Topical Application of Josamycin Inhibits Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice.

BACKGROUND: Patients with atopic dermatitis (AD) have superficial skin colonization by Staphylococcus aureus and an increased number of T helper type 2 (Th2) cells in their peripheral blood. Our previous study showed that josamycin, a macrolide antibiotic, had excellent bactericidal activity against S. aureus strains isolated from AD patients and simultaneously inhibited Th1 and Th2 cell development mediated by Langerhans cells. The purpose of the present study was to evaluate the effect of topical application of josamycin on AD-like skin lesions in NC/Nga mice. METHODS: Josamycin (0.1%) was topically administered to NC/Nga mice with AD-like skin lesions induced by 2, 4, 6-trinitrochlorobenzene (TNCB). The therapeutic effects of josamycin were assessed by measurement of the skin severity scores, histological changes in the lesioned skin, serum levels of total IgE, and expression of interferon (IFN)-γ and interleukin (IL)-4 in lymph nodes and skin lesions. RESULTS: Topical treatment with josamycin significantly suppressed the increase in the skin severity score in NC/Nga mice. This suppressive effect was equal to that of betamethasone, and was associated with a decrease in the density of cellular infiltration into the dermis, the mast cell count in the dermis and the serum IgE level. Furthermore, topical application of josamycin reduced the expression of IFN-γ and IL-4 in auricular lymph node cells and the skin lesions. CONCLUSION: The present results show that topical application of josamycin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of josamycin to AD lesions colonized by S. aureus would be beneficial for control of AD by acting on superficially located S. aureus and by inhibiting the development of Th1 and Th2 cells.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Evaluation of frequency of paediatric oral liquid medication dosing errors by caregivers: amoxicillin and josamycin.

OBJECTIVE: To study reconstitution and preparation dosing errors of liquid oral medications given by caregivers to children. METHODS: A prospective observational study was carried out in the departments of general paediatrics and emergency paediatrics at the Robert-Debré Children's University Hospital. An interview with caregivers involved (1) practical reconstitution and preparation of an oral liquid medication from a prescription drawn at random (amoxicillin (Clamoxyl, dosing spoon) or josamycin (Josacine, dose-weight pipette)) and (2) a questionnaire about their use. RESULTS: One hundred caregivers were included. Clamoxyl and Josacine were incorrectly reconstituted in 46% (23/50) and 56% (28/50) of cases, respectively, with a risk of underdosing of Clamoxyl (16/23) and overdosing of Josacine (23/28). Dose preparation with the dosing spoon was incorrect in 56% of cases, and in 10% of cases with the dose-weight pipette. Female sex, native French speaker, and age were significantly associated with correct reconstitution. Male sex and medication were significantly associated with correct preparation. CONCLUSIONS: This study highlights the high incidence of errors made by caregivers in reconstituting and preparing doses of these liquid oral medicines, which are associated with considerable risks of over- and underdosing. Factors associated with these errors have been identified which could help health professionals to optimise their strategy for educating families about the use of liquid oral medications and the need to check that they understand these instructions.

[DOXYCYCLINE (UNIDOX SOLUTAB®) AND/OR JOSAMYCIN (WILPRAFEN®) IN TREATMENT OF PATIENTS WITH PROSTATITIS IN REAL CLINICAL PRACTICE. RESULTS OF THE TAURUS OBSERVATIONAL PROGRAM].

Treatment of chronic prostatitis is a vital and complicated problem, in which a large number of stamps and "stereotyped" approaches often result in uncured patients. The increasing use of intracellular microorganisms in prostatitis etiology requires a modification in the standard approaches. TAURUS study shows high efficacy of doxycycline (Unidox Solutab®) and/or josamycin (Wilprafen®) in chronic prostatitis. Therapy, studied in this program, according to physicians, was effective in 93.2% of patients. Treatment failure was observed in 1.3% of all patients, another 5.5% of patients had insufficient data for assessment. Low incidence of adverse reactions was observed. In the study population, adverse reactions occurred in 2.6% of patients, of them serious adverse events were registered in 0.7% of patients. The most common adverse event in all treatment groups was diarrhea.

[Combined laser therapy of the reactivated form of cytomegalovirus infection of the urogenital tract in the women of reproductive age].

