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Table 2 Characteristics of studies comparing outcome for continuous versus intermittent administration of piperacillin

From: Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

Study Drug Patient population Dosage Study type Outcome measure Outcome Remarks
Grant 2002 [49] Piperacillin-tazobactam Hospitalized patients 12 g/d CI (n = 47) vs. 4 x 3 g/d II (n = 51) Prospective, open- label controlled study Clinical cure Microbiological cure Days to defervescence Level 1 costs Level 2 costs NS NS CI < II (p  = 0.012) NS CI < II (p  = 0.028)  
Lau 2006 [42] Piperacillin-tazobactam Complicated intra- abdominal infections 12 g/d CI (n = 130) vs. 4 x 3 g/d II (n = 132) RCT Clinical cure Mortality Adverse events NS NS NS  
*Rafati 2006 [16] Piperacillin Septic, critically ill patients 8 g/d CI (n = 20) vs. 4 x 3 g/d II (n = 20) RCT Mortality Rate of decrease APACHE II score Days to defervescence NS CI > II NS Lower antimicrobial dose in CI group
*Lodise 2007 [50] Piperacillin- tazobactam Pseudomonas aeruginosa infections, including both ICU patients (n = 126) and non-ICU patients (n = 68) 3 x 3.375 g/d in extended infusions of 4 h (n = 102) vs. 4 or 6 x 3.375 g/d II (n = 92) Retrospective cohort study 14-day mortality APACHE II < 17 APACHE II ≥ 17 Length of stay: APACHE II < 17 APACHE II ≥ 17 NSExtended infusion < II (p = 0,04) NSExtended infusion < II (p = 0,02) Lower antimicrobial dose in extended infusion group Significant outcome differences only in subpopulation with high severity of illness (APACHE II ≥ 17)
*Lorente 2009 [51] Piperacillin- tazobactam (+ tobramycin 7 mg/kg/d) VAP 16 g/d CI (n = 37) vs. 4 x 4 g/d II (n = 46) Retrospective cohort study Clinical cure: MIC = 4 μg/ml MIC = 8 μg/ml MIC = 16 μg/ml NSCI > II(p  = 0.02) CI > II(p  = 0.02) Significant outcome differences only in infections caused by pathogens with high MICs
  1. *Studies that included critically ill, ICU patients.
  2. NS = nonsignificant; MIC = minimal inhibitory concentration; CI = continuous infusion; II = intermittent infusion; APACHE II = Acute Physiology and Chronic Health Evaluation; VAP = ventilator-associated pneumonia; RCT = randomized, controlled trial; ICU = intensive care unit.