Therapeutic monitoring of amikacin and gentamicin in critically and noncritically ill patients

Abstract

Objective:Therapeutic drug monitoring (TDM) enables individualization in the treatment to optimize clinical benefit and minimize drugs' side effects. Critically ill septic patients represent a challenge for antimicrobial treatment because of pathophysiological impact of sepsis on pharmacokinetics of drugs. The aim of this study was to assess the appropriateness of gentamicin and amikacin dosing in critically and noncritically ill patients, as well as to estimate the need for its regular therapeutic monitoring.Subjects and Methods:It was a prospective study which included 31 patients on gentamicin and 16 patients on amikacin from four different units who met the inclusion criteria. Trough concentrations of drugs were measured in serum just before third or fourth dose of antibiotic, whereas peak concentrations were measured in serum 1 h after the completion of drug administration (steady state). Relevant data on patients' clinical course of disease, comorbidities, and concomitant medication were collected from medical charts in order to identify their possible influence on drugs' concentrations.Results:Peak concentrations of amikacin were in reference range in 81.8% critically ill and in 80% of noncritically ill patients (P = 0.931). Peak concentrations of gentamicin were in reference range in 88.9% critically ill and in 77.3% of noncritically ill patients (P = 0.457).Conclusion:Serum concentrations of aminoglycosides (amikacin and gentamicin) were in reference range in most of the patients in our study, suggesting that dosing of these drugs in the University Hospital Clinical Center, Banja Luka, was adequate. In patients without kidney or liver disease, regular TDM of aminoglycosides is not necessary.

Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions

“…One of the main factors associated with failure in antibacterial therapy in patients with ARC is the inadequate dosage of the drug, which generates subtherapeutic concentrations of the antibiotic, with the consequent lack of efficacy of treatment and the possible emergence of resistant strains. On the other hand, it should be noted that the administration of excessive doses can generate toxic effects, which can increase the length of hospital stay and generate a greater expense in patient care (9).…”

2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in Pseudomonas aeruginosa

“…Crucially, SB002 and SB023 did not exhibit profound cytotoxicity towards any of the human cell lines we tested; although for the most part, they did exhibit a relatively narrow potential therapeutic index (TI < 100). This is not necessarily a major problem; there are several approved antibiotics or classes of antibiotics on the market with narrow TIs, including the aminoglycosides, vancomycin and polymyxin B [30]. SB002 and SB023 were metabolized by cytochrome P450 in human liver microsomes, with half-lives of 81 and 72 min, respectively (Table 4).…”

„Drug Interaction Stewardship“ (DIS) und therapeutisches Drug-Monitoring (TDM) für die antiinfektive Therapie in der operativen Intensivmedizin, eine monozentrische Beobachtungsstudie

“…Auch für einzelne Antibiotika wird häufig ein TDM, insbesondere zur Vermeidung toxischer Nebenwirkungen durch Überdosierung, z. B. bei Aminoglykosiden [60] oder Glykopeptiden [61] durchgeführt.…”