Microbiological Food Safety and a Low-Microbial Diet to Protect Vulnerable People

Abstract

Low-microbial diets are advised by many institutions for people with neutropenia resulting from treatment with immunosuppressive drugs or medical conditions that increase their susceptibility to foodborne disease. In this article, the main microbiological hazards associated with foods are outlined, and a low-microbial diet in which higher-risk foods are replaced by lower-risk foods is described.

Introduction

In order to ensure the microbiological safety of food, providers of food, including those in hospitals and care homes, are required to have in place procedures based on hazard analysis and critical-control point principles (HACCP) (EC, 2004), and to use good hygienic practice. In addition, for especially vulnerable people, many hospitals use low-microbial diets, which avoid foods that are more likely to contain pathogenic microorganisms and substitute foods with a lower risk of the presence of these organisms. Many hospitals and other organizations advise these diets for patients with a low neutrophil count, and the diets are often termed “neutropenic diets” (Tomblyn et al., 2009; UC Davis Cancer Center, USA, 2012; Memorial Sloan-Kettering Cancer Center, USA, 2012; Roswell Park Cancer Institute, USA, 2012; Leukemia & Lymphoma Research, UK, 2013; Scottish Government, 2008; Norfolk and Norwich University Hospitals NHS Foundation Trust UK, 2012), but a low-microbial diet may be advised for other people with conditions that increase their susceptibility to foodborne disease. Increased susceptibility results in illness from infection with a lower number of organisms and the increased risk of severe and long-term complications.

The value of low-microbial diets has been questioned and the differences between recommendations criticized (e.g., Mank et al., 2008; Jubelirer, 2011; Fox and Freifeld, 2012). From a review of randomized controlled trials comparing the effect of the use of a low-bacterial diet with a control diet on infection rate, van Dalen et al. (2012) concluded that the three key studies, in two of which patients were treated with antimicrobial prophylaxis, had serious methodological limitations, and no definitive conclusions could be made.

The purpose of this article is to outline the hazards associated with certain foods: hazards that can have particularly serious effects in vulnerable people, and to indicate safer, alternative foods.

Hazards Associated with Foods and Beverages

Microbial hazards

In the United States between 2000 and 2008, it was estimated that norovirus caused the greatest number of cases of foodborne illness due to known pathogens, followed by nontyphoidal Salmonella spp., Clostridium perfringens, and Campylobacter spp. (Scallan et al., 2011). Leading causes of hospitalization were nontyphoidal Salmonella spp., norovirus, Campylobacter spp., and the protozoan pathogen Toxoplasma gondii, and the main causes of deaths were nontyphoidal Salmonella spp., T. gondii, Listeria monocytogenes, and norovirus.

In the Netherlands, T. gondii and Campylobacter spp. were assessed as the foodborne pathogens with the highest disease burden on a population basis, and T. gondii and L. monocytogenes resulted in the highest burden at an individual level (Havelaar et al., 2012). In the United Kingdom in 2008, Campylobacter spp., norovirus, C. perfringens, and Salmonella spp. were estimated to cause the greatest number of cases of foodborne disease, but L. monocytogenes caused more deaths than any other foodborne pathogen (FSA, 2011). In data reported to the European Union for 2011 Campylobacter spp., Salmonella spp. and viruses (particularly norovirus) were major causes of foodborne disease, while L. monocytogenes caused a high fatality rate (EFSA, ECDC 2013).

Norovirus infection is mild in immunocompetent adults, but in immunocompromised people it can cause protracted and chronic diarrhea, resulting in dehydration, malnutrition, and alteration of the intestinal mucosal barrier (Bok and Green, 2012). Persons ≥65 years old are at greatest risk of norovirus-associated death (Hall et al., 2013).

Nontyphoidal Salmonella spp. cause much more severe illness in immunocompromised than in immunocompetent adults, including invasive and focal suppurative disease (Gordon, 2008). Patients with hematological malignancy had an increased risk of Salmonella or Campylobacter infection compared with patients without malignancy (Gradel et al., 2009). Invasive disease due to Campylobacter spp. is rare, but is more frequent in people with comorbidities and immune-compromising conditions (Louwen et al., 2012).

In immunocompetent people, infection with Toxoplasma is usually asymptomatic or causes only mild symptoms, but the organism survives as cysts in several tissues (latent infection). Congenital toxoplasmosis can result in serious clinical symptoms including stillbirth, neonatal death, and chorioretinitis (EFSA, 2007) In immunocompromised people, toxoplasmosis can result from primary infection but usually results from reactivation of tissue cysts in the host or in transplanted organs or bone marrow transplants and can result in severe, disseminated disease (Israelski and Remington, 1993; Scerra et al., 2013).

