title: Ultrasonically enhanced rifampin activity against internalized Staphylococcus aureus.
abstract: Staphylococcus aureus (S. aureus) is the principle causative agent of osteomyelitis, accounting for 80% of all human cases. S. aureus internalized in osteoblasts escapes immune response, including engulfment by phagocytes. It also escapes the action of a number of antibiotics. Ultrasound increases cell membrane permeability to a number of drugs. Following an internalization assay, we used low-frequency, low-power ultrasound combined with the antibiotic rifampin to target S. aureus internalized in human osteoblasts. Tryptic soy agar (TSA) was used to quantitate the antibacterial effect of rifampin combined with low-frequency ultrasound. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability following exposure to ultrasound. Our data revealed that rifampin successfully penetrates into osteoblasts and kills internalized S. aureus in osteoblasts, while low-frequency ultrasound promotes this process. Ultrasound had a negative impact on the cell viability of osteoblasts; however, this damage was slight and reversible. Ultrasound-enhanced antibiotic efficiency to bacteria internalized in the osteoblasts may contribute to the control of chronic infection to reduce recurrence.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233,  P.R. China.
authors.forename: Si-Feng
authors.initials: SF
authors.lastname: Shi
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.forename: DE-Sheng
authors.initials: DS
authors.lastname: Chen
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guo