Comparison of maxillofacial space infection in diabetic and nondiabetic patients

Dipesh D. Rao, MDS,a Anilkumar Desai, MDS,b R. D. Kulkarni, MD,c K. Gopalkrishnan, MDS, FDSRCS,d and C. Bhasker Rao, MDS, FDSRCPS,e Karnataka, India
S.D.M COLLEGE OF DENTAL SCIENCES AND HOSPITAL

Introduction. Orofacial space infections are common presentations in maxillofacial clinics even in the post-antibiotic era. One of the main factors determining the spread of infection is the host defense mechanism. Diabetes is one of the most common systemic illness suppressing the immunity of an individual and increasing their susceptibility to infections. This study was carried out to compare the spaces involved, the severity of infection, the virulent organism, the efcacy of empirical antibiotics, the length of hospital stay, and the complications encountered in the management of maxillofacial space infection of odontogenic origin in diabetic patients as compared with nondiabetic patients. Methodology. A 4-year prospective study was carried out on patients with maxillofacial space infection of odontogenic origin. The patients were divided into 2 groups on the basis of presence or absence of diabetes. Results. A total of 111 patients were identied out of which 31 were diabetic. The organisms commonly isolated were Streptococcus species with submandibular space being the most common space involved in both the groups. The empirical antibiotic used was amoxicillin plus clavulanic acid combined with metrogyl in 70.27% cases. Conclusion. Streptococcus species is still the most common causative pathogen irrespective of the diabetic status of the patient. The same empirical antibiotic therapy of amoxicillin plus clavulanic acid combined with metrogyl along with hyperglycemia control and surgical drainage of infection yielded satisfactory resolution of infection in the diabetic patients as well. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:e7-e12)

Risk of infection depends on several factors, including host defence mechanisms, functional or anatomical abnormalities of the host, and virulence of the infecting microorganism. It is not only the host defense that determines the outcome of infection, but the timing and appropriateness of antimicrobial treatment as well. Diabetes is a metabolic syndrome characterized by inappropriate elevation of plasma glucose level associated with changes in the lipid, protein, and carbohydrate metabolism for which a relative or absolute lack of insulin is responsible. Associated degenerative coma

Postgraduate, Department of Oral and Maxillofacial Surgery, S.D.M College of Dental Sciences and Hospital, Sattur, Dharwad, Karnataka, India. b Associate Professor, Department of Oral and Maxillofacial Surgery, S.D.M College of Dental Sciences and Hospital, Sattur, Dharwad, Karnataka, ndia. c Professor and Head of the Department, Department of Microbiology, S.D.M. Medical College and Hospital, Sattur, Dharwad, Karnataka, India. d Professor and Head of the Department, Department of Oral & Maxillofacial Surgery, S.D.M College of Dental Sciences and Hospital, Sattur, Dharwad, Karnataka, India. e Director, Craniofacial Unit, S.D.M College of Dental Sciences and Hospital, Sattur, Dharwad, Karnataka, ndia. Received for publication Jan 31, 2010; returned for revision Mar 15, 2010; accepted for publication Apr 8, 2010. 1079-2104/$ - see front matter 2010 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2010.04.016

plications include macroangiopathy, microangiopathy, and neuropathy. The prevalence of diabetes is increasing worldwide with diabetic individuals usually having higher predisposition to infections. Infections represent a frequent and severe systemic complication of diabetes mellitus and are said to be associated with sustained hyperglycemia.1 In addition to impaired host defence mechanism, other factors may also increase the susceptibility of diabetic patients to infection. Microangiopathy impairs leukocyte migration by thickening the capillary basement membrane and macroangiopathy favors acral skin and soft tissue infection. Some reports give Streptococcus as the major causative organism for infection, whereas a few have Klebsiella pneumoniae as the predominate causative organism. In odontogenic infections it has been documented that the organisms that affect diabetic individuals might be different from those in individuals who are not diabetic.2 One unanswered question is whether the increased risk in diabetic individuals is attributable to hyperglycemia itself or other associated features found in diabetic patients. The severity of infection, hospital stay, and complications associated with the infection are considered to be greater in diabetic individuals.3 In view of the preceding scenario, a study was designed with an objective to comprehend the severity of e7

