"This case gives uncomfortable insight into a gap in early detection of infections in immunocompromised, high-risk patient populations. "
Donor-derived Staphylococcus lugdunensis endocarditis of transplanted heart
HISTORY OF PRESENT ILLNESS
A 56-year-old man presented as a transfer from an outside hospital with cardiogenic shock from nonischemic cardiomyopathy for consideration of advanced therapies. Prior to presentation, he had been experiencing worsening orthopnea, leg swelling, and dyspnea on exertion. He did not report any fevers, chills, nausea, vomiting, abdominal pain, difficulty with urination, diarrhea, dizziness, or loss of consciousness.
At the time of transfer, the patient was in low-output heart failure with acute-on-chronic kidney injury. He did not respond to escalating doses of diuretic, and soon required transfer to the intensive care unit for intubation and milrinone infusion. He subsequently needed mechanical support with an Impella device. Transplant evaluation was also opened, and he was actively listed on hospital day 15.
An organ offer became available on hospital day 21, and the patient underwent orthotopic heart transplant. The heart was explanted without issue. The donor heart was inspected, revealing vegetations present on the right atrial wall. These were removed and the heart was irrigated. After removal of the vegetations, the surgery team sent the vegetation to pathology and continued with the procedure. The remainder of the procedure was uneventful, and the patient was transported to the cardiac care unit in stable condition.
The patient had a medical history of nonischemic dilated cardiomyopathy, ventricular tachycardia with biventricular implantable cardioverter-defibrillator (ICD), atrial fibrillation, aortic valve endocarditis in 2010 with bioprosthetic aortic valve replacement and again in 2016 for restenosis, and chronic kidney disease.
Medications included amiodarone, aspirin, bumetanide, and milrinone.
The patient primarily worked as a marine mechanic but had been disabled for years. He had no history of tobacco or illicit drug use but did have a significant history of ethanol use. There was no family history of cardiac conditions. The patient’s donor was a 49-year-old woman from the mid-Atlantic area with a medical history of obesity, epilepsy, and diabetes.
The cause of death was anoxic brain injury due to out-of-hospital cardiac arrest and prolonged resuscitation time. A screening coronary angiogram and transesophageal echocardiogram revealed no issues with the donor heart.
On admission to the hospital, the patient was afebrile with a pulse rate of 74, a blood pressure reading of 104/69 mm Hg, and oxygen saturation of 96% breathing ambient air. The patient appeared somnolent. His exam was notable for elevated jugular venous pressure, diminished breath sounds, and pitting lower-extremity edema.
STUDIES (RELEVANT LABORATORY FINDINGS WITH UNITS OF MEASUREMENT AND NORMAL REFERENCE RANGES, RADIOLOGY FINDINGS, AND OTHER STUDIES RELEVANT TO THE CASE)
Initial studies were notable for a sodium level of 124 mmol/L (reference range, 136-145 mmol/L), a creatinine level of 1.78 mg/dL (reference range, 0.76-1.27 mg/dL), and a white blood cell count of 5500/µL (reference range, 4000-11,000/µL). Right heart catheterization showed the following: markedly elevated pulmonary capillary wedge pressure, mildly elevated systemic vascular resistance, moderately elevated pulmonary vascular resistance, severely depressed cardiac index, markedly elevated pulmonary artery pressure, and elevated right atrial pressure.
The transplant infectious disease (ID) service was consulted 3 times during the hospitalizations. The first occurrence was during the preoperative period. The surgery team wanted to know if additional precautions needed to be taken because of the recipient’s history of endocarditis. The team noted that the imaging and cultures showed no evidence of infection. They recommended postoperative prophylaxis and continuing with transplantation.
Post transplant, the transplant ID team was reconsulted for the vegetation found during the procedure. Per recommendations, the patient was started on vancomycin, cefepime, and doxycycline as empiric treatment for endocarditis. Routine blood cultures collected immediately after surgery were without growth after 5 days, as were blood cultures collected from the donor prior to organ procurement. IgM and IgG testing for Coxiella, Brucella, and Bartonella were negative.
A decision was made to treat the patient empirically for 6 weeks. Transplant medications included basiliximab, steroids, and tacrolimus in addition to prophylactic valganciclovir and nystatin. A transesophageal echocardiogram revealed good graft function and no evidence of endocarditis. The patient was able to be extubated 3 days after transplant.
The transplant ID team was consulted a third time after fungal blood cultures collected immediately post transplant grew Staphylococcus lugdunensis after 12 days of incubation. The vegetations removed from the donor heart were collected in formalin and unable to be sent for culture; however, a pathology report noted fibrinopurulent debris, and Gram stain of the sample revealed gram-positive cocci in pairs. After this result, and confirmation of susceptibilities from the fungal blood culture, antibiotics narrowed to cefazolin to complete a 6-week course.
We present an unexpected transmission of endocarditis in heart transplantation. Based on the documentation from the donor organs, the donor heart had no hemodynamic irregularities or vegetations on prescreening. The vegetation was adhered to the right atrial wall, not perivalvular, which may have contributed to lack of detection by echocardiography.
S lugdunensis is more virulent than other coagulase negative species and is well known to cause endocarditis.1-4 The organ donor had no risk factors to develop endocarditis that we could identify, except placement of intravenous catheters prior to organ harvesting. This organism grew only from fungal blood cultures, as these cultures incubate longer (typically 14 days vs 5 days for routine) and inoculum would have been low after surgical removal and washing of vegetations. Upon review of the literature, findings from one study revealed that about 16% of donor organs had bacterial donor-derived infections because of intensive care and invasive resuscitative efforts.11
Although these infections are not common, they might occur more often than we appreciate. These infections can result in potentially fatal early posttransplant complications, such as bacteremia, myocarditis, and mycotic aneurysms.11 Staphylococcus aureus, Pseudomonas aeruginosa, and Candida species are the most common culprit organisms.11 Sepsis and infections are not absolute contraindications to organ donation.11 The hope is that donor organ infections are detected pre mortem, with antimicrobial therapy to reduce the risk of transmission.12
A study by Lumbreras et al looked at the significance of unrecognized bacteremia in the organ donor on the outcome of transplant recipients.12 This was determined by blood culture results that were reported to be positive after transplantation. The study focused primarily on liver transplants but about 5% of heart donors had bacteremia at the time of organ procurement, but without documented transmission of the isolated bacteria from the donor to the recipient. The authors’ takeaway was that unrecognized bacteremia in the donor did not have a significant effect on the outcome of organ transplant recipients. In this case, it also did not have a meaningful effect on the clinical outcome due to the removal of the vegetations pre transplant as well as protocol-based broad spectrum antimicrobials.
Antithetically, this case gives uncomfortable insight into a gap in early detection of infections in immunocompromised, high-risk patient populations. It highlights current limitations to donor evaluation of potential infections. One of the most common barriers is the narrow period to screen, place, and procure the organs.13 This case may provide an additional insight into the utility of donor organ screening involving in-person visualization of the organ and its internal structure. The recipient transplant surgeon found the vegetation from in-person examination of the organ. It will be hard to determine whether this prescreening is clinically significant based on the rare nature of this case, but this small additional donor organ screening could prevent future bacterial and fungal drug-drug interaction (DDI). Additionally, this case highlights the growing clinical utility of 16S rRNA sequencing in endocarditis and heart transplant.