The relative susceptibility to L. monocytogenes of transplant patients, patients with cancer of the blood, and patients with chronic lymphocytic leukemia was >1000 times that of people with no risk factors (WHO/FAO, 2004; Goulet et al., 2012), while patients with other conditions had a 100–1000-fold increase in susceptibility. It was proposed that food recommendations should be targeted at those groups whose conditions were associated with more than 100-fold increased risk of listeriosis (Goulet et al., 2012).

Foods of concern for vulnerable people

The foods discussed in the following sections are of particular concern to people who are highly susceptible to foodborne disease.

Raw and undercooked meat and poultry

Microorganisms, including Salmonella spp., Shiga toxin–producing Escherichia coli (STEC), Campylobacter spp., Yersinia enterocolitica, T. gondii, hepatitis E virus (HEV), and in some countries the parasites Taenia spp. and Trichinella spp. from animal carcasses can contaminate raw meat and poultry. Outbreaks of infection with Salmonella Typhimurium DT104 and STEC O157 have been associated with consumption of raw beef, as filet américain (steak tartare) and similar foods, and undercooked hamburgers (Bell et al., 1994; Tuttle et al., 1999; Doorduyn et al., 2006; Ethelberg et al., 2007; Kivi et al., 2007). In several countries, pigs are a reservoir for Y. enterocolitica, and consumption of raw minced pork is a main risk factor for infection (Rosner et al., 2012). Undercooked meat (lamb, pork, and beef ) is a major risk for infection with T. gondii (Halos et al., 2010; Ginsbourger et al., 2012). Recent outbreaks of Campylobacter infection were associated with undercooked poultry liver pâté or parfait (CDC, 2013; Edwards et al., 2014). Raw or undercooked pig, wild boar, and deer meat have been linked to infection with HEV, which is found in retail pig liver and pork sausages in several countries (Scobie and Dalton, 2013) and can cause chronic and severe effects in vulnerable people.

To protect vulnerable people, thorough cooking of meat, particularly ground (minced) meat, is essential. Temperatures and times advised for thorough cooking of animal foods are shown in Table 1. These conditions are based on inactivation of non-spore-forming bacteria; heating to 67°C or higher is considered to inactivate tissue cysts of T. gondii (EFSA, 2007). Cooking naturally contaminated pork liver to an internal temperature of 56°C for 1 h failed to inactivate HEV, but cooking to at least 71°C caused inactivation (Feagins et al., 2008); in pork products with a higher fat content, inactivation may require an internal temperature of 71°C for up to 20 min (Barnaud et al., 2012), and extended heating time may be particularly important for such food for vulnerable people (EFSA, 2011b).

Table 1.

Temperatures and Times Advised for Thorough Cooking of Animal Foods: A Food Thermometer Should Be Used to Check the Internal Temperature Reached

Food	Temperature to be reached in all parts of the food	Time at specified temperature	Reference
1. Meat, poultry, eggs, seafood, special attention to minced meats, rolled roasts, large joints of meat, and whole poultry, soups, and stews	70°C	—	WHO (2006)
2. Burgers (ground, minced meat), poultry livers, kidneys and other offal, range of foods	70°C or equivalent temperature/time combination	At least 2 min	ACMSF (2007), FSA (2010) FSA (2013)
3. Raw eggs broken and prepared for immediate service. Fish, meat except as specified in 4, 5, and 6	63°C (145°F) or above	15 s	FDA (2013a)
4. Mechanically tenderized meat, injected meats, ratites, comminuted fish, meat, game animals commercially raised for food, and raw eggs not prepared for immediate service	68°C (155°F) or equivalent temperature/time combination 70°C (158°F) 66°C (150°F) 63°C (145°F)	15 s <1 s 1 min 3 min	FDA (2013a)
5. Whole meat roasts including beef, corned beef, lamb, pork, and cured pork roasts such as ham^a	70°C (158°F) or equivalent temperature/time combination, e.g.: 65°C (149°F)	0 s 85 s	FDA (2013a)
6. Poultry, baluts, wild game animals, stuffed fish, stuffed meat, stuffed pasta, stuffed poultry, stuffed ratites, or stuffing containing fish, meat, poultry or ratites	74°C (165°F) or above	15 s	FDA (2013a)
7. Raw animal food cooked in a microwave oven	≥74°C (165°F)	Allow to stand for 2 min	FDA (2013a)

Raw or undercooked whole muscle, intact beef steak, and other raw or partially cooked animal food may be served or offered for sale in a ready-to-eat form if the food establishment serves a population that is not a highly susceptible population (FDA, 2013a).

