Determination and identification of antibiotic-resistant oral streptococci isolated from active dental infections in adults.

OBJECTIVE: To determine and identify antibiotic-resistant bacteria (ARB) of oral streptococci from active dental infections in adults and its association with age and gender. MATERIAL AND METHODS: This cross-sectional study included 59 subjects from 18 to 62 years old. Ninety-eighth samples obtained from the subjects were cultivated in agar plates containing antibiotics amoxicillin/clavulanic acid (A-CA), clindamycin, and moxifloxacin (concentrations of 16, 32 or 64 µg/ml). PCR assay was performed to identify bacterial species. RESULTS: The bacterial species that showed more antibiotic-resistance (AR) was S. mutans (45.9%), followed by S. gordonii (21.6%), S. oralis (17.6%), S. sanguinis (9.5%), S. salivarius (5.4%) and S. sobrinus (0%). Moreover, clindamycin (59.4%) showed the highest frequency of AR. Moxifloxacin and A-CA showed an susceptibility >99.1%, while clindamycin showed the lowest efficacy (93.3%); there was a significant statistically difference (p < .01). The age group between 26 and 50 years old (32.2%) and females (28.8%) showed more multiresistance. Clindamycin showed a statistical difference (p < .05) when comparing groups by gender. CONCLUSIONS: Clindamycin was the antibiotic with the highest frequency of ARB and lower bactericidal effect. Moxifloxacin and A-CA showed the highest efficacy and the lowest ARB frequency. Streptococcus mutans was the bacterial specie that showed an increased frequency of AR.

The Use of Antibiotics in Odontogenic Infections: What Is the Best Choice? A Systematic Review.

PURPOSE: Odontogenic infections are a common problem in dentistry, and their treatment often requires the use of antibiotics besides the removal of the source of infection, which frequently makes it more difficult for clinicians to make a decision regarding the choice of antibiotic. This study aimed to answer the following questions through the Patient, Intervention, Comparison, Outcome (PICO) format: When should antibiotics be used in dental infections (DIs)? Which are the most effective drugs? How long should antibiotics be administered? MATERIALS AND METHODS: This was a systematic review using the PubMed, Scopus, and Cochrane databases without restriction as to the period researched. The variables analyzed in each article were the number of odontogenic infections in each study, type of study, surgical intervention performed, antibiotics administered, statistical differences between groups studied, and patients' evolution after treatment. RESULTS: The search included 1,109 articles. After the full reading of 46 articles, 16 were included in the final review and 30 were excluded. A sample of 2,197 DI cases was obtained, in which 15 different antibiotics were used, with a 98.2% overall cure rate. CONCLUSIONS: The studies showed that antibiotics were prescribed only in situations of regional and/or systemic body manifestations. In the case of DIs, once drainage has been performed and/or the cause of infection has been removed, all antibiotics tested are equally effective with respect to clinical cure, and the choice of antibiotics is not as successful as the local intervention treatment procedure. When the real need for antibiotic therapy is detected, antibiotics should be used for the shortest time possible until the patient's clinical cure is achieved.

Antibiotics in Endodontics: a review.

The overuse of antibiotics and the emergence of antibiotic-resistant bacterial strains is a global concern. This concern is also of importance in terms of the oral microbiota and the use of antibiotics to deal with oral and dental infections. The aim of this paper was to review the current literature on the indications and use of antibiotics and to make recommendations for their prescription in endodontic patients. Odontogenic infections, including endodontic infections, are polymicrobial, and in most cases, the prescription of antibiotics is empirical. This has led to the increasing use of broad-spectrum antibiotics even in cases where antibiotics are not indicated, such as symptomatic irreversible pulpitis, necrotic pulps and localized acute apical abscesses. In case of discrete and localized swelling, the primary aim is to achieve drainage without additional antibiotics. Adjunctive antibiotic treatment may be necessary in the prevention of the spread of infection, in acute apical abscesses with systemic involvement and in progressive and persistent infections. Medically compromised patients are more susceptible to complication arising from odontogenic infections and antimicrobials have a more specific role in their treatment. Therefore, antibiotics should be considered in patients having systemic diseases with compromised immunity or in patients with a localized congenital or acquired altered defence capacity, such as patients with infective endocarditis, prosthetic cardiac valves or recent prosthetic joint replacement. Penicillin VK, possibly combined with metronidazole to cover anaerobic strains, is still effective in most cases. However, amoxicillin (alone or together with clavulanic acid) is recommended because of better absorption and lower risk of side effects. In case of confirmed penicillin allergy, lincosamides such as clindamycin are the drug of choice.

