Infection and Sepsis
Infection is characterized by an inflammatory response to the presence of microorganisms in the body. This response may include fever, chills, redness, swelling, pus formation and other responses. The most common cause of illness and death in patients with cancer is infection. Patients with cancer who are treated with chemotherapy, radiation therapy, and/or surgery are at increased risk of developing an infection. Mortality, or death, from infection in cancer patients decreased during the late 1900s due to the development of new types of antibiotics, the use of hematopoietic growth factors (HGFs) which activate proliferation (multiplication) and maturation of blood cell lines, and due to the prophylactic (preventive) use of antifungal and antiviral agents. Blood cell lines, markedly decreased due to chemotherapy, are required to fight infections. Most infections in cancer patients are due to bacteria; however, fungal infections are usually the cause of fatal infections.
If left untreated, or if inadequately treated, infection can progress to sepsis. Sepsis is defined as a systemic (total body) inflammatory response to the presence of microorganisms in the body. Several conditions indicate sepsis, including a temperature of greater than 38 degrees Centigrade (100.4 Fahrenheit) or less than 36 degrees Centigrade (96.8 Fahrenheit), heart rate greater than 90 beats per minutes, and respiratory rate greater than 20 breaths per minute. The incidence rate of sepsis in cancer patients is estimated at 45%. Mortality rates from sepsis in cancer patients exceed 30%.
There are many possible causes of infection in the patient with cancer. For example, certain cancers interfere with the body's immune system response, which results in increased risk of infection to the patient. These cancer types include acute leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphoma. Certain therapies used to treat cancer, such as chemotherapy (which interrupts bone marrow production of white blood cells, red blood cells, and platelets), radiation therapy, bone marrow transplantation, and treatments using corticosteroids, can lead to infection in the patient with cancer. The protein-calorie malnutrition that some cancer patients experience can result in suppression of the immune system, which results in increased risk for infection. Many cancer patients develop infections from procedures which break the integrity of the skin, which then leads to the introduction of microorganisms into the body. These procedures include common interventions in the care of cancer patients such as venipunctures, biopsies, insertion of urinary catheters, and use of long-term central venous catheters. Infection rates associated with long-term central venous catheter use in cancer patients is estimated to be as high as 60%. If the cancer patient's immune system is severely compromised, infection can occur from food sources, plants, and/or air the patient comes in contact with.
Myelosuppression is the term used to describe the decrease in numbers of circulating white blood cells (WBC), red blood cells (RBC), and platelets. Myelosuppression is often a side effect of treatment with chemotherapy and/or radiation therapy. Blood counts usually begin to fall one to three weeks after treatment with chemotherapy, depending upon the type of chemotherapy and the lifespan of the blood cell. The counts generally begin to recover to normal levels within two to three weeks. The neutrophil, which is a component of the white blood cells, is the body's first line of defense against infection caused by bacteria. When neutrophils are decreased a state of neutropenia exits. Neutropenia is the single greatest predictor of infection in patients with cancer. Three key factors are important in predicting the potential of a patient to experience an infectious episode when myelosuppressed. These factors include: 1) the degree of neutropenia, i.e., the lower the neutrophil count the more likely the patient will become infected, 2) the duration of the neutropenia,
Bacterial infections in cancer patients develop quickly, especially in the neutropenic patient, and account for 85-90% of the microorganisms associated with neutropenia accompanied by fever. The most serious episodes occur from infections attributed to gram-negative organisms such as Enterobacteriaceae or Pseudomonas aeruginosa. However, infections from gram-positive organisms such as Staphylococcus, Streptococcus, Corynebacteria, and Clostridia have increased in the 1990s, probably due to the increased use of implanted central venous catheters and prophylactic antibiotics (to which these organisms develop an immunity). Other organisms that cause infections in the immunocompromised cancer patient include herpesvirus infections such as herpes simplex virus 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Sources of secondary infections include the fungal infection, Candida albicans. Common causes of secondary infection in severely immunosuppressed patients include CMV, and the filamentous fungi, Aspergillus.
The incidence of sepsis and septic shock increases when the patient remains neutropenic for longer than seven days. Other factors that put the cancer patient at high risk for the development of sepsis include infection with a gram-negative organism, presence of a central venous catheter, history of prior infection, malnutrition, history of frequent hospitalization, increased age of patient, and concurrent (at the same time) presence of other diseases such as diabetes, cardiovascular, gastrointestinal, hepatic, pulmonary, and/or renal disease. Sites of infection that most often lead to sepsis include infection of the lungs, invasive lines, and urinary tract.
