Page 888 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 68: Approach to Infection in Patients Receiving Cytotoxic Chemotherapy for Malignancy 619

Molds produce similar syndromes in compromised hosts, including
necrotizing nasal mucosal infection, sinusitis, endophthalmitis, cerebral
parenchymal infection, pulmonary parenchymal infection, cutaneous
infection, typhlitis, hepatosplenic abscesses, osteomyelitis, and intravas-
cular infections. 402
Infections by these molds are characterized by blood vessel invasion
resulting in thrombosis, which, in turn, causes ischemia and infarc-
tion of distal tissues. 292,293,403,404 This is the mechanism for the clinical
manifestations such as pulmonary cavitary disease, hemoptysis, cutane-
ous infarcts (see Fig. 68-3), stroke-like syndromes due to intracranial
infection (Fig. 68-7), and parenchymal hepatic infarction (Fig. 68-8).
Infection occurs following the germination of inhaled conidia on the
respiratory epithelium with the production of invasive hyphae. 292
Characterization of these infections is important in determining prog-
nosis and outcome of antifungal therapy. In 2002, the National Institute
of Allergy and Infectious Diseases Mycoses Study Group (NIAID/MSG)
of the National Institutes of Health and the European Organization
for the Treatment and Research of Cancer/Invasive Fungal Infections
Cooperative Group (EORTC/IFICG) published an international consen-
sus of diagnostic criteria for invasive fungal infections (IFI) and that
405
was since updated in 2008. The diagnosis of IFI may be classified into
406
FIGURE 68-6. CT scan of the abdomen in a 22-year-old male recipient of high-dose cytara- three levels of probability as “proven,” “probable,” or “possible” based on
bine for relapsed high-grade non-Hodgkin lymphoma. Multiple areas of decreased attenuation the robustness of the evidence supporting the diagnosis. “Proven” IFI
are noted in the hepatic and splenic parenchyma consistent with hepatosplenic candidiasis. requires the demonstration of fungal elements in tissue specimens either
in histopathological tissue sections or in culture. 405,406 Diagnoses of IFI
based on less robust evidence are defined by a composite of host factors,
of abnormal baseline surrogate markers of systemic inflammation such clinical signs and symptoms, and mycological criteria. The revised
405
as the erythrocyte sedimentation rate or the C-reactive protein may also
provide confidence in a treatment effect. One must remember that EORTC/MSG definitions expanded the definition of “probable” and
384
focal hepatosplenic lesions tend to become radiologically detectable
with neutrophil recovery and may disappear during subsequent periods
of severe neutropenia. 373,385,386 Accordingly, the timing of diagnostic
imaging relative to the ANC is important in making an accurate diag-
nosis and response assessment.
The Infectious Diseases Society of America and the Association of
Medical Microbiology and Infectious Diseases, Canada, have suggested
that patients with prolonged neutropenia who are persistently febrile
despite 4 to 7 days of broad-spectrum antibacterial therapy —may
266
be candidates for empirical amphotericin B. 21,65,272,387 This is based on
trials arguing a high risk for invasive fungal infection in this circum-
stance. 273,274,388 Empirical antifungal therapy is significantly higher than
the incidence of documented invasive fungal infection in neutropenic
patients with acute leukemia. 119,389-391 and HSCT recipients. 392-395
The IDSA guidelines recommend the removal of all indwelling vas-
cular access catheters in candidemic patients whenever possible, in
349
order to reduce the risk for metastatic visceral infections and excess
mortality. Previous studies suggest that catheter removal at diagnosis
396
of candidemic episodes reduces the duration of candidemia and mor-
397
tality. More recent studies among candidemic patients receiving either
396
an echinocandin antifungal agent or an amphotericin B formulation
with or without central venous catheters left in situ failed to confirm
those earlier observations, however. 350,362,398
Opportunistic Filamentous Fungal Infections: Opportunistic filamentous
fungal infections are frequently life-threatening complications among
neutropenic patients undergoing remission-induction treatment for acute
leukemia or hematopoietic stem cell transplantation. These infections
are most often caused by Aspergillus species (most often Aspergillus
fumigatus), Fusarium spp, the dematiaceous fungi (black molds), or the
Zygomycetes (eg, Absidia spp, Rhizopus spp, Rhizomucor spp, Mucor spp,
or Cunninghamella spp). 345,399 Invasive aspergillosis in the ICU setting has
been observed at a median rate of 6.3 per 1000 admissions and with a crude
mortality rate of 63%. The isolation of Aspergillus spp from the respiratory
400
401
tract of mechanically ventilated ICU patients is a predictor of mortality
particularly in HSCT recipients (p < .01), hematological malignancies
(p = .02), and those receiving broad-spectrum antibacterial therapy FIGURE 68-7. CT scan of the brain shows an intracerebral infarct in a 27-year-old man
(p = .02). being treated for AML complicated by disseminated aspergillosis.

section05_c61-73.indd 619 1/23/2015 12:48:11 PM