A micromethod for determination of antimicrobial agents in bone

A microtechnique, requiring very small amounts of tissue material, was developed for assay of antimicrobial agents in bone. Without previous homogenization or extraction, small bone pieces (mean weight 0.014 g) from human subjects and pigs were placed into wells in agar plates preinoculated with the test strain. Round and distinct zones of inhibition were formed around the pieces. Standards for ampicillin and flucloxacillin were prepared from freeze-dried bone pieces from human subjects and pigs with known amounts of antibiotics as well as in human plasma and phosphate-buffered saline (PBS). Curves obtained from these standards were linear. Bone pieces from human and pig maxilla gave superimposable curves, but differed from curves obtained in plasma or PBS. The method was used in a pharmacokinetic study of bacampicillin in human maxillary bone and plasma. Bacampicillin tablets (2 X 400 mg) were given to patients before oral surgery. Standardized bone pieces and plasma samples were obtained at different times during surgery. The peak ampicillin concentrations estimated from the population curves were 8.0 mg/l in plasma and 1.1 mg/l in maxillary bone. The elimination half-life of ampicillin was similar in plasma and maxillary bone.