Mandibular Osteoradionecrosis: Defining the Microbial Milieu and Antimicrobial Resistance at the Time of Rescue Flap Surgery.

OBJECTIVE: To report the microorganisms and their antibiotic sensitivity profile from tissue cultures and stains at the time of anterolateral thigh fascia lata (ALTFL) rescue flap for management of mandibular osteoradionecrosis (ORN). METHODS: Retrospective chart review of patients who underwent ALTFL rescue flap for native mandibular ORN between 2011 and 2022. RESULTS: Twenty-six cases comprising 24 patients (mean age 65.4 years, 65.4% male) with mandibular ORN from whom tissue cultures and gram stain were obtained at the time of ALTFL rescue flap. 57.7% grew bacterial species, while 34.6% grew fungal species. Multibacterial speciation was noted in 26.9% of cultures. A combination of bacterial and fungal growth was also seen in 15.4% of cases. All gram-positive cocci (GPC) were pansensitive to antibiotics except for one case of Staphylococcus aureus, which was resistant to levofloxacin. Gram-negative bacilli (GNB) species were isolated in 50.0% of cases. All fungal growth was due to Candida species. No growth was noted in 23.1% of cases. Multidrug resistance was noted in 53.8% of cases when GNB was isolated. CONCLUSION: We report 76.9% of our cases of mandibular ORN had microbial growth from tissue cultures obtained at the time of the ALTFL rescue flap. Fungal growth was noted in a substantial number of cases and should be obtained as a specimen when pursuing culture-driven antibiotic therapy. Most GPCs were pansensitive to antibiotics, while GNBs were often the harbinger of multidrug resistant mandibular ORN. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:166-169, 2024.

Comparison of the histopathological characteristics of osteomyelitis, medication-related osteonecrosis of the jaw, and osteoradionecrosis.

The purpose of this study was to compare the histopathological parameters of chronic/suppurative osteomyelitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoradionecrosis (ORN), and to examine the hypothesis that distinct histological features can be related to a specific disease, allowing for diagnosis based on microscopic evaluation alone. One hundred and ten samples were reviewed by two examiners in a blinded fashion, and a semi-quantitative histomorphometric analysis was performed. The parameters evaluated included the presence or absence of necrotic bone, inflammation, reactive bone formation, bacteria, and osteoclasts. No statistically significant differences were found between groups for any parameter. Necrotic bone was common to all three diagnoses. Inflammation and reactive bone formation were present in all three diagnoses. The presence of bacteria was a prominent feature in all cases. Osteoclasts were scarce in MRONJ and osteomyelitis, and non-existent in ORN. The results of this study failed to identify distinctive microscopic characteristics in any of the three entities that could be used to differentiate between them. Therefore, it is impossible to reach a specific final diagnosis based on microscopic findings alone. The role of microscopic analysis is to serve as an aid to diagnosis that must be complemented by the patient's history and imaging.

Radiation-Induced Necrosis of the Temporal Bone: Diagnosis and Management.

OBJECTIVE: To document our experience with osteoradionecrosis (ORN) of the temporal bone. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care medical center. PATIENTS: Patients who developed exposed necrotic bone of the external auditory canal after radiation therapy to the head and neck. INTERVENTIONS: Temporal bone ORN was managed conservatively in all patients with a combination of systemic antibiotics, antibiotic ear drops, and in-office debridement. Three patients required surgery, two of which were for a cholesteatoma. MAIN OUTCOME MEASURE: The need for surgical intervention in the management of ORN. RESULTS: Twenty-three patients with ORN of the temporal bone comprise the study group. The average age of patients at the time of diagnosis was 58 years (range, 34-75 yr). The parotid gland was the most common primary tumor site (n = 10). The mean lag time from completion of radiotherapy to diagnosis of ORN was 11 years (range, 2-48 yr). The most common presenting symptom was hearing loss (n = 18), followed by tinnitus (n = 13) and otorrhea (n = 13). All 23 patients were managed conservatively with antibiotic therapy and in-office debridement of necrotic bone. None of the patients required temporal bone resection and/or free-flap reconstruction. CONCLUSION: ORN of the temporal bone is a rare adverse event that can occur after radiotherapy for a variety of neoplasms of the head, neck, and central nervous system. Conservative management, which includes directed antibiotic therapy and regular in-office debridement of necrotic bone, can adequately control the disease process and symptomatology, thus avoiding more invasive surgical interventions.

