ABSTRACT: For decades, the concept of a neutropenic diet has implied a strict limitation of foods allowed for consumption, as a presumptive means of reducing the risk of infection in cancer patients. The rationale was to limit the introduction of potentially harmful bacteria into the gastrointestinal tract by the restriction of certain foods that might harbor those organisms. However, this concept has not been substantiated with direct proof, and no universal definition of the neutropenic diet exists. Exactly which foods are restricted varies greatly by institution, but most notable is the restriction of fresh fruits and vegetables. Research evaluating potential benefits of a neutropenic diet is very limited, but the diet is still prescribed in many institutions with the hope that it will prevent foodborne infection and/or bacteremia in neutropenic patients. Review of the pathophysiology of foodborne illness and pertinent studies about the neutropenic diet lead to the conclusion that there is no clear benefit from the longstanding dietary restrictions that may be imposed during neutropenia. Instead, we propose adoption of standard safe food handling methods to allow for a more liberalized diet in the neutropenic patient.
Chemotherapy-associated neutropenia is a well-known risk factor for increased vulnerability of cancer patients to infections. Serious neutropenia-related infections are seen particularly in those with prolonged neutropenic periods associated with treatment of hematologic malignancies or with stem cell transplantation. Bloodstream infections usually occur in about 15% to 25% of patients, most often when the absolute neutrophil count (ANC) is less than 500 neutrophils/μL. Over the last 50 years, efforts to prevent serious bacterial infections in this population have largely included protective isolation measures, prophylactic antibiotics, and dietary restrictions. Despite a lack of supportive data, the neutropenic diet is still utilized in some centers. Re-evaluation of the available data relating to this diet—which is also referred to as the “sterile diet,” the “low-bacteria diet,” or the “low-microbial diet”—is provided here, with the goal of supplanting it with a more current guideline of safe food handling for all cancer patients.
Pathophysiology of Infection in Neutropenic Patients
Gram-positive bloodstream infections (with Staphylococcus species) predominate among neutropenic patients and are primarily derived from skin colonization. In contrast, infections with gram-negative bacilli such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as Candida species (yeasts), are less frequent but more lethal; these organisms typically enter the bloodstream via translocation across the gastrointestinal tract. Starvation and protein malnutrition will promote bacterial translocation in animal models. Disruption of the gut mucosal barrier, as a consequence of cytotoxic chemotherapy–induced mucositis, is also a significant contributing factor. In the 1970s, nonabsorbable prophylactic antibiotics were evaluated for their ability to eradicate normal enteric flora and aerobic gram-negative bacteria, and thereby reduce the gut bacterial burden available for translocation. Limited success was achieved, but the drugs proved to be largely intolerable for patients. During the same era, several studies revealed that enteric flora, including E coli, P aeruginosa, and K pneumoniae, could be cultivated from the surfaces of a variety of foods, usually fruits, cold meats, lettuce, and other fresh vegetables.[5-7] This raised concerns about the possible exogenous acquisition of pathogenic bacteria by the oral route, leading to the “neutropenic diet” concept of restricting specific foods. Typically, in a healthy person, consumed bacteria will pass through the gastrointestinal tract without adhering to the mucosal surface, will be destroyed by stomach acid, or will be competed out of existence by normal endogenous flora. In the cancer patient, each of these mechanisms may be impaired: drugs to reduce stomach acidity may impair bacterial killing in the stomach, gastrointestinal mucositis promotes translocation of bacteria, and antibiotic suppression of endogenous flora prevents bacterial competition and allows overgrowth of potentially pathogenic bacteria.
