Transmission of Multidrug-Resistant Escherichia coli Through Kidney Transplantation --- California and Texas, 2009

On July 6, 2009, the Organ Procurement and Transplantation Network received notification of possible disease transmission. A transplant center in California (TCA) reported a kidney transplant recipient with Escherichia coli urinary tract infection and sepsis suspected to have been contracted from the donated kidney. Upon further investigation, a transplant center in Texas (TCB) reported that the recipient of the other kidney from the same donor developed a perinephric abscess caused by E. coli. The kidney grafts failed in both recipients; however, both recipients survived. E. coli isolates from both recipients demonstrated similar antimicrobial susceptibility profiles. Molecular typing studies conducted at CDC showed that the E. coli isolates from both kidney recipients were identical to an isolate from the donor's urine. On October 30, 2009, the Texas Department of State Health Services requested assistance from CDC to investigate this transplant-associated E. coli transmission and make recommendations to prevent future transmissions. The investigation identified gaps in communicating important donor information that might have adversely affected transplant outcomes. Each organ procurement organization (OPO) should establish protocols that clearly assign responsibilities for receiving, reviewing, and conveying any relevant donor information that becomes available subsequent to organ procurement.

Organ Donor

The donor, a woman aged 56 years, was admitted to the intensive-care unit for a subarachnoid hemorrhage. She was found to have multiple cerebral artery aneurysms and underwent surgery with aneurysm clipping 2 days after admission. Postoperatively, she developed a spasm of the internal carotid artery and subsequent rupture of the vessel during emergent angioplasty. Attempts to stabilize the patient were unsuccessful, and she was pronounced brain dead 7 days after admission. Family consent was obtained to donate her organs, and medical management was assumed by OPO A. Organ recovery was performed on the ninth day after admission.

Three days before being pronounced brain dead and 5 days before organ recovery, the donor became febrile, and urinalyses showed hematuria (red blood cell [RBC] count of 75--100/mm3), pyuria (white blood cell [WBC] count of >200/mm3, a few WBC clumps, and a large amount of leukocyte esterase), and bacteriuria (bacteria 2+ and positive for nitrite). A urine culture performed on the same day was positive for E. coli susceptible to ampicillin, cefazolin, gentamicin, levofloxacin, nitrofurantoin, tobramycin, and trimethoprim/sulfamethoxazole (Table). Four days before organ recovery, the donor received ciprofloxacin for treatment of her urinary tract infection. After urine culture results were available, ciprofloxacin was changed to levofloxacin, which was administered 3 days to 1 day before organ recovery. Two days to 1 day before organ recovery, the patient was administered cefazolin prophylactically in accordance with the OPO's procurement protocol.

A urine specimen collected 2 days before organ recovery showed improved hematuria (RBC count of 3--5/mm3), mild pyuria (WBC count of 5--10/mm3), and mild bacteriuria. At the time these laboratory results were available, OPO A collected the donor's urine for culture in accordance with its organ procurement protocol. The culture was sent to an outside commercial laboratory contracted by OPO A; the result was positive for multidrug-resistant E. coli (Table) and reported to OPO A 2 days after organ recovery.

Left Kidney Recipient

The left kidney recipient, a woman aged 64 years with end-stage renal disease secondary to diabetes and hypertension, chronic hepatitis C infection, and a 4-year history of hemodialysis, had the transplant performed by TCA on the day the kidney was procured by OPO A. Her postoperative course was uneventful, and she was discharged on day 5 after transplant on trimethoprim/sulfamethoxazole, as well as antiviral, antifungal, and immunosuppressive medications. The patient was followed routinely in the postoperative clinic with adjustments in her medications for blood pressure and glucose control. Dosages were not available, except for 1 tablet of trimethoprim/sulfamethoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) administered on day 8 after transplant. No fever was documented, and urinalyses performed during these visits were not suggestive of infection.

On day 26 posttransplant, the patient developed fever and chills and was evaluated in the emergency department. On this visit, her urinalysis was normal, but her creatinine had risen to 2.2 mg/dL from 1.0 mg/dL (normal: 0.6--1.2 mg/dL) on the previous day. Pseudoaneurysm at the arterial anastomosis site was diagnosed, and the recipient underwent left nephrectomy on day 28 after transplant. Urine culture 2 days after nephrectomy showed multidrug-resistant E. coli (Table). OPO A was contacted to assess the outcome of the donor's right kidney transplant.

