The authors are analyzing their results of the treatment with roxithromycin 150 mg of the pelvic inflammatory disease, caused by chlamydia trachomatis. 29 patients with proved chlamydial infection were treated. The most popular diagnosis was cervicitis. 23 patients were totally cured, 4 patients were with considerable better status after the treatment, and 2 of the patients were with insignificant amelioration of the status. A conclusion can be made, that the roxithromycin is a very good alternative of the existing treatment with doxycicline.
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In this study the sensitivity of RADT was low; therefore, the negative results of RADT don't exclude presence of GABHS. High prevalence of GABHS antigen demonstrates not only in patients with RF, but also among healthy children (without RF) of the Kyrgyz Republic. The high prevalence of GABHS at children with RF (47.0%), probably, presents a low sensitivity to antibiotics and irregular secondary prophylaxis. Significant presence of GABHS among healthy children (37.5%) requires improvement of primary prevention to prevent further spread of RF and Rheumatic Heart Disease (RHD) in the country.
There have been reports of an interaction when theophylline and macrolides are given together, and also when carbamazepine is given with macrolides. We compared the kinetics of theophylline and carbamazepine, given alone and then in combination with roxithromycin. Roxithromycin had little effect on the pharmacokinetics of theophylline and none on carbamazepine, and roxithromycin can be given with either of the drugs without any need to alter the dose.
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The macrolide antibiotic roxithromycin has seen widespread clinical use for several decades; however, no population pharmacokinetic analysis has been published. Early studies indicated saturation of protein binding and absorption at doses within the approved range, which may impact pharmacodynamic target attainment since regimens of 150 mg twice daily and 300 mg once daily are used interchangeably in clinical practice. This study aimed to develop a population-based meta-analysis of roxithromycin pharmacokinetics, and utilize this model to inform optimal dosing regimens.
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Small-cell lung cancer (SCLC) patients were randomised to standard or intensified chemotherapy with granulocyte colony-stimulating factor to assess the impact on survival (n = 244). In addition, patients were randomised to prophylactic ciprofloxacin and roxithromycin or placebo to assess the impact on FL (n = 161). The economic evaluation examined the costs and effects of patients taking antibiotics versus placebo. Medical resource utilisation was documented prospectively, including 33 patients from one centre in The Netherlands (NL) and 49 patients from one centre in Germany (GE). The evaluation takes the perspective of the health insurance systems and of the hospitals. Sensitivity analyses were performed.
The infection rate was 5.74%. There were no significant correlations between low birth weight, premature rupture of the membranes, dysmaturity and C. tr. infection. In cases of threatening premature labor, the infection rate was significantly higher in C. tr.-positive patients. In the event of combined low birth weight and perinatal death, the maternal C. tr. infection rate was significantly higher than in normal pregnancies. C. tr.-positive patients treated with roxithromycin had term deliveries. A correlation between poor social circumstances and a high C. tr. infection rate could be proved.
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Roxithromycin, a new introduction into the macrolide class of antibiotics possesses favourable pharmacokinetic properties enabling a once daily dosing. This study evaluates its efficacy, safety and tolerability, previously demonstrated in Europe and North America, in Nigeria patients suffering from lower respiratory tract infections. 32 patients, aged 18-65 years with acute bronchitis/acute exacerbation of chronic bronchitis and pneumonia were administered roxithromycin 300 mg once daily. 25 patients (12 males, 13 females: aged 39.2 +/- 2.7 years) were evaluable for clinical efficacy at the end of the study. The mean duration of treatment was 6.9 +/- 0.5 days. 22 patients (88.0%) responded to therapy. Sputum culture was positive in 5 patients (20.0%): Streptococcus pneumonia and resistant Klebsiella pneumonia. Therapy was discontinued in 3 patients due to non-response. The two patients in whom Klebsiella were isolated did not show any significant clinical improvement. The third non responding patient developed empyema. Gram negative bacilli were identified in the pleural aspirate but no patients with resistant Streptococcus pneumonia improved clinically. Adverse effects were mild, transient and included nausea (4) and diarrhoea (1). The study suggests that roxithromycin is an effective and well tolerated antibacterial in the treatment of lower respiratory tract infection.
