Lack of Efficacy of the Neutropenic Diet in Decreasing Infections among Cancer Patients: A Systematic Review.

The objective of this systematic review is to evaluate the existing evidence supporting the effectiveness of the neutropenic diet in decreasing infection and mortality among cancer patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from database inception until March 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for this review. Individual studies were evaluated using the Oxford Center for Evidence-Based Medicine guidelines. A total of 473 articles were identified and 11 articles were selected after assessing eligibility. Our review showed that the neutropenic diet does not decrease infection rates or mortality among cancer patients. Currently, there is no uniform definition for the neutropenic diet across different institutions. For example, some institutions follow general food safety practices while others avoid foods that increase exposure to microbes and bacteria, and some follow both. Given these differences in practice regarding what constitutes a neutropenic diet, it is advisable that safe food handling and preparation practices recommended by the Food and Drug Administration be uniformly followed for neutropenic patients.

Does a neutropenic diet reduce adverse outcomes in patients undergoing chemotherapy?

OBJECTIVE: This study aimed to compare clinical outcomes of chemotherapy patients who received either a neutropenic diet (ND) or liberalised diet (LD) and to investigate associations between ND and infectious outcomes. METHODS: A retrospective case note audit of patients admitted to Flinders Medical Centre from 2013 to 2017 was conducted. Patients were eligible if they were aged 18 years and above, received chemotherapy and were neutropenic during admission. Demographic and clinical data were collected from medical records. Primary outcomes were occurrence of infections and fever. Secondary outcomes include hospital length of stay and infection-related mortality. RESULTS: Seventy-nine patients received ND while 75 patients received LD. The ND group had more patients with acute myeloid leukaemia (p < .001) and receiving high-toxicity chemotherapy (p = .005). Incidence of febrile neutropenia (p = .016), bacteraemia (p = .044) and number of febrile days (p = .033) was higher in the ND group. ND was not independently associated with occurrence of febrile neutropenia or infections. Subsample analysis of 20 pairs of patients matched on age, sex and cancer diagnosis found no significant differences in clinical outcomes between groups. CONCLUSION: ND was not associated with the prevention of adverse outcomes in chemotherapy patients.

Dissemination of Information on Neutropenic Diet by Top US Cancer Centers: In-line with the Evidence?

Aim: The neutropenic diet is commonly prescribed to cancer patients with neutropenia with the goal of reducing infections. However, multiple randomized trials have proved no benefit with neutropenic diets compared to less restricted diets with regards to reducing infectious risk. We aimed to ascertain if top cancer centers recommended for or against the use of neutropenic diets on their official websites. Methods: We reviewed the websites of the top 20 hospitals in the 2017 US News Best Hospitals for Cancer©, and ascertained recommendations for neutropenic diet (for, against, equivocal, or not addressed). Results: Seven websites (35%) made recommendations for, four (20%) against, and nine (45%) did not address the neutropenic diet. Only five (25%) backed any of their recommendations with evidence (four against, one for), including two (10%) links to abstracts (both against), whereas seven mentioned the FDA safe food handling guidelines (non-exclusive). Type of recommendation made (for or against) did not depend on US News rank (top vs bottom 10; p = 1.00.). Conclusion: The neutropenic diet continues to be recommended on many (35%) websites of top US cancer centers, despite strong evidence against its use. The website content of major US cancer centers should be updated to better guide patients regarding neutropenic diets.

A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients.

BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy. PROCEDURE: Pediatric patients receiving cancer treatment with myelosuppressive chemotherapy were eligible. Neutropenic infection was the primary outcome and defined as (i) fever with neutropenia or (ii) hospital admission and treatment for clinical infection and neutropenia. The rate of neutropenic infection was compared with Student's t-test for independent samples. Documented infections were identified by comprehensive chart review and compared between groups using a χ2 test. RESULTS: One hundred fifty patients were randomly assigned to FSGs (n = 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic leukemia (32%) and sarcoma (32%). There was no significant difference between the groups in the percentage of patients who developed neutropenic infection: FSGs 33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported that following the diet required more effort than those on FSGs alone. CONCLUSION: The ND offers no benefit over FSGs in the prevention of infection in pediatric oncology patients undergoing myelosuppressive chemotherapy and adherence requires more effort for patients and families. Institutions caring for children with cancer should consider replacing ND guidelines with FSGs.

