In vitro minocycline activity on superinfecting microorganisms isolated from chronic periodontitis patients

Chronic periodontitis is the most common type of periodontitis and it is associated with various species of microorganisms. Enteric rods, Pseudomonas, Staphyloccocus and Candida have been retrieved from periodontal pockets of patients with chronic periodontitis and correlated to cases of superinfection. Local or systemic antibiotic therapy is indicated to reinforce the effects of the conventional mechanical therapy. Minocycline has been suggested as one of the most effective drugs against periodontal pathogens. The aim of this work was to evaluate the minimal inhibitory concentration (MIC) of minocycline on superinfecting microorganisms isolated from the periodontal pocket and the oral cavity of individuals with chronic periodontitis. Isolates of Enterobacteriaceae (n = 25), Staphylococcus spp. (n = 25), Pseudomonas aeruginosa (n = 9) and Candida spp. (n = 25) were included in the study. Minimal inhibitory concentrations (MIC) of minocycline were determined using the Müeller-Hinton agar dilution method. Staphylococcus spp. isolates were the most sensitive to minocycline with a MIC of 8 microg/mL, followed by Enterobacteriaceae with a MIC of 16 microg/mL. The concentration of 16 microg/mL inhibited 96% of Candida spp. isolates. The MIC for 88.8% of the isolates of Pseudomonas aeruginosa was 128 microg/mL. A concentration of 1,000 microg/mL was not enough to inhibit 100% of the tested isolates.     

In vitro activity of amoxicillin, clindamycin, doxycycline, metronidazole, and moxifloxacin against oral Actinomyces

Actinomyces spp have been increasingly associated with endodontic infections. However, the antimicrobial susceptibility of this genus has not been studied extensively. The objective of this study was to determine the susceptibility of oral isolates of Actinomyces naeslundii, Actinomyces gerencseriae, Actinomyces israelii, Actinomyces viscosus, and Actinomyces odontolyticus to amoxicillin, clindamycin, doxycycline, metronidazole, and moxifloxacin using in vitro assays. The minimum inhibitory concentration (MIC) of each bacterial isolate was determined by using E-test strips (AB Biodisk, Solna, Sweden). The MIC(90) was 0.19 microg/mL for amoxicillin, 0.25 microg/mL for doxycycline, 0.50 microg/mL for moxifloxacin, and 1.00 microg/mL for clindamycin. However, metronidazole was not active against any of the Actinomyces spp tested (MIC(90)>256 microg/mL).     

二甲胺四环素胶原制剂体外抗菌研究

目的研究胶原蛋白为载体复合二甲胺四环素制成的牙周缓释制剂的抗菌效果,以期寻找辅助治疗牙周炎的新制剂。方法采用杯碟法对含20mg/g盐酸二甲胺四环素的胶原牙周缓释剂和派丽奥软膏进行牙周常见致病菌的抑菌实验,测定最小抑菌浓度（MIC）和抑菌环直径。菌珠选用国际标准菌株牙龈卟啉单胞菌、中间型普里沃氏菌、巨核梭形杆菌、伴放线放线杆菌和粘性放线菌。结果胶原牙周缓释制剂和派丽奥软膏对各实验菌株均有抑菌作用,牙龈卟啉单胞菌、中间型普里沃氏菌、巨核梭形杆菌、伴放线放线杆菌的MIC为0.31mg/L,粘性放线菌的MIC为1.2mg/L。2种药物比较抑菌效果无显著性差异（P〉0.05）。结论胶原牙周缓释制剂对牙周主要致病菌具有良好的抑制作用。     

Effect of Periodontal Therapy With Amoxicillin–Metronidazole on Pharyngeal Carriage of Penicillin‐ and Erythromycin‐Resistant Viridans Streptococci

