Use of Supplemented or Human Material to Simulate PD Behavior of Antibiotics at the Target Site In Vitro

• Main Authors: Alina Nussbaumer-Pröll, Markus Zeitlinger
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Pharmaceutics
• Subjects: adapted growth media; body fluids; in vitro; PD; MIC; TKC
• Online Access: https://www.mdpi.com/1999-4923/12/8/773

In antimicrobial drug development, in vitro antibiotic susceptibility testing is conducted in standard growth media, such as Mueller–Hinton broth (MHB). These growth media provide optimal bacterial growth, but do not consider certain host factors that would be necessary to mimic the in vivo bacterial environment in the human body. The present review aimed to include relevant data published between 1986 and 2019. A database search (PubMed) was done with text keywords, such as “MIC” (minimal inhibitory concentration), “TKC” (time kill curve), “blood”, “body fluid”, “PD” (pharmacodynamic), and “in vitro”, and 53 papers were ultimately selected. Additionally, a literature search for physiologic characteristics of body fluids was conducted. This review gives an excerpt of the complexity of human compartments with their physiologic composition. Furthermore, we present an update of currently available in vitro models operated either with adapted growth media or body fluids themselves. Moreover, the feasibility of testing the activity of antimicrobials in such settings is discussed, and pro and cons for standard practice methods are given. The impact on bacterial killing varies between individual adapted microbiological media, as well as direct pharmacodynamic simulations in body fluids, between bacterial strains, antimicrobial agents, and the compositions of the adjuvants or the biological fluid itself.