The left kidney recipient's urine culture results showed the same multidrug-resistant E. coli as was identified in the donor urine 2 days after organ procurement. In addition, procurement of the left kidney and delivery to TCA was coordinated by a second OPO (OPO B), which collected perfusate solution in which the left kidney was immersed. Cultures of this perfusate solution were available to OPO B on day 3 after organ procurement and showed multidrug-resistant E. coli (Table). Neither of these culture results was documented in the left kidney recipient's medical records. The recipient survived and was discharged on day 13 after nephrectomy.

Right Kidney Recipient

The right kidney recipient was a woman aged 47 years with end-stage renal disease secondary to diabetes mellitus and hypertension and a history of hemodialysis. The transplant procedure was performed by TCB on the day of kidney procurement and the patient received perioperative ceftriaxone and kanamycin. One week after transplant, abdominal tenderness and an increase in creatinine were noted, and ultrasound and scintigraphy showed evidence of acute tubular necrosis (ATN). On the same day, cultures obtained by TCB from perfusate solution used for transporting the right kidney were reported to have scant growth of multidrug-resistant E. coli (Table). These culture results were not documented in the right kidney recipient's medical records. Kidney biopsy results on day nine after transplant were consistent with microangiopathy, early acute cellular rejection, and ATN; perinephric fluid collection was noted on a computerized tomography scan.

The patient was administered prophylactic trimethoprim/sulfamethoxazole during days 1--13 after transplant (80 mg trimethoprim and 400 mg sulfamethoxazole, 1 tablet daily). Her antimicrobials were changed to piperacillin/tazobactam on day 15, after a blood culture performed on day 13 indicated growth of E. coli with antimicrobial susceptibility identical to the perfusate culture isolate. On the same day, the patient complained of flank pain in the kidney area. A computerized tomography scan and Doppler sonogram indicated hemorrhagic fluid suggestive of pyelonephritis and perinephric hematoma in the transplanted kidney. Drainage of the perinephric abscess was performed on day 16 after transplant, and aspirate culture results showed the presence of E. coli with a resistance pattern identical to the isolates from the previous urine and perfusate cultures (Table).

On day 20 after transplant, a laparotomy was performed. An intraoperative biopsy of the transplanted kidney showed findings consistent with infection, including eosinophylic fibrillar glomeruli, thickened vessels, foci of interstitial fibrosis, and ATN suggestive of severe hemolytic uremic syndrome damage. The kidney was removed because of poor probability of future graft function. The patient developed a wound infection with multidrug-resistant E. coli with the same resistance pattern as the previous isolates; however, she recovered and was discharged 33 days after nephrectomy. Results of the donor urine culture obtained by OPO A were not documented in the right kidney recipient's chart (Table).

Reported by

W Chung, MD, Dallas County Health and Human Svcs; N Pascoe, G Heseltine, MD, Texas Dept of State Health Svcs; Y Qazi, MD, USC University Hospital, California.WA Bower, MD, M Kuehnert, MD, M Wise, PhD, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases; Y Zheteyeva, MD, EIS Officer.

Editorial Note

Donor-derived infection in solid organ recipients is a serious concern, and can lead to catastrophic consequences, including graft loss and death of the organ recipient (1--3). However, bacterial infections are relatively common in donors, and transplantation of organs from donors with known bacterial infection is performed, provided that transplant teams are aware of the infection and appropriate antimicrobial therapy is initiated to treat the infection in donor and recipients (4--6).

Timely communication of important donor-related information is critical to ensure appropriate prophylactic antimicrobial therapy and prevent development of infection in organ recipients. This communication is especially important when a multidrug-resistant pathogen is involved, because these organisms might not be susceptible to standard empiric antimicrobial treatment regimens. Since transplantation must be done expeditiously to ensure organ viability, the results of some cultures and tests of specimens collected at the time of organ procurement sometimes become available only after the transplant has been performed (7). Culture results that are available after organ procurement must be communicated promptly to medical teams in transplant centers (8) so that timely and adequate antimicrobial prophylaxis or treatment is initiated in recipients.

