BACKGROUND: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. METHOD: Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n: 19, 500 mg bid), second roxitbromycin (n: 14. 150 mg bid), third clarithromycin (n: 10, 250 mg bid) and fourth azithromycin(n: 10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. RESULTS: When compared with control, erytbromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. CONCLUSION: These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrenfly.
Azithromycin ; Bayes Theorem ; Clarithromycin ; Cytochrome P-450 Enzyme System ; Drug Monitoring ; Erythromycin* ; Humans ; Macrolides* ; Metabolism ; Roxithromycin ; Theophylline*

No abstract available.
Erythromycin*

Macrolide antimicrobial agents including erythromycin, roxithromycin, clarithromycin, and azithromycin are commonly used in the treatment of respiratory tract infections in children. Newer macrolides that have structural modifications of older drug erythromycin show improved change in the spectrum of activity, dosing, and administration. However, recent studies reported that increasing use of macrolide antibiotics is the main force driving the development of macrolide resistance in streptococci. In particular, azithromycin use is more likely to select for macrolide resistance with Streptococcus pneumoniae than is clarithromycin use, a possible reflection of its much longer half life. Recently, erythromycin resistance rates of S. pneumoniae and Streptococcus pyogenes are rapidly increasing in Korea. Two main mechanisms of acquired macrolide resistance have been described, altered binding site on the bacterial ribosome encoded by the ermB gene and active macrolide efflux pump encoded by the mef gene. Relationship between the susceptibility of S. pneumoniae and the response to macrolides has been shown in studies of acute otitis media, but less clear in cases of pneumonia. This article reviews the spectrum of activity, pharmacokinetic properties, mechanisms of action and resistance, and clinical implication of resistance on the treatment of respiratory tract infections in children.
Anti-Bacterial Agents ; Anti-Infective Agents ; Azithromycin ; Binding Sites ; Child ; Clarithromycin ; Erythromycin ; Half-Life ; Humans ; Korea ; Macrolides ; Otitis Media ; Pneumonia ; Respiratory Tract Infections ; Ribosomes ; Roxithromycin ; Streptococcus pneumoniae ; Streptococcus pyogenes

BACKGROUND: The mechanism of erythromycin resistance of Streptococcus pyogenes results from target modification or active efflux. The purpose of this study was to determine the positive rate of ermAM gene modifying 23S rRNA and that of mefA gene related with efflux for erythromycin-resistant S. pyogenes. METHODS: The minimal inhibitory concentrations (MICs) of erythromycin, azithromycin, clarithromycin, and clindamycin against S. pyogenes were tested by agar dilution method. ermAM and mefA genes were amplified by polymerase chain reaction (PCR) for 32 strains of erythromycin-resistant S. pyogenes. RESULTS: Among the 32 erythromycin-resistant S. pyogenes strains, 20 (62.5%) strains were positive for ermAM gene and 10 (31.1%) for mefA gene. Eighteen (90.0%) out of 20 strains with ermAM gene showed high-level erythromycin resistance (MIC> OR =64 microgram/mL), while all ten strains with mefA gene had low-level erythromycin resistance (MIC< OR =16 microgram/mL). CONCLUSION: Two-thirds of the S. pyogenes strains acquired erythromycin resistance by modification of target site, while the others by active efflux. Each mechanism of resistance is closely associated with range of MICs of erythromycin.
Agar ; Azithromycin ; Clarithromycin ; Clindamycin ; Erythromycin ; Polymerase Chain Reaction ; Streptococcus pyogenes* ; Streptococcus*

The efficacy and safety of clarithromycin, roxithromycin and erythromycin stearate in mild pneumonia were compared in an open randomized trial. Eighty-six male patients, doing their obligatory military service, ranging between 19 and 24 years of age (mean 20), were randomly treated: 29 with clarithromycin 500 mg 12-hourly, 30 with roxithromycin 150 mg 12-hourly, and 27 with erythromycin stearate 500 mg 6-hourly, each course being administered for 10 days. Seventy-eight patients were able to be evaluated for efficacy, 28 receiving clarithromycin, 28 roxithromycin, and 22 erythromycin stearate. There were no significant differences among the groups in terms of clinical success rates (clinical cure or improvement: 89% for clarithromycin, 82% for roxithromycin, and 73% for erythromycin stearate, p = 0.32). However, we found that there were significant differences among the groups in terms of clinical cure rates (75% for clarithromycin, 64% for roxithromycin, and 41% for erythromycin stearate, p = 0.04). Adverse events, mostly gastrointestinal, caused discontinuation of treatment in 3.4% of the patients in the clarithromycin group, in 6.6% of the patients in the roxithromycin group, and in 18.5% of the patients in the erythromycin stearate group. The results indicate that there were no statistically significant differences among the three treatment groups in terms of clinical success rates, but that clarithromycin and roxithromycin were better tolerated.
Adult ; Antibiotics, Macrolide/therapeutic use* ; Antibiotics, Macrolide/adverse effects ; Clarithromycin/therapeutic use* ; Clarithromycin/adverse effects ; Comparative Study ; Erythromycin/therapeutic use* ; Erythromycin/analogs & derivatives* ; Erythromycin/adverse effects ; Female ; Human ; Male ; Pneumonia/radiography ; Pneumonia/physiopathology* ; Pneumonia/microbiology ; Pneumonia/drug therapy* ; Radiography, Thoracic ; Roxithromycin/therapeutic use* ; Roxithromycin/adverse effects

