1 Volume 23 2024 e242836 Original Article Braz J Oral Sci. 2024;23:e242836http://dx.doi.org/10.20396/bjos.v23i00.8672836 1 DMD; MSc by Goias Federal University (UFG). Oral and Maxillofacial Surgery of Emergency Hospital of the Northwest Region of Goiânia Governador Otávio Lage de Siqueira (HUGOL), Goiania, Goiás, Brazil. 2 DMD; MSc by Goias Federal University (UFG). Oral and Maxillofacial Surgeon of Emergency Hospital of the Northwest Region of Goiânia Governador Otávio Lage de Siqueira (HUGOL), Goiania, Goiás, Brazil. Corresponding author: T-33 Street, number 125, Bueno district. Goiania, Goias, Brazil Phone: +55 (62) 982296725 E-mail: laizmoreirap@gmail.com Editor: Altair A. Del Bel Cury Received: Mar 05, 2023 Accepted: Oct 23, 2023 Microbiological profile and antibiotic sensitivity of maxillofacial infections in an emergency hospital Laiz Moreira de Paula1* , Eduardo Zancopé2 Aim: To investigate the bacteriological profile of oral and maxillofacial infections and the pattern of sensitivity to a specific group of antibiotics in a reference emergency hospital in Brazil. Methods: This is a prospective cohort institutional study that studied patients affected by oral and/ or maxillofacial infections in a Brazilian emergency hospital, over a 12-month period, of different etiologies, through data collection, culture and antibiogram tests, and monitoring of the process of resolution of the infectious condition. The variables were analyzed using the chi-square and Mann-Whitney tests, using a significance level of 5%. Results: The sample consisted of 61 patients, 62.3% male. The mean age of participants was 34.3 years. Odontogenic infection was the most frequent etiology and the submandibular space was the most affected. The bacterial species Streptococcus viridans was isolated in 21.6% of cases. Levofloxacin, vancomycin and penicillin were the antibiotics with the highest frequency of bacterial sensitivity, while clindamycin and erythromycin showed the highest percentages of resistance. Conclusions: The results suggest that, among the most used antibiotics for the treatment of these infections, penicillin remains an excellent option of choice for empirical therapy. Keywords: Bacteria. Anti-bacterial agents. Focal infection, dental. Surgical wound infection. Oral and maxillofacial surgeons. https://orcid.org/0000-0002-0993-2627 https://orcid.org/0000-0002-6567-4810 2 Paula et al. Braz J Oral Sci. 2024;23:e242836 Introduction Severe infections in the oral and maxillofacial regions are among the most frequent emergency situations that are cared by Oral and Maxillofacial Surgeons. Due to the rapid progress from a single primary space to the deep spaces of the head and neck, it can cause serious complications such as respiratory obstruction, meningitis, medias- tinitis, sepsis and death1. The accelerated clinical worsening of maxillofacial infections can be the result of several factors, such as the patient’s immune status, virulence and antibiotic resistance of pathogenic organisms, inappropriate antibiotic choice or an ineffective surgical approach2. It is known that most infections found in the head and neck region, odontogenic and non-odontogenic, are polymicrobial, predominantly by streptococcus3-5. Although there are numerous other causes for infections in this region, the main etiology are odontogenic infections and in most of the cases the infection will progress to res- olution if the incision and drainage procedures, removal of the infectious focus and the administration of antibiotic therapy are performed effectively6-8. Generally, the choice of the antibiotic is empiric in mild and moderate infections or until the anti- biogram result is obtained9. Since the microbial flora and bacterial resistance varied greatly antibiogram is considered mandatory and has an extreme impact on the empirical choice of antibiotics10-12. Concern about the development of multidrug-re- sistant bacteria, as resistant infections have higher rates of morbidity and mortality and the study of antibiotic sensitivity aim at the clinical improvement of patients and lower hospital costs. Knowing that the behavior of infections differs geographically, local health services