Mass Spectrometry, Collaboration Produce Dramatic Results

Methodist Hospital lab and pharmacy team up to speed targeted treatment of blood infections

CEO SUMMARY: When the Department of Pathology and Genomic Medicine at the Methodist Hospital in Houston, Texas, worked with the Pharmacy Services Department, the outcome was a dramatic reduction in the time needed to more accurately identify and treat the pathogens causing gram-negative bloodstream infections. This successful program reduced the average length of stay by 2.6 days. The hospital estimates that annual savings from this intervention can total $18 million.

THERE ARE FEW DISEASES more critical to diagnose and treat rapidly than bloodstream infections (BSIs). For hospitals, this is a condition associated with high morbidity and mortality, along with high costs.

That makes bloodstream infections a perfect target for the hospital laboratory that wants to step up and add value. One outstanding example can be found at 1,000-bed Methodist Hospital in Houston, Texas.

LOS Reduced by 2.6 Days

The lab, in a innovative collaboration with the pharmacy department, has achieved and sustained a 2.6 day reduction in the average length-of-stay (LOS) for patients diagnosed with BSI. The value of these developments is worth an estimated annual savings of $18 million to Methodist Hospital.

The laboratory did three things that improved diagnostic accuracy and shortened time-to-answer for patients suspected of having a blood system infection. First, the lab implemented work flow redesign that improved individual work processes, starting with the collection of specimens and including start of patient treatment.

Second, the laboratory began using new mass spectrometry technology to shorten the time needed to provide physicians with an accurate answer. Third, the laboratory and the pharmacy worked together to speed up the process of identifying the pathogen and the appropriate antibiotic for each patient with a BSI.

“We accomplished these things under our collaborative antimicrobial stewardship program (ASP),” stated James M. Musser, M.D., Ph.D., who had a lead role in this effort. Musser is Chair of the Department of Pathology and Genomic Medicine at Methodist Hospital and a Professor of Pathology and Laboratory Medicine at the Weill Cornell Medical College of Cornell University. He is also the Director of the Center for Molecular and Translational Human Infectious Diseases Research at the Methodist Hospital Research Institute.

“The goal of this project was to improve the process of diagnosing and treating patients with gram-negative BSIs,” noted Musser. “We first recognized that the process—from drawing the blood to treating the patient—could be improved and accelerated.

“We identified three bottlenecks,” he explained. “First, we wanted to do rapid species-level identification of a pathogen using a mass spectrometer.

“Second, we wanted to run rapid (meaning as rapid as possible) antimicrobial susceptibility testing for these pathogens,” he continued. “This second step led to a question of whether we could more precisely target the antimicrobial therapy for the patient. And that question led to our third bottleneck: how best to inform the treating physicians.”

Musser and the lab staff addressed the first two bottlenecks by using relatively new technology: matrix-assisted laser desorptionionization-time of flight (MALDI- TOF) mass spectrometry. Clinical laboratories worldwide are finding that MALDI-TOF mass spec effectively circumvents many of the drawbacks of traditional testing methods and offers a rapid and relatively inexpensive way to identify bacterial and fungal organisms. Methodist Hospital uses the MALDI Biotyper from Bruker Daltonics Inc., based in Billerica, Massachusetts.

Increased Precision

“Use of mass spec dramatically cut the time needed to identify the pathogen,” stated Musser. “The mass spec was faster than many traditional testing methods, with increased analytical precision over many existing diagnostic methodologies. We also re-engineered our antimicrobial susceptibility testing strategy. To do that, we used material obtained directly from early-positive blood cultures.”

Musser and his team quickly recognized that the third bottleneck—informing physicians about the test results—would be a challenge. “You can think of our effort as a three-headed approach to improving care,” he said. “The crucial issue was to maximally use new technology, re-engineer work flow, and partner with the Department of Pharmacy and their infectious diseases pharmacists.

“Using the mass spectrometer allowed us to do rapid identification of the pathogens, but rapid identification is only part of the solution,” he emphasized. “If we simply report that information in a passive fashion—as most hospital labs do and as we do most of the time when sending reports back to treating physicians on the floor—that wasn’t going to achieve maximal time and cost savings.”

