Clinical and microbiological efficacy of systemic roxithromycin as an adjunct to non-surgical periodontal therapy in treatment of chronic periodontitis. A randomized, double-blinded, placebo-controlled clinical trial.

PURPOSE: The objective of this randomized clinical trial was to evaluate the clinical and microbiological effects of systemic administration of roxithromycin (RXM) as an adjunct to non-surgical periodontal therapy (NSPT) in the treatment of individuals with moderate to severe chronic periodontitis (CP). METHODS: 70 individuals (38 males and 32 females, aged 25 to 60 years) with moderate to severe CP were randomly allocated into two groups. 35 individuals were allocated to full mouth SRP+RXM while 35 individuals were allocated to SRP+ Placebo group. The clinical parameters evaluated were probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and % bleeding on probing sites (%BOP) at baseline (B/L), 1-, 3- and 6-month intervals while microbiologic parameters included percentage of sites positive for periodontopathic bacteria A. actinomycetemcomitans, P. gingivalis and T. forsythia at B/L, 3 and 6 months using polymerase chain reaction. RESULTs: Both groups showed improved clinical and microbiologic parameters over 6 months. RXM group showed a statistically significant reduction in mean PD and CAL gain as compared to the placebo group (P < 0.0001). There was reduction in percentage of sites positive for periodontopathic bacteria over the duration of the study in both groups and a statistically significant reduction in the number of sites positive for A. actinomycetemcomitans in RXM group (P < 0.001).

Effect of adjunctive roxithromycin therapy on interleukin-1ß, transforming growth factor-ß1 and vascular endothelial growth factor in gingival crevicular fluid of cyclosporine A-treated patients with gingival overgrowth.

BACKGROUND AND OBJECTIVE: Systemic macrolide antibiotic administration has been shown to result in the elimination or reduction cyclosporine A-induced gingival overgrowth. Roxithromycin (ROX) is known to have anti-inflammatory, immunomodulatory and tissue reparative effects. This study was to evaluate the effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth and interleukin (IL)-1ß, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal transplant patients. MATERIAL AND METHODS: Thirty-one patients with clinically significant overgrowth and 16 periodontally healthy subjects were included in this randomized, double-blind, placebo-controlled, parallel-arm study. Patients received scaling and root planing (SRP) at baseline and randomized to take either ROX or placebo for 5 d. The clinical parameters, including plaque index, papillary bleeding index, probing depth and gingival overgrowth scores, were recorded. The amounts of IL-1ß, TGF-ß1 and VEGF in gingival crevicular fluid were detected by ELISA. Periodontal parameters as well as gingival crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk post-therapy. RESULTS: Following SRP plus ROX and SRP plus placebo therapy, significant improvements in clinical periodontal parameters of both study groups were observed (p < 0.025). In the ROX group, adjunctive ROX therapy resulted in a greater gingival overgrowth scores reduction compared with those in the placebo group at 4 wk (p < 0.017). Initial amounts of IL-1ß, TGF-ß1 and VEGF for both the ROX and placebo groups were significantly higher than those for healthy subjects (p < 0.017), with no statistical difference between the two study groups. At 1 and 4 wk post-therapy, significant decreases in the amounts of IL-1ß, TGF-ß1 and VEGF were observed in both study groups when compared with baseline (p < 0.025), but there was no difference in the levels of IL-1ß and VEGF between the two study groups. The amount of decrease in TGF-ß1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment (p < 0.017). CONCLUSION: Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-ß1 levels in patients with severe gingival overgrowth. The reduction of gingival crevicular fluid TGF-ß1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth.

Down-regulation of transforming growth factor beta-2 expression is associated with the reduction of cyclosporin induced gingival overgrowth in rats treated with roxithromycin: an experimental study.

