Ann Griswold, PhD
After the patient specimens have been collected and the tests have been performed, after the legwork is complete and the results are in hand, reporting clinical microbiology findings should in theory be the easy part—the final step before an effective treatment plan is formed. But as any seasoned clinical microbiologist knows, that couldn’t be further from the truth.
“There has always been an age-old challenge in what results the microbiology laboratory should report,” says David W. Craft, PhD D(ABMM), microbiology medical director at the Milton S. Hershey Medical Center and an associate professor of pathology at Pennsylvania State College of Medicine. “Unlike other departments in the clinical laboratory—hematology and chemistry, for example—we produce a lot of positive results that shouldn’t be acted on.”
How test results are reported—and whether microbiology reports include commensal organisms or other information that may or may not be clinically significant—can have dramatic consequences for patient care. A test report can muddle the conversation about appropriate treatments, or it can save a patient’s life. And with the advent of new, high-throughput technologies, results that were difficult to report in the past have become even more challenging.
“We now have new methods coming along that produce a lot more information, and not just more information but different types of information,” Dr. Craft says. In years past, microbiology tests simply detected how many and which bacteria were present. Now they do that and more. “We have new technologies like MALDI TOF, which give us chemical libraries, and sequencing, which gives us sequencing databases, and all of that comes with information requests, and again, questions about clinical significance.”
Here, four seasoned microbiologists share their perspectives on clinical test reporting strategies: what results are appropriate to report, how best to report them, and how laboratory test reporting strategies can promote the best possible patient care outcomes.
When it comes to microbiology test result reporting, says Dr. Craft, islands of consensus exist, but between these islands is a great sea of variability.
“There are well-described and defined protocols for the historical problem: dealing with growing commensal organisms that perhaps aren’t of clinical significance,” he says. Plenty of references exist, such as the Clinical Microbiology Procedures Handbook and diagnostic textbooks. But while organisms may be worked up similarly from laboratory to laboratory, he notes, there are clear differences in how organisms are worked up for certain patient populations. Adding to that concern, none of the new high-throughput technologies are well described or standardized with respect to clinical test result reporting.
This can give rise to apparent discrepancies when patients are transferred from one hospital to another. “We might get a patient here at Hershey Medical Center who was worked up in a local community hospital and perhaps referred here because of a complicated case,” says Dr. Craft. “In looking at the microbiology data from the previous hospital, I might see things that seem to be in conflict with how I do my lab work.” The previous laboratory, for example, might have grown an organism that it assumed was clinically insignificant and, as a result, it might have foregone antibiotic susceptibility testing. “I might, on the other hand, say, ‘No, I think that is clinically significant.’ I might do a full identification, confirm what the organism is, and do testing for susceptibility predictions so that the patient can get on the right therapy.”
Neither laboratory is technically wrong, Dr. Craft says. “Each of us made different decisions based on what we thought the clinical staff would need to do.” In most cases, these discrepancies reflect differing perspectives or approaches; rarely do they reflect error.
In the heat of the moment, however, it’s sometimes difficult to appreciate such differences. A few years ago, Dr. Craft’s laboratory received a Saturday morning call from an out-of-state clinician who requested urine culture results for a patient who had visited the ER while on vacation. “The laboratorian reported the results as greater than 100,000 CFUs of coagulase-negative staphylococci, to which the clinician responded, ‘Thank you. Have you done the susceptibility testing on that yet?’ Our laboratory folks correctly said, ‘We don’t routinely perform susceptibilities on coagulase-negative staphylococci in the urine.’ The clinician responded, ‘Well, that’s not how we practice medicine in this state. In our hospital, technicians don’t tell MDs what to do. We tell the technicians what to do.’”
The laboratorian, Dr. Craft’s senior technician at the time, asked if the clinician wanted to speak with the laboratory director, who could be contacted easily on weekends. The clinician did not. The senior technician agreed to run the susceptibility testing, told the clinician the results would be available the next day, and asked for the best phone number to call.