Sepsis manifests (develops) with both local and systemic symptoms that involve the neurologic, endocrine, immunologic, and cardiovascular systems. Signs of sepsis and septic shock include changes in blood pressure, heart rate and respiratory rate, among others. If left untreated, the patient can progress to septic shock which may result in death even if the shock episode is treated.
Strategies that can be used to prevent or minimize infection in the neutropenic patient include:
- Identification of patients at highest risk for infection.
- Avoiding practices by health care team members that increase colonization of microorganisms.
- Implementation of fewer invasive procedures when possible.
Specific interventions in the hospital setting that can be used to prevent or minimize infection include:
- scrupulous handwashing by patient, staff, and visitors.
- good personal hygiene, including an oral care protocol by the patient.
- ambulation (movement).
- aggressive efforts to promote lung expansion.
- elimination of uncooked fruits and vegetables from the diet.
- removal of plants and other sources of stagnant water from the patient's room.
- screening and minimizing outside visitors to avoid those with infection
In addition, the hospitalized patient is assessed by the staff at least every four hours and laboratory results are collected and analyzed to determine risk for and presence of neutropenia.
A newer method to prevent infection in the cancer patient works by decreasing the duration of neutropenia. This method decreases the period of maximum risk for infection by using hematopoietic growth factors (HGFs). These growth factors are administered daily beginning 24 hours after chemotherapy, and shorten the duration and severity of neutropenia. Therefore, the period of risk for infection is shortened. HGFs work by activating the production and maturation of RBCs, WBCs, and platelet cell lines. Specific HGFs stimulate the production and maturation of aggressive neutrophils and macrophages, which are effective in destroying pathogens (bacteria or viruses that cause infection or disease).
Sepsis can be avoided by preventing infection in immunocompromised patients and by recognizing risk factors and altering those factors whenever possible.
Empiric antibiotic therapy is the mainstay of treatment for infection in the cancer patient. Empiric therapy refers to initiation of antibiotic therapy prior to the identification of the infecting organism. Broad-spectrum antibiotics, antibiotics effective against both gram-negative and gram-positive organisms, are administered. Commonly used agents include aminoglycosides, fluoroquinolones, glycopeptides, and beta-lactams such as penicillins, cephalosporins, carbapenems, and monobactams. Empiric antifungal therapy is initiated five to seven days after empiric antibiotic therapy has been started if the patient remains febrile (with a fever). Antiviral agents may be administered if there is evidence of a viral infection. The Infectious Diseases Society of America recommends a minimum of five to seven days further treatment with parenteral (introduced in other ways than intestinal absorption) antibiotic therapy after the fever resolves (returns to normal). Continued monitoring of bacterial and fungal culture results is essential. This allows the use of more tailored antibiotics for the specific infectious agents.
The neutropenic patient with fever can progress quickly to sepsis and septic shock if left untreated. The patient may also progress to septic shock if empiric antibiotic coverage is inadequate. The most common cause of septic shock in cancer patients is infection with gram-negative bacteria. The management of sepsis and septic shock is considered an emergency situation and includes treatment with broad-spectrum antibacterial coverage and maintenance of ventilation, oxygenation, fluid volume, and cardiac output.
See Also Vascular access
Freifeld, A. G., T. J. Walsh, and P. A. APizzo. "Infections in the Cancer Patient." In Cancer: Principles and Practice of Oncology. DeVita, V.T., S. Hellman, and S. A. Rosenberg. Philadelphia: Lippincott, 1997, pp.2659-2704.
Schaffer, S. D., L. S. Garzon, and D. L. Heroux, et al. Infection Prevention and Safe Practice St. Louis: Mosby, 1996.
Wujcik, D. "Infection." In Cancer Symptom Management Boston: Jones and Bartlett, 1999, pp. 307-321.
Shelton, B. "Sepsis." Seminars in Oncology Nursing 15 (August 1999): 209-221.
Toney, J. F., and M. M. Parker. "New Perspectives on the Management of Septic Shock in the Cancer Patient." Infectious Diseases Clinics of North America 10 (1996): 239-253.
Yoshida, M. "Infections in Patients with Hematological Diseases: Recent Advances in Serological Diagnosis and Empiric Therapy." International Journal of Hematology 66 (1997): 279-289.
"Supportive Care for Patients -Fever, Chills, and Sweats."National Cancer Institute CancerNet 16 April 2001 <http://cancernet.nci.nih.gov/coping.html>
Melinda Granger Oberleitner, R.N., D.N.S.
—Adrenal cortex steroids.
Central venous catheters
—Devices used for access to the blood stream. The distal tip of the catheter after insertion is located in the superior vena cava, or above the junction of the right atrium. May be used for blood sampling and for the infusion of any type of fluids, medications, nutritional supplements, and blood components.
—Types of bacteria that do not retain gram stain.
—Types of bacteria that retain gram stain.