title: Clinical Outcomes of Extended Versus Intermittent Infusion of Piperacillin/Tazobactam in Critically Ill Patients: A Prospective Clinical Trial.
abstract: To determine whether critically ill patients receiving extended-infusion (EI) piperacillin/tazobactam would have improved clinical outcomes compared with patients receiving intermittent infusions.
  
  
  
  Single-center, open-label, prospective study.
  
  
  
  Twenty-two-bed intensive care unit (ICU) in a regional hospital in Hong Kong.
  
  
  
  A total of 367 adults who had a diagnosis of either bacterial infection or neutropenic fever and had received treatment with piperacillin/tazobactam for at least 48 hours between December 1, 2013, and August 31, 2015.
  
  
  
  Patients were assigned to receive piperacillin/tazobactam as either a 4-hour EI (182 patients [EI group]) or a 30-minute intermittent infusion (185 patients [non-extended infusion (NEI) group]).
  
  
  
  All patients were followed for at least 14 days after treatment assignment. The primary outcome was the 14-day mortality rate after initiation of piperacillin/tazobactam. Secondary outcomes included in-hospital mortality rate, time to defervescence, duration of mechanical ventilatory support, length of ICU stay, and duration of hospital stay. Both groups demonstrated similar 14-day mortality (11.5% in the EI group vs 15.7% in the NEI group, p=0.29). The mean time to defervescence was significantly reduced in the EI group (4 days in the EI group vs 6 days in the NEI group, p=0.01); no significant differences between groups were noted in the other secondary outcomes. An Acute Physiology and Chronic Health Evaluation II score of 29.5 or higher was found to strongly predict 14-day mortality (p=0.03) by Classification and Regression Tree analysis. In the post hoc analyses, a 14-day mortality benefit was demonstrated in patients in the EI group in whom infectious organisms were identified (mortality rate 9.3% in the EI group vs 22.4% in the NEI group, p=0.01) and in whom respiratory tract infection was diagnosed (mortality rate 8.9% in the EI group vs 18.7% in the NEI group, p=0.02).
  
  
  
  Both the EI and NEI groups demonstrated similar 14-day mortality. Post hoc subgroup analysis revealed a mortality benefit in patients in the EI group who had infectious organisms identified or were diagnosed with respiratory tract infections.
authors.affiliation: Department of Pharmacy, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Sheung-Yin
authors.identifier: 0000-0003-1351-0934
authors.initials: SY
authors.lastname: Fan
authors.affiliation: Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Hoi-Ping
authors.identifier: 0000-0001-7002-3548
authors.initials: HP
authors.lastname: Shum
authors.affiliation: Department of Pharmacy, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Yat-Hei
authors.initials: YH
authors.lastname: Chan
authors.affiliation: Department of Pharmacy, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Sik-Yin McShirley
authors.initials: SM
authors.lastname: Leung
authors.affiliation: Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
authors.forename: Wing-Wa
authors.identifier: 0000-0003-1257-715X
authors.initials: WW
authors.lastname: Yan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: clinical outcome; extended infusion; intensive care; piperacillin-tazobactam; sepsis