Background: Previous studies have focused on antibiotic resistance of Gram‐negative bacteria before and after periodontal therapy. The purpose of this analysis is to assess changes in resistance patterns of the commensal Gram‐positive microbiota. The viridans group streptococci (VGS) have been suggested to serve as reservoirs of resistance genes for more pathogenic streptococci and may be implicated in some non‐oral infections. Methods: In this randomized clinical trial, 80 patients with periodontitis are distributed randomly into two groups. In group A, patients received 375 mg amoxicillin and 500 mg metronidazole three times per day for 7 days during the non‐surgical treatment phase (T1). In group B, the antibiotics were administered during the surgical phase (T2). Resistance of VGS to penicillin and erythromycin was determined by the epsilometer test. Results: At baseline, VGS from 12.5% (group A) and 11.8% (group B) of patients had a minimum inhibitory concentration (MIC) >2 μg/mL to penicillin. Three months after T1, VGS from 15.6% and 16.7% of patients had an MIC >2 μg/mL, respectively. Six months after T2 VGS from 5.9% and 5.9% and 12 months after T2 VGS from 6.1% and 6.3% patients had an MIC >2 μg/mL. There was no effect of therapy with antibiotics, administered either in T1 or T2, on the carriage of penicillin‐resistant VGS. Erythromycin resistance was high at baseline and remained unchanged throughout the study. MICs for penicillin and erythromycin were correlated (P <0.05). Conclusion: Amoxicillin plus metronidazole did not significantly affect the resistance pattern of the VGS to penicillin or erythromycin.     

Bactericidal effects of human neutrophils and sera on selected endodotic pathogenic bacteria in an anaerobic environment

Phagocytosis by normal human neutrophils and the bactericidal activity of normal human pooled serum were measured under anaerobic conditions on six endodontic pathogenic bacterial species from the genera Actinomyces, Bacteroides, Fusobacterium, Peptostreptococcus and Streptococcus. The results revealed that Actinomyces viscosus was not killed either by human neutrophils or by 20 per cent serum; Peptostreptococcus anaerobius was not killed by either 20 per cent or 95 per cent serum; and Bacteroides intermedius was susceptible to both 20 per cent and 95 per cent serum, but was not killed by neutrophils after exposure for 20 minutes. The other species showed intermediate susceptibility patterns. Such results suggest that oral pathogens vary with regard to the bactericidal effects of these two host defense mechanisms, and that this variation may at least in part explain the relative quantities of microbes recovered in certain oral infections.     

Antibiotic susceptibility of anaerobic bacteria from the human oral cavity

Anaerobic, agar-dilution, minimal inhibitory concentrations (MICs) of 18 antibiotics are given for the numerically important bacterial groups from the human oral cavity. Strains are divided into susceptibility categories using the guidelines for interpretation of MICs suggested by the National Committee for Clinical Laboratory Standards. These guidelines are based on data on antibiotic concentrations attainable in serum following various dosage regimens. MICs are also compared with attainable gingival fluid levels where these are known. The highest percentages of strains were susceptible to tetracycline, with 89% of the 139 strains tested susceptible to serum levels and 97% conditionally susceptible to attainable gingival fluid levels. Ninety-eight percent of strains were conditionally susceptible to attainable gingival fluid levels of minocycline, but many strains, including Actinobacillus actinomycetemcomitans, were only moderately susceptible to attainable serum levels of this tetracycline analogue. Carbenicillin was effective against most groups of organisms, with the important exception of A. actinomycetemcomitans, at serum levels attainable with oral formulations of carbenicillin. Only 2% of the total strains tested were resistant to penicillin, while 33% of strains were categorized as moderately susceptible. Clindamycin was active against many strains of Gram-negative bacteria but was not active against A. actinomycetemcomitans, some Bacteroides, Eikenella corrodens, or the anaerobic vibrios. Metronidazole was active against A. actinomycetemcomitans, all five groups of oral Bacteroides tested, and against Capnocytophaga species. Chloramphenicol was active against A. actinomycetemcomitans, but not against most of the other groups of oral organisms. Nearly all groups contained strains non-susceptible to serum levels attainable with the usual doses of erythromycin, spiramycin, vancomycin, kanamycin, neomycin, streptomycin, doxycycline, oxytetracycline, or chlortetracycline; several strains were resistant to maximum attainable serum levels of each of these antibiotics except doxycycline.     

