Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

Abstract

Therapeutic drug monitoring (TDM) of antibiotics has been practiced for more than half a century, but it is still not widely applied for infected patients. It has a traditional focus on limiting toxicity of specific classes of antibiotics such as aminoglycosides and vancomycin. With more patients in critical care with higher levels of sickness severity and immunosuppression as well as an increasingly obese and ageing population, an increasing risk of suboptimal antibiotic exposure continues to escalate. As such, the value of TDM continues to expand, especially for beta-lactams which constitute the most frequently used antibiotic class. To date, the minimum inhibitory concentration (MIC) of infectious microbes rather than classification in terms of susceptible and resistant can be reported. In parallel, increasingly sophisticated TDM technology is becoming available ensuring that TDM is feasible and can deliver personalized antibiotic dosing schemes. There is an obvious need for extensive studies that will quantify the improvements in clinical outcome of individual TDM-guided dosing. We suggest that a broad diagnostic and medical investigation of the TDM arena, including market analyses and analytical technology assessment, is a current priority.

Meropenem use and therapeutic drug monitoring in clinical practice: a literature review

“…meropenem) and TDM has been more recently explored. 8,[14][15][16] Moreover, clinical studies associated with pharmacokinetic modelling and simulations have shown the importance of TDM to guide therapy with meropenem, treating many bacterial infections. 6,17,18 Hence, this literature review aims to assess the data available about meropenem TDM in clinical practice and how it helps to increase clinical and microbiological outcomes and to decrease possible adverse effects.…”

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

“…The SFPT-SFAR suggested TDM guidelines concern, not only the patient’s conditions (i.e., ICU patients with expected beta-lactam PK variability and/or patients with clinical signs potentially related to beta-lactam toxicity; critically ill patients undergoing RRT), the PK parameters to be evaluated according to different modalities of administration (i.e., plasma trough concentration in case of intermittent administration, plasma steady-state concentration in case of continuous administration), the timing (24 to 48 h after the onset of treatment; after any change in dosage; in the event of significant change in the patient’s clinical condition), the kind of tissues (e.g., in the case of central nervous system infection, on blood and cerebrospinal fluid samples collected concomitantly), but also the modality of measurements (i.e., a validated chromatographic method). In relation to this last recommendation, it has to be considered that the method most commonly used for TDM involves immunological assaying that is less laborious compared with high-performance liquid chromatography (HPLC) technology even though less accurate [ 116 ].…”

Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring

“…Most drug dosages were defined in healthy adults during the drug development phase [ 11 ] by assessing the condition of a selective group of patients. However, these characteristics are not representative of all the patients who use these drugs, due to PK variability [ 12 ].…”

“…Monitoring techniques include single or mass-coupled chromatographic methods with a variety of detectors, including ultraviolet or fluorescent detectors (specified below) and immunoassays [ 10 , 11 ]. Many of these techniques have been approved by the Food and Drug Administration (FDA) of the United States [ 12 ].…”