Recent Updates on the Role of Pharmacokinetics-pharmacodynamics in Antimicrobial Susceptibility Testing as Applied to Clinical Practice

Abstract

Given current challenges in antimicrobial resistance and drug development, infectious diseases clinicians must rely on their own ingenuity to effectively treat infections while preserving the current antimicrobial armamentarium. An understanding of pharmacokinetics (PK), pharmacodynamics (PD), antimicrobial susceptibility testing (AST), and how these concepts relate, is essential to this task. In this review, we discuss how and why PK-PD impacts AST and the way infectious diseases are being treated, with a particular focus on vancomycin for methicillin-resistant Staphylococcus aureus, penicillin for Streptococcus pneumoniae, and an update on cephalosporins for Enterobacteriaceae. Finally, we address how new ideas to exploit PK-PD can promote innovative study design and bring about more rapid regulatory review of new antimicrobials.

Coagulase negative staphylococcal sepsis in neonates: do we need to adapt vancomycin dose or target?

“…Therefore vancomycin has become the antimicrobial therapy of choice for targeted or empiric treatment of neonatal sepsis, especially in extremely premature babies [4]. However, despite extensive research and widespread use considerable controversies in vancomycin exposure required for optimal efficacy and consequently in dosing, remain [5, 6]. Poor tissue penetration of vancomycin suggests that different serum concentrations may be required depending on the site of infection, i.e.…”

Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients

“…For beta-lactams, the time that the unbound plasma/tissue concentration exceeds the MIC of a pathogen (tϾMIC) best describes the antimicrobial effect and is associated with a better clinical outcome in the case of infection (no specific thresholds for prophylaxis are available) (32,33). For cefuroxime, the required magnitudes of the tϾMIC to achieve bacteriostatic and bactericidal effects were estimated to be 30 and 41%, respectively (34).…”

A Rapidly Fatal Infection With Haemophilus influenzae Serotype E Harboring blaROB-1: The Dilemma of Safe De-escalation in the Setting of Potential Extended-Spectrum β-Lactamase Production

“…Even with advances such as MALDI-ToF and WGS, susceptibility testing and preliminary results still can vex clinical decision making. Clinical laboratories continue to struggle generating timely and actionable AST reports, due to regulatory and technical barriers [6, 7]. In addition, although WGS has become the “standard-of-care” for epidemiology, evidence for using WGS-inferred AST to guide clinical decision making is lacking [8].…”