The prevalence of cytomegalovirus infection (CMVI) dictates the necessity of its in-depth investigation in the patients presenting with the signs of chronic inflammatory diseases of sexual organs. The objective of the present study was to estimate the effectiveness of combined laser therapy of inflammatory diseases of the urogenital tract accompanied by the reactivation of CMVI concomitant with other infections. The examination of 158 women presenting with cytomegalovirus infection revealed clinical and laboratory characteristics of the microbiocenosis. These data may be used to improve the effectiveness of diagnostic and therapeutic strategies for such patients. The combined treatment of the patients with the reactivated form of CMVI using josamycin and doxycycline monohydrate in combination with panavir and low-intensity laser irradiation based at the "Matrix-Urolog" laser complex resulted in the favourable outcome of therapy in the majority of the patients.

[The influence of ultrasonic radiation on the factors of antimicrobial resistance in the women of reproductive age presenting with mycoplasma infection of the urogenital tract].

The present clinical immunological study included 90 women of reproductive age presenting with mycoplasma infection of the lower urogenital tract. Low-frequency ultrasonic radiation was shown to successfully correct the disbalance in the system of congenital immunity that manifested itself as marked dysfunction of neutrophil granulocytes. The local application of low-frequency ultrasonic radiation normalized concentration of neutrophil defensins in cervical secretion as well as the number and function of neutrophils themselves.

[Effect of combined therapy using complex of natural cytokines and antimicrobial peptides in urogenital infections caused by Chlamydia and Mycoplasma].

AIM: To study efficacy of complex therapy of urogenital infections caused by Chlamydia and Mycoplasma using immunomodulator Superlimph. MATERIALS AND METHODS: Fifty males and thirty six females ages 22 - 47 years old with chronic urogenital infections--cervicitis and vulvovaginitis (females), prostatitis (males)--were studied. PCR and bacteriologic methods were used for diagnostics of mixed infection and microbiota efficiency. Patients were divided on 3 groups according to treatment protocol. Twenty patients (group 1)--standard therapy (josamycin), 48 patients received immunomodulator (suppositorium) before treatment with josamycin (group 2), 18 patients were simultaneously treated with josamycin and immunomodulator (group 3). RESULTS: Combinations of Chlamydia trachomatis, Ureaplasma urealyticum, Gardnerella vaginalis and Mycoplasma genitalium were identified in 30 - 35% of cases before treatment. After treatment with josamycin (group 1) or simultaneous therapy with josamycin and immunomodulator (group 3) considerable suppression of growth and elimination of both main pathogens and members of microbiota. Use of immunomodulator (group 2) in some cases resulted elimination of main pathogens and associated opportunistic microflora. CONCLUSION: Microbiological monitoring in 97% cases demonstrated therapeutic effect of immunomodulator Superlymph on urogenital infections associated with Chlamydia and Mycoplasma and disbiotic microbiota of urogenital tract.

[Evaluation of efficacy and safety of josamycin (Vilprafen) in the treatment of patients with community-acquired pneumonia].

Clinical and bacteriological efficacy ofjosamycin (Vilprafen), a macrolide antibiotic, was studied in 30 out- and inpatients at the age of 18 to 68 years (the average of 43.4+/-16.7 years old) with nonsevere (PORT) community-acquired pneumonia in the case histories. Josamycin was administered orally in a dose of 500 mg every 8 hours for 7 to 10 days. The treatment course was 5 to 10 days (the average of 7.7+/-1.3 days). The recovery was stated in 28 (93.3%) patients and the pathogen eradication was recorded in 16 (88.9%) patients. Moderate side effects not requiring discontinuation of the drug use were observed in 3 patients. The results of the treatment were indicative of the josamycin high efficacy in the treatment of the patients with nonsevere community-acquired pneumonia.

[Efficacy of different schemes of anti-helicobacter therapy in duodenal ulcer]. / Effectivnost' razlichnykh skhem antikhelikobakternoi terapii pri iazvennoi bolezni dvenadtsatiperstnoi kishki.

