Rising incidence of severe maxillofacial space infections in Germany

Objectives Severe maxillofacial space infection (MSI) as an end stage of dentoalveolar diseases or complication of sialadenitis is a potentially life-threatening disease accompanied by complications including airway obstruction, jugular vein thrombosis, descending mediastinitis, sepsis and acute respiratory distress syndrome. The aim of this study was to analyze the incidence and time trends of severe MSI and potentially influencing factors in the German healthcare system over time. Materials and methods Nationwide data regarding the national diagnosis-related-group (DRG) inpatient billing system was received from the German Federal Statistical Office. A retrospective analysis of incidence and time trends of MSI-associated procedures classified with the Operation and Procedure Classification System (OPS), were statistically evaluated using Poisson regression analysis between 2005 and 2022 and were associated with different epidemiological factors. Results The total standardized incidence rate of MSI-associated procedures in the observational period 2005—2022 was 9.8 (♀8.2; ♂11.4) per 100,000 person years. For all age groups a significant increase of 46.1% in severe MSI – related surgical interventions was registered within the observational period. The largest increase (120.5%) was found in elderly patients over 80 years. There were significant differences of the incidences of MSI-associated surgeries between the different federal states in Germany. Conclusions Severe MSI are a growing challenge in German health care especially among elderly patients over 80 years. Clinical relevance Severe MSI is a promising target for prevention. There should be more focus in primary dental and medical care especially in groups depending on social support.


Introduction
Severe maxillofacial space infections (MSI) are defined as cellulitis or abscess formations of the fascial planes and potential spaces of the head and neck [1].Early identification and therapy are crucial in prevention of severe potential life-threatening complications such as upper airway obstruction, descending mediastinitis, pleural empyema, pericarditis, jugular vein thrombosis, sepsis or carotid pseudoaneurysm [2].Even lethal outcomes were documented [3,4].Most common primary sources of MSI are end stage of dental disease, complication of sialadenitis, perioperative complication or malignancy [5].Microbiology typically reveals a mixed bacterial flora, including anaerobic species, that can rapidly progress.Usually, the results of cultures are polymicrobial, and are often caused by oral bacteria.Streptococci are the organisms most commonly cultured from MSI [6].Since the main symptoms of infection are similar between the different etiologies, clinical diagnosis may be difficult [7].Identification of causative factors may require radiological examination with ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI).Historically, with the introduction and widespread availability of antibiotics the incidence and severity of this disease have declined dramatically.The wide availability of dental care is also an important factor in prevention of MSI [8,9].
The pillars of treatment are appropriate antimicrobial therapy, sufficient surgical drainage, endodontic or surgical treatment of causative teeth as well as the early management of complications [5,10].A calculated empirical antibiotic treatment is necessary until culture-guided antimicrobial therapy is available [11].Improving the immunological status can have a significantly positive influence on the course of the disease in patients with systemic risk factors such as diabetes mellitus, end stage renal disease or autoimmune disorders [12].Especially in an aging society with increasing multimorbidity and social imbalance MSI continue to represent a challenge with potentially preventable mortality [13,14].However, population-based data about trends in the incidence of severe MSI due to its different causes are limited and may be inconclusive.
Studies from the UK report that the incidence of MSI has increased within the last decades as growing health inequalities are leading to an increase in hospital admissions due to severe odontogenic infections [15,16].To our knowledge, there is no conclusive data from any other central European country.The purpose of this study was therefore to investigate the nationwide incidence of severe MSI in Germany.For this purpose, the regional, gender-specific and agerelated distribution of patients suffering from severe MSI who required inpatient external incision and drainage in different maxillofacial regions was evaluated.

