<p><strong>BACKGROUND: </strong>Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery.</p>

<p><strong>METHODS: </strong>This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated.</p>

<p><strong>RESULTS: </strong>Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively.</p>

<p><strong>CONCLUSIONS: </strong>For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective cohort study using the Pediatric Health Information System database.</p>

<p><strong>OBJECTIVE: </strong>To describe longitudinal patterns of prophylactic antibiotic use and determinants of antibiotic choice for spinal fusion surgical procedures performed at US children's hospitals.</p>

<p><strong>SUMMARY OF BACKGROUND DATA: </strong>Surgical site infections (SSIs) account for a significant proportion of post-spinal surgery complications, particularly among children with complex conditions such as neuromuscular disease. Antimicrobial prophylaxis with intravenous cefazolin or cefuroxime has been a standard practice, but postoperative infections caused by organisms resistant to these antibiotics are increasing in prevalence. Studies describing the choice of antibiotic prophylaxis for pediatric spinal surgery are lacking.</p>

<p><strong>METHODS: </strong>We included children 6 months to 18 years of age discharged from 37 US children's hospitals between January 1, 2006, and June 30, 2009, with (1) an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code indicating a spinal fusion and (2) combinations of diagnosis codes indicating adolescent idiopathic scoliosis (AIS) (n = 5617) or neuromuscular scoliosis (NMS) (n = 3633). After identifying antibiotics ordered on the operative day, we described variation in broad-spectrum antibiotic use over time and measured associations between patient/surgery characteristics and antibiotic choice.</p>

<p><strong>RESULTS: </strong>Prophylactic antibiotic choice varied across hospitals and over time. Broad-spectrum antibiotics were used in 37% of AIS and 52% of NMS operations. Seven (19%) hospitals used broad-spectrum coverage for more 80% of all cases. For NMS procedures, broad-spectrum antibiotic use was associated with patient characteristics known to be associated with high SSI risk. Use of vancomycin and broad gram-negative agents increased over time.</p>

<p><strong>CONCLUSION: </strong>Broad-spectrum antimicrobial prophylaxis varied across hospitals and was often associated with known risk factors for SSI. These results highlight the need for future studies comparing the effectiveness of various prophylaxis strategies, particularly in high-risk subgroups. This research can inform the development of best practice for SSI prevention in spinal fusion procedures.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective cohort study using the Pediatric Health Information Systems database.</p>

<p><strong>OBJECTIVE: </strong>To determine the association between antifibrinolytic use and red cell transfusions in spinal fusion operations performed at 37 US Children's Hospitals.</p>

<p><strong>SUMMARY OF BACKGROUND DATA: </strong>Evidence from randomized clinical trials and systematic reviews suggests that antifibrinolytic therapy can significantly reduce blood loss in children undergoing scoliosis surgery; however, the effectiveness of these agents as used in surgeries performed at US children's has not been studied.</p>

<p><strong>MATERIALS AND METHODS: </strong>We included children aged 0-18 years with diagnoses indicating adolescent idiopathic scoliosis (AIS) or neuromuscular scoliosis (NMS) for whom a spinal fusion procedure was performed between January 1, 2006 and September 30, 2009. Patients with malignancy, trauma, coagulation disorders, or for whom a cell salvage device was employed were excluded. Multilevel logistic regression was used to determine associations between ε-aminocaproic acid (EACA), tranexamic acid (TXA), and aprotinin (APR) use and blood transfusions, controlling for patient and surgery characteristics.</p>

<p><strong>RESULTS: </strong>Cohorts consisted of 2722 AIS and 1547 NMS procedures. Antifibrinolytic use varied across hospitals (AIS 3.3%, interquartile range, 0%-42%; NMS 12 interquartile range, 0%-46%), and was significantly associated with NMS, posterior fusion, number of vertebrae fused. Overall, 15% of children received EACA, 7% TXA, and 2% APR. The median hospital-specific rate of red cell transfusions was 24% for AIS and 43% for NMS. In AIS operations, EACA use, but not TXA use, was associated with significantly lower odds of transfusion (odds ratio, 0.42; P&lt;0.001 vs. odds ratio, 1.0; P=0.8). In NMS operations, neither EACA nor TXA use was associated with a decrease in odds of red cell transfusions.</p>

<p><strong>CONCLUSIONS: </strong>The effectiveness of antifibrinolytics as used outside of clinical trials is unclear and should continue to be explored. Future prospective research is needed to evaluate which administration protocols will most benefit patients, as well as to determine the comparative effectiveness of these drugs in the context of other blood conservation strategies.</p>