Dramatic improvement in the timely and effective treatment of patients afflicted with sepsis can be achieved with the implementation of modern technologies for identification of offending microbial species and their innate genetic antibiotic treatment targets. Our collaborative team is planning to address this need using a Point-of-Care (POC) device equipped for identification of a bacterial species within 60 minutes of a routine Emergency Department laboratory blood draw or other specimen collection, followed by targeted analysis of its innate genetic antibiotic resistance elements within as little as 7 hours time. This revolutionary improvement in clinical management is critical for improving patient outcomes for a disease syndrome that is not only highly prevalent worldwide, consuming a massive amount of medical resources daily, but that only threatens to continue to worsen given current antibiotic stewardship practices. Early goal-directed therapy (EGDT) is the standard by which medical interventions are now shaped across fields in the modern clinical setting, ranging from trauma and neurosurgery to cardiology and infectious disease. Rapid and accurate diagnoses, paired with aggressive and effective intervention, are manifest to stemming the disease process as well as maintaining economically feasible care and improving long-term morbidity. The effort to apply EGDT to patients at high risk for systemic infection, sepsis, was initiated over a decade ago by Rivers and colleagues in the Emergency Department setting. Systematic approaches to early sepsis identification and intervention including broad-spectrum antibiotic coverage, and adequate fluid volume resuscitation have yielded definite improvements in patient outcomes and health care resource utilization. It has been recognized that one of the limiting factors in treatment of sepsis in the hospital setting is the timeliness of pathogen identification and implementation of appropriate antimicrobial therapy. The current "gold standard" of sepsis microbial identification is blood culture, which takes 3-5 days for a definitive species identification. Antimicrobial agent susceptibility for the given organism is generally garnered within this same time frame. However, in the period it takes from specimen collection to culture results, empiric broad-spectrum antibiotic coverage, often involving multiple antibiotics, must be provided to ensure organism eradication. This proposal aims to use Point of Care (POC) testing, as described by the investigatos' laboratory, to accurately identify pathogenic microorganisms in patients with suspected sepsis within 20 minutes of a laboratory blood draw or urine collection. The scope of the investigators' proposal is feasible in that 20 organisms account for 87% of microbial infections identified by culture-based techniques at University of Michigan Health/Sparrow Hospital, representing the greater Lansing, Michigan area, and 50 microorganisms would account for virtually every microbial infectious species (Khalife, 2011, unpublished data). In preliminary studies the investigators have validated this approach with laboratory-processed samples of Escherichia coli and Staphylococcus aureus. The investigators now are creating panels for multiple types of infections and have validated these efforts on over 30 microorganisms. POC testing will now be expanded to include additional microorganisms commonly encountered in sepsis patients or those with other identifiable infectious sources. Secondarily, antimicrobial resistance genes will be scanned using a functional genomics approach with highly-parallel quantitative PCR as performed by the investigators' laboratory in a previous study exploring the microbiota of porcine gastrointestinal tract. Because there are also human cells in the specimens collected, with separate permission we would like to evaluate the human genome of the patient with the infection to determine characteristics and conditions that may predict a complicated versus uncomplicated disease course.
