As the incidence of invasive fungal infections has risen over the past 20 years, so has the level of concern among oncology nurses. In an interview with The Oncology Nurse-APN/PA, Brenda Shelton, MS, RN, CCRN, AOCN, clinical nurse specialist, The Sidney Kimmel Comp rehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, discusses who is at risk, how nurses can identify them, and steps nurses can take to help these patients. Why is it necessary for oncology nurses to revisit their knowledge of invasive fungal infections? Brenda Shelton (BS): Over the years, we have perfected a large number of cancer treatment regimens. We now have people surviving first-line regimens and moving on to second- and third-line ones, creating added toxicity. This means, we now see patients undergoing therapy who have more prolonged neutropenia and comorbid health conditions, such as autoimmune diseases for which they receive corticosteroids. They are coming to us with multiple risk factors for infections in general as well as fungal infections. What factors have led to the growing incidence of invasive fungal infections? BS: One factor is the resurgence of transplant as a therapeutic option. We really have perfected this treatment and many more patients receive a transplant. We used to have only those patients with optimal organ function receiving an allogeneic transplant. Now we have many variations of allogeneic transplants, including mini-transplants and haplotype transplants and mixed, unrelated donor transplants. Additionally, there are new monoclonal antibodies that induce immune suppression and more patients are on high-dose or extended courses of corticosteroids. Whenever granulocytes or lymphocytes are prolonged excessively, you’re going to find problems with invasive fungal infections. We also have seen an increase in different varieties of fungal diseases. We’ve had a shift from Candida infections that are usually relatively easy to treat to Aspergilli infections that are more difficult to manage. What are the signs and symptoms of invasive fungal infections? How do they differ from those of viral and bacterial infections? BS: It is sometimes very hard to tell bacterial and fungal infections from each other. Look at the risk profile. If a patient is at risk for both bacterial and fungal infections, nurses tend to think bacterial first, and that makes sense early during the immune compromise. Many times, a patient is treated for a bacterial infection, and if he or she does not rapidly respond, a fungal infection is suspected. It is so difficult to sort out, and I recently read that up to 67% of patients are only discovered on autopsy to have had a fungal infection as opposed to the bacterial one being treated. A few very subtle things can help identify a patient with a fungal infection. Mucositis is high on my list of identifiers for probable fungal infection. I also always look at a patient’s skin to see if there are any clues that perhaps signal an untreated fungal infection that has become systemic. In addition, I look for high spikes in fevers or continuous fevers, but it’s not like you can use fevers exclusively because patients on steroids may not have a fever. You should look for thrush, look for fungal infections of the skin, or Candida in the urine, all clues of a possible systemic fungal infection. Lastly, I just recently saw an individual with a systemic fungal infection that had small, hard, and red nodules all over their body. Do these infections occur in hospitalized patients or outpatients or both? BS: Both. Many patients on immunesuppressing therapy for leukemia, lymphoma, or myelodysplastic syndrome (MDS) are outpatients. Transplant patients are inpatients at least initially, but become outpatients if not actively infected. These patients need to come to the clinic frequently and be evaluated thoroughly. We are seeing most of these infected patients start antifungal therapy in the hospital but, because it may require many weeks of treatment, they are at home for part of that time. If they get resistant fungus or if they get a second fungus, those would only be observed at a home visit or when they come into the outpatient area. Caregiver and patient education, therefore, is very important. What actions can high-risk patients take? BS: We advise patients to use standard anti-infection precautions. Fungi are opportunistic and not usually considered contagious. For example, Aspergilli are soil organisms and, when you stir up the soil, whether gardening or traveling through a construction area, you’re going to breathe soil contaminants and increase the risk of Aspergillus sinusitis or an Aspergillis lung infection. We instruct patients to wear high-particulate filtration masks on their way to the hospital because we’re constructing new buildings, and the ground is disturbed with dust and dirt. We tell patients to put on their air conditioners, put up their car windows, and wear the masks from their car into the hospital. For inpatients, especially high-risk transplant patients, we advise them to stay in the HEPA filtration area. The best defense against an oral infection with fungus is really good mouth care. This is frequent, high-quality mouth care. For skin infections, we advise keeping the skin dry and clean, especially recleaning those areas that are in skin folds or become moist, because that’s where fungus likes to grow. Any fungal infection can become systemic in the immune-compromised patient. What agents are available for prophylaxis? BS: The azole agents, in general, are a class of medication that has been used for a number of years. Resistance is developing to some of the early-generation azole agents. So in fact, at this point in time we have posaconazole, voriconazole, itraconozole, and fluconazole. The specifics about how to use these agents are available in their package inserts. That information also is available in the National Comprehensive Cancer Network guidelines. Plus, there is some information sharing about the indications in the Oncology Nursing Society preventing infection guidelines. It is important to know which infection you are worried about the patient having: is it Aspergilli or Candida, because your choice of agents might vary. In addition, you have to look at the specifics of the patient: their ability to take the drug without drug–food or drug–drug interactions. Each patient may require something a little bit different based on these variables. Are nurses at risk, and do they have to take any precautions when treating patients with invasive fungal infections? BS: Nurses are not usually at risk, because, for the most part, they have healthy immune systems. It’s really during times of high life stress that nurses are most compromised. And all of us are always at some risk. We’re all colonized with Candida, but that isn’t a problem for most of us. However, if a nurse has an autoimmune disease, has diabetes, or is on corticosteroids, he or she needs to be careful.
