ABSTRACT
Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can cause a range of diseases, from mild skin infections, to more serious and invasive disease including deep or organ space surgical site infections, life-threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to antibiotic treatments. Despite current infection control measures, the burden of disease remains high. The most advanced vaccine in clinical development is a 4 antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase 2b/3 efficacy study in patients undergoing elective spinal fusion surgery (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has been shown in early phase clinical trials to be generally safe and well tolerated, and to induce high levels of bactericidal antibodies in healthy adults. In this review we discuss the design of SA4Ag, as well as the proposed clinical development plan supporting licensure of SA4Ag for the prevention of invasive disease caused by S. aureus in elective orthopedic surgical populations. We also explore the rationale for the generalizability of the results of the STRIVE efficacy study (patients undergoing elective open posterior multilevel instrumented spinal fusion surgery) to a broad elective orthopedic surgery population due to the common pathophysiology of invasive S. aureus disease and commonalties of patient and procedural risk factors for developing postoperative S. aureus surgical site infections.
Subject(s)
Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Staphylococcal Infections/prevention & control , Staphylococcal Vaccines/therapeutic use , Surgical Wound Infection/prevention & control , Antigens, Bacterial/administration & dosage , Bacteremia/prevention & control , Clinical Trials as Topic , Elective Surgical Procedures , Humans , Orthopedic Procedures , Staphylococcus aureus , Surgical Wound Infection/microbiologyABSTRACT
UNLABELLED: To permit assessment by positron tomography of left ventricular mechanical function, methods were developed to measure ejection fraction and regional wall motion and produce realistic images of the beating heart from ECG-gated PET data. METHODS: Following red cell labeling with 15O-carbon monoxide, seven-slice PET data were collected in list mode and reformatted into 16 time frames. Volume-rendered cine images were created by the depth-weighted maximum-activity method. To determine the left ventricular ejection fraction, background was subtracted in voxels outside the heart and the cubic datasets were rotated to the angle with the best septal separation. Depth weighting was applied to stimulate a 99mTc study, and the beating images were rendered by summing counts along parallel projection rays. These techniques were validated in 16 patients by comparison with planar studies performed with 99mTc-red cells. RESULTS: Visual grading of regional wall motion yielded exact agreement between the PET and 99mTc methods in 62% of walls with agreement with one grade in 94%. Assessment of quantitative regional wall motion agreed closely with an independent threshold edge detection method. CONCLUSION: PET techniques have been developed to measure left-ventricular ejection fraction and regional wall motion and to produce realistic beating images of the cardiac blood pool. This information can be obtained at the same time as measurements of perfusion and metabolism and in the same spatial orientation, thereby permitting quantitative assessment by positron tomography of global and regional mechanical function in relation to flow and metabolism.
