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No statistically significant changes in the chemiluminescence response of the whole blood were noted following in vitro treatment with 0, 2, 10, 25, or 50 micrograms/ml of erythromycin, josamycin, miomycin, roxithromycin, and spiramycin. These results suggest that these macrolide antibiotics are unlikely to impair the phagocytizing abilities of human neutrophils, in agreement with previous findings indicating their lack of influence upon neutrophil chemotaxis.
Due to reported favourable pharmacokinetics, the fluoro-quinolone moxifloxacin appeared to be a promising candidate for adjunctive systemic antibiotic therapy in periodontal infections with A. actinomycetemcomitans.
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Allergic reactions to antibiotics are common in daily clinical allergy practice. Oral drug provocation tests (ODPT) are used to determine safe alternative antibiotics in addition to diagnostic purposes. In one of our previous studies, we have shown that triple test was a safe, time-saving and cost-effective method for determining safe alternatives for patients with non-steroidal anti-inflammatory drug (NSAID) hypersensitivity.
Recent experimental work has shown that a so-called PAE (postantibiotic effect, i.e. persistent suppression of regrowth after short exposure of bacteria to the study drug in vitro) is a feature of most current antibiotics. However, marked quantitative differences were found between different types of antibiotics and also between Gram-positive and Gram-negative organisms studied. A PAE has not yet been demonstrated for roxithromycin, a new macrolide antibiotic. Therefore, we compared the PAE of roxithromycin, erythromycin, and clindamycin against laboratory strains and clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Str. pneumoniae, and Haemophilus influenzae in vitro. Identical multiples of the MIC and identical exposure times resulted in similar PAEs for the three study drugs tested. Good correlations could be found between the area under the in-vitro concentration-vs-time curve (AUC) and PAEs. The longest PAE of 9.6 h was observed after exposure of Str. pneumoniae to 1.9 mg/l of roxithromycin for 6 h.
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A severe episode of Campylobacter jejuni gastroenteritis in a patient with HIV infection was treated with ciprofloxacin and, because of therapeutic failure, subsequently with roxithromycin. After treatment, C. jejuni was again isolated from feces and shown to be resistant to both drugs. We present molecular evidence of the sequential development of both types of resistance in the patient isolate. To our knowledge, this is the first case with documented evidence showing sequential emergence of resistance to fluoroquinolones and erythromycin in a strain of C. jejuni during treatment.
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In this study, we analyzed the effect of RXM on chemokine-induced chemotaxis of Th1, Th2, and regulatory T (Treg) cells established from three normal human peripheral blood lymphocytes by the reported methods.
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We enrolled 1010 consecutive patients with successful coronary stenting into a randomised, double-blind trial. Patients received the macrolide antibiotic roxithromycin 300 mg once daily for 28 days (506), or placebo (504). Primary endpoint was frequency of restenosis (diameter stenosis >50%) at follow-up angiography, and secondary endpoint was rate of target vessel revascularisation during the year after stenting. A prespecified secondary analysis addressed treatment effect with respect to titre of C pneumoniae in serum. Analysis was by intention to treat.
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Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in treating chronic inflammatory diseases of the respiratory tract such as diffuse panbronchiolitis (DPB) and chronic sinusitis. The evaluate the anti-inflammatory action of erythromycin, we examined apoptosis of isolated neutrophils incubated with and without erythromycin. As a result, erythromycin augmented neutrophil apoptosis in a dose-dependent manner, with a maximal effect at 10 micrograms/ml and above. The percentage of neutrophil apoptosis at 12 h was 79.2 +/- 2.3% in medium with 10 micrograms/ml of erythromycin compared with 51.2 +/- 4.1% in control medium (p < 0.005). In a manner similar to that of erythromycin, another macrolide antibiotic, roxithromycin, also increased neutrophil apoptosis. However, there was no effect on apoptosis induced by treatment with josamycin (macrolide antibiotic), ampicillin (beta-lactam.) and cefazolin (cephalosporin antibiotic), or gentamycin (aminoglycoside). These findings suggest that erythromycin shortens neutrophil survival by accelerating neutrophil apoptosis.
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The analysis was based on 113 drug-interaction studies reported in 78 published articles over the period 1983-2006. The articles were used if they contained sufficient information about drug interactions. Information on drug names, doses and the magnitude of the increase in the area under the concentration-time curve (AUC) were collected.
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Propionibacterium acnes (P. acnes) causes an inflammatory acne that is characterized by massive neutrophilic infiltration. IL-8 is thought to play an important role in the pathophysiology of P. acnes, although the mechanisms by which P. acnes up-regulates the release of IL-8, a neutrophilic chemokine, from target cells is not well understood. In this study, we investigated the mechanisms through which heat-killed P. acnes induces IL-8 production in THP-1 cells (a human monocytic cell line). We found that P. acnes is able to directly induce IL-8 production and IL-8 mRNA expression in human monocytic cells in a dose- and time-dependent manner through a mechanism requiring transcription factor NF-kappaB activation. Additionally, P. acnes-induced IL-8 secretion was inhibited by roxithromycin, a macrolide antibiotic, and its inhibitory effect seemed to be partially associated with the inhibition of P. acnes-induced NF-kappaB activation. This is the first study to show that NF-kappaB activation is involved in the IL-8 production of monocytic cells stimulated by P. acnes.
