CEO SUMMARY: At Washington Hospital Center, it was unclear if the use of a rapid molecular assay for blood infections was changing outcomes until a new, real-time lab results reporting protocol required the lab to deliver the test results personally to the attending physician in real time. A study with a control group provided convincing evidence that use of the rapid molecular test, in combination with real time test reporting, may be associated with dramatic reduction in mortality and improved patient outcomes.
FOLLOWING INTRODUCTION OF A MOLECULAR ASSAY and a simple change in laboratory test reporting procedures, Washington Hospital Center (WHC) in Washington, DC, saw a 53% reduction in deaths associated with Staphylococcus aureus bloodstream infections. This achievement demonstrates how a proactive laboratory team can contribute to better outcomes and other benefits.
Recognizing the challenges labs have in delivering real-time test results to busy physicians, the laboratory at Washington Hospital Center, a 926-bed tertiary care facility, developed an unusual way to report results: it called physicians directly to report its PNA FISH test findings. The result was reduced mortality and costs, as well as and more efficient use of antibiotics, said Shmuel Shoham, M.D., Director of Transplant Infectious Diseases at WHC.
Shoham was one of several authors of a study published recently in Therapeutics and Clinical Risk Management. Titled “Impact upon Clinical Outcomes of Translation of PNA FISH-Generated Laboratory Data from the Clinical Microbiology Bench to Bedside in Real Time,” Shoham and colleagues reported that the direct reporting protocol helped: 1) to cut mortality among 101 patients by about half; 2) to decrease median charges from $92,373 to $72,932; and, 3) to reduce use of antibiotics from three days to one day.
The study’s findings are significant because each year, some 350,000 patients in the United States have bloodstream infections, causing more than 90,000 unnecessary deaths and significant costs to the healthcare system. The infection is detected when a blood culture turns positive with bacteria and yeast. Rapid and accurate identification of the specific pathogen is needed to ensure early and appropriate therapy.
“We did this study because it is my belief that information that is not transmitted is information that is potentially lost,” Shoham said. “We needed a way to transmit this information in a timely manner.”
Washington Hospital Center had used the peptide nucleic acid-florescence in situ hybridization (PNA FISH) test since 2003 and introduced the lab reporting protocol in 2006, Shoham explained. The test and the equipment for it were developed by AdvanDx in Woburn, Massachusetts.
“It is exciting to see the results from the Washington Hospital Center study,” said Thais T. Johansen, President and CEO of AdvanDx. “It documents how rapid reporting of PNA FISH results can contribute to significant reductions in unnecessary antibiotic use while improving patient care. Of equal importance, however, is how WHC used real-time reporting of this test to save lives.
“If we extrapolate the data to the rest of the United States, PNA FISH has the potential of saving close to 23,000 patient lives, reducing 514,000 days of antibiotic use, and saving $5 billion in hospital charges,” Johansen added. “In essence, implementing both PNA FISH and real-time reporting of results to clinicians could be much more beneficial than the introduction of a new generation of antibiotics to treat patients with bloodstream infections.”
Speedier Lab Test Reporting
Shoham observed that more research may be needed before clinicians can extrapolate results from Washington Hospital Center to all hospitals in the United States. But he was clear on one lesson learned at WHC. “In terms of costs and mortality, whenever you have a lab test that allows for rapid diagnostic test results, it would be ideal to couple that test with a way to pass the information to the clinician quickly and efficiently,” advised Shoham. “It is clearly a waste of resources to have a rapid diagnostic test when the result then stays in the laboratory computer or is not accessed by the physician.
“We knew that a physician is likely to want the PNA FISH test results right away,” he continued. “The test is run twice a day, and after the lab gets the results, we wanted a way to immediately relay that information to our physicians. So we assigned one of our fellows to be a laboratory clinical liaison. Her job was to call the physician who ordered the PNA FISH test and not just leave a message. Her job was to get the physician on the phone and then she read from a prepared script.
“Depending on the results, she would say one of two things,” Shoham said. “She would say, ‘Your patient has coagulase-negative staphylococci (CoNS) infection in the blood and that is usually associated with a contaminant. It’s your patient and you are the clinician and so you make the call.’ Or, she would say, ‘Your patient has Staphylococcus aureus in the blood, which is rarely a contaminant and is a serious infection. And, you’re the clinician, you make the call.’
“During an analysis of the protocol, we called the clinician on every other run of the PNA FISH test,” Shoham explained. “One group was the control group that got the usual and customary care in our hospital. The other group was given this additional intervention in which we called the clinician. We wanted to see what difference it would make in the outcomes.
“The main difference was that the group that had coagulase negative staph infections had fewer days on antibiotics than was true for patients prior to this new protocol,” noted Shoham. “The physicians were getting a call from an infectious disease fellow who was well respected, and the clinicians tended to listen to what she had to say.
“The results showed reductions in mortality, lower costs, and less use of antibiotics,” he continued. “What that tells us is that it is clinically effective and cost effective to put someone in place in the laboratory to contact the physicians on the floors and deliver those lab test results, in real time, to the physicians on the floors. The cost of having that person in place is well worth it because you get a treatment decision faster, particularly when dealing with something as dynamic as a bloodstream infection. On one hand, it can be life-threatening and immediate action is essential. On the other hand, if the patient is a false positive, you could stop the antibiotic, not use the central line, and maybe send the patient home.
Reports Called To Doctors
“For the lives saved at WHC, the investment was miniscule,” added Shoham. “It required our fellow to spend between one and two hours daily making these calls. Even at $75 an hour, you would be spending $150 a day for someone to make these calls. That’s well worth the investment.