Tetracycline and its derivatives strongly bind to and are released from the tooth surface in active form

Several antibiotics were found to adsorb to saliva-coated enamel and to inhibit in vitro plaque formation by pure cultures of oral bacteria: Actinomyces viscosus, Actinomyces naeslundii and Streptococcus mutans. Tetracycline, minocycline and oxytetracycline adsorbed to the greatest degree, showing 100-fold higher adsorption than spiramycin, the test antibiotics with least adsorption. Inhibition of in vitro plaque formation was found to require both drug substantivity (capacity for adsorption) and antimicrobial activity. Inhibition of plaque formation in the in vitro assay employed correlated well with clinical efficacy.     

In vitro antimicrobial and resistance-modifying activities of aqueous crude khat extracts against oral microorganisms

OBJECTIVES: To assess antimicrobial activities of aqueous crude khat (Catha edulis) extracts against a panel of oral microorganisms and to test their ability to modify bacterial resistance to tetracycline and penicillin in vitro. DESIGN: Lyophilized aqueous extracts were prepared from three khat cultivars. The agar dilution method of the NCCLS was used to test the extracts, at concentrations of 20-1.25 mg/ml, against 33 oral strains. MIC was defined as the lowest concentration at which there was no visible growth. Slight growth was defined as marked growth reduction (MGR). The E-test was used to determine the MICs of tetracycline and penicillin-G for three resistant strains in absence and presence of a sub-MIC of the khat extracts (5mg/ml). RESULTS: Eighteen strains (55%) were sensitive to the extracts (MICs 5-20 mg/ml). Most of these were periodontal pathogens with Porphyromonas gingivalis and Tannerella forsythensis being the most susceptible (MIC 5-10mg/ml). Veillonella parvula, Actinomyces israelii and some streptococci were not sensitive. Except for Lactobacillus acidophilus that showed MGR at 1mg/ml, cariogenic species were neither sensitive. The extracts were active against Streptococcus pyogenes (MIC 10-20 mg/ml) but not against Candida albicans and Staphylococcus aureus. The presence of the khat extracts at a sub-MIC resulted in a 2-4-fold potentiation of the tested antibiotics against the resistant strains. CONCLUSIONS: Khat has water-soluble constituents possessing selective antibacterial activity against oral bacteria. There is preliminary evidence for presence of an antibiotic resistance-modifying component. Further investigation is needed to identify the active components and assess their clinical relevance.     

Topical minocycline for managing symptoms of recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is a common ulcerative condition of the oral mucosa. In this study, minocycline oral rinses were compared to a placebo in patients suffering from frequent episodes of RAS. Thirty‐three patients with RAS were randomly allocated to topical therapy with 0.2% minocycline or a placebo aqueous solution mouthwash. Seven patients also participated in a blind crossover study. The intensity of pain was recorded daily using a visual analogue scale. Minocycline mouthwashes resulted in significant reduction in the severity and duration of pain due to RAS. The findings in the subgroup that participated in the crossover were consistent with outcomes in the randomized study. The findings of this study show that minocycline oral rinses reduce pain in patients with RAS and may have implications for the use of minocycline in other non‐infectious inflammatory ulcerative oral mucosal diseases.     

The effectiveness of scaling and root planing with adjunctive time-release minocycline using an open and closed approach for the treatment of periodontitis

