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A collection of 178 pneumococcal isolates found in Norway during the period 1987-1994 were tested for their susceptibility to benzylpenicillin, macrolides (azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin), fluoroquinolones (ciprofloxacin, sparfloxacin), imipenem, chloramphenicol, and vancomycin by a standard agar dilution procedure. To benzylpenicillin, two strains (1%) showed resistance and 14 strains (8%) intermediate susceptibility. Towards erythromycin, eight strains (4%) showed resistance and four strains (2%) intermediate susceptibility. Cross-resistance was demonstrated among the macrolides. Among the fluoroquinolones, intermediate susceptibility occurred with 42% of the isolates for sparfioxacin and 90% for ciprofloxacin; to the latter 5.1% proved resistant. The sum of intermediate and highly resistant isolates was 53% for chloramphenicol. Both penicillin-resistant strains were isolated during the last 2 years of collection and came from patients of non-Norwegian ethnic background. Imported strains appeared over represented among the strains resistant to penicillin and macrolides. Only imipenem and vancomycin showed full susceptibility for all pneumococci tested. An over representation of serogroup 6 strains was apparent among the strains with intermediate susceptibility and high resistance to benzylpenicillin. It is apparent that high-level resistance has, not so far, become a difficult problem in Norway. Nevertheless, the situation requires monitoring of the resistance level, particularly in meningitis and septic patients, and certainly in patients who cntail a higher than usual possibility of acquiring pneumococci from pools of resistant strains outside Norway (visitors, immigrants and recent returness from abroad).
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Liver microsomes of Wistar rats, induced by phenobarbital, were prepared using ultracentrifuge method. RXM in vitro metabolism was stu died with the microsome incubation. The metabolites were separated and assayed by li quid chromatography-tandem mass spectrometry (LC-MSn), and were further identified by comparison of their mass spectra and LC behavior to synthesized references.
A simple extraction technique has been developed for seven macrolide antibiotics in milk. The procedure involves a modified quick, easy, cheap, effective, rugged, and safe method based on acetonitrile extraction, followed by the addition of a mixture of salts (sodium sulfate, sodium chloride, and potassium carbonate) not yet reported in literature. The method was validated for tylosin and was selective, free of matrix effect, and linear in the range of 0.78-18.75 ng/mL in the final extract, corresponding to 0.125-3 times the maximum residue limit. The limit of detection, limit of quantification, decision limit, and detection capability were, respectively, 0.84, 2.79, 58.4, and 71.7 μg/kg. The overall average recovery at 25, 50, and 75 μg/kg ranged from 89-97%. Repeatability and intermediate precision expressed by relative standard deviations were below 10.5 and 12%, respectively. The extension of the validation for spiramycin, throleandomycin, oleandomycin, roxithromycin, erythromycin, and clarithromycin is under consideration since the procedure proved to be able to efficiently extract all studied macrolides, with recoveries from 74-104% at 50 μg/kg for tylosin, erythromycin, spiramycin, and oleandomycin and 20 μg/kg for throleandomycin, roxithromycin, and clarithromycin.
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A two-compartment model with saturable absorption described the data (n = 63); changes in free drug exposure were simulated using a saturable protein binding model. Simulations indicated that a 300 mg daily regimen achieves a 37% and 53% lower total or free AUC (fAUC), respectively, compared with 150 mg twice daily. These pharmacokinetic differences translated to significantly lower target attainment (fAUC/MIC ratio >20) with a 300 mg daily regimen at MICs of 0.5 and 1 mg/L (51% and 7%) compared with patients receiving 150 mg twice daily (82% and 54%).
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An open non-comparative clinical study to determine the efficacy and tolerance of Roxithromycin 150 mg twice daily was carried out amongst Nigerian patients with acute upper and lower respiratory tract infections. Twenty-four (24) patients (mean age 21.6 years, male 13; females 11 who completed the study presented with acute tonsillitis (33.3%, acute bronchitis (12.5%), lober pneumonia (12.5%), Otitis media (8%), acute pharyngitis (4%) and acute sinusitis (4%). Most of the patients had normal bacterial flora isolated (50.3%). Pathogens isolated included streptococcus pyogenes (21%), moraxella catarhalis (8.3%), streptococcus pneumonia (8.3%) and Klebsiella pneumonia (4%). The quick clinical response, lack of major adverse drug reactions and susceptibility of the bacterial isolates to Roxithromycin were very significant attributes of the drug. In addition, there was complete recovery in 95.8% of the patients. Roxithromycin is therefore a well tolerated and effective drug for the treatment of acute respiratory tract infections in Nigerian patients.
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We included in our study 95 children presenting symptoms of UTI, with repeatedly negative urine cultures, between June 2002 - February 2004. The culture of mycoplasmas and the antibiotic susceptibility testing (doxycycline, roxithromycin, ofloxacin) was performed using the broth and various substrates provided by the kit in a gallery system.
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Macrolides, a class of antimicrobials isolated from Streptomycetes more than 50 years ago, are used extensively to treat sinopulmonary infections in humans. In addition, a growing body of experimental and clinical evidence indicates that long-term (years), low (sub-antimicrobial)-dose 14- and 15-membered ring macrolide antibiotics, such as erythromycin, clarithromycin, roxithromycin and azithromycin, express immunomodulatory and tissue reparative effects that are distinct from their anti-infective properties. These salutary effects are operative in various lung disorders, including diffuse panbronchiolitis, cystic fibrosis, persistent chronic rhinosinusitis, nasal polyposis, bronchiectasis, asthma and cryptogenic organizing pneumonia.The purpose of this overview is to outline the immunomodulatory effects of macrolide antibiotics in patients with asthma.
