 days

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Piperacillin-Tazobactam

Trial Overview The study tests whether administering piperacillin-tazobactam as a prolonged infusion is more effective in patients with obesity compared to the standard short-term infusion method. The goal is to maintain effective drug levels in the body for fighting infection.

How Is the Trial Designed?

Group I: Piperacillin-tazobactam administered in a prolonged infusion Experimental Treatment 1 Intervention

Piperacillin-tazobactam dose will be administered over 3 hours for piperacillin-tazobactam dosages every 6 hours or over 4 hours for piperacillin-tazobactam dosages every 8 hours.

Group II: Piperacillin-tazobactam administered in a standard infusion Active Control 1 Intervention

Piperacillin-tazobactam dose will be administered over 30 minutes for every piperacilline-tazobactam administered in the study (as instructed by the drug's monograph)

Who Is Running the Clinical Trial?

CR-CSSS Champlain-Charles-Le Moyne

Lead Sponsor

Trials

7

Recruited

510+

Citations

1. med.stanford.edu med.stanford.edu/content/dam/sm/bugsanddrugs/documents/antimicrobial-dosing-protocols/SHC-ABX-Obesity-Dosing-Guide.pdf

SHC-ABX-Obesity-Dosing-Guide.pdf Higher dosing not recommended without TDM. patients treated with 500mg q12-8h for anaerobic or mixed anaerobic infections resulted in 85% clinical cure rates, ...

2. academic.oup.com academic.oup.com/ofid/article/6/10/ofz400/5571767

Open Forum Infectious Diseases | Oxford Academic Clinical cure was achieved in 68.4% of obese and 62.4% of nonobese patients (P = .458). No significant difference in outcomes was observed when ...

3. journals.asm.org journals.asm.org/doi/10.1128/aac.01276-16

Population Pharmacokinetics of Piperacillin in Nonobese ... Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese.

4. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/08971900251319072

A Retrospective Study Evaluating the Safety and Clinical ... Background: Piperacillin-tazobactam (PTZ) demonstrates time-dependent bactericidal activity, potentially increasing the need for higher dosing in obese and ...

5. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2842

International consensus recommendations for the use of ... Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2772431X23000059

Impact of extended-infusion piperacillin-tazobactam in a ... Our study showed extended infusion piperacillin/tazobactam to be associated with a lower risk of 14-day mortality, lower incidence of C. difficile infections ...

7. journals.asm.org journals.asm.org/doi/10.1128/aac.01719-23

Updated antimicrobial dosing recommendations for obese ... Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8093170/

Pharmacokinetics and Pharmacodynamics of High-Dose ... The pharmacokinetics, pharmacodynamics, and safety of piperacillin–tazobactam doses up to 9 g every 6 h were evaluated in obese adults. Some patients required ...