The purpose of this study was to determine the effectiveness of scaling and root planing using a closed and open approach (papilla reflection) with and without a locally delivered antibiotic (minocycline hydrochloride microspheres) in the treatment of moderate to advanced chronic periodontitis. Twenty-five periodontal recall patients with four or more probing depths of 5.0 to 9.0 mm and bleeding on probing (BOP) participated in this double-blind trial. Each of four sites per patient was randomly assigned a different treatment: scaling/root planing only; scaling/root planing followed by minocycline placement; gingival papilla reflection followed by scaling/root planing and flap closure; and gingival papilla reflection, scaling/root planing, minocycline placement, and flap closure. At baseline and each subsequent appointment, probing depth, BOP, and clinical crown length were recorded. Patients returned at three months for measurements and supportive periodontal therapy, and at six months for final measurements. Patients followed their usual oral hygiene regimens. Data were analyzed for significant differences using a repeated measure ANOVA and a Student t-test. All treatments resulted in reduction of probing depths (average of 1.76 mm) and a marked reduction in BOP at six months. While the papilla reflection plus minocycline showed the greatest reduction in probing depth (1.91 mm) and the greatest decrease in BOP (20% at three months and 28% at six months), the differences were not significant (p > 0.05). Clinical crown lengths did not change significantly in the treatment sites; therefore, improvements in probing depth can be attributed to improved clinical attachment levels (long junctional epithelium). The combination therapies did not differ significantly from scaling/root planing alone in decreasing probing depths and BOP.     

Treatment of Cervicofacial Actinomycosis: A report of 19 cases and review of literature

Objectives: Actinomycosis is a chronic suppurative granulomatous infection caused by the Actinomyces genus. Orocervicofacial actinomycosis is the most common form of the disease, seen in up to 55% of cases. All forms of actinomycosis are treated with high doses of intravenous penicillin G over two to six weeks, followed by oral penicillin V. Large studies on cervicofacial actinomycosis are lacking. Therefore proper guidelines for treatment and treatment duration are difficult to establish. The aim of this study is to establish effective treatment and treatment duration for orocervicofacial actinomycosis. Study design: A Pubmed and Embase search was performed with the focus on treatment and treatment duration for cervicofacial actinomycosis. The hospital records of all patients presenting to our department with head and neck infection from January 2000 to December 2010 were reviewed, retrospectively. The following data were collected: age, gender, clinical presentation, aetiology, duration of symptoms, microbiological findings, treatment, and duration of treatment. The treatment and treatment duration is subsequently compared to the literature. Results: The literature search provided 12 studies meeting the inclusion criteria. All studies were retrospective in nature. Penicillin or amoxicillin/clavulanic acid are the preferred antibiotic regimens found in the literature. Most of our patients were treated with a combination of penicillin G 12 million units/day and metronidazol 500 mg 3/day, most commonly for a duration of 1 – 4 weeks, being shorter than the 3 – 52 weeks reported in the literature. Conclusion: When actinomycosis is suspected, our review has shown that a surgical approach in combination with intravenous penicillin and metronidazol until clinical improvement is seen, followed by oral antibiotics for 2 – 4 weeks is generally efficient. Key words:Actinomycosis, actinomyces, actinomycosis treatment, cervicofacial infection, actinomycosis diagnosis, head and neck infection.     

Antimicrobial therapy using a local drug delivery system (Arestin) in the treatment of peri-implantitis. I: Microbiological outcomes

OBJECTIVES: To assess the microbiological outcome of local administration of minocycline hydrochloride microspheres 1 mg (Arestin) in cases with peri-implantitis and with a follow-up period of 12 months. MATERIAL AND METHODS: After debridement, and local administration of chlorhexidine gel, peri-implantitis cases were treated with local administration of minocycline microspheres (Arestin). The DNA-DNA checkerboard hybridization method was used to detect bacterial presence during the first 360 days of therapy. RESULTS: At Day 10, lower bacterial loads for 6/40 individual bacteria including Actinomyces gerensceriae (P<0.1), Actinomyces israelii (P<0.01), Actinomyces naeslundi type 1 (P<0.01) and type 2 (P<0.03), Actinomyces odontolyticus (P<0.01), Porphyromonas gingivalis (P<0.01) and Treponema socranskii (P<0.01) were found. At Day 360 only the levels of Actinobacillus actinomycetemcomitans were lower than at baseline (mean difference: 1x10(5); SE difference: 0.34x10(5), 95% CI: 0.2x10(5) to 1.2x10(5); P<0.03). Six implants were lost between Days 90 and 270. The microbiota was successfully controlled in 48%, and with definitive failures (implant loss and major increase in bacterial levels) in 32% of subjects. CONCLUSIONS: At study endpoint, the impact of Arestin on A. actinomycetemcomitans was greater than the impact on other pathogens. Up to Day 180 reductions in levels of Tannerella forsythia, P. gingivalis, and Treponema denticola were also found. Failures in treatment could not be associated with the presence of specific pathogens or by the total bacterial load at baseline. Statistical power analysis suggested that a case control study would require approximately 200 subjects.     