aim to reduce the inappropriate prescription of antibiotics and rationalize their use13-15. The aim of this study is to investigate the bacteriological profile of oral and maxillofa- cial infections and their pattern of sensitivity to a specific group of antibiotics in a Bra- zilian trauma hospital. This information should help surgeons choose the appropriate antibiotic to treat these infections. Materials and methods This study is a prospective, observational and analytical cohort study, which was performed at the department of Oral and Maxillofacial Surgery at the Emergency Hospital of the Northwest Region of Goiânia Governador Otávio Lage de Siqueira (HUGOL), located in the city of Goiania in Brazil. Patients with oral and maxillofa- cial infections were recruited between September 2020 and September 2021. The research was approved by the Ethics Committee of Leide das Neves Ferreira (CAAE: 32548620.7.0000.5082). The inclusion criteria was defined by the presence of infec- tions in the oral and maxillofacial region of any etiology, in the stage of abscess with drainable collection. Exclusion criteria were presence of non-bacterial infec- tions, infections in early stages, impossibility of collecting material for analysis and patients who had already undergone the incision and drainage procedure for the same infection. 3 Paula et al. Braz J Oral Sci. 2024;23:e242836 The diagnosis of the infection was based on clinical or tomographic images. Swelling, hyperemia and local erythema, presence of image suggestive of a drain- able collection on contrast-enhanced facial computed tomography, and a positive result on a fine needle aspiration. All patients or relatives were informed and con- sented to participate in the research by signing the Consent Form. Demographic data as gender and age, detailed medical history, and outcomes of each partici- pant were collected. For sample collection, aspiration puncture procedures or tissue fragment removal from the deepest region of the infected site were performed, after decontamina- tion of the area with saline solution, preferably by an extraoral approach and, when not possible, by an intraoral approach. The sample was stored in a sterile and dry container and transported within 1 hour of collection to the hospital’s laboratory. The tissue fragments collected were immersed in BHI broth (brain heart infusion) for 24 hours in an oven at a temperature of 36°C and the broth, as well as the col- lected secretions, were seeded with disposable loops in a tripartite plate, which contained the media of chocolate agar, blood agar and MacConkey agar and on a single plate with chocolate agar medium. The single plate was placed in an anaerobic jar, and both plates were placed in an oven at 36°C. After 48 hours, the material was removed from the oven and, if there was growth, the identification of the microorganism and the antibiogram were performed through automation, by the Microscan method, according to the criteria established by the CLSI (Institute of Clinical and Laboratory Standards). The frequency of isolated species, identifi- cation by Gram stain and oxygen tolerance were performed. Cultures were tested for the following antibiotics: Penicillin, amoxicillin plus clavulanic acid, clindamy- cin, erythromycin, levofloxacin, vancomycin, ampicillin, ceftriaxone, cefuroxime, linezolid, meropenem, tetracycline, ciprofloxacin, gentamicin, and trimethoprim plus sulfamethoxazole. Data were organized and analyzed using the SPSS software (version 25.0; SPSS Inc., Chicago, IL, USA). Descriptive and bivariate analyzes were performed. Chi-square test was used to verify the association between previous antibiotic use and resistance. The length of hospital stay was compared between participants with and without resis- tance, with and without a positive result in the culture test using the Mann-Whitney test. A significance level of 5% was adopted. Results A total of 61 patients with oral and/or maxillofacial infections participated in this study. The medical history study revealed that from 18 participants that had some systemic disease. The most frequent condition was Diabetes mellitus (n=7, 11.5%). Arterial hypertension, cardiovascular and respiratory diseases were other reported conditions. More than half of the participants (67.2%) reported using antibiotics for their current infection prior to hospital admission. The characteristics of the partici- pants were presented in Table 1. 