Research Project
10317701
ABSTRACT: Osteoarticular infections (OAI) are prevalent medical conditions that disproportionately affect children, which can lead to serious complications including loss of motor function and bone deformity. Rapid and accurate diagnosis of OAI etiologic agents are critical to allow selection of specific and targeted treatment options and improve outcomes for pediatric patients. Yet, in clinical practice, patients are often started on broad spectrum antibiotics pending pathogen identification by culture or polymerase chain reaction, which can take several days for completion. In addition, the high rates of culture-negative OAI and the increased prevalence of antibiotic resistant strains make therapeutic decisions uniquely challenging for OAI. Meanwhile, unspecific therapy regimens with multiple antibiotics can lead to multiple short- and long- term adverse effects. Here, we propose to develop and test the MasSpec Pen (MSPen) technology as an innovative method for rapid and accurate identification of OAI directly from clinical specimens. We developed the MSPen as an easy-to-use handheld device integrated to a high-performance mass spectrometer for rapid (<20 seconds) detection of rich metabolic profiles directly from biological samples. Now, we hypothesize that the MSPen can be developed as a powerful technology for rapid, direct, and accurate identification of etiologic agents from OAI clinical samples, thus advancing treatment for pediatric patients by allowing selection of specific and targeted therapy. Through a collaboration between Prof. Livia S. Eberlin (Department of Chemistry, The University of Texas at Austin), expert in mass spectrometry and developer of the MSPen technology, Dr. Sarmistha B. Hauger (Chief of Pediatric Infectious Disease, Dell Medical School) and Dr. Lindsey Kirkpatrick (Infectious Disease Faculty, Indiana University School of Medicine), whose medical practices are dedicated to the treatment of pediatric infections, we propose to test our hypothesis by carrying out the following specific aims: Aim 1. Optimize the MSPen assay for molecular analysis of pediatric OAI clinical specimens and associated culture isolates. The MSPen provides transformative molecular detection capabilities in the direct analysis of complex biological samples along with operational features that are attractive for routine clinical use. We will refine the device and method to optimize its analytical performance for direct molecular analysis of OAI clinical specimens and corresponding culture isolates. Aim 2. Determine the diagnostic performance of the MSPen for pathogen identification in pediatric OAI samples. The MSPen has the potential to provide molecular information to drive rapid and accurate therapeutic decision- making. We will analyze pediatric OAI samples prospectively collected for our study encompassing clinically-relevant bacteria strains. Statistical classifiers will be developed to classify bacterial pathogens into taxonomical levels using clinical microbiology results as gold-standard. Aim 3. Evaluate the capabilities of the MSPen for the identification of antibiotic resistant bacterial strains. The increasing occurrence of antibiotic resistant bacteria in pediatric patients presenting OAI reveals a critical need for accurate identification of antibiotic susceptibility. We will investigate the capability of the MSPen in identifying antibiotic resistant and susceptible bacteria in clinical samples. Statistical classifiers will be developed to identify resistant or susceptible S. aureus, using clinical microbiology results as gold-standard.