The essential question is whether or not food ingested by a neutropenic patient is a source of pathogenic bacteria that ultimately cause bloodstream or other serious infections. It is essential to understand the types of bacteria, both pathogenic and nonpathogenic, that are present in or on certain foods. Enterobacteriaceae (eg, Klebsiella species, E coli) are quite commonly carried on fresh fruits and vegetables, but since these organisms are essentially “normal flora” in the human colon, they are considered nonpathogens in healthy patients. A recent study from Finland found that Enterobacteriaceae cultured from the surfaces of vegetables had significantly different antibiotic susceptibility profiles from Enterobacteriaceae cultured in stool samples from humans who consumed those vegetables. The conclusion from this observation was that the antibiotic-resistant bacteria isolated from vegetables probably do not play a significant role in colonizing the human gut. In cancer patients, no studies exist that demonstrate a causal role for food-derived enteric bacteria (such as Enterobacteriaceae or Pseudomonas) in subsequent serious infections that occur during neutropenia.[10-12]
Food becomes a real danger to immunosuppressed individuals when it serves as a vehicle for pathogenic bacteria that typically cause illness in humans. Common foodborne pathogens include Campylobacter jejuni, Salmonella, E coli, and Clostridium
perfringens (Table 1). Apart from E coli, these infections are rarely identified in neutropenic patients, but when they do occur they cause high degrees of morbidity and mortality. The primary etiology of foodborne illness is the unsafe handling of foods. In this regard, we stress that safe food-handling methods—rather than specific avoidance of raw fruit and vegetables—are of greatest importance for preventing infections in all patients, including those who are neutropenic. In contrast, the neutropenic diet (as it is understood in most centers) is not known to be definitively protective against foodborne pathogens. To understand how support for the neutropenic diet evolved, we will review the historical and published study information about how the neutropenic diet evolved as a part of cancer care.
Environmental Measures to Prevent Infection: Historical View
In the 1960s, most cancer treatments were administered in an inpatient setting, and patients remained hospitalized for prolonged periods. During this period, the low microbial or neutropenic diet emerged as part of a “total protective environment” approach to managing leukemia patients with prolonged neutropenia. This approach involved myriad environmental cleansing, sterilization, and isolation measures that were implemented when patients became neutropenic, in an effort to reduce exposure to both endogenous and exogenous bacteria.
The neutropenic diet, in which fresh fruits and vegetables were generally forbidden, was an integral part of the total protective environment. In addition, antimicrobial or protective procedures included the use of isolated laminar flow rooms; shaving of the genital area; thorough cleaning of toenails and fingernails; bathing in isopropyl alcohol(Drug information on alcohol) or hexachlorophene; sterilization of clothes and linens; sterilization of food with ethylene oxide; cleansing of the gastrointestinal tract with castor oil and soapsuds enemas; sterilization of the gastrointestinal tract with antibiotics; and sterilization of all items taken into the isolation unit, including newspapers and procedure instruments. Because they are labor-intensive, expensive, and of no proven benefit, most components of the total protective environment are no longer employed. In fact, a number of cancer treatments (eg, autologous stem cell transplants and consolidation therapies for acute leukemia) occur in the outpatient setting, and patients go through periods of neutropenia primarily as outpatients, with few restrictions on diet and activity.[11,16,17] Although total-protective-environment techniques have been mostly abandoned in the 21st century care of cancer patients, a notable exception has been the continued use of the neutropenic diet. This diet—in various forms—has remained a part of patient care based on the theoretical assumption that avoidance of foods that may carry gram-negative-rod bacteria may reduce bloodstream infections. In fact, this has never been proven.
Defining the Neutropenic Diet
No standard definition of the neutropenic diet exists. Indeed, it is unclear what fundamental features constitute a neutropenic diet: What foods should be restricted? How should foods be prepared to render them sterile or at least microbially reduced? When should limitations be instituted and discontinued? Surveys investigating institutional dietary prescriptions for neutropenic patients have revealed a wide range of definitions and practices.[17-19] Great variability exists in terms of specific foods restricted, timing of initiating restrictions, and food preparation methods such as washing and cooking techniques. Commonly prohibited are raw fresh fruits and vegetables, but some centers also avoid fresh-squeezed juices, dried fruits, yogurt and aged cheeses, raw herbs and spices, raw honey, deli meats, nuts, undercooked meats, undercooked seafood, and undercooked eggs for patients.
Food preparation methods to ensure low microbial content, including sterilization and autoclaving, are occasionally employed. These can affect the appearance, taste, and texture of food, thereby decreasing patients’ desire to eat and maintain their nutritional status at a time when it is critically important to maintain caloric intake.
Timing of diet initiation varies among institutions. Some hospitals use the absolute neutrophil count to determine when the diet is initiated, while others may initiate the diet upon hospital admission.[18,19]