Commentary by Rachana Jani MD, PGY-1 and Neal Steigbigel MD, Professor of Medicine (Infectious Diseases/Immunology)
Rachana Jani MD: Walking onto an oncology floor, one cannot help but notice the precautionary signs that segregate these patients from the rest of the hospital. “No fresh fruits or flowers.” “Neutropenic isolation, please see nurse before entering.” The idea of neutropenic precautions first emerged in the 1960s when myelosuppressive therapy came to the forefront of cancer treatment. It only made sense that patients with an impaired immune system be nursed in strict isolation. However, these ideals were based on clinical philosophy and continued based on tradition. It is important to consider that if there was a rationale in the past to implement protective isolation, has it now been outdated by the advent of antimicrobial prophylaxis and systemic growth factors?
Typical strategies to prevent infection among neutropenic patients have included a protective environment, dietary constraints, and protective clothing. With the resource burden associated with maintaining protective measures, there are surprisingly few studies systematically monitoring infection rates in neutropenic patients. In the early eighties, investigators studied the effect of laminar airflow and HEPA filtration in decreasing the rates of infection in neutropenic patients [1,2]. Although they were able to show some protective benefit against infection, particularly Aspergillus infections, there was no measurable effect on mortality. Other studies conducted in early 2000 failed to show a difference between patients treated in protective isolation and those who were not with respect to the median time to fever or a significant difference in mortality rate [3]. Most hospitals also institute low microbial or neutropenic diets, however, no recent studies exist that can associate dietary restriction with decreased rates of infection [4,5]. The efficacy of gloves/masks, cover gowns and single patient rooms has also been studied, again showing no mortality benefit [6,7].
One the other hand, optimal hand hygiene has been shown to be the most effective avenue for prevention [8]. Studies looking at proper handwashing versus any combination of protection found no difference in infection rates or mortality in neutropenic patients [9]. It is important to note that although the majority of deaths from leukemia and solid tumors are related to infection secondary to neutropenia, the majority of infections are a result of translocation of microbial flora, largely from the patient’s gastrointestinal tract [10,11]. It has been shown that suppression of the patient’s endogenous flora with prophylactic antibiotics has the best outcome, regardless of whether the patient has received standard ward care or has been treated in a protected environment [12,13]. There has also been a movement towards personal hygiene as an important factor in preventative care as mucositis and other oral lesions have been shown to be a frequent cause of morbidity and mortality among patients [14].
Is this to confidently endorse the termination of neutropenic precautions? The current evidence for neutropenic precautions is scarce at best. Considerable gaps in literature exist regarding protective intervention and consequently, hospitals vary in their practices. Small sample sizes and confounding factors such as varying isolation protocols make it difficult to accurately interpret the present data. It is well-appreciated that maintaining a protective environment is a costly endeavor in a system with limited resources. Neutropenic precautions also strain the patient’s psychosocial well-being, leading to a heightened sense of isolation from loved ones, healthcare workers, and other patients. In an evidence-based world, the care of hospitalized neutropenic patients has been sustained by habit and custom. To some extent, it seems inappropriate to use scant resources for unsubstantiated protocols. As the current literature stands, it does not support neutropenic precautions to the extent that most institutions implement – instead, it supports hand hygiene and prophylactic antibiotics in the care of the neutropenic patient – so scrub up.
Neal Steigbigel MD: In my opinion this is a very well-written piece and is important. The points to be stressed are:
-infections in such severely neutropenic patients, especially with absolute PMN counts below 100/ml and patients with leukemia (less firm risk data in other groups with neutropenia and least risk data in AIDS patients–the latter usually mobilize PMN’s well although baseline neutropenic–GCSF is much overused) are largely due to their own endogenous
flora and therefore there always has been appropriate skepticism regarding the rationale for the typical “neutropenic precautions” which are aimed at preventing transmission of exogenous pathogens. An example of an exception to that principle is “invasive pulmonary aspergilloisis” which has neutropenia as a major risk factor and in which the microbe is
usually acquired by aerosol from its environmental ubiquity. For that infection, perhaps a strict laminar flow of air through a well maintained HEPA filter in a negative pressure room would help (proof not firm) as well as avoiding areas of hospital with recent construction (which has been shown to be involved in some of those patients).
-the use of prophylactic antibiotics to suppress GI flora in afebrile neutropenic patients is controversial because it selects for emergence of resistant bacteria as potential endogenous invaders in neutropenic pateints. However, once patients with leukemia, other cancers and transplant patients have fever and severe neutropenia, the use of bactericidal antibiotics aimed at endogenous Gram negative bacilli, including both enterobacteriaceae and Pseudomonas areuginosa is associated with evidence of a decrease in mortality and morbidity to justify that. Again there is no good evidence for that regimen being useful for AIDS-associated neutropenia and fever that I know of.
