Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity

Abstract

The new Australian Therapeutic Guidelines: Antibiotic, version 14 have revised the recommendations for the use and monitoring of aminoglycosides. The guidelines have clear distinctions between empirical and directed therapy as well as revised recommendations about the monitoring of aminoglycosides. This has led many clinicians to review their current practice with regard to the use of aminoglycosides. This review summarizes why aminoglycosides are still a valid treatment option and discusses the rationale for current dosing regimens in Gram-negative infections. In particular it focuses on the various methods for monitoring aminoglycosides that are currently being used. The aminoglycoside monitoring methods can be categorized into three groups: linear regression analysis (one compartment model), population methods and Bayesian estimation procedures. Although the population methods are easy to use and require minimal resources they can recommend clinically inappropriate doses as they have constant pharmacokinetic parameters and are not valid in special population groups, that is, renal impairment. The linear regression and Bayesian methods recommend more accurate dosage regimens; however, they require additional resources, such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offer additional advantages, such as calculation of doses based on a single serum concentration and optimization of the patient's previous pharmacokinetic data, in order to determine subsequent dosage regimens. We recommend the Bayesian estimation procedures be used, wherever feasible. However, they require the expertise of healthcare practitioners with a good understanding of pharmacokinetic principles, such as clinical pharmacists/clinical pharmacologists, in order to make appropriate recommendations.

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

“…11 The ratio of the peak concentration to the minimum inhibitory concentration of gentamicin should be maximized to optimize efficacy. 12 This is tempered by the need to avoid excessively large areas under the concentration-time curve (AUC) to minimize the risk of toxicity. 11 For a given individual, the AUC is determined by the administered dose and the individual's gentamicin clearance.…”

Role of Therapeutic Drug Monitoring in Pulmonary Infections: Use and Potential for Expanded Use of Dried Blood Spot Samples

“…For beta-lactam antibiotics it has been shown that dose adjustment is recommended for most drugs 271 in patients with renal impairment, especially when combined with β-lactamase inhibitors [24][25][26][27][28][29][30]. 272…”

“…Cmax [28] Drugs influencing renal clearance [5] LT Commonly accepted [28] Y gentamicin IV Y(R) [29], N(H)ᵠ tobramycin IV Y(R) [29], N(H)ᵠ kanamycin IV Y(R) [29], N(H) [30] amikacin IV Y(R) [29], N(H) [30] streptomycin IV Y(R) [29], N(H) [30] …”

Response to Letters Regarding Article, “Infective Endocarditis After Transcatheter Aortic Valve Implantation: Results From a Large Multicenter Registry”

“…Second, antibiotic prophylaxis might have been futile in approximately half of the patients (ie, those who developed the infection >6 months after the procedure), who in fact had already received antibiotics for tackling sensitive bacteria responsible for the infection in about half of cases. The potential toxicity of aminoglycosides, 6 together with the high rate of comorbidities (including significant kidney failure) in TAVI candidates, raises caution about the universal use of such an aggressive antibiotic regimen in the absence of supportive data.…”