No abstract available.
Dreams* ; Erythromycin*

PURPOSE: We investigated the effect of macrolides on the extracellular matrix (ECM) invasion and expression of cell adhesion proteins in non-small cell lung cancer cells. MATERIALS AND METHODS: Three kinds of macrolides, azithromycin, erythromycin and clarithromycin were treated in several human Non-Small Cell Lung Cancer (NSCLC) cell lines at doses from 0.1 to 1.5microg/ml. ECM invasion was measured by an in vitro chemo-invasion assay using matrigel-coated invasion chambers. RESULTS: Azithromycin inhibited the migration of NCI-H157 and NCI-H1299 cell lines. Erythromycin inhibited the migration of NCI-H157 and NCI-H2066, and clarithromycin had inhibitory effects on the migration of NCI-H358 and NCI-H2009. These results indicate that macrolides inhibit the ECM invasion of the tested NSCLC cells cell line-specifically. Western blot analyses for cell adhesion proteins (CAPs) showed that these were up-regulated by treatment with macrolides in some of the NSCLC cell lines. Based on the results of chemo-invasion assay, we selected each 2-cell line group, one was significantly suppressed by AM (NCI-H157 and NCI-H1299) and the other was less effectively suppressed by EM (NCI-H358 and NCI-H460). The expression levels of cell adhesion proteins increased in a dose-dependent manner in two cell lines in which their ECM invasion was inhibited by AM, however, the other two cell lines showed unchanged expression levels even at higher doses. Furthermore, the expressions of E1AF and matrix metalloproteinases (MMPs) activity were examined by RT-PCR and gelatin zymography, respectively with the selected 4 cell lines. E1AF expression level was found to decrease from the basal level in NCI-H157 and the activity of MMP-9 was also shown to decrease in NCI-H157 and NCI-H1299. Cell adhesion to fibronectin was a little reduced in NCI-H157 from its basal level. CONCLUSION: Consequently, the present study suggests that macrolides inhibit the ECM invasion of NSCLC cells by inducing the altered expression of cell adhesion proteins
Azithromycin ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung* ; Cell Adhesion* ; Cell Line ; Clarithromycin ; Erythromycin ; Extracellular Matrix* ; Fibronectins ; Gelatin ; Humans* ; Macrolides* ; Matrix Metalloproteinases

BACKGROUND: While 7.6% of cultured genital Mycoplasmataceae was identified as Ureaplasma urealyticum, most of them were Ureaplasma parvum (80.3%). This is the first study differentiating between these two species. We investigated the prevalence and antimicrobial resistance of genital Mycoplasmataceae in Korean women. METHODS: A total of 150 specimens submitted to the laboratory for culture of M. hominis and Ureaplasma spp. were included. Detection and antimicrobial susceptibility tests were performed with the Mycoplasma IST2 kit (bioMérieux, France). The identification of Ureaplasma spp. was performed by PCR, and mutations in drug resistance genes were investigated by PCR and sequencing. RESULTS: In total, 66 specimens (44.0%) were positive for genital Mycoplasmatacea: U. parvum, 53 (80.3%); U. urealyticum, 5 (7.6%); M. hominis, 2 (3.0%); mixed infection, 6 (9.1%). Susceptibilities of Ureaplasma spp. to erythromycin, azithromycin, clarithromycin, and doxycycline were 86.0%, 80.7%, 98.2%, and 94.7%, respectively. The susceptibility of Ureaplasma spp. to ofloxacin and ciprofloxacin was 47.4% and 17.5%, respectively. The S83L mutation was found in the ParC subunit of the ofloxacin-resistant (5/7, 71.4%) and the ciprofloxacin-resistant isolates (7/14, 50.0%). One M. hominis isolate showed resistance to erythromycin, azithromycin, and clarithromycin but susceptibility to josamycin, pristinamycin, fluoroquinolones, and tetracyclines. CONCLUSION: The prevalence of genital Mycoplasmataceae in Korean women was 44.0%; most of them were identified as U. parvum. As more than 10% of Ureaplasma spp. showed non-susceptibility to erythromycin and azithromycin (15.5%, 20.7%), a susceptibility test is needed prior to use of these antibiotics. Further study is needed about the clinical features of infections caused by U. urealyticum vs. U. parvum and their associated resistance mechanisms.
Anti-Bacterial Agents ; Azithromycin ; Ciprofloxacin ; Clarithromycin ; Coinfection ; Doxycycline ; Drug Resistance ; Erythromycin ; Female ; Fluoroquinolones ; Humans ; Josamycin ; Mycoplasma ; Mycoplasmataceae* ; Ofloxacin ; Polymerase Chain Reaction ; Prevalence* ; Pristinamycin ; Tetracyclines ; Ureaplasma ; Ureaplasma urealyticum