Analysis of the factors affecting the formation of the microbiome associated with chronic osteomyelitis of the jaw.

Chronic osteomyelitis of the jaw (COMJ) is one of the most intractable diseases among head and neck infections. Antimicrobial agents are routinely administered for COMJ without sufficient bacterial information, resulting in frequent treatment failures. To improve our knowledge of the bacterial aetiology of COMJ and to assist in the development of effective treatments, we performed a comprehensive analysis of the microbiome. Sixteen patients with four clinical types of COMJ (four with suppurative osteomyelitis, three with osteoradionecrosis of the jaw, four with primary chronic osteomyelitis, and five with bisphosphonate-related osteonecrosis of the jaw) were enrolled in this study. Bone samples were subjected to bacterial community comparisons by 16S rRNA gene pyrosequencing. As a result, we clarified that COMJ was caused by a far greater range of bacterial species (12 phyla and 163 genera) than previously reported. Moreover, the bacterial structures in COMJ changed dramatically with disease stage and the condition of the affected bone. Multiple correlation analyses revealed that sequestration and bone exposure could affect the community structure. On the basis of these factors, we reclassified COMJ into three clinical stages: I, inflamed or sclerotic bone without exposure; II, sequestrum without exposure; and III, exposed sequestrum. In stage II, the bacterial diversity was significantly lower, and the anaerobe genera Fusobacterium, Tannerella (formerly Bacteroides) and Porphyromonas were more abundant, than observed during other stages. Because these bacteria habitually reside in any clinical stage, they were considered to constitute the core microbiome of COMJ. Targeting these bacteria should lead to the development of effective preventive measures and cures.

Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw.

UNLABELLED: This study evaluates the diagnostic utility of 3-phase bone scintigraphy for diagnosing osteoradionecrosis of the jaw (ORNJ). METHODS: Thirty-two consecutive patients with a history of radiation to the head and neck region (range, 62-70 Gy; mean, 68 Gy; median, 69 Gy) due to squamous cell cancer and suspected ORNJ underwent 3-phase bone scans after injection of 520 to 750 MBq of Tc-MPD. In addition to planar scans, tomographic images (SPECT) were acquired in the second phase and SPECT/CT images during the third phase. Histopathologic findings (n = 18) and clinical follow-up (n = 14) served as reference standard for osteoradionecrosis. RESULTS: The first, second, and third phases of planar images were rated positive in 18/32 patients (56.3%), 25/32 (78.1%), and 27/32 patients (84.4%), respectively. The late SPECT was positive in all patients (32/32, 100%), respectively. Histopathologic findings available in 18/32 patients (56.3%) confirmed ORNJ in all subjects. Acute inflammation was histologically proven in 18/18 specimens (100%) and additional chronic inflammation in 12/18 (66.7%). In 13/18 (72.2%) specimens, superinfection was evident histopathologically. A photopenic defect with surrounding hypermetabolism, a reported hallmark of ORJN, was found in less than 5%. CONCLUSIONS: The predominant scintigraphic pattern of osteoradionecrosis includes increased bone mineralization phase in all patients. Central photopenia, reportedly a typical bone scan finding in bisphosphonate-induced osteonecrosis, was not characteristic for ORNJ. A differentiation of acute from chronic inflammatory processes was not possible.

Biofilm formations in nasopharyngeal tissues of patients with nasopharyngeal osteoradionecrosis.