In this investigation, several failures to communicate important information were identified. The results from the donor urine culture performed 5 days before organ recovery were entered incorrectly as negative by OPO A in both the donor chart that accompanied the donated organs and in DonorNet, a secure web-based computer system that provides donor information to transplant centers. Multiple cultures were obtained during the course of the organ procurement process by OPO A, OPO B, TCA, and TCB. Cultures from all four entities were positive for multidrug-resistant E. coli, and results were finalized within 2--7 days after organ procurement. However, because neither the OPOs nor the transplant centers maintained communication logs, no means existed to verify that these culture results were shared among the entities. In addition, no documentation was entered in the recipients' medical records of E. coli infection in the organ donor, and no change in the recipients' antimicrobial regimen was noted that might have indicated knowledge of this information. A failure was noted in communicating perfusate culture results from the TCB laboratory to the TCB transplant team, which resulted in delay in initiating appropriate antimicrobial treatment in the right kidney recipient.

Several measures can improve communication during organ procurement from deceased donors. In the package of accompanying documents that OPOs prepare for every donated organ (9), all positive test results (e.g., from urinalysis or blood or urine culture), should be highlighted to draw the attention of physicians in transplant centers. To avoid transcription errors, OPOs should consider double-checking (by at least two OPO staff members) critical donor information against medical records in the donor's hospital. Any pending tests with results that could affect the organ recipient's safety (e.g., culture results) and the dates when these pending results will become available should be noted in documents accompanying the organ. Transplant center case coordinators should contact the OPO on the date of expected availability of laboratory results if the OPO has not already notified the transplant center of these results. All important new donor information should be documented in recipient medical records at transplant centers.

Each OPO should establish a standard protocol for receiving and conveying any relevant donor information that becomes available subsequent to organ procurement. At a minimum, these standard protocols should include establishment of clear lines of communication among designated personnel at the host OPO and all transplant centers, other involved OPOs, and tissue and eye banks, to enable prompt sharing of important information obtained after organ procurement with the medical teams responsible for care of transplant recipients. This information should include information obtained from medical records, family interviews, and laboratory testing. The protocol should include a mechanism to communicate new or updated information within 24 hours of availability of this information to the medical teams caring for the transplant recipients. OPOs should consider developing and maintaining surge capacity for updating pending results and rapidly communicating new medical and laboratory information to transplant centers, so that these functions can continue without interruption or delay even when organ procurement activity is increased above baseline for an OPO or a key point of contact is absent. In addition, communication logs to document transmission and receipt of information should be maintained by transplant centers, OPOs, and tissue and eye banks.

To avoid internal communication failures, transplant center case coordinators should follow up with hospital laboratories on all culture results. These results must be documented in patient's medical records.

Acknowledgments

This report is based, in part, on contributions by R Heyn-Lamb, USC University Hospital, California, and D Seem, MPH, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

References

1. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 2007;357:2601--14.
2. Ison MG, Hager J, Blumberg E, et al. Donor-derived disease transmission events in the United States: data reviewed by the OPTN/UNOS Disease Transmission Advisory Committee. Am J Transplant 2009;9:1929--35.
3. Nelson PW, Delmonico FL, Tolkoff-Rubin NE, et al. Unsuspected donor pseudomonas infection causing arterial disruption after renal transplantation. Transplantation 1984;37:313--4.
4. López-Navidad A, Domingo P, González C, Santiago C. Successful transplantation of organs retrieved from donors with bacterial meningitis. Transplantation 1997;64:365--8.
5. Little DM, Farrell JG, Cunningham PM, Cunningham PM, Hickey DP. Donor sepsis is not a contraindication to cadaveric organ donation. QJM 1997;90:641--2.
6. Cerutti E, Stratta C, Romagnoli R, et al. Bacterial- and fungal-positive cultures in organ donors: clinical impact in liver transplantation. Liver Transpl 2006;12:1253--9.
7. Fischer SA, Avery RK, AST Infectious Disease Community of Practice. Screening of donor and recipient prior to solid organ transplantation. Am J Transplant 2009;9(Suppl 4):S7--18.
8. Organ Procurement and Transplantation Network policy 4.5. Available at http://optn.transplant.hrsa.gov/policiesandbylaws2/policies/pdfs/policy_16.pdf. Accessed December 17, 2010.
9. Organ Procurement and Transplantation Network policy 5.5. Available at http://optn.transplant.hrsa.gov/policiesandbylaws2/policies/pdfs/policy_17.pdf. Accessed December 17, 2010.

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