Optimizing Dosing Regimen of Piperacillin/Tazobactam for Nosocomial Pneumonia

Optimizing Dosing Regimen of Piperacillin/Tazobactam, Prolonged Infusion vs. Regular Infusion, Every 6 Hours, for Nosocomial Pneumonia in ICU Caused by Susceptible Pathogens With Higher MIC

1. To observe clinical and bacteriologic responses of different regimens of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) for treatment of nosocomial pneumonia.
2. To describe the pharmacokinetic profile of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) in patients with nosocomial pneumonia.
3. To assess the safety profiles of piperacillin/tazobactam 4.5g q6h, prolonged or intermittent infusion in patients with nosocomial pneumonia.

Study Overview

• Status: Unknown
• Conditions: Nosocomial Pneumonia
• Intervention / Treatment: Drug: C Group; Drug: E Group

Detailed Description

Enrolled patients will be randomized into therapeutic or controlled group. Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes. Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours. The duration is 7-14 days.

Two sets of blood cultures (for aerobic and anaerobic culture) were obtained before the study and post-treatment period if first blood culture is positive. Cultures from the lower respiratory tract infection were obtained before (within 48 h) the study and on the last day of therapy. The lower respiratory tract specimens obtained either by endotracheal aspiration, bronchoalveolar lavage (BAL), a protected brush procedure (PBP) or as sputum were required to show > 25 polymorphonuclear cells and < 10 squamous epithelial cells per field (at 100× magnification).

The plasma concentration of piperacillin and tazobactam will be determined by LC/MS/MS method. The QC samples will also be analyzed simultaneously with each run for the method stability testing, according to the laboratory standard procedure.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Wang Donghao, Chief; Phone Number: 1021 022-23340123; Email: donghaow@medmail.com.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • TianjinCIH
      • Contact: Wang Donghao, Chief; Phone Number: 1021 022-23340123; Email: donghaow@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, aged 18 to 70 years old.

2. Inpatients with nosocomial pneumonia or bacteremia.

   i. Diagnosis of nosocomial pneumonia

   1. Chest radiographic infiltrate that is new or progressive.

   2. At least two or more of the following clinical findings suggesting infection.

      • New onset of fever, oral temperature T>38.3℃ or T<36℃

        • Purulent sputum

          • WBC > 12×10^9/L or <4×10^9/L, or band form >10%

            • PaO2/FIO2<240mmHg

   ii. Diagnosis of bacteremia: Positive blood culture and the isolated bacterial strain are considered to be infection cause.

3. Patients are infected by piperacillin-tazobactam susceptible pathogen with MIC=4, 8 or 16mg/L.

Exclusion Criteria:

1. The patients who received systematic antibacterial treatment more than 48 hours before enrollment and have clinical response.
2. Severe pyemia with hypotension or/and evidences of failure of organic function (shock: systolic pressure < 90mmHg or diastolic pressure < 60mmHg, requiring more than 4 hours of administration of vasopressor(s)；renal impairment: urine volume < 20 ml∕h or < 80 ml∕4h after excluded any other potentials, acute renal failure need dialysis, CLcr<40 mL/min).
3. Documented infection caused by pathogens beyond the antibacterial spectrum of piperacillin/tazobactam.
4. Previously diagnosed condition which tend to mimic or complicate the course and evaluation of the infectious process, e.g. bronchial obstruction, obstructive pneumonia, activate pulmonary malignancy, pulmonary abscess, empyema and active tuberculosis, which might interfere the course of the infectious disease and evaluation of the disease.
5. History of allergy to penicillins.
6. Pregnancy or breast-feeding women.
7. Any conditions investigator considered might increase the risk of patients or interfere study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: C Group; Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes	Drug: C Group; Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes; Other Names: nosocomial pneumonia; MIC
Experimental: E Group; Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours	Drug: E Group; Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours; Other Names: nosocomial pneumonia; MIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extension of the Piperacillin / tazobactam infusion time effect evaluation	To observe clinical and bacteriologic responses of different regimens of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) for treatment of nosocomial pneumonia.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reducing antibiotic resistance	To describe the pharmacokinetic profile of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) in patients with nosocomial pneumonia.	2 weeks

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Pfizer
• Investigators: Study Chair: Wang Donghao, Chief, Tianjin Medical University Cancer Institute and Hospital

Publications and helpful links

General Publications

• Roberts JA, Kirkpatrick CM, Roberts MS, Dalley AJ, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents. 2010 Feb;35(2):156-63. doi: 10.1016/j.ijantimicag.2009.10.008. Epub 2009 Dec 16.
• Wang H, Chen M, Ni Y, Liu Y, Sun H, Yu Y, Yu X, Mei Y, Liu M, Sun Z, Chu Y, Hu Z, Huang X. Antimicrobial resistance among clinical isolates from the Chinese Meropenem Surveillance Study (CMSS), 2003-2008. Int J Antimicrob Agents. 2010 Mar;35(3):227-34. doi: 10.1016/j.ijantimicag.2009.11.010. Epub 2010 Jan 4.
• Lorente L, Jimenez A, Martin MM, Iribarren JL, Jimenez JJ, Mora ML. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents. 2009 May;33(5):464-8. doi: 10.1016/j.ijantimicag.2008.10.025. Epub 2009 Jan 15.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: February 19, 2013
• First Posted (Estimate): February 22, 2013

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 14, 2016
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Piperacillin/tazobactam; MIC
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia
• Other Study ID Numbers: CIH-WDH-201205001