There are two lessons to this story, Dr. Craft notes. The first is that some test results are simply not significant, and it’s not always obvious to non-microbiologists what is and isn’t relevant. “This is a result we routinely don’t put a lot of clinical significance into, and our medical staff here agrees. I would not grow this organism from someone’s urine and assume they had a bladder or kidney infection. We would assume it was skin contamination, and therefore we wouldn’t do a workup and we wouldn’t do susceptibility testing.” That doesn’t rule out special circumstances. “If urology or infectious disease called about a complicated patient, and they really wanted the susceptibility testing, I’m happy to do it,” he notes. “But my standard algorithm is, we won’t do that unless requested.”
The second lesson is that antagonistic relationships between clinical staff and laboratory staff reflect an important divide in the laboratory community. “How aggressive should we be in thinking for the physicians, and making comments in our reports that may drive therapy?” Dr. Craft asks. The balance between providing therapeutic guidance and remaining strictly interpretive is a difficult one. Should laboratories make sure clinicians understand the microbiology and assume they know how to treat difficult organisms? Or should laboratories assume that clinicians may not know how to treat some of the more difficult or rare organisms, and report based on those assumptions?
The answer is far from straightforward and steeped in controversy. When Dr. Craft posted an informal survey on the American Society for Microbiology’s listserve, he received about 40 responses, divided almost equally between those who felt that interpretive comments were warranted but therapeutic suggestions were solely the clinician’s responsibility, and those who felt that clinical microbiologists are more informed than clinicians about the therapeutic implications of certain microbiology test results and therefore obligated to make recommendations.
“At either end of the spectrum, there’s some polarization,” Dr. Craft says. “It’s really interesting, and it suggests to me that our clinical microbiology directors have fallen into a number of different categories in terms of where they think we should be.”
Susan Sharp, PhD, D(ABMM), FAAM, says microbiologists shouldn’t expect clinicians to be experts in clinical microbiology, nor should they be afraid to share their knowledge with clinicians so clinicians can use it to help care for their patients.
“We, as microbiologists, are the experts in what we do,” says Dr. Sharp, medical director of Airport Way Regional Laboratory, medical director of Sunnyside Medical Center Laboratory, regional director of microbiology in the Department of Pathology at Kaiser Permanente Northwest in Portland, Ore., and associate professor of pathology at Oregon Health and Sciences University. “We potentially know more about what our reports indicate than a majority of our clinicians can appreciate. We have to be their experts; we have to be their consultants; we have to be here to help them determine exactly what those reports mean.”
With the push toward electronic medical records and greater patient transparency, the need for a consensus on test reporting strategies is now greater, Dr. Craft notes. There is discussion about inviting regulatory representatives to an ASM annual meeting to discuss liability and the implications of standardized reporting strategies. “Should we attempt to standardize our comments in test reports the same way we standardize reports in general?” Many questions remain unanswered, he says.
Adding to the problem is that each lab seems to favor a different style of reporting, Dr. Sharp says. “Three of those styles have been published, but there’s still no standardized process for reporting results. That can potentially make it difficult to see patients at two hospitals run by two laboratories that use different reporting structures.”
The lab must communicate the test results as clearly as possible, and it could be as simple as how the test report is formatted, says John Schmitz, PhD, D(ABMLI), professor of pathology and laboratory medicine and associate director of the clinical microbiology/immunology laboratories at the University of North Carolina School of Medicine. “Clinicians need to clearly see what the result is, as opposed to simply providing a reference range. It’s important to involve your primary users in developing the reports. We might show an example of a report to our clinician users, to make sure that what we’re trying to communicate is clearly presented and has all the information they need.”
Even the wording used to describe organisms should be considered carefully, says Dr. Sharp. “Sometimes it’s intuitive to us as clinical laboratory directors and specialists in clinical pathology what these results mean. But the challenge is to make sure that meaning translates to our physician colleagues. Although we think we are talking the same language, we may not always be talking the same dialect.”
Take the word “rare,” for example. “If we report a ‘rare coagulase-negative staphylococci,’ to me that means there are very few organisms present in the culture,” she says. “But I have had physicians call and ask, ‘Well, what’s so rare about this? Is this some kind of rare strain?’ To me, ‘rare’ is simply a quantitation, but to them it can mean ‘exotic,’ like a zebra with spots.”
