The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures.
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One hundred and sixty-nine consecutive patients with peptic ulcer disease as well as gastritis with biopsy-proven H. pylori infection were entered into an open study of omeprazole 20 mg o.m., amoxycillin 500 mg t.d.s., roxithromycin 150 mg b.d., and metronidazole 250 mg t.d.s. Helicobacter pylori status was determined by urease test, histology and culture. Susceptibility to amoxycillin, metronidazole and roxithromycin was determined by the E-test.
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Roxithromycin solutions of different pH were prepared with water, simulate intestinal fluid (SIF) and simulate gastric fluid (SGF) shown to be the stability of these solutions were tested by colorimetry and HPLC.
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Antibiotic sensitivities of peptostreptococci, streptococci, Actinomyces, bacteroid, and fusobacterial strains pathogenic for the periodontium are analyzed. The sensitivities of these bacteria to broad-spectrum penicillins, cephalosporines, lincomycin, and macrolides, and to metronidasole and nitasole are assessed. New macrolide drugs macropen and rulide and gramicidine C, levomycetine, and rifampicin are highly active towards the above microflora. Microbiological indications for oral and local use of these antibiotics are validated. Some narrow-spectrum antibiotics, such as augmentine, cephalexin, and vancomicin are highly active, too; the latter drug is specifically active towards Actinomyces.
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Synergism of ciprofloxacin (CPFX) and roxithromycin (RXM) to bacterial biofilms formed by Pseudomonas aeruginosa was investigated. Measurement of antibacterial activities and morphological observation with a scanning electron-microscope suggested that RXM eradicated the biofilms by unknown mechanism and thereby enhanced the bactericidal activity of CPFX to P. aeruginosa in biofilms.
Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.
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The efficacy and safety of roxithromycin 300 mg once a day was compared with that of erythromycin 500 mg twice a day, both for seven days, in a double blind study of 281 patients (188 men, 93 women) with genitourinary chlamydial infections. At the end of the treatment 251 (89%) patients were evaluable, and at follow up two weeks later 227 (81%) were evaluable. The bacteriological cure rate was close to 100% at the end of both treatment regimens. At follow up 55/75 (73%) evaluable men and 38/39 (97%) evaluable women treated with roxithromycin were chlamydia negative compared with 50/71 (70%) evaluable men and 37/42 (88%) evaluable women treated with erythromycin. Of the 47 who were still chlamydia positive, reinfection could not be excluded in half the men and all the women. Side effects were mainly gastrointestinal and were found in about 15% of patients receiving each treatment, but did not necessitate discontinuing treatment in any case. Roxithromycin seems to be as safe and efficacious as erythromycin in treating chlamydial infections in men and women, and it has the advantage that treatment is by a single daily dose.
Of the different therapies one proton pump inhibitor with two antibiotics gave best results in ulcer healing and H. pylori eradication in ulcer and non ulcer dyspepsia.
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OBJECTIVE: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes. METHODS: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest. RESULTS: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC90S for S. pneumoniae, determined by the Etest, approximately 12-fold. Also, the azithromycin MIC90 for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithromycin were comparable to those to clarithromycin (S. pneumoniae, 93.4% versus 91.3%; S. pyogenes, 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin (S. pneumoniae, 71.3%; S. pyogenes, 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae, confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs. CONCLUSIONS: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes, with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.
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The authors report a case of a 32-year-old patient who has been treated for idiopathic proctitis for 10 years. The inflammation did not react to Salazopyrin and corticosteroid therapy. Significant stenosis has developed. The probability of Chlamydia infection has emerged because of the atypical morphological appearance and therapy resistance of the process. The Chlamydia infection was verified by serological examinations and direct immunofluorescent detection of the pathogen taken from biopsy specimen. The proctitis has been cured by Doxycyclin and roxithromycin therapy. The authors call attention to the different diagnostic significance of the disease considering that strictures requiring surgical operation can develop in cases being unrecognised and treated inadequately. The case is the first report of the disease in Hungary.