AIM: To study clinical efficacy and antihelicobacter activity of combined treatment of duodenal ulcer (DU) with famotidin (qamatel), metronidasol (trichopol) and jozamycin (walpraphen). MATERIAL AND METHODS: A total of 96 patients with uncomplicated DU have been treated (mean age 42.5 +/- 1.5 years). The examination included standard tests, endoscopy, pH-metry (on the treatment days 1, 15 and 28), biopsies and prints from the antral stomach and its body. The sections were stained by Gimse for morphological assessment of duodenal mucosa and detection of Helicobacter pylori (HP). Gastric acid-producing function was examined with intragastric pH-metry. The patients were divided into 3 groups: group 1 received monotherapy with famotidin (20 mg twice a day); group 2 received combined treatment with famotidin (40 mg/day), metronidasol (500 mg twice a day), josamycin (300 mg in 3 doses) for a week with following intake of famotidin alone (40 mg/day) for 3 weeks; group 3 received the same treatment plus clarythromycin. Group 1 patients benefited from the treatment but elimination of pain and dyspeptic syndromes was longer than in groups 2 and 3 (p < 0.05). Ulcer healing to treatment day 28 was observed in 71.8, 90.0 and 88.2%, respectively. Side effects occurred in 0, 10 and 16.7% cases, respectively. CONCLUSION: 1-week schemes of combined treatment with famotidin, metronidasol, josamycin or clarythromycin are highly effective in DU and their side effect rates are not very high.

[Urogenital chlamydia infection: treatment with wilprafen]. / Lechenie vil'prafenom urogenital'nogo khlamidioza.

Antibiotic wilprafen (josamycin) was given in a dose 500 mg per os two times a day for 15 days to 30 male patients with a long history of chronic Chlamydia trachomatis infection (CTI) treated ineffectively. The control examination has not detected Chlamydia in 29 (96.5%) patients. The results demonstrate high efficacy of the drug wilprafen in the treatment of patients with urogenital CTI.

Suppressive activity of macrolide antibiotics on nitric oxide production from nasal polyp fibroblasts in vitro.

The influence of macrolide antibiotics on nitric oxide (NO) generation was examined using human nasal polyp fibroblasts (NPFs) in vitro. Addition of roxithromycin (RXM) at a concentration of > 7.5 microg/ml to cell cultures was shown to suppress NO production in response to stimulation with 25.0 ng/ml tumor necrosis factor (TNF)-alpha. However, jyosamycin (JM) did not suppress NO production from NPFs induced by TNF-alpha stimulation in vitro, even when added to cell cultures at a concentration of 20.0 microg/ml. We then examined the influence of RXM on inducible nitric oxide synthase (iNOS) mRNA expression in NPFs. Addition of RXM at a dose of 7.5 microg/ml to cell cultures caused reduction of iNOS mRNA expression, which was enhanced by TNF-alpha stimulation in vitro.

The effect of josamycine on the control of ileitis in weaned piglets under field conditions.

The aim of this trial was to evaluate the effect of in-feed josamycine on the control of ileitis in weaned piglets. On a farm with a previous history of ileitis outbreaks, 288 piglets at weaning age (25 +/- 2 days old) were allocated into three experimental groups, each group comprising of four pens with 24 piglets in each pen. Group one (T1) served the trial as negative control group (unmedicated), group T2 was administered josamycine at 36 mg/kg of feed and group T3 was administered josamycine at 50 mg/kg of feed. Treatments lasted for 14 days followed by an observation period of 28 days. Administration of josamycine at both inclusion levels tested had a beneficial effect compared with the negative control group, by the reduction of prevalence of diarrhoea, the enhancement of growth performance and the reduction of prevalence of Lawsonia intracellularis in the intestine, as determined either by the PCR method or by specific histopathological examinations. The beneficial effect of josamycine was more pronounced at the inclusion level of 50 mg/kg of feed.

Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts.

The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies. The cytocidal effect of the macrolides was measured as a decrease in colony-forming efficiency and was found to increase with the concentration. To obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the concentration that decreases colony-forming efficiency 50% relative to control cells, was extrapolated from the concentration-response curves. The rank of the macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM > JM > MDM approximately EM. RKM, RXM, CAM, AZM, and JM were at least 1.7-12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic bacteria was estimated to be: > or = 53.8% for RKM, > or = 92.7% for RXM, > or = 94.6% for CAM, > or = 97.1% for AZM, and > or = 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at < or = 3 microM, CAM at < or = 10 microM, and AZM or EM at < or = 3 microM. The MIC90 against periodontopathic bacteria is < or = 4.8 microM for RXM, 5.3 microM for CAM, 2.7 microM for AZM, and 21.8 microM for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions.

Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury.

14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.

In vitro and ex vivo effects of erythromycin A, azithromycin and josamycin on the splenic response to specific antigens and mitogens.

The immunomodulatory properties of antimicrobial agents and their clinical impact have been the focus of worldwide interest in recent years. In this study, the effects of different treatments with 14-, 15- and 16-membered ring macrolides on the mitogen-induced proliferative response of lymphocytes and the splenic response to immunization with sheep erythrocytes have been tested by in vitro and ex vivo assays in a murine experimental model. We observed that the in vivo administration of these antibiotics to mice induces a compensatory mechanism that abrogates the suppression observed by in vitro assays. Thus, physiological parameters may be important when testing the immunopharmacological effects of antibiotics.

[Treatment of acute group A beta-hemolytic streptococcal tonsillitis in children with a 5-day course of josamycin]. / Traitement des angines aiguës à streptocoque beta-hémolytique du groupe A chez l'enfant par la josamycine pendant cinq jours.

MATERIAL AND METHODS: In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days. Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30). In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3). RESULTS: Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis. At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89%. At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients. Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event. CONCLUSION: In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

A new quadruple therapy for Helicobacter pylori using tripotassium dicitrato bismuthate, furazolidone, josamycin and famotidine.

BACKGROUND: In our previous study, a triple therapy using tripotassium dicitrato bismuthate (TDB), josamycin and furazolidone achieved a suboptimal cure rate of Helicobacter pylori infection. AIM: To investigate whether the addition of an antisecretory agent raises the cure rate using this regimen. METHODS: One hundred and twenty H. pylori positive patients with peptic ulcer disease or functional dyspepsia were randomly assigned to receive 1-week quadruple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d., josamycin 1000 mg b.d. and famotidine 20 mg b.d. (BFJF group), or triple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d. and clarithromycin 250 mg b.d. (BFC group). H. pylori status was assessed by histology and culture of gastric biopsy specimens before and at least 4 weeks after completion of therapy. RESULTS: Seven patients (three in the BFJF group and four in the BFC group) dropped out. Eradication rates (intention-to-treat/per protocol) were 90%/95% in the BFJF group and 82%/88% in the BFC group, respectively (P > 0.05). Duodenal ulcer healing rates were 94% (16/17) in the BFJF group and 80% (20/25) in the BFC group, respectively (P > 0.05). Mild side-effects occurred in 11 (18%) patients in the BFJF group and 10 (17%) in the BFC group (P > 0.05). CONCLUSIONS: One-week quadruple therapy consisting of TDB, furazolidone, josamycin and famotidine achieves a high cure rate of H. pylori infection.

[Role of macrolides in antibacterial therapy of otitis media in children]. / Mesto makrolidov v antibakterial'noi terapii srednego otita u detei.

A new macrolide vilprafen (jozamicine) was used as monotherapy or in combination with rhinopront and mucopront in 50 children with inflammation in the middle ear. Otorrhea ceased in 41 patients. Vilprafen is recommended after failure of penicilline or cephalosporine treatment, in allergic reaction to these antibiotics, in simultaneous adenoiditis and exacerbation of chronic tonsillitis.

Suppressive effects of josamycin on the development of altered liver cell foci and chronic nephropathy in a carcinogenicity study.

The carcinogenicity of josamycin was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the compound in their diet at concentrations of 0 (control), 1.25 or 2.5% for 104-weeks; these dose levels were selected on the basis of the results of a subchronic study, in which animals rather rejected 5% josamycin. All surviving rats were killed at wk 106. A variety of tumours developed in all groups, including the control group, but all the neoplastic lesions were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Interestingly, the josamycin treatment significantly reduced the development of altered liver cell foci and chronic nephropathy in a dose-dependent manner. Thus, it was concluded that, under the present experimental conditions, josamycin is not carcinogenic in F344 rats.