Transplant Infectious Disease

Abstract: Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas–kidney allograft recipients were transplanted. Thirty‐nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas–kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P>0.05). All but one patient presented with diarrhea. Twenty‐four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%) and M+oral vancomycin (M+V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15–314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated.

Abstract: The recognition of the importance of Epstein–Barr virus (EBV) infection, including EBV‐associated post‐transplant lymphoproliferative disease (PTLD), has led to a new focus on the prevention of this problem. This paper reviews the scientific rationale behind, and clinical experience with, the use of chemoprophylaxis (using acyclovir or ganciclovir) and immunoprophylaxis (using intravenous immunoglobulin) in the prevention of EBV/PTLD. While some centers have already introduced the use of one or both of these agents as standard prophylaxis against the development of this complication, published data in support of these protocols are currently lacking. Well designed clinical trials are necessary to evaluate the potential role of both antiviral and immunoglobulin agents in the prevention of EBV/PTLD in organ transplant recipients.

Abstract: Background: Polyomavirus (primarily BK virus [BKV]) infection is an important cause of chronic renal dysfunction in renal transplant recipients, but its possible contribution to chronic renal dysfunction in non‐renal solid organ transplant (NRSOT) recipients has not been fully explored.

Methods: We performed a prospective, cross‐sectional study of consecutive NRSOT recipients with unexplained chronic renal dysfunction of at least a 3 months duration. Medical records were reviewed, and polymerase chain reaction was used to amplify BKV‐specific sequences from serum and urine samples. The potential associations between various demographic and transplant variables and BKV infection were assessed.

Results: Thirty‐four consecutive NRSOT recipients (23 lung, 8 liver, 2 heart, 1 heart–lung) with chronic renal dysfunction were enrolled at a median of 3.5 years (range 0.3–12.5 years) post transplantation. Five of the 34 (15%) patients had BKV viruria (range 1040–1.8 × 10⁶ copies/mL), but none had BKV viremia. BK viruria was associated with mycophenolate mofetil use (5 of 19 [26%] vs. 0 of 15, P=0.03) and a history of cytomegalovirus disease (3 of 4 [75%] vs. 2 of 30 [7%], P<0.01). However, the mean estimated creatinine clearance was similar in patients with or without BKV viruria (49 vs. 47 mL/min).

Conclusions: BKV viruria was present in a proportion of NRSOT patients with otherwise unexplained chronic renal dysfunction. The possibility that BKV infection might contribute to chronic renal dysfunction in this setting warrants further investigation.

Abstract: We identified 14 cases of Legionnaires' disease occurring in 2946 solid organ transplant recipients from 1985 to 2007. Most cases were sporadic and community acquired. The recent introduction of the urinary antigen test has accelerated diagnosis and allows prompt institution of adequate therapy. The overall mortality rate in our series was 14.3%.

Abstract: Allogeneic stem cell transplant (ASCT) recipients have severely impaired cell‐mediated immunity as a result of their conditioning regimen, immunosuppressive therapy, and graft‐versus‐host disease (GVHD). Accordingly, they are susceptible to bacterial, viral, and fungal infections. Mycobacterial infections can also occur in these patients, although the incidence is not high, even in countries where tuberculosis (TB) is common. We describe four patients from our hospital who developed pulmonary T tuberculous infection in the post‐transplant period over a 3‐year period. During that time a total of 127 patients have undergone an ASCT, representing an incidence of TB of 2.3%. The pretransplant diagnosis was acute myeloid leukemia in three patients and chronic myeloid leukemia in one case. All four patients were treated with a combination of cyclosporine and corticosteroids for acute and/or chronic GVHD. Three of the four patients were born outside Australia, each from an area where TB is endemic. Two patients died within 2 weeks of the commencement of antituberculous therapy, the third is alive and well, and the fourth died of multi‐organ failure and sepsis after 4 months in hospital. A higher index of suspicion of previous TB exposure and infection is required in the assessment of ASCT recipients, particularly in those born in areas where TB is common or endemic.

Abstract: Human lactoferrin is a natural defense protein belonging to the innate immune system present in several body fluids and secretions, as well as in the secondary granules of polymorphonuclear neutrophils. Lactoferrin and its derivatives have pleiotropic functions including broad‐spectrum anti‐microbial activity, anti‐tumor activity, regulation of cell growth and differentiation, and modulation of inflammatory as well as humoral and cellular immune responses. This is the reason why much research has addressed the potential therapeutic activity of these molecules in different clinical settings, especially regarding infectious diseases and uncontrolled inflammatory conditions. In patients with hematological malignancies treated with a hematopoietic stem cell transplantation (HSCT), morbidity and mortality due to infections and uncontrolled inflammation remains high, despite many advances in supportive care. These life‐threatening complications are a result of the damage caused by the conditioning regimens to the mucosal barrier, and the innate and adaptive, humoral, and cellular immune defenses. These complications necessitate the continued exploration of new treatment modalities. Systemic and probably local levels of lactoferrin are decreased following HSCT. Therefore, the use of lactoferrin, or short peptide derivatives that retain the cationic N‐terminal moiety that is essential for the anti‐microbial and anti‐inflammatory activity, may prove to be a promising versatile class of agents for managing the complications that arise from HSCT.

Abstract: Here we report the case of a 43‐year‐old Japanese woman with acute myelogenous leukemia who underwent 2 unrelated cord blood transplantations (UCBT), terminating in fatal disseminated tuberculosis (TB). The patient did not achieve remission despite intensive chemotherapy, and subsequently underwent UCBT with a standard conditioning regimen. However, engraftment was not achieved. Fifty days after the first UCBT, the patient underwent a second UCBT with a reduced‐intensity conditioning regimen. She developed a pre‐engraftment immune reaction, which responded well to prednisolone, and engraftment was documented. However, 50 days after the second UCBT, the patient presented with high fever and developed pneumonia despite antibiotic and antifungal treatments. Thereafter, Mycobacterium tuberculosis was detected in blood cultures and specimens of bronchoalveolar lavage, thus indicating disseminated TB. Despite anti‐tuberculous treatment, she died on day 85. TB should always be considered as a possible diagnosis when treating febrile immunocompromised patients.

Abstract: Multidrug‐resistant tuberculosis (TB) is an increasing problem worldwide, however only three cases have been previously described in transplant recipients, especially involving lung and heart transplant. We describe a case of multidrug‐resistant TB in an allogenic bone marrow transplant recipient with good response to second‐line therapy.

Abstract: Severe sepsis and progression to septic shock in solid organ transplant recipients is associated with a high mortality. We describe a fulminant case of septic shock in a liver transplant recipient caused by Pasteurella multocida, a gram‐negative coccobacillus most commonly associated with domestic cats and dogs. P. multocida is a rare cause of bacteremia and has not been reported as a cause of septic shock following liver transplantation. In addition to standard therapy, the patient was managed with drotrecogin alfa (activated) recombinant activated protein C (APC), an evidence‐based agent that has been shown to significantly improve outcome in severe sepsis in the non‐transplant population. The known risk factors, clinical course, and outcomes of severe infection associated with P. multocida are also briefly reviewed. This case illustrates the need for transplant recipients and their healthcare providers to carefully consider the risk of severe infection associated with domestic animal exposure.