Antibiotics

Cockcroft-Gault should generally be used to calculate creatinine clearance, as this is the standard in pharmacokinetic studies.

Comparison of Antibiotic Classes
Class Pharmacokinetics Considerations
Aminoglycosides
  • Bactericidal
  • Fast
  • Concentration-dependent
  • Significant post-antibiotic effect
    Duration related to height of peak concentration.
  • Single-daily dosing more effective than multiple daily dosing
  • Poor distribution into tissues
    Less effective in solid organ infections, ↑↑ VD with extravascular fluid shifts.
  • Synergistic in treatment of some Gram positive infections, including:
    • Streptococci
      S. gallolyticus, S. bovis, S. viridans
    • Some Staphlococci and Enterococci
  • Aminoglycosides are structurally dissimilar enough such that resistance is drug-dependent.
  • Consider performing levels:
    • Peak levels 30 minutes after 3rd dose
    • Trough levels 30 minutes prior to 4th dose
    • Peri-IHD levels: Trough levels 30 minutes after IHD

β-lactams
Including:

  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Bactericidal
  • Slow
  • Time dependent
    Ideally 4-5 times MIC, and >0.4 (40%) throughout.
  • Generally significant post-antibiotic effect
    Notable exception of carbapenems.
  • Reasonable tissue penetration
  • More frequent dosing may be more effective
Glycopeptides
  • Mostly bactericidal, bacteriostatic against enterococci
  • Post-antibiotic effect, even if sub MIC
  • Poor distribution into tissues
    Less effective in solid organ infections, ↑↑ VD with extravascular fluid shifts.
  • Vancomycin 20-25mg/L
    Continuous infusion.
Linezolid
  • No drug monitoring
  • Good tissue penetration
  • Drug interactions
    • Serotonin syndrome
  • Thrombocytopaenia
  • No dose adjustment required in renal failure
Quinolones
  • Bactericidal
  • Fast
  • Concentration and time dependent
    Area under the inhibitor curve; i.e. AUC or MIC >125.
  • Some post-antibiotic effect
  • Very high tissue penetration

Carbapenems are also β-lactams, but have been separated here due to different pharmacokinetic properties.

Various formulas for calculating dosing weights include:

  • \(IBW_{Male} = Height - 105\)
  • \(IBW_{Female} = Height - 108\)
  • \(ABW = IBW + 0.4(TBW - IBW)\)

Where:

  • \(IBW\) is ideal body weight
  • \(Height\) is height in cm
  • \(ABW\) is adjusted body weight
  • \(TBW\) is total body weight

Dosing

Dosing of Aminoglycosides
Drug Indication Dosing
Amikacin Conventional CrCl >60: 5-7mg/kg Q8H IV
CrCl 40-60: 5-7mg/kg Q12H IV
CrCl 20-40: 5-7.5mg/kg Q24H IV
CrCl <5: 5mg/kg IV load, then dose by level
IHD: 5-7.5mg/kg IV post IHD
CRRT: 10mg/kg IV load, then 7.5mg/kg IV Q24-48H
High-dose CrCl >60: 15-20mg/kg Q24H IV
CrCl 40-60: 15mg/kg Q36H IV
CrCl 30-40: 15mg/kg Q48H IV
CrCl <30: 7.5mg/kg Q48-72 hours IV
Not recommended for high dosing at this level.
Gentamycin
  • Gram negative infection
    Aim for:
    • Peak: 4-8mg/L
    • Trough: 1-2mg/L
 CrCl >60: 5-7mg/kg Q24H
CrCl 40-60: 5-7mg/kg Q36H
CrCl 20-40: 1.7mg/kg Q24H
CrCl <20: 2mg/kg IV load, then dose as per level
IHD: 2mg/kg IV load, then 1.5mg/kg IV post IHD
CRRT: 1.5-2.5mg/kg Q24-48H IV
  • Gram positive synergy
    Aim for:
    • Peak: 3-4mg/L
    • Trough: <1mg/L
 CrCl >60: 5-7mg/kg Q24H
CrCl 40-60: 5-7mg/kg Q36H
CrCl 20-40: 1.7mg/kg Q24H
CrCl <20: 2mg/kg IV load, then dose as per level
IHD: 2mg/kg IV load, then 1.5mg/kg IV post IHD
CRRT: 1.5-2.5mg/kg Q24-48H IV

All CrCl values are given in mL/min.

