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Cytokine levels in supernatants derived from bone homogenates were measured by enzyme-linked immunosorbent assay for 28 days, after oral administration of roxithromycin at 5 mg/kg/day.
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Two authors independently extracted the data and assessed the risk of bias in the trials. Meta-analyses were used when heterogeneity was considered low. The two primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to AAA surgery in each group over the trial period.
Seventeen patients were included in a clinical open trial of macrolides for treatment of psoriasis vulgaris. PASI scores, itch and ointment scores were used to evaluate their effectiveness. PASI scores dropped from 22.8 to 13.7; this was statistically significant. Itch reduced in 11 out of 13 patients, and the extent of itch reduced significantly by 54% on average. Ointment scores reduced from 44.9 to 34.4, which was also statistically significant. Macrolides are known not only as potent anti-biotics, but also as immunomodulatory agents. These data suggest that macrolides could be used as one of the adjunctive therapies of psoriasis vulgaris, and this study is a first step toward the future evaluation of macrolides in a double blind trial.
The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0.15). Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance. The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC < 1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups. Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs. 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs. 8% in the control group). Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90-100% resistance to erythromycin, regardless of the presence of AP.
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The frequency of Streptococcus pyogenes infections with deep tissue invasion and toxic shock syndrome has increased in the last decade throughout the world.
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We report the case of a 58 year old patient who, after 2 days of treatment with roxithromycin and betamethasone, manifested acute pancreatitis. Other causes of the disease were ruled out. No re-occurrence of pancreatitis was observed in a 16 month follow-up.
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. Despite the limitations of the study due to the small sample size, roxithromycin appears not to be a major teratogen.
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Multidrug resistance is expressed not only by bacteria, but also by tumor cells and by some normal cells of the body. It enables eukaryotic cells to exclude not only cytostatic drugs but also non-cytostatic antibiotics. This was demonstrated in genetically engineered multidrug resistant (MDR) cells infected with the facultative intracellular bacterium Listeria monocytogenes for all macrolide antibiotics tested (azithromycin, clarithromycin, erythromycin, josamycin, roxithromycin and spiramycin). In these cells and in conventionally selected MDR cells higher concentrations of the macrolides were necessary to inhibit the growth of L. monocytogenes than in the respective parental cells. This effect was due to a reduced intracellular accumulation, which was shown with a biological assay for all macrolides tested. For azithromycin, the results of this test were confirmed by measurement of the intracellular concentrations with high-performance liquid chromatography (HPLC). Besides the macrolides, MDR cells excluded also antibiotics of other chemical groups which was shown for ciprofloxacin, clindamycin, rifampicin and the streptogramin derivative RP 59500. In addition, in conventionally selected cells higher concentrations of chloramphenicol, doxycyclin, ofloxacin and trimethoprim than in the respective parental cells were necessary to inhibit the growth of L. monocytogenes. In contrast, when using genetically engineered cells, no significant differences were found for these antibiotics. These differences might be due to a higher expression of multidrug resistance in the conventionally selected cells because these cells were also more effective in excluding rhodamine 123 in a flow cytometric assay. In conclusion, expression of multidrug resistance by eukaryotic cells leads to a reduced concentration of macrolides and other antibiotics in these cells and to an impairment of activity against intracellular bacteria.
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After the 8 weeks of treatment with roxithromycin, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. On the other hand, values of PC20-sulpyrine did not improve after roxithromycin at all. Furthermore, although challenge with sulpyrine caused a significant increase in u-LTE4, pretreatment with roxithromycin or placebo did not affect excretion of u-LTE4.
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To investigate the nasal carriage of antibiotic-resistant pneumococci in children of < 5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi'an.