The information in Table 1 indicates that whole meats and comminuted meats should be cooked to give a temperature of at least 70°C throughout the product, and it would be reasonable to maintain at this temperature for at least 2 min. The temperature should be confirmed by use of a thermometer. This treatment is particularly important for food served to vulnerable people. Because of the possible presence and heat-resistance of HEV, it is prudent not to serve pig liver or pork sausages to vulnerable people.

Deep freezing meat (−12°C or lower) can reduce the risk of infection with T. gondii (EFSA, 2007).

Cooked meat cooled insufficiently after cooking

C. perfringens is of concern in cooked meat products that are then maintained with inadequate cooling. Spores of C. perfringens can survive cooking at 100°C, and growth of the bacteria can occur between 12°C and 52°C. Outbreaks of C. perfringens illness, including fatalities, have occurred in hospitals following inadequate cooling of cooked meat products. In a hospital outbreak in 2010, three patients died who were receiving medications that inhibited intestinal motility (CDC, 2012a).

After cooking, such foods should either be eaten immediately, or kept for a short time at a temperature higher than 63°C, or cooled to 5°C or below in 90 min and reheated to at least 72°C before consumption. In the United Kingdom and the United States, guidelines for cooling cooked foods aim to ensure that no more than a 10-fold increase in numbers of C. perfringens can occur during cooling (Lund and O'Brien, 2009). These guidelines are particularly important for vulnerable people.

Sliced, cooked, ready-to-eat (RTE) meats

In the United States in 2003, cooked, RTE meats were the highest-risk food in relation to listeriosis (FDA/CFSAN, 2013). Contamination may occur after cooking, and during slicing and packaging. Postpacking pasteurization or the inclusion of inhibitors can reduce this risk (FSIS, 2014), and are used by many producers. In the United Kingdom in samples sliced to order, 10.8% contained Listeria spp. and 3.0% contained L. monocytogenes, whereas in prepacked samples 5.8% contained Listeria spp. and 3.8% contained L. monocytogenes (Little et al., 2009b). A higher proportion of prepacked samples, particularly larger packs (≥300 g), than of samples sliced to order contained L. monocytogenes >100/g. In the United States, a higher prevalence and number of L. monocytogenes has been reported in retail-sliced meats than in prepacked meats, and retail-sliced meats posed a greater risk of listeriosis than prepacked samples (Endrikat et al., 2010).

In Canada in 2008, an outbreak of listeriosis resulted in serious illness in 57 people, and was reported as the underlying or contributing cause of death in 22 individuals (Weatherill, 2009). Most of those affected were frail, elderly people living in long-term-care homes; several people were hospitalized because of other diseases such as cancer. The outbreak was caused by deli meats, contaminated after cooking and during slicing, and supplied by a commercial company. In 2006–2007 in a German hospital treating oncology patients, 11 apparently sporadic cases of listeriosis occurred, 5 fatal (Winter et al., 2009). All these patients had an underlying immunosuppressive disease, and the risk of listeriosis appeared to be increased substantially in patients taking corticosteroids and proton pump inhibitors. The cases formed an outbreak that was linked to pre-sliced, RTE scalded sausages supplied to the hospital.

In view of the contamination risk, it is recommended that for susceptible people deli meats should be reheated to steaming hot or 165°F (74°C) before serving (FDA, 2013d).

Pâtés

Pâtés consist typically of a paste of cooked ground meat or fish to which other ingredients may be added after cooking. Contamination may result from undercooking or any addition after cooking. Several outbreaks of listeriosis have been associated with pâté or pâté-like foods (Norton and Braden, 2007). Recent outbreaks of Campylobacter infection were associated with undercooked poultry liver pâté or parfait in catering establishments (see earlier section). For susceptible people, canned or other shelf-stable products should be substituted for refrigerated pâtés and meat spreads, and freshly prepared products should be cooked thoroughly.

Raw and partially cooked eggs

Salmonella Enteritidis can contaminate eggs internally; this and other Salmonella spp. have caused numerous outbreaks associated with raw or partially cooked egg. An outbreak of Salmonella Enteritidis in a London hospital in 2002, which affected 29 people and caused 1 death, was attributed to the use of imported, raw shell eggs and undercooking (Lund and O'Brien, 2009). An outbreak in a hospital and nursing home in the Netherlands that affected 82 patients, 5 of whom died, was caused by bavaroise prepared with raw eggs and underheated (Bruins et al., 2003).

