sultamicillin and Osteonecrosis

Ampicillin in combination with sulbactam is a widely used drug choice for infection prophylaxis, especially in oral and maxillofacial surgery. Clindamycin serves as an alternative in patients with known allergy to β-lactam antibiotics. To ensure effective prophylaxis, it is important to achieve sufficiently high concentrations of active antibiotic substances in the tissues affected by the surgery. To this end, a LC-MS/MS method was developed and validated that allows the quantification of ampicillin, sulbactam and clindamycin in jawbone, plasma, and so-called platelet-rich fibrin (PRF). Validation was performed in accordance with the European Medicines Agency guidelines for bioanalytical method validation. For all matrices, sample processing was carried out by protein precipitation with acetonitrile or methanol 80%, containing the isotope labelled internal standards (IS) of the three drugs. Analytes were separated on a pentaflourophenyl column at 20 °C using gradient elution. Furthermore, detection was accomplished by electrospray ionisation in positive-ion mode (ampicillin, clindamycin and corresponding IS) and negative-ion mode (sulbactam and corresponding IS) in combination with multiple reaction monitoring. Depending on the analyte and the matrix under investigation, calibration curves ranged from 0.14 to 59.8 µg/g (jawbone - ampicillin), 2.0-1000 µg/mL (plasma - ampicillin), and 1.0-495 µg/mL (PRF - ampicillin). All analytes fulfilled the requirements of the guideline regarding sensitivity, linearity, selectivity, carryover, within-run and between run accuracy and precision, matrix effect and extraction recovery in all matrices. The method was successfully applied to measure concentrations of ampicillin, sulbactam and clindamycin in real-life samples obtained in routine clinical practice.

Topics: Ampicillin; Chromatography, High Pressure Liquid; Chromatography, Liquid; Clindamycin; Humans; Osteonecrosis; Platelet-Rich Fibrin; Reproducibility of Results; Sulbactam; Tandem Mass Spectrometry

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe and therapy-resistant disease. The present study was performed to evaluate the role of the duration of preoperative antibiotic therapy within an otherwise standardized treatment protocol of patients with BRONJ stages I and II. One group of patients received a short-term preoperative antibiotic regime (A-ST) and the other a long-term preoperative antibiotic regime (B-LT).. A retrospective chart review was used to analyze 46 patients with BRONJ from 2004 to 2009 who were treated with the same surgical technique and the same postoperative antibiotic treatment. Ten patients were classified as stage I, and 37 as stage II. All patients had intravenous bisphosphonate therapy in their case histories. Surgical treatment included an extended surgical procedure with sequestrectomy, bone smoothing, tension-free tissue covering, and drainage, with attention to neighboring teeth. After surgery, antibiotics were given (median) for 7 days intravenously and orally for another 10 to 12 days. Only patients who fulfilled these criteria were included in the retrospective chart review. In group A-ST 16 patients with 17 operations received antibiotics for 1 to 8 days before operation, whereas in group B-LT 30 patients had preoperative therapy of 23 to 54 days. Postoperative clinical examination followed a standardized protocol. Complete healing with intact soft tissue coverage was regarded as a success.. The mean follow-up in both groups was 17.4 months (median, 11.5 months). Within the overall observation period, only 35% of patients in group A-ST and 70% in group B-LT showed complete healing, but at the time of the last clinical examination, 53% in group A-ST and 87% in group B-LT were free of soft tissue dehiscence. A certain number of soft tissue dehiscences within the observation period could clearly be related to later tooth extractions or pressure sores of dentures; excluding these interfering problems, 47% in group A-ST and 87% in group B-LT were treated successfully. Differences between these groups were significant.. This study indicates that surgical treatment in patients with stage I BRONJ and especially in those with stage II BRONJ in combination with a long-term preoperative antibiotic treatment can lead to a complete healing in 70% to 87% of cases in contrast to 35% to 53% with a short-term regime. The higher success rate after prolonged preoperative antibiotic therapy may be linked to an infectious role in BRONJ etiology requiring adequate treatment. Antibiotics may effectively treat neighboring lightly infected bone, whereas surgery removes the irreversibly infected and necrotic bone. To achieve complete healing, an extended surgical procedure in combination with local mouth rinses and prolonged antibiotic therapy can be recommended for treatment of BRONJ.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Bone Density Conservation Agents; Chlorhexidine; Diphosphonates; Female; Follow-Up Studies; Humans; Injections, Intravenous; Jaw Diseases; Male; Middle Aged; Mouthwashes; Osteonecrosis; Osteotomy; Postoperative Care; Retrospective Studies; Suction; Sulbactam; Suture Techniques; Time Factors; Treatment Outcome; Wound Healing