Update on Focal Infection Management: A Czech Interdisciplinary Consensus

Abstract

Background

The focal infection theory has been used to explain several chronic systemic diseases in the past. Systemic diseases were thought to be caused by focal infections, such as caries and periodontal diseases, and dentists were held responsible for these diseases due to the spread of oral infections. As knowledge of the interrelationship between oral microorganisms and the host immune response has evolved over the last few decades, the focal infection theory has been modified in various ways. The relationship between oral and systemic health appears to be more complex than that suggested by the classical theory of focal infections. Indeed, the contribution of the oral microbiota to some systemic diseases is gaining acceptance, as there are strong associations between periodontal disease and atherosclerotic vascular disease, diabetes, and hospital-associated pneumonia, amongst others. As many jurisdictions have various protocols for managing this oral-systemic axis of disease, we sought to provide a consensus on this notion with the help of a multidisciplinary team from the Czech Republic.

Methods

A multidisciplinary team comprising physicians/surgeons in the specialities of dentistry, ear-nose and throat (ENT), cardiology, orthopaedics, oncology, and diabetology were quetioned with regard to their conceptual understanding of the focal infection theory particularly in relation to the oral-systemic axis. The team also established a protocol to determine the strength of these associations and to plan the therapeutic steps needed to treat focal odontogenic infections whenever possible.

Results

Scoring algorithms were devised for odontogenic inflammatory diseases and systemic risks, and standardised procedures were developed for general use.

Conclusions

The designed algorithm of the oral-systemic axis will be helpful for all health care workers in guiding their patient management protocol.

Introduction

The origins and popularity of the focal infection theory

Hippocrates established the first link between dental disease and widespread disease around 400 BC, when he achieved remission of arthritis by tooth extraction. In the early 19th century, influential American physician Benjamin Rush published similar experiences.¹ When Robert Koch discovered Bacillus anthracis in 1876 and subsequently Mycobacterium tuberculosis in 1882, his work marked not only the beginning of a scientific approach to medicine but also the beginning of an era of hunting for bacterial agents of every known disease, including noninfectious diseases.2, 3, 4 This process occurred in a period philosophically influenced by pragmatism and positivism, whose framework of thought fit the discoveries conveniently.^5,6 Willoughby D. Miller, the father of the chemical-parasitic theory of dental caries, linked oral cavity bacteria to diseases in distant organs.^7,8 The term focal infection was first used by Frank Billings in 1911.^9,10 Billings based his theory on the views of William Hunter, who coined the term oral sepsis. Hunter considered deviated teeth, gingivitis, periodontal lesions, tonsillitis, and other diseases in the mouth to be sources of pus that spread further into the body. He was a critic of restorative dentistry and prosthodontics.¹¹ His lecture at McGill University in Montreal in the year 1911, in which he presented a case of sepsis in a patient who had never removed removable dentures from his mouth, increased the popularity of the focal infection theory in North America.^1,12,13

Amongst the proponents of focal infection theory were prominent and influential physicians, including the founders of the Mayo Clinic, brothers William and Charles Mayo, and Russell Cecil, the author of the most widely used medical textbook at that time. Thus, the theory gained considerable respect in the 1920s, particularly in the US.^14,15 The remediation of apparent and presumed infectious foci has been regarded not only as a treatment but also as a preventive measure for many systemic diseases.¹⁶ Convincing evidence for an association between odontogenic infectious foci and other diseases is lacking, and theories explaining this discrepancy have been developed and proven. Examples include Rosenow's idea of selective localisation and transmutation, whereby one bacterial strain may change to another (eg, viridans streptococci to pneumococci) when expanding from its original location. Transmutation creatively explains the inability to reproduce research results in other independent laboratories.¹⁷ Although convincing to some, studies such as those by W. Price and E. C. Rosenow demonstrated that the validity of the theory had significant methodological flaws (missing control groups and unrealistically large infectious loads).^18,19 Despite these flaws, proponents of the focal infection theory were convincing and influential, almost succeeding in outlawing salvage dentistry, endodontics, and prosthodontics in the US, resulting in the virtual cessation of teaching endodontics.20, 21, 22