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

BACKGROUND: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review. OBJECTIVES: The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000 to 2015). In May 2015, we scanned the National Institutes of Health Register via clinicaltrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) Register (www.controlled-trials.com). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing use of an LBD versus a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: In the original version of this review, we identified three RCTs that assessed different intervention and control diets in 192 participants (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. For the update, we identified no eligible new studies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices, colony-stimulating factors) and outcome definitions also differed between studies. In all included studies, it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the participants diagnosed with an infection. Two studies included adults and one study included children. In all studies, only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies, no statistically significant differences in infection rate were identified between intervention and control diets; another study showed no significant differences between treatment groups in the number of chemotherapy cycles with an infection. None of the studies mentioned infection-related mortality, but in one study, no significant difference in overall survival was observed between treatment groups. Time from onset of neutropenia to fever, duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes, no statistically significant differences between treatment arms were identified. AUTHORS' CONCLUSIONS: At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.

Investigating the use of the neutropenic diet: a survey of U.K. dietitians.

BACKGROUND: Patients with chemotherapy-induced neutropenia are at increased risk of infection. Historically, dietary restrictions commonly referred to as 'clean', 'low bacteria', 'low-microbial' or 'neutropenic' diets have been prescribed to reduce the risk of foodborne infection. Although research does not support their effectiveness, they continue to be used in clinical practice. The present study aimed to investigate the use of dietary restrictions in patients with cancer in the UK by surveying registered dietitians (RDs). METHODS: An online questionnaire was distributed to 573 RDs via local and specialist interest groups of the British Dietetic Association. RESULTS: One hundred and ten questionnaires were returned. Of these, 67.8% of RDs prescribed dietary restrictions to patients, with 'neutropenic diet' being the most commonly used term. Specialist oncology or haematology RDs were more likely to use the diet than nonspecialist RDs (P < 0.005). The variety of foods restricted varied greatly and was often contradicting. Unpasteurised dairy products and raw or lightly cooked meat or fish were most commonly restricted. Less than half (43.6%) of RDs had a policy in place for the use of neutropenic diets, with specialist oncology and haematology RDs more likely to report this (P < 0.005). CONCLUSIONS: Neutropenic dietary advice provided by dietitians in the UK varies greatly. Further high-quality research is required to create an evidence base from which national clinical guidelines can be formed.

Significant inconsistency among pediatric oncologists in the use of the neutropenic diet.

BACKGROUND: The role of the neutropenic diet in the development of infections in oncology and stem cell transplant (SCT) patients is controversial. There is no data on the use of the neutropenic diet among pediatric oncologists. METHODS: A self-administered electronic survey was sent to 1,639 pediatric oncologists at 198 institutions who are members of Children's Oncology Group. A pediatric dietitian and pediatric oncologists developed, pretested, and modified the survey for item clarification. RESULTS: Five hundred fifty-seven physicians (34%) responded representing 174 (87%) of the 198 member institutions. More than half of respondents (57%) report implementing the neutropenic diet at their facility. In a multivariate analysis, being a stem cell transplant (SCT) center was the only significant factor associated with implementing a neutropenic diet (OR: 6.06, 95% CI, 2.88-12.738, P < 0.001) after controlling for years in practice, gender, center size, and academic versus private practice. Among physicians who implemented a neutropenic diet, absolute neutrophil count was the trigger for initiating the diet in oncology patients (72%) while admission and start of preparative regimen was used for SCT patients (84%). The majority of respondents (82%) stop the neutropenic diet when oncology patients are no longer neutropenic while the practice varied significantly with SCT patients. Providers at the same institution were not consistent with implementation of the diet, patient populations placed on the neutropenic diet and parameters for initiation, discontinuation of the diet and specific food restrictions. CONCLUSION: The implementation of the neutropenic diet by pediatric oncologists remains quite variable even among those at the same institution.