In foods served to highly susceptible people, pasteurized eggs or egg products should be substituted for raw eggs in the preparation of certain foods, and soft-cooked eggs should not be served (FDA, 2013a).

Raw and partially cooked finfish

Several foodborne pathogens can contaminate raw fish. Some such as Vibrio spp. and Anisakis simplex occur naturally in seawater while other pathogens, including Salmonella spp., Shigella spp., Staphylococcus aureus, L. monocytogenes, and norovirus can occur on fish from contamination of water in the catchment area, or as a result of unsanitary practices after catching (FDA, 2011).

Where marine fish are consumed raw, Vibrio spp., particularly V. parahaemolyticus, causes diarrheal disease and is common in Asia and the United States, with some outbreaks in Europe (FAO/WHO, 2011). V. vulnificus causes fewer reported cases but in people with liver disease, diabetes, defective iron metabolism, or who are immunocompromised it can result in bacteremia with a high case-mortality. A. simplex and related nematodes cause gastrointestinal and other symptoms, and have been reported mainly in Japan, in coastal regions of Europe, and the United States (Hochberg and Hamer, 2010; EFSA, 2011a). Salmonella and norovirus have been important causes of outbreaks associated with fish in Europe and the United States (NACMCF, 2008; EFSA, ECDC 2013).

Guidelines for cooking fish are included in Table 1. These are based on expectation of a low level of contamination and inactivation of bacteria and may not inactivate viruses, control of which depends on prevention of contamination (NACMCF, 2008). The above cooking will inactivate Anisakis, and immediate evisceration of fish will reduce contamination with this nematode.

Smoked seafood

Smoked seafood, particularly cold-smoked fish, and gravad (marinated) fish, is liable to be contaminated with L. monocytogenes, which can multiply in the fish at refrigeration temperatures (Dass et al., 2011; Kang et al., 2012; Lambert et al., 2012; EFSA 2013b; FDA/CFSAN, 2013). Other pathogens may contaminate the product during processing. Outbreaks of listeriosis and of febrile gastroenteritis have been caused by L. monocytogenes associated with cold-smoked fish (Thomas et al., 2012), and numerous products have been recalled because of contamination.

An outbreak of Salmonella Thompson infection in the Netherlands in 2012, which affected >1000 people, was attributed to smoked salmon (Friesema et al., 2012).

Cold smoking of fish is unlikely to inactivate Anisakis; hot smoking at an internal temperature ≥60°C for at least 1 min is recommended for inactivation. Smoked fish should be reheated to 74°C before serving to susceptible people.

Raw and partially cooked shellfish

Crustaceans (crabs, lobsters, shrimps) are often contaminated with Vibrio spp. Contamination with other pathogens may result from pollution of seawater and contamination during extensive handling after harvesting.

Filter-feeding molluscs (oysters, clams, mussels, and scallops) take in microorganisms from the surrounding water, which may be contaminated from sewage. In the European Union and the United States, shellfish-harvesting areas are classified and controlled according to the level of contamination with E. coli or fecal coliform bacteria.

Many outbreaks have resulted from consumption of crustaceans or molluscan shellfish, particularly raw oysters, contaminated with Vibrio spp. or norovirus (NACMCF, 2008; Iwamoto et al., 2010). Hepatitis A virus and hepatitis E virus are also important causes of severe illness associated with shellfish (Crosson et al., 2012; Shuval, 2003). Monitoring seafood-harvesting areas for fecal coliform bacteria and E. coli does not adequately indicate the risk of vibrios or viruses.

Control of infection transmitted by shellfish includes preventing contamination of harvesting areas, purification (by depuration or relaying), and adequate cooking. Prevention of contamination of harvesting areas is important, as purification may not ensure removal of viruses and heat treatment cannot ensure total inactivation of viruses without affecting the palatability of the product (Lees, 2000; FDA, 2011; Codex Alimentarius, 2012). It is advisable that highly susceptible people choose canned shellfish rather than raw or precooked products.

Raw and unpasteurized milk

Pathogenic microorganisms can contaminate raw milk as a result of systemic infection (direct passage from blood to milk), of mastitis, of contamination from feces or skin, or from the environment. These pathogens include Campylobacter spp., Salmonella spp., STEC, L. monocytogenes, and Brucella spp. Thus, consumption of raw milk is a threat to health (Claeys et al., 2013). Non-spore-forming pathogens are inactivated by pasteurization. “Pasteurized milk” may be contaminated as a result of inadequate pasteurization or by postpasteurization contamination. In the United States, consumption of raw milk is uncommon but during 1993–2006, the incidence of reported outbreaks involving unpasteurized milk products was at least 150 times greater per unit of dairy product consumed than the incidence involving pasteurized products (Langer et al., 2012). Unpasteurized milk should therefore be avoided, particularly by susceptible people.