Dosing of β-lactams
Drug Indication Dosing
Ampicillin
  • Uncomplicated infection
  • Mild infection
 CrCl >50: 1-2g Q6H IV
CrCl 10-50: 1g Q6-8H
CrCl <10: 1g Q12H IV
IHD: 1g Q12H IV
CRRT: 2g Q6-12H IV
  • Meningitis
  • Endovascular
  • Prosthetic joint
 CrCl >50: 2g Q4H IV
CrCl 10-50: 2g Q6-12H IV
CrCl <10: 2g Q12-24H IV
IHD: 2g Q12-24H IV
CRRT: 2g Q6H IV
Piperacillin/tazobactam (tazocin)
  • General infection
 CrCl >40: 3.375mg Q6H IV
CrCl 20-40: 2.25g Q6H IV
CrCl <20: 2.25g Q8H IV
IHD: 2.25g Q12H IV
CRRT: 3.375g Q6H IV
  • Severe infection
  • Sepsis
  • Cystic fibrosis
  • HAP/VAP
  • Pseudomonas
 CrCl >50: 4.5g Q6H IV
CrCl 10-50: 3.375g Q6H IV
CrCl <10: 2.25g Q6H IV
IHD: 3.375g Q12H IV
CRRT: 3.375-4.5g Q8H IV
Cefepime
  • General infection
 CrCl >60: 1g Q8H IV
CrCl 30-50: 1g Q12H IV
CrCl 10-30: 1g Q24H IV
CrCl <10: 500mg Q24H IV
IHD: 0.5-1g IV Q24H daily
After IHD on IHD days.
CRRT: 2g IV load, then 1g IV Q8H
  • Pulmonary infection
  • Neutropenic sepsis
  • CNS infection
  • Pseudomonas infection
  • Severe infection
 CrCl >50: 2g Q8H IV
CrCl 10-50: 2g Q12H IV
CrCl <10: 1g Q12H IV
IHD: 0.5-1g Q24H IV
After IHD on IHD days.
CRRT: 2g IV load, then 1g IV Q8H
Ceftaroline
  • General infection
 CrCl >50: 600mg Q12H IV
CrCl 30-50: 400mg Q12H IV
CrCl 15-30: 300mg Q12H IV
CrCl <15: 200mg Q12H IV
IHD: 200mg Q8-12H IV
  • Endocarditis
  • S. aureus bacteraemia
 CrCl >50: 600mg Q8H IV
CrCl 30-50: 400mg Q8H IV
CrCl 15-30: 300mg Q8H IV
CrCl <15: 200mg Q8H IV
IHD: 200mg Q8-12H IV
Ceftriaxone
  • General infection
 1-2g Q24H IV
No renal dose adjustment required.
  • Endovascular
  • Osteomyelitis
  • Prosthetic joint infection
 2g Q24H IV
  • Meningitis
  • E. faecalis endocaditis
 2g Q12H IV
Meropenem
  • Febrile neutropaenia
  • HAP/VAP
  • Pseudomonas
 CrCl >50: 1g Q8H IV
CrCl 25-50: 1g Q12H IV
CrCl 10-25: 0.5g Q12H IV
CrCl <10: 0.5g Q24H IV
IHD: 500mg Q24H IV
CRRT: 1g Q8H IV
Meropenem
  • Meningitis/encephalitis
  • Cystic fibrosis
  • Severe infection
 CrCl >50: 2g Q8H IV
CrCl 25-50: 2g Q12H IV
CrCl 10-25: 1g Q12H IV
CrCl <10: 1g Q24H IV
IHD: 1g Q24H IV
CRRT: 2g Q12H IV
Dosing of Lincosamides
Drug Indication Dosing
Clindamycin 600-900mg IV Q8H or 150-450mg PO Q6H
No renal dose adjustment required.
Dosing of Nitroimidazoles
Drug Indication Dosing
Metronidazole 500mg Q6-8H PO or 400mg Q6-8H IV  |
No renal dose adjustment required, consider ↓ to Q12H in severe hepatic impairment. |
Dosing of Macrolides
Drug Indication Dosing
Azithromycin 500mg IV/PO Q24H
No renal dose adjustment required.
Dosing of Monobactams
Drug Indication Dosing
Aztreonam
  • General
 CrCl >50: 1-2g Q8H IV
CrCl 10-50: 1g Q8H IV
CrCl <10: 500mg Q8H IV
IHD: 1g Q24H IV
CRRT: 2g IV load, then 1g IV Q8H
  • Severe infection
  • Meningitis
 CrCl >50: 2g Q6-8H IV
CrCl 10-50: 1g Q6-8H IV
CrCl <10: 1g Q12H IV
IHD: 1g Q12H IV
CRRT: 2g IV Q12H IV
Dosing of Oxazolidinones
Drug Indication Dosing
Linezolid
  • General
 600mg Q12H IV/PO No renal dose adjustment required.
Dosing of Sulfonamides
Drug Indication Dosing
Trimethoprim/sulfamethoxazole
  • S. aureus*
  • Gram negative bacteraemia
 CrCl >30: 4-5mg/kg of TMP Q12H
CrCl 15-30: 2-2.5mg/kg of TMP Q12H
CrCl <15:
IHD: 2.5-5mg/kg of TMP Q24H
CRRT: 2.5-5mg/kg Q12H
Trimethoprim/sulfamethoxazole
  • Stenotrophomonas
  • Pneumocystis jirovecii pneumonia
 CrCl >30: 5-7.5mg/kg of TMP Q12H
CrCl 15-30: 2.5-3.75mg/kg of TMP Q12H
CrCl <15: 2.5-3.75mg/kg of TMP Q12H
Use not recommended.
IHD: 5-7.5mg/kg of TMP Q24H
CRRT: 5mg/kg of TMP Q8H
Dosing of Tetracyclines
Drug Indication Dosing
Doxycycline
  • General
 100mg Q12H IV/PO
Consider 200mg load for severe infections.
Dosing of Quinolones
Drug Indication Dosing
Ciprofloxacin
  • General infection
 CrCl ⩾30: 400mg Q12H IV or 500mg Q12H PO
CrCl <30: 400mg Q24H IV or 500mg Q12H PO
IHD: 200-400mg Q12H IV or 250-500mg Q24H PO
CRRT: 400mg Q12H IV or 500mg Q12H PO
  • Pseudomonas infection
 CrCl >50: 400mg Q8H IV or 750mg Q12H PO
CrCl 30-50: 400mg Q8-12H IV or 500mg Q12H PO
CrCl <30: 400mg Q12H IV or 500mg Q24H PO
IHD: 200-400mg Q12H IV or 250-500mg Q24H PO
CRRT: 400mg Q12H IV or 500mg Q12H PO
Moxifloxacin 400mg Q24H IV/PO

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Rubinstein E, Keynan Y. Vancomycin Revisited – 60 Years Later. Frontiers in Public Health. 2014;2. Accessed May 3, 2023.