We investigated the clinical course of patients with severe odontogenic infection. Two third of patients had antibiotic therapy before hospitalisation and their evolution is substantially the same than for the third of patients who did not receive antibiotics before hospitalisation. All patients addressed did not have tooth extraction and/or collection drainage. However, after a well performed treatment, evolution is favourable for the immense majority. Only 6% present an unfavourable course. To gain a better understanding of this group, we looked for predictors of complications based on patient general status, tooth involved and biological markers: 5 predictors were identified: penicillin allergy, CRP level > 200 mg/l, molar mandibular infection, psychiatric disorders and alcohol abuse.
This study is part of the rare prospective studies about severe odontogenic infection [3,11,12], with over 653 patients included, it was one of the largest. Our population with a mean age of 37 years-old, a male dominance, a poor health status, a maximum of mandibular molar infected with submandibular and perimandibular space involvement is similar to the literature [1,3–8,11–17]. Penicillin allergic reported is 7% in our study, 4.1% in Zirk et al. study and 8% in Flynn et al study [3,17]. Multiple tooth involvement, multiple space infected, systemic disease, prescription of non-penicillin antibiotic or of antibiotic combination, empirical antibiotic treatment changed after microbiologic assessment are predictors of hospitalization in patients with acute odontogenic infection [15]. Comparing our population to the data reported by the Institut National de prevention et d’Education pour la santé (INPES), showed that it is more vulnerable than general population with a higher proportion of alcohol, nicotine and drug abuse.
We voluntary focused on simple, objective and presurgical criteria to determine patients with a high risk to need several surgical interventions. Indeed, clinical symptoms of severity as number of spaces involved, dysphagia, dysphonia, dyspnea, tongue protraction limitation, oropharyngeal edema and anterior floor edema are well known by the experimented Oral and Maxillofacial surgeons but are misjudged by other actors as general practitioners, pharmacologists or residents. Moreover, those symptoms sometime worsen during or after surgery. That is why we removed them from the multivariate analysis. CRP level, penicillin allergy, mandibular molar infection, psychiatric disorders and immunodepression allow us to characterize 4 profiles of patients linked to a risk level higher than 25% to need several surgical interventions and to have complex course.
We started from a principle that CRP is frequently measured on admission when infection is suspected. Its measure is objective and repeatable over time. Daily measurement is useful in the detection of sepsis and it is more sensitive than body temperature or white blood cell count [18]. This inflammatory biomarker rise in most pathological situations associated with inflammation as bacterial, viral infection, trauma, systemic disease flare (excepted lupus) or post-surgical period. Normal human CRP concentrations is less than 1mg/l. Its level increases in the first 6 hours after stimulation by interleukine–6 (IL–6) and can reach peak levels approaching 350–400 mg/l after approximately 48 hours; its half-life is of 20 to 24 hours [19]. It is commonly considered that mild inflammation and viral infections cause elevation of CRP in the 10–40 mg/l range. Active inflammation and bacterial infection leads to a CRP level from 40 to 200 mg/l. Levels over 200 mg/l are found in severe bacterial infections and burns [20]. Historically, a plasma CRP level of 50 mg/l or more was highly suggestive of sepsis (sensitivity 98.5%, specificity 75%) [18]. We were guided by those considerations to arbitrary define four level of CRP: <50, 50 to 99, 100 to 199 and > 200 mg/l. Nevertheless, most studies failed to objective correlation between CRP level and severity of the sepsis [21]. Meili et al., (2016), demonstrated that CRP < 100 mg/l is significantly associated with worst acute respiratory tract infections but have moderate prognostic accuracy in primary care patients to predict clinical outcomes [22]. CRP help to diagnose equivocal cases of appendicitis, cholecystitis, pancreatitis and pelvic inflammatory disease but faster and more interpretable tests are available. Moreover, the cut-off is variable between those different diseases: CRP > 12 mg/l have a sensitivity of 98% to diagnose appendicitis, CRP > 30 mg/l have a sensitivity of 78% to diagnose cholecystitis, CRP levels > 210 mg/l discriminated between patients with clinically mild and severe pancreatitis with a sensitivity of 83% and a specificity of 85% [20]. The CRP level linked with severe infection is variable between the different diseases. Ylijoki et al., (2001) study showed to a statistically significant degree (p < 0.001) that CRP concentration on admission is linked with the complicated course of disease, respectively 140.2 mg/l (± 67.5) for patients admitted in intensive care unit [1]. However, it is difficult to define an objective CRP level cut-off between patients with severe odontogenic infection with a high risk of unfavorable evolution. It might be necessary to study systematically CRP level in odontogenic infection. Yet, in the inference tree, the level of CRP > 200 mg/l is self-sufficient to have 27% of risk to need multiple surgical intervention with a complex evolution.
