[An unvaccinated man with a painful arm and jaw]. / Een ongevaccineerde man met een pijnlijke arm en kaak.

BACKGROUND: Clostridium tetani is a gram-positive spore-forming bacterium that produces toxins and grows under anaerobic conditions. Infections with this bacterium can lead to local or generalised forms of tetanus. CASE DESCRIPTION: An 83-year-old man presented to the acute cardiac care unit with a painful left arm and jaw. Because the patient had a hypertonic left arm and was unable to open his mouth fully, the neurologist was consulted. The patient had been to the emergency department 9 days earlier for an infected wound after falling in the garden. He had not been actively or passively immunised against tetanus at that time. On inquiry, it appeared that the patient had also not been vaccinated as a child. We made a clinical diagnosis of tetanus. The patient was admitted and treated with tetanus immunoglobulin, metronidazole, diazepam and painkillers. He was also administered tetanus toxoid and the wound was cleaned. After 1 month and 7 months, the patient was again administered tetanus toxoid. CONCLUSION: Patients with a wound that may have come into contact with road grime, dirt or manure, should always be asked for their vaccination status, especially people from high-risk groups, such as the elderly.

Antiseptic negative pressure instillation therapy for the treatment of septic wound healing deficits in oral and maxillofacial surgery.

INTRODUCTION: Impaired wound healing, chronic wounds and extended soft tissue defects present a crucial problem in reconstructive surgery of the head and neck region, even more after radiation therapy. In such cases the standard is a prolonged open wound treatment. The negative pressure instillation therapy might present an alternative therapy option. MATERIAL AND METHODS: In this study the effects of negative pressure instillation therapy on the healing of chronic wounds in 15 patients diagnosed with impaired wound healing were investigated. These based upon infected osteoradionecrosis and osteomyelitis of the jaw. The parameters investigated as markers of the therapeutic success were serum inflammatory parameters i.e. white blood cell counts, wound smear results and wound surface reduction. RESULTS: The use of negative pressure instillation therapy lead to a reduction of the bacterial load and formation of a stabile granulation tissue in all but one case. The mean inpatient time of the patients was 13.33 ± 4.62 days. Between 2 and 8 dressing changes were needed to reach clinical sufficient wound healing results. Secondary intention wound healing could be obtained in 14 out of 15 cases. The crucial part for the successful application was a watertight enoral suturing as oro-cutaneous fistulae were present in most cases. CONCLUSION: The negative pressure instillation therapy poses a good treatment for wound healing problems and extended size soft tissue defects, even when oro-cutaneous fistulae were present. Especially in cases that contraindicate micro-vascular reconstruction, negative pressure instillation therapy could be a good alternative.

Osteomyelitis of the jaw: time to rethink the bone sampling strategy?

This work aims at describing the diversity of osteomyelitis of the jaw (OJ) and at assessing the relevance of a new method designed to avoid salivary contamination during bone sampling in order to improve microbiological analysis and clinical decision-making. We reviewed medical and microbiological data of patients with a suspected OJ based on clinical and/or CT-scan signs and at least one bone sample made for microbiological analysis. During the study period, a new procedure for intraoral bone sampling was elaborated by surgeons and infectious diseases specialists authoring this article (based on stratified samples, cleaning of the surgical site and change of instruments between each sample). A comparison of the microbiological analyses between the two procedures was performed. From 2012 to 2017, 56 patients were included. Median age was 58 years (11-90), sex ratio: 1.24. Main risk factors were having a dental disease (n = 24) or cancer (n = 21). Nineteen patients with the new sample procedure were compared to 37 patients with standard procedure, especially non-cancer patients (n = 16 and 19, respectively). With the new procedure, a median of 3 (1-7) microorganisms per sample was recovered, vs. 7 (1-14) with the former (p < 0.001), a significant decrease of the microbial density was observed for all types of microbes, especially in deeper samples and cultures were more frequently sterile. The way sampling is managed deeply influences microbiological analysis. This strategy facilitates the distinction between pathogens and contaminants and should constitute the first step toward an evidence-based antimicrobial strategy for OJ.