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The present study evaluates the presence of nine hormones and their conjugates and 20 pharmaceuticals such as anti-inflammatories, lipid regulators, and antibiotics among others in sewage sludge from two sewage treatment plants (STPs) in the Tarragona area (Spain) for the period March 2007 until March 2008. Target analytes have been determined using different methods involving pressurized liquid extraction and liquid chromatography (electrospray ionization) tandem mass spectrometry (MS-MS). Most of the pharmaceuticals and hormones were found at low micrograms per kilogram dry weight levels in the sewage sludge samples analyzed. Some compounds were present in all samples, such as acetaminophen, caffeine, carbamazepine, and ibuprofen, among others. Other compounds, such as estriol, were found only in the STP of Reus. The compounds that showed the highest concentration in both STPs were roxithromycin and tylosin (1,446 and 1,958 microg/kg dry wt, respectively). The presence of these compounds in sewage sludge demonstrated that they are partially or totally removed from the influent wastewater by sorption into the sewage sludge.
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After eating a meal of poultry a 41-year-old man fell ill with severe diarrhoea, persistent high fever of around 39 degrees C, dehydration and somnolence. On admission to hospital physical examination was normal except for signs of dehydration. The blood count showed a leukocytosis (13,300/microliters) with 60% stab-form neutrophils. The erythrocyte sedimentation rate was raised to 49/82 mm. Also increased were the serum concentrations of creatinine (3.5 mg/dl), creatine kinase (179 U/l), lactate dehydrogenase (298 U/l) and C-reactive protein (16.8 mg/dl). Bacteriological and virological examinations of blood and stool were negative. A normal fluid and electrolyte balance was re-established. But as there was no improvement, ampicillin was administered, 2 g three times daily, then ciprofloxacin, 500 mg two times daily, and finally combined with metronidazole, 500 mg three times daily. Despite this treatment a chest radiograph on the tenth day revealed an infiltration in the left basal lung segment, and the legionella titre became positive at 1:2045. The antibiotic treatment was changed to 150 mg roxithromycin two times daily. The fever fell within 3 days and the diarrhoea stopped after 5 days. He was discharged free of symptoms after 24 days.
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Prior studies have suggested that inflammation and possibly bacterial infections play a role in atherogenesis and in the clinical pathogenesis of cardiovascular diseases. Treatment with the macrolide antibiotics has been associated with improved outcome from cardiovascular disease, although the mechanism through which they exert their effects may be unrelated to their antibiotic properties. Drugs that exert a vasodilator effect on arteries have been associated with attenuated atherogenesis and improved outcome from cardiovascular disease.
We recently demonstrated that oral roxithromycin is as effective as intravenous penicillin G in adults with erysipelas. We therefore evaluated the effectiveness of pristinamycin, an antibiotic which is very active on streptococci and Staphylococcus aureus, in non-necrotizing bacterial dermohypodermitis in adults.
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sICAM-1 significantly decreased at 1 month in group R vs group C (371 +/- 181 vs 573 +/- 273 ng/ml, p = 0.005). This decrease was more evident in patients with a positive serology for CP (CP+) (group R 373 +/- 131 vs group C 597 +/- 255 ng/ml, p = 0.014). Antibiotic treatment had no effects on circulating E-selectin levels at 1 month (56.7 +/- 97 vs 49.8 +/- 62 ng/ml, p = 0.54). The restenosis rate (9/50, 18%) was similar in the two groups (group R 5/25 [20%], group C 4/25 [16%]). The restenosis rate was similar in the CP+ vs CP- group (6/35 [17%] vs 3/15 [20%]).
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The presence of Campylobacter pyloridis in the gastric mucosa was recently linked to peptic ulcer disease. This study compared the inhibitory activity of three macrolide compounds (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin against 10 clinical isolates of C. pyloridis. The macrolides were equally effective against the test strains, with MICs ranging from 0.06 to 0.5 microgram/ml; rifampin was less active, with MICs ranging from 0.25 to greater than 1 microgram/ml. Erythromycin and the two new macrolide derivatives are potentially useful agents in the treatment of infections caused by C. pyloridis.