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A prospective study study was conducted over a 14-month period in the dermatology unit of the Cayenne hospital. Two groups of patients were identified: group 1 included patients with impetigo and group 2 patients with infected skin reactions. Epidemiological, bacteriological, toxinological (exofoliatines, leukocidine) and antibiotic data were recorded.
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.
The combination cyclophosphamide and roxithromycin, but not the individual compounds, is toxic to endothelial cells by inducing apoptosis. Inhibition of P-glycoprotein and formation of toxic metabolites are unlikely causes.
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The short-term treatment-oriented administration of RXM reduced the degree of inflammatory change and lowered serum amyloid A in IL-10-deficient mice with severe colitis. Mononuclear cells from the lamina propria of RXM-treated large intestines showed lower production of IFN-gamma than did those from diseased mice that were untreated. Long-term prevention-oriented administration of RXM suppressed the development of severe colitis and decreased production of IFN-gamma and IL-12. In addition to its expected immunosuppressive effect, RXM treatment also decreased the level of Bacteroides vulgatus, a Gram-negative anaerobe.
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The isolation rate of Mycoplasma is higher than that of Neisseria gonorrhoeae and Chlamydia trachomatis in the chronic prostatitis. It is important to detect the susceptibility of Neisseria gonorrhoeae and Mycoplasma for the use of antibiotics in reason.
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In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n=161), group 2 other antibiotics (n=213) and group 3 non-teratogens (n=740).
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The effects of pH on access to the cytochrome P-450 active site, N-demethylation and formation of the cytochrome P-450 Fe(II)-RNO metabolite complex for a series of erythromycin derivatives were examined. Studies were performed with dexamethasone-treated rat liver microsomes containing large amounts of cytochrome P-450 3A isozymes. In addition to factors such as hydrophobicity or hindrance around the dimethyl-amino function, the ionisation state of the N(CH3)2 group played an important role in the recognition and metabolism of the substrate by cytochrome P-450. Esterification of the desosamine in the beta position of the N(CH3)2 group leads to lower pKa values for the R--N+ H(CH3)2 <--> [R--N (CH3)2] + H+ equilibrium. At physiological pH, the amine group is mainly in the unprotonated form. Consequently, easier access to the protein active site and significant formation of cytochrome P-450 Fe(II)-RNO metabolite complex are observed for these derivatives. These results led us to interpret the formation of cytochrome P-450 Fe(II)-RNO metabolite complex as a series of multiple steps equilibria depending on the ionisation state of the N(CH3)2 group, the partition coefficient of the substrate between the microsomal layer and the aqueous media and a series of metabolic reactions leading partially to the final inhibitory nitrosoalkane-cytochrome P-450 Fe(II) complex.
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Roxithromycin (RU 28965), an ether oxime derivative of erythromycin, protected mice against a lethal infection with the virulent RH strain of Toxoplasma gondii. Therapy begun 24 h before, 2 h after, and 24 h after infection with 2 X 10(3) tachyzoites protected 90, 80, and 50% of the mice, compared with 0% of untreated controls (P less than 0.05 to 0.001). Toxoplasma was isolated in less than 20% of surviving roxithromycin-treated mice.
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A simple, rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of azithromycin in rabbit conjunctiva tissues using roxithromycin as internal standard. Following a deproteinization procedure, the samples were eluted isocratically at a flow rate of 0.3mL/min utilizing a mobile phase containing of 10mM ammonium acetate (adjusted pH to 5.2 with 0.1% acetic acid)-methanol (18:82, v/v) and a SHISEIDO CAPCELL PAK C(18) (3.0mmx75mm, 3microm). Azithromycin and its internal standard were measured by a triple-quadrupole mass spectrometer in the selected reaction monitoring (SRM) mode with precursor-to-product qualifier transition m/z 375 [M+2H](2+)-->591 and m/z 837 [M+H](+)-->679 respectively. The method demonstrated that good linearity ranged from 10 to 2000ng/mL with r=0.9998. The lower limit of quantification for azithromycin in conjunctiva tissues was 10ng/mL with good accuracy and precision. The intra- and inter-day precision (RSD) values were below 15% and accuracy (%) ranged from 90% to 110% at all QC levels. The method was applicable to ocular pharmacokinetic studies of azithromycin.
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Randomised controlled trials (RCTs) comparing systemic antibiotics with placebo for chronic rhinosinusitis in adults.
