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Chapter 89 Clinical Approach to Infections in the Compromised Host 1457

malignancy-associated fever, including (1) a prior history of fever at when the infecting inoculum of organisms is large, when diagnostic
the time of initial malignancy diagnosis and (2) response of the fever methods are not sensitive enough for early detection, or when infect-
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to a trial of naproxen. Patients with drug-associated fever often ing agents overcome the effect of the antimicrobial agents. Measures
appear clinically well with relative bradycardia during periods of fever. taken to prevent infection in the preengraftment HSCT patient
Drug fevers typically develop 1 to 3 weeks after the start of a drug include pretransplantation serostatus blood workup, environmental
(β-lactams, sulfas, vancomycin, and phenytoin are among the most measures to prevent infection (including frequent handwashing), and
common inciting agents) and resolve, on average, within 48 hours of common sense.
drug discontinuation unless the patient also has an accompanying
rash. Drug-associated fever with rash and liver function test or
complete blood count abnormalities (e.g., thrombocytopenia and Assessment of Pretransplantation Serostatus
eosinophilia) are often indicative of more severe reactions that should
prompt immediate discontinuation or substitution of the likely Current pretransplant serologic testing of donor and recipient
offending medications. includes assaying for latent viruses (herpesvirus antibodies, hepatitis
panels, and human T-cell lymphotropic virus antibodies [human
T-lymphotropic virus I/II and HIV 1/2]) and syphilis. Antibody tests
INFECTION MANAGEMENT IN THE HEMATOPOIETIC that are checked variably among individual transplantation centers
STEM CELL TRANSPLANT RECIPIENT: A MODEL OF include VZV, EBV, and Toxoplasma.
SEVERE IMMUNE DEFICIENCY
Herpes Simplex Virus
Infection is a major cause of morbidity and mortality in HSCT recipi-
ents. Such patients are susceptible to a wide range of infections, but If the antibody test for HSV indicates prior infection or if the patient
the risk for a particular infection depends on a multitude of factors, provides a clinical history of prior HSV infection (i.e., mucosal sores),
including the type of transplantation, the length of time since trans- latent infection exists and has the potential to reactivate during
plantation, and the development of GVHD. A summary of common periods of T-cell suppression and neutropenia. This patient requires
infections occurring in HSCT recipients is shown in Fig. 89.6. prophylactic medication (e.g., acyclovir or oral valacyclovir), which
targets HSV for the neutropenic phase of transplantation. HSV
Pretransplantation Prophylactic Techniques in lesions can appear as black scabs on the outside of the lips, white- to
yellow-based ulcers when found on oral mucosa, or as an unusually
Hematopoietic Stem Cell Transplant Recipients severe exacerbation of mucositis or esophagitis. HSV prophylaxis
administered until recovery from neutropenia may be helpful even in
Over the four decades during which HSCT has evolved, antimicrobial patients receiving nontransplantation chemotherapy such as acute
prophylaxis regimens have advanced to prevent common or high-risk leukemia induction therapy.
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infections. This is balanced by problems associated with the preven-
tive regimen, including toxicity, overgrowth of resistant organisms,
and sometimes high cost. Algorithms for these preventive regimens Cytomegalovirus
evolve with changes in epidemiology, diagnostic methods, and new
treatment agents for infections. Despite an overall preventive If the candidate is CMV seropositive before transplantation, the
approach, infections still occur when a severe immune defect persists, recipient should be followed with periodic (usually weekly) diagnostic

Phase 1: Phase 2: Phase 3:
Pre-engraftment phase, Post-engraftment phase, Late phase,
<30 days 30–100 days >100
Host Impaired cellular and
immune Neutropenia, mucositis Impaired cellular humoral immunity,
defect acute GvHD immunity, GvHD GvHD

Device Central venous catheter
risk
Allogeneic Respiratory and enteric viruses
patients
HSV Cytomegalovirus
Varicella zoster
Epstein-Barr virus (lymphoproliferative disease)
Facultative gram-negative bacilli Encapsulated bacteria
Staphylococcus epidermidis (e.g., Pneumococcus)
GI tract streptococcus spp.
All Candida spp.
Molds Molds
Pneumocystis jiroveci
Toxoplasma gondii
Syrongyloides stercoralis

Fig. 89.6 TIMING OF INFECTIONS FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANT.
GI, Gastrointestinal; GVHD, graft-versus-host disease; HSV, herpes simplex virus.