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Infections in
Patients With Cancer
A clinical review of risks to patients
with immunocompromised systems
Topics Discussed:
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Risk factors for infections in patients
with cancer
•
Microbial etiology of infection
•
Antimicrobial resistance
•
Impact of febrile neutropenia
•
Risk factors for febrile neutropenia
February 2015
Infections in Patients With Cancer
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Weaknesses in Host Defenses Can Markedly Increase
the Risk of Infection in Patients With Cancer
• Factors that influence the risk of bacterial and fungal infection
in patients with cancer:
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Underlying disease
Immunosuppressive agents
Impaired bone marrow response, especially after multiple
treatment regimens
Advanced age
Tissue damage
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Facts About Infections and Cancer
• Opportunistic fungal infections are an important cause of
infection and tend to occur later in the course of neutropenia
than bacterial infections
• Common sites of infection in cancer patients with neutropenia
include the gastrointestinal tract, skin, and lung
• Specific malignancies may be associated with immune
dysfunctions that predisposes to infection with particular
pathogens
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Infections in Patients With Cancer
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Pathogens and Their Sites of Infection
Sites of Infection and Common Pathogens in Patients With Cancer
Central Nervous System
Skin/Soft Tissue
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L. Monocytogenes
S. Aureus
S. Pneumoniae
S. Bovis
Coagulase-negative
Staphylococci
S. aureus
S. pyogenes
E. coli
P. aeruginosa
Klebsiella spp.
Aspergillus spp.
Respiratory
Bloodstream
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Coagulase-negative
Staphylococci
S. aureus
Gram-negative bacilli
C. albicans
Urinary
Gastrointestinal
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E. coli
Proteus
C. albicans
Candida spp.
Aspergillius spp.
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Infections in Patients With Cancer
Streptococcus spp.
Methicillin-resistant
Staphylococci
Pseudomonas
A. veronii
E. coli
Pseudomonas spp.
E. coli
Klebsiella spp.
C. septicum
C. difficile
Candida spp.
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Infections and Cancer
Infections Associated With Different Cancers
Disease
Prominent Defect
Predominant Infections
Acute leukemia
Neutropenia, skin and
mucosmembrane lesions
Gram-positive cocci, gram-negative bacilli,
Candida spp., Aspergillus spp.,
Fusarium spp., Trichosporon spp.
Hairy cell leukemia
Neutropenia, impaired
T-cell function
Gram-negative bacilli, gram-positive cocci,
mycobacteria
Chronic lymphocytic leukemia,
multiple myeloma
Hypogammaglobulinemia
Encapsulated organisms, S. pneumoniae,
H. influenzae; N. meningitides
Hodgkin’s disease
Impaired T-cell function
Pneumocystis spp., Cryptococcus spp.,
mycobacteria, Toxoplasma spp.,
Listeria spp., Cryptosporidium spp.,
Candida spp.
Bone marrow transplant
recipient
Tissue necrosis
Gram-positive cocci, gram-negative bacilli,
anaerobes
Breast cancer
Local obstruction,
tissue necrosis
Gram-positive cocci, gram-negative bacilli,
anaerobes
Lung cancer
Local obstruction,
tissue necrosis
Mixed aerobic and anaerobic enteric flora
Non-Hodgkin’s lymphoma
T- and B-cell dysfunction
Pneumocystis spp.
Adapted from Kufe DW, et al. eds. Holland-Frei Cancer Medicine. 6th edition. Hamilton, ON: BC Decker, Inc; 2003.
Adapted from Longo D, et al. Harrison’s Principles of Internal Medicine, 18th edition. United States: McGraw-Hill; 2011.
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Microbial Etiology of Infection in Cancer Patients
With Febrile Neutropenia
• Patients with chemotherapy-induced neutropenia frequently
developed fever
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10%–50% of patients with solid tumors
>80% of patients with hematologic malignancies
• Changing paradigms in the microbiology of infections is
causing increasing concern in cancer patients with febrile
neutropenia (FN)
• Within the past 20 years the microbiology of infections has
shifted with gram-positive organisms becoming increasingly
common
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Changes in Types of Infections
• Shift in microbes may be attributable to routine use of central
venous catheters, use of quinolone prophylaxis, and
increased use of proton pump inhibitors
Single-Organism Bacteremias: EORTC-IATG Trials
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Gram-negative
Gram-positive
15
S
10
5
0
I
II
III
IV
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VI
VII
VIII
IX
Data from the European Organization for Research and Treatment of Cancer-International Antimicrobial TherapyGroup (EORTC-IATG) and trials conducted from 1985 to 2000.
Adapted from Viscoli C, et al. Clin Infect Dis. 2005;40(suppl 4):S240–S245.
February 2015
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Changes in Types of Infections
• Shift in microbes may be attributable to routine use of central
venous catheters, use of quinolone prophylaxis, and
increased use of proton pump inhibitors
Origins of Fever Patients With Neutropenia
8%
33%
Unknown
59%
Documented
Hospital
Data from the European Organization for Research and Treatment of Cancer-International Antimicrobial TherapyGroup (EORTC-IATG) and trials conducted from 1985 to 2000.
Adapted from Viscoli C, et al. Clin Infect Dis. 2005;40(suppl 4):S240–S245.
February 2015
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Risk Assessment
• Risk assessment for FN should consider the myelotoxicity of
treatment regimen
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Patients considered to be at high-risk when the treatment regimen has
a >20% risk of FN
• Risk assessment for FN should also consider disease-,
treatment-,and patient-specific risk factors
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February 2015
Risk for FN is dependent upon the underlying malignancy, type and
intensity of chemotherapy regimen, need for concomitant radiation
therapy, and degree of bone marrow involvement
Common patient-related risk factors for FN include advanced age,
poor performance status, poor nutritional status, poor hepatic and/or
renal function, pre-existing neutropenia/infection, and prior
chemotherapy
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Review of Risk Factors
• Risk factors for FN are listed below:
Risk Factors for FN
Disease-Related
Patient-Specific
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Underlying malignancy
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Advanced age (≥65 years)
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Degree advanced age (≥65 years)
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Recent surgery
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Recent surgery
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Poor performance status
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Poor performance status
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Poor nutritional status
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Poor nutritional status
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Renal dysfunction
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Renal dysfunction
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Hepatic dysfunction/elevated bilirubin
Treatment-Related
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Pre-existing neutropenia
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Previous history of severe neutropenia
with similar chemotherapy
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Pre-existing infection/open wounds
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Type of chemotherapy
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Planned relative dose intensity >80%
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Pre-existing neutropenia or
lymphocytopenia
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Extensive prior chemotherapy
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Concurrent or prior radiation therapy
to marrow-containing bone
Adapted from NCCN Clinical Practice Guidelines in Oncology. V.1.2011.
Adapted from Lyman GH. J Natl Compr Canc Netw. 2005;3:557–571.
February 2015
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Infections in Patients With Cancer Key Points
• Patients with cancer have increased susceptibility to bacterial and
fungal infections
• Changing paradigms in microbiology of infections is causing
increasing concern in cancer patients with FN
• Increase in drug-resistant pathogens poses additional challenges in
cancer patients with FN
• FN remains a significant cause of morbidity, mortality and increased
cost in patients with cancer receiving myleosuppressive
chemotherapy
• Evaluation of risk factors for FN should be based on myelotoxicity of
chemotherapy regimen and the assessment of specific disease-,
individual patient-, and regimen-related risk factors
February 2015
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