Amikacin therapeutic drug monitoring: Evaluation of therapy performance and analytical techniques in a developing...

Healthcare systems face several challenges, with microbial infections being one of the main concerns. Therapeutic drug monitoring (TDM) is a strategy that has been encouraged to optimize antimicrobial regimens, particularly those with significant toxicity and narrow therapeutic indices, such as amikacin (AMK). We aimed to evaluate AMK concentrations of patients in a non-routine TDM setting and compare the performance of immunoassay and chromatography methods for routine clinical use.

In this prospective study, peak (C_max) and trough (C_min) plasma samples were collected from 39 adult patients and quantified by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS). Relevant clinical information was collected from medical records. AMK concentrations and clinical data were analyzed to evaluate therapy performance and influencing factors. In addition, fluorescence polarized immunoassay (FPIA) and UPLC-MS/MS were compared with Passing-Bablok regression and Bland-Altman plot analysis.

AMK concentrations varied widely, with a median C_max of 41.40 µg/mL (interquartile range [IQR] 27.60 - 56.75 µg/mL) and a median C_min of 1.87 µg/mL (IQR 0.7 - 6.19 µg/mL). A high proportion of patients (83.1 %) failed to achieve the C_max therapeutic target, while 31.7 % failed to achieve the C_min therapeutic target. Overall, elderly patients and those with reduced renal function had higher C_max target attainment, while the same groups had lower C_min target attainment. The method comparison showed a mean difference of 1.54 % (limits of agreement -42.46 % to 45.54 %) in measured concentrations, with good correlation and no constant or proportional differences.

Many patients failed to reach the C_max target and were at risk of treatment failure, although adequate C_min was achieved more often. TDM with dose adjustments could improve AMK therapy, but further research is needed.