At this point, Musser sought advice from Katherine K. Perez, PharmD, BCPS, a Clinical Specialist in Infectious Diseases in the hospital’s Pharmacy Services Department. “We asked Dr. Perez to get involved and she deserves an immense amount of credit for spearheading this project,” Musser said.

“It was clear that the wisest course of action was for us to push the information out to the treating physicians rather than to passively report the information,” he explained. “But making that part of the improved diagnostic process workflow was critical to success. It requires one-to-one interaction between a pharmacist and the treating physicians.

“Recognizing the problem, she made herself available 24 hours a day, 7 days a week,” recalled Musser. “In that time, she was the person on call to whom we pushed the lab information. Where necessary to alter or otherwise adjust antimicrobial agent therapy, Dr. Perez then directly interacted with either the medical record or the treating physicians.”

When the laboratory identified the pathogen, the laboratory staff would call Perez. She would then review the patient’s electronic medical record and call the treating physician to identify the most effective antimicrobial therapy.

“Initially, the MALDI-TOF MS analysis was done three times daily,” stated Musser. “Later, we added a fourth run. Currently, the lab runs it five times daily. “We want to further shorten turn-around times by offering these diagnostic tests more frequently,” he noted. “For that reason, we’ve purchased a second MALDI- TOF MS. That machine is being brought on line now. When we have two machines, we will be able to run these tests more frequently, perhaps every other hour.

“Typically in a microbiology laboratory a bloodstream infection requires us to withdraw material from the patients’ blood specimen and culture it overnight, which requires at least eight hours and sometimes more than 24 hours,” he noted. “The beauty of mass spec is that you can withdraw the blood from the blood culture bottle and identify the organism at the species level within a half hour. That’s a significant improvement in the time needed to get to species-level identification.

“We then perform antimicrobial agent susceptibility testing directly from the early-positive blood culture, thereby decreasing the time required to institute targeted therapy,” noted Musser. “In addition to adding a second instrument, the lab uses this same approach of rapid testing with antimicrobial stewardship for patients with gram-positive and other types of microbial infections.”

Methodist Hospital laboratory’s contribution to reduced patient length of stay and to lower costs for treating gram-negative BSIs is a useful roadmap that other hospital and health system laboratories can follow to deliver similar value.

2.3 Day Reduction in Length-of-Stay Generates Annual Savings Estimated at $18 Million

EFFORTS to speed up the process of identifying the best antimicrobial agent for patients with gram-negative bloodstream infections paid big dividends at Methodist Hospital in Houston, Texas. Medical personnel there cut average length-of-stay (LOS) by 2.6 days for these patients.

“Personally, I know of no other single process or approach in recent years that has identified on average a 2.6-day decrease in LOS,” declared James M. Musser, M.D., Ph.D., Chair of the Department of Pathology and Genomics Medicine at The Methodist Hospital.

“From an economic standpoint and from an individual patient standpoint, cutting LOS is important,” he said. “This LOS reduction was for the first 100 patients in our study. We believe that for larger numbers of patients, we will show a statistically significant increase in patient survival as well.”

Musser and his colleagues published the results of their research project on December 6, 2012, in the online edition of Archives of Pathology & Laboratory Medicine.

“Many strategies have been proposed and tried to further improve the consequences of these detrimental infections,” the researchers wrote about gram-negative BSIs. “However, our study is the first to demonstrate that integrating rapid molecular analysis by novel application of mass spectrometry with antimicrobial stewardship in near real time significantly enhanced clinical care and financial outcomes.”

The researchers reported a decrease in average LOS from 11.3 days for these patients to 8.7 days. The annual savings are projected to total $18 million.

Cutting LOS helps to control expenses and the researchers showed that costs for each patient treated in the program were $26,162 versus $45,709 for those in a control group. This produced savings of 42%, or $19,547 per patient. Researchers estimated that if the program had been used for all patients with gram-negative bloodstream infections at Methodist Hospital, the savings would total $18 million in a year.


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