Microbiology and antibiotic sensitivity of head and neck space infections of odontogenic origin. Differences in inpatient and outpatient management

Microbiology and antibiotic sensitivity of head and neck space infections of odontogenic origin. Differences in inpatient and outpatient management

Accepted Manuscript Microbiology and Antibiotic Sensitivity of Head and Neck Space Infections of Odontogenic Origin. Differences in Inpatient and Outp...

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Accepted Manuscript Microbiology and Antibiotic Sensitivity of Head and Neck Space Infections of Odontogenic Origin. Differences in Inpatient and Outpatient Management Dr Nils Heim, MD, DMD, Dr Anton Faron, MD, Dr Valentin Wiedemeyer, MD, DMD, Prof. Dr Rudolf Reich, MD, DMD, phD, Head of department, Dr Markus Martini, MD, DMD, Chief resident PII:

S1010-5182(17)30251-2

DOI:

10.1016/j.jcms.2017.07.013

Reference:

YJCMS 2736

To appear in:

Journal of Cranio-Maxillo-Facial Surgery

Received Date: 17 December 2016 Revised Date:

10 June 2017

Accepted Date: 20 July 2017

Please cite this article as: 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, Journal of Cranio-Maxillofacial Surgery (2017), doi: 10.1016/ j.jcms.2017.07.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Title page Title: Microbiology and Antibiotic Sensitivity of Head and Neck Space Infections of Odontogenic Origin. Differences in Inpatient and Outpatient Management Authors:

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1. Dr. Heim, Nils (MD, DMD)1 – Corresponding author – [email protected] 2. Dr. Faron, Anton (MD)1 – [email protected]

3. Dr. Wiedemeyer, Valentin (MD, DMD)1 – [email protected]

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4. Prof. Dr. Dr. Reich, Rudolf (MD, DMD, phD - Head of department)1 – [email protected]

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5. Dr. Dr. Martini, Markus (MD, DMD – Chief resident)1 – [email protected] Department fot Oral and Cranio-Maxillo and Facial Plastic Surgery

Full name of department: Department for Oral and Cranio-Maxillo and Facial Plastic Surgery (Head: Prof. Dr. Dr. Rudolf H. Reich) University of Bonn, Germany

Dr. Nils Heim

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Corresponding author:

Abteilung für Mund-, Kiefer- und Plastische Gesichtschirurgie - Universitätsklinikum Bonn

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Contact:

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Sigmund-Freud-Strasse 25, Haus 11, 2. OG D- 53127 Bonn Germany

phone 0049 (0) 228 287 16867 fax 0049 (0) 228 287 22604 e-mail [email protected]

Financial disclosure There are no financial disclosures or commercial interests from any authors. Conflict of interest There were no conflicts of interest. Acknowledgments None

ACCEPTED MANUSCRIPT Microbiology and Antibiotic Sensitivity of Head and Neck Space Infections of Odontogenic Origin. Differences in Inpatient and Outpatient Management.

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Introduction Patients have been afflicted by orofacial infections since medical records began (Huang et al., 2006). The microbial flora of orofacial infections of odontogenic origin are typically polymicrobial (Nair, 2004). In 1928, Alexander Fleming proved that Penicillium notatum was able to destroy colonies of Staphylococcus aureus. It took more than another decade before Howard Florey and Ernst Chain developed a powdered form of Penicillin that could be admitted to patients. The use of this first antibiotic changed the way odontogenic infections were treated. As an outcome of evolution, only 4 years after mass production of the first antibiotics, antibioticresistant microorganisms were observed. In order to obtain solutions to rising resistance rates, synthetic antibiotics are being continually developed (Hawkey, 2000).

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Dental abscesses usually occur secondary to caries, trauma, or insufficient dental treatment (Shu et al., 2000). The main symptoms of an acute dental abscess are swelling, pain, erythema, and hyperthermia (Robertson et al., 2009). Suppuration is often localized to the affected tooth, but can also spread into other spaces, and can be potentially life threatening as a result of airway compromise, septicemia, cavernous sinus thrombosis, brain abscess, and shock, if not treated at an early stage (Boscolo-Rizzo and Da Mosto, 2009; Tavakoli et al., 2013; DeAngelis et al., 2014). The majority of dental abscesses can be treated sufficiently by surgical intervention, such as incision and drainage of pus (Islam et al., 2008). Bacteria are undoubtedly the main pathogens of odontogenic abscesses. Nevertheless, pathogenesis of dental abscess is complex, and a single causative pathogen cannot be identified (Azenha et al., 2012; Daramola et al., 2009).

