Clostridium infections from allografts traced in CDC study

Better allograft sterilization methods are needed to avoid more infections like these.

Issue: August 2004

The rate of clostridium infection was 0.12% for patients who received sports medicine tissues and 0.36% for those who received femoral condyles from that bank.

A retrospective study of 14 cases of clostridium infection associated with implantation of musculoskeletal allografts suggests that some of these infections and their consequences could have been avoided if the allografts were treated with a sterilization method that rendered them infection-free while maintaining their functional integrity.

Among the cases was one highly publicized case where a 23-year-old man died from a Clostridium sordellii infection after he received contaminated allograft tissue during routine knee surgery in November 2001. This case and others reported on in the Center for Disease Control and Preventionï¿½s Morbidity and Mortality Weekly Report in recent years were included in the study, along with a few others, according to first author Marion A. Kainer, MBBS, MPH. ï¿½Some of them overlap, but not all,ï¿½ she told Orthopedics Today.

The study, published in the New England Journal of Medicine in June, was mostly conducted by investigators employed by the CDC at the time the study began in 2001. The rarity of clostridium infections after orthopedic procedures compelled them to study incidence in association with implantation of musculoskeletal allografts, Kainer said.

ï¿½It is a much easier argument to make to say that these infections were transmitted by these allografts because you donï¿½t have the other risk factors. We excluded anybody who had diabetes. ï¿½ We were very, very strict to make sure that they didnï¿½t have any other risk factors for clostridial infection to be included in the study.ï¿½

Cases reviewed

The study included clostridium infections reported between January 1998 and March 2002 that were associated with orthopedic surgery involving allograft tissue, where surgical site infection was detected within a year of allograft implantation.

For each case, investigators traced the allograft tissue to the tissue banks and other agencies that recovered and/or processed them, reviewing processes used and documentation, and meeting with some personnel who performed them. Among other factors explored were time to refrigeration after the donorï¿½s death, testing and culturing methods, and the patientsï¿½ surgical outcomes.

Investigators performed laboratory studies of nonimplanted tissue from some donors at one tissue bank (Bank A) and did a statistical analysis of variables.

Infections linked to single tissue bank

All 14 patientsï¿½ allografts were processed by Bank A. The rate of clostridium infection was 0.12% for patients who received sports medicine tissues and 0.36% for those who received femoral condyles from that bank.

Investigators surmised that false negative results from microbiological contamination could have occurred, since Bank A performed tissue cultures after recovered tissues were treated with a nonsporicidal antimicrobial solution.

ï¿½Tissues from implicated donors were released despite the isolation of clostridium or bowel flora from other anatomical sites or reports of infections in other recipients,ï¿½ they wrote.

Senior author Lennox K. Archibald, MD, FRCP, said in a press release from Regeneration Technologies, where he is now medical director, ï¿½The message of our CDC study is that while bacterial infection is a relatively uncommon complication in tissue transplantation, the increasing use of musculoskeletal tissue allografts in various surgical procedures renders a real health risk to recipients of tissue that has not undergone a sterilization process.ï¿½

Monitoring, reporting

ï¿½The increasing use of musculoskeletal tissue allografts in various surgical procedures renders a real health risk to recipients of tissue that has not undergone a sterilization process.ï¿½
ï¿½ Marion Kainer

In the orthopedic community, undertreating and underreporting these infections is of concern, according to Douglas W. Jackson, MD, chief medical editor of Orthopedics Today. ï¿½There are a lot of things that make this underreported.ï¿½ Obvious infections may be reported, but cultures are not typically done. Underreporting may be due to medical legal concerns and because those who are treated as outpatients typically return to a hospital for treatment and the graft may not have been placed in that hospitalï¿½s OR, he said.

ï¿½Weï¿½ve got gross underreporting,ï¿½ said Kainer, who stressed the importance of monitoring allografts and the patients who receive them. Surgeons also lack knowledge about tissue processing, and those operating at ambulatory centers may not know from which bank the tissue they use comes, she said. They ï¿½believe that the tissue is sterile because of the way itï¿½s packaged. So it does not even cross their minds that this could be a potential source of infection.ï¿½

The study highlights the importance of using sterile and sporicidal processing. ï¿½In terms of safety, after reviewing all the data I really believe the best way is to have a method which sterilizes tissue but does not affect the functional integrity of it.ï¿½

Some have suggested that exceeding norms for refrigeration after the donorï¿½s death may have hastened proliferation of microorganisms and their spread to the grafts, but Kainer said that was over emphasized. Two donors exceeded the time interval, but others received refrigeration within about four hours, she said. ï¿½Just enforcing the time interval is not going to prevent these infections.ï¿½

For more information:

Kainer MA, Linden JV, Whaley DN, et al. Clostridium infections associated with musculoskeletal tissue allografts. N Engl J Med 2004;350:2564-71.