CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
‘Every program in the country is certainly looking at possible CRE in their endoscopes.’
Lance Peterson, MD
The protocol her hospital developed in-house involves putting the broth on the plate from the beginning. “This allows us to get the colonies a day sooner and allows for more rapid identification of any Gram-negative organisms that might be present. So because we use a MALDI-TOF to rapidly identify these organisms, we can put a result out within 24 hours of getting the broth.”
It’s a labor-intensive process, Dr. Beavis says. “In the GI units, they’re having to squirt water through each of the channels of the scope, then use a brush to clean it, so when we receive a specimen in the microbiology lab, it’s often 200 mLs of fluid with a long brush inside, and we’re spinning that down to concentrate any organisms that might be present.”
Cutting off 24 hours of turnaround time helps in preventing transmission of the organism, Dr. Beavis notes. “While we’re waiting for the culture, the scopes are in quarantine. And the scopes are very expensive; we don’t want to keep them out of service for three or four days while we’re getting the results back.”
However, she adds, “We’re all starting from scratch. The CDC protocol is interim, and there are going to be differences. Each hospital might have to come up with its own protocol.” Microbiology labs in Chicago will be comparing protocols at their next quarterly meeting. Only time will tell, she says, if the measures they are taking will reduce the incidence of the organisms and the possibility of transmitting them from one person to another.
“Every program in the country is certainly looking at possible CRE in their endoscopes,” says Dr. Peterson, noting that NorthShore has a rigorous disinfection program. “The companies modified the scopes a year or two ago which made cleaning the elevator mechanism difficult, and I suspect that’s where the problem is.”
Multiple different genetic mechanisms can cause CRE; it’s not always the same organisms, Dr. Peterson adds. “For a long time, there was no way to screen for CRE, and it had taken a pretty good foothold in New York in the Brooklyn area,” even moving out of the ICU into the normal patient units. But with surveillance, a lot of the hospitals have been able to reduce their rates.
For the past four years, NorthShore’s molecular diagnostics laboratory has been doing its own laboratory-developed PCR screening for CRE in the ICUs, one of perhaps two such labs in the country. “There are culture-based tests for CRE too, but the sensitivity is only in the 75 to 80 percent range, so you’ll end up missing some. I do think this is a big challenge for labs right now.” But developing a commercial assay will also be challenging because it’s hard to find a lot of patients who have the organism.
The CRE cases are few and far between, Dr. Peterson says. “We get maybe six or eight patients from other hospitals or nursing homes who are admitted here, and we put them in contact precautions so it doesn’t spread in our hospital. We screen all of our ICU patients every month, and if we find someone we screen everyone again.”
The Gram-positive rapid diagnostic tests seem to have made a lot of progress in the past five years, Dr. Peterson says. “There are molecular tests that can rapidly identify coag-negative staph and Staphylococcus aureus whether they’re methicillin resistant or not. There are also molecular tests that can identify MRSA and Staphylococcus aureus directly out of skin wounds. Those are not inexpensive, but they’re pretty simple assays to do and generally the answer’s available in an hour or two.”
But the Gram-negatives are the big challenge for the microbiology laboratory, in his view. “We’re seeing new Gram-negative resistant mechanisms arising all the time, first the CRE from New York, then the extended-spectrum beta-lactamases starting in South America, a different CRE from India, and so on. You need a test that can pick them up quickly even though you don’t know the genetics, so you can treat the patient correctly, such as a reliable rapid phenotypic susceptibility test.”
Dr. Peterson
“So the big challenge now and for the next four or five years will be the Gram-negative side of things: How do you pick up very quickly a CRE or even an ESBL? Because with many of these drug-resistant organisms, it doesn’t matter what the genetic mechanism is. Many of these resistant mechanisms are a combination of different things going on in the bacterial cell that you can’t readily pick up with even a larger array of genetic tests.”
With S. aureus, most of the roughly 20 clonal complexes can’t tolerate the mecA gene that drives methicillin resistance, Dr. Peterson says. “So it’s a relatively small genetic pool, whereas for the Gram-negatives there’s all kinds of sequence types or clonal complex types that can pick up resistance mechanisms. We really don’t fully know how to solve that problem.”
But NorthShore has a strong record in controlling infectious disease and is one of the nation’s MRSA containment success stories. It was the first hospital system in North America to start screening everyone for MRSA and putting positives into contact precautions and decolonizing them at the same time, and at the 10-year anniversary of its aggressive program, MRSA is well under control, Dr. Peterson says. “We’re running about two or three infections per 10,000 patients, which is about 10 times lower than most hospitals report. We have almost no bloodstream infections—maybe one or two in all four of our hospitals every year.”
The transmissibility of different hazardous pathogens to laboratory workers is a whole other category of worry, Dr. Schuetz says. On that score she has found herself in frequent discussions with other microbiology laboratory directors about not only Ebola but also Creutzfeldt-Jakob disease.
“We see CJD as a critical pathogen because it’s so important to protect ourselves up front from it, and to try to figure with clinical teams how we can best do this,” Dr. Schuetz says. Of the 1,500 cultures her laboratory does with cerebrospinal fluid each year, one or two a month are to rule out CJD, and they cause the lab to kick into high protective gear.
“Even though the World Health Organization lists CJD as a low infectivity pathogen, it still should be treated with extra precautions, and I think WHO has been a little bit unclear on that. There are particular concerns about transmissibility and exposure to prion disease through exposure to CSF,” Dr. Schuetz says.
The specific protocol for a “14-3-3 order” to test CSF to rule out CJD begins with an immediate stop. “We won’t process the specimen. We call the microbiology pathology resident; then that resident immediately contacts the team to see how high the differential CJD is. If it’s extremely low on the differential, we will still work up the culture, but with extra precautions. If it’s high on the differential, some reference labs would rather not accept the specimen to do viral PCR testing on it until CJD has been ruled out. “
Her laboratory also has to let all the other labs in the hospital know if the specimen is high on the differential. “We let molecular pathology know, and we have to let chemistry and the core labs know in case they’re running tests on it, because there are issues they have with cleaning the instrument and the workspace afterward.” Dr. Schuetz is surprised to hear some labs say they treat CSF from CJD patients the same as anything else. “Having a process in place to work with these types of pathogens is really important.”
Along with C. diff, CRE, Candida, and other microbes, CJD dramatizes the constant need for microbiology to be prepared to deal with challenging new pathogens. Says Dr. Peterson, “It’s very important for all microbiology laboratories to know their patient population and infectious disease probably on an annual basis, sit down and meet with the leadership of infection control, show them what kinds of infections they’ve had, and talk about what kinds of diagnostic testing, if any, needs to change in order to keep up with the kinds of infections you’re seeing in practice.”
[hr]Anne Paxton is a writer in Seattle.