Zinc: A precious trace element for oral health care?

This review will discuss the importance of Zinc in the maintenance of oral health. Zinc (Zn) is a trace element of valuable importance. In the oral cavity, it is naturally present at various sites such as dental plaque, dental hard tissues and saliva. It is proven to be effective against common prevalent oral health problems such as dental caries, gingivitis, periodontitis and malodour. It is being used in various oral health care products to control the formation of dental plaque and inhibiting the formation of dental calculus. It has the potential to sustain and maintain its elevated concentrations for a longer time particularly in the dental plaque and saliva on delivery from the mouth rinses and toothpastes. It has been reported that low concentrations of zinc have the capability to reduce dissolution and promote remineralization under caries simulating conditions. Most importantly low Zn2+ levels in the serum are useful as a tumour marker. Thus taking a note of its potentials, it can be concluded that zinc is a precious element for the maintenance of oral health.

A Retrospective Study of the Effectiveness of Four Different Treatments of Periodontal Disease in Equine Cheek Teeth.

Periodontal disease of equine cheek teeth is common and may lead to tooth loss if left untreated. Limited information is available comparing the effectiveness of treatment methods. The objective of this study was to retrospectively compare the effectiveness of 4 commonly used treatments in reducing periodontal pocket depth (in addition to routine dental treatment and occlusal equilibration). The 4 treatments compared were (1) removal of feed material, lavaging the pocket with dilute chlorhexidine, and then rinsing the mouth with chlorhexidine-containing mouthwash (CL); (2) CL plus placement of metronidazole into the pocket (M); (3) M plus the addition of polyvinyl siloxane temporary filling over the diastema (PVS); and (4) diastema widening to increase the interdental space, then PVS (DW). Pocket measurements were compared before and 2 to 6 months after treatment. Treatment groups CL, M, and PVS showed statistically significant reductions in pocket depth following treatment. The mean pocket depth reduction was the greatest in the DW group (and this was the only group with no cases having an increase in pocket depth), but this was not significant due to the small sample size. Additional analysis to compare effectiveness revealed a confounding effect of initial pocket depth. After accounting for this, DW was associated with smaller improvements than the other treatments, however, this was also based on a small sample size. After accounting for confounders, differences between treatments CL, M and PVS were not found to be significant, although all were associated with statistically significant reductions in pocket depth.

Successful Treatment of Dental Infection-Induced Chronic Cavernous Sinus Thrombophlebitis With Antibiotics and Low-Molecular-Weight Heparin: Two Case Reports.

Two patients developed cavernous sinus thrombophlebitis from a tooth infection. A 36-year-old man experienced a severe headache with bilateral third and sixth cranial nerve palsies after extraction of his left upper third molar. Another 53-year-old diabetic man developed fever, headache, and bilateral complete ophthalmoplegia after a tooth infection. The brain magnetic resonance imaging scans of both patients showed bilateral cavernous sinus partial thrombosis. Broad-spectrum antibiotics plus low-molecular-weight heparin successfully resolved all symptoms. Both patients recovered fully without any recurrence at the 3-month follow-up visit.

Effect of Causative Tooth Extraction on Clinical and Biological Parameters of Odontogenic Infection: A Prospective Clinical Trial.