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A randomized single-blind study of the effects of erythromycin and roxithromycin on chlamydial conjunctivitis was performed on a group of patients, comprising 28 newborns and 27 adults. Treatment used was either 200 mg of erythromycin ethylsuccinate or 50 mg of roxithromycin daily, divided into two doses for the neonatal group or for the adult group, 1000 mg of erythromycin stearate or 300 mg of roxithromycin daily divided into two doses. All patients were treated for ten days. Clinically nine of the neonates and 13 of the adults had unilateral conjunctivitis, whilst the remaining cases were bilateral. At follow-up one month after commencing therapy, all but one (erythromycin-treated) of the 28 neonates and three (two of whom were erythromycin-treated) of the 27 adults were cured. However, 16 (nine neonates and seven adults) were culture-positive for Chlamydia trachomatis in samples from eye and/or nasopharynx. The culture-positive group comprised ten cases (four neonates and six adults) who had been treated with erythromycin and six (five neonates and one adult) with roxithromycin. No major side effects of the therapy were seen. The study indicates that there was no difference in the clinical cure rate for the two drugs either in neonates or in adults. However, the isolation rate of chlamydiae in the adult group differed, with 12 (92%) of the 13 roxithromycin-treated cases becoming culture-negative, whilst this was true for only eight (57%) of the 14 erythromycin-treated cases (P less than 0.007).
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From December 1984 to June 1986, a prospective clinical trial was carried out in 48 patients with acute community-acquired pneumonia, comparing 2 possible therapeutic schemes: one, using only one antibiotic (roxithromycin: RXT) presumptively active on most of the germs usually involved. In a second group, the identification of the germs involved was attempted on the basis of clinical, epidemiological and radiological data, followed by treatment with the antibiotic/s (ATB) known to be more active against the suspected organisms. The dosage of RXT was 300 mg/day, orally during an average of 9 days. The mean duration of treatment in ATB group was 12 days. In both groups, the following microorganisms were identified: RXT group: St. pneumoniae (13 cases), H. influenzae (1), B. catarrhalis (1); mixed infections: St. pneumoniae + H. influenzae (2); Mycoplasma pneumoniae (3) and 4 patients with unidentified germ; in ATB group: St. aureus (3), St. pneumoniae (5), H. influenzae (2), B. catarrhalis (1); mixed infections: St. aureus + Enterobacter + E. coli (1); Mycoplasma pneumoniae (2) and 10 patients with unidentified germ. The therapeutic results were satisfactory (curation rate: 92%) and similar for both groups of treatment, concluding that both schemes are comparable. Therefore, the choice for one or the other scheme should be based on other reasons, such as easy administration and cost of the treatment.
Nasal polyps of six patients (three women and three men; 32.3 ± 5.2 years of age) were acquired during surgery and NPDFs were isolated from surgical tissues. NPDFs were pretreated with macrolides for 2 hours before differentiation induction by TGF-beta1. The mRNA expressions of alpha-smooth muscle actin (SMA), collagen types I and III, and Nox4 were determined by reverse-transcription-polymerase chain reaction, and the expression of alpha-SMA protein was determined by immunocytochemical staining. The amount of total collagen production was analyzed by SirCol collagen dye-binding assay. ROS activity was measured by nitroblue tetrazolium reduction assay and was visualized by fluorescent microscopy.
In a prospective randomized multicenter study Roxithromycin 150 mg or Doxycycline 100 mg was given b.i.d. p.o. for ten days to women with clinically diagnosed cervicitis. All women were seen as outpatients by one of eight licensed gynecologists in their private office in the Essen city area. With a cure and improvement rate of 100% in those women who completed therapy, Roxithromycin (n = 106) was as effective as Doxycycline (n = 104; 98%). At 90% Roxithromycin was as well tolerated as Doxycycline at 93%. Both drugs were clinically and microbiologically effective in eradicating Chlamydia trachomatis.
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Resistance of Haemophilus influenzae from clinical isolates can be predicted on the basis of results of antimicrobial susceptibility of nasopharyngeal isolates. The carriage rate and the antimicrobial susceptibility of H. influenzae isolated in healthy children attending day-care centres in Moscow, Smolensk and Yartsevo was studied. The susceptibility of ampicillin, amoxycillin/clavulanate, cefaclor, erythromycin, roxithromycin, clarithromycin and trimethoprim-sulphamethoxazole were determined by the E-test. The mean carriage rate of H. influenzae was 44%. Resistance of H. influenzae to ampicillin was 2.3%, to amoxycillin/clavulanate 0.7%, to cefaclor 0.7%, to clarithromycin 18.7% and to trimethoprim-sulphamethoxazole 21%. These included strains that showed intermediate-resistance. The antimicrobial resistance profiles varied in different centres. The clinical use of trimethoprim-sulphamethoxazole should be restricted because of the high resistance of H. influenzae to antifolate compounds.
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Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB.
Our findings strongly suggest that 5-I may be useful as a potential therapeutic agent for human rheumatoid arthritis.
