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Addressing Shortcomings in Infection and Sepsis Treatment Should Be Top of the Priority List

Hospitals are increasingly facing the challenge of cutting costs while also improving clinical outcomes. This is certainly true in the infectious disease sector, as unrecognized or ineffectively treated bacterial infections can lead to sepsis, which can be life-threatening. Sepsis is relatively common: each year in the United States, more than 1.6 million adults develop sepsis and approximately 270,000 people die from it.1,2 In fact, sepsis claims more lives annually than breast cancer, prostate cancer, and AIDS, combined.3 As a result, it is important for clinicians and health care executives to reflect upon why sepsis recognition and treatment are crucial for both facilities and patients, and how they can be achieved.

As an infectious disease pharmacist for more than a decade, I have first-hand experience with managing infections and sepsis in hospitals and am familiar with the effects the current process has on patients and health systems alike. Consider the typical diagnosis and treatment protocol for bacteremia. Currently, when a clinician suspects a patient has a bloodstream infection, a blood culture is obtained to confirm if bacteria is present, then, if it is gram positive or negative,  and then to identify the pathogen. This is a process that can take 1to 4 or more days because it requires growing the organism in the lab. During this time, the clinician will start the patient on broad-spectrum antibiotics while they await results to see if they prescribed the appropriate medication. Concurrently, the patient’s condition may begin to improve or decline, the latter of which would mean that the initially prescribed treatment may be ineffective, and the clinician will modify treatment. This happens often—research shows that 40% of patients with bloodstream infections are initially treated ineffectively.4

Initial treatment could require adjustments due to a number of reasons. The specific bacterial pathogen present in the patient’s blood may not be treatable by the antibiotic they were initially receiving. Alternatively, it is possible that a bloodstream infection is not what is causing the symptoms and they have a different diagnosis. In either case, these patients are being exposed to the adverse effects of an antibiotic they did not need in the first place, which can be extremely detrimental to their health, and they are also at risk of developing antibiotic resistance.

The overuse of unnecessary medications can be expensive for hospitals, and treating patients incorrectly can increase their length of stay—two costs that, in theory, should be avoidable. In fact, according to the US Centers for Disease Control and Prevention (CDC), antibiotic stewardship programs, which are implemented to improve the utilization of antibiotics, have regularly saved $200,000 to $400,000 in hospitals and other health care facilities annually.5

Additionally, even more concerning is that if patients do in fact have bacteremia or sepsis, they are at risk of going into septic shock, which can be fatal.

Many of these issues stem from current limitations with blood cultures, primarily that they can take days to reveal the critical information necessary for clinicians to make the most informed treatment plans possible. This shortcoming has huge implications considering each hour of delayed treatment after the onset of hypotension increases mortality risk nearly eight percent.6

Furthermore, not only do blood cultures create delays in receiving results, but they can also produce false negatives. In many cases, critically-ill patients are already receiving antibiotics at the time of blood culture draw, which can render cultures negative. Blood culture often misses 35% to 50% of the organisms for the first blood draw; and, as a result, it is possible that stable appearing patients can be cleared to return home when they still have traces of bacteria in their blood, which can potentially lead to readmissions.7,8 In fact, sepsis is the number one most prevalent and costly cause of hospital readmissions.9 Alternatively, a negative culture in a critically-ill patient results in extended durations of broad-spectrum antimicrobials in an effort to empirically treat the unidentified pathogen.

Clearly, optimal sepsis treatment starts with early sepsis-causing pathogen detection and targeted treatment. Although there is technology that can test susceptibility within hours to target what specific drugs and dosage to use for treatment, none exist today that can do so directly from whole blood and still require waiting for blood culture results first, adding even more time to the infection diagnosis and treatment process. Fortunately, research has proven that US Food and Drug Administration-cleared technology capable of detecting 5 of the most common sepsis-causing pathogens direct from whole blood without the wait of blood cultures can be especially effective. In a pivotal trial including 11 centers and more than 1400 subjects, such technology provided clinicians with test results 2.5 days faster than blood cultures and identified 92 more patient infections than blood cultures. By identifying common sepsis-causing species of bacteria quickly and accurately from whole blood directly, clinicians can improve the empiric therapy they are already providing with specific pathogen details that can foster more targeted treatment plans. As a result, patients can get started on the right therapy faster, which can help prevent progression to sepsis or further complications in already septic patients, as well as the costs and poor clinical outcomes associated with sepsis.

Besides the important fact that prevention should be a priority for any disease as common and life-threatening as sepsis, the negative impact that this disease can have on patient outcomes, hospital costs and readmissions demonstrates a need for improvement in infection management. Blood cultures have been considered the standard of care for diagnosing bacteremia for nearly 100 years. With how far science has advanced over the years, it’s time for clinicians and health care executives to seek out new solutions to the longstanding obstacles in infection diagnosis and treatment.
Dr. Sandy Estrada is the Director of Clinical Affairs at T2 Biosystems. She was previously the Infectious Diseases Clinical Pharmacist for Lee Health in Ft. Myers, FL for 13 years where she served as the co-director of Antimicrobial Stewardship and director of the ID Pharmacy Residency Program. Dr. Estrada earned a BS in Pharmaceutical Science and a PharmD from the University of Toledo College of Pharmacy and has been board certified in Pharmacotherapy since 2002. She is an active member of multiple professional organizations including the Society of Infectious Diseases Pharmacists, American College of Clinical Pharmacy, and American Society of Health-System Pharmacists, and she is currently the president of the Florida Society of Health Systems Pharmacists. Dr. Estrada’s research interests include clinical and economic outcome studies involving antimicrobial stewardship and implementation of molecular diagnostics, and she has spoken on these topics at the regional, national and international level.

  1. Elixhauser A, Friedman B, Stranges E. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Available from:" .
  2. Centers for Disease Control and Prevention. Sepsis. Data & Reports." . Updated September 19, 2018. Accessed September 30, 2018. 
  3. Sepsis Alliance. Sepsis Fact Sheet." . Updated 2016. Accessed September 30, 2018.
  4. Buehler SS, Madison B, Snyder SR, et al. Effectiveness of practices to increase timeliness of providing targeted therapy for inpatients with bloodstream infections: a laboratory medicine best practices systematic review and meta-analysis. Clin Microbiol Rev. 2016 Jan;29(1):59-103. doi: 10.1128/CMR.00053-14.
  5. Centers for Disease Control and Prevention. Antibiotic Use in the United States, 2017: Progress and Opportunities." . Updated October 6, 2017. Accessed September 30, 2018.
  6. Kumar A, Roberts D, Wood KE, 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 Jun;34(6):1589-96.
  7. Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013 May;56(9):1284-92. doi: 10.1093/cid/cit006.
  8. Cockerill III FR, Wilson JW, Vetter EA, et al. Optimal testing parameters for blood cultures. Clin Infect Dis. 2004 Jun 15;38(12):1724-30.
  9. Mayr FB, Talisa VB, Balakumar V, Chang CCH, Fine M, Yende S. Proportion and cost of unplanned 30-day readmissions after sepsis compared with other medical conditions. JAMA. 2017 Feb 7;317(5):530-531. doi: 10.1001/jama.2016.20468.
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