PURPOSE: To prospectively compare changes of body temperature, white blood cell count, fibrinogen, and C-reactive protein between odontogenic infections in which the responsible tooth was removed and odontogenic infections in which the treatment included no extraction. MATERIALS AND METHODS: The sample was composed of patients admitted to the authors' maxillofacial unit for odontogenic infection from 2010 through 2013. One hundred seventy-nine patients were categorized into an extraction or a non-extraction group based on whether the causative tooth was non-restorable or restorable, respectively. Non-restorable teeth were extracted at admission of the patient. Otherwise, the treatment protocol, including incision of the involved space in conjunction with intravenous antibiotics, was the same for the 2 groups. The parameters were measured and recorded at admission and 2 days later. Data records were statistically analyzed by comparing the change of the parameters studied between the extraction and non-extraction groups. P values less than .05 were regarded as statistically significant. RESULTS: One hundred seventy-nine patients fulfilled the inclusion criteria and were enrolled in the study. The mean age of the patients was 39.1 years (minimum, 14 yr; maximum, 81 yr; standard deviation, 15.4 yr). One hundred nine patients (60.9%) were male, and 70 (39.1%) were female. Differences in the mean decrease of axillary temperature, white blood cell count, fibrinogven, and C-reactive protein between the 2 groups were 0.178, 2,300, 1.01, and 0.64, respectively. All these differences were statistically significant (P =.02, .001, .001, and .001, respectively). Also, the mean hospital stay in the extraction group was 1.05 days shorter than in the non-extraction group, with the difference being statistically significant (P = .006). CONCLUSIONS: In odontogenic maxillofacial infections, extraction of the causative tooth is associated with a faster clinical and biological resolution of the infection.

Diagnosis and prescribing pattern of antibiotics and painkillers among dentists.

PURPOSE: To examine the pattern of antibiotic and painkiller prescriptions per diagnosis by dentists. MATERIALS AND METHODS: A cross-sectional study was conducted in Karachi, Pakistan. Dentists in the outpatient departments of the Dr. Isharat-ul-Ebad Khan Institute of Oral Health Sciences (DIKIOHS) filled out a form for each patient visiting during a two-week period. The form included: personal history of the patient, i.e. name, age, sex and education, patient's complaint(s), medical history, dental history, full examination of the teeth and oral cavity, treatment need as far as different specialties are concerned, investigations, provisional diagnosis and treatment given. The WHO ATC system for drug classification was used. The number of prescriptions and defined daily doses (DDD) were recorded. RESULTS: A total of 709 patient forms (355 for male patients and 354 for female patients) were collected and included in the analysis. Of these, 123 (17%) included antibiotics and 455 (64%) painkillers. Caries/pulpitis was the most common diagnosis (n = 222; 31% of cases), of which 48 (21%) were prescribed antibiotics. Amoxicillin and metronidazole were the most common antibiotics prescribed for this diagnosis (n = 25); for caries/pulpitis diagnosis, 44 DDD/100 patients were prescribed. This was also the diagnosis for which painkiller prescription was most common (n = 191; 86%), with 102 DDD/100 patients. CONCLUSION: Our study shows the prescription pattern of antibiotics and painkillers by dentists in Pakistan for the first time. There is a clear need to emphasise correct diagnostic methods and develop contextualised prescription guidelines and educational initiatives, so that the optimum effect of antibiotics and painkillers will be achieved without compromising patients' health.

Comparative evaluation of Sapindus Mukorossi extract with 17% EDTA on smear layer removal in various parts of the tooth root.

OBJECTIVES: This study aimed to compare the effectiveness of an experimental root canal irrigant and 17% Ethylene-di-amine tetra acetic acid for removal of the smear layer in the coronal, middle and apical portions of the root canal. MATERIALS AND METHODS: Ninety human single rooted maxillary and mandibular teeth were selected for this study. The teeth were randomly divided into two experimental groups and one control group as follows: Group A (Ethanolic extract of Sapindus Mukorossi), Group B (17% EDTA), and Group C (Distilled water). The root canals of all three groups were prepared with stainless steel K-files by means of the standard step-back technique and irrigated with 5.25% sodium hypo chloride. The teeth were decoronated, following the irrigation and divided longitudinally into two-halves and visualized using scanning electron microscope (SEM) for the amount of smear layer present utilizing the three-point score system. The observations were noted both before and after the treatment. Nonparametric tests were applied for the comparison and p-value ⩽ 0.05 was considered as statistically significant. RESULTS: It was evident from that smear layer was completely removed in coronal portion of 27 out of 30 teeth in-group A. For middle and apical areas of group A, 24 and 19 teeth showed complete smear layer removal. In-group B it was found that there were 24, 21, and 3 teeth at coronal, middle and apical, areas respectively where smear layer were completely absent. Intra group comparison showed a significant difference (p = 0.002) in smear layer removal was found for group A at coronal, middle and apical thirds. Similarly, a significant difference (p = 0.001) was also found for group B; however heavy smear layer was found among the three parts of the canal for group C. CONCLUSIONS: Ethanolic extract of Sapindus Mukorossi have higher effectiveness in removing the smear layer from the root canal in comparison to 17% EDTA.