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An impaired Eustachian tube is assumed to be an important factor in the pathogenesis of different middle ear diseases. Therefore, several investigators have studied different treatment strategies to improve Eustachian tube function. The aim of this review is to provide a comprehensive summary of the results of these studies on improvement of tubal function. The English language literature was searched systematically to identify all articles that described the effect of different interventions on Eustachian tube function. Although the results were not uniform throughout the different studies and despite several restrictions of the reviewed studies, the results of this review indicate that the function may be improved by medical intervention. However, it seems premature to recommend any of the interventions reviewed in this paper to improve function in humans. More studies, preferably randomized, placebo-controlled trials, should be conducted to assess the efficacy of different interventions.
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Antibiotics whose recognized mode of action comprises inhibition of bacterial protein biosynthesis are also recognized to modulate the expression of bacterial virulence factors when incorporated into culture media at sub-MIC levels. In this respect, one of the new macrolides, roxithromycin, has been examined for its effect on toxin/enzyme production by strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Biosynthesis of staphylococcal coagulase and DNase could be potentiated, whereas that of staphylococcal alpha-hemolysin, streptolysins O and S, and pneumolysin were unaltered. Expression of one structural virulence factor, pneumococcal polysaccharide, was repressed in the drug's presence, resulting in potentiation of phagocytic ingestion of the drug-exposed bacteria. The drug failed to have any effect on ingestion of Staph. aureus or Strep. pyogenes. These studies provide evidence that roxithromycin may exhibit "added value" as an antibiotic in its ability to potentiate the susceptibility of Strep. pneumoniae to host defenses such as phagocytosis.
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Roxithromycin was stable in water, SGF and SIF determined by colorimetry. However, it was found to be stable only in water and SIF but unstable in SGF as determined by HPLC.
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We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration. In vivo tumor growth studies demonstrated that intraperitoneal administration of roxithromycin at 20 mg/kg/day and 50 mg/kg/day reduced tumor size of B16BL6 melanoma to about 56% and 33% (experiment 1), 71% and 48% (experiment 2) of that in the respective controls. Roxithromycin also significantly inhibited pulmonary metastasis of B16BL6 cells in a spontaneous system. The inhibitory activities of roxithromycin on angiogenesis, tumor growth and metastasis were compared with those of a potent angiogenesis inhibitor, TNP-470. These data demonstrated that roxithromycin has potent antiangiogenic and antitumor effects and might have possible therapeutic applications.
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The intraphagocytic activity of erythromycin, roxithromycin and azithromycin against phagocytosed Staphylococcus aureus was compared. Erythromycin and roxithromycin both acted bacteriostatically at concentrations corresponding to 10 X MIC. Azithromycin, however, did not prevent intracellular proliferation of the staphylococci. On comparison of the pH dependency of the antibacterial activity of the three drugs, azithromycin was found to be inactivated earlier in an acidic milieu.
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Tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)(3)(2+))-roxithromycin based electrochemiluminescence (ECL) was enhanced greatly by gold nanoparticles 10 nm in diameter. Capillary electrophoresis (CE) was coupled with the resultant ECL system as a detector for roxithromycin. This ECL emission is explained by the coreactant mechanism where roxithromycin behaves as a coreactant to generate strong reducing species and gold nanoparticles act as "floating nanoelectrodes". The reaction of Ru(bpy)(3)(3+) with the generated strong reducing species on the Pt working electrode as well as on "floating nanoelectrodes" releases Ru(bpy)(3)(2+*), resulting in enhancement of ECL emission. The selectivity of this detection system towards roxithromycin was examined by CE. Under the optimized conditions, the intensity of ECL emission varies linearly with the concentration of roxithromycin from 24 nM to 0.24 mM. The detection limit is 8.4 nM, while without adding gold nanoparticles it is only 84 nM. The detection of roxithromycin in pharmaceutical and urine samples was also performed by the proposed CE-ECL method.
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ME was administered for 8-20 weeks in 68 adults with chronic sinusitis cases. The effect was evaluated in each factor from radiographic findings (R0-R3 according to the severity of the images), nasal findings (N0: no polyp, N1: a single polyp and N2: multiple polyps), allergic factors (A0: no allergy, A1: nasal allergy, A2: bronchial asthma) and objective nasal symptoms. In addition, an effect after polypectomy and histological examination were assessed for N1 and N2 groups.