Use of neutropenic diet in the nutritional care of pediatric cancer patients with neutropenia: a scoping review.

OBJECTIVE: to carry out a scoping review with the purpose of mapping the scientific evidence on the use of the neutropenic diet in neutropenic pediatric cancer patients. SOURCE OF DATA: The scoping review protocol was prepared in accordance with the PRISMA-ScR and the checklist before the literature search was performed. Articles on nutritional management in adults or on the treatment of other diseases, and articles that were not in Portuguese or English and published before the year 2000, were excluded. Data were extracted based on the Cochrane Consumer and Communication Review Group form. SUMMARY OF THE FINDINGS: Three hundred and forty scientific articles were identified, with the final sample of this review consisting of nine studies. Although the neutropenic diet has been part of the nutritional management of pediatric cancer patients for more than 20 years, there is still great variation in the criteria for indicating use and starting and discontinuing it, as well as in the nutritional composition of the diet. Furthermore, there is no consensus on the impact of using a neutropenic diet on different clinical and nutritional outcomes. CONCLUSION: In the absence of guidelines that standardize the use of a neutropenic diet in pediatric patients with neutropenia, there are heterogeneous approaches reported in the literature, even within the same institution. The available literature presents an absence of evidence on the use, viability, and effectiveness of the neutropenic diet in oncological children with neutropenia. More studies are needed to identify the real impact of the neutropenic diet on clinical and nutritional outcomes.

Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation.

The use of a neutropenic diet (ND) after hematopoietic stem cell transplantation (HSCT) was instituted more than 30 years ago as a means of preventing infection from organisms colonizing the gastrointestinal tract. Evidence supporting this practice is lacking, however, and the actual efficacy of the ND remains unknown. Institutional policy at Northwestern Memorial Hospital discontinued the use of ND in 2006. We conducted a retrospective study of 726 consecutive HSCT recipients, 363 who received an ND and 363 who received a general hospital diet, to determine the incidence of microbiologically confirmed infections during and after transplantation. Our findings indicate a higher rate of infections in the HSCT recipients who received an ND.

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

BACKGROUND: Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infections, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent the occurrence of infections and (infection-related) mortality in cancer patients receiving chemotherapy causing episodes of neutropenia, but much remains unclear. OBJECTIVES: The primary objective was to determine the efficacy of an LBD versus a control diet in preventing the occurrence of infection and to decrease (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. Secondary objectives were to assess the time to first febrile episode, the need for empirical antibiotic therapy, diet acceptability and quality of life. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 3 2011), Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library, issue 3 2011), PubMed (from 1946 to 20 October 2011), EMBASE (from 1980 to 20 October 2011) and CINAHL (from 1981 to 20 October 2011). In addition, we searched several conference proceedings (from 2000 to either 2010 or 2011) and reference lists of relevant articles. To identify ongoing trials we contacted researchers working on this topic and we scanned the National Institute of Health Register and the ISRCTN Register (www.controlled-trials.com; searched May 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the use of an LBD with a control diet with regard to infection rate, (infection-related) mortality, time to first febrile episode, need for empirical antibiotic therapy, diet acceptability, and quality of life in adult and paediatric cancer patients receiving chemotherapy causing episodes of neutropenia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, 'Risk of bias' assessment and data extraction. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified three RCTs assessing different intervention and control diets in 192 patients (97 randomised to intervention diet; 95 to control diet) with different types of malignancies. Co-interventions (e.g. protective environment, antimicrobial prophylaxis, central venous catheter care, oral care, hygiene practices and colony-stimulating factors) and outcome definitions also differed between studies. In all included studies it was standard policy to give empirical antibiotics (and sometimes also antimycotics) to (some of) the patients diagnosed with an infection. Two studies included adults and one study included children. In all studies only a scant description of treatment regimens was provided. All studies had methodological limitations. Pooling of results of included studies was not possible. In two individual studies no statistically significant difference in infection rate between the intervention and control diet was identified; another study showed no significant difference in the number of chemotherapy cycles with an infection between the treatment groups. None of the studies mentioned infection-related mortality, but in one study no significant difference in overall survival between the treatment groups was observed. Time from onset of neutropenia to fever, the duration of empirical antibiotics and antimycotics, diet acceptability (i.e. following the diet easily and following the diet throughout all chemotherapy cycles) and quality of life were all evaluated by only one study; for all outcomes no statistically significant differences between the treatment arms was observed. AUTHORS' CONCLUSIONS: At the moment there is no evidence from individual RCTs in children and adults with different malignancies that underscores the use of an LBD for the prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions, and intervention and control diets. Since pooling of results was not possible and all studies had serious methodological limitations, no definitive conclusions can be made. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.

