In the U.S., each year 2 million people are seriously infected by bacteria resistant to antibiotics designed to treat their infections. The cost of antibiotic resistance was estimated to exceed $35 B. Nosocomial bloodstream infections (BSIs) including catheter-related BSIs, are important causes of patient morbidity and mortality. The annual incidence of BSIs is >750,000 cases with a 30% mortality rate, and the proportion of antibiotic-resistant bacteria causing BSIs is increasing. Increasing rates of multidrug-resistant bacteria require use of broad-spectrum antibiotics to avoid inadequate antibiotic coverage, but these drugs are often expensive, and their use promotes bacterial resistance. Rapid initiation of appropriate antibiotic therapy is strongly associated with decreased mortality rates in BSIs. In contrast, inappropriate antibiotic therapy and 3 hr delay in antibiotic administration after septicemia diagnosis have been associated with higher patient mortality. All antimicrobial stewardship programs (ASPs) today are to place patients with BSIs and other infection types on targeted appropriate antibiotic therapy based on AST results as quickly as possible. Rapid delivery of definitive antimicrobial susceptibility testing (AST) results is key to allow minimal use of broad-spectrum therapy and effective appropriate antibiotic regimen. At Linima Field Diagnostics, we have developed an instant antimicrobial susceptibility test (iAST) using piezoelectric plate sensors (PEPSs) that offers unparalleled speed (in 20 min) and sensitivities. Live bacteria coated on the PEPS surface can instantly broadens the top of the resonance peak of the PEPS due to the metabolic stresses generated by the bacteria, which is instantly reduced by the application of an antibiotic. A novel PEPS iAST was engineered by monitoring the decrease of the width of the top of the resonance peak of live bacteria-coated PEPS with an increasing antibiotic concentration. The goal is to demonstrate PEPS iAST in 20 min to both susceptible and resistant bacteria regardless they are fast or slowing growing. Preliminary results showed that PEPS iAST accurately determined antibiotic minimum inhibitory concentrations (MICs) for both susceptible and resistant Escherichia coli (EC) or Staphylococcus aureus (SA) but also for slow-growing Klebsiella pneumoniae (KP) and in 20 min. It is expected that PEPS iAST when developed will permit early application of appropriate antibiotic therapy to not only save lives and but also decrease antibiotic resistance.
Public Health Relevance Statement: Bacteria are increasingly more resistant to antibiotics and more infections, hospital-associated or otherwise, are increasingly due to multi-resistant bacteria. The proposed instant antimicrobial susceptibility test will complete the test in 20 minutes to permit early appropriate antibiotic therapy to save lives and reduce antibiotic resistance.
Project Terms: antibiotic design; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; antimicrobial; Antimicrobial susceptibility; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; bacterial resistance; base; Blood; Catheter-related bloodstream infection; cell motility; Clostridium difficile; commercialization; cost; design; Development; Diagnosis; Diagnostic; digital; economic cost; Engineering; Equipment; Escherichia coli; Flow Cytometry; Frequencies; genome sequencing; Goals; Growth; Health Care Costs; Hospitals; Hour; Incidence; ineffective therapies; Infection; Klebsiella pneumoniae; Laboratories; magnetic beads; Measurement; Mechanics; Metabolic stress; Metabolism; Methods; Microbiology; microcalorimetry; Minimum Inhibitory Concentration measurement; Monitor; Morbidity - disease rate; mortality; mortality risk; Multiple Bacterial Drug Resistance; nanometer; next generation sequencing; novel; Patients; Pharmaceutical Preparations; Phase; Productivity; programs; prototype; Pseudomonas aeruginosa; Regimen; Resistance; sensor; Sepsis; Septic Shock; Septicemia; Shock; Source; Speed; Staphylococcus aureus; Stream; Stress; Surface; System; targeted treatment; Test Result; Testing; Thinness; Time; Universities; vibration; whole genome; Width; Work