4 Paula et al. Braz J Oral Sci. 2024;23:e242836 Table 1. Characteristics of study participants (n=61). Variables n (%) Gender Male 38 (62,3) Female 23 (37,7) Age (yo) Mean: 34,3 (SD:14,4) <17 4 (6,6) 18-35 31 (50,8) 36-60 24 (39,3) >60 2 (3,3) Systemic disease No 43 (70,5) Yes 18 (29,5) Previous antibiotic use No 20 (32,8) Yes 41 (67,2) Etiology Fracture postoperative infections 7 (11,5) Post extraction infections 9 (14,8) Odontogenic infections 30 (49,2) Infected wounds after suturing 5 (8,2) Infected cystic lesions 5 (8,2) Skin or mucosal infections 5 (8,2) n: absolute frequency; %: relative frequency. Anatomical single space infections occurred in 20 patients (32.8%), while infections involving multiple spaces occurred in 41 patients (67.2%). The submandibular space was most frequently affected (57.4%) (Graph 1). 5 Paula et al. Braz J Oral Sci. 2024;23:e242836 In fr ao rb ita l Bu cc al Su bm an di bu la r La te ro ph ar yn ge al Su bm en ta l Su bl in gu al N ec k Te m po ra l Ex te rn al e ar M an di bl e bu cc al Fr on ta l Pe rio rb ita l Ca ni ne N as al s ep tu m Re tro ph ar yn ge al M ed ia st in um Pa ra ph ar yn ge al M as se te rie Pt er yg om an di bu la r M ax ill ar y bu cc al Lo w er li p M en ta l 40 35 30 25 20 15 10 5 0 4 17 2 2 22 5 1 2 2 1 1 4 7 7 11 16 19 35 3 3 9 7 Graph 1. Absolute frequency of affected anatomical regions. All patients underwent incision and abscess drainage procedure under local or gen- eral anesthesia, removal of the cause of infection and empirical antibiotic therapy. Patients with severe infection were initially prioritized for airway maintenance. 39 patients required hospitalization for treatment of the infection (63.9%), while 22 patients were followed up on an outpatient basis (36.1%). The length of hospital stay averaged 5.4 days (SD: 7.9; 0-44), 6 patients (9.8%) required intensive care and only 1 patient died. Regarding empirical antibiotic therapy, 9 different antibiotic protocols were used in the treatment of 61 participants. Ceftriaxone/clindamycin (55%), clindamy- cin (13.3%) and amoxicillin associated to clavulanic acid (13.3%) were the most frequent prescriptions. The culture test and antibiogram were positive in 37 cases (60.7%) and in 21 cases (56.7%) bacterial resistance to at least 1 antibiotic was found. Forty bacteria were identified, 16 of which were different species (Graph 2). Streptococcus viridans (21.6%; n=8) and Streptococcus anginosus (16.2%; n=6) were the most frequently isolated bacteria. Of the bacterial species found, 34 were Gram-positive (85%) and 6 were Gram-negative (15%). The percentage of facultative anaerobic bacteria was 95%, fol- lowed by aerobics at 5%. 6 Paula et al. Braz J Oral Sci. 2024;23:e242836 9 8 7 6 5 4 3 2 1 0 3 B1 5 B2 1 B3 2 B4 2 B5 1 B6 1 B7 2 B8 1 B9 3 B10 8 B11 1 B12 6 B13 2 B14 1 B15 1 B16 Graph 2. Absolute frequency of bacteria isolated in the culture test. B1: Enterococcus faecalis; B2: Streptococcus constellatus; B3: Pseudomonas aeruginosa; B4: Streptococcus pneumoniae; B5: Streptococcus intermedius; B6: Escherichia coli; B7: Proteus mirabilis; B8: Staphylococcus epidermidis; B9: Streptococcus oralis; B10: Staphylococcus aureus; B11: Streptococcus viridans; B12: Klebsiella oxytoca; B13: Streptococcus anginosus; B14: Klebsiella pneumoniae; B15: Streptococcus sinensis; B16: Micrococcus sp. Regarding the etiology, the bacteria isolated in odontogenic infections were: Strep- tococcus pneumoniae, Streptococcus viridans, Streptococcus sinensis, Streptococcus constellatus, Streptococcus anginosus, Enterococcus faecalis, Klebsiella pneumoniae e Micrococcus sp. In post extraction infections, the bacteria Streptococcus intermedius and Klebsiella oxytoca were isolated. And in the postoperative infections of fractures of the facial bones were isolated: Streptococcus viridans, Streptococcus constellatus, Staphylococcus aureus, Staphylococcus epidermidis e Enterococcus faecalis. Levofloxacin (n=31) and vancomycin (n=33) were the antibiotics with the highest absolute frequency in terms of sensitivity, followed by penicillin (n=24) and linezolid (n=19). Clindamycin and erythromycin were the antibiotics with the highest absolute frequency of bacterial resistance (13 cases each). One patient identified with Klebsi- ella pneumoniae was resistant to all antibiotics tested. Among the most common Gram-positive bacteria, Streptococcus viridans and Strep- tococcus constellatus were 100% sensitive to penicillin, vancomycin and levofloxa- cin. Streptococcus viridans was resistant to clindamycin and tetracycline in 25% of cases, while Streptococcus constellatus was resistant to clindamycin, erythromycin and ceftriaxone in 60%, 40% and 20% of cases, respectively. Streptococcus angi- nosus was also sensitive to levofloxacin and vancomycin in 100% of cases and to penicillin in 83.3%. Its resistance was 16.6% for penicillin, clindamycin, erythromycin and ampicillin. Among the 6 Gram-negative bacteria found, it was possible to iden- tify resistance to ampicillin, cefuroxime, ciprofloxacin and gentamicin in 2 cases each and resistance to amoxicillin/clavulanic acid, ceftriaxone and meropenem in 1 case each. 7 Paula et al. Braz J Oral Sci. 2024;23:e242836 Staphylococcus aureus and Staphylococcus epidermidis were resistant to penicillin, clindamycin and erythromycin in all cases. They showed satisfactory sensitivity to levofloxacin, vancomycin, linezolid and ciprofloxacin. Graph 3 shows the percentages of resistance, sensitivity and intermediate observed for each antibiotic administered. Penicillin Amoxicillin plus clavulanic acid Clindamycin Erythromycin Levoflexacin Vancomycin Ampicillin Ceftriaxone Cefuroxime Linezolid Meropenem Tetracycline Ciprofloxacin Gentamicin Trimethoprim plus sulfamethoxazole 0% 20% 40% 60% 80% 100% Resistance Sensivity Intermediate 20.5 61.5 0 0 0 0 0 0 0 0 0 0 5.1 5.1 33.3 41 5.1 79.5 2.6 10.3 84.6 33.312.8 7.7 23.1 2.6 2.625.610.3 48.7 5.1 41 20.5 20.5 10.3 7.7 2.6 2.612.8 12.8 20.57.7 33.3 41 2.6 Graph 3. Relative frequency (%) of resistance, sensitivity and intermediate observed for each antibiotic. In the evaluation of factors associated with antimicrobial resistance, it was observed that the period of hospitalization was similar between participants with (median 4.0 [minimum-maximum 0-31]) and without resistance (4.0 [minimum-maximum 0-44] (p=0.852). There was no significant association between antimicrobial resistance and previous use of antibiotics. The frequency of previous antibiotic use was similar between participants with (52.4%) and without resistance (47.6%) (p=0.074). The length of hospital stay was similar between participants with positive (4.0 [0-44]) and negative (4.0 [0-11]) results in the culture test and antibiogram (p=0.495). There was no significant difference in the median of hospitalization between the types of bacteria isolated in each participant (p=0.230). Discussion Oral and maxillofacial infections often require hospital care when not treated in their initial course. The present study evaluated patients affected by these infec- tions in an emergency hospital in order to present their characteristics and stan- dardize the prescription of antibiotics during treatment. Most articles are limited to the study of infections of odontogenic origin7, since they are the most com- 8 Paula et al. Braz J Oral Sci. 2024;23:e242836 monly diagnosed and treated infections by Oral and Maxillofacial Surgeons16,17. In this study, other etiologies were also included, such as postoperative infections, infected cystic lesions and skin infections, since they are also frequent clinical situations in emergency services and can progress to a severe stage if not treated correctly6,7,18,19. Another limitation of some studies is the inclusion of patients who were followed up only during hospitalization20. Our study evaluated inpatients and outpatients. The sample was predominantly composed of male individuals (62.3%) aged between 18-35 (50.8%). This patient profile is consistent with the characteristics found in other studies6,16,21. Diabetes mellitus is an immunosuppressive systemic disease closely related to the worsening