OBJECTIVE: Determine the presence of nasopharynx biofilms in patients with nasopharyngeal cancer (NPC) and osteoradionecrosis (ORN) and patients with NPC but no ORN. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: We enrolled 27 patients with NPC from our outpatient clinic during January 2010 to June 2012. These patients were diagnosed with NPC between 1980 and 2012, and all had received radiotherapy. Of these 27 patients, 15 presented with ORN, and 12 did not. The nasopharynx biopsied specimens were processed and analyzed within 2 hours of collection with the FilmTracer LIVE_DEAD Biofilm Viability Kit (Molecular Probes, Invitrogen, Carlsbad, California). A blinded investigator determined the formation of biofilms by fluorescence microscopy. Bacterial cultures were collected. RESULTS: Eleven of 15 (73%) ORN patients had biofilm formations in nasopharynx biopsy specimens. Five of these samples (45%) yielded positive cultures, and 4 of these cultures indicated the presence of methicillin-resistant Staphylococcus aureus (MRSA). Only 1 of 12 NPC patients without ORN had nasopharynx biofilm formation, and all culture results were negative. CONCLUSION: Biofilm formations were common in nasopharynx samples of NPC patients with ORN but rare in samples of NPC patients without ORN. The presence of biofilms, especially MRSA, may have a role in the disease progression of ORN or may contribute to the chronicity and resistance to antibiotic treatment.

The clinical spectrum of Actinomyces-associated lesions of the oral mucosa and jawbones: correlations with histomorphometric analysis.

OBJECTIVES: To characterize the clinical manifestations of Actinomyces-associated lesions of the oral mucosa and jawbones, and to correlate the clinical course and treatment requirements with the findings of histomorphometric analysis. STUDY DESIGN: The study was a 10-year retrospective analysis of archived cases with microscopic identification of Actinomyces infection. Actinomyces colonies were identified, using hematoxylin-eosin, Gram, and periodic acid-Schiff stains, exhibiting filamentous morphology with color variation between center and periphery. Only colonies with adjacent tissue reaction (inflammation, fibrosis) were analyzed. Actinomyces density (AD) was calculated by dividing total number of colonies by tissue surface, Actinomyces relative surface (ARS) was calculated by dividing total bacterial surface by tissue surface. RESULTS: The study included 106 cases (48 male, 58 female; aged 13-84 years, mean 50.5 years). Cases presented a wide clinical spectrum, involving jawbone and/or oral soft tissues. Cases included osteomyelitis associated with bisphosphonates, osteoradionecrosis, osteomyelitis unrelated to radiation or bisphosphonates, periapical lesions, odontogenic cysts, periimplantitis, and lesion mimicking periodontal disease. The AD correlated with median length of antibiotic treatment (R = 0.284; P = .028). CONCLUSIONS: Because we were able to identify 106 such cases, the results indicate that Actinomyces-associated lesions may not be as rare as would be expected from the relatively low number of cases in the literature. Actinomyces-associated lesions presented in a wide spectrum of clinical settings and a variety of contributing factors. Quantitative analysis of the number of bacterial colonies (representing bacterial load) could help in evaluating the aggressive potential of the lesion and help in treatment planning.

Actinomyces--gathering evidence of human colonization and infection.

The roles of the 'classical'Actinomyces spp. as colonizers of oral cavities of man and animals, in development of intra-oral infections and as agents of actinomycosis have been well documented. This mini-review focuses on perceptions of human colonization and infection that have emerged in the past decade, largely as a result of advances in classification, identification and direct detection from clinical material. Arguably, of the greatest importance is the recognition of actinomycosis as a major factor and indicator of poor prognosis in both infected osteoradionecrosis and bisphosphonate-associated osteonecrosis of the jaws. Among recently described species, Actinomyces graevenitzii has been isolated almost exclusively from oral and respiratory sites and may be a causative agent of actinomycosis. Conversely, several other Actinomyces spp. are isolated commonly from superficial soft tissue infections. Members of the genus Actinobaculum, which is closely related to Actinomyces, are strongly associated with urosepsis. Isolation and identification of Actinomyces and related genera by conventional methods remain difficult. Diagnosis is commonly belated and based solely upon histological findings. Development of direct detection methods may aid patient management and further elucidate clinical associations.

Actinomycosis of the jaws--histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis.