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Table I. Comparison of spaces involved in diabetic and nondiabetic patients

Space involved Submandibular Buccal Ludwigs angina Submasseteric Submental Temporal Canine Pterygomandibular Lateral pterygoid Mediastinitis Sublingual pts, patients. Diabetic (31 pts) 12 9 7 7 6 5 3 3 1 1 0 % 38.71 29.03 22.58 22.58 19.35 16.13 9.68 9.68 3.23 3.23 0.00 Nondiabetic (80 pts) 49 30 13 20 15 8 6 12 5 0 3 % 61.25 37.50 16.25 25.00 18.75 10.00 7.50 15.00 6.25 0.00 3.75 Total (111pts) 61 39 20 27 21 13 9 15 6 1 3 % 54.95 35.14 18.01 24.32 18.92 11.71 8.11 13.51 5.41 0.90 2.70

infection, nature of microorganisms, antibiotic sensitivity of the microorganisms, and the length of hospital stay in diabetic individuals and to compare it with nondiabetic individuals. PATIENTS AND METHODS A prospective study was carried out for 4 years on patients who reported with maxillofacial space infection of odontogenic origin in our hospital. A total of 111 patients who needed hospitalization for surgical drainage of the infection were included in the study and divided into 2 groups:

Group I: Thirty-one patients who had a fasting blood glucose level more than 130 mg/dL (7.2 mmol/L) or had a known history of diabetes but had controlled sugar levels were also included in the diabetic group. Group II: Eighty patients were included in the nondiabetic group who presented with maxillofacial space infection and had normal blood glucose levels at the time of reporting, no history of diabetes, and their sugar levels always remained within normal limits during hospital stay without hypoglycemic agents. The patients who were not included in the study were

the other was used for Gram staining. The specimen was then immediately sent for microbiological investigation. The sample was inoculated on blood agar and MacConkeys agar and incubated at 37C for 24 hours. The growth was identied by standard techniques. The antibiotic sensitivity testing was done by Kirby Bauer disk diffusion method. The susceptibility tests were performed as per Clinical Laboratories Standard Institution (CLSI) guidelines. The results were reported as sensitive, moderately sensitive, or resistant to the different antibiotics. The diabetic and nondiabetic groups were compared on the following parameters: 1. 2. 3. 4. 5. 6. 7. The spaces involved (on clinical examination) Fever The white blood cell (WBC) count The organisms isolated from the culture The sensitivity of the organisms Need to change the empirical antibiotic The duration of hospital stay

The results obtained were subjected to unpaired t test and chi square test comparisons. RESULTS The age group of diabetic individuals was (mean SD) 47.97 10.11years and of the nondiabetic individuals was 43.70 14.64 years. The space most commonly involved in both the diabetic and nondiabetic individuals was the submandibular space, followed by the buccal space and submasseteric space (Table I). Patients presented with Ludwigs angina in 22.58% of diabetic and in 16.25% of nondiabetic patients. The diagnosis of the involved spaces was always conrmed intraoperatively. On presentation, the axillary body temperature was measured and 64.52% of diabetic patients were febrile on presentation whereas only 37.50% of nondiabetic

Patients with head and neck space infection of nonodontogenic origin. Patients who did not require hospitalization and surgical drainage of the infection. Patients with unknown antibiotic intake before reporting.

Written consent was obtained from all the patients and the study received ethical clearance from the institutions ethical board. Pus samples from the site of infection were collected on the operating table under general anesthesia while draining the infection. The samples were collected on 2 different swabs: one swab was used for culture whereas

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Table II. Organisms isolated from diabetic and nondiabetic patients

