Each Hour Counts: Physician and Pharmacist Perspectives on the Value of Rapid Blood Culture Testing

Sepsis, the host’s immune response to a serious infection, can be triggered by bacteria or fungi circulating in the bloodstream. Sepsis that results from bacteremia causes nearly 500,000 hospitalizations each year in the U.S. and accounts for 11% of intensive care unit (ICU) admissions.¹ Mortality associated with these infections is extremely high and can range anywhere from 25% to 80%.² Septicemia is not only burdensome due to its high associated rates of mortality, but also because of the excessive cost associated with treating this disease. Septicemia has consistently ranked as the most expensive condition to treat in U.S. hospitals. In 2011, treatment of septicemia resulted in an aggregate cost of $20.3 billion, which was 5.2 percent of the total aggregate cost of all hospitalizations.³ When compared to the average cost of a patient admitted to the intensive care unit (ICU) who does not acquire a bloodstream infection, those that do remain in the ICU 8 days longer and 24 days in the hospital longer, resulting in $36,000 to $40,000 in additional costs per patient.⁴

Time to appropriate therapy has been proven to be a critical determinant for patient outcomes. Kumar et al. demonstrated a 7.6% mean decrease in survival rates for each hour that optimal therapy is delayed following the start of sepsis-related hypotension.⁵ Conventional culture-based diagnostics, which remain the gold standard for identification of the bloodstream pathogens, are not ideal as they are associated with very slow turnaround times which can stretch upwards of 3-4 days. With long time- to-identification, a patient might remain on the inappropriate empiric therapy, predisposing them to a higher risk of mortality. Patients in the ICU receiving inadequate antimicrobial treatment for bloodstream infections have an associated mortality rate of 61.9%, while patients receiving appropriate therapy only have an associated mortality rate of 28.4%.⁶

To complicate matters, emergence of antimicrobial resistant bacteria has made management of septic patients even more challenging. This ever-evolving threat is driven by both appropriate and inappropriate antibiotic usage. Bacteria evolve to overcome threats to their survival which potentially shortens the effective lifespan of available therapeutics. The loss of the ability to effectively treat infection will deteriorate the quality of care that a healthcare provider can offer. With certain organisms becoming resistant to all available first- and second-line antimicrobials, clinicians are forced to treat with more toxic and more expensive drugs that do not have guaranteed activity against the given pathogen. Even when antimicrobials are available, patients with resistant infections have higher associated morbidity and mortality than patients with non-resistant infections, have increased length-of-stay in the hospital, and often have lasting side effects from the infection or treatment. More than two million people are infected with resistant infections in the U.S. annually, with more than 20,000 people dying from these infections.⁷ The economic burden in the U.S. alone for treating these resistant infections exceeds $20 billion per year.⁷ Carbapenem-resistant Enterobacteriaceae, or CRE, is currently one of the most impending threats throughout the world as these bacteria are resistant to nearly all available antimicrobials and have appropriately been coined “nightmare bacteria” and “superbugs.” In 2013, the Centers for Disease Control and Prevention (CDC) released a landmark report on antibiotic resistance threats in the U.S. This report classified the threat associated with resistant organisms as either urgent, serious, or concerning and measures that can be taken by healthcare providers to minimize the spread of resistant bacteria and prolong the efficacy of the available antimicrobials. The four core actions to fight the spread of resistant bacteria include: prevent infection and prevent the spread of resistance; tracking resistant bacteria, improving the use of available antibiotics; and promoting the development of new antibiotics and new diagnostic tests for resistant bacteria.⁷

Molecular based diagnostic tests have emerged as the first viable solution to culture for the detection of bloodstream pathogens. Rapid diagnostic tests for bloodstream infections have been able to accelerate the time to bacterial identification and antimicrobial resistance detection by as many as 2 days over traditional phenotypic methods, allowing clinicians the opportunity to place the patient on the optimal therapy much quicker. Clinical implementation of these tests has been associated with improved patient outcomes, enhanced antimicrobial stewardship, more effective infection control, and has led to reduction in healthcare costs.^8-13 The increase in adoption of rapid sepsis diagnostic tests has been driven, in large part, by clinical studies that have captured the clinical and economic impact of these tests.

This webinar will review the current guidelines for the management of septic patients and discuss the impact that rapid blood culture diagnostics are having on the clinician’s ability to manage patients with bloodstream infections and antimicrobial stewardship initiatives.

