Background: Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common.Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. Methods:We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. Results: Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for lowgrade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. Conclusion: Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted. K E Y W O R D S cytomegalovirus, heart transplantation, letermovir, lung transplantation 2 of 6 | ARYAL et AL. 1 | INTRODUC TI ON Cytomegalovirus (CMV) infection is a common complication among thoracic organ transplant recipients and often results in increased morbidity and mortality. 1 Ganciclovir and its prodrug, valganciclovir, are used for antiviral prophylaxis after thoracic organ transplantation in recipients with moderate or high risk of CMV infection. They are also the first-line drugs used in the treatment of CMV infection, and both share the same mechanism of action through inhibition of viral DNA polymerase. While these medications are effective, their use is limited by adverse effects and the risk for development of antiviral resistance. It is estimated that 7%-35% of thoracic organ transplant recipients develop leukopenia with 3%-15% of them affected by neutropenia, which can be associated with an increased risk of infection and death. 2 The hematologic complications of valganciclovir/ganciclovir therapy are often compounded by concomitant medication use in transplant recipients. Moreover, therapeutic failure may occur due to the development of resistance mediated by mutations in the genes UL97 and UL54. 3...
Background In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. Methods We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. Results We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor’s county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. Conclusions Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.
Cyberlindnera fabianii is a yeast present in soil rarely associated with invasive infection. Due to advanced diagnostic and therapeutic techniques, pathogenicity is increasingly recognized. A 37-year-old male with B cell lymphoma on rituximab developed multiple organ dysfunction syndrome secondary to C. fabianii bacteremia. Specialized species identification techniques were required after failure of standard methods. Despite extracroporeal membrane oxygenation (ECMO) the patient died on day 26 after admission.
A 24-year-old woman with ΔF508/Y1092X cystic fibrosis (CF) complicated by severe obstructive lung disease (FEV of 30% predicted) was admitted for IV antibiotics for planned sinus surgery resulting from severe chronic sinusitis causing frequent exacerbations and declining lung function. She had persistent airway infection with multidrug-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and growth of a fungus presumed to be an airway colonizer, identified as Stephanoascus ciferrii 1 year before presentation. Two days after surgery, she developed acute respiratory failure requiring mechanical ventilation. On day 4 of mechanical ventilation, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was initiated for refractory respiratory failure. The following day, she was listed for bilateral lung transplant and was transplanted 4 days later. Following transplantation, she was decannulated from ECMO; however, over the next 12 hours, oxygenation deteriorated requiring reinstitution of VV-ECMO for presumed severe primary graft dysfunction. Despite treatment with broad spectrum antimicrobial coverage with piperacillin/tazobactam, ciprofloxacin, linezolid, micafungin, voriconazole, and ganciclovir, she failed to improve and developed complex bilateral pleural effusions.
Incidence of Burkitt's lymphoma post‐transplant lymphoproliferative disorder (BL‐PTLD) in solid organ transplant (SOT) recipients in 1.4%‐1.6% with unknown cure rate. We report a case of Epstein‐Barr virus (EBV) positive, late‐onset BL‐PTLD in a 24‐year‐old EBV donor positive/recipient negative female. This is the first reported case of advanced BL‐PTLD post‐heart transplant in an adult. This is also the first reported case of treatment of advanced BL‐PTLD in a heart transplant recipient with a combined chemotherapy regimen without anthracyclines to avoid cardiotoxicity. The patient received 6 cycles of R‐COEP (rituximab with cyclophosphamide, vincristine, etoposide, prednisone) over 6 months and subsequently 3 cycles of high‐dose methotrexate (MTX) over 3 months for CNS prophylaxis. She remains without evidence of disease at 19 months post‐treatment. This case demonstrates that an anthracycline‐free regimen can be the therapy option for patients with BL‐PTLD after heart transplantation.
Scombroid fish poisoning (SFP), the most common fish-related illness worldwide, is a histamine response caused by the heat stable toxin histamine. A healthy 48-year-old woman and co-author of this paper developed palpitations, tachycardia and hypotension 10 min after a tuna steak dinner. She subsequently developed numbness of her face, flushing, conjunctival erythema, abdominal pain, nausea, vomiting, diarrhoea, headache and chest pain. Her ECG revealed tachycardia with ST depression. Her hypotension did not respond to fluid resuscitation, and she required phenylephrine. Based on exposure history, clinical syndrome, exclusion of other diseases and consultation with poison control, a diagnosis of scombroid poisoning was established. The state health department was notified. The patient was weaned off vasopressors, dosed famotidine and discharged 43 hours after fish ingestion with no symptoms and normal ECG. SFP is an often misdiagnosed and underreported illness with the potential to cause life-threatening hypotension.
A 65-year-old female with a history of right lung transplantation (LTx) for chronic obstructive pulmonary disease (COPD) 9-years prior complicated by grade 3 bronchiolitis obliterans syndrome (BOS) was admitted to the hospital for chest pain and dyspnea on exertion (DOE). Her bronchoscopy revealed fluffy, endobronchial lesions that were adherent to the right sided anastomosis resulting in mild obstruction of the right mainstem bronchus. Pathology from biopsies of the endobronchial lesions revealed hyphal fungal organisms consistent with Aspergillus species. Following antifungal therapy with voriconazole, her follow up bronchoscopy 37 days post the original bronchoscopy revealed resolution of the endobronchial lesions. The patient’s case is unique in: presentation 9 years post-transplantation, the absence of prior Aspergillus colonization, and the appearance of the endobronchial lesions. Following Ltx, immunosuppression in combination with allograft exposure to the environment increases the risk of opportunistic infections, especially saprophytic infections including Aspergillus.
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