sf-837 and rokitamycin

Clinical efficacy and safety of TMS-19-Q.GC tablet (TMS), a new macrolide preparation, were compared with those of midecamycin (MDM) in superficial suppurative skin and soft tissue infections. The study was made by the double-blind controlled trial at the dosage of daily 600 mg in TMS group and 1,200 mg in MDM group. Total 218 cases (106 in TMS, 112 in MDM) were analyzed and the final global improvement rating were 82.1% in TMS and 83.9% in MDM. The clinical effectiveness of TMS was favorable and significantly different from MDM in the aged patients (greater than or equal to 60 years old) and the patients infected with susceptible strains (MIC less than or equal to 3.13) of Staphylococcus aureus. TMS is prepared with a specific formulation to make the absorption easier in the patients with lower acidity of gastric juice, and the favorable effect of TMS is considered to be a contribution of the devise in older patients. Slight adverse reactions were observed at 5.0% (6 cases) in TMS and 2.4% (3 cases) in MDM. In conclusion, TMS at the daily half dose of MDM is as effective as MDM in superficial suppurative skin and soft tissue infections.

Topics: Age Factors; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Leucomycins; Male; Miocamycin; Skin Diseases, Infectious; Suppuration; Tablets

Topics: Bacterial Infections; Clinical Trials as Topic; Double-Blind Method; Humans; Leucomycins; Miocamycin; Pneumonia; Pneumonia, Mycoplasma

The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies. The cytocidal effect of the macrolides was measured as a decrease in colony-forming efficiency and was found to increase with the concentration. To obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the concentration that decreases colony-forming efficiency 50% relative to control cells, was extrapolated from the concentration-response curves. The rank of the macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM > JM > MDM approximately EM. RKM, RXM, CAM, AZM, and JM were at least 1.7-12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic bacteria was estimated to be: > or = 53.8% for RKM, > or = 92.7% for RXM, > or = 94.6% for CAM, > or = 97.1% for AZM, and > or = 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at < or = 3 microM, CAM at < or = 10 microM, and AZM or EM at < or = 3 microM. The MIC90 against periodontopathic bacteria is < or = 4.8 microM for RXM, 5.3 microM for CAM, 2.7 microM for AZM, and 21.8 microM for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions.

Topics: Alkaline Phosphatase; Anti-Bacterial Agents; Apoptosis; Azithromycin; Cell Survival; Cells, Cultured; Clarithromycin; Collagen Type I; Dose-Response Relationship, Drug; Erythromycin; Fibroblasts; Gene Expression; Humans; Josamycin; Lethal Dose 50; Leucomycins; Miocamycin; Periodontal Ligament; RNA, Messenger; Roxithromycin; Statistics as Topic; Time Factors

The purpose of our investigation was to monitor current trends in the susceptibility patterns of clinical bacterial isolates to roxithromycin (RXM). We measured the MICs of macrolide antibiotics, such as RXM, erythromycin (EM), clarithromycin (CAM), rokitamycin (RKM) and midecamycin (MDM), and other classes of antibacterial compounds against various clinical isolates at seven institutions between October and December in 1994 and 1995. RXM had excellent antibacterial activities for S. pyogenes, S. agalactiae, M. (B.) catarrhalis and methicillin sensitive S. aureus. Against methicillin sensitive S. epidermidis, RXM activity was fairly good but about 20% of the strains had MIC > or = 128 micrograms/ml. The activity against S. pneumoniae was not so potent and similar to activities of EM, CAM, MDM, and clindamycin. The vast majority of methicillin resistant S. aureus and S. epidermidis were also resistant to macrolide antibiotics and other classes of compounds tested. In conclusion, RXM is an unique macrolide antibiotic by retaining potent activity against S. pyogenes, S. agalactiae, S. aureus except MRSA, M. (B.) catarrhalis and M. pneumoniae.

Topics: Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cephalosporins; Clarithromycin; Clindamycin; Drug Resistance, Microbial; Erythromycin; Humans; Leucomycins; Methicillin Resistance; Miocamycin; Moraxella catarrhalis; Mycoplasma pneumoniae; Penicillin Resistance; Penicillins; Roxithromycin; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes

A survey of five Nocardia spp. with respect to susceptibility towards three macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia spp. have different susceptibility profiles. Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glycosylation, reduction, deacylation, or a combination thereof.

Topics: Biotransformation; Erythromycin; Glycosylation; Inactivation, Metabolic; Leucomycins; Microbial Sensitivity Tests; Miocamycin; Nocardia; Oxidation-Reduction; Phosphorylation

Nine antimicrobial agents, the new macrolides, rokitamycin and midecamycin acetate, and seven other antibiotics, tetracycline, minocycline, doxycycline, josamycin, erythromycin, spiramycin, and norfloxacin, were studied for their antimicrobial activity against 100 strains of Ureaplasma urealyticum, using a microtiter broth dilution technique. The new macrolides, rokitamycin and midecamycin acetate, had the highest activity, with the MIC against 90% of isolates tested (MIC90) being less than or equal to 0.05 microgram/ml. MICs90 of erythromycin, josamycin, doxycycline, minocycline and tetracycline ranged from 0.1 to 0.78 micrograms/ml. Norfloxacin was least active, with a MIC90 of 12.5 micrograms/ml. Five of 100 strains tested were resistant (MIC greater than or equal to 12.5 micrograms/ml) to tetracycline, and two were resistant to minocycline and doxycycline; all of these were susceptible to rokitamycin and midecamycin acetate.