Bad to the Bone: On In Vitro and Ex Vivo Microbial Biofilm Ability to Directly Destroy Colonized Bone Surfaces without Participation of Host Immunity or Osteoclastogenesis.

Bone infections are a significant public health burden associated with morbidity and mortality in patients. Microbial biofilm pathogens are the causative agents in chronic osteomyelitis. Research on the pathogenesis of osteomyelitis has focused on indirect bone destruction by host immune cells and cytokines secondary to microbial insult. Direct bone resorption by biofilm pathogens has not yet been seriously considered. In this study, common osteomyelitis pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Streptococcus mutans) were grown as biofilms in multiple in vitro and ex vivo experiments to analyze quantitative and qualitative aspects of bone destruction during infection. Pathogens were grown as single or mixed species biofilms on the following substrates: hydroxyapatite, rat jawbone, or polystyrene wells, and in various media. Biofilm growth was evaluated by scanning electron microscopy and pH levels were monitored over time. Histomorphologic and quantitative effects of biofilms on tested substrates were analyzed by microcomputed tomography and quantitative cultures. All tested biofilms demonstrated significant damage to bone. Scanning electron microscopy indicated that all strains formed mature biofilms within 7 days on all substrate surfaces regardless of media. Experimental conditions impacted pH levels, although this had no impact on biofilm growth or bone destruction. Presence of biofilm led to bone dissolution with a decrease of total volume by 20.17±2.93% upon microcomputed tomography analysis, which was statistically significant as compared to controls (p <0.05, ANOVA). Quantitative cultures indicated that media and substrate did not impact biofilm formation (Kruskall-Wallis test, post-hoc Dunne's test; p <0.05). Overall, these results indicate that biofilms associated with osteomyelitis have the ability to directly resorb bone. These findings should lead to a more complete understanding of the etiopathogenesis of osteomyelitis, where direct bone resorption by biofilm is considered in addition to the well-known osteoclastic and host cell destruction of bone.

Bacteria take control of tolls and T cells to destruct jaw bone.

Bone undergoes a continuous cycle of remodeling for maintenance and healing. For almost a decade it has been appreciated that the immune system is intricately linked to bone homeostasis. Both acute and chronic inflammatory responses have been shown to impact bone health. A common form of inflammatory disease that causes bone destruction is the chronic infectious disease known as periodontitis (PD). PD is a bacteria-driven inflammation of the tooth-supporting apparatus that leads to resorption of the alveolar (jaw) bone, often leading to tooth loss. At the host-bacteria interface, Toll-like receptors (TLRs) play an instructive role in the development of innate and T cell adaptive responses to oral bacteria. Specifically, it is becoming apparent that TLR2-mediated inflammatory responses represent the major arm of the host immune response during periodontitis, and form an important link between periodontal infection and ensuing periodontal bone loss. This review summarizes the role of TLR2-mediated interplay between immune cells and bone cells in a periodontal disease setting.

Electrically conductive bacterial nanowires in bisphosphonate-related osteonecrosis of the jaw biofilms.

OBJECTIVE: Bacterial biofilms play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this preliminary study was to test the hypothesis that the extracellular filaments observed in biofilms associated with BRONJ contain electrically conductive nanowires. STUDY DESIGN: Bone samples of patients affected by BRONJ were evaluated for conductive nanowires by scanning electron microscopy (SEM) and conductive probe atomic force microscopy (CP-AFM). We created nanofabricated electrodes to measure electrical transport along putative nanowires. RESULTS: SEM revealed large-scale multispecies biofilms containing numerous filamentous structures throughout necrotic bone. CP-AFM analysis revealed that these structures were electrically conductive nanowires with resistivities on the order of 20 Ω·cm. Nanofabricated electrodes spaced along the nanowires confirmed their ability to transfer electrons over micron-scale lengths. CONCLUSIONS: Electrically conductive bacterial nanowires to date have been described only in environmental isolates. This study shows for the first time that these nanowires can also be found in clinically relevant biofilm-mediated diseases, such as BRONJ, and may represent an important target for therapy.