of the clinical picture of oral and maxillofacial infections, dis- semination to deep spaces, emergence of complications, increased length of stay and the need for intensive care1,8,18,22. In our study, this condition was present in 7 patients (11.5%), 4 of whom required intensive care and 1 died. The mean hospital stay for these patients was 15.4 days and all of them had infections that involved multiple anatomical spaces. However, it was not possible to identify whether the severity was related to diabetes mellitus, the spread of the disease or the proposed treatment plan for each patient. The indiscriminate use of antibiotics is evidenced by the fact that 67.2% of the patients recruited for the study used some antibiotic prior to hospital admission as the only method of treatment. Most of these individuals did not have the prescription in hand and did not remember the name of the medication used. Therefore, it was not pos- sible to obtain information about these drugs and continue the therapeutic regimen already started, nor to know if the patients were self-medication. The submandibular space was the most affected anatomical region, confirming the information reported in several studies13,23-26. Then, the most frequent spaces were: sublingual, buccal and submental. Some infections have spread to high-severity spaces that directly threaten the airways and vital structures, such as the deep spaces of the neck and the mediastinum. Aspiration puncture or tissue fragment removal from infected sites were performed in all patients before the surgical procedure and the beginning of antibiotic therapy to avoid changes in the pathogenic microbiota. The swab collection method is not accepted by the hospital protocol, due to the high risk of contamination that this method offers27. In the entire sample, only 37 patients (60.7%) were positive for bac- terial culture and 39.3% of the samples were sterile. The factors that possibly caused this large number of samples that did not have bacterial growth include incorrect collection or transport technique, presence of bacteria sensitive to previously used antibiotics, failures in laboratory processing and lack of supplies to perform more spe- cific methods for the identification of bacteria. , such as molecular techniques16,21,28. The aspiration collection method is able to capture more anaerobic bacteria than the swab method, however, some microorganisms may not have supported the aspira- tion, transport and culture process17,23. For many years, the microbiology of infections remained inconsistent, but nowadays it is possible to identify the polymicrobial nature of these infections, their constantly 9 Paula et al. Braz J Oral Sci. 2024;23:e242836 changing flora and resistance pattern. Our study concluded that Streptococcus viridans remains the most common pathogen found in head and neck infections, as reported in previous studies4,9,11,23,24,28,29. After them, Streptococcus anginosus and Streptococcus constellatus were the most frequently found microorganisms in our sample. Streptococcus constellatus is associated with the formation of satellite abscesses and more aggressive infectious processes10. Staphylococcus aureus and Enterococcus faecalis were identified in 3 cases each, and Staphylococcus aureus is characterized by being present in skin infections, oral mucosal abscesses and secondary infections, while Enterococcus faecalis is more commonly found in oral mucosal infections19. Klebsiella pneumoniae, Pseudomonas aeruginosa and Esche- richia coli were identified in smaller numbers and are characterized by being patho- gens found in the respiratory system, oral mucosa and skin infections, especially in immunocompromised individuals19. In the present study, it was possible to test the sensitivity of the bacteria found to 15 types of antibiotics, of different classes, including beta-lactams, cephalospo- rins, quinolones and others. All bacteria were sensitive to linezolid and vancomy- cin. These results were supported by Sebastian et al.11 (2019) and by Kim et al.2 (2017), respectively. Bacterial sensitivity to clindamycin is quite varied among studies published in the literature. This antibiotic is