Complications, such as gastroesophageal reflux disease, aspiration pneumonia, and diarrhea, are problems associated with liquid EN products in the past; however, the use of semi-solid EN products has been reported can circumvent these complications [3,4,5,6,7,8]. In addition, semi-solid EN can be administered over a short time [9], which facilitates physiological movement of the stomach and gastrointestinal tract function [4,5,6,7,8], and its slow absorption has been reported to help prevent hyperglycemia [20] and pressure ulcers [21]. However, semi-solidified enteral nutrients are more viscous compared with liquid nutrients, which may cause infection if retained in the catheter lumen. Various manufacturers currently market semi-solid EN products with different ingredients and physical properties. Semi-solid EN products that stay in the catheter lumen vary adheres to the catheter after injection, which depends on their physical properties [22]. In recent years, Japan has switched to small-diameter connector products for EN administration that comply with the International Standard ISO80369-3 to prevent misconnection with infusion lines; however, the complicated structure of these connectors raises concerns with respect to microbial contamination [23] and proper handling is required. Because bacterial growth due to improper handling associated with liquid EN [24,25,26,27] and subsequent infections [28, 29] have been reported, we consider that semi-solidified EN products with high viscosity are more likely to cause infection. Because no effective method has yet been established, infection control is necessary when handling enteral feeding catheters [30, 31]; however, current guidelines [3] do not provide detailed control methods and are not standardized. As a result, pharmacists must provide necessary information and guidance based on their knowledge of the proper use of drugs, but the handling of enteral nutritional supplements is not well-established [32].

Our study aimed to investigate how the characteristics of EN products affect the growth of microorganisms. The bacteria E. coli, S. marcescens, and the fungus C. albicans, which can be problematic in the treatment of infectious diseases, were evaluated.

The results indicated that the growth of E. coli and S. marcescens increased over time from 0 to 24 h in RACOL®-NF SemiSolid for Enteral Use, Hine®jerry AQUA, and Mermed Plus®. Bacterial growth depends on the nature of the bacterial species as well as composition, pH, and osmotic pressure [33], which suggests that the neutral range pH of EN may be a factor in bacterial growth. In total nutrient admixture (17.6% glucose, 5% amino acids, 4% lipid; pH 5.6, osmolality 1778) infusions, it was reported that many bacteria such as S. aureus, S. marcescens, and Pseudomonas aeruginosa did not grow, but only C. albicans and two isolates of Staphylococcus saprophyticus did [34]. It was also reported that bacteria such as S. aureus, S. marcescens and Bacillus cereus cannot grow in total parenteral nutrition (TPN) solutions without lipid due to the acidity (pH5.6 or lower), but C. albicans can grow regardless acidity [35]. Furthermore, it has been reported that neutral range pH, low osmolarity peripheral parenteral nutrition solutions are better environment for the growth of various microorganisms than low pH, high osmolarity TPN solutions [17]. All of the enteral nutrients in which no growth was observed had a pH value less than pH 4, indicating that pH exhibited a marked influence on the differences in bacterial growth in the enteral nutrient products. In addition, the viscosity and calorie content in which growth was observed varied, suggesting that these factors have little effect on bacterial growth. In contrast, when C. albicans was present, growth was observed in all nine types of EN products. Almost all fungi have been reported to be able to grow at low pH [36]. The fact that C. albicans can raise environmental pH at low pH [37] suggests that C. albicans, unlike bacteria, can grow at low pH, regardless of the composition of the enteral nutritional supplements. In this study, we did not use S. aureus because other studies have reported its growth in EN [15, 16]. However, further examination for S. aureus would be helpful to characterize microbial growth in EN.

The guidelines [3] state that administration of EN other than RTH preparations should be completed within 8 h after opening, and within 24 h for RTH preparations. However, our study revealed that bacterial and fungal growth increased slowly during the first 8 h and then rapidly over the next 24 h. RTH preparations are considered effective at preventing contamination in enteral feedings [12], but even with RTH preparations, the risk of infection may increase with inappropriate use, such as dilution of nutritional supplements or inadequate management of enteral feeding catheters. Contamination of enteral feeding catheters, which can cause blockage, may be caused by viscous enteral feedings, such as semi-solid EN, inadequate cleaning of the catheter resulting in residue on the catheter, and improper administration through the catheter. For drug administration, caution is required because there are many cases in which changes in the combination of EN supplements and pharmaceuticals may occur. Even with RTH preparations, the risk of infection can be reduced by prompt discontinuation of use after opening the package. In general, when using an enteral feeding catheter to administer enteral nutritional supplements and drugs, it should be thoroughly washed with 20 to 30 mL of water before and after use. In nursing homes and home medical care sites, which have increased in recent years, catheter management methods have become dependent upon caregivers, and it is unclear whether appropriate management is being performed.

From the results of this study, we found that if microorganisms contaminate enteral nutrients, even RTH preparations with a low infection risk, they may proliferate if the product is not used appropriately. Importantly, low-pH preparations can inhibit bacterial growth. In addition, because microbial growth is a concern regardless of physical properties, it is necessary to gather evidence so that appropriate management can be implemented regarding the handling of EN supplements and catheters.