Usefulness of vancomycin treatment individualization via Bayesian algorithms: a 5-year study in critical patients

Abstract

Aim: Compare two vancomycin dosing strategies in critical patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Materials & methods: Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). Results: The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity. The speed of decrease observed in CRP and PCT was greater for the Bayesian strategy (p = 0.045 and 0.0009, respectively). Conclusion: Applying Bayesian algorithms to vancomycin dosage individualization allows for administering much higher doses than with standard regimens, facilitating a quicker clinical response in the absence of nephrotoxicity.

Article highlights

• Critical patients treated with vancomycin present high inter-individual variability in both clearance and half-life, estimated at 65.3 and 99.1%, respectively.

• Critical patients under vancomycin treatment present intra-individual variability in clearance and half-life, with a magnitude justifying periodic control of concentrations throughout the duration of the treatment.

• The variability of total daily doses required by critical patients presents up to a 60-fold difference between patients who require lower doses and those who require higher doses, indicating the need to individualize dosage schemes for each particular patient.

• The dosing strategy guided by Bayesian algorithms, compared with the strategy guided solely by renal function, presented superior clinical effectiveness when considering remission speed for PCR and PCT.

• The dosing strategy guided by Bayesian algorithms, when compared with the strategy guided entirely by renal functionality, was not related with higher kidney damage rates, despite requiring substantially higher total daily doses.

• It is essential to remember that the science which makes dosing individualization possible is ‘clinical pharmacokinetics’, and thus every mathematical-statistical analysis must always be accompanied by an integral clinical vision for the patient, in order to design dosage schemes which can satisfy their needs in a timely way as well as the changes in their clinical evolution across the treatment.

• Returning to the roots of pharmacokinetics, based upon deep knowledge of the molecule and its behavior in the human body under different physio-pathological conditions, would make it possible to improve the effectiveness/toxicity profile of vancomycin, as well as other antibiotics characterized by high inter- and intra-individual variability.

• Maintaining standard dosage schemes based on guides or recommendations which only consider body weight or kidney function contributes to under-usage of the frontline pharmacotherapy arsenal, and to mediocre clinical results which could favor the development of drug resistance.

Keywords: :

• Bayesian
• critical ill patient
• dosage
• inflammatory parameters
• kidney damage
• MRSA
• pharmacokinetics
• therapeutic drug monitoring
• vancomycin
• variability

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained institutional review board approval from Ethics Committee of Regional Clinical Dr. Guillermo Grant Benavente Hospital (Chile) for the research described.

A consent waiver was granted owing to the retrospective nature of the study.