The financial burden of acute odontogenic infections: the South Australian experience.

BACKGROUND: Acute odontogenic infections are a common surgical emergency managed by public hospitals in Australia which cause considerable patient morbidity and occasionally, mortality. Despite posing a significant public health burden, Australian data evaluating the cost of the management of these patients are lacking. This study assessed the patient and treatment variables associated with inpatient management of deep odontogenic infections, and their respective financial impact, at a statewide Oral & Maxillofacial service. METHODS: A retrospective audit was carried out of patients with deep odontogenic infections at our institution, over a 7-year period. The primary outcome was the total cost of admission. Secondary outcomes included treatment received, operating room time, return-to-theatre, length of admission (LOS), and intensive care unit (ICU) use. Cost variables were assessed against the total LOS and ICU use to determine clinical predictors affecting outcome. RESULTS: Four hundred and sixty two patients met the inclusion criteria. The average cost per patient was $12 228 Australian Dollars. After multivariate analysis, variables most significantly associated with increased cost of care and LOS were high-risk infections with airway compromise, high admission white cell count and age. CONCLUSION: Hospital-based management of deep-space odontogenic infections engender significant costs compared to early primary care intervention such as a dental extraction ($181/extraction).

Antibiotic resistance in severe odontogenic infections of the South Australian population: a 9-year retrospective audit.

BACKGROUND: The aims of this study were to evaluate the microbiological trends in severe odontogenic infections requiring hospital admission in the South Australian Oral and Maxillofacial Surgery Unit. Rates of antibiotic resistance to empirical antibiotic regimens were determined to quantify the clinical implications of antibiotic-resistant odontogenic infections. METHODS: A retrospective case audit was performed on all odontogenic infections admitted to the Royal Adelaide Hospital over a 9-year period. Data was collected regarding demographics, microbiological culture and sensitivity results, and clinical outcome variables. RESULTS: Of a total of 672 patients, microbiology data was available for 447 cases. Penicillin-resistant organisms were identified in 10.8% of patients, who required a significantly longer length of hospital admission (mean, 9.93 days) and higher rates of non-response to initial surgical therapy (40%). CONCLUSIONS: There were moderate rates of antibiotic-resistant odontogenic infections within the South Australian population. Patients within this subgroup demonstrate markedly poorer clinical outcomes. Effective treatment of odontogenic infections involves early operative intervention, with adjunctive use of appropriate antibiotic therapy that involves close monitoring of response to removal of the cause and use of first-line antibiotic agents. Cases that fail to respond require urgent specialist review in order to reduce morbidity and mortality outcomes.

Targeted antitumor prodrug therapy using CNGRC-yCD fusion protein in combination with 5-fluorocytosine.

BACKGROUND: The enzyme-prodrug system is considered a promising tool for tumor treatment when conjugated with a targeting molecule. The asparagine-glycine-arginine (NGR) motif is a developing and interesting targeting peptide that could specifically bind to aminopeptidase N (APN), which is an NGR receptor expressed on the cell membrane of angiogenic endothelial cells and a number of tumor cells within the tumor tissues. The objective of this study was to develop a novel targeted enzyme-prodrug system using 5-fluorocytosine (5-FC) and an NGR-containing peptide fused with yeast cytosine deaminase (yCD), i.e. CNGRC-yCD fusion protein, to target APN-expressing cells within the tumor tissues and to convert 5-FC into 5-fluorouracil (5-FU) to kill tumors. RESULTS: Both yCD and CNGRC-yCD proteins were cloned into the pET28a vector and expressed by an Escherichia coli host. Both yCD and CNGRC-yCD proteins were purified and the yields were approximately 20 mg/L with over 95 % purity. The binding assay demonstrated that the CNGRC-yCD fusion protein had specific binding affinity toward purified APN recombinant protein and high-APN-expressing cells, including human endothelial cells (HUVECs) and various types of human tumor cell lines, but not low-APN-expressing tumor cell lines. Moreover, the enzyme activity and cell viability assay showed that the CNGRC-yCD fusion protein could effectively convert 5-FC into 5-FU and resulted in significant cell death in both high-APN-expressing tumor cells and HUVECs. CONCLUSIONS: This study successfully constructs a new targeting enzyme-prodrug system, CNGRC-yCD fusion protein/5-FC. Systematic experiments demonstrated that the CNGRC-yCD protein retained both the APN-binding affinity of NGR and the enzyme activity of yCD to convert 5-FC into 5-FU. The combined treatment of the CNGRC-yCD protein with 5-FC resulted in the significantly increased cell death of high-APN-expressing cells as compared to that of low-APN-expressing cells.