Actinomycosis of the jaws is a rare disease, which has been recently described in patients with infected osteoradionecrosis (IORN) and bisphosphonate-associated osteonecrosis (BON). We investigated our archive material for Actinomycosis of the jaws with special regard to underlying disease. Out of a total number of 45 patients with Actinomycosis, 43 (93.5%) suffered from BON (58.7%) or IORN (35.6%), while there were only 3 patients (6.7%) without anti-tumor treatment. In all cases, we found direct association of Actinomyces colonies with bone; in the surrounding medullary space, mixed inflammatory infiltrates with variable amounts of osteoclasts were a typical finding. Pseudoepitheliomatous hyperplasia occurred in 60.9% of patients. Cell-rich vessel obliteration was seen in less than 25.9% of BON patients, while hyalinized vessel obliteration was obtained in 37.5% of IORN patients. Additionally performed polymerase chain reaction (PCR) on paraffin-embedded and ethylene diamine tetracetic acid (EDTA)-decalcified tissue specimens confirmed the presence of Actinomyces israelii in seven of seven cases analyzed. We conclude that Actinomycosis of the jaws is a particular complication in patients with BON and/or IORN. Patients with Actinomycosis of the jaws during or after these forms of anti-cancer therapy are suggested to represent a distinct patient cohort with a relevant impairment of their general condition.

Bacterial biofilms may explain chronicity in osteoradionecrosis of the temporal bone.

OBJECTIVE: To identify biofilm formation within a case of temporal bone osteoradionecrosis. PATIENT: Single-case patient presenting with temporal bone osteoradionecrosis. INTERVENTION(S): Antibiotic therapy and then surgical debridement of the temporal bone. MAIN OUTCOME MEASURE(S): Histologic identification of biofilm formation within the affected temporal bone specimen. RESULTS: Positive identification of biofilm formation in multiple sections of the temporal bone specimen removed from a patient affected by osteoradionecrosis. CONCLUSION: This is the first evidence that temporal bone osteoradionecrosis involves biofilm formation. Such a pathogenic mechanism may explain the recalcitrance of this disease process and offer new strategies in formulating therapeutic interventions.

Infected osteoradionecrosis of the mandible: follow-up study suggests deterioration in outcome for patients with Actinomyces-positive bone biopsies.

Infected osteoradionecrosis (IORN) is one of the major complications of oral cancer radiotherapy. Recent studies showed a high prevalence of Actinomyces in IORN. In this study, the clinical follow up of IORN patients (n=25; 20 male, 5 female) with regard to Actinomyces detection in the mandible was analyzed. Within 1.6-119 months of follow up, disease control was achieved in almost 90% of the patients with Actinomyces-negative bone biopsies, but only in 25% of the Actinomyces-positive group. The presence of Actinomyces was associated with a significantly higher risk of treatment failure (P=0.004; Fisher's exact test). This held true when the data were controlled for 'extent of bone destruction', 'type of surgery' and 'soft-tissue closure' in a logistic regression analysis (P=0.018; Wald test). Since Actinomyces was detected in a significant number of patients with non-healing mucosal defects, this microbe may promote the persistence of chronic non-healing inflammatory processes. Actinomyces positivity defines a subpopulation with a clinically deteriorated course of mandibular IORN.

Osteonecrosis of the jaws in patients treated with bisphosphonates - histomorphologic analysis in comparison with infected osteoradionecrosis.

