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Objective Oral mucositis (OM) caused by infection facilitated by myelosuppression and immunosuppression can be controlled through oral care. We investigated changes in oral anaerobic bacterial flora during the onset of OM with hematopoietic stem cell transplantation (HSCT). Methods This study included 19 patients who underwent HSCT. All received professional oral care before initiating the preparative regimen. We assessed OM, oral health and obtained microbial samples from the oral cavity during 5 assessment points: before initiating the preparative regimen; the day before HSCT (day 1); and at 7, 14, and 30 days after HSCT. Microbial species were identified by using a mass spectrometer. Results The number of patients with serious OM increased initially after HSCT and decreased thereafter. Many Streptococcus species were identified before HSCT, but these gradually decreased and were replaced by coagulase-negative staphylococci. An increase in Candida species after HSCT and the identification of Enterococcus species were significantly associated with OM. Nutritional status recovery and prognosis were significantly worse in patients who developed OM. Conclusions To the best of our knowledge, this study is the first which shows that anaerobic bacteria were identified in patients' oral flora before and after HSCT by using a mass spectrometer. These results indicate that Enterococcus species and Candida species may have been associated with OM. OM affected the patients' improvement in nutritional status and their prognosis. We concluded that it is important to provide more complete oral care instructions and interventions to prevent these bacterial infections.

Introduction Approximately 70%-90% patients receiving hematopoietic stem-cell transplantation (HSCT) have oral mucositis (OM). HSCT-induced OM is a major complication of preparative regimens. The oral cavity of healthy individuals harbor several bacterial species. For example, the cheek and tongue harbor a number of Streptococcus species, while the predominant genera in the saliva are Prevotella, Streptococcus, and Veillonella. The resident flora are considered to be deeply linked with OM because they prevent colonization by exogenous organisms having pathogenic potential for local and systemic infections. However, the precise bacterial substitution occurring in HSCT patients with OM remains unclear. Here, we prospectively examined oral bacterial flora changes using VITEK MSTM (SYSMEX bioMérieux Co., Ltd., Tokyo, Japan)-an automated mass spectrometry (MS) microbial-identification system using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) technology. It can detect about 650 bacterial and 105 fungal species. We aimed to determine whether oral microbial in HSCT can be detected by VITEK MSTM. Patient and Methods This prospective study included 16 patients (10 males, 6 females; median age 52 years) who underwent HSCT for hematological malignancies (auto-PBSCT = 3 patients, allo-PBSCT = 3 patients, CBT = 10 patients; preparative regimen: MAC = 11 patients, RIC = 2 patients, auto = 3 patients) in our hospital between December 2015 and July 2016. All were treated in reverse isolation in a laminar airflow-equipped room and received drugs to prevent bacterial, fungal, and herpes virus infection. We used VITEK MS for analyzing oral bacterial flora. OM was diagnosed according to NCICTCAE v4.0 and WHO scale, and oral health was assessed using the Revised Oral Assessment Guide (ROAG). Microbial samples were obtained using swabs from bilateral buccal mucosa, palate, and tongue. Samples were then incubated at 37‹C for 72-96 hours both aerobically and anaerobically. Finally, VITEK MS was used to identify bacterial species in samples. We evaluated the patients before initiating preparative regimen (1st), day −1 before HSCT (2nd), 7 days after HSCT (3rd), 14 days after HSCT (4th), and 30 days after HSCT (5th). Results The percentage of patients with high-grade OM (CTCAE Grade 2-5, and WHO Grade 1-4) increased in days 7-14 and decreased at day 30 (Table). Total bacterial species numbers gradually decreased from days -1 through to 30. Many Streptococcus sp could be detected at the 1st or 2nd time point, but these speciesgradually decreased and were replaced with coagulase-negative staphylococci (CNS; Staphylococcus epidermidis in 10 patients, S. haemolyticus in 5 patients, S. lentus in 3 patients, andS.warneri in 3 patients). Before HSCT, Prevotella sp and Veillonella sp in the oral flora were detected in 10 and 9 patients, respectively. However, by 14 days after HSCT, Prevotella sp and Veillonella sp were isolated less often than other points. Candida sp was detected only after the preparative regimen. Discussion and Conclusion This is the first prospective study to demonstrate microbial substitution in oral bacterial spices in HSCT patients using VITEK MS. VITEK MS allowed for the reliable identification of clinically relevant bacteria. We found that the oral bacterial species changed from Streptococcus sp, Prevotella sp, or Veillonella sp to CNS or Candida sp after HSCT. Our results suggest that oral microbial substitution possibly underlies high-grade OM after HSCT. We also suspect that microbial substitution is partly modified by antibiotics, considering that all study patients were treated with antimicrobial agents (including beta-lactam antibiotics). Indeed, the presence of many beta-lactam sensitive Streptococcus sp decreased, whereas that of beta-lactam resistant strains (CNS and Candida sp)increased. Finally, this study involved a small and heterogeneous patient population with varying characteristics. Therefore, our results require confirmation in a larger number of patients over a longer period. Disclosures Hironaka: MEXT Supported Program for the Strategic Research Foundation at Private Universities: Research Funding.