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The aim of this study was to evaluate whether susceptibility and resistances of bacteria to antibiotics have an influence on how patients have to be treated (inpatient or outpatient management) or not. Secondly, the aim was to highlight the susceptibility rate of isolated strains to the tested antibiotics.

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Patients and Methods A 28-month retrospective study evaluated hospital records of 107 patients who had been treated for head and neck infections of odontogenic origin. All patients in this study underwent surgical incision and drainage. Patient characteristics reviewed were gender, age, bacteria identified, and antibiotic resistance from culture and sensitivity. The specimens were obtained by performing a swab of the lesions using Transwab – M40-Amies (gel medium). In order to eliminate the microbial flora on skin and mucosa, disinfection of affected tissue was performed before incision. Intraoral disinfection was achieved using chlorhexidine, and extraoral disinfection was carried out with povidone-iodine. Extraoral incision was performed in 52 cases of single-space intraoral infection, and in 55 cases of multiple-space infection. All patients who underwent inpatient management received IV antibiotic therapy during and after surgery. The antibiotic therapy for outpatient-managed patients was ampicillin/sulbactam 375mg, administered twice a day (in the morning and evening) for adult patients. Children were treated with the same medication, with dose adapted to the infants’ weight. If a patient affirmed a penicillin allergy, we administered clindamycin 600mg three times a day. Children received lower doses according to their bodyweight. In cases in which the dentist had already initiated therapy with amoxicillin or clindamycin, we stuck to that medication, and additionally performed sufficient incision and drainage of the abscess. The standard antibiotic therapy for inpatient-managed patients consisted of ampicillin/sulbactam, administered three times a day in a dose according to the patients’ body weight (<70kg = 3×/2g; >70kg = 3×/3g). Renal dysfunction was checked and the dose was adjusted if necessary. If patients reported allergic reactions or skin sensations in connection

ACCEPTED MANUSCRIPT with previously administered penicillin, clindamycin (600mg three times a day) was administered instead. Again, children received lower doses according to their body weight.

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Results There were 65 male (61%) and 42 female (39%) patients, ranging in age from 5 to 91 years, with a mean age of 48.3 years (±21 SD). 52 patients underwent outpatient management and 55 patients inpatient management. Where there were signs of rapidly spreading infection, multiplespace infections, or potentially life-threatening conditions secondary to airway compromise or septicemia, patients underwent inpatient management. Of the outpatient-managed patients, 40 received ampicillin/sulbactam (ampi) and 10 patients received clindamycin (clinda). In two cases we advised the patients to continue the antibiotic therapy with amoxicillin 1000mg (amox) twice a day.

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Inpatient-managed patients received IV antibiotic therapy. 51 patients received ampicillin/sulbactam (ampi). In two cases we additionally administered metronidazole, and in one case cotrimoxazole was also administered. In all three cases a severe infection led us to the decision for additional antibiotic therapy. A microbiologist was consulted in order to suggest the drug of choice. Four patients received clindamycin, due to a prior-reported allergic reaction to penicillin. In two cases, one additional antibiotic was administered (metronidazole and ciprofloxacin) (Figure 1). A total of 92 bacterial strains were isolated from 107 patients, accounting for 0.86 isolates per patient. Swabs from 37 patients showed no growth from cultures. Candida albicans (11 isolates) and Candida dublinensis (1 isolate) were also identified. The bacteria were found to be 71.7% gram-positive. Gram-negative specimens were isolated in 28.3% of cultures.

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Of the 92 isolated strains, 73 were aerobic (Table 1) and 19 anaerobic (Table 2).

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Overall, 46 bacterial strains were isolated from patients who underwent outpatient treatment, and 34 bacterial strains from those who underwent inpatient treatment. 32.6% of the strains isolated from outpatient-treated individuals showed resistances against one or more of the tested antibiotics. Isolated strains of inpatient treated individuals showed resistances in 52.9% of cases. The predominantly isolated microorganisms were Staphylococci, Streptococci, and Prevotella. Of all isolates, Staphylococci accounted for 18.5% (17 isolates), group C Streptococci for 14.1% (13 isolates), viridans Streptococci for 18.5% (17 isolates) and Prevotella for 15.2% (14 isolates). Antibiotics evaluated for resistance included ampicillin, cefazolin, clindamycin, erythromycin, gentamicin, levofloxacin, metronidazole, penicillin, piperacillin/tazobactam, and sulfamethoxazole/trimethoprim. Staphylococci showed susceptibility to ampicillin (100%), cefazolin (100%), clindamycin (82.4% – outpatient management (o): 1; inpatient management (i): 2), erythromycin (76.5% – o: 2; i: 2), gentamicin (100%), levofloxacin (82.4% – o: 2; i: 1), penicillin (58.8% – o: 5; i: 2), piperacillin/tazobactam (100%), and sulfamethoxazole/trimethoprim (100%). Viridans Streptococci demonstrated sensitivity rates to ampicillin (100%), cephazolin (100%), clindamycin (84.6% – o: 0; i: 2), erythromycin (100%), gentamicin (92.3% – o: 1; i: 0), levofloxacin (100%), penicillin (100%), piperacillin/tazobactam (100%), and sulfamethoxazole/trimethoprim (92.3% – o: 1; i: 0). Group C Streptococci exhibited susceptibility to ampicillin (92.3% – o: 0; i: 1), cephazolin (100%), clindamycin (84.6% – o: 1; i: 1), erythromycin (100%), levofloxacin (100%), penicillin (100%), piperacillin/tazobactam (100%), and sulfamethoxazole/trimethoprim (92.3% – o: 0; i: 1).

