Bacterial Infection in Patients With Cancer: Focus on Prevention

Patients with cancer have a significant risk for infection due to theirtreatment with chemotherapy, radiation, or surgery," stated DebraWujcik, RN, MSN, AOCN, clinical director at Vanderbilt Cancer Center inNashville, Tennessee, at the 1996 Oncology Nursing Society Meeting in Philadelphia."There are some proven strategies that we can put into place to helpminimize and prevent infection," she added.

Although the actual incidence of infection in patients with cancer isdifficult 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 lengthof the neutropenia," said Ms. Wujcik.

Factors Contributing to Infection Risk

The risks of infection are related to the compromised host defensesand 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 overthe years, due to the development of beta-lactam antibiotics and fluoroquinolones,"the types of infections have changed as resistant and opportunisticorganisms emerge," said Ms. Wujcik.

Two variables that contribute substantially to the risk of infectionin patients with cancer are malignancy-related immunosuppression and treatmentprocedures. Certain cancers cause specific defects in the immune response,increasing the risk for infection. For instance, patients with acute leukemiamay suffer a quantitative defect (neutropenia) and a qualitative defectof the neutrophils--"the cells are just not effective in fightinginfection..., and this easily results in bacterial, fungal, and viral infections,"Ms. Wujcik explained. Other examples of malignancy-related immunosuppressionare seen in patients with chronic lymphocytic leukemia and multiple myeloma,who have a humoral immune defect, and in patients with Hodgkin's diseaseand non-Hodgkin's lymphoma, who have a defect in cellular immunity, makingthem susceptible to viral and fungal infections.

Ironically, various modalities used to treat cancer also contributeto the risk of infection in patients with cancer. Both myelosuppressivechemotherapy and radiation therapy, cause neutropenia and altered mucosalbarriers. Stomatitis is a toxic effect of specific chemotherapeutic agents,as well as a side effect of radiation to the head and neck. Through bacterialtranslocation, endogenous microorganisms move into the bloodstream.

Also seriously affecting immune function are corticosteroids, whichcan place patients at risk not only for the typical bacterial, fungal,and viral infections but also for cytomegalovirus and Pneumocystis cariniipneumonia. Corticosteroids decrease the number of white blood cells andalso alter the function of neutrophils. The adherence of neutrophils toepithelial cells is diminished, and consequently, cells are not deliveredto the sites of infection. "In addition, lymphocytes, monocytes, andeosinophils are redistributed to extravascular spaces, making them lessaccessible to the sites of infection," Ms. Wujcik stated.

Treatment-related infection can be caused by procedures that break theintegument of the skin, such as intravenous therapy, venipuncture, andbiopsy. Depending on the disease and type of treatment, the rate of infectionassociated with central venous catheters, including infections in the tunneland 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 neutropenicfebrile patients is the range of organisms that are capable of causinginfection." Bacterial infections are the most common first infectionsseen in patients with cancer. These infections usually arise from the endogenousflora colonizing the skin, respiratory tract, genitourinary tract, andgastrointestinal tract.

Although the most serious infections are caused by gram-negative organisms,"Ms. Wujcik noted that "gram-positive infections have become more predominantin the past decade." Possible reasons for this increase in gram-positiveinfections include the increased use of indwelling catheters and prophylacticantibiotics.

A smaller, but substantial proportion of infections in cancer patientsare attributed to colonization by organisms acquired from the local environment,said Ms. Wujcik. The major sources of infection are from organisms in uncookedfoods, organisms inhaled (specifically, Aspergillus species), and organismspassed directly from caregivers touching patients.

Viral organisms causing infection in patients with cancer include theherpesvirus, 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 capableof being reactivated at any time, but particularly during periods of immunosuppression

Fungal infections are secondary infections; these infections usuallyoccur in patients who have received antibiotics for fever but also candevelop in patients with prolonged neutropenia. Once gram-negative organismsbegin to colonize, and especially after empiric antibiotics have been initiated,there is an increased risk of infection with Candida organisms or otherfungi. In essence, Ms. Wujcik suggested that if a patient has a fever formore than 5 to 7 days, has been receiving broad-spectrum antibiotics, andno source of infection has been found, a secondary fungal infection shouldbe considered.

Low- vs High-Risk Patients

Distinguishing patients at low risk for infection from those at highrisk is a crucial issue. "As we try to move patients out of the hospitalsetting, or even prevent them from being hospitalized in the first place,we have to become more skilled at looking at which patients are reallygoing to come out of this risk period faster or be in the risk period sucha short time that it's safe to allow them to stay home and be treated inthe outpatient setting," said Ms. Wujcik.

Patients at low risk for infection demonstrate evidence of impendingrecovery of bone marrow, usually indicated by an increasing monocyte countfollowed by an increasing absolute neutrophil count (ANC) and plateletcount. According to Ms. Wujcik, sometimes "the indication of returningfunction of bone marrow can be seen 4 to 5 days before the ANC actuallygets to be greater than 500 mm3." Low risk of infection can sometimesbe determined at the onset of fever, during hospitalization, or at thetime of discharge from the hospital.