Criticism and decline

As preventive tooth extractions increased, criticism of the focal infection theory increased. One of the first was the pioneer of dental radiology, Edmund C. Kells, who rejected unwarranted tooth extractions.²³ The results of independent studies also testified against treating chronic diseases by surgically eradicating the putative foci of focal infection. The first study was by Kopeloff, Cheney, and Kirby (1922), and it refuted surgical interventions, including tooth extractions, in 2 independent samples of psychiatric patients. Their work was the first significant epidemiologic research in psychiatry.24, 25, 26 In addition, Russell Cecil, originally a prominent proponent of the focal infection theory, found that neither tonsillectomy nor complete tooth extraction significantly affected the course of the disease in a cohort of 200 patients with rheumatoid arthritis.²⁷ In 1940, Reimanand and Havens published a critical review that rejected focal infections as the sole cause of other diseases.²⁸ The American Dental Association devoted an entire issue (6/1951) of its official journal (Journal of the American Dental Association) to focal infection and favoured conservative methods of treating teeth with nonvital pulp.²⁹ The introduction of antibiotics (ATB) to clinical use after World War II marked the retreat of the focal infection theory in mainstream medicine for nearly 40 years.³⁰ In the case of bacterial endocarditis, a consensus persists on the need to prevent streptococcal bacteremia, including the recommended ATB prophylaxis (high-dose ATB prior to the procedure) for invasive dental procedures.³¹

New context

With the development of modern culture methods and the identification of bacteria (a significant problem in the past was the identification of anaerobic bacteria), research has focused on understanding the aetiology of endodontic and periodontal infections.^32,33 Later, bacteria, or parts of their genetic information, were found at distant sites.34, 35, 36 Three mechanisms of metastatic infection have been described: (1) attachment of the original oral bacteria to another site of the organism (infective endocarditis), (2) exposure to bacterial toxins (diabetes), and (3) immune reactions (nephritis).³⁷ The resurgence of the focal infection theory was marked in the early 1990s by epidemiologic studies revealing a higher risk of acute myocardial ischaemia in patients with poor oral health.^38,39 These findings changed the perception of periodontology from a locally oriented discipline to a more broadly focused “periodontal medicine.”^40,41 Gradually, periodontal pathology and associated premature tooth loss were again linked to a range of systemic diseases, including, for example, Alzheimer's disease and premature birth.^42,43 In most cases, it remains unclear whether this is a mere coincidence, a manifestation of aberrant complex immune response mechanisms, or a direct effect of the original oral microorganisms.^15,44

The oral microbiota

With advances in knowledge, the effects of oral bacteria on pathologies in other parts of the human body have been shown to be indirect. The classical Koch paradigm for a specific pathogen that causes a specific disease was not applied in these cases. The only exceptions are metastatic infections arising from haematogenous spread, typically from brain abscesses.⁴⁵ Microorganisms in the oral cavity form a complex ecosystem comprising saprophytes, commensals, and opportunistic and obligate pathogens. Many bacterial strains present in the oral cavity have the ability to form biofilms; in this environment, the interactions between strains vary, and the microorganisms in the biofilm also interact differently with the host immune system.46, 47, 48, 49 These microorganisms form the oral microbiota, an integral component of the human microbiota.^50,51 In the microbiota concept, microorganisms are not merely passengers of the host organism, but enter into complex reciprocal relationships with it.⁵² Alterations in the composition and interrelationships of the microbiota and its reciprocal interactions with the host explain many systemic diseases or predispositions.53, 54, 55, 56, 57, 58 Although most chronic systemic diseases are undoubtedly multifactorial with a large proportion of lifestyle influences, they can be said to be, in some way, a reincarnation of focal infections.⁵⁹ Therapy and prevention of these diseases, however, are not currently carried out by mindless tooth extractions but by emphasising comprehensive oral health.⁶⁰

The role of the dentist

With dramatic changes in knowledge and opinions regarding the relationship between oral and overall health, the situation has become increasingly opaque. However, the conclusions of many studies have been contradictory.⁶¹ In this situation, it is difficult for dentists to navigate correctly in their fields and in entirely different areas.^62,63 Despite this, dentists are often asked for a binding statement on the possible aetiology of the patient's problems in odontogenic infection or are required to rule out this infection before a risky surgical procedure or other therapy.64, 65, 66 The lack of clear recommendations and guidelines further complicates this situation. Consequently, there is considerable inconsistency in approaches to the problem of focal infections, even in a single country. Legal risks often lead to unnecessarily devastating therapeutic plans that reduce the patients’ quality of life.