ACCEPTED MANUSCRIPT Prevotella exhibited susceptibility to penicillin (100%), clindamycin (78.6% – o: 3; i: 0), gentamicin (100%), and levofloxacin (100%).

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Regarding the distribution of bacterial strains and resistances found in the four most common bacteria (Staphylococcus, group C Streptococci, viridans Streptococci, and Prevotella), Staphylococcus was found in 10 cases in outpatient management with six resistant isolated strains (60%). In seven cases Staphylococcus was found in patients who were treated under inpatient conditions and was resistant in five instances (71.4%). Group C Streptococci were found in four outpatient cases (one resistant strain = 25%) and nine inpatient cases (three resistant strains = 33%). Viridans Streptococcus appeared in 12 outpatient cases (two resistant strains = 16.6%) and five inpatient cases (two resistant strains = 40%). Prevotella was mostly isolated in patients treated under outpatient conditions (13 strains, of which three were resistant = 23.1%). In one case a non-resistant Prevotella strain was isolated in an inpatienttreated abscess (Figure 2).

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Discussion Dental abscess is a frequently occurring infection routinely treated as an office procedure. Certain factors, such as host resistance, anatomy, and virulence of the bacteria, are of vital importance regarding the spread of infection. This study investigates patients with head and neck infections of odontogenic origin, who were either treated under inpatient or outpatient conditions. All patients received surgical incision and drainage. The mean age of our patients was 48.3 years (±21 SD), which is slightly higher than in other studies (Sanchez et al., 2011; Zirk et al., 2016). We observed a male dominance (61%), which was similar to recent studies (Zirk et al., 2016).

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Currently only little literature on outpatient-management of head and neck infection is available. All patients presented the typical clinical findings of pain and swelling (Robertson et al., 2009). All 52 patients treated under outpatient conditions reported with single-space involvement, whereas multiple-space infections were reported in most of the 55 patients treated under inpatient conditions. In fact multiple-space infections of odontogenic origin of the head and neck are seen more frequently (Storoe et al., 2001).

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Bacteria that were isolated included both aerobic and anaerobic species (Stefanopoulos and Kolokotronis, 2004). Staphylococci were one of the four predominantly isolated bacteria. Historically, Staphylococcus species have not been considered members of the oral flora or to play a preponderant role in the pathogenesis of head and neck infections of odontogenic origin. However, recent studies have showed that Staphylococci are more frequent colonizers of the oral cavity than previously thought (Smith et al., 2008), and have been reported in up to 17.5% of acute dental abscesses (Walia et al., 2014). Our results were slightly higher, with a Staphylococci rate of of 18.5%. Viridans and group C Streptococci are commonly implicated in dental abscess. The viridans group of Streptococci includes the oralis, mitis, sanguinis, salivarius, and mutans groups (Fowell et al., 2012). Prevotella species have been reported as the most common isolates in different studies (Siquiera and Rocas, 2009). In our present study, 14 strains (15.2%) of Prevotella species were isolated. This finding correlates with the other studies reported in the literature (Kuriyama et al., 2012). Of the total 92 isolates, 73 (79.3%) were aerobes, of which 63 were Gram-positive aerobes (86.3%) and 10 were Gram-negative aerobes (13.6%). The difference between the Grampositive and the Gram-negative aerobes was significant. Out of the 92 isolates, 19 were anaerobes (20.7%). Our findings showed a significant difference between the incidence of aerobes and anaerobes. Furthermore, particular attention must be paid to the use of antibiotics effective against Gram-negative organisms, with 28.3% of the isolated strains in our study being Gram-negative.