Resolving the inconsistencies in clinical microbiology test reporting may require future collaboration and ongoing discussion between the ASM and the Infectious Diseases Society of America, Dr. Craft suggests. “I think all of us, at least those of us who are trained in fellowship programs in medical microbiology, are comfortable working with our infectious disease staffs, we have trained many of those infectious disease fellows, and I think there’s a natural relationship between ASM and IDSA as a result.” Dr. Craft sees benefit in working with the IDSA to vet various test reporting strategies in the future.
“If we are forced from a regulatory standpoint… to incorporate some of these practices into our electronic medical records, then we are really going to have to get together and decide how we are going to do some of this reporting.”
In the quest to adopt new technologies for microorganism detection, the clinical microbiology laboratories at the University of North Carolina are at the nation’s leading edge. The sheer amount of data generated by these new technologies is impressive, the labs have found. But these impressive datasets present formidable challenges for clinical test reporting, says Melissa B. Miller, PhD, D(ABMM), associate professor of pathology and laboratory medicine, director of the clinical molecular microbiology laboratory, and associate director of the clinical microbiology-immunology laboratory at UNC School of Medicine.
“One of the biggest things that labs are struggling with, now that we have MALDI TOF, is that we can get such detailed and accurate identifications. Sometimes they’re almost too detailed,” Dr. Miller says. A few years ago, a clinical microbiology test might have classified a gram-positive rod as a diphtheroid, or perhaps a corynebacterium, depending on the laboratory’s preference. Back then, Dr. Miller recalls, physicians would look at the report, think “skin contaminant,” and move on.
Thanks to new technologies like MALDI TOF, modern labs can report the exact species of corynebacterium. That has some laboratories wondering how much information is appropriate, Dr. Miller says. “Do you name the particular species of corynebacterium? Do you still call it ‘diphtheroids’? Do you just call it to the genus level?” From the laboratory perspective, she says, assigning a name to something gives the sense that it’s important. From that perspective, providing in-depth information on innocuous results may inadvertently mislead clinicians, Dr. Miller worries.
“As we do more MALDI TOF-based identifications, we are dissecting what used to be known as ‘skin flora,’” she says. “It’s important to strike a balance between learning about these organisms and not presenting unnecessary information, just because that information is available to us.”
There’s a fine line between necessary and unnecessary information, however. What may seem on first glance to be a commensal organism could actually hold the key to a patient’s mysterious illness. A few years ago, Dr. Miller recalls, a woman presented at the UNC Hospitals with a chronic breast abscess. “Repeated cultures were positive,” she recalls. “We had reported diphtheroids in the past; we had reported skin flora in the past. Our reports were basically indicating that these were poorly collected specimens. This poor woman had been sick for ages, and these reports were in no way helpful to the clinician.”
It wasn’t until Dr. Miller saw a breast aspirate containing pure diphtheroids that she realized the organisms were more than simply skin contaminants. “We thought, what in the world? She’s had diphtheroids multiple times; this is clearly a chronic problem. So we sequenced it, and it was Corynebacterium kroppenstedtii.”
At the time, Dr. Miller had never heard of the organism, so she did a literature search. “Lo and behold, the first five or so papers that came up showed it was associated with mastitis. It’s a lipid-loving corynebacterium,” she recalls. “There is a clear association with this organism and mastitis. The thing is, if I didn’t recognize that species, I can’t expect an OB/GYN physician to know that organism. So we really had to think about the best way to report this.”
In the end, Dr. Miller’s laboratory reported the finding at the species level, with a short descriptive sentence: “This organism has been associated with granulomatous mastitis and breast abscesses.” They also included a reference that described the organism and its association with mastitis. “By putting a name on the organism, we were saying, ‘Hey, this is important.’ By adding a sentence or two explaining why it’s important, I hoped the physician would realize that we’d finally identified the pathogen.”
Her strategy worked. The physician called the lab after reading the report, a productive discussion ensued, and the patient was treated and recovered. In the years since, her laboratory has identified several additional cases of C. kroppenstedtii, and it has programmed its computer system to send the same comment and literature reference with each positive result.
This isn’t just an issue for high-throughput technology, notes Dr. Sharp. It also holds true for one of the most fundamental tests of all—the Gram stain. “One of the most useful and informative tests we can do in the microbiology laboratory is a stat Gram stain. A well-made, -read, and -reported Gram stain helps physicians triage their patients and decide how to treat their patients.” Providing the most detailed information possible from that original Gram stain can be very helpful, she says.