Oral mucosal morphea: a new variant.

Morphea is a cutaneous disorder characterized by an excessive collagen deposition. While in almost all cases the sclerosing process exclusively affects the skin, there are anecdotal cases in which associated mucosal involvement has been described. We here report the case of a woman developing a whitish indurated plaque over the left upper vestibular mucosa and hard palate leading to dental mobility and exposure of the roots of several teeth. Cone beam computed tomography of the left maxilla showed bone resorption involving the upper cuspid to the second molar region with widened periodontal ligament spaces, while light microscopy studies demonstrated epithelial atrophy and fibrosis of the dermis extending into the submucosa with hyalinization of subepithelial collagen. Our observation expands the spectrum of clinical presentations of morphea and provides the first example of isolated oral morphea. Its recognition is important to avoid significant local complications.

[Traditional practices and exploitation of medicinal plants in odontostomatology in Ivory Coast]. / Pratiques traditionnelles et valorisation des plantes médicinales en odonto-stomatologie en Côte d'Ivoire.

Traditional medicine of which is a part traditional odontology occupies an important place within the African societies. It often constitutes the first appeal (80 % of the population) because of the high cost of the care, the incapacity of the human and material resources but also the faiths of the populations. This reality makes valuation of the traditional odontology a necessity. This study comes within this framework. It's a contribution for a better knowledge of practices and plants used in traditional odontology in Ivory Coast. So, after a presentation of some traditional knowledge's and their fields of application, the authors review studies made on the efficiency of plants in the prevention of tooth decay and the treatment of some oral diseases. The objective of these researches is to elaborate effective and financially affordable traditional improved drugs.

Intraoral management of odontogenic infection associated with severe trismus under local anesthesia.

Trismus is defined as a tonic contraction of the muscles of mastication. It can also refer to limited mouth opening of any cause. Trismus is a classical symptom of masticatory space infections and it can be a sign of an infection in the anterior compartment of lateral pharyngeal space. Common causes in clinical practice followed by trismus are odontogenic infection which can be periodontal or pericoronal. This article will present a clinical report on intraoral management of mandibular odontogenic infection accompanied by severe trismus under local anesthesia using modified Akinosi technique in an outpatient environment. Treatment and postoperative period were routine. This kind of approach provides access to the infection at an early stage without general anesthesia, it shortens the hospital treatment and it enables faster recovery. KEY WORDS: Local Anesthesia, Odontogenic infection, Trismus.

Duration for apical barrier formation in necrotic immature permanent incisors treated with calcium hydroxide apexification using ultrasonic or hand filing.

BACKGROUND/PURPOSE: Traumatic injury usually results in pulp necrosis of immature permanent incisors in children aged 7-10 years. Calcium hydroxide apexification is the most common treatment for necrotic, immature permanent teeth. This study compared the duration for apical barrier formation in necrotic immature permanent incisors treated with calcium hydroxide apexification using ultrasonic or hand filing. METHODS: Thirty-two trauma-induced necrotic immature permanent incisors with or without a periapical lesion (PL) were selected from children aged 7-10 years. They were evenly divided into four groups. Teeth in groups 1 (with PL) and 2 (without PL) were treated with ultrasonic filing, and teeth in groups 3 (with PL) and 4 (without PL) were treated with hand filing. The canals were cleaned with 0.2% chlorhexidine solution during treatment and then compactly filled with calcium hydroxide. The patients were followed up once every 1-3 weeks to change the intracanal medication and to detect when the apical barrier formed. RESULTS: The mean duration for apical barrier formation was 11.1 +/- 1.1 weeks, 11.8 +/- 1.0 weeks, 13.3+/-0.9 weeks and 13.4 +/- 0.7 weeks for groups 1, 2, 3 and 4, respectively. Student's t test showed significant differences in the mean duration for apical barrier formation between groups 1+2 and 3 + 4 (p = 0.000), groups 1 and 3 (p = 0.000), and groups 2 and 4 (p = 0.002). These results indicated that teeth treated with ultrasonic filing required a shorter mean duration for apical barrier formation than teeth treated with hand filing regardless of the presence of PL or not. CONCLUSION: Ultrasonic filing with 0.2% chlorhexidine as an irrigant is effective for disinfection of the root canal and can shorten the duration for apical barrier formation in necrotic permanent incisors treated with calcium hydroxide apexification.

