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Curr Opin Infect Dis. 2018 Dec;31(6):555-565. doi: 10.1097/QCO.0000000000000494.

How to optimize antibiotic pharmacokinetic/pharmacodynamics for Gram-negative infections in critically ill patients.

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School of Medicine, Griffith University, Gold Coast.
Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia.
Department of Intensive Care, Erasme Hospital, Universite Libre de Bruxelles, Bruxelles, Belgium.
Faculty of Medicine, University of Queensland Centre for Clinical Research, The University of Queensland.
Department of Intensive Care Medicine and Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.



Optimized antibiotic dosing regimens improve survival rates in critically ill patients. However, dose optimization is challenging because of fluctuating antibiotic pharmacokinetics both between patients and within a single patient. This study reviews the pharmacokinetic changes that occur in critically ill patients, along with the pharmacodynamics and toxicodynamics of antibiotics commonly used for the treatment of Gram-negative bacterial infections to formulate a recommendation for antibiotic dosing at the bedside.


Recent studies highlight that critically ill patients do not achieve therapeutic antibiotic exposures with standard antibiotic dosing. Although dose increases are required, the method of administration, such as the use of β-lactam antibiotic continuous infusions and nebulized aminoglycoside administration, may improve efficacy and limit toxicity. In addition, the increased availability of therapeutic drug monitoring and antibiotic dosing software allow the formulation of individualized dosing regimens at the bedside.


When prescribing antibiotic doses, the clinician should consider antibiotic pharmacokinetic and pharmacodynamic principles. Before initiating high-dose antibiotic therapy, therapeutic drug monitoring may be considered to assist the clinician to optimize antibiotic treatment and minimize potential toxicity.

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