BACKGROUND: Gingival overgrowth (GO) is a common side effect of the chronic use of cyclosporine (CsA), an immunosuppressant widely used to prevent rejection in transplant patients. Recent studies have reported elevated levels of specific cytokines in gingival overgrowth tissue, particularly TGF-beta, suggesting that this growth factor plays a role in the accumulation of extracellular matrix materials. The effectiveness of azithromycin, a macrolide antibiotic, in the regression of this undesirable side effect has also been demonstrated. METHODS: In this study, we created an experimental model for assessing the therapeutic effect of roxithromycin in GO and the expression of transforming growth factor beta (TGF-beta2) through immunohistochemistry. We used four groups of rats totaling 32 individuals. GO was induced during five weeks and drug treatment was given on the 6th week as follows: group 1 received saline; group 2 received CsA and was treated with saline on the 6th week; group 3 received CsA and, on the 6th week, ampicilin; and group 4 received CsA during 5 weeks and, on the 6th week, was treated with roxithromycin. RESULTS: The results demonstrated that roxithromycin treatment was effective in reducing cyclosporine-induced GO in rats. Both epithelial and connective tissue showed a decrease in thickness and a significant reduction in TGF-beta2 expression, with a lower number of fibroblasts, reduction in fibrotic areas and decrease in inflammatory infiltrate. CONCLUSION: The present data suggest that the down-regulation of TGF-beta2 expression may be an important mechanism of action by which roxithromycin inhibits GO.

Roxithromycin reduces cyclosporine-induced gingival hyperplasia in renal transplant patients.

Gingival overgrowth (GO) is a common side effect of chronic cyclosporine use. The average prevalence of GO is about 30%, ranging from 10% to 85% in various series, due to diverse aggravating risk factors: drug interactions with calcium channel blockers, age, cyclosporine dose, bacterial plaque, and genetic predisposition. Recent studies have demonstrated elevated levels of specific cytokines particularly transforming growth factor-beta (TGF-beta) in hyperplastic gingival tissue, suggesting that this growth factor plays a role in the accumulation of the extracellular matrix. Until recently treatment for this complication was only surgical. Nowadays, several studies have been performed to evaluate the effects of antibiotic treatment on the regression of GO. In the present study, we used roxithromycin, a macrolide antibiotic that has inhibitory effect on TGF-beta production by inflammatory cells. The results suggested that roxithromycin may be an important therapeutic tool to reduce cyclosporine-induced GO.

Multicenter double-blind study of the efficacy and tolerance of roxithromycin versus erythromycin ethylsuccinate in acute orodental infection in adults. Odontogenic Infections Study Group.

A total of 194 patients with orodental infection were randomized either to roxithromycin 150 mg twice daily plus placebo or to erythromycin 1 g twice daily plus placebo for a mean duration of 8 days. The infections consisted of cellulitis, pericoronitis, and adenopathy, or any two in combination. In the 176 cases in which efficacy was evaluable, outcome was satisfactory in 94% and 91% of cases treated with roxithromycin and erythromycin, respectively (p = 0.45). Patients were evenly distributed with respect to demographic characteristics, diagnosis, and concomitant treatment. Surgery was performed in 63%, primarily for abscess formation in cellulitis (p less than 0.001); 18% of patients with an abscess did not undergo surgery. The success rate was identical irrespective of whether surgery was performed, including in those with an abscess. Tolerance was evaluated in 1986 patients. Unwanted effects, elicited by direct questioning, were reported in approximately 20% of cases per group (19% for roxithromycin and 21% for erythromycin). They consisted of mild gastrointestinal upsets which caused treatment to be withdrawn in eight cases (four per group). Thus, roxithromycin and erythromycin twice daily for orodental infection are similar in both efficacy and tolerance.

[The clinical efficacy of roxithromycin in patients with acute odontogenic infections]. / Efficacia clinica della roxitromicina in pazienti affetti da infezioni odontogene acute.

The clinical efficacy of a macrolide antibiotic, roxithromycin, was evaluated in 24 patients affected by acute odontogenic infections. Patients were treated with a first dose of 300 mg p.o. which was followed by 150 mg p.o. 12-hourly for the following two days. Total responses were evaluated by an arbitrary scale. The results showed that an excellent and good response was obtained in 99.96% of treated patients. On the basis of clinically compared data and the drug safety it may be concluded that roxithromycin can be successfully used in the treatment of odontogenic infections.

[Roxithromycin in dental infections]. / La roxitromicina nelle infezioni odontostomatologiche.

