INFECTIONS IN PATIENTS WITH CANCER: INTRODUCTION

Infections are a common cause of death and an even more common cause of morbidity in patients with a wide variety of neoplasms. Autopsy studies show that most deaths from acute leukemia and half of deaths from lymphoma are caused directly by infection. With more intensive chemotherapy, patients with solid tumors have also become more likely to die of infection. Fortunately, an evolving approach to prevention and treatment of infectious complications of cancer has decreased rates of infection-associated mortality and will probably continue to do so. This accomplishment has resulted from three major steps:

The concept of “early empirical” antibiotics reduced mortality rates among patients with leukemia and bacteremia from 84% in 1965 to 44% in 1972. With better availability (and early use) of broad-spectrum antibiotics, this figure has recently dropped to 20–36%.

“Empirical” antifungal therapy has lowered the incidence of disseminated fungal infection; in trial settings, mortality rates now range from 7 to 21%. An antifungal agent is administered—on the basis of likely fungal infection—to neutropenic patients who, after 4–7 days of antibiotic therapy, remain febrile but have no positive cultures.

Use of antibiotics for afebrile neutropenic patients as broad-spectrum prophylaxis against infections promises to decrease both mortality and morbidity even further.

A physical predisposition to infection in patients with cancer (Table 82-1) can be a result of the neoplasm’s production of a break in the skin. For example, a squamous cell carcinoma may cause local invasion of the epidermis, which allows bacteria to gain access to the subcutaneous tissue and permits the development of cellulitis. The artificial closing of a normally patent orifice can also predispose to infection: Obstruction of a ureter by a tumor can cause urinary tract infection, and obstruction of the bile duct can cause cholangitis. Part of the host’s normal defense against infection depends on the continuous emptying of a viscus; without emptying, a few bacteria present as a result of bacteremia or local transit can multiply and cause disease.

Table 82-1 Disruption of Normal Barriers that May Predispose to Infections in Patients with Cancer

Type of Defense	Specific Lesion	Cells Involved	Organism	Cancer Association	Disease
Physical barrier	Breaks in skin	Skin epithelial cells	Staphylococci, streptococci	Head and neck, squamous cell carcinoma	Cellulitis, extensive skin infection
Emptying of fluid collections	Occlusion of orifices: ureters, bile duct, colon	Luminal epithelial cells	Gram-negative bacilli	Renal, ovarian, biliary tree, metastatic diseases of many cancers	Rapid, overwhelmingbacteremia; urinary tract infection
Lymphatic function	Node dissection	Lymph nodes	Staphylococci, streptococci	Breast cancer surgery	Cellulitis
Splenic clearance of microorganisms	Splenectomy	Splenic reticuloendothelial cells	Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Babesia, Capnocytophaga canimorsus	Hodgkin’s disease, leukemia, idiopathic thrombocytopenic purpura	Rapid, overwhelming sepsis
Phagocytosis	Lack of granulocytes	Granulocytes (neutrophils)	Staphylococci, streptococci, enteric organisms, fungi	Hairy cell, acute myelocytic, and acute lymphocytic leukemias	Bacteremia
Humoral immunity	Lack of antibody	B cells	S. pneumoniae, H. influenzae, N. meningitidis	Chronic lymphocytic leukemia, multiple myeloma	Infections with encapsulated organisms, sinusitis, pneumonia
Cellular immunity	Lack of T cells	T cells and macrophages	Mycobacterium tuberculosis, Listeria, herpesviruses, fungi, other intracellular parasites	Hodgkin’s disease, leukemia, T cell lymphoma	Infections with intracellular bacteria, fungi, parasites

A similar problem can affect patients whose lymph node integrity has been disrupted by radical surgery, particularly patients who have had radical node dissections. A common clinical problem following radical mastectomy is the development of cellulitis (usually caused by streptococci or staphylococci) because of lymphedema and/or inadequate lymph drainage. In most cases, this problem can be addressed by local measures designed to prevent fluid accumulation and breaks in the skin, but antibiotic prophylaxis has been necessary in refractory cases.

A life-threatening problem common to many cancer patients is the loss of the reticuloendothelial capacity to clear microorganisms after splenectomy. Splenectomy may be performed as part of the management of hairy cell leukemia, chronic lymphocytic leukemia (CLL), and chronic myelocytic leukemia (CML) and in Hodgkin’s disease. Even after curative therapy for the underlying disease, the lack of a spleen predisposes such patients to rapidly fatal infections. The loss of the spleen through trauma similarly predisposes the normal host to overwhelming infection for life after splenectomy. The splenectomized patient should be counseled about the risks of infection with certain organisms, such as the protozoan Babesia (Chap. 204) and Capnocytophaga canimorsus (formerly dysgonic fermenter 2, or DF-2), a bacterium carried in the mouths of animals (Chaps. 140 and e14). Since encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) are the organisms most commonly associated with postsplenectomy sepsis, splenectomized persons should be vaccinated (and revaccinated; Table 82-2 and Chap. 116) against the capsular polysaccharides of these organisms. Many clinicians recommend giving splenectomized patients a small supply of antibiotics effective against S. pneumoniae, N. meningitidis, and H. influenzae to avert rapid, overwhelming sepsis in the event that they cannot present for medical attention immediately after the onset of fever or other symptoms of bacterial infection. A few amoxicillin/clavulanic acid tablets are a reasonable choice for this purpose.