BACKGROUND: Patients treated with bisphosphonates because of bone metastases have been shown to develop osteonecrosis of the jaws. In the present study, we examined the histologic findings of these cases. As similarities between this disorder and infected osteoradionecrosis (IORN) are described, both lesions were compared. METHODS: We investigated eight patients with bisphosphonate treatment and osteonecrosis (four female, four male; median age: 65.6 years; cancer: multiple myeloma in five patients, breast cancer in three patients; mandibular involvement in five patients, maxillar involvement in three cases), and 10 patients suffering from IORN (all male; median age: 61.3 years; cancer: squamous cell carcinoma in nine patients, adenoid cystic carcinoma in one patient; mandibular involvement in all cases). Multicentric and bilateral involvement was common in the bisphosphonate group. Histologically, the bone revealed diffuse and patchy areas of necrosis in the bisphosphonate group, while in IORN osteonecrosis was larger and not diffusely distributed. RESULTS: In all cases, we found Actinomyces attached to the necrotic bone tissue. In five of eight bisphosphonates cases, and in six of 10 IORN cases, numerous osteoclasts could be detected close to vital bone exhibiting signs of bone resorption. Pseudoepitheliomatous hyperplasia (PH) was revealed in five of eight bisphosphonate patients, and in seven of 10 IORN patients. CONCLUSION: We conclude that Actinomyces is involved in the chronic, non-healing inflammatory processes as a characteristic feature of both diseases. Together with the associated presence of increased osteoclast numbers, we suggest that both factors may be involved in osteolytic mechanisms.

Actinomyces in infected osteoradionecrosis--underestimated?

Infected osteoradionecrosis (IORN) is a severe complication of radiation therapy for head and neck cancer. Infected osteoradionecrosis can lead to fracture and often requires subsequent jaw resection. It is known that irradiated bone is highly susceptible to infections, mainly with Candida species and cariogenic bacteria. Only very few data exist on Actinomyces in IORN. The study population consisted of 31 patients (7 female, 24 male; median age, 58.3 years). All patients exhibited clinical and radiological signs of IORN (infection, mucosa or skin fistula, and sequestrated bone). To detect Actinomyces colonies, histological examination was performed using several staining procedures (hematoxylin-eosin, Gram, Grocott, periodic acid-Schiff). In addition, a semi-nested polymerase chain reaction (PCR) approach was designed targeting the 16S ribosomal RNA gene. We found prominent Actinomyces colonies in 20 (64.5%) of 31 patients. Most of these lesions were localized in the mandible (16/20). Most interestingly, Actinomyces were almost exclusively found attached to the necrotic bone. PCR testing confirmed the presence of Actinomyces-specific DNA sequences (Actinomyces israelii). We show that Actinomyces is considerably more frequent in IORN than previously demonstrated. We suggest that these organisms are involved in the chronic, nonhealing inflammatory processes and the purulent discharge, which are known as characteristics of IORN. It remains to be investigated whether Actinomyces could be involved in the osteolytic mechanisms. From the histopathologic perspective, detection of Actinomyces is important because these bacteria have been shown to be associated with prolonged treatment duration.

Scanning and transmission electron microscopy demonstrates bacteria in osteoradionecrosis.

According to the current concept of osteoradionecrosis such tissue has become hypoxic, hypovascular and hypocellular and it has previously failed to show any bacterial growth. By using a molecular method, i.e., DNA-DNA hybridization, the presence of microorganisms in radionecrotic bone has formerly been demonstrated by us. The aim of the present study was to visualise bacteria in such bone by using scanning and transmission electron microscopy. Fourteen deep medullar specimens from resected radionecrotic mandibles were studied. Microorganisms were detected in 9 of the 14 samples (64%). The bacteria seen included rods, spirochetes and cocci, with rods being the predominant cells. One sample also contained yeasts (blastoconida and pseudohyphae). The data from this study strongly suggest an association between microorganisms and osteoradionecrosis. This may call for a revision of its presumed pathophysiology, including the possibility of an infectious etiology.

DNA-DNA hybridization demonstrates multiple bacteria in osteoradionecrosis.

Bone necrosis secondary to radiation was previously attributed to trauma of devitalized bone and microbiological sepsis. However, conventional microbiological technique has failed to demonstrate microorganisms throughout osteoradionecrotic bone, claimed to be hypoxic, hypovascular and hypocellular. The aim of the present study was to examine such bone for bacteria using DNA-DNA hybridization. Compared to standard culture methods this technique enables the investigation of a vast number of bacteria in a fairly short time. Twelve deep medullary specimens from resected radionecrotic mandibles were studied. A multitude of bacterial species were detected, most of them anaerobic. Porphyromonas gingivalis was the most predominant organism, followed by Fusobacterium nucleatum subspecies polymorphum. All samples contained Actinomyces, Prevotella and F. nucleatum. The results of this study indicate that bacteria, particularly anaerobes, may play a more fundamental role in the pathophysiology of osteoradionecrosis than being merely surface contaminants.