often used to treat oral and maxillofacial infections, but high resistance has been observed in recent years. Some recent articles report that clindamycin is still highly indicated for the treatment of infections, due to its excellent coverage against Gram+ cocci and anaerobic bacteria11,14,16,25,27. Adversely, the present study concluded that clindamycin was the antibiotic that presented the highest frequency of bacterial resistance, among the most used antibiotics, information that is also compatible with several other studies found in the litera- ture5,12,22,29,30. What justifies this difference between the reports are the variations in the techniques used for the culture and identification of bacteria and the gradual changes that occur in the microbiota due to the reckless use of the drug, according to the reflection of local practice31. In previous studies, bacterial resistance to erythromycin was compatible with that of clindamycin2,12,22, as well as in ours. The association of clindamycin with ceftriaxone was presented in the study by Gómez-Arámbula et al.5 (2015), which concluded that clindamycin showed great resistance and that ceftriaxone is more indicated as a pro- phylactic therapy for mandibular fractures than for infections already installed. The use of penicillin was considered the first choice in the treatment of these infections for decades, until the emergence of several bacteria resistant to this antibiotic2,9,14,21. Penicillin was the third antibiotic with the highest frequency of antibiotic sensitivity in the present study. These results, added to those found in the literature12,17,27,30, suggest that the use of penicillin as the first choice should be continued, due to its good sus- ceptibility to aerobic and anaerobic microorganisms3. Therapy with amoxicillin, a semisynthetic antibiotic derived from penicillin, is an excel- lent choice due to its high effectiveness, minimal side effects, low cost, patient tolera- bility and availability in most public services17. Amoxicillin associated with clavulanic 10 Paula et al. Braz J Oral Sci. 2024;23:e242836 acid, a broad-spectrum combination, can be used in cases of severe infections due to the high level of resistance to beta-lactams, previously reported20,22,25. The use of clindamycin should be reserved for patients allergic to penicillin3,12,20. The patients studied showed clinical improvement and cure of the infection in 98.3% of the cases, even with the presence of bacteria resistant to the antibiotics frequently prescribed. Liau et al.14 (2018) concluded that patients who presented antibiotic resistance had a worse clinical response, increased length of stay, need for intensive care and surgical re-approach. These results were not similar to those found in the present study, as well as in the studies by Kim et al.2 (2017) and from Yuvaraj et al.27 (2012). Some factors must be raised as hypotheses of clinical wors- ening of patients, such as ineffective surgical approaches, failure to identify and remove the causative infectious focus, spread of infection to deep spaces, presence of immunosuppressive systemic diseases, among others. Antibiotic therapy works as an adjuvant therapy for surgical approaches to remove the infectious focus, inci- sion and drainage of the abscess and copious irrigation16,32, which are of valuable importance in reducing the concentration of microorganisms and the infectious bio- logical load in the patient3,7,25. There are some limitations in our study, such as the small sample size, the frequent use of antibiotics prior to the study, the presence of several samples with negative results for culture, in addition to the lack of specific culture medium for transporting restricted anaerobic samples and lack of inputs to carry out molecular methods of identification of bacteria. Our results can be used to decrease antibiotic misuse in the local population and further studies, including time and larger samples, will confirm and extend our results. Conclusion Antibiotic therapy is one of the requirements for the management of infections of the maxillofacial region, as it has the role of preventing bacteremia and helps the immune system to fight