Material and methods

We established an interdisciplinary working group under the supervision of the Czech Dental Chamber in 2022 to rationalise dental examinations and treatment procedures in patients with systemic disease or before aggressive therapy. The intended outcome was to group oral pathologies, systemic diseases, and therapeutic procedures according to their risk of infectious complications. In this group, 2 endodontists, 2 periodontologists, and 2 oral surgeons represented the relevant scientific societies in dental medicine. General medicine societies were represented by a cardiosurgeon, orthopaedist, cardiologist, diabetologist, ENT surgeon, paediatrician, oncologist, and haematologist-oncologist. Additionally, a maxillofacial surgeon coordinated group activities.

The panel members reviewed the available literature and developed a position statement for each specialty in cooperation with their scientific societies. Each society performed its own literature search (MedLine database) using a specific set of keywords. At least one search was performed with the words “infectious,” “inflammatory,” “dental,” “odontogenic,” and “oral” included in the search criteria. Infectious complications and their possible relationships with oral cavity microorganisms were identified for each specialisation. A consensus was reached by voting on each position statement. Afterward, we summarised the most common conditions and procedures and the most severe complications. This resulted in disciplinary tables categorising pathologic conditions and procedures into 3 tiers based on risk (high, medium and low risk, marked red, yellow and green in the original tables), and a schematic recommendation for further action based on a combination of oral cavity–related (odontogenic) and systemic risks.

Results and discussion

Odontogenic risk

To create a guide for dentists, the first step was categorising oral pathologies according to the degree of infection risk. Historically, endodontic infections in the root canals of deciduous teeth and periapical granulomas have been considered risk factors, even in endodontically well-treated teeth. However, chronic and acute periodontitis represent large, unconfined infectious foci. The affected area can reach several tens of square centimeters in the generalised forms of periodontitis. Interactions between bacteria and the immune system over such large areas can evoke systemic responses.^15,44,67,68

Similarly, dental implants affected by peri-implantitis or peri-implant mucositis are at risk.⁶⁹ Based on these data, oral pathologies were categorised with an emphasis on periodontal status (Table 1). Individuals with no odontogenic risk were also distinguished as those with vital or high-quality endodontically treated teeth, no periodontal disease, and good oral hygiene. Toothless people without jawbone pathology are also categorised as having no odontogenic risk.

Table 1.

Odontogenic risks.

High risk	Medium risk	Low risk
Active periodontal pocket with inflammatory exudation Diffuse (active) periodontitis: periodontal pockets 5 mm or more, BOP+ Periodontal abscess in a multirooted tooth The risk in these cases increases the tooth mobility and grade of mobility: Fistula with inflammatory exudation Denticio difficilis Acute apical periodontitis Chronic apical periodontitis with fistula Chronic apical periodontitis not bordered Peri-implantitis IMI = 4	Insufficient endodontic treatment of the root canal, bordered chronic periodontitis present, lamina corticalis intact, the focus larger than 2 mm Semi-impacted teeth Cysts Peri-implant mukositis IMI = 2, 3 Caries close to the pulp or penetrating the pulp++ with periapical clearance Initial periodontitis Furcation lesions uncleaned or uncleanable Periodontal abscess in a single-rooted tooth The risk in these cases increases the tooth mobility and grade of tooth mobility Chronic plaque-related gingivitis with pseudo pockets	Sufficient endodontic treatment of the root canal, bordered chronic periodontitis present, lamina corticalis intact, clearance up to 2 mm Insufficient endodontic treatment of the root canal without periapical enlargement and lamina corticalis intact Impacted teeth Caries close to the pulp or penetrating the pulp++ without periapical clearance Poor oral hygiene without clinical findings on periodontium Gingivitis without pseudo pockets

⁺Caries close to or penetrating the pulp (cannot be accurately distinguished in X-ray images), toxins already present in the periapical section, must be considered in cases of profound immunosuppression.

Dentin caries, pulpitis, and compromised prosthetic works do not represent an infectious focus but should be solved prior to challenging general treatment.

The severity of periodontitis increases with the number and depth of the periodontal pockets and their inflammatory activity. According to radiologic findings, defining "quiet periapical lesions" as intact periapical lamina corticalis is more appropriate. Alternatively, the periapical aperture can be enlarged.