Roxithromycin (RXM) has been widely used in asthma treatment; however, the mechanism has not been fully understood. The aim of our study was to investigate the underlying mechanism of RXM treatment in mediating the effect of transforming growth factor (TGF)-β1 on airway smooth muscle cells (ASMCs) proliferation and caveolinn-1 expression.
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The study of macrolide-ribosome interactions has been investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY). A new medically important macrolide antibiotic, roxithromycin, with the replacement of the 9-keto group in erythromycin by a 9-oxime chain, was studied in the complex state with the bacterial ribosome. Analysis of transferred nuclear Overhauser effect (TRNOE) experiment resulted in a set of constraints for all protons pairs. These constraints were used in structure determination procedures based on molecular modelling to obtain a bound structure compatible with the experimental NMR data. The results compared with the conformational analysis of the substrate in solution indicate that only one specific conformation is preferred in the bound state while in the free state the sugar ring moities were relatively disordered. The bioactive macrolide antibiotics studied roxithromycin and erythromycin which displayed a strong NMR response, are metabolized in RU39001 and erythralosamine respectively which do not retain antimicrobial activity. The inactive major metabolites were used to define if TRNOEs observation may be characteristic of a biological activity. These control experiments gave essentially blank TRNOESY spectra. This study shows that Mg2+ does not play a direct role for the low affinity binding site studied by TRNOE what is in agreement with an hypothesis of two distinct binding levels, with a low affinity binding level necessary for the tight binding one.
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Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjusted P = 0.032 and 0.058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12.5% and 6.25% vs 4.37% and 0%, unadjusted P = 0.065 and 0.029, respectively), and at day 180 (14.6% and 7.29% vs 8.69% and 2.17%, unadjusted P = 0.259 and 0.17, respectively). Anti-C, pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm (P = 0.03). Elevated C-reactive protein levels predicted the need for revascularization.
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This study presents data from 73 neonatal and 60 adult patients with chlamydial conjunctivitis who were studied by culture, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) tests. All patients had visited three or more doctors before the diagnosis was established. Fourteen of the adults had consulted an ophthalmological emergency unit complaining of a foreign body sensation in the eye. The symptoms started monocularly in all 133 cases, however, the fellow eye was affected after 2-7 days in 54 of the neonates and in 5-30 days in 20 of the adult patients. The duration of symptoms before the etiological diagnosis was established was 5-198 days (mean 24 and median 15 days) in the neonates and 7-120 (mean 29 and median 22 days) in the adults. The conjunctivitis was mild, moderate and severe in 7, 72 and 48 of the neonatal eyes, when the etiological diagnosis was established. The corresponding figures for severity of conjunctivitis in the adult group were 9, 57 and 14. Nasopharyngeal colonization occurred in 56 (77%) of the children and in 35 (58%) of the adults. In the adults, only two males complained of symptoms of genital infection. In 46 (77%) adults one or more of the chlamydial diagnostic tests performed on genital samples was positive for Chlamydia trachomatis. Forty-five of the neonates were treated with erythromycin 40-50 mg per kg body weight divided in four daily doses for 14 days, while 35 of the adults were given 250 mg x 4 x 14 of erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations.
