Epidemiologic Notes and Reports Update: Yersinia enterocolitica Bacteremia and Endotoxin Shock Associated with Red Blood Cell Transfusions -- United States, 1991

From April 1987 through August 1988, four cases of Yersinia enterocolitica bacteremia associated with red blood cell (RBC) transfusions were reported to CDC (1,2). This report summarizes findings from the investigation of an additional six cases reported from six different states from January 1989 through February 1991 (2).

Patients, blood donors, and blood processing centers involved were in Alabama, Colorado, Georgia, Minnesota, Mississippi, New Mexico, Ohio, Oklahoma, and Tennessee. Each of the six patients developed fever and hypotension within 50 minutes after the start of transfusion. One patient developed explosive diarrhea within 10 minutes after the start of transfusion. Four of the six patients died from complications from blood contamination; the interval between transfusion and death ranged from 12 hours to 37 days.

All cultures and Gram stains of tubing segments from blood bags were negative. In each case, however, cultures of residual RBCs from the bag grew only one serotype of Y. enterocolitica; serotypes involved included 0:5,27 (four cases), 0:3 (one case), and 0:20 (one case). Cultures of blood from three patients were positive for the same Y. enterocolitica serotype as the isolate from the respective blood bag. Cultures of blood were negative for two patients (one of whom was already receiving antimicrobial therapy to which the organism was sensitive); blood from one patient was not cultured.

The RBC units had been stored at 39.2 F (4 C) for a mean of 33 days (range: 25- 42 days) before transfusion. One of the units had been washed 20 hours before transfusion. All donors were interviewed; three of the donors gave histories of a diarrheal illness within 30 days of donation, one had onset of diarrheal illness on the day of donation, and two reported no diarrheal illness. Reported by: CH Woernle, MD, State Epidemiologist, Alabama Dept of Public Health. RE Hoffman, MD, State Epidemiologist, Colorado Dept of Health. JD Smith, Georgia Dept of Human Resources. MT Osterholm, PhD, State Epidemiologist, Minnesota Dept of Health. FE Thompson, MD, State Epidemiologist, Mississippi State Dept of Health. CM Sewell, DrPH, State Epidemiologist, New Mexico Health and Environment Dept. TJ Halpin, MD, State Epidemiologist, Ohio Dept of Health. GR Istre, MD, State Epidemiologist, Oklahoma State Dept of Health. R Hutcheson, MD, State Epidemiologist, Tennessee Dept of Health and Environment. Office of Compliance, Center for Biologics Evaluation and Research, Food and Drug Administration. Div of Mycotic and Bacterial Diseases and Hospital Infections Program, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Bacteremia is a rare complication of blood transfusion, but it should be considered whenever a severe unexplained transfusion reaction occurs--particularly when fever and hypotension occur. From April 1987 through February 1991, seven deaths occurred among the 10 reported patients with RBC transfusion-associated Y. enterocolitica in the United States. During this period, an additional five cases were reported outside the United States (three in France (3-5) and one each in Australia (6) and Belgium (7)).

From April 1987 through February 1991, Y. enterocolitica was responsible for seven of the eight total transfusion-associated fatalities linked to bacterial contamination of RBCs that had been reported to the Food and Drug Administration (FDA) (FDA, unpublished data). Because nonfatal transfusion-associated Y. enterocolitica bacteremia is not required to be reported in the United States, its incidence is unknown. The reason for the apparent increase in reported transfusion-associated Y. enterocolitica bacteremia is unknown. However, surveillance data suggest that the incidence of Y. enterocolitica gastroenteritis may be increasing and the serotypes involved may be changing (CDC, unpublished data).

The investigation reported here suggests that blood contamination resulted from asymptomatic Y. enterocolitica bacteremia in the blood donors at the time of donation. Under conditions of cold storage and iron enrichment from RBCs, Y. enterocolitica can proliferate after a lag phase of 10-20 days (8). The absence of bacteria in the low-volume tubing segments tested is consistent with a low level of bacterial contamination at the time of collection.

