Bone Concentration of Ampicillin/Sulbactam: A Pilot Study in Patients with Osteonecrosis of the Jaw

Int J Environ Res Public Health. 2022 Nov 13;19(22):14917. doi: 10.3390/ijerph192214917.

Abstract

Osteonecrosis of the jaw (ONJ) occurs typically after irradiation of the head and neck area or after the intake of antiresorptive agents. Both interventions can lead to compromised bone perfusion and can ultimately result in infection and necrosis. Treatment usually consists of surgical necrosectomy and prolonged antibiotic therapy, usually through beta-lactams such as ampicillin/sulbactam. The poor blood supply in particular raises the question as to whether this form of antibiosis can achieve sufficient concentrations in the bone. Therefore, we investigated the antibiotic concentration in plasma and bone samples in a prospective study. Bone samples were collected from the necrosis core and in the vital surrounding bone. The measured concentrations in plasma for ampicillin and sulbactam were 126.3 ± 77.6 and 60.2 ± 35.0 µg/mL, respectively. In vital bone and necrotic bone samples, the ampicillin/sulbactam concentrations were 6.3 ± 7.8/1.8 ± 2.0 µg/g and 4.9 ± 7.0/1.7 ± 1.7 µg/g, respectively. These concentrations are substantially lower than described in the literature. However, the concentration seems sufficient to kill most bacteria, such as Streptococci and Staphylococci, which are mostly present in the biofilm of ONJ. We, therefore, conclude that intravenous administration of ampicillin/sulbactam remains a valuable treatment in the therapy of ONJ. Nevertheless, increasing resistance of Escherichia coli towards beta-lactam antibiotics have been reported and should be considered.

Keywords: ARONJ; MRONJ; ONJ; ampicillin; antibiotic bone concentration; beta-lactam; jaw bone; osteonecrosis of the jaw; osteoradionecrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Escherichia coli
  • Humans
  • Osteonecrosis*
  • Pilot Projects
  • Prospective Studies
  • Sulbactam* / therapeutic use

Substances

  • sultamicillin
  • Sulbactam
  • Ampicillin
  • Anti-Bacterial Agents

Grants and funding

A.S. is supported by the Interdisciplinary Center for Clinical Research (IZKF). S.H. was supported by the Else Kröner-Fresenius Foundation (EKFS) and the Interdisciplinary Center for Clinical Research (IZKF) Würzburg. O.S.-C. reports receiving an endowed professorship grant (Horphag Research Ltd.).