infections. The standardization of empirical antibiotic ther- apy used in a local population can be established through knowledge of the charac- teristics and sensitivity pattern of the local pathological flora, through culture and antibiogram tests. Conflicts of interest None. Data Availability Datasets related to this article will be available upon request to the corresponding author. Author Contribution Laiz Moreira de Paula: conceptualization, methodology, formal analysis, investiga- tion, manuscript writing, project administration. Eduardo Zancopé: validation, manu- 11 Paula et al. Braz J Oral Sci. 2024;23:e242836 script writing, review and editing, visualization, supervision. All authors actively partic- ipated in discussing the manuscript’s findings and have revised and approved the final version of the manuscript. References 1. Dai T, Cheng J, Ran H, Xu B, Liu Y, Qiu Y. Application of disposable multifunctional drainage tube-assisted irrigation in patients with severe multi-space infections in oral and maxillofacial head and neck regions. J Craniofac Surg. 2020 Mar/Apr;31(2):e202-5. doi: 10.1097/SCS.0000000000006236. 2. Kim MK, Chuang SK, August M. Antibiotic resistance in severe orofacial infections. J Oral Maxillofac Surg. 2017 May;75(5):962-8. doi: 10.1016/j.joms.2016.10.039.   3. Ogle OE. Odontogenic infections. Dent Clin North Am. 2017 Apr;61(2):235-52. doi: 10.1016/j.cden.2016.11.004. 4. Adamson OO, Adeyemi MO, Gbotolorun OM, Oduyebo OO, Odeniyi O, Adeyemo WL. Comparison of sensitivity of bacteria isolated in odontogenic infections to ceftriaxone and amoxicillin-clavulanate. Afr Health Sci. 2019 Sep;19(3):2414-20. doi: 10.4314/ahs.v19i3.15.  5. Gómez-Arámbula H, Hidalgo-Hurtado A, Rodríguez-Flores R, González-Amaro AM, Garrocho-Rangel A, Pozos-Guillén A. Moxifloxacin versus Clindamycin/Ceftriaxone in the management of odontogenic maxillofacial infectious processes: a preliminary, intrahospital, controlled clinical trial. J Clin Exp Dent. 2015 Dec;7(5):e634-9. doi: 10.4317/jced.52627.  6. Kumari S, Mohanty S, Sharma P, Dabas J, Kohli S, Diana C. Is the routine practice of antibiotic prescription and microbial culture and antibiotic sensitivity testing justified in primary maxillofacial space infection patients? A prospective, randomized clinical study. J Cranio-Maxillofac Surg. 2018 Mar;46(3):446-52. doi: 10.1016/j.jcms.2017.11.026.  7. Ibiyemi ST, Okoje-Adesomoju VN, Dada-Adegbola HO, Arotiba JT. Pattern of orofacial bacterial infections in a Tertiary Hospital in Southwest, Nigeria. J West African Coll Surg. 2014 Oct-Dec;4(4):112-41. 8. Juncar M, Juncar RI, Onisor-Gligor F. Ludwig’s angina, a rare complication of mandibular fractures. J Int Med Res. 2019 May;47(5):2280-7. doi: 10.1177/0300060519840128. 9. Kang SH, Kim MK. Antibiotic sensitivity and resistance of bacteria from odontogenic maxillofacial abscesses. J Korean Assoc Oral Maxillofac Surg. 2019 Dec;45(6):324-31. doi: 10.5125/jkaoms.2019.45.6.324. 10. Taub D, Yampolsky A, Diecidue R, Gold L. Controversies in the Management of Oral and Maxillofacial Infections. Oral Maxillofac Surg Clin North Am. 2017 Nov;29(4):465-73. doi: 10.1016/j.coms.2017.06.004. 11. Sebastian A, Antony PG, Jose M, Babu A, Sebastian J, Kunnilathu A. Institutional microbial analysis of odontogenic infections and their empirical antibiotic sensitivity. J Oral Biol Craniofacial Res. 2019 Apr-Jun;9(2):133-8. doi: 10.1016/j.jobcr.2019.02.003. 12. Plum AW, Mortelliti AJ, Walsh RE. Microbial flora and antibiotic resistance in odontogenic abscesses in Upstate New York. Ear Nose Throat J. 2018 Jan-Feb;97(1-2):E27-E31. doi: 10.1177/0145561318097001-207. 13. Juncar M, Onişor-Gligor F, Bran S, Juncar RI, Băciuţ MF, Dumitraşcu DI, et al. Efficiency of empirically administered antibiotics in patients with cervical infections of odontogenic origin. Clujul Med 2015;88(1):65-8. doi: 10.15386/cjmed-399.  12 Paula et al. Braz J Oral Sci. 2024;23:e242836 14. Liau I, Han J, Bayetto K, May B, Goss A, Sambrook P, et al. Antibiotic resistance in severe odontogenic infections of the South Australian population: a 9-year retrospective audit. Aust Dent J. 2018 Jun;63(2):187-92. doi: 10.1111/adj.12607. 