In contrast, when CRP level is lower than 50 mg/l or unknown, immunodrepression is self-sufficient to have a risk level of 25% to need multiple surgeries. General health status of patients significantly impact the course and outcome of severe odontogenic infection. Seppänen et al., (2008), showed in their study that among patients with odontogenic infection, 85% of healthy patients developed local complications whereas 75% of medically compromised patients developed systemic infection complications with a need for longer hospital and a higher risk to die [8]. In Optiz et al. (2015), study, among 816 patients included, 14 (1.7%) where affected by severe complications after odontogenic infections [7]. All of them had predisposing factors such as diabetes mellitus, obesity, immunosuppression and arterial hypertension with its systemic consequences. In this group, long-term alcohol and nicotine abuse where also noticied. In our multivariate analysis, alcohol abuse appeared as a statistically significant risk factor to have severe complication but this factor does not stand out in the inference tree. Tung-Yiu et al., (2000), reported among 422 odontogenic infection 11 cases of cervical necrotizing fasciitis, 7 of them had immunocompromising conditions [23]. Patients with relevant comorbidities are known to have a worse prognosis and longer hospitalisation compared to patients without concomitant diseases.
If CRP level is between 50 and 200 mg/l and the patient allergic to penicillin, the risk factor to have multiple surgeries is 30%. Among the 47 patients allergic to penicillin, 33 (70%) received antibiotic therapy but only 5 received the first-line antibiotics specifically recommended by ANSM before admission in our Department. Still before being admitted, face to the failure of the antibiotic treatment, all patients had a non-justified antibiotic therapy modification and any causal tooth extraction. This contradicts guidelines from the ANSM which state that antimicrobials should be prescribed as an adjunct to removal of the source of infection. Therefore prescription of oral antibiotics without operative intervention represents an inadequate level of treatment for dentoalveolar infections. Prescription of oral antibiotics alone expose patients to more courses of antibiotics which can lead to development of antibiotic resistance. The incidence of routinely antibiotics resistance in deep space head and neck infection is: in the aerobic spectrum, 18% for clindamycin, 14% for macrolides and 7% for penicillin G, in the anaerobes 11% for clindamycin, 6% for metronidazole and 8% for penicillin G [24]. In Farmahan et al. study resistance to amoxicillin was 26.6% and to both amoxicillin and metronidazole was 18.7% [14]. But in Poeshl et al. study they did not observe any clinical antibiotic failure for patients treated by an association of amoxicillin and clavulanic acid. In contrast, for patients treated by clindamycin, they observed 3 clinical failures, which necessitated further surgical interventions and a change in the antibiotic regime [24]. The first line antibiotic therapy recommended by ANSM in severe odontogenic infection is an association between amoxicillin and clavulanic acid. For patients allergic to penicillin, the impossibility to use this first choice is a loss of chance. Moreover the high resistance rate for clindamycin is a matter of concern for those patients. Combination of high resistance rate for clindamycin and of a second choice antibiotic may explain most unfavourable course of patients allergic to penicillin.
If CRP level is between 50 and 200 mg/l and the patient not allergic to penicillin, two criteria must be add to obtain a risk factor of 33%: mandibular molar infection and psychiatric disorders. Mandibular molar is the most frequent tooth involved in severe odontogenic infection [3,5,7,11,13,14] and is responsible of infection spreading preferentially in the submandibular space [13,15,17,25,26]. Moreover, in our study it is also strongly correlate with unfavourable evolution. When the point of departure of the infection is the mandibular molar, the submandibular space is often involved, followed by floor oedema and tongue protraction limitation or extension to masseter and pterygoid muscles provoking trismus [25]. Then infection can spread into the parapharyngeal space and be responsible of respiratory distress and dysphagia [25,27] and along jugular and carotidien vessels to mediastinum [10,26,28,29]. The issue then was to understand why infection stay compartmentalised or dispersed. However, mandibular molar infection is not sufficient to have adverse evolution, it requires an association with psychiatric disorders. Patients with mental illness have markedly elevated rates of physical disorders compared to the general population. It is widely linked to factors as lifestyle, adverse psychotropic effects, alcohol and drugs abuses and poor health care [30]. A large review of the literature from Matevosyan et al. (2010) reports that patients with psychiatric disorders have more missing teeth, gross caries, decay, periodontal disease and xerostomia [31]. The worst predictive factors of oral health outcomes in this population are old age, type and onset mental illness. A lack of awareness and a poor perception in oral health are associated with poor oral hygiene and excessive consumption of sugar and lipids. Moreover those patients have poor access to dental care [31]. The use of treatments or drugs limiting pain perception, late consultation and limited access to appropriate treatment determine the risk for low-noise infection spreading to cervico-facial space and oral health adverse outcomes among adults with psychiatric disorders.