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Analytical methods have been developed for the determination of eight acidic pharmaceuticals and two metabolites, seven antibiotics and the parasiticide ivermectin in a selected river sediment. The sediments were solvent extracted with ultrasonic assistance. A solid phase extraction (SPE) clean-up step was performed thereafter. The acidic compounds clofibric acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, 2-hydroxy-ibuprofen, indomethacin, ketoprofen, naproxen and the parasiticide ivermectin were measured in the negative mode by LC-APCI-tandem MS, whereas the antibiotics clarithromycin, erythromycin, roxithromycin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim were detected in the positive mode by LC-ESI-tandem MS. Bezafibrate could not be determined in the sediment using the method developed. The limit of quantification (LOQ) ranged from 0.4 to 8 ng g(-1) for the acidic pharmaceuticals, sulfadiazine and ivermectin and was 20 ng g(-1) for the other antibiotics.
These results strongly suggest that RXM inhibits neutrophil transmigration into inflammatory sites and results in favorable modification of the clinical status of inflammatory diseases.
Firstly, the rat ovalbumin (OVA) model was built according to the previous papers. Rat ASMCs were prepared and cultured, and then TGF-β1 production in ASMCs was measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the proliferation of ASMCs was determined using cell counting kit (CCK-8) assay. Additionally, the expressions of caveolin-1, phosphorylated-ERK1/2 (p-ERK1/2) and phosphorylated-AKT (p-AKT) in ASMCs treated with or without PD98059 (an ERK1/2 inhibitor), wortannin (a PI3K inhibitor), β-cyclodextrin (β-CD) and RXM were measured by Western blot. Finally, data were evaluated using t-test or one-way ANOVA, and then a P value < 0.05 was set as a threshold.
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Macrolides are well known for their high lipid solubility and good tissue penetration. The pharmacokinetic properties of roxithromycin, a new semisynthetic macrolide, appear to be very interesting in healthy adult patients. Five paediatric pharmacokinetic studies are summarized and show that the pharmacokinetic properties of roxithromycin in paediatrics are very similar to those previously reported in adults and suggest that the same dose every 12 h is appropriate in paediatrics, 2.5 mg/kg. The diffusion of roxithromycin into upper respiratory tract tissues appears to be good in children.
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In vitro susceptibilities of Rickettsia rickettsii and Rickettsia conorii to roxithromycin, pristinamycin, and the pristinamycin compounds, P1 and P2, were determined by a dye uptake assay and a plaque assay. The MICs were 1 microgram/ml for roxithromycin, 2 micrograms/ml for pristinamycin, greater than 256 micrograms/ml for P1, and 2 micrograms/ml for P2. Compounds P1 and P2 did not share synergetic activity. The toxicity of each compound was determined by a dye uptake assay. Toxic concentrations were 128 micrograms/ml for roxithromycin, 32 micrograms/ml for pristinamycin, greater than 256 micrograms/ml for P1, and 32 micrograms/ml for P2. Roxithromycin and pristinamycin could be useful in the treatment of Rocky Mountain spotted fever and Mediterranean spotted fever.
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We investigated the clinical factors (CT images, endoscopic nasal findings and allergic factors) involved in resistance of chronic sinusitis to macrolide therapy (ME) retrospectively.
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The spectrum of antibiotic susceptibility of Borrelia burgdorferi has been only partially defined. In the present study the effectiveness of 12 antimicrobials, belonging to six different antibiotic classes have been tested against Borrelia burgdorferi s.s. (N=3), Borrelia garinii (N=3), Borrelia afzelii (N=3), Borrelia valaisiana (N=1), and Borrelia bissettii (N=1) isolates. These isolates were analysed by a new standardised colorimetric minimal inhibitory concentration (MIC) method based upon colour changes that result from actively metabolizing spirochaetes after 72 h of incubation. Piperacillin (MIC90: 0.08 mg/l), ceftriaxone (MIC90: 0. 04 mg/l), cefotaxime (MIC90: 0.15 mg/l), azithromycin (MIC90: 0.015 mg/l), roxithromycin (MIC90: 0.05 mg/l) and quinupristin/dalfopristin (MIC90: 0.12 mg/l) gave the lowest MIC values. Minimal inhibibitory activity of amoxycillin (MIC90: 1.04 mg/l), cefixime (MIC90: 1.33 mg/l), cefoperazone (MIC90: 0.83 mg/l) tetracycline (MIC90: 0.29 mg/l) and minocycline (MIC90: 0.30 mg/l) was slightly lower, whereas borrelia were resistant to amikacin (MIC90: >128 mg/l). Mean minimal borreliacidal concentrations (MBCs) were representatively determined for piperacillin (MBC: 1.8 mg/l), ceftriaxone (MBC: 2.0 mg/l), azithromycin (MBC: 0.82 mg/ml), roxithromycin (MBC: 1.8 mg/l), quinupristin/dalfopristin (MBC: 5.0 mg/l), minocycline (MBC: 5.8 mg/l), and amikacin (MBC: >128 mg/l) by using conventional subculture for three weeks in combination with dark-field microscopy. B. garinii proved to be the most susceptible of the genospecies tested. Our study showed excellent in vitro antimicrobial activity of all classes of antibiotics tested, except the aminoglycosides and hence their suitability for therapy of Lyme disease.