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Infections in Patients With Cancer

February 2015 Infections in Patients With Cancer

A clinical review of risks to patients with immunocompromised systems

Topics Discussed:

• Risk factors for infections in patients with cancer

• Microbial etiology of infection

• Antimicrobial resistance

• Impact of febrile neutropenia

• Risk factors for febrile neutropenia

Infections in Patients With Cancer 2

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:− Underlying disease− Immunosuppressive agents− Impaired bone marrow response, especially after multiple

treatment regimens− Advanced age− Tissue damage

February 2015

Infections in Patients With Cancer 3

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

February 2015

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Pathogens and Their Sites of Infection

February 2015

Sites of Infection and Common Pathogens in Patients With Cancer

•L. Monocytogenes•S. Aureus•S. Pneumoniae•S. Bovis•Coagulase-negative•Staphylococci

Central Nervous System

•Coagulase-negative•Staphylococci•S. aureus•Gram-negative bacilli•C. albicans

Bloodstream

•E. coli•Proteus•C. albicans•Candida spp.•Aspergillius spp.

Urinary

•S. aureus•S. pyogenes•E. coli•P. aeruginosa•Klebsiella spp.•Aspergillus spp.

Skin/Soft Tissue

•Pseudomonas spp.•E. coli•Klebsiella spp.•C. septicum•C. difficile•Candida spp.

Gastrointestinal

•Streptococcus spp.•Methicillin-resistant•Staphylococci•Pseudomonas•A. veronii•E. coli

Respiratory

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Infections and Cancer

Infections Associated With Different Cancers

Disease Prominent Defect Predominant Infections

Acute leukemia Neutropenia, skin andmucosmembrane lesions

Gram-positive cocci, gram-negative bacilli,Candida spp., Aspergillus spp.,Fusarium spp., Trichosporon spp.

Hairy cell leukemia Neutropenia, impairedT-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 transplantrecipient

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.

February 2015

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Microbial Etiology of Infection in Cancer PatientsWith Febrile Neutropenia

• Patients with chemotherapy-induced neutropenia frequently developed fever− 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

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

S

I II III IV V VI VII VIII IX0

5

10

15

20Gram-negative Gram-positive

Single-Organism Bacteremias: EORTC-IATG Trials

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

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

Origins of Fever Patients With Neutropenia

59%33%

8%

Unknown Documented Hospital

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Risk Assessment

February 2015

• Risk assessment for FN should consider the myelotoxicity of treatment regimen− 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− 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

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

Disease-Related

• Underlying malignancy

• Degree advanced age (≥65 years)

• Recent surgery

• Poor performance status

• Poor nutritional status

• Renal dysfunction

Treatment-Related

• Previous history of severe neutropenia with similar chemotherapy

• Type of chemotherapy

• Planned relative dose intensity >80%

• Pre-existing neutropenia or lymphocytopenia

• Extensive prior chemotherapy

• Concurrent or prior radiation therapy to marrow-containing bone

Patient-Specific

• Advanced age (≥65 years)

• Recent surgery

• Poor performance status

• Poor nutritional status

• Renal dysfunction

• Hepatic dysfunction/elevated bilirubin

• Pre-existing neutropenia

• Pre-existing infection/open wounds

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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