Materials and methods
The national diagnosis-related groups (DRG) inpatient billing system includes data from all hospitals in Germany that use the DRG system.More than 99% of inpatient treatments are covered.Hospitals are required by law to provide comprehensive information about hospital care, including patient demographics, diagnoses, comorbidities, complications and procedures.
Surgical procedures from the years 2005 to 2022 were coded according to the OPS (Operation and Procedure Classification System), a German modification of the ICPM (International Classification of Medical Procedures).All diagnoses were coded according to the ICD-10GM (German version of the International Classification of Diseases and Related Health Problems, 10th Edition).Detailed lists of all procedures regarding extraoral incision and drainage of severe MSI per year (coded 5-270.0 to 5-270.9;5-270.xand 5-270.y in the OPS) were provided by the German Federal Statistical Office (Statistisches Bundesamt-Destatis.Genesis-Online.Data license by-2-0).MSI-associated procedures per year (PPY) were calculated and reported.Mean age of patients was calculated.The normality of the distribution of continuous variables was tested by Kolmogorov-Smirnov test.Continuous variables with normal distribution were presented as mean and standard deviation.Means of 2 continuous normally distributed variables were compared by independent samples Student's t-test.The differences were considered significant at p < 0.05.In addition, population-adjusted rates of MSI-associated surgeries per 100,000 person years were calculated using population data also provided by the German Federal Statistical Office and reported with 95% confidence interval.In order to avoid seasonal influences, the MSI-associated infection procedures were analyzed on an annual basis.We performed the main analysis for the entire population and the analyses stratified by sex, age group and federal state.We computed crude and age-sex standardized incidence rates of severe MSI for each calendar year, taking the German population of the latest census 2011 as standard population using 0-14, 15-34, 35-59, 60-79 and ≥ 80 years as age classes to exclude bias due to demographic heterogeneity over time.To ascertain male and female incidence rates, age standardization was performed with the aforementioned age classes using the age distribution of the male and female standard population resulting in different weights for both genders.The calculation of the 95% confidence intervals (95% CI) of crude and standardized incidences was performed by the delta method.Separate Poisson regression models were computed to investigate time trends, fitted with incidence rates of MSI as dependent variables and age group, gender, federal state and year of MSI starting from baseline year 2005 as independent variables.The age class 15-34 years, female sex and federal state of Baden-Württemberg were used as reference group.All models were adapted by descale adjustment to account for overdispersion of the outcome variable.Statistical analysis was performed using IBM SPSS Statistics Version 29.0 (IBM Deutschland GmbH, Böblingen, Germany).

Results
In the observational period 2005-2022 a total of 144,881 MSI-associated procedures were registered in Germany and could be included in the study.The distribution regarding age, gender and year of cases treated for severe MSI is presented in Table 1 and Fig. 1.The majority of cases were older than 35 years (68.4%) and male (57.2%).The mean age increased within this period from 45.0 years between 2005 and 2013 to 48.6 years between 2014 and 2022 (p < 0.01).The age and gender standardized incidence rates of procedures associated with severe MSI are shown in Table 2, Figs. 2 and 3 for the total population and stratified by gender and age.The total standardized incidence rate of MSI-associated procedures in the observational period 2005-2022 was 9.8 per 100,000 person years [95% CI: 9.7-9.8]ranging from 7.6 [7.4-7.8] in 2005 to 11.6 [11.4-11.8] in 2019.In 2022 the incidence was 11.1 [10.9-11.3],an increase of + 45.7% within the observational period.Gender distribution slightly shifted from 59.5% in males and 40.5% in females in 2005 to 56.7% and 43.3% in 2022, respectively.In males the overall incidence was 11.4 [11.3-11.5]spreading from 9.1 [8.8-9.4] in 2005 to 13.6 [13.3-14.0] in 2019, in females the total incidence rate was 8.2 [8.1-8.3]varying between 6.2 [6.0-6.5] in 2005 and 9.7 [9.4-10.0] in 2019.

Discussion
Despite good access to dental care, availability of antibiotic therapy and good socioeconomic conditions, severe MSI is a persistent challenge in general and oral healthcare.Its main cause is end stage dentoalveolar disease leading from caries, periodontal disease to cellulitis and abscess formation.It is still an important cause of hospitalization in oral and maxillofacial surgery departments [13].However, reliable population-based data about long-term trends, age and gender distributions in the incidence of severe MSI are limited and may be inconclusive due to its different causes and clinical presentations.Most available data were collected from single center case series and therefore may not be representative.To our knowledge, this is the first populationbased study to investigate the incidence of severe MSI using Germany's DRG inpatient billing data base, which includes data on the entire population of Germany.
During the observational period from 2005-2022 we were able to detect a significant increase in the incidence of severe MSI requiring external incision and drainage in Germany.The phenomenon of rising incidence of severe MSI affects the entire society and is not limited to distinct regions, genders or age groups.These results were in accordance with other data describing an increase in maxillofacial infections.Robertson  hospitals of National Health System in the United Kingdom rising from 1.71 per 100,000 person years in the year 2000 to 5.36 per 100,000 person years in 2020 [15].Similar data for the UK were published by Thomas et al. in 2008 [16].Allareddy et al. analyzed 29,228 hospitalizations due to oral infections between 2004 and 2010 in the USA with an increasing number over time [17].Seppänen et al. describe an increase of maxillofacial space infections requiring hospital care in the Helsinki and Uusimaa Hospital District in Finland representing more than 25% of the population in Finland with an increase from 5.3 per 100,000 inhabitants in 1995 to 7.2 per 100,000 inhabitants in 2005 [18].Yang et al. saw a slight increase in head and neck space infections in Taiwan from 2.47 per 100,000 person years in 2007 to 3.71 per 100,000 person years 2016 [19].

