Antibacterial and biocompatibility studies of triple antibiotics-impregnated external ventricular drainage: In vitro and in vivo evaluation

Abstract

Hydrocephalus is a neurological disease caused by an unusually high level of cerebrospinal fluid (CSF), which can be relieved by external ventricular drainage (EVD) insertion. However, the infection can lead to complications during the use of EVD. In this study, EVD was impregnated with three synergistic antibiotics, including rifampicin, clindamycin, and trimethoprim, to improve the antibacterial property. The impregnated drainage was studied for its characteristics in vitro and in vivo. Drug loading determination revealed that rifampicin had the highest concentration in the tube, followed by clindamycin and trimethoprim, respectively. In vitro cytotoxicity and hemolytic studies showed no toxic effects from antibiotics-impregnated EVD on fibroblast and red blood cells. For antibacterial testing, the impregnated EVD exhibited antibacterial activity against Staphylococcus aureus MRSA and Staphylococcus epidermidis up to 14 and 90 days, respectively. Moreover, biocompatibility and drug release into the bloodstream and surrounding tissues were investigated by implantation in rabbits for 30 days. Histology and morphology results showed that fibroblast cells began to adhere to the drainage surface and inflammatory cell numbers were noticeably small after the long-term implantation. In addition, there was no drug leakage to the bloodstream and surrounding tissues. Hence, this impregnated EVD can potentially be used for antibacterial application.