15. Jagadish Chandra H, Sripathi Rao BH, Muhammed Manzoor AP, Arun AB. Characterization and antibiotic sensitivity profile of bacteria in orofacial abscesses of odontogenic origin. J Maxillofac Oral Surg. 2017 Dec;16(4):445-52. doi: 10.1007/s12663-016-0966-7. 16. Singh M, Kambalimath DH, Gupta KC. Management of odontogenic space infection with microbiology study. J Maxillofac Oral Surg. 2014 Jun;13(2):133-9. doi: 10.1007/s12663-012-0463-6. 17. Farmahan S, Tuopar D, Ameerally PJ. A study to investigate changes in the microbiology and antibiotic sensitivity of head and neck space infections. Surgeon. 2015 Dec;13(6):316-20. doi: 10.1016/j.surge.2014.02.006.  18. Park J, Lee JY, Hwang DS, Kim YD, Shin SH, Kim UK, et al. A retrospective analysis of risk factors of oromaxillofacial infection in patients presenting to a hospital emergency ward. Maxillofac Plast Reconstr Surg. 2019 Nov;41(1):49. doi: 10.1186/s40902-019-0238-9.  19. Dahlén G. Non-odontogenic infections in dentistry. Periodontol 2000. 2009 Feb;49(1):7-12. doi: 10.1111/j.1600-0757.2008.00298.x. 20. Götz C, Reinhart E, Wolff KD, Kolk A. Oral soft tissue infections: causes, therapeutic approaches and microbiological spectrum with focus on antibiotic treatment. J Cranio-Maxillofac Surg. 2015 Nov;43(9):1849-54. doi: 10.1016/j.jcms.2015.08.002. 21. Rasteniene R, Puriene A, Aleksejuniene J, Pečiuliene V, Zaleckas L. Odontogenic maxillofacial infections: a ten-year retrospective analysis. Surg Infect (Larchmt). 2015 Jun;16(3):305-12. doi: 10.1089/sur.2013.264. 22. López-González E, Vitales-Noyola M, González-Amaro AM, Méndez-González V, Hidalgo-Hurtado A, Rodríguez-Flores R, et al. Aerobic and anaerobic microorganisms and antibiotic sensitivity of odontogenic maxillofacial infections. Odontology. 2019 Jul;107(3):409-17. doi: 10.1007/s10266-019-00414-w. 23. Shakya N, Sharma D, Newaskar V, Agrawal D, Shrivastava S, Yadav R. Epidemiology, microbiology and antibiotic sensitivity of odontogenic space infections in central India. J Maxillofac Oral Surg. 2018 Sep;17(3):324-31. doi: 10.1007/s12663-017-1014-y. 24. Shah A, Ramola V, Nautiyal V. Aerobic microbiology and culture sensitivity of head and neck space infection of odontogenic origin. Natl J Maxillofac Surg. 2016 Jan-Jun;7(1):56-61. doi: 10.4103/0975-5950.196126.  25. Fating NS, Saikrishna D, Vijay Kumar GS, Shetty SK, Raghavendra Rao M. Detection of bacterial flora in orofacial space infections and their antibiotic sensitivity profile. J Maxillofac Oral Surg. 2014 Dec;13(4):525-32. doi: 10.1007/s12663-013-0575-7. 26. Zhang C, Tang Y, Zheng M, Yang J, Zhu G, Zhou H, et al. Maxillofacial space infection experience in West China: a retrospective study of 212 cases. Int J Infect Dis. 2010 May;14(5):e414-7. doi: 10.1016/j.ijid.2009.08.002.  27. Yuvaraj V, Alexander M, Pasupathy S. Microflora in maxillofacial infections-A changing scenario? J Oral Maxillofac Surg. 2012 Jan;70(1):119-25. doi: 10.1016/j.joms.2011.02.006.  28. Kityamuwesi R, Muwaz L, Kasangaki A, Kajumbula H, Rwenyonyi CM. Characteristics of pyogenic odontogenic infection in patients attending Mulago Hospital, Uganda: a cross-sectional study. BMC Microbiol. 2015 Feb:15:46. doi: 10.1186/s12866-015-0382-z.  29. Weise H, Naros A, Weise C, Reinert S, Hoefert S. Severe odontogenic infections with septic progress - A constant and increasing challenge: a retrospective analysis. BMC Oral Health. 2019 Aug;19(1):173. doi: 10.1186/s12903-019-0866-6.  13 Paula et al. Braz J Oral Sci. 2024;23:e242836 30. Heim N, Faron A, Wiedemeyer V, Reich R, Martini M. Microbiology and antibiotic sensitivity of head and neck space infections of odontogenic origin. Differences in inpatient and outpatient management. J Cranio-Maxillofac Surg. 2017 Oct;45(10):1731-5. doi: 10.1016/j.jcms.2017.07.013. 31. Patankar A, Dugal A, Hariram H, Kshirsagar R, Mishra A, Singh V. Evaluation of microbial flora in orofacial space infections of odontogenic origin. Natl J Maxillofac Surg. 2014 Jul-Dec;5(2):161-5. doi: 10.4103/0975-5950.154820. 32. Walia IS, Borle RM, Mehendiratta D, Yadav AO. Microbiology and antibiotic sensitivity of head and neck space infections of odontogenic origin. J Maxillofac Oral Surg. 2014 Mar;13(1):16-21. doi: 10.1007/s12663-012-0455-6.