Author (year) Country | Type of ICUa | Study design | Infection | Illness acuity | Study antibiotic | Control group | Intervention group | |
---|---|---|---|---|---|---|---|---|
 |  |  |  | APACHE II | SAPS II |  |  |  |
Randomized controlled trials | ||||||||
Georges (1999) France [12] | NR | RCT | Pneumonia or bacteremia with gram-negative bacilli | Â | 47 | Cefepime | 2Â g q12h | 4Â g/d as CI |
Hanes (2000) USA [13] | T | RCT | Nosocomial pneumonia | 12 | Â | Ceftazidime | 2Â g q8h (0.5-h infusion) | LD, 2Â g (0.5-h infusion), then 60Â mg/kg/day as CI |
Nicolau (2001) USA [14] | MS, N | RCT | VAP | 15 | Â | Ceftazidime | 2Â g q8h (0.5-h infusion) | No LD 3Â g over 24Â h as CI |
Wysocki (2001) France [15] | MS | RCT | Any methicillin-resistant staphylococcal infections | Â | b | Vancomycin | 15Â mg/kg q12h (1-h infusion) | LD, 15Â mg/kg over 1Â h, then 30Â mg/kg as CI |
Bujik (2002) Netherlands [16] | S | RCT (partial) | Severe intraabdominal infection | 15 | Â | Ceftazidime | 1.5Â g tid (20-min infusion) | LD, 1Â g over 20Â min, then 4.5Â g/d as CI |
Georges (2005) France [17] | M, T | RCT | Nosocomial pneumonia or bacteremia | Â | 45 | Cefepime | 2Â g q12h (0.5-h infusion) | No LD; 4Â g CI |
Rafati (2006) Iran [18] | General | RCT | Sepsis from any source | 15 | Â | Piperacillin alone | 3Â g q6h (0.5-h infusion) | LD, 2Â g over 0.5Â h, then 8Â g/24Â h as CI |
Roberts (2007) Australia [19] | General | RCT | Sepsis from any source | 18 |  | Ceftriaxone | LD = 500 mg, then 2 g q24h | LD, 500 mg, then 2 g/24 h as CI |
Sakka (2007) Germany [20] | NR | RCT | Nosocomial pneumonia | 27 | 44 | Imipenem | 1Â g q8h (40-min infusion) | LD, 1Â g over 40Â min, then 2Â g/24Â hr as CI for 3Â days, then 1Â g q8h over 40Â min |
Adembri (2008) Italy [21] | M, T | RCT | Sepsis; glycopeptide resistant or failure | Â | 45 | Linezolid | 600Â mg q12h (0.5-h infusion) | LD, 300Â mg, Day 1: 900Â mg CI, Day 2 onward: 1,200Â mg CI |
Wang (2009) China [32] | NR | RCT | Acinetobacter pneumonia | 19 | Â | Meropenem | 1Â g q8h (1-h infusion) | 500Â mg q6h as 3-h EI |
Chytra (2012) Czech [22] | M | RCT | Severe infection from any source | 22 | Â | Meropenem | 2Â g q8h (0.5-h infusion) | LD, 2Â g over 0.5Â h, then 4Â g/d as CI |
Dulhunty (2012) Australia [29] | NR | RCT | Severe sepsis | 22 | Â | Ticarcillin/clavulanate, piperacillin/tazobactam, or meropenem | Dose determined by MD | Dose determined by MD |
All as intermittent infusion | All as CI | |||||||
Cohort studies | ||||||||
Schentag (1984) USA [23] | NR | Cohort | Gram-negative nosocomial pneumonia | NR |  | Cefmenoxime | Fixed dose 1–2 g q6-8 h | Integration of patient-specific PCK with bacteria-specific killing kinetics (doses ranged from 0.5 g q8h to 2 g q4h) |
Lorente (2006) Spain [24] | MS | Cohort | VAP with gram-negative bacilli | 15 | Â | Meropenem | 1Â g q6h (0.5-h infusion) | LD, 1Â g over 0.5Â h, then 1Â g q6h as CI |
Itabashi (2007) Japan [33] | NR | Cohort | Gram-negative pneumonia | NR | Â | Meropenem | 500Â mg q12h (0.5- to 1-h infusion) | 500Â mg q12 as 4-h EI |
Lodise (2007) USA [25] | NR | Cohort | Pseudomonal infections of any source | 16 | Â | Piperacilin/tazobactam | 3.375Â g q4 or 6Â h | 3.375Â g q8h as 4-h EI |
Lorente (2007) Spain [26] | MS | Cohort | VAP with gram-negative bacilli | 16 | Â | Ceftazidime | 2Â g q12h (0.5-h infusion) | LD, 1Â g over 0.5Â h, then 2Â g q12h as CI |
Lorente (2009) Spain [31] | MS | Cohort | VAP with gram-negative bacilli | 16 | Â | Piperacillin/tazobactam | 4.5Â g q6h (0.5-h infusion) | LD, 4.5Â g over 0.5Â h, then 4.5Â g q6h as CI |
Nicasio (2010) USA [27] | MS, N | Cohort | VAP | 19 | Â | Cefepime, or meropenem | MD discretion (0.5Â h-infusions)a | VAP pathway derived by local MICs and PD analysis using Monte Carlo simulations (3-h infusions) |
Dow (2011) USA [30] | MS | Cohort | Any infection except CF | 25 | Â | Piperacillin/tazobactam, or meropenem | P/T 3.375Â g q6h or Meropenem 500Â mg q6h (0.5-h infusions) | P/T 3.375Â g q8h as 4Â h EI, Meropenem 500Â mg q6h as 3-h EI |
Yost (2011) USA [28] | NR | Cohort | Any gram-negative infection | ~14c | Â | Piperacillin/tazobactam | Variable nonextended infusions of piperacillin/tazobactam, cefepime, ceftazidime, imipenem, meropenem, doripenem | 3.375Â g q8h as 4-h EI |
Akers (2012) USA [34] | Burn | Cohort | Gram-positive bacteremia | NR |  | Vancomycin | 1 g q8h (dose adjustment to achieve trough levels 15–20 μg/ml) | 3 g as CI (dose adjustment to achieve steady-state levels 20–25 μg/ml) |
Lee (2012) USA [35] | NR | Cohort | Gram-negative infections | NRd | Â | Piperacillin/tazobactam | 2.25-4.5Â g q6-8Â h (0.5-h infusion) | 3.375Â g q8h as 4-h EI |
Arnold (2013) USA [36] | NR | Cohort | Gram-negative infections | 20 | Â | Cefepime, meropenem, or piperacillin/tazobactam | Cefepime 2Â g q8h, meropenem 1Â g q8h, piperacillin-tazobactam 4.5Â g q6h (0.5-h infusions) | Same dose/medications as 3-h infusions |
Hsaiky (2013) USA [37] | NR | Cohort | Gram-negative infections | 16 | Â | Doripenem | 0.5Â g q8h (1-h infusion) | 0.5Â g q8h (4-h infusion) |