Topics: Drug Resistance, Microbial; Humans; Leucomycins; Miocamycin; Ureaplasma urealyticum

The macrolide antibiotics midecamycin acetate (MOM), erythromycin (EM), midecamycin (MDM), josamycin (JM) and rokitamycin (RKM) showed killing activity against Mycoplasma pneumoniae strain FH-P24. The activity of MOM, EM and JM was not influenced by the number of organisms inoculated, but that of RKM was markedly decreased by a large inoculum. Scanning electron microscopic observations showed many long filaments crossing over each other with small colonies when the organisms were cultivated on a glass surface without any drug for 72 h. When they were exposed to four times the MIC of MOM, the filamentous forms were decreased and the colonies did not grow to a large size. However, after exposure to the other macrolides, the colonies grew larger. Transmission electron micrographs revealed that intracellular vacuolization of the organisms was induced by exposure to MOM, EM and JM, but a mixture of vacuolized cells and "young" organisms was observed after exposure to MDM and RKM. In hamster tracheal organ cultures, the number of organisms was greatly decreased by exposure to four times the MIC of MOM, and the remaining filamentous and colonized organisms were lysed. However, treatment with four times the MIC of the other macrolides induced hardly any lysis of the organisms. In transmission electron micrographs, filamentous and rounded organisms filling the ribosome-like matrix could be seen on the epithelial surface. Treatment with four times the MIC of these macrolides decreased the number of organisms and vacuolized filamentous organisms could be seen on the epithelial cells.

Topics: Animals; Anti-Bacterial Agents; Cricetinae; Erythromycin; Glass; Leucomycins; Microscopy, Electron; Microscopy, Electron, Scanning; Miocamycin; Mycoplasma pneumoniae; Organ Culture Techniques; Trachea

The absorption and excretion of rokitamycin (RKM) in dry syrup form for children were studied following oral administration to fasted healthy volunteers with high gastric acidity as a suitable model to estimate bioavailability of RKM in children. In a comparative study on tablet and dry syrup forms, peak plasma concentrations of RKM and areas under plasma concentration-time curve (AUC) values were calculated using the trapezoidal rule. RKM dry syrup gave about 84 and 86% of these values for RKM tablet. Urinary recovery of RKM in 8 hours with the administration of dry syrup was also about 80% of the value obtained with tablet. Judging from these results, the bioavailability of RKM administered as dry syrup, was fairly close to that obtained with RKM tablet. The AUC values were dose dependent when examined with dose levels of 300, 500 and 800 mg administered as RKM dry syrup. The AUC value and urinary recovery of RKM administered as dry syrup were 3-4 times higher than these values for midecamycin acetate administered also as dry syrup.

Topics: Absorption; Adult; Humans; Leucomycins; Miocamycin

Plasma and urinary antibiotic concentrations measured by 3 different bioassay methods were compared to each other in vitro, after oral administrations of rokitamycin (RKM) tablet, midecamycin acetate (MOM) tablet or josamycin (JM) tablet at a dose of a potency of 600 mg to each of nine healthy volunteers. Method I (RKM bioassay method) was an agar-well method using the agar medium described in the Minimum Requirements for Antibiotic Products of Japan (MRAPJ medium, pH 6.5), method II (MOM bioassay method) was an agar-well method using mycin-assay agar (pH 8.0) and method III (JM bioassay method) was an agar-well method using nutrient agar (pH 7.8). Micrococcus luteus ATCC 9341 was used as the test organism in all the assay method. With any of the bioassay methods tested, plasma concentrations of RKM were determined to be higher than those of MOM or JM. When the three different bioassay methods were compared, method II and III gave consistently higher values than method I for plasma concentrations of any of the drugs tested. These higher values obtained by method II and III appeared to be due to their inability to correctly assay potencies of metabolites of these antibiotics. Using in vitro assay method, potencies of metabolites were found to be estimated higher than they should when method II and III were used. Method I, on the other hand, determined relative potencies of these antibiotics and their metabolites correctly, reflecting differences in MIC values of original antibiotics and their metabolites. Method I, therefore, should be used as the method of preference to determine concentrations of these drugs in body fluids.

Topics: Administration, Oral; Adult; Biological Assay; Humans; Leucomycins; Male; Miocamycin

Topics: Adult; Biological Availability; Drug Stability; Erythromycin; Gastric Acid; Humans; Leucomycins; Middle Aged; Miocamycin; Solubility; Tablets