Interactions of sanguinarine and zinc on oral streptococci and Actinomyces species

Sanguinaria extract, which contains benzophenanthridine alkaloids, has been used as a folk medicine for many years. Minimum inhibitory and minimum bactericidal concentrations (MIC and MBC values) for sanguinarine were determined for common and etiologically important plaque bacteria. Because the efficacy of sanguinarine is believed to be enhanced by zinc, isobolograms were assessed to determine their mode(s) of interaction. Hydrogen ion concentration influenced the inhibitory activity of both sanguinarine and zinc. For sanguinarine, at the optimum pH (6.5), MIC values were 4 or 8 micrograms/ml for Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguis, Actinomyces viscosus and Actinomyces naeslundii. MIC values were 0.125-0.50 mmol Zn/ml. MBC values ranged from 1 to 8 mmol Zn/ml at pH 5.5. Isobologram data revealed that sanguinarine and zinc interacted synergistically. Viadent oral rinse, which contained 300 micrograms sanguinaria extract/ml and 0.2% zinc chloride (14.9 mmol Zn/l), was inhibitory to all strains tested. MIC values were 1 or 2% (ml Viadent oral rinse/100 ml aqueous solution) for all strains except A. viscosus for which the MIC value was 12% (vol/vol).     

Oral mucosal pigmentation secondary to minocycline therapy: report of two cases and a review of the literature

Minocycline is a semisynthetic broad-spectrum antimicrobial agent that was first introduced into clinical practice in 1967. The most common use of minocycline is for the long-term treatment of acne vulgaris. A well-recognized side effect of minocycline treatment is pigmentation, which has been reported in multiple tissues and fluids including thyroid, skin, nail beds, sclera, bone, and teeth. While there have been several reports of oral pigmentation following minocycline therapy, these have been, for the most part, pigmentation of the underlying bone with the overlying oral mucosa only appearing pigmented. We report two cases of actual pigmented oral mucosal lesions on the hard palate secondary to minocycline therapy with the accompanying histopathology, followed by a discussion of minocycline-induced oral pigmentation and a differential diagnosis of these lesions.     

Antimicrobial Action of Minocycline Microspheres Versus 810‐nm Diode Laser on Human Dental Plaque Microcosm Biofilms

Background: The purpose of this study is to investigate the antimicrobial effects of minocycline hydrochloride microspheres versus infrared light at 810 nm from a diode laser on multispecies oral biofilms in vitro. These biofilms were grown from dental plaque inoculum (oral microcosms) and were obtained from six systemically healthy individuals with generalized chronic periodontitis. Methods: Multispecies biofilms were derived using supra‐ and subgingival plaque samples from mesio‐buccal aspects of premolars and molars exhibiting probing depths in the 4‐ to 5‐mm range and 1‐ to 2‐mm attachment loss. Biofilms were developed anaerobically on blood agar surfaces in 96‐well plates using a growth medium of prereduced, anaerobically sterilized brain–heart infusion with 2% horse serum. Minocycline HCl 1 mg microspheres were applied on biofilms on days 2 and 5 of their development. Biofilms were also exposed on days 2 and 5 of their growth to 810‐nm light for 30 seconds using a power of 0.8 W in a continuous‐wave mode. The susceptibility of microorganisms to minocycline or infrared light was evaluated by a colony‐forming assay and DNA probe analysis at different time points. Results: At all time points of survival assessment, minocycline was more effective (>2 log₁₀ colony‐forming unit reduction) than light treatment (P <0.002). Microbial analysis did not reveal susceptibility of certain dental plaque pathogens to light, and it was not possible after treatment with minocycline due to lack of bacterial growth. Conclusion: The cumulative action of minocycline microspheres on multispecies oral biofilms in vitro led to enhanced killing of microorganisms, whereas a single exposure of light at 810 nm exhibited minimal and non‐selective antimicrobial effects.     