⁺⁺Caries close to or penetrating the pulp (cannot be accurately distinguished in X-ray images): Toxins are already present in the periapical section, sometimes with clearance.

Dentin caries, pulpitis, and compromised prosthetic works do not represent an infectious focus but should be solved prior to challenging general treatment.

BOP, bleeding on probing; IMI, implant mucosal index.⁷⁰

Orthopaedics

In orthopaedics, periprosthetic joint infections (PJIs) are associated with poor oral health. The risk of these infections is relatively low (approximately 1%); however, because the number of total joint arthroplasties (TJA) is high, the number of patients at risk is significant.71, 72, 73, 74 Infections with microorganisms in the oral cavity are undoubtedly responsible for only a fraction of these complications; however, the risk is not negligible.⁷⁵ Biofilm-forming bacterial strains are particularly dangerous.^76,77 Infectious complications of TJA significantly reduce quality of life, often endangering the lives of affected patients and representing a significant economic burden for the health care system.78, 79, 80 The general health of patients and any history of PJI are essential for determining the risk of orthopaedic surgery (Table 2).81, 82, 83

Table 2.

Orthopaedic risks

High risk	Medium risk	Low risk
Procedures of primary TJA: •Patients with immunodeficiency •Posttransplant conditions •Biological treatment of autoimmune and oncologic diseases •Chronic use of immunosuppressive drugs •Chronic liver failure (Child-Pugh B, C) •Chronic renal insufficiency grade III-IV •Haemato-oncologic diseases •History of PJI	Procedures of primary TJA: •Patients who did not attend to the regular preventive dental examination in the last 2 years •DM •Liver failure (Child-Pugh A) •Renal insufficiency grade I-II •History of erysipelas •CVI grade III-IV •BMI above 30 and below 18.5 •Poor oral hygiene •Smokers •History of alcohol or other addictive substance abuse	Patients prior to primary TJA with regular dental checkups without any risks mentioned above.
Procedures of revision TJA: •Patients prior to the initiation of the chronic PJI sanitation, if it is possible to delay the surgery •Patients prior a TJA revision surgery for aseptic reasons

TJA, total joint arthroplasty; PJI, periprosthetic joint infection; DM, diabetes mellitus; CVI, chronic venous insufficiency; BMI, body mass index.

Cardiology and cardiovascular surgery

Infective endocarditis is confirmed to be associated with oral cavity diseases. Patients with infective endocarditis and congenital cyanotic heart defects are particularly at risk. Another risk factor is the material implanted in the bloodstream, such as in valve replacement.^84,85 In these patients, ATB prophylaxis is recommended before invasive dental procedures.^86,87

This situation is different for patients with coronary heart disease. Extensive epidemiologic studies have shown an association amongst aggressive periodontitis, edentulousness, and acute coronary syndrome.³⁸ Periodontitis affects the levels of mediators of the inflammatory cascade that contribute to the formation and destabilisation of atherosclerotic plaques.⁸⁸ Table 3 shows the risk distribution of the cardiac surgical procedures.

Table 3.

Cardiac surgery risks.

High risk	Medium risk	Low risk
Surgical or interventional procedures on heart valves and/or thoracic aorta with the assumption of implantation of foreign material and a high risk of IE (including TAVI, Mitraclip, homografts, stentgrafts) Surgical procedures for congenital heart disease with the assumption of implantation of foreign material Implantation of mechanical cardiac support Patients with IE (dental focus may be the cause of IE) Patients in whom foreign material has been implanted in the heart or thoracic aorta in an emergency or emergent situation without prior removal of foci	Operations on large vessels (except thoracic aorta) with the assumption of replacement of the vessel with an artificial prosthesis or implantation of SG	Any other heart surgery Interventional procedure on the heart or blood vessels with implantation of foreign material with low risk (stents, occluders, stimulation electrodes)

IE, infective endocarditis; TAVI, transcatheter aortic valve implantation; SG, StentGraft.

