The epidemiology of fracture-related infections in Germany

The epidemiology of fracture-related infection (FRI) is unknown, which makes it difficult to estimate future demands and evaluate progress in infection prevention. Therefore, we aimed to determine the nationwide burden’s development over the last decade as a function of age group and gender. FRI prevalence as a function of age group and gender was quantified based on annual ICD-10 diagnosis codes from German medical institutions between 2008 through 2018, provided by the Federal Statistical Office of Germany (Destatis). The prevalence of FRI increased by 0.28 from 8.4 cases per 100,000 inhabitants to 10.7 cases per 100,000 inhabitants between 2008 and 2018. The proportion of fractures resulting in FRI increased from 1.05 to 1.23%. Gender distribution was equal. Patients aged 60–69 years and 70–79 years comprised the largest internal proportion with 20.2% and 20.7%, respectively, whereby prevalence increased with age group. A trend towards more diagnoses in older patients was observed with a growth rate of 0.63 for patients older than 90 years. Increasing rates of fracture-related infection especially in older patients indicate an upcoming challenge for stakeholders in health care systems. Newly emerging treatment strategies, prevention methods and interdisciplinary approaches are strongly required.


Results
In 2018, a total number of 7253 FRI cases were listed in Germany. In comparison to 5556 cases in 2008, the overall prevalence substantially increased with a growth rate of 0.28 from 8.4 cases per 100,000 inhabitants to 10.7 cases per 100,000 inhabitants. Accordingly, the proportion of fractures resulting in FRI increased from 1.04 to 1.23% ( Table 2).
The internal gender distribution was equal with 50.8% male cases and 49.2% cases in 2018, whereby the prevalence of FRI was slightly higher in the male population (11.1 cases per 100,000 inhabitants) than for the female population (10.3 cases per 100,000 inhabitants) (Fig. 1, Table 3).
Regarding the prevalence for distinct age groups, cases per 100,000 inhabitants steadily increased with age. For 2018, 35 cases were calculated per 100,000 per inhabitants aged 90 years or older, 24.9 cases per 100,000 per inhabitants aged 80-89 years and 19.5 cases per 100,000 per inhabitants aged 70-79 years, whereas only 3.4 cases were estimated per 100,000 per inhabitants aged 20-29 years and 4.1 cases per 100,000 per inhabitants aged 30-39 years. Relative to the year 2008, a trend towards more FRI diagnoses in older patients can be observed. Highest growth rates were found for patients aged 90 years or older (0.63) and patients aged 70-79 years (0.28) ( Table 4, Fig. 2).  www.nature.com/scientificreports/ Regarding the constituent ratio, explaining the internal proportion of infection, in 2018 patients aged 70-79 years comprised the largest cohort with 20.7%, followed by patients aged 60-69 years (20.2%) and patients aged 50-59 years (19.3%). Comparing the age distribution as a function of gender, it becomes apparent that older patients were predominantly female. For instance, 6.30% of female cases were aged 90 years or older compared to 1.11% male cases, 23.47% female patients aged 80-89 years versus 8.58% male cases in this increment and 24.64% women aged 70-79 years in relation to 16.89% men of this age. In the age increments 50-59 years, more male cases were registered than female cases (23.60% versus 14.84%). The same applied for patients aged 40-49 years with 13.17% male cases compared to 6.05% affected women (Fig. 3).

Discussion
In this population-based study, trends in the epidemiology of fracture-related infections were described and prevalence was analyzed as a function of gender and age group. To the best of our knowledge, this study is the first one describing the nationwide burden of FRI.
A literature review estimated that fracture-fixation device infections comprise < 5% of all implant associated infections 14 , whereas a single center cohort study at Geneva University Hospital pooling clinical data on orthopaedic infections reported that 24% of all cases involved osteosynthetic material 15 . In general, prevalence data on FRI vary in the literature. For instance, a multi-center study carried out in India included 787 participants with tibia fractures, estimating the incidence of infection as 1.6% for closed fractures and 8.0% for open fractures 16 19,20 . Additionally, a review on open femoral shaft fractures treated with intramedullary nailing estimated an infection rate of 6%, whereas another review reported infection rates in the range of 0.9-11.6% comparing outcomes of open tibial fractures 21,22 . In light of the diversity of findings, describing the nationwide burden of FRI seems useful. Here, an overall FRI rate of 1.23% was estimated for the year 2018 based on calculated total numbers of fracture cases, which is lower than previously reported. Differences might be explainable by the distinct considered fracture types and sites, heterogeneity in the study design as well as center-specific treatment procedures. Further, our analysis revealed that the prevalence of FRI increased with a rate of 0.28 from 8.4 cases per 100,000 inhabitants to 10.7 cases per 100,000 inhabitants between 2008 and 2018. The distribution of male and female cases was equal in our analysis, whereas research increasingly addresses immune response gender differences 23,24 . The observed trend towards more FRI diagnosis in older patients possibly reflects demographic changes such as population decline and aging, which challenge the healthcare system not only in Germany. In consideration that prevention strategies and improved treatment algorithms for optimal patient care moved into focus of orthopedic research 2,10,25 , the increase of infection rates over the last decade seems surprisingly high. This might be attributable to heightened prevalence of obesity, which has risen substantially and the fact that Germany is rated among the countries with the highest prevalence of tobacco use in Europe 26,27 . Further, an extrapolation of hospital-based data to the German population revealed 16,742 severely injured persons per year and at least 5.8 million German inhabitants have received a medical diagnosis of type 2 diabetes, which may contribute to rising FRI numbers [28][29][30] . Table 4. Historic development from 2008 through 2018 of all fracture-related infection cases as a function of age group. Data is shown as total numbers, percentage and prevalence per 100,000 inhabitants of the considered age group.