College of American Pathologists
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Acting on anthrax— what one lab learned

February 2002
Mark Uehling

Nov. 17 was an ordinary Saturday morning in the microbiology lab at 160-bed Griffin Hospital in Derby, Conn. Then a bottle came off the Bac T Alert continuous-read blood culture analyzer. It was positive for gram-positive rods.

That wasn’t unthinkable—the lab had seen the same thing a few months earlier. But then there was a second bottle. Same thing. A third. And a fourth, all positive, all from a 94-year-old woman named Ottilie Lundgren. She had been admitted because of fever, dehydration, general malaise, and shortness of breath. The working diagnosis was an unexotic, unexciting urinary tract infection.

A few days later, Lundgren was on the front pages of most of the world’s major newspapers, her house was encircled in police tape, and the hospital that identified her bacteria as Bacillus anthracis had visitors from the CDC and the FBI.

The tale of how the microbiology laboratory at Griffin Hospital detected anthrax in an unlikely patient is not just intriguing for its lessons about bioterrorism. It’s also a lesson in lab management—a vindication of mundane managerial decisions that were not in favor of forming a core lab or forcing key senior technologists with decades of experience to be cross-trained.

A case in point is Griffin Hospital’s Harold Hebb, a 61-year-old, 30-year veteran of the microbiology bench. When the first bottle came off the Bac T Alert unit, anthrax was the farthest thing from his mind. Contamination seemed to be one possibility, he says. "I was thinking a Bacillus species or even a Clostridium," Hebb says. "But all four tubes, two tubes from one site on the patient, two tubes from another site. Two different times. That patient was still pumping that organism through her bloodstream. It had to be real. It had to be from her blood." (The lab had also found gram-negative rods in her urine.)

Hebb dutifully reported the results to the hospital floor. At that point, one of Griffin’s two infectious disease specialists, Lydia Barakat, MD, appeared in the microbiology lab, as she often does. As Hebb recalls, "She didn’t know the patient. But she half-seriously and half-jokingly said, ’Oh, looks like anthrax.’ And I said, ’Come on, Lydia, where in the hell does a 94-year-old lady in the backwoods of Oxford [Conn.] get a case of anthrax?’" To this day, no one knows.

What remains clear, under the microscope, is that the organisms in Lundgren were a far cry from the anthrax Hebb had last seen during his U.S. Army medical technologist training at Fort Sam Houston in Texas. Says Hebb: "This looked different. This thing had this big mishmash of dark blue spaghetti strands crisscrossing each other all over the field. It was a wild strain in the sense that it was coming from a living person, so the growth was more robust."

As Hebb admits, a close working relationship with the infectious disease physicians was part of the reason the diagnosis was made correctly. Anthrax, he says, wasn’t high on his own list of possibilities.

Hebb believes easy communication with the infectious disease staff—the product of close, regular collaboration for years—was the key. "These are two great people," Hebb says of Griffin’s infectious disease physicians. "They are always down here. They are an integral part of this department and this hospital. We expect to see them on a daily basis."

Hebb is reluctant to speak highly of himself. But he allows that a full-time technologist specializing in microbiology may have had an edge in detecting a rare organism like Bacillus anthracis. "There are cross-trained people who can be very good in micro," he says. "But a person who does microbiology all of the time is more likely to pick up on some of the esoteric stuff a little faster."

Sylvia Corbit, the section supervisor in the hospital’s microbiology department, says Hebb did not have to scramble to find information on anthrax. It was all at his fingertips. "We had collected all that stuff months before," Corbit says. "He took out all the CAP articles we had, CDC information, books that we had received previously so we would be ready."

In fact, the laboratory had even encountered gram-positive rods in the recent past. Says Corbit: "One of the technologists remembered that I had said, ’That’s only one [bottle]. But if it had been more than one, we have to think anthrax.’ It was in everyone’s mind that if it was more than one bottle, we should start worrying. Everybody was aware enough to think, rule this out and let the doctors know your suspicion."