By Brenda Shelton, MS, RN, CCRN, AOCN The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland
MK is a 65-year-old man diagnosed 9 months ago with refractory anemia with excess blasts (RAEB type of myelodysplastic syndrome [MDS]). He has required intermittent biweekly red blood cell and platelet transfusions. Two months ago, he developed oral thrush that was treated with nystatin swish and swallow. The infection cleared over a 2-week period, and he had no further complaints until the past 3 weeks. He had described progressive fatigue and some breathlessness, but displayed normal vital signs and resting oxygen saturation. His lab results showed lower than usual anemia and thrombocytopenia requiring more frequent transfusions. Today MK presented for an unscheduled nurse visit with a new fever and cough.
His assessment showed use of accessory muscles for breathing with exertion, diminished bibasilar breath sounds with crackles in the right lung, and new petechiae and red nodules on the lower extremities. Blood was drawn for hematology, chemistry with hepatic profile, and bacterial/mycology/viral cultures. A second set of cultures from the Hickman catheter was drawn. Suspected Clinical Complications and Immediate Interventions Given MK’s diagnosis of MDS with blasts, he had been experiencing dysfunctional white blood cells (WBCs) for the past 9 months. His oral thrush provided evidence that his leukopenia with WBC dysfunction recently had become more symptomatic. In a patient with prolonged neutropenia, infection with opportunistic micro b es, fungal organisms, or viral organisms is more common than experienced by other patients. Although the initial presentation clearly showed infection, this patient also should be considered high risk for all common and unusual infectious organisms. In addition, because patients with in- dwelling venous catheters are at high risk for bloodstream infections, it is reasonable to draw cultures from the intravenous line as well as peripherally. A shorter time to positivity of the line-drawn blood cultures is one clue that the infection may involve the catheter. Based on the presenting symptoms, it was highly likely that MK was experiencing a respiratory infection. It was also worrisome that MK was showing more depressed blood counts with peteichiae. This could mean the systemic infection and inflammatory process are further depleting his limited blood cells. In addition, it could indicate a more serious complication of infection: disseminated intravascular coagulation. Further hematologic testing with fibrinogen level, prothrombin time, fibrin degradation products, and D-dimer were obtained to detect this complication. The red nodular lesions were particularly concerning given his recent history of a Candida infection. Septic emboli from systemic candidiasis may present as red, nodular skin lesions. MK needed immediate antimicrobials, such as antipseudomonal penicillins, extended-spectrum cephalosporins, or carbapenems, to cover common bacterial pathogens. Because of the risk of Staphylococcus aureus related to the indwelling venous catheter, vancomycin also was recommended while awaiting results of the blood cultures. Given this patient’s chronic immune suppression, respiratory symptoms, recent oral fungal infection, and skin lesions, most clinicians also would prescribe an antifungal agent that could treat either aspergillus or candidiasis. MK was placed on oxygen 4L by nasal cannula. A chest x-ray was ordered and vital signs taken every 30 minutes, including oxygen saturation. Intravenous fluids 0.9% normal saline were started through the patient’s Hickman catheter at 100 mL/hr. According to the febrile neutropenia protocol, MK was started on imipenem every 6 hours and admission planned. An infectious disease consult also was requested. MK was admitted and his temperature spiked to 39.0°C with chills and hypotension (88/50 mm Hg) later that evening. Three liters of fluid were given with resolution of the blood pressure (100/60 mm Hg), but his oxygen requirements increased to 50% by face mask to maintain an oxygen saturation at 92%. All cultures were negative to this point, but vancomycin was added to the antibiotic regimen to cover a potential line infection. Significant lab values were:
In addition, chest x-ray showed diffuse lower lung infiltrates, and a follow-up computed tomography (CT) scan was ordered but had not yet been completed. The infectious disease consultant saw the patient and requested the CT scan be performed immediately, as well as drawing of b-D-glucan and galactomannan levels and the addition of antifungal coverage with caspofungin. Rationale for Recommendations The additional recommendations were made because of concern that an invasive fungal infection was the etiology of MK’s symptoms of sepsis. The CT scan is a more sensitive diagnostic test for aspergillus than a chest x-ray, and the presence of lesions suspicious for aspergillus may alter the choice of antifungal agent. The b-D-glucan serum level is a nonspecific blood test that may be elevated in patients with invasive fungal infection. The galactomannan assay is also a potential marker of fungal infection, but is specific for aspergillus. The prescribers chose an antifungal agent with known efficacy against both fungal organisms, a tolerable adverse profile, and availability in intravenous form, so as not to interfere with immediate treatment. Could This Infection Have Been Prevented? MK has a disease known to cause significant immunosuppression, placing him at high risk for infections. There are several subtypes of MDS, and not all carry the same concerns with WBC dysfunction. It is essential for clinicians to recognize these at-risk patients and consider early oral antifungal prophylaxis with an azole. It also could have been presumed that the oral fungal infection, although it appeared to resolve with topical therapy, required systemic antifungal therapy as a result of this patient’s severity of immunosuppression. Oral prophylaxis for fungal infection may include fluconazole, itraconazole, voriconazole, or posaconazole. Once the patient had symptoms of oral thrush, the agent could have been changed to andulafungin, caspofungin, or micafungin; or the patient could have changed to a therapeutic dose of voriconazole or posaconazole. Given the severity of symptoms and length of immunosuppression, if there was concern for infection with other more unusual fungal organisms, it would have been reasonable to prescribe amphotericin or one of its liposomal derivatives.
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