ACCEPTED MANUSCRIPT Candida albicans was isolated in 11 cases (12%) and Candida dublinensis in one case (1.1%). The occurrence of Candida in the pus of odontogenic abscesses was higher than reported in literature (Walia et al., 2014).

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Our study had an average of 0.86 isolate per sample from 107 patients. This is significantly lower than for samples obtained by aspiration, with up to 3.3 isolates per sample (Lewis, 1985). In terms of samples collected by swabbing – similar to the procedure we performed – our results were slightly lower compared with other studies, ranging from 1.1 to 1.4 isolates per sample (Hunt and Meyer, 1983; Epstein and Scoop, 1977). In 37 cases (34.6 %) swabs showed no results of bacterial growth. Reasons for this might include the pus composition (Madigan et al., 2012). In advanced abscesses leucocytes can weaken or eliminate so many of the bacteria that isolating and cultivating any becomes unlikely. Nevertheless, bacterial strains are still present in the abscess.

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Resistance to the tested antibiotics in Staphylococcus was noted in 11 cases (64.7%) with a low susceptibility to penicillin (58.8%). This correlates with other studies reported in the literature (Barker, 1999). Outpatient-treated patients showed a higher rate of resistance (five cases), than patients treated under inpatient conditions (two cases). These findings lead us to assume that the differences in susceptibility of Staphylococcus in dental abscess, treated under either inpatient or outpatient conditions, show no evidence for the rate of spreading or the development of serious, progressive symptoms. Reduced susceptibility was also noted to clindamycin (83.4%), erythromycin (76.5%), and levofloxacin (83.4%). However, there was no significant difference between the strains treated under inpatient or outpatient conditions.

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Viridans Streptococci were isolated in 17 cases and showed resistance in two cases in each group (inpatient vs. outpatient management). However, 12 of the isolated microorganisms were found in the outpatient-treated group, while only five were found in the inpatient-treated group. Thus, the percentage of resistant bacteria was significantly higher in the inpatient group (40%), than in the outpatient group (16.6%). Viridans Streptococci viridans were 100% susceptible to penicillin as well as to erythromycin and cephazolin, which correlates with findings in the literature (Kuriyama, 2002). The rate of susceptibility to clindamycin was 84.6%. Both resistant strains were found in the inpatient group. These findings show that penicillin still appears to be a highly effective antibiotic in the treatment of viridans Streptococci.

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Group C Streptococci showed a slightly higher resistance rate in the inpatient group (Figure 2). 100% of the isolates were susceptible to penicillin, while only 84.6% susceptibility to clindamycin was noted. The high susceptibility to penicillin suggests that it should be used in preference against group C Streptococci, whereas clindamycin should not be used as the firstresort antibiotic. Prevotella was the predominant Gram-negative isolate (53.8%) (Warnke et al., 2008). In contradiction to the literature, Prevotella showed no resistance to penicillin in our study (Boyanova, 2010). Surprisingly, only one of 14 cases (7.1%) of Prevotella had to be treated under inpatient conditions. Prevotella showed a 78.6% sensitivity rate to clindamycin, whereas it exhibited high susceptibility to gentamicin (100%) and levofloxacin (100%). Thus, clindamycin was not shown to be an effective drug of choice against Prevotella. Patients who required inpatient treatment tended to have multiple-space abscesses. Statistical analysis showed inpatients to have significantly higher numbers of resistant microorganisms (52.9%) than outpatients (32.6%). However, it is conjecturable that microorganisms causing serious progressive symptoms, and showing greater tendency to spread, are more likely to be resistant to the regular antibiotics, with the consequent complications requiring inpatient management, including administration of IV antibiotics. Cultures and sensitivities commonly showed greater growth in aerobes (79.3%) than in anaerobes. The most common bacteria

ACCEPTED MANUSCRIPT isolated were Staphylococci, viridans Streptococci, group C Streptococci and Prevotella. Staphylococci showed a susceptibility rate of 58.8% to penicillin, whereas viridans Streptococci, group C Streptococci, and Prevotella were 100% susceptible to penicillin. Clindamycin showed a reduced susceptibility rate in all of the four predominant groups of microorganism (Figure 2).

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Conclusion Microorganisms that show low susceptibility to one or more of the standard antibiotic therapy regimes have a significantly higher chance of causing serious health problems, a tendency to spread, and are more likely to require inpatient management, with administration of IV antibiotics. Penicillin continues to be a highly effective antibiotic against viridans Streptococci, group C Streptococci and Prevotella, whereas clindamycin could not be shown to be effective as an empirical drug of choice for a large number of odontogenic infections.

No conflict of interest. No ethical approval needed.