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Dirithromycin is a recently developed oral antibiotic, and has been shown to be effective in the treatment of respiratory tract, skin and soft tissue infections. Dirithromycin is administered once daily which may contribute to patient compliance. In this paper we review the data from studies conducted in Europe, USA, Israel and South Africa over a six-year period to assess the safety and efficacy of dirithromycin in the treatment of a variety of acute infectious illnesses, and to compare it with structurally related antibiotics (erythromycin base, roxithromycin, and miocamycin) given orally. A total of 7437 patients have been enrolled from a total of 66 studies and trials, 4263 (57.3%) treated with dirithromycin and 3174 (42.7%) treated with a comparator antibiotic. Patients received either 500 mg dirithromycin (two tablets once daily), 1000 mg erythromycin base (250 mg qid), 300 mg roxithromycin (150 mg bid), or 1200 miocamycin (600 mg bid); the length of therapy ranged from 7 to 14 days. These studies have shown that dirithromycin has a safety profile similar to the comparator agents. The most frequently reported adverse events for both dirithromycin and comparator treatment groups were gastrointestinal in nature. The majority (99%) of adverse events reported from patients treated with dirithromycin were considered mild or moderate in severity. Early discontinuation of antibiotic therapy was infrequent (3-4%) in both treatment groups, and considered to be possibly drug-related in 2-3% of the population. The safety profile of dirithromycin in elderly patients was comparable to that recorded in the overall patient population. The incidence and nature of abnormal clinical laboratory evaluation were similar in dirithromycin and comparator groups. Notable alterations in laboratory tests of haematological or hepatic function were infrequent and were not associated with clinical manifestations. Routine monitoring of standard clinical laboratory tests in patients prescribed dirithromycin does not appear to be necessary.
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A liquid chromatographic method for the determination of macrolide antibiotics is described using a cyanopropyl column which proved to be as efficient or superior to the normally used apolar reversed-phase columns. The recovery of the macrolides from water and plasma was 80-90%. Using 0.5 ml of plasma, 30 ng/ml of clarithromycin, 50 ng/ml of roxithromycin and 10 ng/ml of azithromycin could be determined with acceptable precision and accuracy. The method has been employed in pharmacokinetic studies in humans for the determination of roxithromycin, clarithromycin and azithromycin in plasma, serum and other biological matrices. The particular selectivity of the cyanopropyl phase may also allow the simultaneous determination of erythromycin and its prodrug esters.
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Two studies were conducted on healthy male Chinese volunteers. Study A was an open-label, two-period, one-sequence crossover study (n=21). Each participant received a single nasal spray dose of BCQB 180μg on day 1. After a 7-day wash-out period, subjects received 20mg of paroxetine from day 8 to 17, and were co-administered 20mg of paroxetine and BCQB 180μg on day 18. In study B, participants (n=12) were randomly assigned to two groups. In period I, group A received BCQB 180μg on day 1, followed by the same dose four times daily from day 4 to 10, then, on day 11 a single dose of 150mg roxithromycin with BCQB 180μg were co-administered. In parallel, group B received a single dose of roxithromycin 150mg on day 1, followed by 300mg of roxithromycin from day 4 to 10, then, on day 11 a single dose of BCQB 180μg with roxithromycin 300mg were co-administered. After a wash-out time of 7days the respective treatments of each group (A and B) were swapped in period II. Blood samples were collected for pharmacokinetic analysis. Statistical comparison of pharmacokinetic parameters was performed to identify a possible drug interaction between treatments. Tolerability was evaluated by recording adverse events.
To investigate the metabolic profile of roxithromycin in dogs and the effects of oral and intravenous administrations on the metabolism of roxithromycin.