References

[1] Angus DC, Wax RS. Epidemiology of Sepsis: An Update. Crit Care Med 2011; 29: S109–S116.
[2] Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348: 1546–1554.
[3] Torio CM, Andrews RM. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer: HCUP Statistical Brief #160. 2013. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.pdf (Accessed September 2015).
[4] Pittet D, Tarara D, Wenzel RP. Nosocomial Bloodstream Infection in Critically Ill Patients: Excess Length of Stay, Extra Costs, and Attributable Mortality. JAMA 1994; 271: 1598–1601.
[5] Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589–1596.
[6] Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118: 146–155.
[7] CDC. Antibiotic Resistance Threats in the United States. 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf (Accessed September 2015).
[8] Sango A, McCarter YS, Johnson D, Ferreira J, Guzman N, Jankowski CA. Stewardship Approach for Optimizing Antimicrobial Therapy through Use of a Rapid Microarray Assay on Blood Culture Positive for Enterococcus Species. J. Clin. Microbiol. 2013; 51(12): 4008-11.
[9] Buchan BW, Ginocchio CC, Manii R, Cavagnolo R, Pancholi P, Swyers L, Thomson RB Jr, Anderson C, Kaul K, Ledeboer NA. Multiplex Identification of Gram-Positive Bacteria and Resistance Determinants Directly from Positive Blood Culture Broths: Evaluation of an Automated Microarray-Based Nucleic Acid Test. PLoS Medicine. 2013.
[10] Wojewoda CM, Sercia L, Navas M, Touhy M, Wison D, Hall GS, Procop GW, Richter SS. Evaluation of the Verigene Gram-Positive Blood Culture Nucleic Acid Test for Rapid Detection of Bacteria and Resistance Determinants. Journal of Clinical Microbiology. 2013; 51(4): 1188-92.
[11] Alby K, Daniels LM, Weber DJ, Miller MB. Development of a Treatment Algorithm for Streptococci and Enterococci from Positive Blood Cultures Identified with the Verigene Gram-Positive Blood Culture Assay. Journal of Clinical Microbiology. 2013; 51(11): 3869-71.
[12] Mancini N, Infurnari L, Ghidoli N, Valzano G, Clementi N, Burioni R, Clementi M. Potential Impact of a Microarray-Based Nucleic Acid Assay for Rapid Detection of Gram-Negative Bacteria and Resistance Markers in Positive Blood Cultures. J. Clin. Microbiol. 2014; 52(4). 1242-5.
[13] Box MJ, Sullivan EL, Ortwine KN, Paramenter MA, Quigley MM, Aguilar-Higgins LM, MacIntosh CL, Goerke KF, Lim RA. Outcomes of Rapid Identification for Gram-Positive Bacteremia in Combination with Antibiotic Stewardship at a Community-Based Hospital System. Pharmacotherapy 2015; 35(3): 269-76.

Speakers

Marin H. Kollef, M.D., FACP, FCCP, Professor, Medicine, Division of Pulmonary and Critical Care Medicine, Director, Medical Intensive Care Unit, Barnes-Jewish Hospital, Director, Respiratory Care Services, Barnes-Jewish Hospital

Dr. Kollef attended the U.S. Military Academy at West Point for his undergraduate training and the University of Rochester for his M.D. degree. Dr. Kollef completed his residency in Internal Medicine and his fellowship in Pulmonary and Critical Care Medicine at Madigan Army Medical Center in Tacoma, Washington. He served as the director for the medical ICU at Fitzsimons Army Medical Center from 1988 to 1992. During that time he also served as a general medical officer in support of the 1st Infantry Division during Operation Desert Storm. Dr. Kollef came to Washington University and Barnes-Jewish hospital in 1992. He is currently a professor of medicine at Washington University School of Medicine and the Director of Critical Care Research and Respiratory Care Services at Barnes-Jewish Hospital. Dr. Kollef was awarded Virginia E. and Sam J. Golman Chair in Respiratory Intensive Care Medicine in 2009. He has received numerous teaching awards and is a recognized expert in the performance of clinical outcomes research in the ICU setting. His clinical research focus has been the understanding and prevention of nosocomial infections and the improved care of mechanically ventilated patients. Dr. Kollef has published extensively in the areas of ventilator-associated pneumonia prevention/treatment and the importance of antibiotic resistance in the ICU setting.

Message Presenter

Brad J. Crane, PharmD, BCPS, Clinical Pharmacy Specialist, Critical Care/Infectious Diseases, Director, Antimicrobial Stewardship Program, Blount Memorial Hospital

Brad Crane, PharmD, BCPS is a Clinical Pharmacy Specialist in Infectious Diseases at Blount Memorial Hospital in Maryville, Tennessee. He graduated with his doctorate in pharmacy from the University of South Carolina in Columbia, SC. He completed post-graduate training with a pharmacy practice residency and a critical care specialty residency at the University of Tennessee Medical Center in Knoxville, TN. Dr. Crane was a critical care pharmacist for 10 years before he justified and transitioned into his current role as the Infectious Diseases Pharmacist and Director of the Antimicrobial Stewardship Program. Dr. Crane is a Board-Certified Pharmacotherapy Specialist and is a current member of the Society of Infectious Diseases Pharmacists (SIDP), Making a Difference in Infectious Diseases Pharmacotherapy (MAD-ID), American College of Clinical Pharmacists (ACCP), and American Society of Health-System Pharmacists (ASHP). He is a Clinical Assistant Professor (Part-Time) for the University of Tennessee College of Pharmacy and has presented at several professional meetings on antimicrobial stewardship and rapid diagnostic testing topics.

Message Presenter