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.
Highlights
The need for precise measurement of antimicrobial agents in the blood of patients to follow treatment success or failure was Author Johan W
Antibiotic pharmacokinetics (PK) is commonly defined as ‘what does the body do to the drug’ during its complete cycle in vivo, whereas pharmacodynamics (PD) relates to ‘what the drug does to the microorganism in vivo’, the interplay between the two, ‘PK/PD’, defining the optimum antimicrobial activity achievable for the unbound drug concentrations at the site of infection
therapeutic drug monitoring (TDM) should be clearly positioned as an integral part of the antimicrobial stewardship program in hospitals given its pivotal role in antibiotic treatment optimization
Summary
The need for precise measurement of antimicrobial agents in the blood of patients to follow treatment success or failure was Author Johan W. Unpredictable drug concentrations in plasma and other body compartments due to altered volume of distribution and clearance may result from factors as diverse as acute pathophysiology during critical care admission (such as sepsis and immuno-suppression), obesity [10], early ages [11], advanced age, surgical prophylaxis for longer invasive procedures [12], cystic fibrosis [13], the use of techniques for organ replacement in case of organ failure (extracorporeal membrane oxygenation (ECMO)) and renal replacement therapy (RRT) [14, 15] To add to these significant alterations of PK in critically ill patients, the PD target might be different depending on the indications. Sub-optimal dosing and its clinical consequences is a domain of important research that should be thoroughly included in any development protocol for new antimicrobials
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