Oral health of adults with serious mental illnesses: a review.

(A) To assess the prevalence of suboptimal oral health in adults with SMI in studies published in 1971-2009; (B) To describe approaches that promote oral health among adults with SMI. A total of 57 randomized, quasi-randomized, cross-section, and cohort studies from samples of 38-4,769 mental health consumers are identified through database, journal, and Internet searches (Cochrane, FASTSTATS, PUBMED, WHO.int). Selected studies are inclusive for the sample, reported statistical power, and external validity. Oral health adverse outcomes (xerostomia, sialorrhoea, dental caries, extracted teeth, malocclusion, periodontal disease, edentulous, oral cancer) are considered as measurable outcomes. This review suggests a substantial prevalence of suboptimal oral health (61%) among individuals with serious mental illnesses. The following outcomes are mostly met: xerostomia, gross caries, decayed teeth, and periodontal disease. Poor oral hygiene, higher intake of carbonates, poor perception of oral health self-needs, length of psychotropic treatment, and less access to dental care determine suboptimal oral health among this population. Further replication of this research should generate gender-wise ethnic cohorts, including detailed observations of environmental factors, and medical problems that contribute to suboptimal oral health. This review highlights the importance of bridging dental health education to psychiatric rehabilitation programs.

Antibiotic prescription patterns for treating dental infections in children among general and pediatric dentists in teaching institutions of Karachi, Pakistan.

BACKGROUND: Antibiotics are regularly prescribed by dental professionals in their practice, for the purpose of dental treatment as well as for the prevention of infection. The inappropriate use of antibiotics is a significant factor in the rise of antibiotic resistance. There is an immediate need for the advancement of prescribing guidelines and instructive polices to encourage the rational and appropriate utilization of medications especially antibiotics in dentistry. OBJECTIVE: The aim of this study was to identify the frequency of antibiotic prescription for treating dental infections in children among dentists in teaching institutions of Karachi, Pakistan and whether they are adhering to the prescribed international guidelines. METHODS: A cross-sectional study was conducted in three private and two public colleges of Karachi. After taking written informed consent and checking the inclusion criteria, a total of 380 participants were interviewed using a pre-designed validated questionnaire which included demographic profile and clinical case scenarios. Data were entered and analyzed on SPSS version 20. Inferential analysis was performed using chi-square test. The significance level was set at 0.05. RESULTS: Of the 380 subjects, a majority (71.3%) treated 15 or less children per month (n = 271) while 28.7% of dentists (n = 109) treated more than 15 children per month. Overall adherence to American Academy of Pediatric Dentistry guidelines was low from 26.1% to 44.2%. The difference between adherence of dentists with low and high volume of pediatric patients was significantly different for case scenarios 1, 3, 4 and 5 (p<0.001 for all) where dentists who treated 15 or less children per month were more likely to be adherent to standard antibiotic prescription guidelines than those who treated more than 15 children per month. CONCLUSIONS: This study shows that majority of dentists, particularly dentists with high volume of pediatric patients lacked adherence to professional guidelines for prescribing antibiotics for treating dental infection in children. There seem to be a lack of harmony between the recommended professional guidelines and the antibiotic prescribing pattern of dentists. Regular updates and continuing medical education for the health professionals regarding comprehensible and specific professional guidelines may lead to improved adherence of antibiotics prescription amongst dentists.

Dental opioid prescribing rates after the up-scheduling of codeine in Australia.

The misuse of pharmaceutical opioids is a major public health issue. In Australia, codeine was re-scheduled on 1 February 2018 to restrict access; it is now only available on prescription. The aim of this study was to measure the change in dental opioid prescriptions, one year before and after the codeine re-scheduling in Australia and to assess dental prescribing rates of opioids for 2018 by population and by clinician. Data was extracted for dental opioids for the year immediately prior and after the codeine up-schedule (1 February 2017-31 January 2019) from the publicly-available national prescription database (Pharmaceutical Benefits Scheme). Descriptive statistics, T-tests and odds ratios were used to identify significant prescribing differences. Codeine, codeine/paracetamol, oxycodone and tramadol use increased significantly the year after the codeine restriction than the previous year (13.8-101.1%). Australian dentists prescribed 8.6 prescriptions/1,000 population in 2018, with codeine/paracetamol accounting for most prescriptions (96%). The significant increase in opioid prescribing highlights that Australian dentists may be contributing to the misuse of pharmaceutical opioids. Educational efforts should be targeted at the appropriate use of opioids and patient selection. Dentists should be added to the prescription monitoring system SafeScript so they can make informed decisions for patients who are potentially misusing opioids.