Pediatric Lyme arthritis is more benign in younger children. Lyme arthritis should be excluded as a possible cause of arthritis prior to the administration of intraarticular steroids.
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The in vitro activity of telithromycin (HMR3647), a new ketolide, against Mycoplasma pneumoniae was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it was more active than four other macrolides, minocycline, and levofloxacin; its MICs at which 50 and 90% of the isolates tested were inhibited were both 0.00097 microg/ml, justifying clinical studies to determine its efficacy for treatment of M. pneumoniae.
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Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.
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Throat swabs were collected from 3529 children with respiratory tract infection, who visited the pediatric outpatient department or received treatment in the pediatric ward of our hospital from September 2010 to September 2011. The swabs were cultured to detect MP. The drug sensitivity of MP to azithromycin, roxithromycin, erythromycin, acetylspiramycin and clarithromycin was evaluated.
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HMR3647 is a semisynthetic representative of a new group of drugs, the ketolides, derived from erythromycin A. Since macrolides have been shown to accumulate in human polymorphonuclear cells (PMNs), we have investigated the ability of the molecule HMR3647 to enter human PMNs as well as other cell types, such as peripheral blood mononuclear cells and cell lines of hematopoietic and nonhematopoietic origin. In these experiments, HMR3647 was compared to erythromycin A, azithromycin, clarithromycin, and roxithromycin. Our results show that HMR3647 is specifically trapped in PMNs, where it is concentrated up to 300 times. In addition, it is poorly released by these cells, 80% of the compound remaining cell associated after 2 h in fresh medium. By contrast, it is poorly internalized and quickly released by the other cell types studied. This differs from the results obtained with the macrolide molecules, which behaved similarly in the different cells studied. In addition, subcellular fractionation of PMNs allowed us to identify the intracellular compartment where HMR3647 was trapped. In PMNs, more than 75% of the molecule was recovered in the azurophil granule fraction. Similarly, in NB4 cells differentiated into PMN-like cells, almost 60% of the molecules accumulated in the azurophil granule fraction. In addition, when HMR3647 was added to disrupted PMNs, 63% accumulated in the azurophil granules. Therefore, this study shows that the ketolide HMR3647 specifically accumulates in PMN azurophil granules, thus favoring its delivery to bacteria phagocytosed in these cells.
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Universal quantitative models using NIR reflectance spectroscopy were developed for the analysis of API contents (active pharmaceutical ingredient) in roxithromycin and erythromycin ethylsuccinate tablets from different manufacturers in China. The two quantitative models were built from 78 batches of roxithromycin samples from 18 different manufacturers with the API content range from 19.5% to 73.9%, and 66 batches erythromycin ethylsuccinate tablets from 36 manufacturers with the API content range from 28.1% to 70.9%. Three different spectrometers were used for model construction in order to have robust and universal models. The root mean square errors of cross validation (RMSECV) and the root mean square errors of prediction (RMSEP) of the model for roxithromycin tablets were 1.84% and 1.45%, respectively. The values of RMSECV and RMSEP of the model for erythromycin ethylsuccinate tablets were 2.31% and 2.16%, respectively. Based on the ICH guidelines and characteristics of NIR spectroscopy, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. Our study has shown that it is feasible to build a universal quantitative model for quick analysis of pharmaceutical products from different manufacturers. Therefore, the NIR method could be used as an effective method for quick, non-destructive inspection of medicines in the distribution channels or open market.
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RXM suppressed UVB-induced apoptosis of SVHK cells. UVB-irradiated SVHK cells showed decreased SOD, GPx, GR, and catalase activities. RXM pretreatment suppressed the decrease in these enzyme activities with the maximal effect detected at 10microM of RXM. The effect was associated with suppression of UVB-induced superoxide and H(2)O(2) production.
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Macrolides, one of the oldest antibiotic classes, are widely used in out-patient, clinics and hospitals. The major improvement in developing newer derivatives concerns pharmacokinetic properties. Increased half-lives, persisting concentrations in tissues, interstitial fluids and macrophages confer upon newer macrolides significant advantages as compared to the parent compound erythromycin. Roxithromycin, a newer macrolide has a high peak serum concentration, providing very high levels both in the interstitial fluid and intracellularly. Pharmacodynamic approaches are still limited with macrolides, however the very high inhibitory quotient established for tissue concentrations and interstitial fluid suggests the potential clinical efficacy of these drugs.
Two hundred and forty-two patients over 16 years of age with community-acquired lower respiratory tract infection (LRTI), matched for age and sex, were randomised to receive either roxithromycin 150 mg b.i.d. or amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for 7 days, with a further 7 days if insufficient response was seen. Clinical efficacy at 7 days was 69% for roxithromycin and 56% for amoxycillin/clavulanic acid (p = 0.05) and at study end it was 91% for both antibiotics. There were fewer second treatment courses in the roxithromycin group (26% vs. 38%, p = 0.04) and a shorter treatment duration (8.29 days vs. 9.34 days, p > 0.05). Twelve patients (9.8%) treated with roxithromycin and 19 (17.1%) treated with amoxycillin/clavulanic acid had adverse effects possibly, or probably, related to the antibiotic. Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, greater cost-effectiveness, more convenient dosage regimen (b.i.d.), and superior tolerability profile.