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We determined the long-term effect of a 30-day roxithromycin therapy on intima-to-media thickness (IMT) progression of the common carotid artery in 272 consecutive Cp-positive and Cp-negative patients with ischemic stroke in a prospective, double-blind, randomized trial with a follow-up of 4 years. Cp IgG (> or =1:64) or IgA (> or =1:16) antibodies were initially found in 125 (46%) patients. During the 3 years before antibiotic therapy, Cp-positive patients showed an enhanced IMT progression even after adjustment for other cardiovascular risk factors (0.12 [0.11 to 0.14] versus 0.07 [0.05 to 0.09] mm/year; P<0.005). The 62 Cp-positive patients given roxithromycin showed a reduced IMT progression during the first 2 years compared with the Cp-positive patients without therapy (0.07 [0.045 to 0.095] versus 0.11 [0.088 to 0.132] mm/year; P<0.01). However, IMT progression increased again during the third and fourth year to similar values as before treatment. No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up.
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Several lines of evidence have demonstrated an association between a variety of chronic bacterial infections and atherosclerotic cardiovascular disease. This has led to the proposal that antibiotic therapy might be helpful in the secondary prevention of atherosclerosis. A variety of smaller pilot studies have been reported testing this hypothesis and several large multicenter trials are also underway. The purpose of this review is to summarize the results of these studies and comment on their implications for the treatment of atherosclerosis.
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NPs were spherical with a relatively mono-dispersed size distribution. The particle size of nanoparticles ranged from 150 to 200 nm. NPs with entrapment efficiency of up to 80.0±6.5% and drug loading of up to 13.0±1.0% were prepared. In vitro release study showed an early burst release of about 50.03±0.99% at 6.5 h and then a slow and steady release of RXN was observed after the burst release. In vitro antibacterial effects determined that the minimal inhibitory concentration (MIC) of RXN loaded PEG-PLGA NPs were 9 times lower on S. aureus, 4.5 times lower on B. subtilis, and 4.5 times lower on S. epidermidis compared to RXN solution. In conclusion it was shown that polymeric NPs enhanced the antibacterial efficacy of RXN substantially.
A simple and sensitive high-performance liquid chromatographic micro-method for the determination of roxithromycin in human plasma and urine is described. A dichloromethane extract of the sample was chromatographed on a C18 reversed-phase column with acetonitrile-83 mM ammonium acetate-methanol (55:23:22, v/v) adjusted to pH 7.5 with acetic acid as the mobile phase. Roxithromycin and the internal standard, erythromycin, were detected by dual coulometric electrodes operated in the oxidative screen mode. The applied cell potential of the screen electrode was set at +0.7 V and the sample electrode at +0.9 V. The intra- and inter-assay coefficients of variation were less than or equal to 7.0%. The detection limit (signal-to-noise ratio = 3) was 0.1 microgram/ml for both plasma and urine. A study of drug stability during sample storage at 4, 20 and 37 degrees C showed no degradation of roxithromycin. The method is convenient for clinical monitoring and pharmacokinetic studies.
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Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and cardiovascular events. There are controversial results regarding the beneficial effects of antibiotic therapy on future cardiovascular end points.
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Five hundred and forty-three patients (60.8%) were bacteria-positive. A total of 598 strains (30 kinds of bacteria) were obtained from the sputum samples. Of them, 533 strains (89.1%) were gram-negative and 57 were gram-positive (9.8%). Escherichia coli (E. coli) and Kleb-siella pneumoniae (K. pneumoniae) were common in gram-negative strains. They were susceptive to piperacillin/tazobactam, amikacin, ciprofloxacin, and levofloxacin, especially to imipenem. Streptococcus pneumoniae (S. pneumoniae) and Stapthylococcus aureus (S. aureus) were common in gram-positive strains. S. pneumoniae was susceptive to penicillin and cefazolin sodium, but S. aureus was resistant. Both were high susceptive to vancomycin, and resistant to roxithromycin.
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Depending on the test system used, there are large differences in the prevalence of anti- C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.