None listed
Conditions
Brief summary
Antibiotic resistance and its associated increasing mortality are ever-growing problems in Hong Kong. Infectious Diseases Society of America stated that the optimization of the antimicrobial dosing, based on pharmacokinetic (PK) and pharmacodynamic (PD) characteristics, was an important part of antibiotic stewardship . In view of the growing need to fight against resistant pathogens, piperacillin-tazobactam (Pip-Tazo) extended 4-hour infusion has been catching worldwide attention in the past few years. Piperacillin-Tazobactam is a widely use broad-spectrum beta-lactam antibiotic in hospitals in Hong Kong for the treatment of bacterial infections. The bactericidal effect of Pip-Tazo is maximized by maintaining the free drug concentration (Cf) above the minimum inhibitory concentration (MIC) for greater than fifty percent of time (T) . PK and PD studies carried out in the past decade on Pip-Tazo’s time-dependent killing (50% CfT>MIC) property had revealed that by extending its infusion time from 30 minutes to 4 hours, the probability of attaining the target (50% CfT>MIC) was highly increased for pathogens with MIC greater than 1mcg/ml , . Further studies had lent support to the clinical efficacy of Pip-Tazo extended infusion. A retrospective cohort study had shown that the 14-day mortality rate and median duration of hospital stay were significantly reduced for patients who received extended 4-hour infusion of Pip-Tazo compared to those who received intermittent 30-minute infusion for patients with Acute Physiological and Chronic Health Evaluation–II (APACHE II) scores greater than 173. Another retrospective study had also demonstrated significant mortality reduction for extended 4-hour infusion of Pip-Tazo . To the knowledge of the investigators, there had not been any prospective clinical trial studies carried out on Chinese population on the clinical outcomes of extended 4-hour infusion of Pip-Tazo in comparison to traditional non-extended 30-minute infusion of piperacillin-tazobactam. It had been expected that the patients receiving extended 4-hour infusion of Pip-Tazo would have a lower 14-day and in-hospital mortality rate, shorter time to defervescence, shorter number of days receiving mechanical ventilator support and length of ICU and hospital stay in comparison to the traditional 30-minute infusion. The results of this research may guide the future dosing strategy of Pip-Tazo.
Interventions
Intervention group would receive extended 4-hour intravenous infusion of Piperacillin-Tazobactam. Piperacillin-Tazobactam extended 4-hour infusion would be dosed according to renal function.
Creatinine clearance (estimated by Cockcroft Gault equation) >/= 20ml/min: 4.5gram every 8 hours
Creatinine clearance (estimated by Cockcroft Gault equation) < 20ml/min: 4.5gram every 12 hours
Participants would receive the extended 4-hour intravenous infusion of Piperacillin-Tazobactam after treatment assi
Intervention group would receive extended 4-hour intravenous infusion of Piperacillin-Tazobactam. Piperacillin-Tazobactam extended 4-hour infusion would be dosed according to renal function. Creatinine clearance (estimated by Cockcroft Gault equation) >/= 20ml/min: 4.5gram every 8 hours Creatinine clearance (estimated by Cockcroft Gault equation) < 20ml/min: 4.5gram every 12 hours Participants would receive the extended 4-hour intravenous infusion of Piperacillin-Tazobactam after treatment assignment until Piperacillin-Tazobactam was decided to be discontinued by attending physician according to clinical condition and culture sensitivity results.
Sponsors
Fan Sheung Yin
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients were eligible if they were aged 18 years or older; were hospitalized in an acute medical unit or intensive care unit; either had received a diagnosis of bacterial infection or suffered from neutropenic fever; planned to receive treatment of Piperacillin-Tazobactam for at least 48 hours.
Exclusion criteria
Patients would be excluded if they are pregnant, had received more than 48 hours of effective antibiotics, as defined by specimen culture sensitivity results, within five days of initiation of extended 4-hour infusion or traditional 30-minute infusions of Piperacillin-Tazobactam; had been receiving other beta-lactam antibiotics concomitantly.
Outcome results
None listed