Organism isolated Enterococcus Escherischia coli Fusobacterium Klebsiella pneumoniae Streptococcus spp. Staphylococcus aureus Pseudomonas No growth/Gram positive Mycobacterium Actinomycetes spp. pts, patients. Diabetic (31 pts) 2 0 0 4 5 2 2 11/5 1 0 % 6.66 0.00 0.00 12.90 16.13 6.45 6.45 51.61 3.23 0.00 Nondiabetic (80 pts) 5 2 1 3 21 0 3 19/15 1 1 % 6.25 2.50 1.25 3.75 26.25 0.00 3.75 42.50 1.25 1.25 Total (111 pts) 8 2 1 5 26 2 5 50 2 1 % 7.21 1.80 0.90 4.50 23.42 1.80 4.50 45.05 1.80 0.90

individuals had raised temperatures, which is statistically signicant (P .01). The WBC count of both the diabetic and the nondiabetic groups was more than 12,000 cells/mm3 with no signicant difference (P .67). All the patients were started on intravenous antimicrobial therapy immediately on presentation. The diabetic patients received insulin therapy, which was titrated by the physician on their basis of their daily blood glucose levels. Seventy-eight patients of the 111 cases were started on amoxicillin plus clavulanic acid combination and metrogyl as the empirical antibiotic. Only 3 of 31 diabetic patients and 8 of 80 nondiabetic patients were resistant to amoxicillin of which 1 diabetic patient and 3 nondiabetic patients were found to be resistant to the clavulanic acid combination as well. Overall there was need to change the antibiotics in only 12.61% of total cases. In the samples collected, the sterile swab for culture had bacterial growth in 56 patients of which 15 were diabetic and 46 were nondiabetic patients. The Gram staining was positive in an additional 6 diabetic and 15 nondiabetic patients. There was polymicrobial growth in 4 and 3, diabetic and nondiabetic individuals, respectively. Of the organisms isolated, Streptococcus spp. was the most common bacteria in both the diabetic (16.13%) and the nondiabetic groups (26.25%). Klebsiella pneumoniae was the second most common organism in diabetic patients, present in 12.9% of patients (Table II). The diabetic patients were found to have a comparatively longer hospital stay than the nondiabetic patients with the mean number of days being (mean SD) 9.51 8.16 days and 6.15 3.64 days, respectively (P .003) DISCUSSION The treatment of orofacial infections is part of an everyday practice in oral and maxillofacial surgery.

Odontogenic abscess-forming infection usually spreads into the potential anatomical spaces present in the oral and maxillofacial region. The area of least resistance usually governs the spread with the host defense mechanism and virulence of the organism playing an important role as well.4 The poor host response is multifactorial and diabetes has long been considered as one of the factors reducing host response. One of the serious complications of diabetes includes predisposition to infections. Diabetic individuals are not only at high risk for infectious disease but it is also believed that they often respond poorly to infections once they occur.5 The mechanisms in which diabetes predisposes to infection may be attributable to hyperglycemia, disturbed neutrophil bactericidal function, cellular immunity, and complement activation. The mentioned defects of the immune system along with the vascular abnormalities present in diabetic patients render them at higher risk for a variety of invasive infections such as pyogenic bacterial infections, necrotizing infections, and fungal infections. Many authors have carried out the comparison of infection type and treatment outcome between diabetic and nondiabetic patients. A sundry of results have been obtained. In a study that compared the deep neck space infections in diabetic and nondiabetic patients, the authors concluded that patients with diabetes mellitus were more susceptible to deep neck infection.6 However, the association between maxillofacial space infections of odontogenic origin and diabetes mellitus has been rarely mentioned. The most commonly involved space in both the diabetic and nondiabetic patients in this study was the submandibular space, followed by the buccal space and submasseteric space. In a few studies, the parapharyngeal space was the most commonly involved space in diabetic patients,7,8 whereas the submandibular space or the buccal space was found to be more involved in nondiabetic individuals.8,9