Novel antimicrobial agents for the management of maxillofacial and neck infections.

BACKGROUND: Maxillofacial and head & neck infections often jeopardize patients' lives. Regional intracranial spread to the cavernous sinus, but also to the mediastinum is common for those left untreated. The divergence of the upper peptic and respiratory tracts from the pharynx, the presence of the brain vasculature, the fine sensory instruments for vision, hearing and taste-smell, and the unique feature of mucosa directly attached to facial bones in the paranasal sinuses, oral cavity and external auditory meatus make this region the most exposed to infections in the human body. Special immune mechanisms have evolved in this area, however infections are still very common. METHODS & RESULTS: We review the unique pathophysiological features of maxillofacial and head & neck infections. We describe novel investigational anti-infective agents, and analyze their potential clinical utility with regard to mechanisms of action and site preference. DISCUSSION: We emphasize on the need for more antimicrobial drug research and discuss on the current skews in pharmaceutical research and manufacturing practices that make new categories of antimicrobial drugs an exceptional entity. Drug patents may need to be expanded both longitudinally in terms of time period but also squarely, potentially including the drug class in the patent rather than the drug itself. Clinicians need to be aware of these limitations and prescribe antibiotics to their patients with parsimony.

Periodontopathogen and Epstein-Barr virus contamination affects transplanted bone volume in sinus augmentation.

BACKGROUND: Bone microbial contamination can impair osteogenesis. Human herpesviruses-associated vasculitis can cause vascular damage within the osseous graft and host. This study is conducted to substantiate specific contamination and assess the impact 6 months after sinus augmentation. METHODS: Culture- and polymerase chain reaction (PCR)-based identification were done on harvested bone particles and unstimulated whole saliva in a group of 30 patients undergoing maxillary sinus augmentation. Patients were divided into two groups: those with and those without a history of periodontitis. Radiographic evaluation was done to assess and compare bone healing and volume gain at baseline and 6 months post-transplantation. RESULTS: Seventeen patients had a history of periodontitis, and 13 did not. Ten showed culture- and PCR-negative results and belonged to the periodontally healthy group. The 17 patients with periodontitis showed culture- or PCR-positive results for the targeted periodontal pathogens. Patients with periodontitis were 2.3 times more likely to have positive salivary Epstein-Barr virus type 1 (EBV-1) than those with no history of periodontitis. The likelihood of having moderate to pronounced bone volume loss 6 months postaugmentation was 7.5 times greater in those patients presenting contamination with ≥3 specific pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, or Prevotella intermedia) versus those with only one (P <0.05). The odds ratio (OR) of pronounced volume loss was 16.3 times higher in those contaminated with a combination of salivary EBV-1 and ≥3 of the previously mentioned species versus only EBV-1 (P <0.05). Individuals showing positive salivary EBV-1 had bone bacterial contamination associated 57% of the time. The OR of having bone microbial contamination in patients with a history of periodontitis was 37.5 times higher than in individuals without periodontitis. CONCLUSIONS: This study confirms contamination of bone, harvested intraorally, with key periodontopathogens in individuals undergoing sinus augmentation. Specific microbial contamination can impair osteogenesis. Saliva may act as a vehicle to transport EBV and other pathogens into the sinus. Increased bone volume loss seems to be associated with the occurrence of specific periodontal anaerobic species, salivary EBV-1, or the combination of both.

Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid.