Prospects on Nano-Based Platforms for Antimicrobial Photodynamic Therapy Against Oral Biofilms.

Objective: This review clusters the growing field of nano-based platforms for antimicrobial photodynamic therapy (aPDT) targeting pathogenic oral biofilms and increase interactions between dental researchers and investigators in many related fields. Background data: Clinically relevant disinfection of dental tissues is difficult to achieve with aPDT alone. It has been found that limited penetrability into soft and hard dental tissues, diffusion of the photosensitizers, and the small light absorption coefficient are contributing factors. As a result, the effectiveness of aPDT is reduced in vivo applications. To overcome limitations, nanotechnology has been implied to enhance the penetration and delivery of photosensitizers to target microorganisms and increase the bactericidal effect. Materials and methods: The current literature was screened for the various platforms composed of photosensitizers functionalized with nanoparticles and their enhanced performance against oral pathogenic biofilms. Results: The evidence-based findings from the up-to-date literature were promising to control the onset and the progression of dental biofilm-triggered diseases such as dental caries, endodontic infections, and periodontal diseases. The antimicrobial effects of aPDT with nano-based platforms on oral bacterial disinfection will help to advance the design of combination strategies that increase the rate of complete and durable clinical response in oral infections. Conclusions: There is enthusiasm about the potential of nano-based platforms to treat currently out of the reach pathogenic oral biofilms. Much of the potential exists because these nano-based platforms use unique mechanisms of action that allow us to overcome the challenging of intra-oral and hard-tissue disinfection.

Development of Denticap, a matrix based sustained release formulation for treatment of toothache, dental infection and other gum problem.

Toothache is a serious problem worldwide. To give relief from this intolerable toothache, doctors prescribe painkillers along with antibiotics. Most of the painkillers, if not all, produce hyperacidity and gastric irritation upon oral administration. Oral antibiotics have slow onset of action and undergo hepatic "first-pass" effect. Moreover, available dental formulations are mostly liquid and last only few hours upon application, before being washed out by saliva. To overcome the above-mentioned problems, a soft polymeric mold containing antibiotic and analgesic drugs and having an appropriate consistency to adhere to the tooth, was developed for sustained drug release to provide better relief in dental patients. Eudragit L 100-55, carbopol 971 P, gum karaya powder and ethyl cellulose were used to prepare the mold "Denticaps" containing Lidocaine hydrochloride and Amoxicillin trihydrate individually and in combination, by mixing and solvent evaporation technique. Different physicochemical characterization studies such as mucoadhesion test, water absorption capacity and swelling index were carried out. In vitro drug release studies showed sustained release of Lidocaine hydrochloride and Amoxicillin trihydrate in simulated saliva for 24 h. Further studies are warranted to succeed with these formulations in humans. Upon success, this type of dosage form may open up new avenues towards dentistry.

Penetration of moxifloxacin into rat mandibular bone and soft tissue.

OBJECTIVE: Based on its in vitro activity and spectrum of activity, the new 8-methoxyquinolone antibiotic moxifloxacin (MXF) seems suited for the antibiotic therapy of odontogenic infections. Penetration into the relevant tissue is another prerequisite for clinical efficacy. For this reason, the levels of MXF in plasma, soft tissue, and mandibular bone were determined in an animal model with Wistar rats. MATERIAL AND METHODS: Samples of 49 rats were analyzed. Tissue samples were homogenized and proteins were precipitated. The pharmacokinetic evaluation was conducted based on non-compartmental analysis. RESULTS: The concentration-time courses of tissues show a more plateau-shaped curve compared to plasma. Calculated AUC (area under the curve) ratios tissue:plasma were M. masseter:plasma = 2.64 and mandibles:plasma = 1.13. CONCLUSIONS: Administration of antibiotics is considered an important part of therapy during and/or after surgical procedures in the maxillofacial area. Because of the good penetration into bone and muscle tissues demonstrated in Wistar rats, MXF might be an option for clinical application in this indication.