Optimizing Dosing Regimen of Piperacillin/Tazobactam for Nosocomial Pneumonia

Phase 2

• Conditions: Nosocomial Pneumonia
• Interventions: Drug: E Group; Drug: C Group

• Registration Number: NCT01796717
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2012-03
• Status Verified: 2012-08
• Study First Submitted: 2012-08-30
• Study First Submitted QC: 2013-02-19
• Study First Posted: 2013-02-22
• Last Update Submitted: 2016-02-14
• Last Update Posted: 2016-02-17
• Primary Completion: 2016-11
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E Group	E Group	Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours
C Group	C Group	Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

TianjinCIH; 🇨🇳 Tianjin, Tianjin, China