CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Part of the problem may stem from discrepancies between the relatively stringent recommendations for testing hemodialysis fluids set by the International Organization for Standardization (ISO), and the older, more liberal standards established in 2004 by the Association for the Advancement of Medical Instrumentation and required of labs that are reimbursed by the Centers for Medicare and Medicaid Services. The detection limits in the U.S. are somewhat less stringent than those used abroad, Dr. Arduino notes, and not all labs adhere to the same standards. Labs that go the extra mile by adhering to ISO standards are more likely than other labs to identify contaminants in dialysis fluids.
When patients are treated for injuries that involve foreign objects, Dr. Leber says, the challenge lies in determining what objects are appropriate to culture. In some cases, the patient does not have an infection and the culture is a preemptive measure. In these cases, there’s little evidence to guide the decisionmaking.
“There’s a movement toward evidence-based medicine to verify the utility of our practices in the laboratory,” says Dr. Leber. “But in a lot of instances, there is no evidence. Sometimes things are done a certain way because we’ve just been doing it that way for many, many years.”
Over the course of her career, Dr. Leber has been asked many times to culture a foreign object, but none compare to the time she was asked to culture a pencil that had been extracted from a child’s brain tissue. The child had fallen onto the sharpened pencil, and during the surgery, a sterile baggie containing the pencil was sent to the pathology laboratory.
“Would you have cultured it? Are there any benefits to culturing that pencil, in terms of guiding the physician?” In most cases, Dr. Leber says, the activity is similar to a fishing expedition. In the case of the pencil, her concerns were multifold. “No. 1, if it’s cultured, the organisms we grow are not necessarily those that will take seed and cause infection. No. 2, the pencil was not handled sterilely by the EMS and everybody who handled the child on the way to surgery, so the organisms that grow may not represent what actually was in the brain. And third, there is no way the surgeons were going to be able to routinely access that site again to get cultures. So this was an irretrievable sample.”
After mulling it over, the third concern gave Dr. Leber pause. Conversations with the clinician revealed his concern about the presence of highly resistant organisms on the pencil that might alter that therapy, so Dr. Leber reluctantly agreed to culture it. “We had a one-time ability to culture something that might potentially relate to a deep-seated infection in the brain. So we went against what would otherwise be the guidance,” she says. In the end, the culture didn’t alter the patient’s therapy and she’s still not convinced it was a good use of resources.
“But this is the dilemma,” she says. “Often what happens is that laboratory technicians or managers are forced to either acquiesce to clinicians’ demands and culture things that don’t make clinical sense, or they have to have some kind of evidence or starting point to explain why it’s not a good idea.”
Most object-related injuries are treated empirically based on the flora at the body site and what’s known about the injury, she says. “If you have a penetrating wound into the gut, you’re going to treat based on the enteric flora in the gut. If you get injured in water, you’re going to cover for water-related organisms, like Pseudomonas.”
But the answer is not always obvious. Consider a child who gets a wood splinter embedded in her hand. The child’s pediatrician might try to remove the entire splinter, but suppose a small part remains and the child develops a slow, smoldering abscess. Once the rest of the thorn is removed, the site of infection will be cultured—but should the foreign material be cultured as well? “Sometimes you look at an injury, and there will be a part of the object that is left behind. So it’s more of a chronic injury. In those cases, there’s more evidence to suggest that it might be useful to culture that object.”
In the case of the pencil, she says, there were no evidence-based guidelines to light the path. “It’s all based on historical practice,” Dr. Leber notes. “You can’t predict if someone will get an infection. So there might be labs out there that just routinely would take these objects and culture them.”
The lesson, she says, is that sometimes it’s necessary to say no. “If you have a very strong microbiology lab where the physicians respect their expertise, the microbiologists might say, ‘No, we don’t culture those things,’ and they won’t. Other times, clinicians might throw their weight around a little and get the lab to culture these objects. But the message is that you can say no to these requests, because they’re not always a good use of resources.”
Evidence-based medicine and strong communication between laboratories and clinicians are crucial not just when culturing foreign objects but also when it comes to autopsy cultures.“Autopsy cultures are a standard activity, but there is so much variety among facilities,” says Carol Rauch, MD, PhD, associate professor of pathology, microbiology, and immunology; associate medical director of clinical laboratories; associate medical director of Vanderbilt Pathology Laboratory Services; and medical director of the One Hundred Oaks Diagnostic Laboratories at Vanderbilt University School of Medicine.
The usefulness of autopsy cultures depends in large part on the quality of the specimen.
Dr. Rauch
“In an autopsy environment, unless you have a good specimen, it’s very easy to grow things that have nothing to do with what infected the patient,” she notes. “You might grow what was in a contaminated environment, or what came out of a patient site that already had a lot of bacteria and fungi living there. Reporting that information isn’t helpful, and it may be dangerous if it’s misinterpreted.”
Dr. Rauch shares the concerns of Dr. Leber and others that laboratory directors are charged with the important task of helping clinicians determine what cultures might yield meaningful results, and what cultures might be a waste of resources, either because the results would have negligible impact or because the results would be extremely difficult to obtain.
Microbiologists have well-stocked toolboxes: Specialized media can be used to grow fastidious organisms; incubation times can be extended to allow slowly growing organisms to be identified in culture. But the request to perform a culture must be based on a solid clinical question. If not, the answers will be meaningless or misleading. “Microbiology laboratories answer clinical questions. To do that, we need a good specimen and ideally some information about what the clinician is thinking so that we can frame what we do in the laboratory.”
