Microbiology

Allogeneic HSCT recipients who continue to require indwelling intravascular devices and who have disrupted mucosal barriers from chronic GVHD remain at-risk for bacterial infections from these sites. In addition, because of humoral immunodeficiency, these patients are at higher risk of infection with encapsulated organisms such as S. pneumoniae and H. influenzae. These typically present as bacteremia, pneumonia, or sinusitis.

Allogeneic HSCT recipients are at-risk beyond day 100 for a number of viral infections. As many will be out of hospital, CRV infections continue to pose a threat. Late-onset CMV disease is increasingly common, and in a recent study developed in 17.8% of allogeneic HSCT recipients a median of 169 days after transplantation.55 Mortality was 46%, and 38% of survivors had a second episode a median of 79 days following the first episode. Risk factors at 3 months for late CMV disease and death included GVHD, absolute lymphopenia <100 lymphocytes/cc, CD4 T-lympho-cyte count <50 cells/cc, prior CMV antigenemia, and absent CMV-specific T-cell responses. Beyond 3 months, continued antigenemia or CMV DNA detection in peripheral leucocytes or plasma predicted late disease and death.

VZV is common following HSCT and occurs in both autologous and allogeneic HSCT recipients.56 Eighty-six percent of cases occur within the first 18 months, with a median onset at 5 months.556 Risk factors include age >10, radiation as part of the conditioning regimen, and VZV seropositivity.56 Patients with der-matomal disease are at-risk for cutaneous or visceral dissemination, especially in the setting of GVHD. Atypical presentations of VZV with few vesicles or pain in the abdomen or back can occur. Atypical generalized zoster presents with multiple vesicular lesions without a dermatomal distribution. In those with der-matomal disease, the presence of more than 10 lesions outside the dermatome defines cutaneous dissemination. Visceral dissemination may involve the lungs, liver, or CNS.

EBV infection is common following HSCT, especially in EBV seronegative patients with a seropositive donor. Symptomatic disease is less common and may include fever with a mononucleosis-like illness, aplas-tic anemia, meningoencephalitis, or posttransplant lymphoproliferative disorder (PTLD). PTLD is the most feared manifestation of EBV infection and arises due to polyclonal or monoclonal B-cell activation in the setting of inadequate EBV-specific T cell immune surveillance. PTLD may present as a mono-like illness, as focal mass lesions in various sites, such as the lung or brain, as intestinal bleeding or perforation, or as widespread disease involving multiple organs, mimicking lymphoma. Onset typically occurs 3-5 months following HSCT. The incidence varies from <1% in matched related allogeneic HSCT recipients to up to 18% in certain high-risk groups, including recipients of matched unrelated, mismatched or T-cell depleted allografts, and those who receive GVHD prophylaxis with T-cell specific monoclonal antibodies or antithymocyte glob-ulin.57'58

Mycobacterial infections due to M. tuberculosis and nontuberculous mycobacteria are rare but reported following HSCT and typically present with a median onset at 4-5 months following transplantation.5960 Nontuberculous mycobacterial infections present as catheter-related infections, or as pulmonary, cutaneous, or disseminated disease. M. tuberculosis most often produces reactivation pulmonary disease, but rarely presents with pleural, nodal, cutaneous, marrow, or CNS involvement.

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