CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Dr. Hurst
Widespread overuse of antibiotics for respiratory infection continues, but “this has given us a structure in which to approach making it more appropriate,” Dr. Hurst says. “If we can change the paradigm and get away from the old football scores of treatment—six, seven, 10 days of therapy—and using a procalcitonin level to say, ‘I think that whatever was going on has improved,’ we don’t necessarily need to go to seven days or 10 days. At day three, that might be enough for this respiratory infection that maybe wasn’t that serious and had been taken care of with just a couple doses of antibiotics. Or maybe they were never necessary to begin with, and we are able to stop altogether.”
St. Anthony’s also uses the Vidas assay to assess the potential for de-escalating antibiotic therapy in sepsis patients. “There’s that patient who’s kind of smoldering, if you will,” Dr. Hurst says. “They’re really sick and you’re not sure if they’re getting better, you’re not sure if they’re getting worse. [Procalcitonin] gives us a marker to follow and say, ‘Are things headed in the right direction? Is there potential we need to switch antibiotics and either broaden coverage, or are we on the right path and we confirm that we don’t need to start additional antibiotics?’”
“This does not replace clinical judgment,” Dr. Hurst adds.
The case of the patient with COPD is one case among many in which physicians at St. Anthony’s are using a PCR assay to identify pathogens and coupling the PCR result with procalcitonin to have the data they need to stop antibiotic use, Dr. Hurst says. “If you have influenza or a parainfluenza or coronavirus detected by respiratory PCR, and you have respiratory symptoms, seeing procalcitonin at that undetectable range [<0.05 ng/mL] gives us a lot more confidence in being able to say this isn’t a post-viral bacterial pneumonia, we can hold off on starting antibiotics.”
The FDA clearance of BioMérieux’s stewardship claims should convince more physicians to use procalcitonin testing for lower respiratory tract infection patients, says Dr. Gilbert of Providence Portland Medical Center.
“Based on the fact that the FDA reviewed all the available literature, both international and studies from the United States, the FDA agreed there’s a substantive body of knowledge that makes the assay worthwhile and that you can trust the results.” That is, “If there’s a normal procalcitonin and the patient has acute exacerbated chronic bronchitis, the likelihood the patient has a bacterial infection is somewhere under five percent, three percent—very, very unlikely.”
In 2008, Providence Portland Medical Center was struggling, as was the rest of the country, with antibiotic stewardship, “in particular the overuse of anti-infectives for both upper and lower respiratory tract infections,” Dr. Gilbert says.
Most pressing, though, were patients admitted to the hospital with community-acquired pneumonia. Dr. Gilbert believed so strongly in the promise of procalcitonin to help combat the infection that he initiated a series of three studies sequentially correlating procalcitonin levels with the microbiologic cause of the patient’s respiratory tract infection.
Dr. Gilbert
“We wanted to know why it was that physicians, academicians, who have been trying for years and years to determine the etiology of community-acquired pneumonia were painfully inadequate in their attempts,” he tells CAP TODAY. Limiting the attempts to sputum culture and sensitivity and blood cultures led to discovery of the cause of pneumonia in only roughly 20 percent of patients on average. Adding urine tests and looking for the urine antigens Legionella pneumophila and Streptococcus pneumoniae increased the diagnostic yield by an additional 10 or 15 percent.
“That’s where we were,” Dr. Gilbert says, “and the first thing that was obvious was the patients who are sick enough to get into the hospital often cannot produce a sputum. If we intubate them, then of course we can get secretion from the airway, but if they’re sick and weak, they have trouble giving us a sputum.”
“We had to do better,” Dr. Gilbert says. “So we created a diagnostic bundle.” The bundle was sputum, if available, blood cultures, urine antigens, PCR nasal swabs for pneumococcus and Staph aureus, the BioFire respiratory multiplex PCR panel for 17 viruses, and one or two serum PCT levels.
“We had a much bigger net, if you will, looking for pathogens. With that, plus the procalcitonin, we identified the etiology, especially separating bacterial from virus, in 70 percent of patients,” Dr. Gilbert says.
The results of the first two studies were virtually the same and have been published (Gelfer G, et al. Diagn Microbiol Infect Dis. 2015;83:400–406 and Gilbert D, et al. Diagn Microbiol Infect Dis. 2016;86:102–107). A third, larger study is underway, this time using a second-generation BioFire multiplex PCR panel with 40 targets. Dr. Gilbert predicts the results will drive pathogen detection above 70 percent.
“Of course, that has a dramatic impact on customizing the antibiotic regimen for the patients, and the duration of therapy is much less,” he says.
As results from the first two studies were shared locally and then in the literature, he says, enthusiasm for procalcitonin testing among physicians at Providence Health medical centers rose.
In illustrating procalcitonin’s clinical utility, Dr. Gilbert describes a hypothetical type of patient with chronic obstructive pulmonary disease. Such patients, who are often colonized, especially with the pathogens Haemophilus and then less often with pneumococcus and Moraxella, come into the hospital with an acute exacerbation of their COPD and possible pneumonia. “We do our bundle and we find Moraxella or pneumococcus or Haemophilus, but their procalcitonin is normal. That proves to us that those potential pathogens are colonizing and not invading, and hence there’s no need for antibiotic therapy.”
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Amy Carpenter Aquino is CAP TODAY senior editor.