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Of the 7 antibiotics tested, clarithromycin showed the greatest activity against C. trachomatis isolates with MIC90 of 0.032 μg/mL and MBC90 of 0.064 μg/mL, followed by doxycycline with MIC90 0.064 μg/mL and MBC90 0.064 μg/mL, and azithromycin with MIC90 0.160 μg/mL and MBC90 0.320 μg/mL. Azithromycin had roughly the same MIC50 values (0.08 μg/mL) as the other serovars isolates tested, and other antibiotics showed a 2- to 4-fold difference in MICs50 between serovars. In addition, an increase in the azithromyin MIC was observed by 8 hours and the ofloxacin MIC by 16 hours. At 24 hours, the azithromycin MICs were greater than 40 μg/mL and ofloxacin MICs were greater than 64 μg/mL.
The in vitro activity of azithromycin (CP 62,993 or XZ-450) against Haemophilus influenzae was greater than that of three other macrolides. However, azithromycin was four- to eightfold less active than erythromycin against the gram-positive cocci and against Listeria monocytogenes. Erythromycin and azithromycin were similar in their activity against Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis.
We studied the immunological and histopathological factors that affect the prognosis of chronic rhinosinusitis under long-term low-dose macrolide therapy. Sixteen patients with chronic rhinosinusitis were given 200 mg clarithromycin or 150 mg roxithromycin orally once a day without other concurrent treatments for 2-3 months. Measurement of the serum IgE level, blood cell count and differential leukocyte count of the peripheral blood, cytological assessment of the nasal smear and computed tomographic (CT) scans of the paranasal sinuses were performed before treatment. The opacity of the sinuses was estimated and scored by the CT images. After treatment, anterior ethmoidal mucosa samples were collected, an infiltrated inflammatory cells, interferon (IFN)-gamma-positive cells and interleukin (IL)-4-positive cells were examined histologically and immunohistochemically. The severity of nasal symptoms was scored before and after treatment, and the improvement rate of the score (symptomatic improvement rate) was calculated. Patients with normal levels of serum IgE (=250 U/ml) showed a significantly higher symptomatic improvement rate than those with high levels of serum IgE (42.1 +/- 11.2 vs. 4.9 +/- 3.1%, p = 0.046). The symptomatic improvement rate was inversely correlated with the eosinophil counts in the peripheral blood (r = -0.51, p = 0.04), in the nasal smear (r = -0.54, p = 0.045) and in the sinus mucosa (r = -0.54, p = 0.02). Meanwhile, the CT score, the number of IFN-gamma-positive cells and IL-4-positive cells in the sinus mucosa and neutrophil counts in the nasal smear and in the sinus mucosa failed to correlate with the symptomatic improvement rate. These results suggest that macrolide therapy is indicated for patients without atopy or smear/tissue/peripheral blood eosinophilia. On the contrary, the severity of the disease, Th1/Th2 dominance in the sinus mucosa and neutrophilia are unlikely to be prognostic factors of chronic rhinosinusitis under long-term low-dose marolide therapy.
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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.
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.
Infantile exposure to macrolides has been associated with hypertrophic pyloric stenosis causing projectile vomiting, dehydration, electrolyte abnormalities, and in rare cases death possibly via macrolide interaction with gastric motilin receptors. Large population-based cohorts have suggested that exposure to macrolides via breastmilk may be associated with pyloric stenosis.
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Seven RCTs were found in the systematic review and six studies were included in the present meta-analysis. Macrolides treatment showed a significant reduced rate of pulmonary exacerbation (RR = 0.55, 95%CI = 0.43-0.70) compared with control groups. However, subgroup analysis failed to find any significant changes in total 46 patients (RR = 0.20, 95%CI = 0.03-1.58) for treatment not more than 3 months. The incidence rates of total adverse events showed no significant difference among the macrolides group and control groups.
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To test the efficacy of short-term administration of RXM, elder IL-10-deficient mice (16-20 weeks old) with established colitis were orally treated for 10 days with RXM (20 mg/kg per day). To test the long-term preventive effects of RXM, for 20 weeks young adult IL-10-deficient mice (4-5 weeks old) also were administered RXM orally (20 mg/kg per day).
Low dose Roxithromycin has good long term curative effect in treating chronic sinusitis. Low dose Roxithromycin can greatly urge the apoptosis of endothelial cell.
