The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

Abstract

Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

Personalized Antibiotic Therapy for the Critically Ill: Implementation Strategies and Effects on Clinical Outcome of Piperacillin Therapeutic Drug Monitoring—A Descriptive Retrospective Analysis

“…Therefore, the optimal diagnostic choice currently seems to be chromatography combined with mass spectrometry (LC-MS), which is mostly based on locally developed standards [ 16 ]. Although the application of LC-MS requires a sophisticated infrastructure including trained personnel and extensive apparatuses, the number of hospitals incorporating LC-MS in routine analysis is increasing [ 18 ]. This might be explained due to decreased costs of LC-MS equipment compared to earlier eras, but also as a consequence of improved sensitivity and speed [ 18 , 19 ].…”

“…Although the application of LC-MS requires a sophisticated infrastructure including trained personnel and extensive apparatuses, the number of hospitals incorporating LC-MS in routine analysis is increasing [ 18 ]. This might be explained due to decreased costs of LC-MS equipment compared to earlier eras, but also as a consequence of improved sensitivity and speed [ 18 , 19 ]. The application of this technique enables fast turnaround times, which in turn benefits patient care.…”

Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro

“…Unfortunately, DDI can play a significant role in the increase in mortality and morbidity of cancer patients [4]. This is not surprising as the complicated health situation of cancer patients necessitates in many instances the concomitant administration of a wide range of medications such as immunosuppressant and anti-infective agents along with antineoplastic agents [5]. A study by Poulikakos et al, showed a mortality rate of 100% of cancer patients after an influenza infection even though a proper treatment was received [6].…”

Mass spectrometry or immunoassay: est modus in rebus

“…Several papers in this issue of Clinical Chemistry and Laboratory Medicine emphasize the wide range of applications of MS based methods [23][24][25][26][27][28][29][30]. The review by El-Najjar et al [23] highlights the crucial role of TDM of antibiotics in cancer patients: immunoassays are not available for all the classes of these drugs due to the difficulty in β-lactams ring reactivity or degradation.…”

“…The review by El-Najjar et al [23] highlights the crucial role of TDM of antibiotics in cancer patients: immunoassays are not available for all the classes of these drugs due to the difficulty in β-lactams ring reactivity or degradation. Therefore, LC-MS/MS methods have become the method of choice.…”