et al. report an increasing number of hospital admissions due to odontogenic infections in the
Odontogenic infections are the main cause of MSI and can usually be found in more than 80% of all cases [20][21][22].The caries experience among younger adults (35-44 years) in Germany has declined from 16.1% in 1997 and 14.6% in 2005 to 11.2% in the last national oral health study in 2014 [23][24][25].Also caries experience in younger seniors (65-74 years) has declined from 23.6% in 1997 and 22.1% in 2005 to 17.7% in 2014 [23][24][25].At first sight the improvement in societal oral health is contractionary to the increase in severe MSI.The increase might be more associated to individual social subgroups.Caries prevalence, number of missing teeth and edentulism as measures of oral health are significantly associated with lower income and lower education in Germany [26].The association of these social factors with oral health and reduced utilization patterns increased over the last decades [27].This may lead to a social disparity in oral health and, as a result, to an increase in severe infections in most disadvantaged groups.This is in alignment with data from the UK by Moles et al. reporting an increasing incidence of dental abscesses which is mostly driven by poorer people and strongly associated with the relative deprivation of the area of residence [28].
The phenomenon of rising incidence of severe MSI s not limited to individual genders or age groups.Nevertheless, some epidemiological factors are more predisposing than others.Male gender is an important predisposing factor as there is a consistent male preponderance in every study year  which is in accordance with the literature showing that odontogenic infection are more prevalent in males [21,[29][30][31].
We also found incidence differences between age groups that were observed consistently over the 18-year observational period.Elderly people over 80 years of age have the highest incidence rates of severe MSI and they also share the strongest increase over time followed by older adults between 60 und 79 years.Seemingly contradictory at first glance, dental diseases including caries, tooth loss and edentulism decline in the German society as well as globally [32,33].This means a higher number of teeth is preserved in elderly people.There they are "teeth at risk" for dental disease and may act as a source of infection, especially when accompanied by systemic diseases associated with age such as dementia, tremor, diabetes, which have a negative impact on personal oral hygiene and oral health [34].Together with a lower level of medical utilization due to limited mobility, this may result in a situation that is predisposing to advanced maxillofacial infections.This could be possibly a contributing factor for the increase in the number of MSI in these age groups.In patients with systemic diseases, the spread of the odontogenic infection requiring inpatient treatment and the occurrence of complications during the course of the disease are more common than in patients without systemic diseases [12,18,35,36].As systemic risk factors and comorbidities like diabetes, obesity, cardiovascular disease and mental disorders are on the rise, the risk for severe MSI may also increase over time especially in the age groups most affected by these conditions [37][38][39][40].Further studies are needed to identify potential risk factors and risk groups for severe odontogenic infections [41].MSI are usually caused by a polymicrobial variety of aerobic and anaerobic bacteria [20,21,42,43].A shift in the microbiological composition within odontogenic infections have been determined in preceding studies [42,44].Streptococcus species are the most frequently identified bacteria in MSI followed by Prevotella species and Staphylococcus species [45][46][47].Antibiotic resistance is a common phenomenon in odontogenic infections with prevalence of more than 40% to at least one antibiotic agent [45,48].Accordingly, increased attention must be paid to the initial empiric antibiotic therapy.Penicillin-group antibiotics continue to be highly effective against Streptococci, Prevotella and Staphylococci while Clindamycin could not be shown to be effective as an empirical drug of choice for a high number of odontogenic infections [20,29,49].In a recent study on antimicrobial resistances in oral-and maxillofacial infections in more than 20,000 clinical isolates from dental  [48].Moreover increasing resistance against clindamycin is an emerging problem in different bacteria and along different clinical settings [50][51][52][53][54][55].The German S3-guideline on odontogenic infections recommends clindamycin only as a second-line antibiotic in the presence of an allergy to penicillin group antibiotics [56].Nevertheless clindamycin is with more than 23.4% of all antibiotic prescriptions still the second most prescribed antibiotic among dentists in Germany [57].In contrast to Germany clindamycin is rarely dentally prescribed in other industrialized countries like Great Britain, Norway or Canada [58][59][60].
Increased resistance rates for clindamycin require clarification among dentists in order to prescribe antibiotics according to national and international guidelines and the current scientific knowledge.
Increasing number of MSI requiring inpatient treatment with external incision leads to an increasing burden for the health system.There is only scarce data on costs caused by odontogenic infections in Germany [61].Most Studies on this topic were conducted in the USA and Great Britain [62][63][64].Due to the differences in the health systems, it is only insufficiently possible to transfer the results to Germany.Nevertheless, with an increasing incidence of inpatient treatments of MSI a relevant increase in financial expenditure for these conditions seems likely.Since reimbursement by statutory health insurance cannot fully cover the costs of treating these patients, this type of disease represents an economic burden not only for the cost bearer but also for the treating department [61].
This study is subject to certain strengths and limitations, which are mainly related to the dataset that was available for analysis.First, the specific reimbursed OPS codes from the national DRG system database only represent MSI treated by external incision and drainage in the analyzed years.MSI treated non-surgically are not included in the dataset.Second, the study only includes MSI cases requiring a hospital admission that led to the billing of a DRG.Patients treated as outpatients or who use other reimbursement schemes could not be included.
Since statutory health insurance in Germany provides a fully accessible and affordable healthcare system for every citizen and MSI is a serious and progressive disease that requires immediate medical attention and hospitalization, we assume that we can cover the vast majority of the German population and provide a comprehensive overview.Selection bias in MSI determination due to socioeconomic status is limited by the population-based approach.The completeness of our description is only limited by the dataset itself, which provides information at only an aggregated level and in limited detail without information about a specific cause or severity of the infection; therefore, a more advanced analysis including anamnestic and diagnostic information was not possible.This would, however, be interesting to evaluate the reasons for the increasing rate of severe MSI further.Nevertheless, the DRG inpatient billing data base provides an excellent tool for German researchers to perform large-scale clinical epidemiology investigations on procedures and diseases.The use of claims data also avoided recall bias and misclassification bias that may result from studies based on self-reported data.
To the best of our knowledge, as initially aimed, this study is the first to examine the incidence, time trends and epidemiological distribution of severe MSI at a national level in Germany after more than twenty years.It can contribute to an analysis on the influence of population structure and oral health care on the occurrence of severe MSI.The description of negative effects can contribute to the future addressing of risk groups who may take profit from early oral health care motivation or intervention.For this purpose, the investigation of the direct influence of social background should be expanded.

