organ transplantation complications Heart and Lungs transplantation Early infection.

HEART TRANSPLANTATION
Early Infections Sternal wound infection and mediastinitis are
early complications of heart transplantation.

An indolent course is
common, with fever or a mildly elevated white blood cell count preced-
ing the development of site tenderness or drainage
.

Clinical suspicion
based on evidence of sternal instability and failure to heal may lead to
the diagnosis. Common microbial residents of the skin (e.g., S. aureus,
including methicillin-resistant strains,

and Staphylococcus epidermidis)
as well as gram-negative organisms (e.g., Pseudomonas aeruginosa) and
fungi (e.g., Candida) are often involved. In rare cases, mediastinitis
in heart transplant recipients can also be due to Mycoplasma hominis
since this organism requires an anaerobic environment


for growth and may be difficult to see on conventional medium,
the laboratory should be alerted that its involvement is suspected.
M. hominis mediastinitis has been cured with a combination of surgical
debridement (sometimes requiring muscle-flap placement) and the
administration of clindamycin and tetracycline.

Organisms associated
with mediastinitis may sometimes be cultured from pericardial fluid.
Middle-Period Infections T. gondii residing in the
heart of a seropositive donor may be transmitted to a seronegative
recipient. Thus serologic screening for T. gondii infection is important
before and in the months after cardiac transplantation.

Rarely, active
disease can be introduced at the time of transplantation. The overall
incidence of toxoplasmosis is so high in the setting of heart transplanta-
tion that some prophylaxis is always warranted. Although alternatives
are available, the most frequently used agent is TMP-SMX, which pre-
vents infection with Pneumocystis as well as with Nocardia and several
other bacterial pathogens. CMV also has been transmitted by heart
transplantation.

Toxoplasma, Nocardia, and Aspergillus can cause CNS
infections. L. monocytogenes meningitis should be considered in heart
transplant recipients with fever and headache.


CMV infection is associated with poor outcomes after heart trans-
plantation. The virus is usually detected 1–2 months after transplan-
tation, causes early signs and laboratory abnormalities (usually fever
and atypical lymphocytosis or leukopenia and thrombocytopeni

at 2–3 months, and can produce severe disease (e.g., pneumonia) at
3–4 months. An interesting observation is that seropositive recipients
usually develop viremia faster than patients whose primary CMV
infection is a consequence of transplantation.

Between 40 and 70% of
patients develop symptomatic CMV disease in the form of (1) CMV
pneumonia, the form most likely to be fatal; (2) CMV esophagitis and
gastritis, sometimes accompanied by abdominal pain with or without
ulcerations and bleeding;

and (3) the CMV syndrome, consisting of
CMV in the bloodstream along with fever, leukopenia, thrombocy-
topenia, and hepatic enzyme abnormalities. Ganciclovir is efficacious
in the treatment of CMV infection; prophylaxis with ganciclovir or
possibly with other antiviral agents may reduce the overall incidence
of CMV-related disease.


Late Infections EBV infection usually presents as a lymphoma-
like proliferation of B cells late after heart transplantation, particu-
larly in patients maintained on intense immunosuppressive therapy.
A subset of heart and heart–lung transplant recipients may develop
early fulminant EBV-LPD (within 2 months).

Treatment includes the
reduction of immunosuppression (if possible), the use of glucocorticoid
and calcineurin inhibitor–sparing regimens, and the consideration of
therapy with anti–B cell antibodies (rituximab and possibly others).
Immunomodulatory and antiviral agents continue to be studied.

Gan-
ciclovir prophylaxis for CMV disease may indirectly reduce the risk of
EBV-LPD through reduced spread of replicating EBV to naïve B cells.
Aggressive chemotherapy is a last resort, as discussed earlier for HSC
transplant recipients.