By the Sunday after Lundgren’s admission to the hospital on a Friday, the bugs from her blood had grown out. "They used extra plates," Corbit reports. "They looked at the colony types and described what they saw. It was pretty nondescript. It was a gray, nonhemolytic little colony. On Monday, it looked like a plate of purple spaghetti. It was kind of creepy looking. Listeria never looks like that."

The next obvious test was a wet-prep for motility. The techs "smeared a little colony on some saline, put a coverslip on the slide, and just looked at it under a microscope to see if it moved," Corbit says. "Some [Bacillus] have flagella and can swim, and some can’t. Anthracis can’t. This was nonmotile."

But Corbit still wasn’t completely convinced. She called a friend at Connecticut’s state lab and said that the hospital did not have the ability to do polymerase chain reaction or other ultra-sophisticated tests. Was there anything else that could nail down the identification?

Her source "suggested a different motility test with semi-solid agar," Corbit says. "You stab the agar and just incubate it. You look to see if there is a straight line where you stabbed the agar, or if it appears cloudy out from the center. If it appeared cloudy throughout the tube, that would be positive motility. If it stays where you stabbed it, that’s negative motility. I set that up on Monday."

By then, however, events had overtaken Griffin Hospital. Connecticut state health authorities wanted every plate, every slide. Just about everything was bundled up and sent by special courier. By the next day, the news media had begun to descend with satellite trucks and microphones.

For their part, Corbit and her colleagues could reflect on the fact that their standard procedures had worked. "Microbiology is so specialized that it is not something you can remember if you’re doing it once every six weeks or three months," she says. "That is a big reason for keeping microbiologists reading the plates, looking at the colonies and morphologies."

Corbit continues: "There is way too much involved to be a jack of all trades and master of none. I can’t do everything. But I acknowledge that. I know microbiology. I know when to send up the flags and say, ’We’ve got a major thing here, and I need help.’"

Interestingly, the recent bioterrorism scare had not occasioned a big shift at Griffin. Earlier anthrax cases during the autumn had not caused the laboratory to tweak its procedures. "There was no hysteria. We were doing our job. We would have done the same thing a year ago," says Stephanie Wain, MD, chairman of pathology and laboratory medicine.

A busy surgical pathologist, Dr. Wain says the infectious disease physicians make rounds in the microbiology laboratory and stay on top of what is unfolding there to a greater degree than she and Griffin’s other pathologist can. "Infectious disease had a very important role here," she says. "They treated the patient. They put the clues together."

Dr. Wain says Connecticut authorities performed more precise tests to identify Bacillus anthracis. First, she says, the state lab "did a gas chromatography study to identify the lipids on the surface of the organism. That exactly matched Bacillus anthracis. At the same time, they set up a phage study. The anthrax-specific virus attacks the organism, which results in a hole in the center of the colony. This test also was positive. Those two test results were so exact and accurate that they told the governor."

Dr. Wain praises veteran MTs like Hebb. "That weekend, we were lucky to have our most experienced microbiologists in there," Dr. Wain says. "You definitely need the expertise in all fields." At Griffin, she notes, each laboratory supervisor has 20 years of expertise.

She and Griffin’s hospital and lab administrators are not averse to cross-training as such. Some techs there are cross-trained. Dr. Wain and her senior staff simply wanted to keep the most experienced MTs like Hebb in place as specialists, as experts in their own right.

"The administrator a few years ago entertained the idea of using a commercial lab and getting rid of the lab in the hospital because we were considered a cost center," Dr. Wain recalls. To change that thinking, Griffin’s laboratory built up its outpatient volume to support the optimal staffing. "Eight years ago, we were carved out of most outpatient lab contracts," says Dr. Wain. "Today, we participate in all HMO contracts, serve 22 nursing homes and 50 physician offices. We aggressively marketed the lab among HMOs, doctors, and nursing homes."

