Optimizing Use of Aminoglycosides in the Critically Ill

Abstract

In the era of increasing bacterial resistance and a lack of development of new antimicrobials for the treatment of gram-negative infections, aminoglycosides (AGs) are more commonly used in combination with other antimicrobials for the treatment of life-threatening infections in the intensive care unit (ICU). AGs display concentration-dependent killing activity; thus the rate and extent of bacterial killing increase with increasing peak (Cmax) drug concentrations. Optimizing AG dosing requires attainment of a pharmacodynamic target ratio (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is associated with a more rapid rate of resolution of infection. Extended-interval AG dosing has been shown to attain this target in the general patient population while decreasing the risk of nephrotoxicity compared with multiple daily dosing. However, ICU patients have pharmacokinetic differences compared with patients who are less ill, including increased volume of distribution and variable clearance, which may make attainment of this target difficult. The need for extended-interval aminoglycoside dosing with Cmax monitoring and MIC determination of the pathogen may be needed to optimally treat serious infections in the critically ill.

Therapeutic Drug Monitoring of Biologics for Inflammatory Bowel Disease

“…In the Belgian referral center analysis, adalimumab-treated patients who ended up discontinuing therapy had significantly lower serum trough levels as early as weeks 2-4. 29 Based on this, a potential approach for TDM could be modeled after the individualized dosing used for aminoglycoside antibiotics, 70 wherein dosing is determined and adjusted based on the patient's specific clearance and the minimum inhibitory concentration of the organism being treated. In the case of anti-TNF agents, the dose could be changed or concomitant medications could be added or adjusted in patients with rapid or increasing clearance in order to boost concentrations, reduce immunogenicity, and potentially avoid loss of response.…”

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis

“…45 These medications may also be added to other antibiotics for synergy in the treatment of difficult-to-eradicate gram-positive infections such as endocarditis. 46 As a class, aminoglycosides have concentrationdependent bactericidal activity via irreversible binding to the 30S ribosomal subunit of susceptible bacteria, inhibiting bacterial protein synthesis.…”

“…Patient-specific pharmacokinetic calculations should be considered for critically ill patients and others with altered V d by obtaining serum samples for determination of drug level at 2 different times (eg, 3 and 10 hours after administration of a dose) to ensure that the goal for peak level of drug and appropriate dosing interval has been selected. 60 Assay of a serum sample obtained at random may also be useful to assess aminoglycoside clearance. Bedside nurses' understanding of the monitoring plan is imperative so that blood samples for serum drug levels are obtained at appropriate times to ensure dose optimization.…”

Actualités en antibiothérapie — Aminosides toujours et encore: bon usage et suivi thérapeutique

“…Les plus fréquents sont d'origine plasmidique (gènes codant des enzymes modifiant la structure des molécules) et sont responsables d'une résistance d'emblée de haut niveau [5]. D'autres mécanismes existent : efflux, imperméabilité ou mutation des protéines ribosomales [5]. La fréquence élevée de ces résistances néces-site la réalisation d'un antibiogramme.…”