Ice cream

In commercial production of ice cream, the mix of ingredients is pasteurized before freezing (ICMSF, 2005). Hard ice cream is frozen to −25° to −30°C, and soft-serve ice cream is usually drawn from the freezer at about −6° to −7°C. The mix for soft-serve ice cream is transported to retail outlets, where it is stored soft-frozen and dispensed to consumers.

Numerous outbreaks of salmonellosis have been linked to ice cream, usually to home-made products prepared with unpasteurized milk or cream or raw eggs (CDC, 1994; ICMSF, 2005). An outbreak of infection with STEC in 2007 resulting in hemolytic uremic syndrome in five children was associated with ice-cream produced at a farm, made with pasteurized milk, and probably recontaminated (Schrijver et al., 2008). Pathogenic bacteria can survive in ice cream for long periods; L. monocytogenes in ice cream had probably survived in the environment and on production equipment for several years (Miettinen et al., 1999). Particularly for susceptible people, ice cream should be made with pasteurized milk and pasteurized egg products, and equipment should be cleaned effectively and regularly to prevent survival of any pathogens. It is probably advisable for susceptible people to avoid soft-serve ice cream because of difficulty in ensuring regular cleaning of production equipment (Little and De Louvois, 1999).

Soft cheeses

Outbreaks of infection with Salmonella spp., STEC, L. monocytogenes, S. aureus, and Brucella spp. have been caused by contaminated soft cheeses made with raw or pasteurized milk (Desenclos et al., 1996; Rampling, 1996; Langer et al., 2012). Correct pasteurization will inactivate these bacteria in the milk, but measures are also needed to prevent postpasteurization contamination during production of the cheese.

An outbreak of listeriosis in Germany in 2006–2007 linked to red smear cheese (fermented with Brevibacterium linens) made with pasteurized milk affected 189 people, many with underlying medical conditions; 26 of these people died (Koch et al., 2010). In 2007, an outbreak of listeriosis in a tertiary-care hospital in Norway affected 17 patients, most of whom had predisposing conditions and/or were receiving immunomodulating therapy, and contributed to 3 deaths (Johnsen et al., 2010). The outbreak was caused by Camembert cheese made from pasteurized milk and produced at a small, local dairy; the outbreak strain of L. monocytogenes was retrieved from the floor, cheese cases, and brine used in cheese production.

Because of the risk of contamination and the ability of L. monocytogenes to multiply in soft and mold-ripened cheeses, these products should be avoided by susceptible people.

Yogurt and probiotics

Yogurt is generally produced commercially by fermentation of pasteurized milk using starter cultures of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, or alternative Lactobacillus sp. The final product should contain abundant, viable, starter bacteria (min 10⁶ colony-forming units/g); if the product has been heat treated after fermentation, the requirement for viable microorganisms does not apply (Codex Alimentarius, 2003). Postproduction heat treatment has been used to extend the shelf-life. If the final product is heat-treated after fermentation, the product should be designated “pasteurized yogurt” or “long-life yogurt” (Tamime and Robinson, 2007). Such yogurt may not be widely available.

Probiotics are live organisms that are stated to have many health benefits. They may include species of Lactobacillus, Enterococcus, Streptococcus, Bifidobacterium, Bacillus, and the yeast Saccharomyces boulardii. These are either added to foods, particularly yogurt, or used as supplements.

Systemic infections have been associated with use of probiotics, particularly L. rhamnosus GG, in immunocompromised patients (Boyle et al., 2006; Liong, 2008; Luong et al., 2010; Kochan, 2011). It was concluded that “until more safety data are available for immunocompromised patients, physicians should avoid giving probiotics, as their benefits in this population remain controversial” (Luong et al., 2010).

A recent report concluded that there is a lack of assessment and systematic reporting of adverse events in probiotic intervention trials, and that interventions are poorly documented. The available evidence in randomized controlled trials was reported not to indicate an increased risk; however, rare adverse effects are difficult to assess. The authors concluded that the current literature is not equipped to answer questions on the safety of probiotic interventions with confidence (Hempel et al., 2011). Further information is needed on this topic.

There is a lack of clear distinction between “live” yogurt and probiotic yogurt. On the basis of present information, it is advisable that highly susceptible people should only use commercial, plain yogurt made from pasteurized milk and with the traditional starter cultures.