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The rapid, selective and sensitive liquid chromatographic-ion trap mass spectrometric (LC-MS(n)) method was developed and validated for determination of three major components (isovaleryspiramycins, ISV-SPMs) of a novel macrolide antibiotic bitespiramycin and their major active metabolites (spiramycins, SPMs) in rat plasma. The analytes ISV-SPMs, SPMs, internal standard roxithromycin and azithromycin were extracted from plasma samples by liquid-liquid extraction, and chromatographed on a C(18) column using two mobile phase systems. Detection was carried out on an ion trap mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI). Three components (ISV-SPM I, II, III or SPM I, II, III) could be simultaneously determined within 6.5 min. Linear calibration curves were obtained in the concentration ranges of 4-200 ng/ml for ISV-SPM I and SPM I, 12-600 ng/ml for ISV-SPM II and SPM II, and 18-900 ng/ml for ISV-SPM III and SPM III. The intra- and inter-run precision (RSD), calculated from quality control (QC) samples were less than 8.8 and 10.4% for ISV-SPMs, and 9.3 and 11.2% for SPMs, respectively. The method was applied for the evaluation of the pharmacokinetics of bitespiramycin in rats following peroral/intravenous administration.
The efficacy of ME was less in patients with polyposis; CT scans indicating severe findings, bronchial asthma and polyps with increased eosinophil infiltrations. Polypectomy resulted in significant improvement in the efficacy of ME.
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Rovamycin and roxithromycin were comparatively studied for their effects in 25 patients with chronic bronchitis and posttuberculous changes in the lung. Ten patients received oral rovamycin, 3,000,000 IU, twice daily and 15 had oral roxithromycin, 150 mg, twice daily. The therapy averaged 9 days. Clinical cure was observed in 90% of cases on rovamycin and in 86.7% on roxithromycin. There were no adverse effects of these drugs. The findings suggest that due to their high therapeutical and bacteriological activities, both rovamycin and roxithromycin show their good clinical efficacy in the treatment of exacerbations of chronic bronchitis in patients with residual posttuberculous changes.
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The carriage rate of S. pneumoniae in the 3 centers varied from 44.9% to 66.0% (mean, 55.9%). Susceptibility testing was performed with 305 (74.4%) of 410 isolates. Only 23 (7.5%) of 305 pneumococcal isolates were penicillin-intermediate (range, 2.8 to 12.8%) with no penicillin-resistant strains. All tested pneumococci were susceptible to amoxicillin/clavulanate. Macrolides possessed comparable activity against S. pneumoniae, at 4.6% resistant strains for both erythromycin (range, 1.1 to 17.1%) and clarithromycin (range, 1.7 to 17.1%). The highest level of resistance was observed with TMP-SMX, 53.4% (range, 43.8 to 70.9%). Of 23 strains 20 (87.0%) with intermediate resistance to penicillin were serotyped. The most prevalent serotype was 14 (5 isolates), followed by serogroups 19 (4) and 23 (4).
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The occurrence and removal of 19 antibiotics (including four macrolides, eight sulfonamides, three fluoroquinolones, three tetracyclines, and trimethoprim) were investigated in two ecological (constructed wetland (CW) and stabilization pond (SP)) and two conventional wastewater treatment processes (activated sludge (AS) and micro-power biofilm (MP)) in a county of eastern China. All target antibiotics were detected in the influent and effluent samples with detection frequencies of >90%. Clarithromycin, ofloxacin, roxithromycin and erythromycin-H2O were the dominant antibiotics with maximum concentrations reaching up to 6524, 5411, 964 and 957 ng/L, respectively; while the concentrations of tiamulin, sulfamerazine, sulfathiazole, sulfamethazine, sulfamethizole and sulfisoxazole were below 10 ng/L. Although the mean effluent concentrations of target antibiotics were obviously lower than the influent ones (except ciprofloxacin), their removals were usually incomplete. Principal component analysis showed that the AS and CW outperformed the MP and SP processes and the AS performed better than the CW process in terms of antibiotics removal. Both the AS and CW processes exhibited higher removal efficiencies in summer than in winter, indicating biological degradation could play an important role in antibiotics removal. Because of the incomplete removal, the total concentration of detected antibiotics increased in the mixing and downstream sections of a local river receiving the effluent from a typical wastewater treatment facility practicing AS process. Nowadays, ecological wastewater treatment processes are being rapidly planned and constructed in rural areas of China; however, the discharge of residual antibiotics to the aquatic environment may highlight a necessity for optimizing or upgrading their design and operation.