Roxithromicin is a semisynthetic macrolide antibiotic, with similar antibacterial activity to erythromycin. It is characterized by an excellent pharmacokinetic profile and a good tissue penetration. Particularly at the dose of 300 mg per day the dental tissue diffusion is extremely good, and this is important to oppose the oral cavity infections. Oral cavity infections can be either odontogenic or non odontogenic. Odontogenic infections are typically primary and are caused by commensal bacteria (oral Streptococci, Bacteroides sp., Veillonella sp. and Fusobacterium sp.). The antibacterial spectrum of roxithromycin is very large and includes many of the most frequent strains responsible for oral cavity infections. A very interesting characteristic of roxithromycin is its penetration in macrophages (uptake) that allow a more rapid inhibition of bacterial activity. To evaluate the clinical efficacy and tolerance of roxithromycin in the treatment of odontogenic infections, an open study was performed. This study evaluated both the microbiological and clinical aspects. Thirty patients (21 females and 9 males) who had not been previously treated with antibiotic or antibacterial drugs, affected by infective dysodontiasis, gingivitis and periodontal diseases, received 300 mg per day (once a day) of roxithromycin for an average period of 6 days. The symptomatology considered was: intumescence, redness, pain, lymphangitis and presence of trismus. Clinical symptomatology was assessed at the start and at the end of the treatment. The symptomatological improvement due to roxithromycin was rapid and very effective. After 6 days of therapy, the improvement was statistically significant (p < 0.01) compared to basal conditions. No adverse reactions or side-effects were complained during the study. No changement were detected in laboratory parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

[A microbiological evaluation of the use of roxithromycin in oral odontogenic infections]. / Valutazione microbiologica dell'uso di roxitromicina in infezioni orali odontogeniche.

Odontogenic infections are the primary infections caused by indigenous oral bacteria, when a factor changes their perfect equilibrium. We studied 30 samples from patients with odontogenic infections that were submitted to therapy with roxithromycin. Our results showed that 79% of aerobic and 71% of anaerobic bacteria, responsible for odontogenic infections, were sensitive to roxithromycin.

[A trial of the use of rulid, sumamed and makropen in the combined treatment of generalized periodontitis at a stage of exacerbation]. / Opyt primeneniia rulida, sumameda i makropena v kompleksnom lechenii generalizovannogo parodontita v stadii obostreniia.

In vitro study of the antibacterial activity of macrolide antibiotics azitromycin (sumamed), midicamycin (macropen), roxitromycin (rulide), and erythromycin demonstrated their high activity towards clinical strains of bacteroids, fusobacteria, peptostreptococci, streptococci, and corynebacteria. These antibiotics were effective in the treatment of 62 adult patients with severe and moderate generalized periodontitis. Rulide and sumamed were the most effective, macropen and erythromycin were inferior to them.

International Congress on Chemotherapy.

AIDS: Presentation highlights are provided from the Nineteenth International Congress on Chemotherapy in Montreal. Some of the new data on anti-HIV therapeutics include phase I/II data on Agouron's protease inhibitor AG1343; information on the new protease inhibitor palinavir PRO2000 (a gp120/CD4 binding inhibitor); and liposomal (fat-enclosed) formulations of both foscarnet and exonuclease (a cellular enzyme that destroys viral DNA). Two additional studies from Brazil on the efficacy and safety of roxithromycin for cryptosporidiosis (the Food and Drug Administration (FDA) has not approved roxithromycin for sale in the U.S.) are discussed, as is the use of imiquimod treatment for genital warts.^ieng

Efficacy of roxithromycin in adult patients with rheumatoid arthritis who had not received disease-modifying antirheumatic drugs: a 3-month, randomized, double-blind, placebo-controlled trial.

