What the Clinical Microbiologist Should Know About Pharmacokinetics/Pharmacodynamics in the Era of Emerging Multidrug Resistance: Focusing on β-Lactam/β-Lactamase Inhibitor Combinations

Abstract

As a class, β-lactamase inhibitors have proved successful in extending the clinical utility of β-lactam antibiotics by circumventing β-lactamase-mediated resistance. However, the rapid evolution of these β-lactamases calls for a critical reevaluation of the relationships between susceptibility, drug exposures, and bacterial response. The existing paradigm for in vitro susceptibility testing and development of β-lactam/β-lactamase inhibitor combinations may not optimally facilitate clinical use. Thus, alternative approaches for pairing these combinations and evaluating in vitro susceptibility are needed to provide better guidance to clinicians.

Keywords: Combination therapy; Gram-negative bacteria; Optimal dosing; Pharmacokinetics/pharmacodynamics; Susceptibility testing.