Table 1 Characteristics of included studies
No. | First author, year | Country | Design | Double blinding | Number of study participants, total (P vs I) | Age, P vs I, median | APACHEII, P vs I, median | Sepsis definition or type of infection | Organism | Antibiotics | Prolonged infusion | Intermittent infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Angus, 2000 | Thailand | RCT | NR | 21 (10 vs 11) | 43 vs 48 | 21 vs 15 | Septic melioidosis | Only Gram-negative | β-Lactam (unknown in detail) | 12 mg/kg loading dose, followed by 4 mg/kg/h by constant rate infusion | 40 mg/kg every 8 h, intermittent bolus injection |
2 | Nicolau, 2001 | USA | RCT | No | 35 (17 vs 18) | 46 vs 56 (mean) | 13.9 vs 15.5 (mean) | Nosocomial pneumonia | Mostly Gram-negative | β-Lactam (ceftazidime) plus tobramycin | Ceftazidime, 3 g/day, continuously; tobramycin, 7 mg/kg/day | Ceftazidime: 2 g, over 30 min, every 8 h; tobramycin, 7 mg/kg/day |
3 | Georges, 2005 | France | RCT | No | 50 (26 vs 24) | 50 vs 46 (mean) | a45 vs 44 (aSAPS II, median) | Nosocomial pneumonia or bacteremia | Mostly Gram-negative | β-Lactam (cefepime) plus amikacin | Cefepime, 4 g/day, continuously; amikacin, 20 mg/kg loading dose, followed by 15 mg/kg/day | Cefepime, 2 g, over 30 min, twice daily; amikacin: 20 mg/kg loading dose, followed by 15 mg/kg/day |
4 | Rafati, 2006 | Iran | RCT | NR | 40 (20 vs 20) | 50.1 vs 48.0 (mean) | 16.4 vs 14.2 (mean) | Septic patients with SIRS (Sepsis-2) | Only Gram-negative | β-Lactam (piperacillin) plus amikacin | Piperacillin, 2 g loading dose, followed by 8 g/day, continuously; amikacin, 15 mg/kg/day | Piperacillin, 3 g, over 30 min, every 6 h; amikacin, 15 mg/kg/day |
5 | Lau, 2006 | USA | RCT | No | 258 (128 vs 130) | 51.5 vs 48.0 | 7 vs 7 | Complicated intra-abdominal infections | Gram-negative and Gram-positive | β-Lactam (piperacillin–tazobactam) | 2.25 g loading dose, followed by 13.5 g/day, continuously | 3.375 g, over 30 min, every 6 h |
6 | Roberts, 2007 | Australia | RCT | No | 57 (29 vs 28) | 41 vs 56 | 20 vs 17 | Sepsis (SIRS criteria) | Mixed | β-Lactam (ceftriaxone) | Continuous infusion, 2 g/day | Intermittent bolus, 2 g every 24 h |
7 | Roberts and Kirkpatrick, 2009 | Australia | RCT | No | 10 (5 vs 5) | 57 vs 55 | a5 vs 3 (aSOFA, median) | Sepsis (SIRS criteria) | Only Gram-negative | β-Lactam (meropenem) | Continuous infusion, 3 g/day | Intermittent bolus, 1 g every 8 h |
8 | Chytra, 2012 | Czech Republic | RCT | No | 214 (106 vs 108) | 44.9 vs 47.2 (mean) | 21.4 vs 22.1 (mean) | Sepsis (Sepsis-2) | Mostly Gram-negative | β-Lactam (meropenem) | Continuous infusion, loading dose 2 g; 4 g every 24 h | 30 min; 2 g every 8 h |
9 | Dulhunty, 2013 | Australia, Hong Kong | RCT | Yes | 60 (30 vs 30) | 54 vs 60 (mean) | 21 vs 23 (mean) | Severe sepsis (Sepsis-2) | Mixed | β-Lactam (piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem) | Continuous infusion, clinician chosen from piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem | Intermittent bolus, clinician chosen from piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem |
10 | Dulhunty, 2015 | Australia, New Zealand, Hong Kong | RCT | Yes | 432 (212 vs 220) | 64 vs 65 | 21 vs 20 | Severe sepsis (Sepsis-2) | Mixed | β-Lactam (piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem) | Continuous infusion clinician chosen from piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem | Intermittent bolus clinician chosen from piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem |
11 | Laterre, 2015 | Belgium | RCT | NR | 28 (14 vs 14) | 68 vs 65 | 17 vs 16 | Pulmonary or abdominal infection in ICU | Mostly Gram-negative | β-Lactam (temocillin) | Loading dose (2 g) administered over 30 min in 50 mL of water for injection followed by infusion (6 g in 48 mL of water for injection infused at a rate of 2 mL/h) | 2 g of temocillin (in 50 mL of water for injection) every 8 h injected over a 30 min period |
12 | Abdul, 2016 | Malaysia | RCT | No | 140 (70 vs 70) | 54vs 56 | 21 vs 21 | Severe sepsis (Sepsis-2) | Mostly Gram-negative | β-Lactam (cefepime, meropenem or piperacillin/tazobactam) | aContinuous infusion | bIntermittent bolus |
13 | Zhao, 2017 | China | RCT | No | 50 (25 vs 25) | 68 vs 67 | 19.4 vs 19.7 | Severe sepsis and septic shock (Sepsis-2) | Only Gram-negative | β-Lactam (meropenem) | Loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day | Initial dose of 1.5 g followed by 1 g for every 8 h |