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conferenceseries
.com
Volume 7
Clinical Microbiology: Open Access
Clinical Microbiology 2018
July 16-17, 2018
July 16-17, 2018 Melbourne, Australia
2
nd
International Conference on
Medical and Clinical Microbiology
The hollow fiber infection model: Principles and practice
John James Stewart Cadwell
FiberCell Systems Inc., USA
E
merging antibiotic resistance presents a serious global health threat. 2 million people in the United States were infected
with antibiotic resistant bacteria in 2014 and more than 20,000 died as a direct result of these infections, many more
from complications. Antimicrobial resistance has been identified as one of the three greatest threats to human health.
Antibiotic discovery and development require static susceptibility testing to screen compounds,
in vitro
Pharmacodynamics/
Pharmacokinetic (PK/PD) studies to model drug dynamics and efficacy and testing in animal models to provide critical
information prior to the clinical evaluation of new antibiotics. The one compartment PK/PD model typically consists of an
open central reservoir containing the organism of interest, a source of diluent and a waste reservoir: (1) Open system, not bio
safe, (2) bacteria numbers change over time, (3) large volume requires large amount of drug and diluent and (4) rapid changes
in drug concentration not possible, cannot model short half-lives. Animal models have many shortcomings though they have
served as a primary development tool for many years: (1) PK/PDmay not match human values, (2) cannot sample same animal
over time, (3) difficult to study large numbers of bacteria to reveal resistance and (4) many infections cannot be modeled in a
mouse or other animal. To address these shortcomings the two-compartment
in vitro
pharmacokinetic model utilizing hollow
ber bioreactors was developed, the Hollow Fiber Infection Model (HFIM). The advantages of the HFIM are as follows: (1)
Closed, bio-safe system, (2) large number of organism can be tested, revealing resistance, (3) Precisely simulates human PK/
PD, (4) repetitive sampling over time, both drug and organism, (5) total kill can be determined, (6) single use, disposable,
reproducible, (7) two drug models can be tested, (8) can model both dosing curve and elimination curve and (9) can look at
bacteria in different growth phases and in combination with cells. The clinical utility of the HFIM has been demonstrated and
is now endorsed by the EMA. An overview of historic PK/PD models is presented and the utility of the system as it relates to
antibiotics and other drugs are discussed.
Biography:
John James Stewart Cadwell has received his degree in Pharmacology from the University of Miami in 1981. He spent additional
time studying at the University of Nottingham and the National Institute of Medical Research at Mill Hill, UK. In 2000 he
founded FiberCell Systems Inc., a company specializing in the research and supply of hollow fiber bioreactors. He has over 10
publications in the field and three patents relating to hollow fiber systems and is considered a world expert in the field.
jcadwell@fibercellsystems.comJohn James Stewart Cadwell, Clin Microbiol 2018, Volume 7
DOI: 10.4172/2327-5073-C2-036