Several studies suggest that hospitalized patients with a fever thathas resolved, blood cultures that are negative, and early signs of returnof bone marrow function "can probably be safely discharged from thehospital and managed at home," concluded Ms. Wujcik. In these low-riskpatients, it may be possible to continue daily IV antibiotics at home.Alternatively, selected low-risk patients may be switched to oral antibioticsbefore discharge.

Patients at high risk for infection have febrile neutropenia, a lowwhite blood count, and other factors that place them at risk. Such factorsmay include the development of mucositis, diarrhea, advanced disease, overtorgan dysfunction, or any sign of clinical instability. Clearly, thesepatients should not be considered candidates for early discharge from thehospital or outpatient antibiotic therapy.

Preventive Strategies

Taking steps to minimize or prevent infection in patients with cancerhas always been a part of standard oncologic nursing care. In light ofthe changes occurring in the health-care environment today, preventivestrategies have become even more essential. "We are in an era...wherewe are being pressured to move the care of the patient to the outpatientsetting or the home setting," said Ms. Wujcik. "And, we are beingchallenged 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-carepersonnel on how to avoid practices that may increase colonization; anddecreasing the use of invasive procedures.

A fundamental key to the prevention of infection involves handwashingby anyone who comes into contact with patients. Furthermore, patients themselvesshould be instructed about the need for proper personal hygiene and preventiveoral care. Visitors should be kept to a minimum, but patients should beadvised to avoid anyone with signs of an infection. Other measures thatmay help decrease colonization include removing live plants and flowersand sources of stagnant water from the environment.

In inpatient settings, the ANC can be used as a guide for deciding whento initiate empiric treatment. Although the actual ANC at which treatmentshould be initiated varies among institutions, it is a worthwhile parameterfor health care professionals to lower the rate of colonization of organismsthrough diet and environmental changes and to detect infection early throughmore 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 strategiesmay 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 datafrom randomized clinical trials.

"Environmental modification remains a challenge," said Ms.Wujcik. While attempting to identify the ideal environment for treatingpatients with cancer without increasing their risk of infection, health-careprofessionals have traveled the spectrum from a generally relaxed atmosphereto complete reverse isolation. There appears to be a documented mortalitybenefit for placing at least one select group of patients--ie, those withaplastic anemia who are receiving a bone marrow transplant--in a laminar-airflowenvironment, Ms. Wujcik said. However, there is less clear evidence forthe use of a reverse-isolation or hepafiltered environment. Furthermore,the question of whether the additional cost of such technology is justifiedremains to be answered.

Similarly, a wide spectrum of guidelines for bowel regimens may be employed,depending on the circumstances. On the one hand, complete sterilizationof the gut with oral antibiotics may be recommended for a select groupof patients, eg, patients with aplastic anemia undergoing bone marrow transplantin a laminar-airflow environment. On the other hand, stool softeners maybe 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 prophylaxisshould be initiated, and which group of patients are ideal candidates,"we know that the fluoroquinolones have potent activity against gram-negativeaerobes and they are especially effective

in patients who have a hematologic malignancy and are undergoing bonemarrow transplantation," stated Ms. Wujcik. However, general prophylacticuse of fluoroquinolones for all patients with cancer is controversial.Some studies clearly show that quinolones decrease gram-negative infectionsbut not gram-positive infections in bone marrow transplant recipients.

Ms. Wujcik referred to the use of preventive antibiotics in this settingas a "balancing act"; it is difficult to determine which agentscan be used prophylactically and not cause problematic resistant organisms.

Hematopoietic growth factors may prevent infection by shortening theduration and severity of febrile neutropenic episodes but have not beenshown to change mortality overall. After myelosuppressive chemotherapy,there is a typical drop in the ANC. With the administration of growth factors24 hours after chemotherapy, the period of risk has been decreased in somepatient populations. However, these growth factors are not suitable forall patients undergoing all types of chemotherapy and are particularlyinappropriate for low-risk patients. Furthermore, they are expensive toadminister and are sometimes not covered by medical insurance.

Home Care

"Prevention of infection in the home setting is a whole differentchallenge," said Ms. Wujcik. Documented standards for outpatient homecare should be clarified over the next few years. First and foremost, patientsand families must be taught what signs and symptoms to watch for. Patientsneed to monitor their temperature and be instructed when to call for medicalassistance. Patients also should report such symptoms as cough, burningon urination, sore mouth, and any area that appears to be infected.

Patients also need to be educated about risk factors for infection andsteps they should take to decrease possible colonization. Avoiding peoplewith infectious illnesses and strict handwashing by the patient and allpersons who come into contact with him or her are two important preventivemeasures. Various self-care guides on infection are available.

In conclusion, patients with cancer are at risk for infection for multiplereasons. According to Ms. Wujcik, "strategies to minimize and preventinfection in patients with mild to moderate short-term neutropenia aregenerally successful.... Complete prevention or elimination of infectionhas not been accomplished in some of our high-risk populations, such asthose patients undergoing bone marrow transplantation or intensive chemotherapy."