From October 22 through November 3, 1994, three cases of Ochrobactrum anthropi meningitis were diagnosed among pediatric patients at a hospital in Utah (hospital A). The three patients had undergone neurosurgical procedures in which pericardial grafts processed at hospital B were used to close defects of the dura mater. This report summarizes the case investigations, which document that the cases resulted from human pericardial tissue grafts contaminated with O. anthropi.

A preliminary investigation revealed that the patients were not hospitalized on the same ward in hospital A and did not have surgery on the same day. Although the first two patients received pericardial tissue from one donor, the third patient received tissue from a different donor. The solutions used to process the pericardial grafts before implantation were Hanks' balanced salt solution (HBSS), 25% albumin, dimethyl sulfoxide, gentamicin, and penicillin. The grafts from the two pericardial-tissue donors had been prepared using the same lots of solutions.

Because of suspected bacterial contamination of the processing solutions, samples were analyzed from all available solutions that had been used to process the pericardial grafts. The only positive cultures were from samples obtained from two unopened bottles (one with the plastic wrapper intact and one with the wrapper removed) of HBSS (lot no. 17N2041) manufactured by Life Technologies, Inc. (Grand Island, New York). The bottles were labeled "Sterile -- For in vitro diagnostic use; For cell culture or further manufacturing uses." The HBSS was for in vitro use but not for use in animals and humans. O. anthropi was isolated from the unwrapped, unopened bottle of HBSS, and Pseudomonas stutzeri was isolated from the wrapped, unopened bottle. None of the HBSS used to process the pericardial tissue from the two donors was available for analysis; however, the solution also was from lot no. 17N2041. Frozen pericardial tissue was available from one donor; cultures of this tissue also grew O. anthropi and P. stutzeri.

To evaluate the laboratory techniques used to process the tissue grafts at hospital B, CDC and hospital B conducted a joint investigation. The investigation indicated that procedures to process tissue grafts generally were performed aseptically; however, investigators observed instances when sterile technique was not used. This finding suggests that extrinsic contamination of the pericardial grafts with O. anthropi could have occurred during processing or freezing. After notification of the manufacturer and the Food and Drug Administration (FDA) about intrinsic contamination of the HBSS with P. stutzeri, the manufacturer issued a voluntary recall of the implicated lot of HBSS. CDC, in collaboration with the state health department and FDA, is conducting an ongoing investigation to determine the cause of intrinsic contamination of the HBSS.

Reported by: JC Christenson, MD, AT Pavia, MD, ML Woods, MD, K Carroll, MD, School of Medicine, Univ of Utah; C Nichols, MPA, State Epidemiologist, Utah Dept of Health. Center for Devices and Radiological Health, Food and Drug Administration. Hospital Infections Program, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: O. anthropi (formerly CDC Group Vd, Achromobacter spp.) is a motile, gram-negative bacillus found in the environment (1); it has only rarely been reported as a human pathogen (2-5). The investigation described in this report documents a cluster of nosocomial meningitis cases resulting from O. anthropi infection transmitted by contaminated human pericardial tissue grafts that probably were contaminated during processing with the implicated lot of HBSS. The source of contamination of the HBSS with O. anthropi is unknown.

As transplantation of tissues of both human (allograft) and animal (xenograft) origin increases, infection-control problems -- including infection with unusual human pathogens -- may become increasingly common. After harvesting tissue grafts, contamination can occur during the extensive processing procedures or during preservation procedures before implantation. Furthermore, recipients of certain tissue grafts (e.g., solid organs such as kidney and heart) require immunosuppression to reduce the risk for graft rejection, and immunosuppression can result in susceptibility to organisms that may have contaminated the graft tissue. Multiple viral, bacterial, fungal, and parasitic agents have been linked to infections associated with tissue grafts (6).

As tissue transplants become more widespread, more stringent infection-control guidelines will be needed. Issues in the tissue-banking industry -- such as tissue preparation with solutions marketed for in vitro use only -- need to be addressed. In addition, routine infection-control practices (assessing sterility of transplant tissue before and after processing and storage) and post-transplant infection surveillance are critical.

To determine the magnitude of this problem, clinicians who identify patients with infections associated with the use of HBSS manufactured by Life Technologies, Inc., are requested to report such cases through the state health department to FDA's MedWatch Program, telephone (800) 332-1088 ({301} 738-7553), and CDC's Hospital Infections Program, National Center for Infectious Diseases, telephone (404) 639-6413.

References

1. Holmes B, Popoff M, Kiredjian M, Kersters K. Ochrobactrum anthropi gen. nov., sp. nov. from human clinical specimens and previously known as group Vd. Int J Syst Bacteriol 1988;37: 406-16.

2. Alnor D, Frimodt-Meller N, Espersen F, Frederiksen W. Infections with the unusual human pathogen Agrobacterium species and Ochrobactrum anthropi. Clin Infect Dis 1994;18:914-20.

3. Kern WV, Oethinger M, Kaufhold A, Rozdzinski E, Marre R. Ochrobactrum anthropi bacteremia: report of four cases and short review. Infection 1993;21:306-10.

4. Cieslak TJ, Robb ML, Drabick CJ, Fischer GW. Catheter-associated sepsis caused by Ochrobactrum anthropi: report of a case and review of related nonfermentative bacteria. Clin Infect Dis 1992;14:902-7.

5. Ezzedine H, Mourad M, Van Ossel C, et al. An outbreak of Ochrobactrum anthropi bacteraemia in five organ transplant patients. J Hosp Infect 1994;27:35-42.

6. Gottesdiener KM. Transplanted infections: donor-to-host transmission with the allograft. Ann Intern Med 1989;110:1001-16.

   
   

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