KSHV-associated disease, including Kaposi’s
sarcoma and primary effusion lymphoma, has been reported in heart
transplant recipients. GVHD prophylaxis with sirolimus may decrease
the risk of both rejection and outgrowth of KSHV-infected cells. Anti-
tumor therapy is discussed in; Prophylaxis for Pneumocystis
infection is required for these patients (see “Lung Transplantatio

2)LUNG TRANSPLANTATION
Early Infections It is not surprising that lung transplant recipi-
ents are predisposed to the development of pneumonia. The combi-
nation of ischemia and the resulting mucosal damage, together with
accompanying denervation and lack of lymphatic drainage, probably
contributes to the high rate of pneumonia (66% in one series).

The
prophylactic use of high doses of broad-spectrum antibiotics for the
first 3–4 days after surgery may decrease the incidence of pneumonia.
Gram-negative pathogens (Enterobacteriaceae and Pseudomonas
species) are troublesome in the first 2 weeks after surgery (the period
of maximal vulnerability).

Pneumonia can also be caused by Candida
(including drug-resistant strains of C. auris), possibly as a result of col-
onization of the donor lung, and by Aspergillus and Cryptococcus. Many
centers use antifungal prophylaxis (typically fluconazole or liposomal
amphotericin B) for the first 1–2 weeks.


Mediastinitis may occur at an even higher rate among lung trans-
plant recipients than among heart transplant recipients and most
commonly develops within 2 weeks of surgery. In the absence of
prophylaxis, pneumonitis due to CMV (which may be transmitted as
a consequence of transplantation) usually presents between 2 weeks
and 3 months after surgery, with primary disease occurring later than
reactivation disease.


Middle-Period Infections The incidence of CMV infection,
either reactivated or primary, is 75–100% if either the donor or the
recipient is seropositive for CMV. CMV-induced disease after solid
organ transplantation appears to be most severe in recipients of
lung and heart–lung transplants.

Whether this severity relates to the
mismatch in lung antigen presentation and host immune cells or is
attributable to nonimmunologic factors is not known. More than half
of lung transplant recipients with symptomatic CMV disease have
pneumonia. Difficulty in distinguishing the radiographic picture of
CMV infection from that of other infections or from organ rejection fur-
ther complicates therapy.

CMV can also cause bronchiolitis obliterans
in lung transplants. The development of pneumonitis related to HSV

has led to the prophylactic use of acyclovir. Such prophylaxis may also 1039
decrease rates of CMV disease, but ganciclovir is more active against
CMV and is also active against HSV.

The prophylaxis of CMV infec-
tion with IV ganciclovir—or increasingly with valganciclovir, the oral
alternative—is recommended for lung transplant recipients. Antiviral
alternatives are discussed in the earlier section on HSC transplantation.
Although the overall incidence of serious disease is decreased during
prophylaxis, late disease may occur when prophylaxis is stopped—a
pattern observed increasingly in recent years.

With recovery from
peritransplantation complications and, in many cases, a decrease in
immunosuppression, the recipient is often better equipped to combat
late infection.


Late Infections The incidence of Pneumocystis infection (which
may present with a paucity of findings) is high among lung and heart–
lung transplant recipients. Some form of prophylaxis for Pneumocystis
pneumonia is indicated in all organ transplant situations
Prophylaxis with TMP-SMX for 12 months after transplantation may be
sufficient to prevent Pneumocystis disease in patients whose immuno-
suppression is not increased.


As in other transplant recipients, EBV infection in lung and heart–
lung recipients may cause either a mononucleosis-like syndrome or
EBV-LPD. The tendency of the B cell blasts to present in the lung
appears to be greater after lung transplantation than after the trans-
plantation of other organs, possibly because of a rich source of B cells
in bronchus-associated lymphoid tissue.

Reduction of immunosup-
pression and switching of regimens, as discussed in earlier sections,
cause remission in some cases, but mTOR inhibitors such as rapamycin
may contribute to lung toxicity. Airway compression can be fatal, and
rapid intervention may, therefore, become necessary. Th

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