Other medical disciplines

Patients with TJA scheduled for cardiac surgery procedures are the most common group requiring dental clearance before hospital admission. There are other conditions where the relationship with pathologies or microorganisms in the oral cavity could be relevant. This is particularly true in immunocompromised patients or those predisposed to infectious diseases. In immunocompromised patients (those with cancer, transplant, or primary immunodeficiencies), a previously silent infectious lesion may acutely exacerbate locally and induce distant complications.⁸⁹ This is dangerous for patients who have cancer with episodes of febrile neutropaenia during aggressive chemotherapy regimens, some of which are associated with poor oral health.^90,91 Invasive mycotic infection is an example of a local complication.⁹² Local odontogenic inflammation could trigger jaw osteonecrosis, so patients should also undergo dental checkups before treatment initiation and before antiresorptive treatment or radiotherapy of the maxillofacial region. In addition to inflammation, extracting unrepairable teeth can cause osteonecrosis; therefore, tooth roots and weakened teeth must be addressed.⁹³ The influence of oral health on the compensation and complications of diabetes is often discussed, and the relationship between diabetes and periodontitis is controversial. Periodontal involvement is more common in individuals with diabetes and is associated with a more severe disease course. Conversely, individuals with diabetes and active odontogenic infections have poorer glycaemic control and a higher risk of other diabetic complications, including atherosclerosis.94, 95, 96 Patients with uncotrolled diabetes have a higher risk of inflammatory complications after invasive dental treatment.97, 98, 99 The specific oncology, ENT, and diabetology tables are provided in Supplementary File 1.

Rheumatoid arthritis has a special status as a disease at the origin of focal infection theory. Although a direct causal relationship has not been confirmed, relationships based on immune or immunologic mechanisms have been suggested.^100,101

Poor oral health and insufficient dental hygiene are risk factors for pneumonia in elderly and immunocompromised people. Direct inoculation by microaspiration and disrupting protein layers that protect mucosal surfaces by periodontitis-associated enzymes are possible mechanisms.102, 103, 104 The relationship between odontogenic infections and pneumonia in patients receiving artificial pulmonary ventilation is different but significant. A higher incidence of "ventilator-associated" nosocomial pneumonia has been observed in patients with poor oral health. Careful nursing care of the oral cavity of critically ill patients reduces the incidence of this complication.^105,106

Combination of risks and recommendations for further action

Any of the 7 possible risk combinations can be used for a patient after classifying their systemic and odontogenic risks. For clarity, these are shown as traffic light analogues (red, high risk; yellow, medium risk; green, low risk; and 3× green for patients with no risk). Each combination was associated with a basic recommendation for further action, including optimal patient referral to a specialised department (see Fig. 1, Fig. 2 and Supplementary File 2). All tables and risk combinations are available at https://fokusy.cz/en/.

Fig. 1.

No and low odontogenic risk. The traffic lights on the left side of the figure represent the degree of systemic risk according to the respective table (eg, orthopaedics). The traffic light to the right represents the dental risk (in this case, none or low). The text is a quick reference guide for dental risk estimation and provides general recommendations for clearance and dental treatment.

Fig. 2.

High odontogenic risk. The principle is the same as that illustrated in Figure 1. Here, the dental risk is high; therefore, the treatment and clearance issues differ.

Conclusion

The relationship between oral and general health is complex. Microbiota that are indigenous to the oral cavity may impact the host health both locally and systemically Therefore, the ideal state is a balance between the microbiota and the entire organism. Interfering with this balance, the overuse of antibiotics, ill-advised radical remediation, and untreated active infectious foci may lead to unexpected outcomes. This is especially true in immunocompromised patients and those undergoing high-risk surgery. Today's level of medical specialisation has rendered an individual specialist in one field incapable of assessing all the risks associated with disease and the therapeutic approaches in different areas. Inadequate communication between specialists can in addition may lead to further issues. The national consensus and classification tools presented here were developed to facilitate the orientation of physicians in their daily practice. Using analogies to road traffic signs seeks to simplify and structure medical care. The tools we produced clearly distinguished 3 centers: a care-attending dentist (usually green), a regional specialist (orange), and a multidisciplinary centre (usually a hospital [red]). Early referral to a dentist at the appointment stage for procedures with longer waiting times (eg, implant replacements, transplants, and cardiac surgery) provides time to indicate a more sophisticated and cost-saving treatment plan. The entire system is continuously being improved and more information added, and published in www.fokusy.cz. in multiple languages. The authors are grateful for any feedback, comments, additions, and possible applications in this regards.