Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration

Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from multiple daily dosing to extended-interval dosing, with concomitant reduction in nephrotoxicity. Currently, AG daily dose is calculated according to the patients' adjusted body weight, assuming a common minimal inhibitory concentration (MIC) value.We hypothesize that once pathogen identity and actual MIC become available, AG daily doses may be further adjusted, using the same PK-PD indices.In order to investigate this hypothesis, we are conducting a prospective clinical study in which AG doses will be adjusted based on patient- and pathogen-specific factors, while assessing efficacy and safety.

Adult patients (≥18yr)Any infection treated with IV gentamycin or amikacin and approved by the consultant infectious diseases specialist, excluding neurosurgical infections, pneumonia, endocarditis or endovascular infectionsNormal renal function or mild renal impairment (eGFR≥40ml/min)On extended-interval AG and an expected remaining AG course of at least 4 daysAt least one microbiological specimen with identification of an AG-susceptible pathogen and MIC determination andSigned informed consent formExclusion Criteria:Age<18yrNeurosurgical infections, pneumonia, endocarditis or endovascular infectionseGFR<40ml/minEmpirical aminoglycoside treatmentNon Gram-negative pathogenNo MIC available for the pathogenExpected remaining treatment duration of less than 4 days