Despite multiple advances in the management of PD, infections remain a crucial complication to be addressed and are a major predisposing factor for mortality, PD cessation, and hospitalization [1,2,3, 26, 27]. In particular, evidence on methods of PD catheter exit-site care is lacking. Therefore, we evaluated the effectiveness of SPI, which has attracted attention in other fields as an enhancer of ulcer and wound healing. Our multivariate model demonstrated that SPI use was associated with reduced risk of secondary ESI. However, its use did not show significant reductions in catheter infection-related surgical interventions or peritonitis. Concomitant TI at the first onset of ESI was a predictor. These findings indicated that SPI could be effective in preventing ESI, with early ESI diagnosis likely important for avoiding later invasive procedures and complications.

ESI incidence varies across time periods, facilities, and countries, generally ranging between 0.13 and 1.28 per patient-year [1, 6, 19, 28,29,30]. This wide variation may be partially attributed to the diverse definitions of ESI (such as presence of purulent drainage from the exit site or exit-site score ≥ 4) or diagnoses based on subjective observations [7, 20, 31]. The incidence of ESI in our study was higher (0.70 per patient-year), compared with the recent average rate in Japan (0.40 per patient-year) [32]. In contrast, we recorded an incidence of all-cause peritonitis of 0.20 per patient-year, near the Japanese average, achieving the target recommended by the International Society for Peritoneal Dialysis (ISPD) of 0.40 [7, 32]. Between 10 and 20% of all peritonitis cases have been estimated to be preceded by catheter infections, despite variations depending on the type of causative pathogen [33, 34]. As expected, the proportion of these patients was relatively high at 27.1%. Gram-positive bacteria were predominant in this study, consistent with findings in previous reports [5, 19, 33]. The details regarding the frequency discrepancy between peritonitis and ESI remain unclear. Nevertheless, the subjective reliance of ESI diagnosis on observational assessment may have had an impact. Additionally, the meticulous inspection of exit sites by physicians and nurses during each visit could have contributed to a higher probability of detecting ESI. Overall, the data on PD-related infections obtained from our hospital did not deviate significantly from the Japanese norms.

The ISPD guidelines recommend daily topical antibacterial treatments (although this recommendation has been downgraded according to the 2023 update), whereas the Japanese Society for Dialysis Therapy (JSDT) recommends the opposite opinion. We followed the recommendations by the JSDT in principle and therefore used these treatment less frequently [7, 8]. In our clinical setting, we confirmed that for exit sites in poor condition (assessed by the medical staff), physician-instructed SPI use prevented subsequent ESI. In those in good condition, SPI was not used because as it could take more handling time compared with conventional disinfectants. Sucrose, one SPI component, has been shown to enhance wound healing, sterility maintenance, and infection control [10, 12,13,14]. Although all forms of life require water for growth, sugars absorb exudates from their surroundings and mechanically clean necrotic tissue by creating an osmotic pressure difference [14, 35]. Sugars prevent and eliminate biofilms produced by a variety of organisms and function as a modulator of fibroblasts and keratinocytes [10, 12]. Povidone-iodine, the other component of SPI, is a well-known disinfectant with broad-spectrum antibiotic activity. However, this povidone-iodine component is cytotoxic and decreases fibroblast and macrophage survival, which may delay wound healing and promote secondary skin injury [36]. The iodine concentration in SPI is 3%, lower compared with more commonly used preparations (10%). Since its toxicity is concentration-dependent, SPI, with a low concentration of iodine and slow-release properties, is considered less harmful [37, 38]. Shiraishi et al. demonstrated that SPI with a low iodine concentration had sufficient antibiotic activity, despite taking slightly longer to sterilize compared with conventional povidone-iodine solutions [39]. The above SPI characteristics appear to favor its application to PD catheter exit-site care.

The therapeutic effect of SPI on existing ESI was also evaluated; unlike its preventive effects, no obvious beneficial effects were observed. However, we could not exclude the possibility that the small number of treatment efficacy-related outcomes made it difficult to appropriately evaluate these effects. The SPI group survival was not inferior to that in the non-SPI group. Therefore SPI use might have a positive impact. Given that SPIs have a lower risk of antimicrobial resistance and microbial substitution than do topical antibiotics, their use appears to be an effective, low-risk therapeutic option [40, 41].

Few studies have explored the risk factors for ESI. Based on the limited evidence available, ESI history, poor compliance with exit-site care, and mechanical injuries have been strongly associated with ESI occurrence [19, 20]. Moreover, there are no consistent findings regarding other factors, including age, sex, dialysis modality, or comorbidities [6, 19, 20, 30, 42]. We found no significant association between ESI development and any factor other than SPI use. Very few studies have directly evaluated subsequent outcomes of ESI. Au et al. reported that in patients with ESI caused by Serratia species, the presence of TI increases the risk of subsequent troublesome clinical courses [43]. In the present study, concomitant TI predicted events of surgical intervention and subsequent peritonitis regardless of the type of bacterium. These findings highlight the importance of early detection before progression of ESI to TI.

This study has several limitations. First, since this was a retrospective observational study, we were unable to adjust for some potential confounding factors, including a history of catheter pulling and mechanical stress, potentially leading to the modest predictive accuracy of all Cox models. As a matter of course, the direct causality between SPI use and low frequency of ESI development is also unclear. The patients with high presumably adherence to exit-site care might have been prioritized to receive SPI, taking time for management. Second, there are concerns regarding selection bias arising from the single-center design. Due to the limited sample size, the impact of SPI on the types of causative pathogens could not be evaluated. Also, only patients with a history of ESI were included in this study. This might limit the generalizability of our findings. However, the assessment of ESI relies on subjective rather than objective observations [20]. In terms of diagnostic consistency, this single-center design may have some merit. Furthermore, the situation surrounding PD-related infections was consistent with previous reports. Third, the patients did not routinely receive topical antibacterial therapy in the present study (in accordance with the recommendation by the JSDT, not the ISPD), the results of which should be interpreted with caution. However, it is noteworthy that although the SPI group used less local antimicrobial therapy, it had showed beneficial outcomes. Fourth, over the extensive 10-year observation period, a multitude of medical staff has been involved in the care for patients undergoing PD. Although accurate assessment is challenging, there is a possibility that the discretion in the use of SPI may not have been consistent. Finally, we compared the effectiveness of SPI with that of a disinfectant (mainly, povidone-iodine [10%]) under poor exit-site conditions. Our results may reflect the shortcomings of high-concentration povidone-iodine, such as local irritability. Indeed, several guidelines do not actively recommend its use [7, 8]. However, because this agent remains one of the most popular antiseptic materials for exit-site care in the real world, we suggest that the results of this study may have implications in daily clinical practice [44].

In conclusion, our study demonstrated that SPI use could be associated with a low risk of subsequent ESI in patients with PD and a history of ESI. Further definitive randomized controlled studies are required to confirm the efficacy of SPI.