Page 1279 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

886 PART 7: Hematologic and Oncologic Disorders

Clostridium difficile infection presents with diarrhea and can be treated patients at high risk of reactivation of the latter. Reactivation of myco-
with oral metronidazole. bacterial infections may be present as localized to the lung or dissemi-
Culture-negative, neutropenic fevers which persist despite appropri- nation disease and atypical forms are more common. The T cells in the
ate antibiotic coverage, especially in patients with a history of prolonged cord blood transplant patients are much more naïve than those in the
neutropenia prior to transplant, should trigger an evaluation for hepatic volunteer donor grafts, and viral infections play a greater role in infec-
and sinopulmonary fungal infections. Many transplant centers will use tious complications of cord blood transplants.
prophylaxis for fungal organisms most characteristic of their location
but persistent neutropenic fevers, especially in the setting of imaging ■ LATER POSTTRANSPLANT
studies consistent with invasive fungal infection will also require adjust- Most patients have adequate neutrophil counts. Mucosal barriers
ment of antifungal therapy. 40,41 destroyed during chemotherapy and radiotherapy are now restored, but
■ POSTENGRAFTMENT may again be disrupted by GI involvement with GVHD—again increas-

Patients have recovered their neutrophil counts but often continue to ing the risk of gram-negative bacteremia. Opportunistic infections due to
delayed recovery of immune function (T and B cells) are also observed
need central venous catheters for treatments. Bacterial infections thus during this period. Bacterial infections to be considered, especially in
remain a risk but to a lesser degree than when the patient is neutropenic. the setting of treatment for GVHD, are those observed with immuno-
T-cell function is suppressed by medications used to prevent GVHD globulin deficiency—encapsulated organisms such as Pneumococcus,
in the posttransplant period. B-cell production of immunoglobulins is Haemophilus influenzae, and Klebsiella spp. Often patients with delayed
reduced and may recover more slowly after unrelated and mismatched B-cell immunoglobulin recovery especially in the setting of GVHD will
transplants compared to matched, related transplants. Immunoglobulin receive prophylaxis for encapsulated organisms. The development of
levels are monitored early posttransplant and according to recom- these infections in the immunocompromised patient can be life threat-
mendations from the Centers for Disease Control (CDC), should be ening and result in ICU admission. Community-acquired pneumonias
repleted for levels <400 to reduce the risk of infections. Opportunistic should be considered in the differential diagnosis of fevers and pul-
and viral infections now play a greater role. With the universal practice monary symptoms during this time. Community-acquired respiratory
of prophylaxis with acyclovir, infections by herpes simplex or varicella viruses such as influenza, parainfluenza, respiratory syncytial virus,
are exceedingly rare in the early postengraftment period. Similarly, adenovirus, and less commonly metapneumovirus have been associated
45
Pneumocystis jiroveci pneumonia (PCP) in a patient who has received with lower respiratory infections and substantial morbidity and mortality
adequate prophylaxis is also very uncommon. It should be considered in HSCT patients. The risk of reactivation of a mycobacterial infection
if patient compliance with prophylaxis is in question. A history of cyto- continues until immune recovery and is greater when additional immu-
megalovirus (CMV) in the patient or donor and previous Epstein-Barr nosuppressive therapy is needed to treat GVHD. Disease caused by
virus (EBV) infection in the patient can result in reactivation of these resistant herpes viruses may occur in the late postengraftment period
viral infections posttransplant. A list of viral infections which should especially in the setting of prolonged exposure to antivirals for prophy-
be considered in the early postengrafted patient is shown in Table 94-4. laxis or treatments. Similarly, breakthrough fungal infections may occur
Viral infections can present as bacterial culture-negative fevers. Often in patients on intense immunosuppressive therapy for severe GVHD.
routine monitoring for these infections is performed in the appropriate In autologous HSCT, the risk of infection generally occurs during the
setting. Some transplant centers will provide prophylaxis with gan- conditioning and the transient period of neutropenia posttransplant.
ciclovir, foscarnet, or valganciclovir to patients at high risk for CMV Bacteria are the most common pathogens and include both gram-
reactivation in the pretransplant and postengraftment periods. Newer positive and gram-negative organisms as most patients will have a
approaches currently in clinical trials include the use of adoptive immu- central venous catheter in place and many of the conditioning regimens
notherapy with donor-derived cytotoxic T cells (CTLs) directed against will cause disruption of the normal GI and oropharyngeal mucosal
one or more viruses such as EBV, CMV, and adenovirus. These have barriers. Fungal infections are much less common as diseases such as
been derived or generated from adult donors as well as more recently, lymphoma and myeloma, which comprise the largest group of patients
cord blood. 42-44 Toxoplasma, though less commonly a pathogen than undergoing autologous HSCT, rarely experience prolonged periods of
CMV, can produce serious and life-threatening reactivation infections. neutropenia during therapy for their disease pretransplant. Suppressed
Agents such as trimethoprim/sulfamethoxazole and atovaquone with T-cell function may result from the chemotherapy and radiotherapy
activity against both Pneumocystis and Toxoplasma have been used in used in the conditioning. Prophylaxis with acyclovir and trimethoprim/
sulfamethoxazole for PCP is continued for 1-year posttransplant.
Immunoglobulin deficiency may be prolonged in patients who received
TABLE 94-4 Viral Infections in the Post-HSCT Setting rituximab as part of their lymphoma therapy and immunoglobulin
Pathogen Organ Involvement supplementation may be needed for many months posttransplant.
Adenovirus Sinopulmonary, GI (intestinal, hepatobiliary), GU, viremia PULMONARY COMPLICATIONS
BK virus GU (bladder, kidney)
Cytomegalovirus Viremia, pulmonary, GI, GU Pulmonary complications develop in up to 60% of allogeneic HSCT
recipients and are the immediate cause of death in approximately 50%
Epstein-Barr virus Viremia, lympatic, pulmonary of cases. Respiratory failure is the most frequent reason for ICU admis-
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Hepatitis B and C GI (liver) sion after HSCT. Infectious pulmonary complications remain common
6
Human herpes virus-6 (HHV-6) Viremia, bone marrow, pulmonary, GI (hepatic), in allogeneic HSCT patients because these recipients require the use
encephalitis, skin of immunosuppressive agents after transplantation to prevent or treat
GVHD (see the section “Infectious Complications”). However, the effec-
Herpes simplex Skin and mucous membranes
tive use of broad-spectrum antimicrobial prophylaxis has reduced the
Influenza Sinopulmonary incidence of infectious pulmonary complications and increased the role of
Metaneumovirus Pulmonary noninfectious lung injury syndromes in the morbidity and mortality
of these patients. These noninfectious pulmonary complications can
Parainfluenza Sinopulmonary
be divided into those that occur early after HSCT (pulmonary edema,
Respiratory syncytial virus Sinopulmonary diffuse alveolar hemorrhage [DAH], and periengraftment respiratory
GI, gastrointestinal; GU, genitourinary. distress syndrome [PERDS]) and those that occur later (bronchiolitis

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