Impact of dental clearance on bacteremia in hematopoietic cell transplantation

Infection is a concern in hematopoietic cell transplantation (HCT), being leading cause of morbidity and mortality (Gudiol et al., 2014). Consequently, guidelines recommend the pre-HCT elimination of oral infectious sites, known as dental clearance, in order to mitigate systemic dissemination (Rankin et al., 2008; Yamagata et al., 2006) and avert fatalities (Elad et al., 2008). Nevertheless, certain studies have reported no discernible improvement following pre-HCT dental clearance (Hong et al., 2018), doubts its necessity. With the objective of examining the relationship between pre-HCT dental clearance and bacteremia during the pre-engraftment phase resulting from bacteria predominantly found in the oral cavity (BPFOC), we gathered data from 681 patients who underwent either allogeneic or autologous HCT at Hadassah Medical Center in Jerusalem, Israel (Table 1). These patients were classified into three groups: (1) patients who underwent complete dental clearance; (2) patients who did not receive any pre-HCT dental assessment or clearance; and (3) patients who received dental evaluation but had only partial or no dental clearance. We conducted blood bacterial cultures, initiated in the event of fever (≥38.0°C/100.4°F) (Freifeld et al., 2011), up to 1 month post-hematopoietic cell transfusion. A skilled nurse collected the samples using aseptic technique, obtaining two sets (each comprising one anaerobic and one aerobic bottle; BD BACTEC™ Blood Culture Media, NJ, US) from distinct lumens of a peripherally inserted central catheter. For groups 1 and 3, we compiled data on dental morbidity, and dental treatment. While this study encompasses a substantial cohort of 681 patients, a noteworthy constraint lies in the relatively limited subset that underwent comprehensive dental assessment and completed the prescribed dental treatment plan. Additionally, the laboratory protocol employed was not fine-tuned for optimal detection of oral microorganisms, thus the reported findings may represent an underestimation of the actual microbial landscape. Another factor contributing to the potential underestimation of bacteremia from the oral cavity is the likelihood of a microbial shift in immunocompromised patients and those with OM. This shift may introduce microorganisms not typically found in the oral microflora. Consequently, instances where bacteria originate from the oral cavity might not be identified as such. Despite these limitations, the data yield interesting findings that hold statistical significance, providing valuable clinical insights. Dental clearance and maintaining oral health are of paramount importance, particularly for young individuals and those experiencing oral symptoms. In such cases, merely extracting infected teeth is insufficient; a comprehensive dental clearance is warranted. The findings of this study can elucidate the abovementioned disparities observed in research, some indicating the advantages of dental clearance (Yamagata et al., 2006), while others point to its ineffectiveness (Melkos et al., 2003; Sultan et al., 2017). In populations with accessible dental care and good oral health, studies may not detect statistically significant benefits from dental clearance (Dean et al., 2023; Nuernberg et al., 2016; Sultan et al., 2017). Nevertheless, on an individual level, it becomes evident that preparatory dental care holds significance when dental morbidity is involved. To streamline resources and alleviate the patient's burden, it becomes imperative to identify those individuals who will derive benefits from dental clearance. This decision should also consider the necessity of dental treatment to prevent and mitigate OM (Elad et al., 2015; Elad et al., 2020). Considering that bloodstream infections during the pre-engraftment period after allogeneic HCT are primarily associated with the presence of neutropenia, (severe) mucositis, and central venous catheters (Gudiol et al., 2014), it is plausible that the anti-mucositis effect of dental and oral care may indirectly result in a reduction in bloodstream infections. Moreover, the determination of the scope of dental treatments before HCT should also consider that patient will be unable to undergo elective non-urgent dental procedures during the post-transplant phase in time of immune reconstitution, typically spanning up to 1 year (Elad et al., 2021). In summary, this study underscores the critical importance of thorough dental assessment and clearance as an essential element of the care protocol for patients with (symptomatic) dental conditions undergoing either autologous or allogeneic HCT, with a specific focus on young individuals. To reduce the risk of bacteremia resulting from oral pathogens, the removal of infected teeth alone may prove insufficient; therefore, it is imperative to diligently follow the complete dental treatment plan for such patients. The study protocol received approval from the Institutional Review Board of Hadassah Medical Center, with a waiver of consent for participation due to the retrospective design of the study. Yehuda Zadik: Conceptualization; investigation; writing – review and editing; writing – original draft. Andrey Krasovsky: Writing – original draft; formal analysis; investigation; data curation; writing – review and editing. Refael Cohen: Writing – review and editing; visualization. Andra Rettman: Writing – review and editing; visualization. Doron J. Aframian: Supervision; writing – review and editing. Batia Avni: Writing – review and editing; validation. Avi Peretz: Writing – review and editing; validation. Naama Keshet: Methodology; conceptualization; investigation; writing – review and editing. None. The data that support the findings of this study are available from the corresponding author upon reasonable request.