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

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.

Mandibular Osteoradionecrosis: Defining the Microbial Milieu and Antimicrobial Resistance at the Time of Rescue Flap Surgery

“…We know from recent bioavailability studies that intraosseous concentrations of ampicillin/sulbactam in ORN are sufficient to treat Streptococcal and Staphylococcal species with intravenous therapy. 20 Our cohort did not reveal clindamycin resistance to GPC. A previous study demonstrated this resistance in mandibular infections.…”

Osteoradionecrosis of the Jaw—Comparison between Bone and Soft Tissue Injury and Their Influence on Surgical Outcomes—A Retrospective Cohort Study

“…The effect of antibiotic therapy on necrotic bone is largely unclear. Only a few studies have looked at the actual concentration of antibiotics in necrotic bone [24,25]. These studies describe low but sufficient concentrations of beta-lactam antibiotics to eradicate most bacteria, such as Streptococci and Staphylococci, which are typically present in ORN.…”

Unveiling Medication-Related Osteonecrosis of the Jaw: A Rapid Review of Etiology, Drug Holidays, and Treatment Strategies

“…Studies on the systemic administration of ampicillin/sulbactam and clindamycin for MRONJ demonstrate their effectiveness in reaching therapeutic jawbone concentrations [23,62]. Ampicillin/sulbactam showed that a reduced duration of oral administration could be sufficient for MRONJ prevention [23], while clindamycin achieved sufficient concentrations in both vital and necrotic bone samples to combat common bacteria associated with MRONJ [62]. These findings underscore the viability of tailored antibiotic therapy as a comprehensive strategy for the prevention and treatment of MRONJ.…”

“…This indicates that reduced oral antibiotic administration duration can be sufficient for MRONJ prevention when combined with proper preventive measures [61]. Studies on the systemic administration of ampicillin/sulbactam and clindamycin for MRONJ demonstrate their effectiveness in reaching therapeutic jawbone concentrations [23,62]. Ampicillin/sulbactam showed that a reduced duration of oral administration could be sufficient for MRONJ prevention [23], while clindamycin achieved sufficient concentrations in both vital and necrotic bone samples to combat common bacteria associated with MRONJ [62].…”