Raw vegetables and salads

Fresh (salad) vegetables are recognized increasingly as responsible for outbreaks of foodborne disease, particularly associated with Salmonella, STEC, and norovirus (Lynch et al., 2009; Olaimat and Holley, 2012; Painter et al., 2013). Salmonella on leafy vegetables eaten raw was the major hazard in foods of nonanimal origin in Europe (EFSA, 2013a); another risk was norovirus and leafy greens eaten raw. In 2010, a nosocomial outbreak of listeriosis that affected 10 patients, 5 of whom died, was caused by contaminated, diced celery (Gaul et al., 2013). The patients reported were aged between 56 and 93 years, and all had ≥1 immunocompromising condition or were receiving corticosteroid or acid-reducing treatments.

Most of the contamination of RTE produce is traced back to preharvest sources (e.g., irrigation water, fertilizers) (EFSA, 2013a). Guidance on hygienic practices during primary production and packing has been published by several organizations (CFA, 2007; FSA, 2009; Codex Alimentarius, 2010; FDA, 2013b), but in some parts of the world fresh vegetable crops continue to be irrigated with untreated sewage water (Castro-Rosas et al., 2012). Commercial methods and washing before serving cannot reliably decontaminate produce, emphasizing the importance of preventing contamination. Cooked or canned, rather than raw vegetables, should be supplied to susceptible people.

Raw vegetable sprouts

Raw or minimally processed, sprouted seeds are a concern because pathogenic bacteria, particularly Salmonella spp. and STEC, may contaminate the seeds and multiply during germination and sprouting (EFSA, 2011c). In 2011, an outbreak of infection with E. coli O104 in Germany, which affected >3800 people causing 54 deaths, was caused by contaminated fenugreek sprouts (Frank et al., 2011). In the United States, recommendations for the safety of sprouted seeds included treatment of seeds before sprouting to give 5-log reduction of Salmonella and E. coli O157 (NACMCF, 1999 ). Several types of treatment have been used to decontaminate seeds with minimum effect on germination, the most commonly used in the United States being chlorine, but very few treatments consistently give a 5-log reduction (EFSA, 2011c). Cooked, rather than raw, vegetable sprouts should be supplied to susceptible people.

Fresh fruits

Considerations relating to raw vegetables and salads apply similarly to fruits. Outbreaks due to contaminated raw fruits include Salmonella infections associated with tomatoes, peppers, and melons; the parasite Cyclospora associated with raspberries; norovirus and hepatitis A virus associated with frozen raspberries, strawberries, and blueberries (Berger et al., 2010; Gillesberg Lassen et al., 2013); and L. monocytogenes associated with cantaloupes (CDC, 2012b). For susceptible people, fruits should be canned or cooked, or fruits should be washed well before peeling immediately before consumption.

Dried fruits

Sultanas, raisins, dried vine fruits, and dried figs showed relatively high contamination with fungi, particularly Aspergillus spp. (Iamanaka et al., 2005; Romero et al., 2005; Gashgari et al., 2011; Palumbo et al., 2011; Heperkan et al., 2012; AlAskari et al., 2012; Ozer et al., 2012). Invasive fungal infections, particularly those due to Aspergillus spp., are an important risk in immunocompromised patients, mainly as respiratory pathogens, but infections also occur via the gut (Kazan et al., 2011). For susceptible people, dried fruits should be limited to products that are cooked in food.

Unpasteurized fruit or vegetable juices

Unpasteurized apple juice has been associated with outbreaks of STEC, Salmonella spp., and Cryptosporidium spp., and unpasteurized orange juice with outbreaks of Salmonella spp., Shigella spp., enterotoxigenic E. coli, and hepatitis A virus, while other pathogens have also been associated with unpasteurized juices (Vojdani et al., 2008; Danyluk et al., 2012). Foodborne pathogens may survive for weeks in fruit juices with a pH 3.6–4.0, particularly at refrigeration temperatures.

The U.S. Food and Drug Administration (FDA) requires processing of juices to provide a 5-log reduction of the pathogen of most concern, usually E. coli O157:H7 or Salmonella. Juices served to susceptible people should be pasteurized.

Herbs and spices

Salmonella spp. can be present on fresh herbs (Elviss et al., 2009), which are often added to foods that are consumed raw. Outbreaks of salmonellosis associated with the use of fresh herbs demonstrate the risk to consumers (Elviss et al., 2009; Pakalniskiene et al., 2009; Public Health England, 2013).