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Roxithromycin (RXM), active against prokaryotes, has beneficial side effects such as anti-cancer activities on mammalian cells, but the mechanisms underlying these effects remain unclear. We found that RXM inhibited the cellular differentiation of the rice blast fungus Magnaporthe oryzae. Hence, we screened the targets of RXM by the T7 phage display method with fungal genomic DNA, and identified MoCDC27 (M. oryzae Cell Division Cycle 27) as a candidate. We generated mocdc27 knockdown mutants that the appressoria formation was less affected by RXM. A complemented mutant restored sensitivity against RXM to the level of the wild type. These results suggest that MoCDC27 was involved in the inhibition of appressorium formation by RXM, and that the complex of RXM-MoCDC27 affected another molecule involved in appressorium formation. The T7 phage display method with fungal genomic DNA can be a useful tool in the quest for drug target.
When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtained with roxithromycin, followed by clarithromycin and azithromycin. The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin. With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen. Intra-group subject variations (adults, children, the elderly etc.) were smaller than anticipated. Roxithromycin is found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour.
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The efficacy of macrolides against extracellular pathogens depends on extracellular levels of free drug and the organisms' patterns of susceptibility to the macrolides. The effect of macrolides against most bacteria is considered time-dependent. The size of inoculum affects erythromycin's activity against streptococci and, moreover, against staphylococci. The optimal effect is observed at a pH of 8. A significant postantibiotic effect (PAE), lasting approximately 9 hours, has been shown with erythromycin and roxithromycin against gram-positive cocci. Azalides share the same properties. For the streptogramin synercid, a dose-dependent bactericidal activity within a range of low concentrations has been demonstrated. The serum area under the curve appeared to be the best predictor of in vivo effect on the mouse thigh model. Synercid also exhibited a prolonged PAE (approximately 10 hours) against the main pathogens of its spectrum. A better knowledge of the pharmacodynamic properties of macrolides and streptogramins is essential for definition of proper dosing regimens.
Tuberculosis (TB) is a growing international health concern, since it is the leading infectious cause of death in the world today. Moreover, the resurgence of TB in industrialized countries and the worldwide increase in the prevalence of Mycobacterium avium complex (MAC) infections in immunocompromised hosts have prompted the quest for new antimycobacterial drugs. In particular, the appearance of multidrug-resistant (MDR) strains of M. tuberculosis, which exhibit in vitro resistance to at least two major antituberculous drug (usually INH and RFP) and cause intractable TB, has greatly contributed to the increased incidence of TB. Because of the global health problems of TB, the increasing rate of MDR-TB and the high rate of a co-infection with HIV, the development of potent new antituberculous drugs without cross-resistance with known antimycobacterial agents is urgently needed. In this article, I reviewed the following areas. First, I briefly reviewed some new findings (mainly reported after 2000) on the pharmacological status of rifamycin derivatives (rifabutin, rifapentine, and rifalazil), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), and new macrolides (clarithromycin, azithromycin, and roxithromycin). Second, I described other types of agents which are being developed as antimycobacterial drugs. Some of the agents discussed are already under preliminary clinical investigation, and others appear to be promising candidates for future development. In this review, the status of the development of new antimycobacterial, especially antituberculous agents including oxazolidinone (PNU-100480), 5'-nitroimidazole (CGI 17341), 2-pyridone (ABT-255), new riminophenazines, nitroimidazopyran (PA-824), new ketolides (ABT-773, telithromycin) and defensins (human neutrophil peptide-I), was examined. Third, the development of new antitubercular drugs was discussed according to the potential pharmacological target. New critical information on the whole genome of M. tuberculosis recently elucidated and increasing knowledge on various mycobacterial virulence genes will promote the progression in the identification of genes that code for new drug targets. Using such findings on mycobacterial genomes, drug development using quantitative structure-activity relationship may be possible in the near future. In this review, I described the screening of drugs that have an inhibitory activity against dTDP-rhamnose synthesis of M. tuberculosis, as a new drug target of the organism. In addition, I discussed the usefulness of antisense oligo DNAs specific to mycobacterial genes encoding certain metabolic enzymes or virulence factors that play roles in the bacterial escape from antimicrobial mechanisms of host macrophages. Fourth, I reviewed the drug vehicles which enable efficacious drug delivery to their target in vivo. The usefulness of poly (DL-lactide-co-glycolide) microsphere technology, which enables the encapsulated drugs to deliver the requested doses of them for prolonged time periods by a single shot without causing any toxicity and, moreover, enables the highly targeted delivery of the drugs to host macrophages, was discussed. Fifth, I described adjunctive immunotherapy for the management of patients with mycobacterial infections by giving certain immunomodulators in combination with antimycobacterial drugs. Adjuvant clinical trials using IL-2 or GM-CSF have been found to be efficacious to some extent in improving patients with tuberculosis or disseminated MAC infections. However, it seems that these immunopotentiating cytokines as well as IFN-gamma and IL-12 are not so promising for the therapeutic agents of mycobacterial infections because of the possible induction of immunosuppressive cytokines during adjuvant therapy and, in some cases, severe side-effect. Thus, the development of new classes of immuno-modulators other than cytokines, particularly those with no severe side-effect, is needed. This review dealt with ATP and its analogues which potentiate macrophage antimycobacterial activity via a purinergic P2X7 receptor. Finally, I described the roles of type II alveolar epithelial cells in the establishment of mycobacterial infections in the host lungs and the profiles of drug susceptibilities of M. tuberculosis and MAC organisms replicating within the type II pneumocytes. These findings are useful to precisely assess or predict the in vivo therapeutic activity of a given antimycobacterial drug from its in vitro activity. In this article, I have thoroughly reviewed the status of the development of new antimycobacterial drugs. There are a number of difficulties in the drug-design for the development of new drug formulations with increased potential for antimycobacterial effects, excellent pharmacokinetics, and tolerability. It should be emphasized that the most urgent goal of chemotherapy of tuberculosis and MAC infections, especially that associated with HIV infection, is to develop highly active, low-cost drugs which can be used not only in industrialized countries but also in developing countries, since the incidences of AIDS-associated intractable tuberculosis is rapidly increasing in the latter.