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We evaluated the effect of roxithromycin therapy (150 mg twice daily for 30 days) on the progression of the intima-to-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective and randomized trial with a follow-up of 2 years in 272 consecutive patients with ischemic stroke aged over 55 years in whom the first IMT measurement and Cp testing (IgG and IgA) were performed at least 3 years before the roxithromycin treatment. Cp IgG antibodies (> or =1:64) were initially found in 123 (45%) patients and IgA antibodies (> or =1:16) in 112 (41%) 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 [95% CI, 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 significantly decreased IMT progression after 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). No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up. No change of IMT was observed in Cp-negative patients given roxithromycin (n=74) compared with those without therapy (0.06 [0.03 to 0.09] versus 0.07 [0.05 to 0.09] mm/year).
Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease. The influence of macrolides on the expansion rate of abdominal aortic aneurysms (AAAs) remains unknown. The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs.
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CT infection rates (14.99%), UU infection rates (23.24%), UU + MH infection rates (29.05%),CT + UU + MH infection rates (9.17%) and total infection rates (88.99%) in infertility group is higher than those (order: 2.80%, 6.99%, 8.39%, 4.55%, 29.02%) in the control group, comparisons of two groups are statistically significant differences (P < 0.05), the susceptibility of UU to roxithromycin (sensitivity is 96.05%), josamycin (sensitivity is 96.05%), tetracycline (sensitivity is 82.89%), vibramycin( sensitivity is 92.11%) and clarithromycin (sensitivity is 96.05%) were relatively high and low to ciprofloxacin and acetyl spiramycin. The susceptibility of MH to josamycin (sensitivity is 95.83%), vibramycin (sensitivity is 91.67%), minocin (sensitivity is 83.33%) and actinospectacin (sensitivity is 75.00%) were relatively high and low to erythromycin, azithromycin, roxithromycin and clarithromycin. UU + MH was only sensitive to josamycin (sensitivity is 90.52%), high resistance (77.89% -91.58%) to erythromycin, azithromycin, acetyl spiramycin, ciprofloxacin, ofloxacin, azithromycin and clarithromycin.
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Roxithromycin is a semi-synthetic 14-membered-ring macrolide antibiotic in which the erythronolide A lactone ring has been altered to prevent inactivation in the gastric milieu. The in-vitro activity of roxithromycin is well documented and similar to that of other macrolide antibiotics. Roxithromycin is active against gram-positive and gram-negative cocci, gram-positive bacilli and some gram-negative bacilli, but has no significant effect on the predominant faecal flora. It also displays good activity against atypical pathogens, such as Mycobacterium avium complex, Helicobacter pylori and Borrelia spp. It penetrates and accumulates within cells, such as macrophages and polymorphonuclear neutrophils (PMNs), where it is distributed between the cytosol and cellular granules. Once inside the cells, it is active against intracellular pathogens, such as Legionella, Chlamydia, Mycobacterium, Rickettsia and Borrelia spp. Like other macrolides, roxithromycin displays a significant post-antibiotic effect which is dependent on the pathogens under study, the concentration of roxithromycin and the duration of exposure. In vivo, roxithromycin is as effective or more effective than other macrolides in a wide range of infections.
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As Helicobacter pylori plays an important role in the aetiopathogenesis of peptic ulcer, therapeutic strategies aimed at maintaining long term remission have shifted from the control of intragastric pH to targeting H. pylori. According to recent international guidelines the clinical goals--rapid ulcer healing and prevention of relapse--can be best accomplished by combination therapy consisting of an antisecretory drug (proton pump inhibitor or ranitidine) and 2 antimicrobial agents (preferable amoxicillin, clarithromycin or metronidazole). When applying such multidrug regimens, possible synergy between the agents suggests that pharmacokinetic considerations might help to improve H. pylori eradication rates, which should be above 85 to 90% on an intention-to-treat basis. The present review summarises the pharmacokinetic properties and interaction potential of all drugs presently used in the various H. pylori eradication regimens, with emphasis on particular patient populations such as the elderly and those with renal impairment. The drugs considered are omeprazole, lansoprazole, pantoprazole, rabeprazole, ranitidine and ranitidine bismutrex, bismuth salts, amoxicillin, clarithromycin, azithromycin, roxithromycin, metronidazole, tinidazole and tetracycline. When addressing the clinically important questions of the efficacy, safety and costs of the recommended regimens, the impact of drug disposition on H. pylori eradication should not be neglected.
