TDM of antibiotics in clinical practice

Czech version

Authors: I. Kacířová ^1,2; M. Grundmann ¹
Authors‘ workplace: Ústav klinické farmakologie, LF OU, Ostrava ¹; Oddělení klinické farmakologie, Ústav laboratorní diagnostiky, FN Ostrava ²
Published in: Kardiol Rev Int Med 2015, 17(1): 57-64
Category: Internal Medicine

Overview

A key strategy in optimizing aminoglycosides and vancomycin therapy is therapeutic drug monitoring. It is a specific method of clinical pharmacology used to monitor the therapy using measurement of drug serum concentrations followed by interpretation by a clinical pharmacologist/ pharmacist and good cooperation with the clinician. Therapeutic drug monitoring helps clinicians to quickly optimize aminoglycosides and vancomycin dosing regimens to maximize the clinical effect, minimize the toxicity of the drugs, decrease mortality and morbidity and reduce costs. Aminoglycosides (amikacin and gentamicin) constitute one of the oldest classes of antimicrobials. Despite their relative toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice. They are bactericidal agents used against aerobic gram‑ negative infections, and in combination with a cell wall active antimicrobial‑based regimen (e. g. b‑ lactams), also against gram‑ positive cocci. Aminoglycosides have a concentration‑ dependent bactericidal effect and a long post‑antibiotic effect. There is accumulating evidence to show that large, single, daily doses (or more correctly, extended interval dosing) of aminoglycosides are associated with lower nephro‑ and ototoxicity and comparable, if not superior, clinical outcomes than the same total dose administered in small, multiple doses. A general therapeutic range of aminoglycosides does not exist. Every patient has his/ her own optimal target concentration based on the microorganism susceptibility, co‑ administered antibacterials, immune status and co‑ administration of other nephro‑or ototoxic drugs. Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/ L to avoid development of resistance, nevertheless, trough concentrations > 20 mg/ L are not recommended because of the risk of nephrotoxicity. For serious gram‑ positive infections vancomycin trough concentrations of 15– 20 mg/ L are recommended. In non‑complicated infections (urinary tract infections or mild‑ to‑ moderate skin and soft tissue infections) trough concentrations of 10– 15 mg/ L should be sufficient. For continuous infusions of vancomycin target steady‑ state concentration values of 15– 25 mg/ L is optimal. We demonstrate some case reports of therapeutic monitoring of aminoglycoside antibiotics and vancomycine from our routine practice.

Keywords:
therapeutic monitoring – amikacin – gentamicin – vancomycin

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