Aminoglycosides’ Dosage in Hematological Malignancies and Febrile Neutropenia: Extended Interval or Conventional Dosage?

Abstract

A patient with acute myeloid leukemia presented various episodes of febrile neutropenia, for which there was no positive response to antibiotic treatments. Following an episode of bacteremia by extensively drug-resistant Klebsiella pneumoniae, amikacin was prescribed, pharmacokinetic analyses of its plasma concentrations were performed and the dosage interval was narrowed to 12 and 8 h in order to counteract the reduced postantibiotic effect due to the patient being immunocompromised. The patient responded positively, with procalcitonin decreasing and body temperature normalizing. Recovery was finally achieved, without renal or auditory damage. This case proposes tightening dosage intervals for aminoglycosides as an effective strategy in immunocompromised patients. Aminoglycosides are given over extended intervals (24 h), considering concentration-dependent effectiveness, nephrotoxicity and postantibiotic effect. Leukocytes appear to play a determining role in the postantibiotic effect, with no proposed dosing strategy for strongly immunocompromised patients.

Keywords::

• amikacin
• aminoglycosides
• febrile neutropenia
• immunocompromised patients
• oncohematology
• personalized medicine
• pharmacokinetics
• pharmacokinetic/pharmacodynamic
• postantibiotic effect
• therapeutic drug monitoring

Acknowledgements

The authors acknowledge and thank JPM (RIP) for his participation in this study, as well as his family, who can see in this case report the final legacy he leaves to them, in the hope that it will be helpful for many patients.

Financial & competing interests disclosure

Kits of amikacin for quantitative analysis, via immunoanalysis, was kindly provided by Roche Chile Ltd. These kits were used both as standards for the analytical technique validation and as a reagent in all quantitative determinations. The authors have no other relevant affiliations or 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 apart from those disclosed.

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 the Scientific Ethics Committee of Concepción Health Service (Chile) for the research described. In addition, they have obtained verbal and written informed consent from the patient and the patient’s family for the inclusion of their medical and treatment history within this work.