Detecting Lundgren’s anthrax was a vindication of that strategy, Dr. Wain contends. "We kept the microbiology lab in the hospital," she says. "That was a prominent lesson learned. Don’t sever that, as a lot of hospitals are doing with core central labs in off-campus sites. Have the microbiology technologists and the ID physicians working together closely."

As a result of the Lundgren case, Dr. Wain reports, there is now a deeper appreciation of what the laboratory can do within the hospital. "There is this feeling, mostly from our administration, like ’Wow, we do have a good lab. Our people really are good.’ And there is this attitude that we were able to do something in a small community lab without having to resort to a bigger lab down the street."

As Dr. Wain recounts, even the news media were a little perplexed about why the cultures had not been sent to the larger academic hospital, Yale-New Haven Hospital, a short drive away. "The public and doctors need to understand that laboratories our size can do 99 percent of what larger labs can do with the same expertise and efficiency," Dr. Wain says.

This line of thought had been conveyed to the medical staff last fall in two grand rounds on bioterrorism. For herself, Dr. Wain had read up on the regulations and the latest advisories from the CDC and OSHA. "We had educated the doctors and our lab that we are capable of handling these specimens," Dr. Wain says. "We were telling physicians that we are a biosafety level 2 facility, and we can take these specimens. People have this perception that the community lab can’t do anything."

Her hospital can also handle patients. Dr. Wain notes with some pride that the physicians treating Lundgren did not immediately begin pumping her full of antibiotics. They waited to see what might be ailing her. That decision was sound clinical practice, of course, and it made the detection of the organism easier. "You’d think that’d be common," Dr. Wain says. "But there are times people get treated with antibiotics and then they get cultures done." Lundgren eventually received vancomycin, ceftazidime, ampicillin/ sulbactam, ciprofloxicin, and clindamycin. None of it worked because B. anthracis was the culprit.

Dr. Wain says the anthrax case brought to light an important communication gap, one that all pathologists should be alert to.

"Since the beginning of the outbreak of anthrax in this country, there had been little communication between the state health department and our laboratory. Any information about the detection of anthrax and other bioterrorism information was communicated with the infectious disease department. I received all my information and education through the CAP and CDC Web site and other Internet sources," she says. Even when the health department diagnosed the anthrax case, her lab wasn’t notified; the health department communicated only with the infectious disease department. Whether the autopsy was to be at Griffin Hospital also was not taken up directly with the pathologists.

Says Dr. Wain: "I found out later that there is a list serve on the Internet through the health department and that pathologists in the state are not on it. When the case settled down, I spoke to the physician in charge of the state health department and told him of my dismay at the lack of communication with the lab. He agreed there should be better communication." Dr. Wain then contacted the president of the Connecticut Society of Pathologists and asked to have the e-mail addresses of the chairpersons of pathology in Connecticut sent to the health department.

"Pathologists need to be diligent and alert to these issues. It is not uncommon for clinicians to bypass pathologists," she says.

Dr. Wain says it is naive for a hospital to presume it will never see anything unusual simply because of its location or its size. "We should never say, it can never happen here. It can happen anywhere if it can happen at Griffin Hospital. We were not thought to be at risk."

Nor were they ever in such demand. After Lundgren’s death, Specialty Laboratories and Mayo Medical Laboratories asked for samples of the Griffin anthracis organism for research. (Griffin had held back a small number of plates and gels in case the state of Connecticut lost something in transit.) But Dr. Wain consulted the CDC, and she was instructed not to distribute any organisms. Nor, it turns out, will the CDC.

In the end, it seems, the only change at Griffin was to equipment. Mulling over their Salmonella and Listeria, their TB and HIV, and a few other cultures in storage, the laboratory staff realized their refrigerator needed one small alteration. So on the Wednesday that Lundgren died, a hospital engineer was summoned to fix the refrigerator. "We had to get someone up from Environmental to get a lock and key," Dr. Wain says. "We had a lock, but we never had a key."

Mark Uehling is a writer in Chicago.