Sepsis and antibiotic stewardship: the importance of rapid ID, rapid AST and right drug-bug match

A study released in August 2013 by the Healthcare Cost and Utilization Project (HCUP) and the Agency for Healthcare Research and Quality, a division of the U.S. Department of Health and Human Services, noted that sepsis is currently the most expensive condition to treat.¹ The study, which looked at cost data from 2011, reported that sepsis cost an aggregate of $20.3 billion across the United States. Medicare payments for hospital inpatient services were $139 billion in 2012.² That means the national annual expenditure for sepsis represents 15% of all Medicare inpatient coverage, and this expenditure is growing due to the aging Baby Boomer generation and the resulting spike in patient volumes. Each year, approximately 750,000 Americans get sepsis,³ and more than 200,000 die.⁴ For most clinical teams, a big piece of the protocol for sepsis is starting IV antibiotics, often empiric antibiotics, quickly. While saving the patient is paramount, we cannot ignore the long-term impact this approach has on antibiotic resistance.

We do have tools that can help us curb sepsis while also practicing good antibiotic stewardship. The key to fighting sepsis in the age of resistance is smart use of the tools at our disposal that enable us to quickly ascertain sepsis risk, identify the specific pathogens causing the infection, and match the most appropriate antimicrobial.

The emergence of new antibiotic resistance mechanisms has resulted in a number of new challenges for clinicians. Therapeutic decisions are more complicated. Concern over outcomes has facilitated the need to place patients on appropriate therapy sooner. At the same time, clinical teams are also under pressure to step down therapy sooner in order to decrease resistance. The laboratory’s role is to provide the pathogen IDs and the antibiotic-susceptibility tests faster. 

In our lab, we’ve utilized an automated antimicrobial identification system, which we’ve found to be a fast and accurate way to combine pathogen identification with antibiotic susceptibility profiling. This is in contrast to growth-based systems, which require overnight incubation and thus delay results and subsequent therapy. 

Before I came to New York Hospital-Queens, my team at my previous lab had a great deal of success through streamlining the system’s workflow. We were able to significantly reduce the time it took to transition patients away from empiric antibiotics to targeted therapy. One of the ways we did this was by loading samples into the system throughout the day instead of loading all cultures by batch at the end of the shift. 

We also saw the need for expedited reporting of results, especially results for drug-resistant organisms. We utilized a facet of our microbial identification technology called auto-posting. Here’s how auto-posting works:

• An isolate is identified.
• Antibiotic susceptibility tests are completed.
• These two results are then analyzed through the system to confirm the drug-bug match.
• Results are then automatically posted to the laboratory information system (LIS) and to the hospital information system (HIS), effectively sharing the results with the lab and clinical teams simultaneously.

This way, we can post an actionable result the same afternoon the isolate is identified. Obviously this has tremendous impact on patients at risk for sepsis. By our also alerting Infection Control, patients with multidrug resistant organisms (MDRO) can be isolated more quickly to prevent their spread. Prior to beginning our drug-bug match auto-posting, we saw 36% of Klebsiella pneumonia isolates produced carbapenemase. After a year of implementing our auto-posting protocol, we reduced carbapenemase-producing Klebsiella to 23%. (See Figure 1.)

Speed is certainly of the essence when it comes to instigating targeted therapy. Stepping down therapy is also critical if we are to combat the growth of antimicrobial resistance. This is another reason it is critical to quickly ascertain the right drug-bug match. By fighting the infectious pathogen with only the most effective antimicrobial and weaning the patient off powerful antibiotics sooner, we can effectively work to save the patient and protect the armamentarium of antibacterial drugs.

As we move forward and continue to look for new ways to deliver actionable pathogen ID and antimicrobial susceptibility test (AST) information to clinicians, it behooves us to look at the capabilities of new mass spectrometry technology for microbiology. Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry has the ability to identify organisms, including the most dangerous resistant organisms seen in hospitals, in as little as a few minutes. By integrating a MALDI-TOF instrument with an automated antimicrobial identification system, a species identification can be made available hours earlier, followed by the antibiotic susceptibility profile. I am extremely excited about the potential provided by mass spectrometry regarding the decreased time required to identify various microbiological pathogens, especially from positive blood cultures. 

Last, we are about to introduce a rapid assay for procalcitonin (PCT), which is the earliest known biomarker to indicate the presence of a bacterial blood infection. This test is used to help diagnose undifferentiated septic patients. But there’s a second very important benefit related to stewardship. The revised 2012 Surviving Sepsis Campaign (SSC) guidelines from the Society of Critical Care Medicine (SCCM)⁵ recommend that PCT be used to help discontinue antibiotics when a bacterial infection has been effectively treated. PCT is a very sensitive indicator. The molecule mirrors the trajectory of a bacterial infection quite closely. So, if the drug-bug match is good and a patient responds quickly to treatment, a normal PCT level can be used to discontinue antibiotics sooner, according to the SCCM. This is good for the patient and also helps curtail resistance.