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We previously reported antiangiogenic activity of roxithromycin and clarithromycin, 14-membered ring macrolide antibiotics. In the present study, we examined the antitumor effects of roxithromycin and clarithromycin, alone and in combination with several cytotoxic drugs, on mouse B16BL6 melanoma cells in vivo and in vitro. Both roxithromycin and clarithromycin potentiated the inhibition of tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin and vindesine in vivo. However, neither roxithromycin nor clarithromycin, altered the cytotoxicity of 4-hydroperoxycyclophosphamide, cis-diamminedichloroplatinum(II), Adriamycin or vindesine in an in vitro cell proliferation assay. These results suggest that the antiangiogenic activity of roxithromycin and clarithromycin may provide beneficial effects in combination with cytotoxic therapies against solid tumors.
This paper describes a simple spectrofluorometric method for the analysis of 4 macrolide antibiotics. The method is based on the condensation of 10% (w/v) malonic acid and acetic acid anhydride under the catalytic effect of tertiary amine groups of the studied macrolides. The relative fluorescence intensity of the condensation product was measured at 397/452 nm (excitation/emission) for azithromycin dihydrate and at 392/445 nm (for clarithromycin, erythromycin ethylsuccinate, and roxithromycin. All variables affecting the reaction conditions were studied. The effects of potential interference due to common excipients, such as starch, lactose, sucrose, glucose, gum acacia, and magnesium stearate, as well as trimethoprim and sulfisoxazole acetyl formulated in primomycin capsules and pediazole oral suspension, respectively, were studied. A validation study for the proposed method was carried out according to U.S. Pharmacopeia 2002. The linearity ranges were 3-80 ng/mL for all of the cited macrolides. The limit of detection range was 0.74-1.20 ng/mL, while the limit of quantitation range was 2.47-4.02 ng/mL. The method was applied for the assay of the studied macrolides in pure pharmaceutical formulations and in spiked biological fluids. Results were compared with those obtained from the reported method, where calculated t- and F-values indicated high accuracy and good precision for the proposed method.
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This study investigated the residues of antibiotics present in the Yellow River and its tributaries. Ofloxacin, norfloxacin, roxithromycin, erythromycin, and sulfamethoxazole, were found in the river with mean concentrations from 25 to 152 ng/L, and in certain tributaries from 44 to 240 ng/L. The other four analytes were all below the limits of quantification. The results indicated that the detected antibiotics in the middle and lower Yellow River were primarily from its tributaries and ambient wastewater discharge. The concentrations of the antibiotics detected in the river were greater than that in other rivers in Europe. The antibiotics in the river and its tributaries at ng/L concentrations found in this study are unlikely to induce lethal toxicity to aquatic organism but could cause chronic ecological effects.
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A very favorable outcome after chemotherapy of 122 cases of M. kansasii lung disease was reported by Dr. Mizutani, who emphasized RFP as the "Key drug", and concluded that three-drug combination (not two-drug), including RFP (RFP.INH.EB or SM) for 1 year, could be a standard regimen for M. kansasii lung disease at the time of the moment. In addition, the following itemes were discussed. (1) In cases resistant to RFP, one could possibly replace RFP by TH, one of new quinolones (NQ), or the new macrolide (NM) (clarithromycin, CAM). (2) In low grade resistant cases to INH (0.1 microgram /ml) or EB (2.5 micrograms/ml), the replacement of the drugs may not be necessary, however, in higher-grade resistance to INH or EB, many cases were looked for the change of drugs according the results of the questionnaire done by the author. The present status of basic preclinical evaluations of new drugs were presented by Dr. Tomioka, who summarized in vitro and in vivo antimycobacterial activities of NMs and NQs. The most potent activity among NMs was demonstrated in CAM, which is probably the candidate for M. kansasii and possibly for M. avium complex (MAC) disease, followed by roxithromycin (RXM) and azithromycin (AZM) in sequence. NQs including the ones under development were generally potent against Mycobacterium tuberculosis, M. kansasii and M. fortuitum. NQs were not potent enough for MAC. In addition, the author discussed more suitable in vitro techniques which should reflect in vivo evaluations, and proposed the observation of in vitro bactericidal activity using both Cmax (maximal in vivo concentration) and C (0-8h) (the average concentration during 8 hours after administration) of drugs, and also the assessment of bactericidal activities of drugs in