An Artificial Capillary in Vitro Kinetic Model of Antibiotic Bactericidal Activity

Abstract

An in vitro model is described that simulates serum and tissue levels of antibiotic, allowing the exposure of bacteria to changing concentrations of antibiotic with little dilution of the inoculum. A bacterial suspension is placed in the outer chamber of a unit through which runs a bundle of 150 polysulfone hollow fibers that retain proteins of >10,000 daltons. These “capillaries” are in contact with the tubular lumen of a perfusion system. Antibiotic is injected into the tubing and circulated by a pump. At desired intervals given volumes of perfusate are removed and replaced with antibiotic-free broth (resulting in decreasing drug concentrations), or a constant level can be maintained. Samples from the outer chamber are taken for determination of bacterial counts and antibiotic levels. This method allows for the in vitro determination of persistent antibiotic effects and comparison of bolus and continuous infusions as well as the effects of single or combined antibiotics on bacterial killing and regrowth.