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Table 3 Antimicrobial agents for the treatment of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii infections in critically ill patients: MIC breakpoints (European Committee of Antimicrobial Susceptibility Testing, guidelines 2015) and first-line daily doses

From: Mechanisms of antimicrobial resistance in Gram-negative bacilli

Antimicrobial agent MIC breakpoint (mg/L) for susceptibility Usual daily dosea (intra-venous) Comment
Enterobacteriaceae P. aeruginosa A. baumannii
Piperacillin ≤8 ≤16 ND 4 g/6 h Consider extended or continuous infusion after a LD
Piperacillin–tazobactam ≤8 ≤16 ND 4 g–500 mg/6 h Consider extended or continuous infusion after a LD
Aztreonam ≤1 ≤1 IR 2 g/6–8 h Consider extended or continuous infusion after a LD
Ceftazidime ≤1 ≤8 ND 2 g/6–8 h Consider extended or continuous infusion after a LD
Cefepime ≤1 ≤8 ND 1–2 g/8 h Consider extended or continuous infusion after a LD
High doses for P. aeruginosa infections
Ertapenem ≤0.5 IR IR 2 gr/24 h Once-daily administration
Meropenem ≤2 ≤2 ≤ 2 1–2 g/8 h Consider extended infusion after a LD
Imipenem ≤2 ≤4 ≤ 2 1 g/6–8 h No extended infusion (instability)
Gentamicin ≤2 ≤4 ≤ 4 6–8 mg/kg/24 h Once-daily administration
Tobramycin ≤2 ≤4 ≤ 4 6–8 mg/kg/24 h Once-daily administration
Amikacin ≤8 ≤8 ≤ 8 25–30 mg/kg/24 h Once-daily administration
Ciprofloxacin ≤0.5 ≤0.5 ≤ 1 400 mg/8 h  
Colistin ≤2 ≤4 ≤ 2 4.5 MU/12 h after a LD of 9 MU Nebulized administration may be considered for VAP
Tigecycline ≤1 IR ND 50 mg/12 h after a LD of 100 mg High-dosing regimen (100 mg/12 h after a LD of 200 mg) has been proposed for severe and/or A. baumannii infections, notably VAP
Fosfomycin ≤32 ND ND ND High doses may be considered (in combination) for extensively drug-resistant Gram-negative bacilli
  1. Based on references [53], [18], [116], [170], [171] and [172].
  2. Extended infusion means administration over a 3- to 4-h period.
  3. MIC minimal inhibitory concentration, ND not defined, IR intrinsic resistance, LD loading dose, VAP ventilator-associated pneumonia.
  4. aDaily doses of beta-lactams, fluoroquinolones and colistin must be adjusted in patients with renal failure.