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Ludwigs angina is one of the most common presentations in patients with diabetes in a substantial number of the reported studies.6,7 In this study, 7 (22.58%) diabetic and 13 (16.25 %) nondiabetic patients reported with Ludwigs angina. The difference between the 2 groups was statistically insignicant. This low signicance can be attributed to the poor socioeconomic background of the patients, where the host defenses might be altered in nondiabetic individuals as well. Pyrexia occurs owing to the hypothalamicthermoregulation centers response to chemicals induced by bacterial cell components such as endotoxins or cell wall fragments. On presentation, the patients in the diabetic group were found to be more febrile than those without diabetes. This result indicates that the patients who have diabetes and suffer from infection may have higher penchant toward bacteremia. The result is in unison with other studies, which show a signicant statistical correlation between raised body temperatures owing to decreased host response in diabetic patients.10 The cellular, biochemical, or molecular basis of the decline in host defenses leading to increased infections in diabetic patients is yet to be conclusively established. WBCs and especially the neutrophilic polymorphonuclear leukocytes (PMNs) play an essential role in resistance toward infectious agents. Reduced PMN function is associated with increased bacterial susceptibility, especially in diabetic individuals.11 Acute bacterial infections trigger neutrophil release from the bone marrow and thus an increase in these cells in the peripheral blood is a useful indicator of infection. In this study as well, the WBC count in both the diabetic and nondiabetic groups was raised above 12,000 cells/mm3 and infection per se can thus be held responsible for increased WBC levels irrespective of the underlying coexisting diabetic status. Perhaps WBC count is more useful in assessing the improvement or regression of a patients response to therapy, rather than predicting the actual patient status.12 The patients requiring hospital admission and surgical drainage received preoperative intravenous empirical antibiotics and this was followed postoperatively with intravenous and oral antibiotics based on the cultural and sensitivity reports. A combination of amoxicillin plus clavulanic acid and metrogyl was used in 70% of cases; 64.52% in diabetic and 72.50% in nondiabetic patients. The next commonly used empirical antibiotic regime was the combination of cefaperazone sulbactum and metrogyl in 7.50% of nondiabetic individuals and, along with gentamycin, it was used in 9.68% of diabetic individuals. This change in empirical antibiotic was done because of the patients previous history of antibiotic administration. Use of beta-lactam as empirical antibiotics in spite of the apparent rise of

in vitro resistance, infections are still responding.7,9 However, addition of metronidazole into the regimen has also been preferred.13 Studies conducted to identify the empirical antimicrobial therapy for odontogenic infections have stated the use of amoxicillin with metronidazole as one of the most effective regimens.14-16 Pottumarthy et al.17 studied the sensitivity of Streptococcus species to antimicrobials and found that amoxicillin/clavulanate exhibited good potency. The administration of amoxicillin with clavulanic acid as empirical antibiotic in our cases has proven effective in the resolution of infection and only 3 of 31 diabetic and 7 of 80 nondiabetic patients were found to be resistant to amoxicillin. This suggests that presently there is no need to subject the patients to another antibiotic regimen. The combination of amoxicillin and clavulanic acid along with metrogyl can work effectively in both the diabetic and nondiabetic patients. Organisms commonly isolated from odontogenic space infections include the Streptococcus species in most studies.9,18,19 Klebsiella pneumoniae has been isolated as the predominant infectious organism in diabetic patients.2,7 In the present study, Streptococcus species was found to be the most common organism isolated in 16.13% of diabetic and 26.25% nondiabetic patients. The second most common organism isolated in the diabetic group was Klebsiella pneumoniae in 12.90% patients. There was a high occurrence of no growth in our culture reports. A total of 45% of cases yielded no growth but on direct smear examination, Gram stain showed the presence of organisms in 40% of those cases. The presence of organisms on Gram stain and failure to grow on aerobic cultures is a common nding. This may be attributable to anaerobic infections, collection of sample after antibiotic dose, and occasionally loss of organisms during handling, transportation, and processing of the samples. Polymicrobial infections were present in 4 diabetic and 3 nondiabetic patients. The failure to isolate anaerobic organisms had no effect on the treatment outcome, as most of the patients had good resolution of the infection. Consequently, the role of the same empirical antibiotic (amoxicillin/clavulanic acid metrogyl) in both aerobic and anaerobic organism infection cannot be overlooked. The complications encountered in both groups included the need for reexploration and respiratory distress. Deep neck space infections are difcult to identify and have been reported more frequently in diabetic patients.2,6 In this study there was a need for reexploration in 6 cases, 3 each in the diabetic and the nondiabetic groups.

