Background and Importance Antiresorptive agent-related osteonecrosis of the jawbone (ARONJ) is a severe complication after therapy with bisphosphonates or denosumab. The current ARONJ guideline by the German Dental and German Oral and Maxillofacial Associations states the administration of systemic antibiotics intended as an adjunct to surgery to be obligatory in all operative ARONJ treatment. Penicillin-based antibiotics (alone or in combination with beta-lactamase inhibitors or metronidazole) are the agents administered most frequently. Knowledge of the achievable antibiotic concentrations is important specially as the efficacy of antibiotic treatment depends significantly on the penetration to the infection site.

Aim and Objectives The aim of this study was to obtain qualitative and quantitative data on penicillin G concentrations in bone affected by ARONJ following intravenous administration and get comparable results to other concentrations measured with the same extraction method.

Material and Methods Samples of necrotic bone and pre- and intraoperative blood samples were obtained at 18 to 72 min after completion of a single perioperative infusion with 10 million IU (6000 mg) of penicillin G from a total of 19 patients meeting all inclusion criteria. The bone samples were extracted with phosphate buffer solution in a proportion of 1:10 as in the comparative studies. After deproteinisation with acetonitrile, we used LC-MS (q-TOF) to analyse the bone extracts and the serum samples. To evaluate minimum inhibitory concentrations in µg/ml the bone concentrations (µg/g) were multiplied by 1.5.

Results As expected, the values of the bone concentrations were lower than comparable results reported for healthy jawbone (median concentrations 2.7µg/g vs. 17.4µg/g). The calculated bone concentrations in µg/ml were: 14 samples > 1µg/mL, 2 samples > 0,1µg/mL and 3 samples < 0,1µg/mL. With regard to bacteria commonly found in bone affected by ARONJ, the minimum inhibitory concentrations (MIC/MIC90) values for penicillin G were mostly exceeded. The median intraoperative serum concentration was 116µg/mL.

Conclusion and Relevance The conventional analytical method, developed in the hospital pharmacy led to comparable results and was relevant to evaluate the preoperative infusion of penicillin G. As oral administration of antibiotics is common in clinical practice, a similar study might be carried out focusing on antibiotics administered orally.

Conflict of Interest No conflict of interest.