Spices are produced in many countries, and a high proportion of supplies in North America and Europe are imported (FDA, 2013c). Spices are liable to be contaminated with bacteria, particularly Salmonella spp., and outbreaks of salmonellosis associated with spices have been reported in North America and in Europe. The majority of spices may undergo pathogen reduction steps, but contamination can occur after these processes, and some spices may not receive such treatments.

Spices are often contaminated with molds, including Aspergillus spp. (Bouakline et al., 2000; ICMSF, 2005). Sprinkling food with pepper just before eating may produce an aerosol, exposing a patient to airborne contamination. Gut aspergillosis, associated with A. fumigatus or A. flavus, has been linked to consumption of food that was extremely rich in spices (Kazan et al., 2011). Patients at profound risk for aspergillosis should not be given pepper or spice that has not been sterilized (Denning, 1998).

For susceptible people, herbs and spices should only be used in foods that are then cooked.

Nuts and seeds

Salmonella is of concern on shelled and unshelled nuts, and outbreaks of salmonellosis have been associated with nuts (Little et al., 2009a, 2010). Following outbreaks of salmonellosis associated with almonds, treatment of almonds to give a minimum 4-log reduction, or a 5-log reduction (FDA verified, “pasteurized”) of Salmonella is mandatory in the United States (Pan et al., 2012). Fungi, particularly Aspergillus spp., are present frequently on shelled and unshelled nuts bought at retail (Bayman et al., 2002).

Some RTE retail seeds, particularly sesame seeds, contain Salmonella, and products such as halvah, containing sesame seeds, have been associated with outbreaks of salmonellosis (Brockmann et al., 2004; Willis et al., 2009; FDA, 2013c).

For susceptible people, shelled roasted nuts, canned, or bottled nuts, and nuts and seeds baked in products should be used.

Bakery products with unheated additions

Bakery products with fillings that were unheated or contaminated after heating have caused numerous outbreaks of disease (Smith, 2004). Outbreaks caused by cakes and pastries filled with cream or custard include a hospital outbreak of STEC and a protracted nursing home outbreak of Salmonella infection (O'Brien et al., 2001; Frank et al., 2007). Bakery products or breakfast cereals with nuts or seeds added after heating are also liable to be contaminated.

Cooked bakery products without cream or fillings should be used for susceptible people.

Sandwiches

Outbreaks of listeriosis acquired in hospitals have been linked to sandwiches with various fillings, and attributed to cross-contamination at manufacturers and inappropriate storage temperatures (>8°C) in hospitals (Little et al., 2012). Three studies of sandwiches served in hospitals and residential care homes in the United Kingdom between 2005 and 2010 found L. monocytogenes in 2.5–3.1% of samples. L. monocytogenes was found in 7% of retail sandwiches in the United Kingdom, in 0.4% at >100 colony-forming units/g (Little et al., 2009b).

For susceptible people, sandwiches should contain lower-risk fillings (e.g., canned meat or fish, or hard cheese).

Drinking water

In developed countries, water treatment results in tap water that is mainly pathogen-free, but contains many microbes. Water distribution systems may contain opportunistic pathogens such as “nontuberculous mycobacteria,” Legionella spp., Pseudomonas aeruginosa, Stenotrophomonas maltophilia, other Gram-negative bacteria and protozoa (Hunter, 2008; Cunliffe et al., 2011). Cryptosporidium spp. may survive water treatment processes.

Immunocompromised people may be at risk of infection with opportunistic pathogens in drinking water. End-line water filters were advised to provide drinking water for immunocompromised patients, provided that robust systems are in place to ensure that the filter cartridges are changed appropriately (Hall et al., 2004). Guidelines to minimize the risk of P. aeruginosa in water supplies for healthcare settings have been published (Department of Health, 2013). An outbreak of infection with P. aeruginosa in intensive care units, which affected 19 patients, 4 of whom died, was attributed to contaminated bottled, still water (Eckmanns et al., 2008).

Severely immunocompromised people are at particular risk of Cryptosporidium infection. United Kingdom guidance is that anyone whose T-cell function is compromised should be advised to boil and cool their drinking water from whatever source (CMO, 1999). This includes tap or bottled water, and ice cubes should also be produced from boiled and cooled water.

Ice

Ice intended for cooling drinks may be contaminated with potentially pathogenic microorganisms, usually in low numbers (Hunter, 2008). An outbreak of infection with Stenotrophomonas maltophilia in hematology patients was traced to an ice-making machine on the ward. It is recommended that ice made in automated ice machines should not be given to immunocompromised patients.