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The major complications were descending mediastinitis, carotid space abscess, and residual lateral pharyngeal space infection in the nondiabetic group. In the diabetic group a case of descending mediastinitis occurred after surgical drainage of the primary space infection. Death occurred in 1 patient owing to diabetic ketoacidosis, which ensued even after starting the patient on careful hypoglycemic measures. None of our patients underwent tracheostomy for airway management as reported in other studies.2 The outcome of most of the infections with similar presentation was the same when the diabetes was brought under control using insulin therapy titrated as per the physicians advice. This is similar to a study that compared the outcomes of patients with infection having controlled diabetic and nondiabetic individuals; the authors found that in spite of the higher incidence of septic shock in patients with diabetes the response to treatment after glycemia control in both patient groups was similar.7,20 Therefore, consultation with a diabetologist is recommended to control random blood sugar levels to less than 130 mg/dL. The severity of the infection usually depends on the number of spaces involved, site of the space involved, the toxic state of the patient, general health condition of the patient, associated systemic illness, and the timing of presentation. The patient with greater severity of infection needs to stay in the hospital longer until there is improvement in the toxic state of the patient and the infection has subsided. In this study, when the hospital stay was compared between diabetic and nondiabetic patients it was found that there was a highly signicant difference. The diabetic patients had stay duration of (mean SD) 9.51 8.16 days, whereas that of the nondiabetic individuals was 6.15 3.64 days (P .0033). The high difference in hospital stay in spite of similar outcome to surgical drainage and response to antibiotics of both the groups can be attributed mainly to the protocol of correcting the blood glucose levels of diabetic patients before discharge. Rapid resolution of the infection and dramatic improvement in the patients general status has been noted when simple basic fundamentals of intravenous antibiotics and drainage of the infection are performed.21 It has also been reported that improved management of diabetic individuals will lead to better prognosis without any difference between the diabetic and nondiabetic patients with similar severity of infection.22 Thus, this study gives insight into the management protocol to be used for patients with diabetes. The patients, irrespective of the diabetic status, usually respond well to the basic treatment principles for space

infections with empirical antibiotics along with glycemia control. CONCLUSION The corner stone of management of space infection of the oral and maxillofacial region remains the same in diabetic and nondiabetic patients. The results obtained from our study lead to the following conclusions: (1) Diabetic patients have a higher penchant toward bacteremia that can be determined because more patients were febrile at presentation (64.52%). (2 The commonly involved space in both the diabetic and the nondiabetic patients was the submandibular space, 38.71% and 61.25% patients respectively, whereas Ludwigs angina was present in 22.50% and 16.25% patients, respectively. (3 The response to empirical antibiotic therapy of amoxicillin/clavulanic acid metrogyl along with surgical drainage of the infection under general anesthesia provides satisfactory outcome when the diabetic patients have controlled glucose levels. Hyperglycemia can be thus considered as the major contributing factor for the altered host response in diabetic patients. (4 The organisms commonly isolated in both the groups are Streptococcus species and antibiotics that address these organisms should be used as the rst line of drugs. This can avoid unnecessary use of broad-spectrum antibiotics and reduce antibiotic resistance. (5 The longer duration of hospital stay in diabetic patients can be attributed to the control of glucose levels rather than to the resolution of infection. Contrary to the popular belief that diabetic patients have different causative organisms and need a broader spectrum of antibiotics in management of maxillofacial space infections, the authors wish to defer because of the presented ndings.
The authors sincerely thank Dr. Y. S. Rai Dean and Dr. Niranjan Kumar, Medical Director, S.D.M College of Medical Sciences and Hospital, Dharwad, for allowing us to use the facilities required for the study. The authors would also like to thank Dr. S. Amur and Dr. V. K. Joshi for providing their expert advice throughout the course of the study. The contribution of Dr. S. Gokul in formatting the article is sincerely appreciated. REFERENCES
1. Pozzilli P, Leslie RD. Infections and diabetes: mechanisms and prospects for prevention. Diabet Med 1994;11:935-41. 2. Chang CM, Lu FH, Guo HR, Ko WC. Klebsiella pneumoniae fascial space infections of the head and neck in Taiwan: empha-

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