The disturbing news that a Minnesota man died last November after receiving a contaminated osteochondral allograft may well prompt surgeons to ask more questions about the safety of cadaveric tissue, and to become more well-informed about procurement and processing procedures. ORTHOPEDICS TODAY (Jan. 2002) reported that Cryolife Inc. processed the allograft tissue in this instance.

In addition to the Minnesota case, four other patients—three in Florida and one in Louisiana—suffered post-surgical septic arthritis after receiving donor tissue in anterior cruciate ligament repairs over the last two years; none died but all required further surgeries and lengthy antimicrobial therapy. The FDA is still establishing rules for good practices in handling tissue. It is important to note that Northwest Tissue Services policies and procedures have been very stringent and specific to prevent contamination from its grafts. In its 14 years of operation, the Tissue Services has distributed nearly 57,000 allografts without a single case of documented infection. “Most procedures in which our tissue is used are not life-saving,” explains director Margery Moogk. “Transplant procedures can almost always be scheduled when tissue is available. We have procedures in place to identify contamination at several junctures in the evaluation of donors and in the procurement and processing of tissue.”

In consultation with University of Washington laboratory medicine experts, the Tissue Services developed a list of “unacceptable” organisms. “If cultures are positive for these organisms,” notes Moogk, “we don’t process the tissues.”

Northwest Tissue Services policies do not allow irradiation as a way of eliminating these infectious agents. “Our conservatism is based on the knowledge that sterilization and decontamination are statistically defined processes,” says Moogk. “There’s no question that sterilization will reduce the bioburden, but we know that these processes might still allow a contaminant to survive. We’re not going to put unacceptable organisms through that process and say that none of them have survived to transmit infection to the recipient.”

Case studies
Articles in the Dec. 7, 2001, issue of Morbidity and Mortality Weekly, a publication of the Centers for Disease Control and Prevention, document the investigations of the Minnesota, Florida and Louisiana cases. In April 2000, two of the Florida patients received contaminated allografts from the same donor, whose tissue was processed at a Texas tissue bank. In one case, culture aspirate from a patient’s infected knee tested positive for Pseudomonas aeruginosa, Staphylococcus aureus, and Enteroccoccus faecalis; in the second case, a culture from the infected site also showed P. aeruginosa. Both allografts had been irradiated.

The allografts implicated in the other two cases, dating from October 2000, also came from a common donor. The ORTHOPEDICS TODAY article reported that both allografts were processed at Regeneration Technologies Incorporated and that “the tissue had been released before undergoing terminal sterilization with gamma irradiation.” During tissue processing the allografts had been cultured and showed Klebsiella oxytoca, Hafnia alvei and Citrobacter werkmanii/youngae; two of these organisms were later detected in aspirate drawn from one of the patients, and one was detected in aspirate drawn from the other.

In the fatal Minnesota case, the graft was infected with Clostridium sordellii; a culture from the donor’s other knee also tested positive for C.sordellii. The CDC is also investigating several additional reports of clostridium infection in knee-surgery patients, according to an article published in the January 20, 2002, issue of The New York Times. In all cases, the CDC reports that the contaminants were not introduced in the operating room through any lapse in infection-control procedures.

At the Northwest Tissue Services, allografts are cultured both at procurement and after they are washed in antibiotics and processed. “We culture each tissue before it is exposed to antibiotics because we don’t want to kill or inhibit growth of an organism before we have a chance to detect it,” explains Moogk. If 25 percent or more of a donor’s total procurement tissue cultures are positive for unacceptable organisms, Tissue Services policy requires discard of all that donor’s tissues.

Processing cultures also play an important role in the successive screening of tissue. “Each time we handle tissue, we repeat culturing to confirm that we haven’t introduced any contamination,” Moogk notes. The Tissue Services also procures and processes all of its own tissue, lending important continuity to microbiological testing and evaluation, and providing greater control over all aspects.

The record
More than 90 percent of tissue from the Northwest Tissue Services is released as aseptic without irradiation. Although most surgeons prefer allografts that have not been irradiated, the Tissue Services does provide irradiated tissue, but only when tissue cultures show organisms designated as “acceptable.” Such organisms include normal, non-pathogenic skin flora and environmental organisms.

Beyond culture results, a graft’s microbiological profile frequently will be based on cause of death, medical records, and other donor screening information. “We pursue information from the donor’s clinical caregivers,” Moogk explains. “We review the donor’s chart for indications of infection that might not have risen to the level of observation during a hospital stay.” In addition, the donor’s blood and/or bone marrow are cultured to verify that there are no signs of sepsis.

University of Washington laboratory medicine consultants are closely involved both in helping develop microbiological policies and in evaluating individual cases. Tissue Services staff and the consultants meet regularly on routine matters and also as policies are reviewed and updated. “When we start recovering a new type of tissue, our consultants are committed to developing new testing processes for that tissue,” explains Moogk.

The Tissue Services seeks and welcomes feedback from surgeons regarding the quality of its tissue. “We encourage clinicians to inform us if there’s even a suspicion that our tissue might have been involved in a patient infection,” says Moogk. “Clinicians are often apologetic for calling; they recognize that an infection has most likely come from the operation.” In its 14-year history, follow-up inquiries have never implicated an allograft provided by the Tissue Services in a recipient infection. Records of tissues transplanted from the same donor are always reviewed to verify that no infections were reported.

“Often surgeons implant our tissues deep inside a knee joint, spine, or hip, sometimes in patients who are just coming out of chemotherapy, whose immune systems may not be at peak. Even the most healthy bodies might have trouble fighting contamination in these locations,” says Moogk. “We take the risk of infection very seriously.”

(Editor’s note: Morbidity and Mortality Weekly Report is found online at http://www.cdc.gov/mmwr/.)