Patients with cancer have a significant risk for infection due to their treatment with chemotherapy, radiation, or surgery," stated Debra Wujcik, RN, MSN, AOCN, clinical director at Vanderbilt Cancer Center in Nashville, Tennessee, at the 1996 Oncology Nursing Society Meeting in Philadelphia. "There are some proven strategies that we can put into place to help minimize and prevent infection," she added.
Although the actual incidence of infection in patients with cancer is difficult to determine, fever is due to infection nearly 80% of the time, with the remaining 20% usually attributed to the disease process itself. "The risk of infection is directly related to the depth and the length of the neutropenia," said Ms. Wujcik.
Factors Contributing to Infection Risk
The risks of infection are related to the compromised host defenses and the sequelae of treatment, possibly due to the absence of neutrophils, disruption in the barriers to infection, and shifts in the microbial flora. Although the mortality attributed to such infections has decreased over the years, due to the development of beta-lactam antibiotics and fluoroquinolones, "the types of infections have changed as resistant and opportunistic organisms emerge," said Ms. Wujcik.
Two variables that contribute substantially to the risk of infection in patients with cancer are malignancy-related immunosuppression and treatment procedures. Certain cancers cause specific defects in the immune response, increasing the risk for infection. For instance, patients with acute leukemia may suffer a quantitative defect (neutropenia) and a qualitative defect of the neutrophils--"the cells are just not effective in fighting infection..., and this easily results in bacterial, fungal, and viral infections," Ms. Wujcik explained. Other examples of malignancy-related immunosuppression are seen in patients with chronic lymphocytic leukemia and multiple myeloma, who have a humoral immune defect, and in patients with Hodgkin's disease and non-Hodgkin's lymphoma, who have a defect in cellular immunity, making them susceptible to viral and fungal infections.
Ironically, various modalities used to treat cancer also contribute to the risk of infection in patients with cancer. Both myelosuppressive chemotherapy and radiation therapy, cause neutropenia and altered mucosal barriers. Stomatitis is a toxic effect of specific chemotherapeutic agents, as well as a side effect of radiation to the head and neck. Through bacterial translocation, endogenous microorganisms move into the bloodstream.
Also seriously affecting immune function are corticosteroids, which can place patients at risk not only for the typical bacterial, fungal, and viral infections but also for cytomegalovirus and Pneumocystis carinii pneumonia. Corticosteroids decrease the number of white blood cells and also alter the function of neutrophils. The adherence of neutrophils to epithelial cells is diminished, and consequently, cells are not delivered to the sites of infection. "In addition, lymphocytes, monocytes, and eosinophils are redistributed to extravascular spaces, making them less accessible to the sites of infection," Ms. Wujcik stated.
Treatment-related infection can be caused by procedures that break the integument of the skin, such as intravenous therapy, venipuncture, and biopsy. Depending on the disease and type of treatment, the rate of infection associated with central venous catheters, including infections in the tunnel and exit site, as well as bacteremia, can be as high as 60%.
Wide Range of Possible Pathogens
According to Ms. Wujcik, "one of the difficulties in treating neutropenic febrile patients is the range of organisms that are capable of causing infection." Bacterial infections are the most common first infections seen in patients with cancer. These infections usually arise from the endogenous flora colonizing the skin, respiratory tract, genitourinary tract, and gastrointestinal tract.
Although the most serious infections are caused by gram-negative organisms," Ms. Wujcik noted that "gram-positive infections have become more predominant in the past decade." Possible reasons for this increase in gram-positive infections include the increased use of indwelling catheters and prophylactic antibiotics.
A smaller, but substantial proportion of infections in cancer patients are attributed to colonization by organisms acquired from the local environment, said Ms. Wujcik. The major sources of infection are from organisms in uncooked foods, organisms inhaled (specifically, Aspergillus species), and organisms passed directly from caregivers touching patients.
Viral organisms causing infection in patients with cancer include the herpesvirus, varicella zoster, cytomegalovirus, and Epstein-Barr virus. With some of these viral infections, there is a characteristic latency: an infection early in life produces a dormant infection that is capable of being reactivated at any time, but particularly during periods of immunosuppression
Fungal infections are secondary infections; these infections usually occur in patients who have received antibiotics for fever but also can develop in patients with prolonged neutropenia. Once gram-negative organisms begin to colonize, and especially after empiric antibiotics have been initiated, there is an increased risk of infection with Candida organisms or other fungi. In essence, Ms. Wujcik suggested that if a patient has a fever for more than 5 to 7 days, has been receiving broad-spectrum antibiotics, and no source of infection has been found, a secondary fungal infection should be considered.
Low- vs High-Risk Patients
Distinguishing patients at low risk for infection from those at high risk is a crucial issue. "As we try to move patients out of the hospital setting, or even prevent them from being hospitalized in the first place, we have to become more skilled at looking at which patients are really going to come out of this risk period faster or be in the risk period such a short time that it's safe to allow them to stay home and be treated in the outpatient setting," said Ms. Wujcik.
Patients at low risk for infection demonstrate evidence of impending recovery of bone marrow, usually indicated by an increasing monocyte count followed by an increasing absolute neutrophil count (ANC) and platelet count. According to Ms. Wujcik, sometimes "the indication of returning function of bone marrow can be seen 4 to 5 days before the ANC actually gets to be greater than 500 mm3." Low risk of infection can sometimes be determined at the onset of fever, during hospitalization, or at the time of discharge from the hospital.