The recent appearance of Y. enterocolitica as a bacterial contaminant of RBCs underscores the need for careful monitoring during the infusion of all blood components. CDC, FDA, and representatives of blood banking and medical organizations are assessing alternatives to prevent septic and/or endotoxic shock resulting from Y. enterocolitica contamination of RBCs. Potential measures include: 1) screening blood donors for a recent history of gastrointestinal illness; 2) reducing the shelf life of RBCs; and 3) testing RBC units greater than or equal to 25 days old for endotoxin or the presence of bacterial organisms. However, of the six donors in this report, three would not have been excluded by a program to screen donors for a history of gastrointestinal illness; moreover, such a program could potentially exclude 1%-13% of the current donor population (FDA, unpublished data).

Reducing the shelf life of RBCs to 25 days might reduce RBC availability at blood centers, particularly those that import blood, and result in shortages during critical periods of the year when blood products are already in short supply. In one study, 5%-61% (median: 16.5%) of all RBC units transfused from 10 blood centers were greater than or equal to 28 days old (FDA, unpublished data).

Recent data suggest that testing of older units (i.e., greater than or equal to 25 days old) for endotoxin and/or microorganisms may be a simple and rapid method to determine endotoxin or microbial contamination (CDC unpublished data). When RBCs were inoculated with low levels (1 colony-forming unit (CFU)/mL) of Y. enterocolitica, greater than or equal to 1 ng/mL of endotoxin was detected by 26 days when bacterial counts were 107-108 CFU/mL, and hematologic stains detected bacteria by day 21 when counts were 105 CFU/mL. The preliminary results of this pilot study suggest that the screening of all blood units greater than or equal to 25 days old by the acridine-orange, Wright, or Wright-Giemsa stains may be a simple and effective method to detect Y. enterocolitica contamination of RBCs.

When transfusion-associated bacteremia or endotoxemia is suspected, the residual blood in the bag should be examined by a hematologic stain (i.e., acridine-orange, Wright, or Wright-Giemsa), and blood in the bag and samples of the recipient's blood should be cultured (6,9). The blood bag and bacterial isolates should be saved until an investigation can be completed. Physicians are requested to report, through state health departments, transfusion-associated Y. enterocolitica infections to the Epidemiology Branch, Hospital Infections Program, Center for Infectious Diseases, CDC; telephone (404) 639-3407. Fatalities must be reported by the transfusion service to the Office of Compliance, Center for Biologics Evaluation and Research, FDA; telephone (301) 295-8191.

References

1. CDC. Yersinia enterocolitica bacteremia and endotoxin shock associated with red blood cell transfusion--United States, 1987-1988. MMWR 1988;37:577-8.

2. Tipple MA, Bland LA, Murphy JJ, et al. Sepsis associated with transfusion of red cells contaminated with Yersinia enterocolitica. Transfusion 1990;30:207-13.

3. Mollaret HH, Wallet P, Gilton A, Carniel E, Duedari N. Yersinia enterocolitica transfusional septic shock: analysis of 19 cases. Medecine et Maladies Infectieuses 1989;19:186-92.

4. Janot C, Briquel ME, Streiff F, Burdin JC. Infectious complications due to transfusion acquired Yersinia enterocolitica. Transfusion 1989;29:372-3.

5. Janot C, Burdin JC, Briquel ME, Streiff F, Gaucher P. Post-transfusion infectious complications caused by Yersinia enterocolitica. Rev Fr Transfus Immunohematol 1988;31:661-5.

6. Elrick J. A case study--fatal gram-negative shock following blood transfusion. Yersinia News 1988;5:1-2.

7. Jacobs J, Jamaer D, Vandeven J, Wouters M, Vermylen C, Vandepitte J. Yersinia enterocolitica in donor blood: a case report and review. J Clin Microbiol 1989;27:1119-21.

8. Arduino MJ, Bland LA, Tipple MA, Aguero SM, Favero MS, Jarvis WR. Growth and endotoxin production of Yersinia enterocolitica and Enterobacter agglomerans in packed erythrocytes. J Clin Microbiol 1989;27:1483-5

9. Simmons BP. CDC guidelines for the prevention and control of nosocomial infections: guideline for prevention of intravascular infections. Am J Infect Control 1983;11:183-99.

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