Guidelines for a Low-Microbial Diet

Many conditions increase the susceptibility of people to foodborne pathogens (Lund and O'Brien, 2011). Numerous outbreaks of foodborne disease caused by Campylobacter spp., C. perfringens, STEC, L. monocytogenes, Salmonella spp., and norovirus have affected vulnerable people in hospitals or other healthcare settings (Lund and O'Brien, 2009).

Components of a basic low-microbial diet are listed in Table 2, recognizing that these may need to be modified in the light of further information and research.

Table 2.

Low-Microbial Diet

Type of food	Higher risk; avoid:	Lower-risk alternative, suitable for a low-microbial diet
Meat and poultry	Raw or undercooked meat or poultry	Meat or poultry cooked to a safe minimum internal temperature (e.g., 70°C for 2 min; use a food thermometer)
Hot dogs; sliced, cooked deli meats	Hot dogs, deli meats and luncheon meats that have not been reheated	Hot dogs, deli meats, and luncheon meats that have been reheated to 74°C
Pâtés	Refrigerated pâtés or meat spreads	Canned pâtés or meat spreads, or other shelf-stable products
Eggs	Soft-boiled eggs; foods that contain raw/undercooked eggs	Hard-boiled egg. When preparing recipes that call for raw or undercooked eggs, use pasteurized egg.
Fish	Raw or undercooked fish (e.g., sushi)	Fish cooked to at least 63°C for 15 s, comminuted or farmed fish heated to 68°C for 15 s or 70°C for 1 s
Smoked fish	Refrigerated, smoked fish	Smoked fish reheated to 74°C
Shellfish	Raw and precooked shellfish	Canned shellfish
Milk	Unpasteurized milk	Pasteurized milk
Ice cream	Soft-serve ice cream	Small tubs of ice cream or wrapped bars produced using pasteurized milk and pasteurized egg
Cheese	Soft cheeses, especially those made from unpasteurized milk. Mold-ripened cheeses.	Hard cheeses made from pasteurized milk. Processed cheese
Yogurt and probiotics	Yogurt made with unpasteurized milk; “probiotic” yogurt	Plain yogurt made with pasteurized milk and traditional starter cultures
Vegetables, salads	Raw vegetables, including lettuce/salads	Cooked or canned vegetables
Vegetable sprouts (alfalfa, bean, etc.)	Raw vegetable sprouts	Cooked vegetable sprouts
Fresh fruit	Unpeeled fruit or ready-peeled fruit, frozen fruit	Fruit that that can be peeled, canned fruit
Dried fruit	Uncooked products	Products cooked in food
Fruit or vegetable juices	Unpasteurized or freshly squeezed fruit or vegetable juice or smoothies	Pasteurized juices
Herbs and spices	Uncooked products	Products cooked in food
Nuts, seeds	Nuts raw or roasted in shells; raw seeds	Processed, shelled roasted nuts, canned or bottled nuts, nuts and seeds present in baked products
Bakery products and cereals	Cakes with perishable fillings (cream, custard) or with nuts or dried fruits added after baking Uncooked cereal products, products with seeds or nuts added after cooking or baking	Bread, biscuits, cooked cereals, cakes without cream or fillings
Sandwiches	Sandwiches containing higher-risk ingredients	Sandwiches filled with lower-risk ingredients (e.g., canned meat or fish, hard cheese)
Drinking water	Tap water that has not been boiled, bottled mineral or spring water, water from coolers or water fountains	Boiled and cooled tap water, carbonated bottled water, water from taps with microfilter
Ice	Ice from ice machine or trays	Ice made from boiled and cooled water

In addition to neutropenic patients, guidance regarding foods to avoid is also needed for other vulnerable people. The FDA (2013d) has published information for several groups of vulnerable people, giving advice on purchasing, storing, and cooking foods and on selection of lower-risk rather than higher-risk foods.

Conclusions

Microbiological safety of food is particularly important for immunocompromised and other susceptible people. It is essential to obtain food from reputable suppliers who comply with legal requirements, have in place an appropriate food safety management system based on HACCP principles, and use safe handling techniques. The incidence of unsafe batches of food may be occasional, but the consequences for vulnerable people can be severe and fatal. Evidence from outbreaks and from sporadic cases of foodborne infection in vulnerable people (Marcus et al., 2009; Galan et al., 2011) indicates the need for a low-microbial diet.

It is important that general agreement be reached on recommendations for a low-microbial diet, and on provision for reviews of the diet in the light of developments in the microbiological safety of food.

Footnotes

Acknowledgments

I am grateful for constructive criticism from Dr. Tony C. Baird-Parker during the writing of this article.

Disclosure Statement

No competing financial interests exist.

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