macrophages as better choices. As additional comments, the results of in vitro activities of NQs and NMs against MAC were supplemented by two authors, Dr. Tsuyuguchi and Dr. Kawahara. The assessment using 7 H 9 liquid medium by the former author demonstrated the potent activities of both CS-940* and sparfloxacin (SPFX), followed by AM-1155*, ciprofloxacin (CPFX), levofloxacin (LVFX), OPC-17116*, NM-394* in sequence. The author gave attention also to a high Cmax in CS-940*. In vitro activities with 7 H 11 agar medium reported by Dr. Kawahara demonstrated generally higher activities against M. avium than M. intracellulare, and reported potent activities of CPFX, SPFX, LVFX, grepafloxacin (GPFX), AM-1155*, and DU-6859 a* among 14 NQs tested. The author reported a rather potent activity of CAM against MAC followed by RXM and AZM in sequence. There was an impression that the MICs in both liquid and agar medium were comparable. (* : under development). The present status in the treatment of MAC lung disease was precisely reported by Dr. Harada, who summarized the results of survey both in 13 National Chest Hospitals (by questionnaire) and in the author's Hospital. The former survey demonstrated that 73% of the cases with the initial chemotherapy became consecutively negative for 6 months in the span of 9 months observation, which clearly showed the early response of MAC disease was rather favorable, in spite of very few cases with 4 drug-or more combinations. However, longer the follow up, the percentage of negative cases went down, which suggested bacteriological relapse occurred in relatively high percentage of the early converted cases. The evaluation of 117 cases of pulmonary MAC disease in the author's Hospital disclosed 2 drug-combination, RFP and INH, was clearly less potent than 3-drug combination, RFP.IHN.SM or EB, and 1 year after the begining of initial chemotherapy, around 60% of cases were negative, while only a little more than 40% of cases were negative in retreatments. The author suggested that around 50% of MAC lung disease may progress with episodes of "relapse". Death occurred 20% in the cases
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These findings show that 14-MRMLs clearly attenuated the expression of VCAM-1mRNA, and tended to attenuate the induction of ICAM-1 and TNF-alpha mRNA, and subsequently inhibited leucocyte, especially neutrophil migration into the airspace during the early phase of BLM-induced lung injury and finally inhibited lung fibrosis. This might be one potent mechanism of the anti-inflammatory effects of 14-MRMLs in BLM-induced acute lung injury. The findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.
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During a 3-year period, we retrieved the results from placental and amniotic membrane cultures obtained at delivery in cases of maternal fever, chorioamnionitis, and PPROM, and from blood cultures obtained from neonates with early-onset sepsis (EOS) in three participating hospitals. Sensitivity of pathogens to antimicrobial agents was performed using routine microbiologic techniques.
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Municipal wastewater treatment plants (WWTPs) are an important source of pharmaceuticals released into the environment. Understanding how various pharmaceuticals are distributed and handled in WWTPs is a prerequisite to optimize their abatement. Here we investigated the spatial distribution and removal efficiencies pharmaceuticals in China's WWTPs. A total of 35 pharmaceuticals in wastewater samples from 12 WWTPs at different cities of China were analyzed. Among these detected pharmaceuticals, caffeine showed the highest concentration (up to 1775.98ngL(-1)) in the WWTP influent. In addition, there were significant regional differences in pharmaceutical distribution with higher influent concentrations of total pharmaceuticals detected in WWTPs in the northern cities than the southern ones. The state-of-the-art treatment processes were generally inefficient in removing pharmaceuticals. Only 14.3% of pharmaceuticals were removed effectively (mean removal efficiency>70%), while 51.4% had a removal rate of below 30%. The anaerobic/anoxic/oxic (AAO)-membrane bioreactor (MBR) integrated process and sequencing batch reactor (SBR) showed better performance than the AAO and oxidation ditch (OD) processes. Ofloxacin, erythromycin-H2O, clarithromycin, roxithromycin and sulfamethoxazole in WWTP effluents exhibited a high or medium ecological risk and deserved special attention.
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The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts.
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Endocervical swabs were taken from fifty normal pregnant women (normal group) and fifty-eight women with spontaneous abortion due to embryonic death. The swabs were used for ureaplasma urealyticum (UU) and mycoplasma hominis (MH) Cultivation respectively. The isolation rates of the two groups were comparedf.
