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Table 1 Characteristics of selected studies for meta-analysis

From: Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

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

 

47

Cefepime

2 g q12h

4 g/d as CI

Hanes (2000) USA [13]

T

RCT

Nosocomial pneumonia

12

 

Ceftazidime

2 g q8h (0.5-h infusion)

LD, 2 g (0.5-h infusion), then 60 mg/kg/day as CI

Nicolau (2001) USA [14]

MS, N

RCT

VAP

15

 

Ceftazidime

2 g q8h (0.5-h infusion)

No LD 3 g over 24 h as CI

Wysocki (2001) France [15]

MS

RCT

Any methicillin-resistant staphylococcal infections

 

b

Vancomycin

15 mg/kg q12h (1-h infusion)

LD, 15 mg/kg over 1 h, then 30 mg/kg as CI

Bujik (2002) Netherlands [16]

S

RCT (partial)

Severe intraabdominal infection

15

 

Ceftazidime

1.5 g tid (20-min infusion)

LD, 1 g over 20 min, then 4.5 g/d as CI

Georges (2005) France [17]

M, T

RCT

Nosocomial pneumonia or bacteremia

 

45

Cefepime

2 g q12h (0.5-h infusion)

No LD; 4 g CI

Rafati (2006) Iran [18]

General

RCT

Sepsis from any source

15

 

Piperacillin alone

3 g q6h (0.5-h infusion)

LD, 2 g over 0.5 h, then 8 g/24 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

1 g q8h (40-min infusion)

LD, 1 g over 40 min, then 2 g/24 hr as CI for 3 days, then 1 g q8h over 40 min

Adembri (2008) Italy [21]

M, T

RCT

Sepsis; glycopeptide resistant or failure

 

45

Linezolid

600 mg q12h (0.5-h infusion)

LD, 300 mg, Day 1: 900 mg CI, Day 2 onward: 1,200 mg CI

Wang (2009) China [32]

NR

RCT

Acinetobacter pneumonia

19

 

Meropenem

1 g q8h (1-h infusion)

500 mg q6h as 3-h EI

Chytra (2012) Czech [22]

M

RCT

Severe infection from any source

22

 

Meropenem

2 g q8h (0.5-h infusion)

LD, 2 g over 0.5 h, then 4 g/d as CI

Dulhunty (2012) Australia [29]

NR

RCT

Severe sepsis

22

 

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

 

Meropenem

1 g q6h (0.5-h infusion)

LD, 1 g over 0.5 h, then 1 g q6h as CI

Itabashi (2007) Japan [33]

NR

Cohort

Gram-negative pneumonia

NR

 

Meropenem

500 mg q12h (0.5- to 1-h infusion)

500 mg q12 as 4-h EI

Lodise (2007) USA [25]

NR

Cohort

Pseudomonal infections of any source

16

 

Piperacilin/tazobactam

3.375 g q4 or 6 h

3.375 g q8h as 4-h EI

Lorente (2007) Spain [26]

MS

Cohort

VAP with gram-negative bacilli

16

 

Ceftazidime

2 g q12h (0.5-h infusion)

LD, 1 g over 0.5 h, then 2 g q12h as CI

Lorente (2009) Spain [31]

MS

Cohort

VAP with gram-negative bacilli

16

 

Piperacillin/tazobactam

4.5 g q6h (0.5-h infusion)

LD, 4.5 g over 0.5 h, then 4.5 g q6h as CI

Nicasio (2010) USA [27]

MS, N

Cohort

VAP

19

 

Cefepime, or meropenem

MD discretion (0.5 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

 

Piperacillin/tazobactam, or meropenem

P/T 3.375 g q6h or Meropenem 500 mg q6h (0.5-h infusions)

P/T 3.375 g q8h as 4 h EI, Meropenem 500 mg q6h as 3-h EI

Yost (2011) USA [28]

NR

Cohort

Any gram-negative infection

~14c

 

Piperacillin/tazobactam

Variable nonextended infusions of piperacillin/tazobactam, cefepime, ceftazidime, imipenem, meropenem, doripenem

3.375 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

 

Piperacillin/tazobactam

2.25-4.5 g q6-8 h (0.5-h infusion)

3.375 g q8h as 4-h EI

Arnold (2013) USA [36]

NR

Cohort

Gram-negative infections

20

 

Cefepime, meropenem, or piperacillin/tazobactam

Cefepime 2 g q8h, meropenem 1 g q8h, piperacillin-tazobactam 4.5 g q6h (0.5-h infusions)

Same dose/medications as 3-h infusions

Hsaiky (2013) USA [37]

NR

Cohort

Gram-negative infections

16

 

Doripenem

0.5 g q8h (1-h infusion)

0.5 g q8h (4-h infusion)

  1. M, mixed; MS, medical surgical; T, trauma; C, coronary; CV, cardiovascular; N, neurosurgical; NR, not reported. aPiperacillin/tazobactam used as 24 h infusions in control group and not used in the intervention group. bOnly mean SAPS score [86] equal to 14 provided.
  2. cOnly midpoint of range provided.
  3. dMedian SOFA [87] score of 9.
  4. APACHE II, mean or median acute physiology and chronic health evaluation II score of enrolled patients [88]; CI, continuous infusion; EI, extended infusion; LD, loading dose; MIC, minimum inhibitory concentration; PD, pharmacodynamic; PCK, pharmacokinetic; RCT, randomized controlled trial; SAPS II, mean or median simplified acute physiology score II score of enrolled patients [89]; SOFA, sequential organ failure assessment score [87]; VAP, ventilator-associated pneumonia.