Aspergillosis of the temporomandibular joint following irradiation of the parotid region: a case report.

We report a case of aspergillosis in the right temporomandibular joint (TMJ) with a history of parotid carcinoma and post-irradiation otitis. Previous treatment attempts with surgery and antibiotics were unsuccessful. Radical debridement of the glenoid fossae, supplemented with amphotericin B and adjunct hyperbaric oxygen (HBO) therapy, was provided to resolve the symptoms. This case report highlights the need to be aware of the possibility of invasive mycosis in immunocompromised patients.

Treatment of necrotic infection on the anterior chest wall secondary to mastectomy and postoperative radiotherapy by the application of omentum and mesh skin grafting: report of a case.

We report herein the case of a patient who initially underwent right radical mastectomy for breast carcinoma in 1988, followed by left breast-conserving surgery in 1997. On both occasions she was given postoperative radiation therapy of 50 Gy. Repeated dressings and the administration of antibiotics failed to heal ulcerative infected lesions that had formed on the anterior chest wall in early 1998. In 1999, the sternum and surrounding tissue were debrided and the anterior chest wall was reconstructed by omentum transposition and mesh skin grafting. The patient is currently well and alive without any evidence of recurrence of either infection or breast cancer.

Opportunistic actinomycosis in osteoradionecrosis of the jaws in patients affected by head and neck cancer: incidence and clinical significance.

Actinomycosis is occasionally an opportunistic infection occurrence in patients with osteoradionecrosis (ORN). A retrospective study (1992-97) of 50 patients with ORN of the jaws was done to evaluate the incidence and its clinical significance in the management of ORN. Actinomycosis was diagnosed in 12% of ORN cases. In 36 of the 50 patients including five cases of actinomycosis, the ORN was considered to be resolved after treatment. The median treatment duration of ORN was significantly longer (P<0.007) in patients with actinomycosis (29.7 months) than those without the disease (13.4 months). In conclusion, bone biopsy should be considered in cases of ORN with unsatisfactory response to its specific therapies, aiming to identify possible opportunistic actinomycosis infection.

Osteomyelitis of the mandible.

The presenting characteristics and clinical courses of 60 patients with mandibular bone infections are described. Fifteen of the patients had posttraumatic osteomyelitis, 13 had odontogenic osteomyelitis, and 28 had osteoradionecrosis. Most infections (93%) were polymicrobial, and anaerobes played an important role. Types of surgical procedures and use of adjunctive hyperbaric oxygen are described. There were minimal differences in presentation or response to treatment between these four different groups. A clinical staging system for mandibular bone infections is proposed and results of treatment are retrospectively analyzed by stage. The results support the concept that initial treatment planning can be safely and successfully based on the stage of the disease.

Coverage of the infected wound.

Fifty-four consecutive patients with chronic wounds were identified by the following criteria: (1) established infection for 6 months, (2) exposure of bone, mediastinum, or other vital structure, (3) mechanical and/or vascular limitations to delayed closure techniques, (4) no response to wound debridement in prolonged antibiotic therapy. These wounds were divided into four groups: osteomyelitis (21), pressure sore (17), soft tissue wound (10), and osteoradionecrosis (6). Wound treatment in all patients included debridement, muscle flap closure, and culture specific antibiotic therapy. These consecutively treated patients over a 4-year period presented with an average duration of chronic infection of 2.9 years. Ninety-three per cent of these patients after treatment have demonstrated stable coverage without recurrent infection with a minimum of 1 year and a maximum of 4.6 years follow-up. The results demonstrate safe, effective coverage (93% of patients) of chronic infected wounds associated with long bone and pelvic osteomyelitis as well as chronic perineal sinuses following proctocolectomy and osteoradionecrosis. Debridement with short-term (average 12 days) antibiotic therapy has been effective when muscle flap coverage is provided.