Intravenous bisphosphonates-the potent inhibitors of osteoclast-mediated bone resorption are among the most commonly prescribed drugs in the management of multiple myeloma (MM). Zoledronic acid (ZA) is a new generation potent intravenous bisphosphonate that has been approved for the treatment and prevention of bone lesions, and/or hypercalcemia associated with MM. Osteonecrosis of the jaw (ONJ) is an emerging serious side effect of the new generation bisphosphonates with a growing number of reports related to this pathological entity. ONJ usually appears following oral surgical and dental procedures but sometimes occur spontaneously. These cases are mostly seen and treated by dentists and oral surgeons. The aim of this study was to discuss the frequency, characteristics, risk factors, management and histopathological features of ZA induced ONJ based on the literature and illustrated with five own cases. Thirty-two patients with MM who received ZA for a median period of 26.5 +/- 18.7 months (min: 5 months, max: 76 months) were evaluated. ONJ was detected in five patients and mean drug duration time was 34 months. The frequency was 15% and the patients were usually symptomatic. There was no significant difference in terms of the duration of ZA in patients with and without ONJ. Management of these established cases were performed with medical treatment, minor debridement, sequestrectomy, and combining bone resection with autologous platelet rich plasma. Our data indicate that ZA therapy has a major role in the development of ONJ a fact that should be considered by physicians treating MM patients.

Osteonecrosis of the jaw: what do bisphosphonates do?

Osteonecrosis of the jaw is a new disease, partly caused by bisphosphonates. It is commonly assumed that the bisphosphonates somehow cause cell death (osteocyte necrosis) within the jawbone, which makes it prone to chronic infection. In this article, an alternative pathogenetic theory is suggested, based on the normal effect of bisphosphonates. According to the new theory, the bone is alive until it is injured and infected, and the reduced resorptive ability due to bisphosphonates hinders the formation of a fresh bone surface for re-establishment of bone cell coverage. The theories are compared, based on the recent, very scarce literature. None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis.

Lymphadenitis cervicalis due to Mycobacterium interjectum in immunocompetent children.

UNLABELLED: This report presents two cases of cervical lymphadenitis due to Mycobacterium interjectum in healthy young children, identified by sequencing of the 16S rRNA gene. Surgical resection combined with chemotherapy resulted in cure. CONCLUSION: The attention of clinicians needs to be drawn to an emerging mycobacterial pathogen which might be overlooked or misidentified in routine laboratory testing.

Actinomyces vaccimaxillae sp. nov., from the jaw of a cow.

A previously undescribed Actinomyces-like bacterium was isolated from a lesion in the jaw of a cow. Based on its cellular morphology and the results of biochemical testing, the organism was tentatively identified as a member of the genus Actinomyces. Comparative 16S rRNA gene sequencing studies showed that the bacterium represents a hitherto unknown species within the genus Actinomyces, and is related to a group of species that includes Actinomyces turicensis and its close relatives. It is proposed that the unknown organism be classified as Actinomyces vaccimaxillae sp. nov. (the type strain is CCUG 46091T =CIP 107423T).

Opportunistic osteomyelitis in the jaws of children on immunosuppressive chemotherapy.

PURPOSE: Four children with an osteomyelitic process in the jaw bones while on cytotoxic chemotherapy were treated by radical surgery and antimicrobial chemotherapy. PATIENTS AND METHODS: Symptoms (local swelling and pain in the jaw, necrotic gingivitis, and spontaneous loss of teeth) appeared 3 weeks, 4 weeks, and 8 months after diagnosis of leukemia, and 8 days posttransplant in a patient with severe aplastic anemia. Three had the process in the mandible and one in the maxilla. Specific diagnoses of Aspergillus flavus, Saccharomyces cerevisiae, and Actinomyces species were obtained histologically from surgical samples. Treatment was radical surgery to remove all infected and necrotic tissue: removal of a substantial part of the mandible and loss of seven to eight permanent teeth in those with mandibular lesions. Actinomycosis was treated with penicillin for 2 years. The patients with fungal lesions received amphotericin B for 2, 5, and 6 months, with adjuvant itraconazole, fluconazole, or 5-fluorocytosine for 9-12 months. Anti-cancer chemotherapy was continued. RESULTS: All the bony lesions healed. The patient with acute myeloid leukemia died in relapse 1 year postdiagnosis; her aspergillus osteomyelitis had been inactive for 8 months. The other three patients are alive and well 1.9, 2.1, and 1.9 years after termination of antimicrobial therapy. CONCLUSIONS: We emphasize the necessity of specific diagnosis from appropriate surgical samples and conclude that in patients undergoing chemotherapy bony lesions caused by opportunistic microorganisms may be curable with aggressive surgery and prolonged medication.

