The observed incidence rates indicate a consistent decline in CDI over time, aligning with recent claims data studies [17, 25] and providing updated epidemiological insights. The estimated hospital incidence is slightly lower than previously reported [6, 16], likely due to methodological differences; inpatient cases in this study could only be reliably identified upon discharge and subsequent readmission. Furthermore, under the definition of inpatient CDI cases applied in this study, readmissions within 10 days were not classified as new CDI events. It should be noted, however, that the presented data only cover the period up to 2022. According to the most recent data from the German National Reference Center for Nosocomial Infections (NRZ), a renewed 18% increase in hospital-treated CDI cases was recorded in 2024, indicating a potential reversal of the previous downward trend [25].

Our study also examined the burden of recurrent CDI. Approximately 13% of patients experienced at least one recurrence, emphasizing that recurrences remain a significant concern. The risk of a second recurrence (18%) underscores the growing burden of recurrent CDI, particularly in inpatient settings, where recurrence rates were higher. In contrast, recurrence rates were lowest in the outpatient sector, suggesting potential differences in patient characteristics or treatment approaches. These differences may, in part, be explained by the generally lower clinical severity observed in outpatient cases, as reflected by the substantially lower 30-day and 1-year mortality rates in this group. Patients treated in outpatient settings are likely to be younger, have fewer comorbidities, and present with milder disease courses, all of which may contribute to a reduced risk of recurrence compared with those treated in inpatient settings. Notably, third recurrences were relatively rare, though the limited number of cases may have affected reporting. Overall, recurrence rates were considerably lower than in the previous German claims data studies by Lübbert et al. from 2016 [23] and by Tricotel et al. published in 2024 [23]. These notably lower recurrence rates compared with earlier studies might also reflect a shift in the composition of circulating CDI ribotypes, potentially involving a decrease in hypervirulent strains. Although ribotyping data were not available in this study, this hypothesis is supported by clinical observations and warrants further investigation. From a clinical perspective, the observed trend is consistent with the milder disease courses documented, especially in outpatient settings.

Nevertheless, our analysis demonstrated that approximately 43% of all recurrences were treated in the outpatient setting. This finding aligns with the ongoing trend toward outpatient care in the German healthcare system. However, it also highlights the importance of implementing up-to-date clinical guidelines to ensure guideline-adherent treatment of CDI in all care settings. Furthermore, a thorough patient history should be obtained, as the results indicate that only a small proportion of recurrences are correctly identified as such. The limited use of specific recurrence coding suggests that recurrent CDI cases may be undercoded or inconsistently documented in routine data.

During the study period, outpatient CDI treatment patterns shifted substantially, with a notable decline in metronidazole use, particularly for recurrent cases. This decrease between 2017 and 2022 aligns with guideline recommendations discouraging metronidazole use as first-line treatment for CDI [15]. In parallel, vancomycin prescriptions increased, especially for first and second recurrences. Although the use of fidaxomicin increased slightly, its overall use remained comparatively limited. While these trends indicate a tendency toward guideline-concordant outpatient management of CDI, it is important to acknowledge a major limitation of our study: Treatment administered during inpatient stays could not be assessed. Since inpatient cases tend to be more severe, it is likely that fidaxomicin is used more frequently in this setting. Nonetheless, these findings reflect an adaptation of treatment practices in accordance with updated guidelines, favoring more effective therapies for recurrent CDI cases [13, 14].

The incidence of severe CDI cases declined from 2017 to 2022, mirroring the overall incidence observed in other studies [16]. However, the observed rates remain considerably higher than the figures reported by the RKI [26,27,28,29,30] and also account for approximately 38% of all annual CDI cases in the study population. This discrepancy may reflect differences in case definitions, reporting practices, or data sources. It should also be emphasized that severe cases were identified on the basis of claims data, which may contribute to the differences in reported rates. Notably, Heudorf et al. also identified signs of under-reporting in CDI-associated mortality, further highlighting potential limitations in national surveillance and documentation systems [31]. According to the RKI, potential reasons for this discrepancy include the limited acceptance of the reporting criteria, which are perceived by physicians as too complex and associated with additional administrative burden. These findings reinforce the ongoing need for close collaboration between public health authorities and hospital hygiene departments [32]. It should be noted that all deaths within the specified time horizon were included in the analysis without distinguishing the cause of death.

The occurrence of CDI was associated with a 1.9- to 2.1-fold increase in 1-year mortality compared with matched control patients, independent of the care setting. Mortality risk varied on the basis of the number of recurrences, with the highest risk observed in patients experiencing two or more episodes. These findings confirm that recurrent CDI is a strong predictor of adverse long-term outcomes. In contrast, the slight decrease in mortality among patients without recurrences suggests potential improvements in general CDI management. However, the pronounced increase in mortality among patients with multiple recurrences underscores the urgent need for effective prevention and treatment strategies. Given the low case numbers in this subgroup (fewer than ten cases per group), further studies with larger datasets are necessary to confirm these findings.

Our study findings indicate a steady decline in CDI-related mortality over the study period. However, these rates remain higher than those published by Lübbert et al. in 2016, and are in line with the more recent observations by Antunes et al. [33], who also analyzed CDI outcomes within the German healthcare system [23, 33]. In consequence, CDI remains a significant contributor to mortality, particularly among elderly individuals and patients who are hospitalized. The observed age-related mortality is consistent with previous research, reaffirming advanced age as the most critical risk factor for CDI-related death. Mortality was highest among inpatient cases, especially when CDI was documented as a secondary diagnosis. The role of comorbidities in CDI-related mortality was evident, with renal insufficiency identified as a significant risk factor.