Characterization of minocycline transport by human neutrophils

BACKGROUND: Tetracyclines are used in periodontal therapy as antimicrobial agents and as inhibitors of matrix metalloproteinases. Neutrophils appear to accumulate minocycline and other tetracyclines through a mechanism that has not been fully characterized. METHODS: The transport of minocycline and other tetracyclines by isolated human neutrophils was characterized by measuring the increase in cell-associated fluorescence. RESULTS: Quiescent neutrophils took up minocycline through a saturable, concentrative, sodium-dependent mechanism with a Michaelis constant (K(m)) of 153 micro g/ml (501 microM) and a maximal velocity of 240 ng/minute/10(6) cells. The efficiency of minocycline transport was not influenced significantly by a two-unit variation in extracellular pH and was not enhanced upon cell activation with phorbol myristate acetate. Neutrophil incubation in medium containing 10 micro g/ml minocycline, doxycycline, or tetracycline yielded steady-state intracellular/extracellular concentration ratios of approximately 64.0, 7.5, or 1.8, respectively. The dilution of extracellular minocycline or doxycycline triggered efflux from cells loaded with these antibiotics. Minocycline transport was competitively inhibited by the organic cations carnitine, diphenhydramine, and verapamil, but penicillin and other organic anions failed to produce inhibition. CONCLUSION: Transport of tetracyclines by neutrophils could potentially enhance the effectiveness of these agents in periodontal therapy by enhancing or sustaining their therapeutic levels at inflammatory sites and by enhancing the killing of phagocytosed bacterial pathogens.     

复方苦参漱口液对口腔常见致病菌的抑制作用

目的:研究复方苦参漱口液对口腔常见致病菌的体外抑制作用。方法:对嗜酸乳杆菌等6种口腔常见致病菌的标准菌株采用培养基体外培养增殖,测定苦参漱口液的最低抑菌浓度、MIC50、MIC90;平板法测定抑菌强度,并与茶多酚作比较。结果:复方苦参漱口液对6种标准菌株的最低抑菌浓度均低于原液浓度。对致龋菌,复方苦参漱口液取得与茶多酚相似的抑菌效果;对黏膜致病菌,复方苦参漱口液的抑菌作用强于茶多酚。平板抑菌环结果:复方苦参漱口液和茶多酚之间比较无显著差异。结论:复方苦参漱口液有良好的抑菌作用。     

In vitro activity of moxifloxacin compared to other antimicrobials against streptococci isolated from iatrogenic oral bacteremia in Spain

BACKGROUND/AIMS: Systemic dissemination of oral bacteria to distant body sites may be the cause of focal infections. The unsuitable use and overexposure to antimicrobial therapy in clinical dental practice may contribute to the worldwide problem of antimicrobial resistance. The aim of this study was to determine the susceptibilities of streptococci isolated from the bloodstream after dental extractions against penicillin, ampicillin, amoxicillin, erythromycin, clindamycin, and a new fluoroquinolone, moxifloxacin. PATIENTS AND METHODS: Eighty-four patients who required dental extractions were studied. Venous blood samples were collected from each patient at baseline (before dental manipulation) and 30 s after dental extractions. The samples were processed in the Bactec 9240. The isolated bacteria were identified by conventional microbiological techniques. The antimicrobial susceptibility of 81 streptococci was determined by the E-test method. The NCCLS performance standards were followed. RESULTS: 88.9-92.5% of the streptococci were sensitive to beta-lactam agents tested with a minimum inhibitory concentration (MIC)(90s) ranging from 0.094 to 0.19 mg/l. The resistance to erythromycin and clindamycin was 40.8% (MIC(90HR) = 256 mg/l) and 21% (MIC(90HR) = 256 mg/l), respectively. The MIC(90) to moxifloxacin was 0.125 mg/l. CONCLUSION: Most of the streptococci isolated from the bloodstream after dental extractions were susceptible in vitro to penicillin, ampicillin, and amoxicillin. The high percentage of streptococci resistant to erythromycin and clindamycin could restrict their usefulness as prophylactic drugs. All the isolates showed a low MIC of moxifloxacin in vitro, making it a promising antimicrobial alternative for the prevention of streptococcal focal infections associated with certain dental manipulations, when the administration of beta-lactam agents is not indicated.     

