Journal of Pharmaceutical Microbiology

The Hollow Fiber Infection Model, Principles and Practice

Emerging antibiotic resistance offers 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 detection and growth 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 offer critical information prior to the clinical evaluation of new antibiotics. Animal models have many shortcomings
though they have served as a primary development tool for many years: 1) PK/PD may not match human values 2) Cannot sample the
same animal over time 3) Hard to study large statistics of bacteria to reveal resistance 4) Several infections cannot be demonstrated
in a mouse or other animal. To address these shortcomings the Hollow fiber infection model (HFIM) was developed. The advantages
of the HFIM are as follows: 1) Closed, bio-safe system 2) Huge number of organisms can be tested, revealing resistance 3) Quite simulates
human PK/PD 4) Repetitive sampling over time, together drug and organism 5) Whole kill can be determined 6) Solitary use, disposable,
reproducible 7) Double drug models can be evaluated 8) Can model both the dosing curve and elimination curve 9) Can look at bacteria
in various growth phases and in combination with cells. The clinical utility of the HFIM has been established and is now recognized by the
EMA. An outline of historic pk/pd models is offered and the utility of the system as it relays to antibiotics and other drugs are discussed

Author(s):

John James Stewart Cadwell

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