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Abdominal aortic aneurysm is a common condition that may be lethal when it is unrecognized. Current guidelines suggest repair as the aneurysm diameter reaches 5.0 to 5.5 cm. Most aortic aneurysms are detected incidentally when imaging is done for other purposes or through screening programs. Ninety percent of these aneurysms are below the threshold for intervention at the time of detection. A number of studies have sought to determine factors that lead to progression of aneurysmal disease that might be amenable to intervention during this period of observation. We review these studies and make recommendations for the medical management of small abdominal aortic aneurysms. On the basis of our current knowledge of the causes of aneurysm, a number of approaches have been proposed to prevent progression of aneurysmal disease. These include hemodynamic management, inhibition of inflammation, and protease inhibition. The American College of Cardiology/American Heart Association clinical practice guidelines rules of evidence have helped to define strength of evidence to support these approaches. Level A evidence (from large randomized trials) is available to indicate that observation of small aneurysms in men is safe up to a size of 5.5 cm and that propranolol does not inhibit aneurysm expansion. Level B evidence (from small randomized trials) suggests that roxithromycin or doxycycline will decrease the rate of aneurysm expansion. A number of studies agree that tobacco use is associated with an increased rate of aneurysm expansion. Level B and C evidence is available to suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may inhibit aneurysm expansion. There are animal data but no human data demonstrating that angiotensin-converting enzyme inhibitors or losartan, an angiotensin receptor blocker, will decrease the rate of AAA expansion. A pharmacological agent without important side effects that inhibited aneurysm expansion could change current approaches to aneurysm treatment. Additional studies are needed to clarify the potential role of doxycycline, roxithromycin, and statin therapy in the progression of aneurysmal disease.
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The antimycobacterial spectrum of roxithromycin, a semisynthetic 14-membered ring macrolide, was determined against 28 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs by BACTEC methodology at two different pH values, i.e., 6.8 and 7.4. The MICs obtained at pH 7.4 were 1 to 2 dilutions lower or more than those obtained at pH 6.8 for some of the species. Roxithromycin possessed promising MICs against such potential pathogens as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, and rare pathogens like M. chelonei subsp. chelonei and M. chelonei subsp. abscessus but not against M. simiae. Roxithromycin showed lower MICs against M. fortuitum var. peregrinum than M. fortuitum var. fortuitum.
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This method was found to be simple, rapid, sensitive and accurate for determination of RM in human serum.
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Since roxithromycin inhibits CYP3A4, which is involved with cyclophosphamide metabolism, a drug-drug interaction could have been responsible. In addition, roxithromycin is an inhibitor of the drug transporter P-glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial cells. Alternatively, since cyclophosphamide has been reported to induce apoptosis, roxithromycin could have rendered endothelial cells more vulnerable for apoptosis.
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The influence of roxithromycin (RXM), a macrolide antibiotic, on endogenous corticosterone (CS) levels was examined in BALB/c mice. Mice were sensitized intraperitoneally with two doses of Keyhole Limpet Hemocyanin at 1 week intervals. Mice were given orally 2.5 mg/kg RXM once a day for 14 days starting 7 days after the first sensitization. RXM administration caused markedly increase in endogenous plasma CS levels which was peaked at 60 min after the administration. However, josamycin did not influence on endogenous CS levels in plasma. Injection of dexamethasone inhibits the plasma CS hyperproduction induced by RXM treatment.
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The effect was studied on gastrointestinal motor activity of three different macrolides (erythromycin, roxithromycin and midecamycin acetate), administered by mouth in therapeutic doses. This placebo-controlled study was performed in 12 normal human subjects by means of intraluminal pressure measurements in the gastric antrum, duodenum and upper jejunum. In each subject, three manometries were done for 5 h in the interdigestive period and for 3 h postprandially. In the interdigestive period, midecamycin acetate did not affect the characteristics of the gastric migrating motor complex (MMC) and did not increase the number of antral contractions or the gastric motility index as compared to the placebo. Erythromycin and roxithromycin increased the number of antral contractions (24.5 +/- 11 versus 15.2 +/- 7 and 28.4 +/- 12 versus 14.9 +/- 5.9 respectively) and the motility index (4.05 +/- 0.5 versus 3.17 +/- 0.6 and 4.38 +/- 0.2. versus 3.64 +/- 0.7 respectively) as compared to the placebo. In the postprandial period, the number of antral contractions was not significantly increased by any of the three antibiotics. The postprandial antral motility index was not significantly increased by midecamycin acetate. In contrast, the postprandial antral motility indexes after erythromycin (4.4 +/- 0.5) and after roxithromycin (4.3 +/- 0.2) were significantly greater than after the placebo. In the upper small intestine, erythromycin elicited an increased number of phase-III-like activity events and roxithromycin shortened the MMC cycle length. Midecamycin acetate had no effect on interdigestive upper jejunal motility. The postprandial jejunal motor activity was not altered by any of the three antibiotics neither during the interdigestive nor the postprandial periods.(ABSTRACT TRUNCATED AT 250 WORDS)