, Volume 78, Issue 6, pp 621–641 | Cite as

Individualising Therapy to Minimize Bacterial Multidrug Resistance

  • A. J. Heffernan
  • F. B. Sime
  • J. Lipman
  • J. A. Roberts
Review Article


The scourge of antibiotic resistance threatens modern healthcare delivery. A contributing factor to this significant issue may be antibiotic dosing, whereby standard antibiotic regimens are unable to suppress the emergence of antibiotic resistance. This article aims to review the role of pharmacokinetic and pharmacodynamic (PK/PD) measures for optimising antibiotic therapy to minimise resistance emergence. It also seeks to describe the utility of combination antibiotic therapy for suppression of resistance and summarise the role of biomarkers in individualising antibiotic therapy. Scientific journals indexed in PubMed and Web of Science were searched to identify relevant articles and summarise existing evidence. Studies suggest that optimising antibiotic dosing to attain defined PK/PD ratios may limit the emergence of resistance. A maximum aminoglycoside concentration to minimum inhibitory concentration (MIC) ratio of > 20, a fluoroquinolone area under the concentration–time curve to MIC ratio of > 285 and a β-lactam trough concentration of > 6 × MIC are likely required for resistance suppression. In vitro studies demonstrate a clear advantage for some antibiotic combinations. However, clinical evidence is limited, suggesting that the use of combination regimens should be assessed on an individual patient basis. Biomarkers, such as procalcitonin, may help to individualise and reduce the duration of antibiotic treatment, which may minimise antibiotic resistance emergence during therapy. Future studies should translate laboratory-based studies into clinical trials and validate the appropriate clinical PK/PD predictors required for resistance suppression in vivo. Other adjunct strategies, such as biomarker-guided therapy or the use of antibiotic combinations require further investigation.



Aaron Heffernan would like to acknowledge funding from a Griffith School of Medicine Research Higher degree scholarship. Fekade Sime would like to acknowledge funding from a University of Queensland Post Doctoral Fellowship. Jason Roberts would like to recognise funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).

Compliance with Ethical Standards

Conflict of interest

Jason Roberts would like to declare collaborations with MSD, Bayer, Astellas, Pfizer, bioMerieux and Accelerate Diagnostics but none of which are considered relevant to the content of this paper. Aaron Heffernan, Fekade Sime and Jeffrey Lipman have no conflicts of interest to declare.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of MedicineGriffith UniversityGold CoastAustralia
  2. 2.Centre for Translational Anti-Infective Pharmacodynamics, School of PharmacyThe University of QueenslandBrisbaneAustralia
  3. 3.UQ Centre for Clinical Research, Faculty of MedicineThe University of QueenslandHerstonAustralia
  4. 4.Department of Intensive Care MedicineRoyal Brisbane and Women’s HospitalBrisbaneAustralia
  5. 5.Pharmacy DepartmentRoyal Brisbane and Women’s HospitalBrisbaneAustralia

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