Susceptibility of oral bacteria to Melaleuca alternifolia (tea tree) oil in vitro

The in vitro activity of Melaleuca alternifolia (tea tree) oil against 161 isolates of oral bacteria from 15 genera was determined. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) ranged from 0.003 to 2.0% (v/v). MIC90 values were 1.0% (v/v) for Actinomyces spp., Lactobacillus spp., Streptococcus mitis and Streptococcus sanguis, and 0.1% (v/v) for Prevotella spp. Isolates of Porphyromonas, Prevotella and Veillonella had the lowest MICs and MBCs, and isolates of Streptococcus, Fusobacterium and Lactobacillus had the highest. Time kill studies with Streptococcus mutans and Lactobacillus rhamnosus showed that treatment with > or = 0.5% tea tree oil caused decreases in viability of >3 log colony forming units/ml after only 30 s, and viable organisms were not detected after 5 min. These studies indicate that a range of oral bacteria are susceptible to tea tree oil, suggesting that tea tree oil may be of use in oral healthcare products and in the maintenance of oral hygiene.     

Minocycline reduces gingival collagenolytic activity during diabetes

Diabetes increases gingival collagenase activity, an effect that may be mediated by endogenous tissue changes and exacerbated by an overgrowth of Gram-negative organisms in the gingival crevice (see Ramamurthy & Golub 1983, McNamara et al. 1982). In an attempt to reverse this collagenolytic abnormality, we administered an appropriate antibiotic, minocycline (a semisynthetic tetracycline), to diabetic rats and humans. Adult male conventional or germfree rats were made diabetic with streptozotocin, and half of these animals were administered minocycline (20 mg per day) by tube feeding for 3–4 weeks prior to sacrifice. The buccal gingiva, entire skins, and mandibles were dissected and tested for collagenolytic enzyme activity, collagen content, and alveolar bone loss, espectively. In a preliminary study, minocycline (200 mg per day) was administered for 7 days to an insulin-dependent diabetic adolescent human and an adult non-diabetic human; the twin brother of the diabetic was treated with penicillin. Gingival fluid collagenase activity was measured (using [³H-methyl] collagen as substrate in a new microassay) in 8 periodontal pockets in each subject before and after antibiotic therapy. Examination of collagenase digestion products by SDS-polyacrylamide gel electrophoresis and fluorography was also carried out. In rats, minocycline treatment: (1) suppressed the abnormally elevated collagenolytic enzyme activity in gingiva of diabetic rats, even under germfree conditions; (2) inhibited PMN leukocyte collagenase activity in vitro, an effect that was reversed by the addition of calcium ions (penicillin-streptomycin had no effect on the activity of this enzyme); and (3) retarded the abnormal loss of skin collagen and alveolar bone in diabetic rats. In a preliminary study on humans, minocycline therapy reduced the collagenase activity of gingival crevicular fluid, an effect not produced by penicillin. Our data suggests that (1) tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism al least in part unrelated to its antibacterial efficacy, and (2) this mechanism may provide a new therapeutic approach for suppressing excessive collagen resorption which occurs during periodontal disease and which can occur during other pathologic conditions.