Page 552 - Clinical Immunology_ Principles and Practice ( PDFDrive )

530 Part four Immunological Deficiencies

with myeloma treated with bortezomib is around 13–22% and intervention are similar among those undergoing SOT. This
in relapsed/refractory mantle cell lymphoma around 10.3%, with predictable temporal pattern has enabled the institution of specific
age ≥65 years as the only predictive factor. 44 prophylactic strategies and in the development of an infection
differential diagnosis. 45
INFECTIONS IN SOLID ORGAN TRANSPLANTATION
CLINICaL PEarLS

KEY CoNCEPtS Infections in Solid-Organ Transplant Recipients
Determinants of the Risk for Infections in • Most infections occur in the first 6 months following transplantation.
Transplant Recipients • In the first month, most infections are nosocomial or are related to
surgical procedures or preexisting infection in the donor or
recipient.
• Epidemiological exposures (e.g., residing in a Histoplasma endemic
area) • Infections between 1 and 6 months following transplantation are
• Immunosuppressive drugs commonly secondary to the use of immunosuppressive drugs, with
• Antimicrobial prophylaxis a predominance of cytomegalovirus infection.
• Type of transplantation (e.g., cord transplant vs matched related donor • Infections after 6 months are usually due either to chronic viral infection,
transplantation) acquired earlier, or to chronic allograft dysfunction, necessitating
• Time after transplantation repeated courses of high-dose immunosuppression.

Despite significant improvement in the survival of SOT recipients, Infections in the First Month After Transplantation
infectious complications remain a major cause of morbidity and Infections in this period are generally associated with technical
mortality. The risk of infection is determined by the interaction complications of the surgery or have a nosocomial etiology.
of various factors, such as age of the recipient, type of transplanta- Donor-transmitted infections (e.g., Chagas disease) or reactivation
tion, invasive procedures, dose and duration of immunosup- of prior infections (e.g., colonization and infection with
pressive drugs, epidemiological exposures of both donor and multidrug-resistant [MDR] bacteria) can also occur. 45
recipient, use of antimicrobial prophylaxis, donor–recipient
serological status to certain infections (e.g., CMV infection, EBV Infections 1–6 Months After Transplantation
infection, toxoplasmosis), and ongoing viral replication (so-called Before routine antimicrobial prophylaxis, this period was typically
45
indirect effects). Assessment of a recipient’s risk for infection characterized by the presence of OIs, such as PJP and CMV
should help tailor specific prophylactic strategies and infectious infection; the incidence of these infections has been significantly
workup when an infection is suspected. reduced or delayed with TMP-SMX prophylaxis and CMV
Age is an important determinant of susceptibility to infections; prophylactic or preemptive therapy. Reactivation of latent infec-
it impacts the likelihood of prior exposures to microbial patho- tions, such as TB, Chagas disease, endemic mycoses, and cryp-
gens, either by primary infection or vaccination. History of tococcosis, can occur. Viral infections, such as those with BK
exposure can have either positive or negative effects. Older patients virus, adenovirus, RSV, HBV, and EBV, are common (Fig. 37.4).
are more likely to have encountered pathogens that can remain Invasive fungal infections, specifically Aspergillus and non-
latent and reactivate at the time of transplantation (e.g., CMV); Aspergillus mold infections, can be problematic during this period
younger patients have a higher risk of acquiring primary infections of heightened immune suppression. 45
after transplantation, and these infections tend to be more severe
than disease secondary to reactivation of a latent infection. In Infections 6 Months After Transplantation
addition, preexisting immunity can have a protective effect against This period is less well defined; patients with satisfactory allograft
clinical disease (e.g., EBV-associated PTLDs). 45 function develop more severe manifestations of community-
The type of allograft affects the specific infectious risk, usually acquired infections but have a lower risk of OIs. Patients with poor
as a result of technical factors associated with the transplantation allograft function and, therefore, increased immunosuppression
procedure, but is also inherent to the transplanted organ. For or those with ongoing chronic viral reactivation are at high risk of
example, urinary tract infections are most common after kidney OIs, such as invasive fungal infections, late-onset CMV infection,
transplantation, as a result of either catheter placement or ureteric nocardiosis, PJP, listeriosis, and EBV-associated PTLD. In addition,
stenting. BK virus is ubiquitous, but BK virus–associated trans- lung transplant recipients with chronic graft dysfunction are
plant nephropathy is most common after kidney transplantation, at high risk of recurrent bacterial pneumonia. Similarly, liver
and it is an important cause of allograft loss. Infection after liver transplant recipients with chronic graft dysfunction frequently
transplantation frequently results from leaks from biliary and develop biliary strictures and recurrent cholangitis. 45
GI anastomoses. Cardiac assist devices in heart transplant
recipients are a frequent source of infection. Tracheal anastomotic INFECTIONS IN HEMATOPOIETIC STEM
infections, particularly caused by fungi, are a significant complica- CELL TRANSPLANTATION
tion of lung transplantation. In single lung transplantations,
recurrent infections of the native lung, such as with GNB or Survival after HSCT has significantly improved during the last
fungi, can extend to the transplanted lung. In small intestine decade. Factors contributing to the increase in survival are the
transplantation, opportunistic and nonopportunistic viral infec- use of less toxic, nonmyeloablative conditioning regimens, use
tions of the GI tract (e.g., with norovirus) are common; these of peripheral blood stem cells (PBSCs) that leads to faster
can be severe and even life threatening. 45 neutrophil recovery, and use of antimicrobial preventive thera-
46
Despite all the differences in individual risk of infection, the pies. Despite these advances, infections are still a frequent cause
general patterns of infection in the absence of antimicrobial of morbidity and mortality.