[Diet of neutropenic patients in pediatric oncology service; the experience of the university hospital of Strasbourg (HUS)]. / L'alimentation des patients neutropéniques d'un service d'onco-hématologie pédiatrique; l'expérience des hôpitaux universitaires de Strasbourg (HUS).

OBJECTIVE: This article clarifies the choices made by the HUS concerning the ways of preparing food reserved to neutropenic children hospitalized in pediatric oncology service. We will describe the results of microbiological analysis of food realized from 2002 to 2007. METHODS: A specific team prepares this food which is canned and treated by "appertisation" (autoclaving). Each dish portion produced is provided to the service only if the microbiological results are conform, that is to say free of organisms. RESULTS: Three thousand and seventy-eight dishes were analysed: 82.9% of the analysed packs were conform. The contamination ratio decreased significantly (P<0.001) from 2002 to 2007. The organisms which cause the majority of dishes contamination are Bacillus (44.7%) and environmental mould exhibiting sterile mycelium (8.7%). The food which is the most frequently "nonconform" is the dry food with a contamination rate of 37.9%. The identified concentrations remain mainly lower than 50 colony-forming units per millilitre (CFU/mL): 66.2% for the bacteria and 97.2% for the fungi. CONCLUSION: Considering the lack of consensus on the acceptable microbiological thresholds and on the food protection level, the HUS make it a rule to have a maximal precautionary principle. Currently, this principle appears to us to be a safety option required for the patients hospitalized in pediatric oncology service.

The benefit of the neutropenic diet: fact or fiction?

There really should not be a debate about the use of neutropenic diet for cancer patients. Its usefulness has never been scientifically proven. However, neutropenic diets remain in place in many institutions even though their usefulness is controversial. Neutropenic diets were once thought to be important in protecting patients from having to succumb to infection from neutropenia while undergoing chemotherapy. Although food may contain harmful organisms and research has shown that bacterial translocation is possible, recent studies have been unable to obtain significant differences between placebo and intervention groups. The dietetic challenges neutropenic patients struggle with include decreased quality of life, malnutrition, gastrointestinal side effects, food aversion, and impaired cell-mediated immunity from vitamin deficiency. Unanswered questions in regard to the neutropenic diet include the following: (a) which food should be included; (b) which food preparation techniques improve patient compliance; (c) which patient populations benefit most; and (d) when should such a diet be initiated. Without scientific evidence, the best advice for neutropenic patients is to follow food safety guidelines as indicated by government entities.

Bacterial translocation is reduced by a specific nutritional combination in mice with chemotherapy-induced neutropenia.