BACKGROUND: It has been reported that antibodies to oral anaerobic bacteria are elevated in the serum and synovial fluids of patients with rheumatoid arthritis. Macrolide antibiotics are active against oral anaerobic bacteria. OBJECTIVE: The aim of this work was to evaluate the clinical efficacy of roxithromycin in patients with early seropositive rheumatoid arthritis. METHODS: This was a double-blind trial. We enrolled adult patients with early rheumatoid arthritis who had not previously received disease-modifying antirheumatic drugs and randomized them to receive either once-daily oral roxithromycin 300 mg or once-daily oral placebo for 3 months. The primary efficacy variable was the percentage of patients who had a 20% improvement according to the American College of Rheumatology (ACR) criteria (an ACR 20 response) at 3 months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively). The 28-joint disease activity score (DAS28) was also calculated. Clinical remission was defined as DAS28 score <2.6, and a low level of disease activity was defined as DAS28 score <3.2 but > or =2.6. Adverse event data (eg, example, type, severity, time of occurrence, time to resolution) were obtained from physical examinations and patient self-reporting. RESULTS: The roxithromycin group had 16 patients (mean [SD] age, 45 [4] years; 11 women, 5 men; all white). The placebo group had 15 patients (mean [SD] age, 42 [5] years; 10 women, 5 men; all white). A significantly greater percentage of patients treated with 300 mg of roxithromycin experienced an ACR 20 re- sponse at 3 months, compared with those who received placebo (75% [n = 12] vs 20% [n = 3]; P = 0.002). Greater percentages of patients treated with 300 mg of roxithromycin also achieved ACR 50 responses (56% [n = 9] vs 7% [n = 1]; P = 0.003) and ACR 70 responses (44% [n = 7] vs 0%; P = 0.004) compared with patients who received placebo. At month 3, DAS28 response rates were significantly greater with once-daily roxithromycin 300 mg than with once-daily placebo (P < 0.001). Adverse events were reported for 11 patients (69%) in the roxithromycin group and 7 patients (47%) in the placebo group. The most common adverse events (>5%) were nausea, abdominal pain, headache, and dry mouth. There were no dose-limiting toxic effects. One participant in the roxithromycin group withdrew from the study because of severe emesis; two withdrew from the placebo group because of lack of efficacy. CONCLUSIONS: In these adult patients with rheumatoid arthritis, 3-month treatment with roxithromycin significantly improved the signs and symptoms of rheumatoid arthritis and was generally well tolerated. Future studies should investigate the relationship between disease activity and serum or joint antibodies to anaerobic bacteria.

[Diffusion of roxithromycin in gingival tissue]. / Diffusion gingivale de la roxithromycine.

The gingival penetration of roxithromycin was evaluated at steady-state in twenty nine patients treated by 150 mg orally every 12 h during five days. Tissue specimen were sampled at 2 h (n = 6), 4 h (n = 6), 6 h (n = 5), 8 h (n = 6) and 12 h (n = 6) after the 10th administration. One blood sample was drawn at the same times. Serum and tissue concentrations of roxithromycin were measured by high performance liquid chromatography (HPLC). Serum peak level, measured at the 4th h, reached 6.60 +/- 1.15 micrograms/ml. The tissue peak concentration was 4.63 +/- 1.84 micrograms/g at the 8th h. Between the 4th and 10th hour after administration, the tissue concentrations are above 2 micrograms/g, i.e. above roxithromycin MIC 90 against most of the encountered pathogens in stomatologic infections.

Therapeutic possibilities of long-term roxithromycin treatment for chronic diffuse sclerosing osteomyelitis of the mandible.

The clinical efficacy of long-term roxithromycin treatment was examined objectively in nine patients with chronic diffuse sclerosing osteomyelitis of the mandible. Roxithromycin was administered orally at a dose of 300 mg/day for between 68 days and 66 months. In seven of the nine cases (77.8%), the symptoms disappeared 1-12 months after the start of therapy. Radiography showed that osteolytic changes (evident from 'moth-eaten' appearance of bone) had improved but that osteosclerosis had persisted or become more predominant by the end of therapy. Therefore, the optimum duration of treatment should be decided according to the amelioration of symptoms along with the disappearance of osteolytic findings in radiographs. Diarrhoea and stomach discomfort occurred in one case, and liver dysfunction in another, but these adverse reactions were relatively mild. The mechanism of action of roxithromycin in this study is not yet fully understood, but our results indicate that long-term roxithromycin treatment may be useful for diffuse sclerosing osteomyelitis of the mandible and should be attempted before surgical treatment is considered.

Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role.

The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-L-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-L-arginine assay, (2) significant inhibition of lambda-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.