BACKGROUND: Ureaplasma urealyticum and Mycoplasma hominis are associated with an increased risk of pregnancy complications, such as preterm birth and premature membrane rupture. The purpose of this study was to determine the isolation rates and antimicrobial susceptibilities of genital mycoplasma in a sample of pregnant women from Jinju, Korea. METHODS: Vaginal swabs were obtained from 258 pregnant women between 2004 and 2008 and tested for the presence of U. urealyticum and M. hominis at Gyeongsang National University Hospital. The identification and antimicrobial susceptibilities of U. urealyticum and M. hominis were determined with a commercially available kit, the Mycoplasma IST2 Kit (bioMe- rieux, Marcy-l'Etoile, France), and evaluated according to standards set by the Clinical and Laboratory Standards Institute (CLSI). RESULTS: U. urealyticum only was detected in 105 specimens (38.6%), while M. hominis only was detected only in 2 specimens (1.8%). Seven specimens (6.7%) were positive both for U. urealyticum and M. hominis. Susceptibilities of U. urealyticum to azithromycin, erythromycin, clarithromycin, and doxycycline were 75.2%, 82.9%, 88.6%, and 88.6%, respectively, while almost all of the isolates were susceptible to josamycin (99.0%) and pristinamycin (100%). The susceptibility of U. urealyticum to ofloxacin and ciprofloxacin was 56.2% and 15.2%, respectively. CONCLUSION: The rate of isolation of genital mycoplasma in pregnant women was 44.2% in Jinju; most of the mycoplasma were U. urealyticum. U. urealyticum and M. hominis were highly resistant to quinolones, but susceptible to josamycin. Therefore, empirical treatment without prior identification and determination of the antimicrobial susceptibility of genital mycoplasma will fail in many cases.
Azithromycin ; Ciprofloxacin ; Clarithromycin ; Doxycycline ; Erythromycin ; Female ; Humans ; Josamycin ; Korea ; Membranes ; Mycoplasma ; Mycoplasma hominis ; Ofloxacin ; Pregnancy Complications ; Pregnant Women ; Premature Birth ; Pristinamycin ; Quinolones ; Rupture ; Ureaplasma ; Ureaplasma urealyticum

BACKGROUND: As invasive streptococcal infections are increasing recently and the resistance rate to either erythromycin or clindamycin is elevating, epidemiologic surveillance and appropriate guideline for antibiotic use are required. Geographical epidemiologic characteristics with T typing and antibiotic resistance rate were investigated. METHODS: Distributions of T types according to geographical areas and sources of specimens were analyzed with 82 strains of Streptococcus pyogenes isolated from clinical samples in Seoul and Chinju. Antibiotic susceptibility test was performed for penicillin G, cephalothin, erythromycin, azithromycin, clarithromycin, clindamycin, chloramphenicol, and ofloxacin with agar dilution method. Antibiotic resistance rates were analyzed according to geographical areas, sources of specimens and T types. RESULTS: The most common T types were T12, T1 and T28 in decreasing order. The distribution of T types between Seoul and Chinju was different. While T1, T3, and T6 were frequent in throat or other respiratory specimens, T12, T28, and B3264 were common in blood or closed pus. The resistance rate to erythromycin, azithromycin, and clarithromycin was 20%, 13% to clindamycin, and 49% to tetracycline, respectively. None of the isolates were resistant to penicillin G, cephalothin, chloramphenicol, or ofloxacin. The isolates from Chinju showed higher resistance rate than the strains from Seoul. The isolates from blood or closed pus had higher resistance rate compared to those of throat or sputum. T28 and T6 strains presented higher resistance rate than other T types. CONCLUSIONS: As distributions of T types were variable according to geographical areas or sources of specimens, continuous microbiological and epidemiological surveillance for invasive streptococcal infections are needed. Minimizing unnecessary antibiotic use or acknowledging the severity of resistance are necessary, because the resistant proportions are increasing against macrolide, clindamycin and tetracycline.
Agar ; Azithromycin ; Cephalothin ; Chloramphenicol ; Clarithromycin ; Clindamycin ; Drug Resistance, Microbial ; Epidemiological Monitoring ; Erythromycin ; Gyeongsangnam-do ; Ofloxacin ; Penicillin G ; Pharynx ; Seoul ; Sputum ; Streptococcal Infections ; Streptococcus pyogenes* ; Streptococcus* ; Suppuration ; Tetracycline