Table and figure legends:

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Conflict of interest/ethical approval:

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Table 1. Number of aerobic organisms. Gram (+/−); shape: c = coccus, r = rod, fungus Table 2. Number of anaerobic organisms. Gram (+/−); shape: c=coccus, r=rod

References:

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Figure 1. Administered antibiotics in inpatient (ip) and outpatient (op) management. ampi = ampicillin/sulbactam; clinda = clindamycin; amoxi = amoxicillin; metro = metronidazole; cotrim = cotrimoxazole; cipro = ciprofloxacin Figure 2. Microorganisms categorised into inpatient and outpatient isolates, and according to antibiotic resistances.

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ACCEPTED MANUSCRIPT Epstein S, Scoop IW: Antibiotics and the intraoral abscess. J Periodontol 48: 236, 1977 Fowell C, Igbokwe B, MacBean A: The clinical relevance of microbiology specimens in orofacial abscesses of dental origin. Ann R Coll Surg Engl 94: 490–492, 2012 Hawkey PM: Mechanisms of resistance to antibiotics. Intensive Care Med 26: S9, 2000

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Kuriyama T, Karasawa T, Nakagawa K et al.: Bacteriology and antimicrobial susceptibility of Gram-positive cocci isolated from pus specimens of orofacial odontogenic infections. Oral Microbiol Immunol 17: 132, 2002 Kuriyama T, Absi EG, Williams DW, Lewis MA: An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin resistance. Br Dent J 198: 759–763, 2005 Lewis MAO, MacFarlane TW, McGowan DA: Quantitative bacteriology of acute dentoalveolar abscess. J Med Microbiol 21: 101, 1985

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Robertson D, Smith AJ: The microbiology of the acute dental abscess. J Med Microbiol 58: 155– 162, 2009

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Sanchez R, Mirada E, Arias J, Pano JR, Burgueno M: Severe odontogenic infections: epidemiological, microbiological and therapeutic factors. Med Oral Patol Oral Cir Bucal 16(5): e670–676, 2011 Shu M, Wong L, Miller JH, Sissons CH: Developement of multi-species consortia biofilms of oral bacteria as an enamel and root caries model system. Arch Oral Biol 45: 27–40, 2000 Siqueira JF, Jr, Rocas IN: Diversity of endodontic microbiota revisited. J Dent Res 88: 969–981, 2009 Smith AJ, Jackson MS, Bagg J: The ecology of Staphylococcus species in the oral cavity. J Med Microbiol 50, 940–946, 2001 Stefanopoulos PK, Kolokotronis AE: The clinical significance of anaerobic bacteria in acute orofacial odontogenic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98(4): 398– 408, 2004 Storoe W, Haug RH, Lillich TT: The changing face of odontogenic infections. J Oral Maxillofac Surg 59: 739, 2001

ACCEPTED MANUSCRIPT Tavakoli M, Bagheri A, Faraz M, Salehirad S, Roghaee S: Orbital cellulitis as a complication of mandibular odontogenic infection. Ophthal Plast Reconstr Surg 29(1): e5–7, 2013 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

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Warnke PH, Becker ST, Springer IN, Haerle F, Ullmann U, Russo PA, et al.: Penicillin compared with other advanced broad spectrum antibiotics regarding antibacterial activity against oral pathogens isolated from odontogenic abscesses. J Craniomaxillofac Surg 36(8): 462–467, 2008

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Zirk M, Buller J, Goeddertz P, Rothamel D, Dreiseidler T, Zoller JE, Kreppel M: Empiric systemic antibiotics for hospitalized patients with severe odontogenic infections. J Craniomaxillofac Surg 44(8): 1081–1088, 2016

ACCEPTED MANUSCRIPT Table 1 Aerobic organisms Gram

Shape

Number of aerobes

Actinobacter baumanii Candida albicans Candida dubliniensis Citrobacter freundii Enterobacter cloacae Gemella haemolysans Hämophilus parainfluenza Klebsiella oxytoca Pseudomonas putida Staphylococcus Group A Streptococcus Group C Streptococcus Group K Streptococcus Streptococcus gordonii S. viridans Group Total

− + + − − + − − − + + + + + +

c/r Fungus Fungus r r c r r r c c c c c c

1 11 1 1 1 1 3 3 1 17 1 13 1 1 17 73

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Strains

ACCEPTED MANUSCRIPT Table 2 Anaerobic organisms Shape

Bacteroides uniformis Enterococcus Fusobacterium Parvimonas micra Prevotella Total

− + − + −

r c r c r

Number of anaerobes 1 2 1 1 14 19

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Gram

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Bacterial strains

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Figure 1

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Figure 2