Conclusion
The study suggests an increasing incidence rate of severe MSI in Germany over the last decades.This is not limited to certain regions, genders or age groups.Elderly patients over 80 years of age represent the social group that poses the greatest challenge.They present the highest increase in incidence over time and are beyond this the fastest growing age group in an aging society.Thus, severe MSI is an increasing challenge even in countries with comprehensive health care like Germany.As severe MSI is a promising target for prevention there have to be more focus on early detection and management of odontogenic infections.

from 8 .
3 [7.3-9.2]  in 2005 to 18.3[17.3-19.4] in 2022 and the strongest increase of 120.5% during this period.Looking at the 16 federal states individually the overall incidence of surgical procedures associated with severe MSI within the observational period ranged from 5.8 [5.6-6.0] in Schleswig-Holstein to 16.3 [15.8-16.9] in Saarland as shown in Table 3.A single year minimum was seen in Schleswig-Holstein in 2006 with 4.2 [3.4-4.9].A single year maximum was registered in Saarland with 22.3 [19.4-25.2] in 2017.

Fig. 1 a
Fig. 1 a Age-gender-diagram of the total number of MSI-associated procedures 2005-2022.b Age-gender-diagram of the German population based on census 2011

Table 2
Incidence of severe MSI-associated procedures in Germany 2005-2022.Incidence rates (95% confidence interval) per 100,000 person years standardized to the German population based on the Census 2011

Table 3
Regional incidence of severe MSI in all 16 federal states of Germany 2005-2022.Incidence rates (95% confidence interval) per 100,000 person years standardized to the German population based on the Census 2011

Table 4
Results of the Poisson models for total population and stratified by gender and age group(Germany, 2005(Germany,  -2022)   )

Table 5
Results of the Poisson models stratified by federal state (Germany, 2005-2022).Relative risk for severe MSI (95% Confidence interval)