-hand washing before and after handling patients remains the most important part of “standard precautions” though no evidence that it is more important for neutropenic patients–although that may seem logical.
References:
Centers for Disease Control and Prevention: Guidelines for preventing opportunistic infections among hematopoeitic stem cell recipients:Recommendations of the CDC, the Infectious Disease Society of America and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep 49:RR-10,2000.
Fenelon LE. Protective isolation: who needs it? J Hosp Inf 1995; 30: 218-222.
3. Mank A, van der Lilie H. Is there still an indication for nursing patients with prolonged neutropenia in protective isolation? An evidence based nursing and medical study of 4 years experience for nursing patients with neutropenia without isolation Eur J Onc Nurs 2003; 7; 17-23.
4. French M, Levy-Milne R, Zibrik D. A survey of the use of low microbial diets in pediatric bone marrow transplant programs. J Am Diet Assoc 2001; 101 (10):1194-1198.
5. Larson et al. Evidence based nursing practice to prevent infection in hospitalized neutropenic patients with cancer. ONS 2004; 31:717-723.
6. Kenny H, Lawson E. The Efficacy of cotton cover gowns in reducing infection in nursing neutropenic patients: an evidence-based study. Int J Nurs Prac 2000; 6: 135-139.
7. Duquette-Peterson L et al. The role of protective clothing in infection prevention in patients undergoing autologous bone marrow transplantation. ONS 1999; 26: 1319-1324.
8. Gould D. Nurses’ hand decontamination practice: results of a local study. Journal of Hospital Infection 1994; 28:15-30.
9. Hayes-Lattin B et al. Isolation in the allogenic transplant environment: how protective is it? BMT 2005; 36:373-381
10. Elting L, Rubenstein E, Rolston K, Bodey G. Outcomes of Bacteremia in Patients with Cancer and Neutropenia: Observations from Two Decades of Epidemiological and Clinical Trials. CID 1997; 25: 247-257.
11. Oren I, Haddad N, Finkelstein R, Rowe JM. Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters. Am J Hem 2000; 4:457-262.
12. Cullen M, Steven N, Billingham L. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 2005; 353:988-998.
13. Leibovici L, Paul M, et al. Antibiotic prophylaxis in Neutropenic Patients. Cancer 2006:107 (8): 1743-1751.
14. Khan SA, Wingard JR. Infection and mucosal injury in cancer treatment. NCI 2001; 29:31-36.
Image courtesy of Wikimedia Commons, Scanning electron micrograph of Pseudomonas aeruginosa bacteria
5 comments on “Neutropenic Precautions Demystified”
As a dietitian, and now a patient with AML having recently received a BMT, I am following a neutropenic diet. I was placed on this diet from day one admission and must adhere to the restrictions for 100 days. After that time, I may be a little more lax and add back lettuce, tomatoes and the forbidden foods. However, I must avoid fast food restaurants, buffets, deli meat/cheese, salad bars for at least a year.
I find the food safety and sanitation points of FDA/CDC to be very good and acceptable. I find some of the particular food restrictions comical. I should avoid cold block cheese because
“it might develop mold.” The same applies to cream cheese, shelf salsa, spaghetti sauce in the jar, etc.
Commonsense tells one if you keep food too long, and see mold growing you should not eat. However, when you buy a small block of cheese or cottag cheese with a date, and eat before the expiration date, I question what harm you are doing.
I think keeping leftovers in the refrigerator too long and then reheating and heating may pose problems. Foods should be frozen or eaten in 2-3 days. I have been instructed to keep in the fridge only 1 day or 7 days in the freezer after frozen.
“For that infection, perhaps a strict laminar flow of air through a well maintained HEPA filter in a negative pressure room would help (proof not firm) as well as avoiding areas of hospital with recent construction (which has been shown to be involved in some of those patients).”
I believe you mean _positive_ pressure room?
What seems to be missing in this article (and probably in the studies), when comparing the cost benefit ratio, is the cost of treating all the minor infections that would occur if the various precautions were not observed. Since a neutropenic patient is nearly incapable of fighting the most minor of infections, without the assorted additional precautions, the hospital could be diverting additional resources to helping patients overcome many minor infections. This also doesn’t factor in the patient’s quality of life, continually being sick with a variety of minor infections adds an additional, unpleasant burden to their treatment and recovery. It may be cliche, but in this case it is likely that an ounce of prevention is worth a pound of cure.
In giving prophylactic antibiotics, does C-Difficule then become a problem?
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