Personalized antibiotic therapy – a rapid high performance liquid chromatography–tandem mass spectrometry method for the quantitation of eight antibiotics and voriconazole for patients in the intensive care unit

Abstract

Abstract Objectives For a long time, the therapeutic drug monitoring of anti-infectives (ATDM) was recommended only to avoid the toxic side effects of overdosing. During the last decade, however, this attitude has undergone a significant change. Insufficient antibiotic therapy may promote the occurrence of drug resistance; therefore, the “one-dose-fits-all” principle can no longer be classified as up to date. Patients in intensive care units (ICU), in particular, can benefit from individualized antibiotic therapies. Methods Presented here is a rapid and sufficient LC-MS/MS based assay for the analysis of eight antibiotics (ampicillin, cefepime, cefotaxime, ceftazidime, cefuroxime, linezolid, meropenem, and piperacillin) applicated by continuous infusion and voriconazole. In addition a dose adjustment procedure for individualized antibiotic therapy has been established. Results The suggested dose adjustments following the initial dosing of 121 patient samples from ICUs, were evaluated over a period of three months. Only a minor percentage of the serum levels were found to be within the target range while overdosing was often observed for β-lactam antibiotics, and linezolid tended to be often underused. The results demonstrate an appreciable potential for β-lactam savings while enabling optimal therapy. Conclusions The presented monitoring method provides high specificity and is very robust against various interferences. A fast and straightforward method, the developed routine ensures rapid turnaround time. Its application has been well received by participating ICUs and has led to an expanding number of hospital wards participating in ATDM.