Dr. Rauch recalls when a technologist in her lab was once asked to work up 11 organisms discovered during an autopsy, at the request of a trainee who seemed to not understand the issues or extensive work involved. “That is tremendously laborious, and the growth of many organisms very likely reflects a contaminated specimen rather than organisms related to disease in the patient,” she notes. “Excessively manipulating tissue or the body can increase the chances of false-positive results, and having 11 organisms is a red flag for not reflecting an actual disease process.”
Often this type of request reflects what Dr. Rauch calls a “worry about it later” approach by the person ordering the cultures—an approach that is increasingly difficult to justify in today’s resource-constrained environment.
With strong teamwork between laboratories and clinicians, Dr. Rauch argues, autopsy cultures can provide important clues that can improve patient care overall. Last year, Vanderbilt’s clinical microbiology team illustrated just how valuable autopsy microbiology can be, when they cared for the index case in a large fungal meningitis outbreak. “Our patient’s diagnosis was made during life and the infection was treated, but unfortunately this particular infection was fatal,” she says. The patient’s illness had challenged clinicians and laboratory personnel at Vanderbilt to think out of the box. When the patient died, the team was still evaluating the smoking gun.
In a New England Journal of Medicine article (Pettit AC, et al. 2012; 367[22]:2119–2125), Dr. Rauch and colleagues described the index case as an immunocompetent man with persistent neutrophilic meningitis but no evidence of sinopulmonary or cutaneous disease. An autopsy was performed to help confirm and analyze unusual antemortem findings that included growth of a mold, Aspergillus fumigatus, from cerebrospinal fluid.
The early stages of the outbreak investigation were filled with challenges that pushed the boundaries of routine autopsy culture. “We needed to obtain many more specimens and higher-volume specimens. We needed to hold our cultures for longer incubation periods. We were sending a lot of specimens through the public health system to the CDC, where new tests were being developed rapidly, including a new fungal PCR test to identify a broad group of fungi.”
The CDC Infectious Diseases Pathology Branch examined many cases, further aiding the outbreak investigation and management. A clinical microbiology fellow at Vanderbilt assisted in obtaining high-quality autopsy specimens for use in multiple laboratory tests, and state and federal public health partners quickly applied communication systems, new laboratory tools, guidance documents, expert panels, and other tools.
During the search for agents involved in the outbreak, autopsy culture findings were front and center. “Given the often ho-hum attitude toward autopsy, it was refreshing to see that it also continues to play an important role in important problems,” Dr. Rauch says. Although the initial case was an infection with Aspergillus fumigatus, most of the cases in the outbreak attributed to contaminated medication injections have been infections by Exserohilum rostratum.
Above all, the experience underscored the importance of teamwork. “Our efforts are strongest when we all work together and connect our different areas of expertise to serve others,” Dr. Rauch says.
Of the various types of infection that require clinical culture, prosthetic joint infections are among the most severe. “The stakes are high,” says Aaron Tande, MD, a clinical and research fellow in the Mayo Clinic’s Division of Infectious Diseases. “A prosthetic joint infection typically requires at least one—usually more than one—major orthopedic surgery, and then a prolonged period of IV and possibly oral antibiotics.”When such an infection occurs, the prosthetic joint may need to be surgically removed and cultured to diagnose the infection and determine the most appropriate therapy. But isolating organisms from these devices is no easy task, particularly when patients have already been treated with one course or more of antibiotics.
There is some consensus in this area: The Infectious Diseases Society of America’s guidelines for diagnosis and management of prosthetic joint infection have clearly stated what constitutes a prosthetic joint infection, for example. In cases of suspected infection, the guidelines recommend assessing inflammatory markers, culturing tissue from the area around the prosthesis, and obtaining fluid from inside the joint before the operation to measure white blood cell counts and see if the fluid can be cultured.
But several uncertainties remain. In particular, Dr. Tande points to the controversy over the role of sonication to dislodge any bacteria from the device into the surrounding fluid, which is then cultured to check for contaminants. The method is particularly useful for recovering microbes from the prosthetic joints of patients who have been treated with antibiotics before surgery.
“It’s a newer technique. Most studies have shown that it is more sensitive than tissue culture, but it takes some time for these things to make it into the guidelines,” he notes. The real controversy is about whether the use of sonication is worth the extra hassle. Culturing prosthetic joints is much more labor-intensive than culturing periprosthetic tissue, and sonication only increases the complexity of the culturing process. “The question is, how much more advantageous is it to use sonication?”
Another uncertainty in culturing prosthetic tissues and periprosthetic tissues relates to incubation times. “Some bacteria that cause prosthetic joint infections, like Propionibacterium acnes, are classically described as slow growers,” Dr. Tande says. “This forces microbiologists to extend incubation times, which carries the risk of environmental contaminants and false-positives.”
These challenges can be overcome, at least in part by close collaboration between laboratories and clinicians. “A team-based approach can prove essential if something doesn’t smell right from the lab’s standpoint,” he says. “Clinicians want to know if the microbiology lab has suspicions about a sample, or if clinicians need to provide additional information that might better help to frame a result.
“In the end,” he adds, “it’s all about trying to help patients through improved methods of diagnosing and treating infections.”
Ann Griswold is a writer in Annapolis, Md.