“In our study, notification of PNA FISH results by phone seemed to be the main factor in decreasing mortality,” Shoham explained. “Those patients were put on antibiotics sooner because we reported the results directly to those physicians—who would then aggressively treat the infection.
“The question now is this: Can we extrapolate from this one study to say that using this notification technique will significantly reduce mortality across the whole United States?” Shoham asked. “I’m not sure. Obviously, getting accurate information into the hands of clinicians faster allows them to make better decisions and that improves outcomes. But before we can make a definitive statement about the value of this reporting technique, I’d like to see this study replicated over a period of time.
Fewer Days, Less Costs
“And, I have another question: Could we automate the delivery of this information so the lab’s computer sends the results to the physicians’ beeper, meaning that, as long as the doctor is wearing a beeper, he or she would get the result via text message?” he asked. “Or, perhaps we could program the lab information system so that, once the result is available, the computer could automatically page the clinician who wrote the order. The whole principle behind having a rapid diagnostic test is to produce and deliver the results quickly and efficiently to the person who has prescribing ability.”
Shifting Clinical Paradigm
It is uncommon to find a laboratory test that can play a direct role in reducing patient deaths by as much as 83%, as was achieved at Washington Hospital Center. However, the events at WHC hold a more important lesson for lab directors and pathologists.
Simply said, it wasn’t a rapid molecular lab test that made a difference; it was a combination of that lab test and a different level of laboratory service that unlocked the dramatic, even stunning, improvements in detection and treatment of bloodstream infections.
Remember, the PNA FISH test was launched in 2003 and delivered modest clinical benefits. But it was not until 2006, when WHC’s lab instituted real-time reporting of PNA FISH results to attending physicians, that patient deaths began to decline by amazing amounts: 82% reduction in mortality rate for ICU patients with Staphylococcus aureus; 80% drop in mortality rate for intensive care unit patients; and, 53% drop in overall mortality (per the study in Therapeutics and Clinical Risk Management).
WHC’s achievements should inspire visionary laboratorians. Laboratory testing and lab consultative services have the greatest clinical leverage and added value when laboratory medicine specialists move beyond their walls to become collaborative, consultative partners with clinicians.
Use of Rapid Molecular Test, Real-Time Reporting Contributes to Fewer Deaths, Better Outcomes
BLOODSTREAM INFECTIONS resulting from Staphylococcus bacteria are a concern for healthcare providers and hospital administrators because they are a leading cause of hospital-acquired infection and mortality.
These infections are initially diagnosed when a culture of a patient’s blood turns positive with gram-positive cocci in clusters (GPCC), indicative of staphylococci. Because conventional laboratory identification methods can take 48 hours or longer, it means treating clinicians can’t determine whether: a) the blood culture was positive due to true infection, requiring aggressive antibiotic therapy, b) whether the gram-positive indication was due to blood culture contamination with coagulase-negative staphylococci (CoNS), a group of common skin bacteria, so that no antibiotic therapy is required.
This contributes to situations where patients with true infections are undertreated and where patients with contaminated blood cultures (false positives) are often unnecessarily treated with antibiotics.
Seeing the need for increased caution regarding bloodstream infections, Washington Hospital Center conducted a study with 202 patients. The patients with positive blood cultures containing GPCC were enrolled and blindly randomized into a “notification” group or a “usual care” group. For the 101 patients in the notification group (NG), PNA-FISH results and information on the identified bacteria were reported directly to the treating clinicians, whereas for the 101 patients in the usual care group (UCG), data were entered into the hospital’s laboratory information system as usual. Here are the results:
- 61 patients with Staphylococcus aureus; 32 in NG vs. 29 in UCG
- 141 patients with CoNS; 69 in NG vs. 72 in UCG
- 53% drop in overall mortality; 8 deaths in NG vs. 17 deaths in UCG
- 80% drop in mortality rate for intensive care unit patients; 10% (2 deaths) for NG vs. 48% (11 deaths) for UCG
- 82% reduction in mortality rate for ICU patients with Staphylococcus aureus; 10% for NG vs. 56% for UCG
- 67% drop in median antibiotic use after notification of results; median of 1 day for NG vs. 3 days for UCG
- 100% cut in median antibiotic use for CoNS patients after notification of; 0 days for NG vs. 2.5 days for UCG
- A reduction of $19,441 in median hospital charges: $72,932 median charges for NG vs. $92,373 for UCG.
The published study is: “Impact upon Clinical Outcomes of Translation of PNA FISH-Generated Laboratory Data from the Clinical Microbiology Bench to Bedside in Real Time.” Therapeutics and Clinical Risk Management, 2008:4(3) 637-640.
Molecular Assay Delivers Results in about 3.5 Hours
DNA FISH IS AN EXAMPLE OF HOW ADVANCES IN MOLECULAR TECHNOLOGIES are providing labs with new capabilities to diagnose disease. It is a highly-sensitive and specific fluorescence in situ hybridization (FISH) assay that uses PNA (peptide nucleic acid) probes to target species-specific ribosomal RNA (rRNA) in live bacteria and yeast.
PNA FISH was developed by AdvanDX, which is based in Woburn, Massachusetts. (www.advandx.com). According to AdvanDX, “the properties of the non-charged, peptide backbone of PNA probes enable the use of FISH assays in complex sample matrixes, such as blood and blood cultures, which facilitates the development of simple, yet accurate, tests that don’t require the extensive sample preparation necessary for other nucleic acid technologies .” Microbiology labs can use PNA FISH tests “to provide rapid and accurate identification of bloodstream pathogens directly from positive blood cultures in hours instead of days.” The test takes about 3.5 hours to run versus 48 hours for more traditional methods and is performed on an instrument that costs about $5,000.