Bacterial foci in the teeth, oral cavity, and jaw--secondary effects (remote action) of bacterial colonies with respect to bacteriospermia and subfertility in males.

Bacteriospermia requiring medical treatment were diagnosed in more than 70% of the subfertile patients who had since 1988 attended the gynecological clinic at the RWTH hospital in Aachen. In 23% of all cases specific treatment with antibiotics did not reduce the concentrations of bacteria in sperma. Thirty-six patients with bacteriospermia resistant to antibiotic therapy were then subjected to dental examination. A high incidence of potential dental foci was found in all patients. In a test group of 18 patients these sources of potential infection were eliminated. Between dental operations and therapy swabs were taken to determine bacterial levels and bacteriological composition. It could be demonstrated that the bacterial spectrum of the intraoral samples was almost identical with the spermiograms. Six months following completion of dental treatment a further spermiogram analysis was carried out. In the test group about two thirds of the spermiograms proved sterile. Spermatological parameters, such as motility, density and morphology, had also clearly improved. In the control group the findings of the spermiogram remained poor. This study indicates that a direct causal relationship exists between bacterial colonies (dental foci) and therapy-resistant bacteriospermia which probably leads to subfertility.

Jaw disease in macropod marsupials: bacterial flora isolated from lesions and from the mouths of affected animals.

Bacterial infections of the jaws are a common cause of death in macropods. Lesions and oral cavities from 50 affected animals yielded wide ranges of aerobic and anaerobic organisms. The most frequent isolate from lesions (81%) was Fusobacterium necrophorum, generally combined with other bacteria, but in 5 lesions, in pure culture. It was also isolated from 61% of mouths and this was the chief difference between the oral flora of affected and normal macropods. Other groups of organisms isolated from over 50% of lesions were: Gram-negative aerobic and anaerobic rods, streptococci, anaerobic Gram-positive cocci. Actinomycetes were isolated from 29% of lesions and from one lesion in pure culture. Differences in the flora were detected between lesions in bone and soft tissue and between closed and open lesions. Antibiotics were given to 22 animals, but without significant differences in frequencies of isolation of organisms between treated and untreated groups, and with no permanent elimination of infection. It was concluded that, while different organisms might be present in the complex of "jaw disease", the pathogenic agent in the majority of cases was F. necrophorum. Actinomycetes were capable of producing lesions in bone, but their role in "jaw disease" remains undefined.

Jawbone cavities and trigeminal and atypical facial neuralgias.

The possible role of dental and oral disease in the etiology of idiopathic trigeminal and atypical facial neuralgias has been examined. Among thirty-eight patients with idiopathic trigeminal neuralgia and twenty-three patients with atypical facial neuralgia, there was in nearly all instances a close relationship between pain experienced and the existence of cavities in alveolar bone and jawbone of the patients. The cavities were at the sites of previous tooth extractions and, although at times more than 1 cm. in a given diameter, were usually not detectable by x-rays. A new method for their detection and localization was developed empirically, based on the observation that peripheral infiltration of local anesthetic into or very close to the bone cavity rapidly abolished trigger and pain perception by patients during persistence of the anesthetic action. Histopathologic examination of bone removed from cavities by curettage revealed, in both idiopathic trigeminal and atypical facial neuralgias, a similar pattern characterized by a highly vascular abnormal healing response of bone. Some lesions presented a mild chronic inflammatory (lymphocytic) infiltration. Preliminary microbiologic studies of material from the walls of the cavities showed the existence within them of a complex, mixed polymicrobial aerobic and anaerobic flora. Treatment consisted of vigorous curettage of the bone cavities, repeated if necessary, plus administration of antibiotics to induce healing and filling-in of the cavities by new bone. Responses of patients to the above treatment consisted of marked to complete pain remissions, the longest of which has been for 9 years. Complete healing leads to complete and persistent pain remissions. It was concluded that in both idiopathic trigeminal and atypical facial neuralgias, dental and oral pathoses may be major etiologic factors.