Clinical Microbial Species and Antibiotic Resistance Identification in Patients Presenting to the Emergency Department With Three of Four Systemic Inflammatory Response Syndrome (SIRS) Criteria - is Rapid Identification Possible and Accurate?

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 20 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 timeframe.
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 our 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 our proposal is feasible in that 20 organisms account for 87% of microbial
infections identified by culture-based techniques at Sparrow Hospital, representing the
greater Lansing, Michigan area, and 50 microorganisms would account for virtually every
microbial infectious species (Khalife, 2011, unpublished data). To date we have validated
this approach with laboratory-processed samples of Escherichia coli and Staphylococcus
aureus. POC testing will now be expanded to include additional microorganisms commonly
encountered in sepsis patients. Secondarily, antimicrobial resistance genes will be scanned
using a functional genomics approach with highly-parallel quantitative PCR as performed by
our laboratory in a previous study exploring the microbiota of porcine gastrointestinal
tract.

Inclusion Criteria:

Adult patients with 3 of 4 systemic inflammatory response syndrome (SIRS) characteristics
(1. tachycardia, 2. fever or hypothermia, 3. tachypnea, 4. leukocytosis), who have blood
cultures drawn and urine collected for the evaluation of suspected sepsis, and/or other
bodily fluids collected for culture and sensitivity analysis.

Patients with other sources of infection with less than 3 of 4 SIRS criteria

Exclusion Criteria:

Pediatric patients Adult patients with less than 3 of 4 systemic inflammatory response
syndrome (SIRS) characteristics