Several studies suggest that hospitalized patients with a fever that has resolved, blood cultures that are negative, and early signs of return of bone marrow function "can probably be safely discharged from the hospital and managed at home," concluded Ms. Wujcik. In these low-risk patients, it may be possible to continue daily IV antibiotics at home. Alternatively, selected low-risk patients may be switched to oral antibiotics before discharge.
Patients at high risk for infection have febrile neutropenia, a low white blood count, and other factors that place them at risk. Such factors may include the development of mucositis, diarrhea, advanced disease, overt organ dysfunction, or any sign of clinical instability. Clearly, these patients should not be considered candidates for early discharge from the hospital or outpatient antibiotic therapy.
Taking steps to minimize or prevent infection in patients with cancer has always been a part of standard oncologic nursing care. In light of the changes occurring in the health-care environment today, preventive strategies have become even more essential. "We are in an era...where we are being pressured to move the care of the patient to the outpatient setting or the home setting," said Ms. Wujcik. "And, we are being challenged to look at how cost-effective we can be...."
Strategies for preventing infection are based on fundamental steps: identifying patients at risk; educating patients, family members, and health-care personnel on how to avoid practices that may increase colonization; and decreasing the use of invasive procedures.
A fundamental key to the prevention of infection involves handwashing by anyone who comes into contact with patients. Furthermore, patients themselves should be instructed about the need for proper personal hygiene and preventive oral care. Visitors should be kept to a minimum, but patients should be advised to avoid anyone with signs of an infection. Other measures that may help decrease colonization include removing live plants and flowers and sources of stagnant water from the environment.
In inpatient settings, the ANC can be used as a guide for deciding when to initiate empiric treatment. Although the actual ANC at which treatment should be initiated varies among institutions, it is a worthwhile parameter for health care professionals to lower the rate of colonization of organisms through diet and environmental changes and to detect infection early through more frequent sign and physical assessments.
Preventive strategies focusing on diet, the environment, bowel regimens, oral antibiotics, and growth factors have been evaluated in recent years, although clinical data proving the benefit of some of these strategies may be lacking. For instance, a common dietary suggestion is to avoid uncooked (or at least unpeeled and unwashed) fruits and vegetables to decrease colonization. However, this practice is based on anecdotal evidence rather than on data from randomized clinical trials.
"Environmental modification remains a challenge," said Ms. Wujcik. While attempting to identify the ideal environment for treating patients with cancer without increasing their risk of infection, health-care professionals have traveled the spectrum from a generally relaxed atmosphere to complete reverse isolation. There appears to be a documented mortality benefit for placing at least one select group of patients--ie, those with aplastic anemia who are receiving a bone marrow transplant--in a laminar-airflow environment, Ms. Wujcik said. However, there is less clear evidence for the use of a reverse-isolation or hepafiltered environment. Furthermore, the question of whether the additional cost of such technology is justified remains to be answered.
Similarly, a wide spectrum of guidelines for bowel regimens may be employed, depending on the circumstances. On the one hand, complete sterilization of the gut with oral antibiotics may be recommended for a select group of patients, eg, patients with aplastic anemia undergoing bone marrow transplant in a laminar-airflow environment. On the other hand, stool softeners may be worthwhile for a wider range of patients with cancer to relieve constipation, thus avoiding invasive treatment procedures.
The prophylactic role of oral antibiotics is being closely studied. Although we do not know the best combination of antibiotics, when prophylaxis should be initiated, and which group of patients are ideal candidates, "we know that the fluoroquinolones have potent activity against gram-negative aerobes and they are especially effective
in patients who have a hematologic malignancy and are undergoing bone marrow transplantation," stated Ms. Wujcik. However, general prophylactic use of fluoroquinolones for all patients with cancer is controversial. Some studies clearly show that quinolones decrease gram-negative infections but not gram-positive infections in bone marrow transplant recipients.
Ms. Wujcik referred to the use of preventive antibiotics in this setting as a "balancing act"; it is difficult to determine which agents can be used prophylactically and not cause problematic resistant organisms.
Hematopoietic growth factors may prevent infection by shortening the duration and severity of febrile neutropenic episodes but have not been shown to change mortality overall. After myelosuppressive chemotherapy, there is a typical drop in the ANC. With the administration of growth factors 24 hours after chemotherapy, the period of risk has been decreased in some patient populations. However, these growth factors are not suitable for all patients undergoing all types of chemotherapy and are particularly inappropriate for low-risk patients. Furthermore, they are expensive to administer and are sometimes not covered by medical insurance.
"Prevention of infection in the home setting is a whole different challenge," said Ms. Wujcik. Documented standards for outpatient home care should be clarified over the next few years. First and foremost, patients and families must be taught what signs and symptoms to watch for. Patients need to monitor their temperature and be instructed when to call for medical assistance. Patients also should report such symptoms as cough, burning on urination, sore mouth, and any area that appears to be infected.
Patients also need to be educated about risk factors for infection and steps they should take to decrease possible colonization. Avoiding people with infectious illnesses and strict handwashing by the patient and all persons who come into contact with him or her are two important preventive measures. Various self-care guides on infection are available.
In conclusion, patients with cancer are at risk for infection for multiple reasons. According to Ms. Wujcik, "strategies to minimize and prevent infection in patients with mild to moderate short-term neutropenia are generally successful.... Complete prevention or elimination of infection has not been accomplished in some of our high-risk populations, such as those patients undergoing bone marrow transplantation or intensive chemotherapy."