“All of us know that when we see gram-positive cocci in clusters that these are staphylococci, but most clinicians do not. Reporting this as ‘gram-positive cocci in clusters suggestive of staphylococci’ would convey significantly more useful information to our clinicians. Many of us could certainly do more education with our specimen Gram stain reporting than we currently do.”
Dr. Miller credits the one-line description and literature reference as the keys to successful laboratory reporting, particularly when faced with an over-abundance of data. “If you make the report too long, nobody reads it. So it’s a balance between including information that’s going to be helpful for the patient but not including too much information.” Ideally, the report should include just two lines that explain what the organism is associated with, and whether there’s any prediction for susceptibility or resistance. A reference to susceptibility data might be included for particularly challenging cases.
“Some laboratories include commentary when they report results,” Dr. Sharp notes. “If you’re going to use commentary to help the end user, our physicians, read the reports, it should be short and to the point. Then there’s a chance the end user will actually read it, understand it, and interpret the results correctly.”
Dr. Miller agrees: “Use as few words as possible, but make those words have a high impact.”
Proper screening and evaluation of laboratory specimens is key to reporting high-quality results, notes Dr. Sharp. Take Clostridium difficile toxin reporting—a notoriously difficult reporting process that has endured numerous upgrades over the past decade. Currently, many laboratories use a two-step algorithm that includes an enzyme immunoassay test for the presence of the GDH antigen and toxins associated with the organism. If there is a discrepancy between the GDH and toxin results, the specimen is tested by a PCR assay. “As the laboratory director,” Dr. Sharp says, “I preferred to have either a positive or negative result for reporting, regardless of what methodology was used.
“But in order to be compliant, we needed to include the methodology associated with each of the tests performed. Unfortunately, it couldn’t be as simple as just one report stating positive or negative for toxigenic C. difficile.” Currently, if the laboratory needs to reflex a specimen to the PCR assay, it must report out both the EIA and the PCR result, which can be confusing to some clinicians. “It can be a very difficult reporting issue,” she says.
The importance of strong testing regimens is perhaps most obvious in the realm of antibody testing. Unlike direct tests like bacterial culture and molecular diagnostics, antibody testing is an indirect indicator of an infection. As such, these results can be highly difficult to interpret and report, particularly when the serological results conflict with the culture results, Dr. Schmitz of UNC notes.
These challenges are apparent in the struggle to diagnose sexually transmitted diseases. “Syphilis testing historically has involved antibody-based testing, because the organism that causes syphilis is not culturable and there are no readily available molecular diagnostic tests,” he says. In the absence of other methods, laboratories have until recently used an algorithmic approach that begins with a screening nontreponemal test, and confirms positive results via treponemal antibody tests.
In the past few years, some laboratories have opted to perform the confirmatory treponemal test first, followed by the nontreponemal test if the first test is positive—a protocol known as the “reverse algorithm.” “The challenge, then, is that two differing testing algorithms are used throughout the country, and the ultimate results from those tests may not be straightforward,” says Dr. Schmitz. The test will be interpreted properly only if laboratories clearly indicate which algorithm (and which components of the algorithm) they use. Even then, clinicians with limited infectious disease expertise may not be familiar with the new algorithm.
The same is true for HIV testing, where the goal is to test as many as possible. “This is another infection where the diagnosis is based primarily on antibody testing, because the molecular-based diagnostics are not a cost-effective way to screen for infection,” says Dr. Schmitz. The fourth-generation antibody tests used today detect both antibody and antigen, which means that positive results must be followed up with supplemental tests to confirm the diagnosis.
“One of the issues is that the fourth-generation HIV screening tests are very sensitive. We occasionally run into situations where the screening test is positive but the supplemental test is negative,” he says. The interpretation of such results can be complex, with several possibilities at play. In some cases, a third assay—an HIV RNA PCR test—is performed to rule out acute HIV infection.
“So the algorithms for HIV, like syphilis, have evolved, and communicating the interpretation of these results has likewise changed over time as the sensitivity of these screening tests has increased.”
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Ann Griswold is a writer in Annapolis, Md.