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This study investigates the oxidation of pharmaceuticals during conventional ozonation and advanced oxidation processes (AOPs) applied in drinking water treatment. In a first step, second-order rate constants for the reactions of selected pharmaceuticals with ozone (k(O3)) and OH radicals (k(OH)) were determined in bench-scale experiments (in brackets apparent k(O3) at pH 7 and T = 20 degrees C): bezafibrate (590 +/- 50 M(-1) s(-1)), carbamazepine (approximately 3 x 10(5) M(-1) s(-1)), diazepam (0.75 +/- 0.15 M(-1) s(-1)), diclofenac (approximately 1 x 10(6) M(-1) s(-1)), 17alpha-ethinylestradiol (approximately 3 x 10(6) M(-1) s(-1)), ibuprofen (9.6 +/- 1.0 M(-1) s(-1)), iopromide (<0.8 M(-1) s(-1)), sulfamethoxazole (approximately 2.5 x 10(6) M(-1) s(-1)), and roxithromycin (approximately 7 x 10(4) M(-1) s(-1)). For five of the pharmaceuticals the apparent k(O3) at pH 7 was >5 x 10(4) M(-1) s(-1), indicating that these compounds are completely transformed during ozonation processes. Values for k(OH) ranged from 3.3 to 9.8 x 10(9) M(-1) s(-1). Compared to other important micropollutants such as MTBE and atrazine, the selected pharmaceuticals reacted about two to three times faster with OH radicals. In the second part of the study, oxidation kinetics of the selected pharmaceuticals were investigated in ozonation experiments performed in different natural waters. It could be shown that the second-order rate constants determined in pure aqueous solution could be applied to predict the behavior of pharmaceuticals dissolved in natural waters. Overall it can be concluded that ozonation and AOPs are promising processes for an efficient removal of pharmaceuticals in drinking waters.
Patients with erythema migrans can fail to respond to antibiotic therapy. Persistent or recurrent erythema migrans, major sequelae such as meningitis and arthritis, survival of Borrelia burgdorferi and significant and persistent increase of antibody titres against B. burgdorferi after antibiotic therapy are strong indications of a treatment failure. Most, if not all, antibiotics used so far have been associated with a treatment failure in patients with erythema migrans. Roxithromycin and erythromycin are definitely or probably ineffective. However, doxycycline, amoxicillin, cefuroxime, ceftriaxone, azithromycin and high-dose penicillin V perform comparably well.
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The influence of Erythromycin, Roxithromycin, Amoxicillin, Tetracycline and Sulfamethoxazole on municipal sludge in batch reactors was investigated. The study was focused on extracellular polymeric substances (EPS) as indicator of bacteria sensitivity to toxic agents. The EPS were analysed by UV-Vis and FT-IR spectroscopies and by size exclusion chromatography. It was found that Erythromycin and Roxithromycin induced a significant increase of bound EPS in flocs. This was attributed to a protection mechanism of the bacteria. Erythromycin was the only antibiotic which inhibited COD and nitrogen removal.
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In this article, I have thoroughly reviewed the status of development of new antimycobacterial drugs, particularly fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, and moxifloxacin), new macrolides (clarithromycin, azithromycin, and roxithromycin), rifamycin derivatives (rifabutin, rifapentine, and KRM-1648), and others. The main purpose of this review was to describe the in-vitro and in-vivo activities of these drugs against Mycobacterium tuberculosis and Mycobacterium avium complex. In addition, the therapeutic efficacy of these drugs in the clinical treatment of mycobacterial infections has also been briefly mentioned.
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To review the potential association between Chlamydia pneumoniae (CP) infection and coronary artery disease (CAD), and to describe possible therapeutic interventions.