Table 82-2 Vaccination of Cancer Patients Receiving Chemotherapy

	Use in Indicated Patients
Vaccine	Intensive Chemotherapy	Hodgkin’s Disease	Hematopoietic Stem Cell Transplantation
Diphtheria-tetanus a	Primary series and boosters as necessary	No special recommendation	12, 14, and 24 months after transplantation
Poliomyelitis b	Complete primary series and boosters	No special recommendation	12, 14, and 24 months after transplantation
Haemophilus influenzae type b conjugate	Primary series and booster for children	Immunization before treatment and booster 3 months afterward	12, 14, and 24 months after transplantation
Hepatitis A	Not routinely recommended	Not routinely recommended	Not routinely recommended
Hepatitis B	Complete series	No special recommendation	12, 14, and 24 months after transplantation
23-Valent pneumococcal polysaccharide c	Every 5 years	Immunization before treatment and booster 3 months afterward	12 and 24 months after transplantation
4-Valent meningococcal conjugate d	Should be administered to splenectomized patients and patients living in endemic areas, including college students in dormitories	Should be administered to splenectomized patients and patients living in endemic areas, including college students in dormitories	Should be administered to splenectomized patients and patients living in endemic areas, including college students in dormitories
Influenza	Seasonal immunization	Seasonal immunization	Seasonal immunization
Measles/mumps/rubella	Contraindicated	Contraindicated during chemotherapy	After 24 months in patients without graft-versus-host disease
Varicella-zoster virus	Contraindicated e	Contraindicated	Contraindicated

^a The Td (tetanus-diphtheria) combination is currently recommended for adults. Pertussis vaccines have not been recommended for people >6 years of age in the past. However, recent data indicate that the Tdap (tetanus–diphtheria–acellular pertussis) product is both safe and efficacious in adults.
^b Live-virus vaccine is contraindicated; inactivated vaccine should be used.
^c The seven-serotype pneumococcal conjugate vaccine is currently recommended only for children. It is anticipated that future vaccines will include more serotypes and will be recommended for adults.
^d Currently licensed for people 11–55 years of age.
^e Contact the manufacturer for more information on use in children with acute lymphocytic leukemia.

The level of suspicion of infections with certain organisms should depend on the type of cancer diagnosed (Table 82-3). Diagnosis of multiple myeloma or CLL should alert the clinician to the possibility of hypogammaglobulinemia. While immunoglobulin replacement therapy can be effective, in most cases prophylactic antibiotics are a cheaper, more convenient method of eliminating bacterial infections in CLL patients with hypogammaglobulinemia. Patients with acute lymphocytic leukemia (ALL), patients with non-Hodgkin’s lymphoma, and all cancer patients treated with high-dose glucocorticoids (or glucocorticoid-containing chemotherapy regimens) should receive antibiotic prophylaxis for Pneumocystis infection (Table 82-3) for the duration of their chemotherapy. In addition to exhibiting susceptibility to certain infectious organisms, patients with cancer are likely to manifest their infections in characteristic ways.

Table 82-3 Infections Associated with Specific Types of Cancer

Cancer	Underlying Immune Abnormality	Organisms Causing Infection
Multiple myeloma	Hypogammaglobulinemia	Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
Chronic lymphocytic leukemia	Hypogammaglobulinemia	S. pneumoniae, H. influenzae, N. meningitidis
Acute myelocytic or lymphocytic leukemia	Granulocytopenia, skin and mucous-membrane lesions	Extracellular gram-positive and gram-negative bacteria, fungi
Hodgkin’s disease	Abnormal T cell function	Intracellular pathogens (Mycobacterium tuberculosis, Listeria, Salmonella, Cryptococcus, Mycobacterium avium)
Non-Hodgkin’s lymphoma and acute lymphocytic leukemia	Glucocorticoid chemotherapy, T and B cell dysfunction	Pneumocystis
Colon and rectal tumors	Local abnormalities a	Streptococcus bovis (bacteremia)
Hairy cell leukemia	Abnormal T cell function	Intracellular pathogens (M. tuberculosis, Listeria, Cryptococcus, M. avium)

^a The reason for this association is not well defined.

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