Immune function is compromised in many cancer patients, leading to an increased risk of (infectious) complications. Chemotherapy-induced neutropenia is a common cause of treatment-induced immune suppression. In the present study, the effect of a specific nutritional combination (SNC) on bacterial translocation was studied in a model of chemotherapy-induced neutropenia in C3H/HeN mice colonized with Pseudomonas aeruginosa PAO-1. Dietary intervention started after stable colonization with P. aeruginosa to compare the SNC containing high protein, l-leucine, fish oil, and specific oligosaccharides to an isoenergetic control diet. After 3 wk, the mice were treated with cyclophosphamide to induce neutropenia. This rendered the mice susceptible to Pseudomonas translocation, which was quantified 5 d later. Intervention with the SNC resulted in a reduced incidence and intensity of bacterial translocation to the liver (P < 0.05) and a similar trend in the lungs (P ≤ 0.057). In addition, the SNC reduced the fecal pH (P < 0.05) and decreased P. aeruginosa counts in fecal samples (P < 0.05). Moreover, plasma concentrations of proinflammatory cytokines were correlated with the reduced bacterial translocation to the liver (ρ > 0.78; P < 0.001). In conclusion, dietary intervention with the SNC significantly reduced the incidence and severity of P. aeruginosa translocation in a mouse model of chemotherapy-induced immune suppression. Several mechanisms might have played a role, including the modulation of the intestinal microbiota, an improved gut barrier function, immune function, and a reduced inflammatory state. These results suggest an opportunity to develop new applications in cancer patients, with the aim to reduce infectious and other complications.

Current practice in nutrition after allogeneic hematopoietic stem cell transplantation - Results from a survey among hematopoietic stem cell transplant centers.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is frequently associated with impaired oral intake and malnutrition, which potentially increases morbidity and mortality. Therefore, nutrition is one of the major challenges in the post-transplant period. METHODS: To document the current clinical approach in nutritional treatment, we designed a questionnaire concerning the current practice in nutrition after alloHSCT and distributed it to German speaking centers performing alloHSCT in Germany, Austria and Switzerland between November 2018 and March 2020. Twenty-eight (39%) of 72 contacted centers completed the survey, 23 from Germany, two from Austria and three from Switzerland, representing 50% of alloHSCT activity within the participating countries in 2018. RESULTS: All centers reported having nutritional guidelines for patients undergoing alloHSCT, whereby 86% (n = 24) provided a low-microbial diet during the neutropenic phase. The criteria to start parenteral nutrition (PN) directly after alloHSCT seemed to be consistent, 75% (n = 21) of the corresponding centers started PN if the oral nutritional intake or the bodyweight dropped below a certain limit. In the setting of intestinal graft-versus-host disease (GvHD) the current practice appeared to be more heterogenous. About 64% (n = 18) of the centers followed a special diet, added food stepwise modulated by GvHD symptoms, while only four centers regularly stopped oral intake completely (intestinal GvHD grade >1). Half of the centers (54%, n = 15) applied a lactose-free diet, followed by 43% (n = 12) which provided fat- and 18% (n = 5) gluten-free food in patients with intestinal GvHD. Supplementation of micronutrients in acute intestinal GvHD patients was performed by 54% (n = 15) of the centers, whereas vitamin D (89%, n = 25) and vitamin B12 (68%, n = 19) was added regularly independently of the presence of GvHD. Only 5 (18%) participating centers ever observed a food-associated infection during hospitalization, whereas food-associated infections were reported to occur more often in the outpatient setting (64%, n = 18). CONCLUSION: The survey documented a general consensus about the need for nutritional guidelines for patients undergoing alloHSCT. However, the nutritional treatment in clinical practice (i.e. lactose-, gluten- or fat-free in intestinal GvHD) as well as the use of food supplements was very heterogeneous. In line with current general recommendations the centers seemed to focus on safe food handling practice rather than providing a strict neutropenic diet. More high-quality data are required to provide evidence-based nutrition to patients during and after alloHSCT.

Neutropenic diets to prevent cancer infections: updated systematic review and meta-analysis.

INTRODUCTION: Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review. MATERIALS AND METHODS: We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection. RESULTS: We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50). CONCLUSION: There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.

