Comment on: Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study

We recently perused the multicentre study by Vena et al.¹ that was published in JAC with great attention and interest. The study reported that adequate empirical antibiotic combination therapy was associated with improved survival in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections. Nevertheless, we believe that there are certain fundamental aspects that warrant consideration when interpreting the findings of the study.

Firstly, acute kidney injury (AKI) is a frequent complication in septic shock patients, which occurs in 40%–60% of sepsis patients and is associated with significant disease burden and worse clinical outcomes.^2,3 AKI in critically ill patients is associated with an increased risk of mortality and prolonged hospital stay compared with AKI caused by other aetiologies. Patients with sepsis and AKI complications have a higher mortality rate than those without AKI.^2,3

Another important point is that the antibiotic selection for combination therapies in the study was amikacin or colistin in 17/27 (70.8%) of patients. The most widely recognized adverse effects associated with these two antibiotics, which restrict their utilization, is the potential risk of drug-related nephrotoxicity.⁴ It is possible that clinicians may have avoided the use of nephrotoxic antibiotics when selecting antibiotics for patients with AKI, which will directly influence the choice of combination therapy. Studies have shown that there are fewer treatment-limiting conditions in patients on combination therapy.^3,5

Lastly, the pharmacokinetics of antibiotics differ in sepsis patients due to alterations in volume of distribution and antibiotic clearance. Furthermore, the presence of hyperdynamic circulation, fluid balance changes and the development of organ dysfunction, such as AKI, in addition to renal replacement therapy, contribute to a highly complex situation. This situation can vary significantly between patients and even within individual patients over the course of a single day. Therapeutic drug monitoring is recommended to ensure optimal antibiotic dosing in this patient group.^3,6

In summary, the study presents significant findings regarding combination and monotherapy in patients with P. aeruginosa bloodstream infections who developed septic shock. However, for a more comprehensive understanding and interpretation of the study, it is important to consider AKI-related conditions, if any, before antibiotic initiation.

Funding

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Transparency declarations

All of the authors declare that they have all participated in the design, execution and analysis of the paper, and that they have approved the final version. Additionally, there are no conflicts of interest in connection with this paper, and the material described is not under publication or consideration for publication elsewhere.

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