Advancing precision-based antimicrobial dosing in critically ill patients

Abstract

Treatment of infections among critically ill patients remains problematic, with ongoing challenges in antimicrobial dosing optimisation. Strategies, such as modelinformed precision dosing (MIPD), may be effective solutions but as yet without documented clinical benefit.In a paper published in the December issue of Intensive Care Medicine, Ewoldt and colleagues conducted the DOLPHIN trial to evaluate whether a MIPD intervention (therapeutic drug monitoring [TDM] and use of dosing software) in critically ill patients prescribed beta-lactam antimicrobials and ciprofloxacin decreased length of stay (LOS) in the intensive care unit (ICU) when compared to standard dosing alone [1]. The investigators should be commended for the first ever multicentre trial evaluating the potential benefits of MIPD in critically ill patients. The organisational aspects of conducting a multicentre study with essentially two interventions (TDM and dosing software) are challenging.Included in the primary analysis of the trial were 388 patients (MIPD group; n = 189, standard dosing group; n = 199). Contrary to their hypothesis, the investigators found a similar median LOS among both groups, with the MIPD group having a non-significant increase of 2 days on average compared to the standard dosing group (10 days vs 8 days, respectively). In addition, pharmacodynamic (PD) target attainment in the MIPD group remained low, ranging from 55.6 to 71.4%. Do these recent findings mark the beginning of the end to evaluating MIPD as a clinically relevant dose optimisation strategy in critically ill patients? In our opinion, no. We believe that there were some limitations with the study which should be addressed in future studies that test the benefits associated with precision-based antimicrobial dosing.

Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

“…Meta-analyses of individualised antimicrobial dose optimisation con rm the achievement of higher rates of target exposures and have suggested reductions in treatment failure and adverse outcomes such as nephrotoxicity [28,29]. More work is undoubtedly necessary to assess the bene t of the approach [30], and it is hoped that ndings from our study provide further impetus to examine this important research question in the context of a suitably powered randomised clinical trial.…”

Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

“…Innovative approaches such as wearable biosensors that provide rapid quantification of antibiotic concentrations, could reduce these delays and facilitate earlier TDM and dose optimisation [ 33 ]. More work is undoubtedly necessary to assess the benefit of the approach [ 34 ], and it is hoped that findings from our study provide further impetus to examine this important research question in the context of a suitably powered randomised clinical trial.…”

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review

“…Dosing nomograms, clinician-based predictions, or dosing software (e.g., BestDose ® , Antibiotics kinetics ® , MwPharm++ ® , TDMx ® , etc.) allow for further individual dosage adjustment [ 19 , 20 , 21 , 22 ]. TDM is already successfully implemented on a large scale; A-TEAMICU reported that TDM was used in 61% of ICUs surveilled [ 9 ].…”