Effect of Neutropenic Diet on Infection Rates in Cancer Patients With Neutropenia: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Neutropenic diets are commonly prescribed to cancer patients with neutropenia with the intention of reducing rates of infection. These diets are restrictive and are associated with lower patient satisfaction and possibly malnutrition. Further, it is unclear if these restrictive diets are effective in reducing infection. We performed a meta-analysis on the rates of infection reported in trials comparing the neutropenic diet to unrestricted diets in cancer patients with neutropenia. METHODS AND MATERIALS: A comprehensive database search for all published randomized controlled trials comparing infection rates in cancer patients receiving a neutropenic diet versus an unrestricted diet was performed for all publications in English language from database's inception until September 12, 2017. The search strategy, study selection, and subsequent analysis adhered to PRISMA guidelines. Random effects modeling was used to obtain pooled relative risks. The primary outcome measure was the rate of infection. RESULTS: Five randomized controlled trials with a total of 388 patients were included in the final analysis. Patients mostly had acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or sarcoma. Infection was noted in 53.7% patients in the neutropenic diet group, as compared with 50% in the unrestricted diet group. No significant difference in infection rate was observed between the neutropenic diet versus unrestricted diet groups, pooled risk ratio (RR) 1.13 (95% CI, 0.98-1.30; P=0.10). CONCLUSIONS: This meta-analysis of randomized controlled trials suggests that the use of neutropenic diet was not associated with decreased risk of infection in neutropenic cancer patients. The continued use of neutropenic diets should be questioned.

Examining low bacterial dietary practice: a survey on low bacterial food.

Patients with haematological malignancies have periods of neutropenia caused by the disease process and subsequent treatments, during which time they are at an increased risk of developing life threatening infections. Historically, many measures have been initiated to protect patients during this time. One such measure has been to provide a low bacterial diet to minimise the number of pathogens ingested from food. However, scientific literature lacks any substantial evidence confirming whether this is beneficial in the management of these patients while guidelines are often unclear and give conflicting advice. A detailed survey was carried out to examine the use of low bacterial diets considering criteria, conditions and specific dietary products. One hundred and eight questionnaires were completed, mainly European. Ninety-five (88%) centres used guidelines to advise practice for inpatients. Although 88% of the hospitals have guidelines, when these were examined there were enormous differences in both the guidelines themselves and the way in which they are implemented. The restrictions seen are varied and sometimes even contradict each other. Forty-eight (44%) of the respondents imposed restrictions on all products mentioned. Conditions for starting or stopping dietary restrictions were also diverse. This survey highlights the need to attempt to standardise dietary restrictions in a patient group for whom good nutrition is paramount.

Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial.

PURPOSE: Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. PATIENTS AND METHODS: We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. RESULTS: Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. CONCLUSION: The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti-infective policies.

Clinical features of hematological disorders caused by copper deficiency during long-term enteral nutrition.

OBJECTIVE: Copper deficiency has been reported to cause hematological disorders. However, its clinical and hematological characteristics are not fully understood. Therefore, we investigated bedridden patients suffering from copper deficiency and tried to clarify the clinical features of hematological disorders caused by this condition. PATIENTS AND METHODS: Five patients with typical copper deficiency who had been dependent upon enteral nutrition for a long period of time due to various diseases were investigated. We measured hematological parameters and observed the response to copper supplementation therapy and the recovery process of hematological disorders. RESULTS: Their mean age was 82.6+/-10.4 years and the mean duration of enteral nutrition was 16.4+/-5.2 months. Their serum copper concentration was extremely decreased (range, 3 to 8 microg/dl). All five patients had anemia and neutropenia. On the other hand, platelet count remained within the normal range. After copper supplementation therapy, hemoglobin concentration increased from 6.8+/-0.7 g/dl to 9.9+/-0.7 g/dl within a few months (p<0.01). Neutrophil count also increased from 750+/-370/microl to 3,690+/-1,210/microl in a few weeks (p<0.01). Mean corpuscular volume (MCV) decreased from 94.3+/-7.3 fl to 86.0+/-4.8 fl (p<0.05). Elevated serum ferritin and erythropoietin (EPO) levels were normalized after the improvement of anemia. CONCLUSION: Bicytopenia (anemia and neutropenia) with normal platelet count is a feature of hematological disorders caused by copper deficiency. MCV tends to indicate macrocytic anemia. Serum ferritin and EPO levels are elevated. These hematological abnormalities are improved within a few months after copper supplementation therapy.