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388 Part V: Therapeutic Principles Chapter 24: Treatment of Infections in the Immunocompromised Host 389

failed to show an increase in the incidence of bacteremia with discon- partly because different definitions and outcomes were applied, differ-
tinuation of prophylaxis, in at least two cases, institutional cessation of ent doses of antifungal agents were administered, and the numbers of
120
quinolone prophylaxis resulted in an increased incidence of bacteremia study patients have often been small.
caused by Gram-negative organisms, which was reversed by reinstitution As with antibacterial prophylaxis, the clearest benefit of antifun-
of fluoroquinolone prophylaxis. 121,122 In summary, there is, at present, a gal prophylaxis is seen in patients expected to have severe, prolonged
clear role for quinolone prophylaxis in some patients. However, because neutropenia, particularly allogeneic transplant recipients. Antifun-
of increasing resistance to these drugs, it is important to continuously gal prophylaxis is not indicated in patients who are undergoing che-
22
monitor their efficacy and discourage their unnecessary use. motherapy with low levels of myelotoxicity. When deciding whether
The use of granulocyte-macrophage colony-stimulating factor and to treat prophylactically, drug toxicity must be taken into account. In
granulocyte colony-stimulating factor to raise the absolute neutrophil addition, prophylactic use of antifungal agents may select for more
count has been shown to decrease the incidence of fever in patients on resistant strains of fungus and lead to breakthrough infection with
high risk chemotherapy regimens, elderly patients, and patients with organisms inherently resistant to the agent used for prophylaxis. For
certain comorbid conditions. 123,124 However, there is no definitive evi- example, certain prophylactic regimens active against Candida may
dence that prophylaxis with these agents reduces infection-related mor- actually increase the incidence of Aspergillus infections. The ability
145
tality or overall survival. 125 of antifungal agents to prevent systemic infection in high-risk patients
Low-bacteria diets are often recommended to patients expected to has been shown in several studies, but their ability to reduce all-cause
experience neutropenia, but their effectiveness at preventing infection mortality has not been definitively established. 146
has not been shown. Similarly, the efficacy of reverse isolation, though Several azole drugs have been studied as prophylactic agents. A
126
often employed as a prophylactic measure, has not been demonstrated. 127 number of studies document a statistically significant reduction in
superficial and invasive fungal infections when fluconazole is used
147
Viral Infections prophylactically. However, breakthrough infection with Aspergillus,
Acyclovir and its prodrug valacyclovir are effective at preventing recur- Candida glabrata, and Candida krusei have occurred with fluconazole
148
83
128
rent herpes simplex infections in patients receiving chemotherapy. prophylaxis. Itraconazole and voriconazole have a broader spectrum
Long-term treatment with acyclovir also prevents reactivation of vari- of activity, are more effective at preventing Aspergillus infection, and are
149
129
cella-zoster virus in hematopoietic stem cell transplant recipients, as generally well tolerated. Prophylaxis with posaconazole is associated
130
well as in patients undergoing chemotherapy for multiple myeloma. with a reduced risk of Aspergillus infection, and a trend toward lower
Varicella-zoster immunoglobulin is recommended as postexposure mortality. 150
prophylaxis for high-risk, nonimmune patients. 131 Echinocandins have become popular antifungal prophylactic
Hematopoietic stem cell transplant recipients have a high risk of agents. Caspofungin has been shown to be as effective as itraconazole
151
CMV infection. Patients at particular risk include those who are seroposi- in preventing Aspergillus and Candida infections. Micafungin was
tive before transplantation, seronegative patients who receive transplants shown to be superior to fluconazole at preventing systemic fungal infec-
152
from seropositive donors, and those who receive highly immunosup- tions in hematopoietic stem cell transplant recipients. Anidulafungin,
pressive conditioning regimens prior to transplantation. 132,133 The use of the newest echinocandin, remains to be studied as a prophylactic agent.
CMV seronegative blood components can markedly decrease the trans- P. jiroveci pneumonia can be prevented with trimethoprim-sul-
153
mission of CMV to seronegative patients; leukocyte reduction similarly famethoxazole. Dapsone and atovaquone have each been used as a
135
136
134
prevents transmission. Ganciclovir, oral valganciclovir, and CMV second-line prophylactic agent in hematopoietic stem cell transplant
immune globulin infusions have been used to prevent CMV infection recipients, and in some cases may be preferred based on the risk of mar-
in transplant recipients. Ganciclovir and valganciclovir frequently cause row suppression from trimethoprim-sulfamethoxazole. 154,155 Although
myelosuppression, which may complicate the management of neutro- P. jiroveci is a ubiquitous organism, institutional variability in the inci-
137
penic patients on these medications. In addition, the emergence of dence of infection is observed; therefore, the need for prophylaxis varies.
CMV antiviral resistance has been reported in association with preven-
138
tive treatment. CMV prophylaxis among patients receiving conven-
tional chemotherapy has not been as widely studied, but currently there INFECTIONS IN HEMATOPOIETIC STEM
is no evidence supporting its use in this population. Many centers take CELL TRANSPLANTATION RECIPIENTS
139
a preemptive approach, screening patients regularly for CMV viremia
and initiating therapy only when CMV is detected. Prophylactic immu- Patients receiving hematopoietic stem cell transplants are at risk for the
notherapy may have benefit in patients unable to tolerate the potential same infections occurring in patients rendered neutropenic by chemo-
myelotoxicity of antiviral therapy. Recent randomized controlled therapy. Graft-versus-host disease and the immunosuppressive agents
140
trials have suggested that novel anti-CMV agents letermovir and brin- used to treat it result in a particularly high incidence of infection in this
cidofovir may be effective at preventing CMV replication in stem cell group of patients. CMV and varicella zoster virus, are especially trou-
156
transplant recipients. 141,142 blesome. Infection in stem cell transplant patients has been reviewed
Immunizations with killed vaccines such as influenza are recom- and is discussed in Chap. 23.
mended. Live-attenuated vaccines, such as measles and zoster, should
be avoided during immunosuppression. 143 REFERENCES
Fungal Infections 1. Bodey GP, Buckley M, Sathe YS, Freireich EJ: Quantitative relationships between circu-
The high mortality rate of invasive fungal infections in neutropenic lating leukocytes and infection in patients with acute leukemia. Ann Intern MedIntern
Med 64:328, 1966.
patients makes their prevention extremely important. Antifungal pro- 2. Ramphal R: Changes in the etiology of bacteremia in febrile neutropenic patients and
phylaxis in these patients has been studied for more than 2 decades, the susceptibilities of the currently isolated pathogens. Clin Infect Dis 39:S25, 2004.
yet there is still a great deal of controversy surrounding its efficacy. 3. Reilly AF, Lange BJ: Infections with viridans group streptococci in children with cancer.
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Pediatr Blood Cancer 49:774, 2007.
Studies on prevention of fungal infections in neutropenic patients are 4. Wadhwa PD, Morrison VA: Infectious complications of chronic lymphocytic leukemia.
difficult to evaluate. Results of the various studies have been conflicting, Semin Oncol 33:240, 2006.

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