Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ERYTHROMYCIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed2001

Precursor-directed production of erythromycin analogs by Saccharopolyspora erythraea.

Diketide N-acetylcysteamine (diketide NAC) thioester precursors were fed to 6-Deoxyerythronolide B synthase (DEBS) ketosynthase-1 inactivated (KS1 degree) Saccharopolyspora erythraea strains to produce 13-substituted erythromycin analogs. This direct feeding process potentially represents a simplified production process over the current analog production system. Titers of these analogs were observed to increase linearly with the diketide concentration up to a precursor-specific saturation level. However, the rate of product formation was lower and the rate of diketide consumption higher with S. erythraea than was previously observed with a recombinant strain of Streptomyces coelicolor. Several strategies were pursued to address the issue of these high diketide consumption rates: (1) elucidation of the locale of diketide degradation, (2) addition of beta-oxidation inhibitors to the cultures, and (3) addition of a sacrificial diketide enantiomer to occupy putative degradative enzymes. Additionally, repeated addition of diketide to an S. erythraea KS1 degrees culture indicated that the titer of these erythromycin analogs is also currently limited by a shorter production period than observed during erythromycin synthesis by the parent strain. These results indicate potential avenues for expanding the use of this precursor-directed system from the generation of limited quantities of erythromycin analogs to a large-scale production system for these compounds.

Anti-Bacterial Agents↗
PubMed1998

Effect of the prokinetic agent, erythromycin, in the Richardson ground squirrel model of cholesterol gallstone disease.

Impaired gallbladder motility and delayed intestinal transit contribute to cholesterol gallstone formation by impeding the enterohepatic circulation of bile salts and causing gallbladder stasis. The therapeutic value of erythromycin, a prokinetic motilin analog, was evaluated in an animal model of gallstone formation. Eighty ground squirrels were fed either a trace- (control) or a high- (1%) cholesterol diet. Half of each diet group received either erythromycin stearate or placebo orally twice daily for 4 weeks. Biliary lipid secretion and bile salt pool size were determined via common duct cannulation. Gallbladder contractile response to cholecystokinin (CCK) was studied in vitro. Intestinal transit was evaluated in vivo by 51Cr marker. In the placebo-treated group, fed the high- versus the trace-cholesterol diet, bile salt secretion decreased (trace-cholesterol + placebo, 21.0 +/- 1.8 nmol/min/g liver vs. high-cholesterol + placebo, 9.3 +/- 1.4 nmol/min/g liver), cholesterol saturation index (CSI) doubled (trace-cholesterol + placebo, 0.61 +/- 0.06 vs. high-cholesterol + placebo, 1.30 +/- 0.04), nucleation time shortened (trace-cholesterol + placebo, > 21 days vs. high-cholesterol + placebo, 6.4 +/- 1.0 days), cholesterol crystals formed, gallbladder contractility diminished, and intestinal transit was delayed (each P < .05). Erythromycin treatment of animals on the high-cholesterol diet restored gallbladder contractility and intestinal transit to control levels, increased bile salt secretion, reduced the total bile salt pool, lowered the cholesterol saturation of bile, lengthened the nucleation time, and so reduced crystal formation (each P < .05). Erythromycin enhances gallbladder motility and hastens intestinal transit, promoting more rapid enterohepatic cycling of bile salts. This increases bile salt secretion, improves cholesterol solubility, and reduces crystal development.

Animals↗
PubMed1982

Pharmacokinetics of erythromycin in normal and alcoholic liver disease subjects.

The objective of this study was to compare the pharmacokinetic behavior of erythromycin in normal volunteers with that in subjects with alcoholic liver disease. Six normal volunteers received 500 mg erythromycin as an intravenous infusion or as two 250-mg enteric-coated tablets in a crossover fashion. The pharmacokinetics of erythromycin after intravenous administration was best described as a two-compartment model. The elimination half-life was 1.6 +/- 0.7 hours (mean +/- S.D.) after the intravenous dose and 2.0 +/- 0.7 hours after the oral dose. In patients with alcoholic liver disease the elimination half-life after oral administration of two 250-mg enteric-coated tablets was 3.2 +/- 0.5 hours, significantly different from that in normal subjects, probably due to impaired metabolism. The difference in half-life does not require dosage adjustment in this patient population. The systemic availability of erythromycin was 33.5 per cent (range 10.5 to 79.3 per cent).

Administration, Oral↗
PubMedDate not supplied

Oral neomycin sulfate and erythromycin base before colon surgery: a comparison of serum and tissue concentrations.

It is accepted that the use of oral neomycin sulfate and erythromycin base before colon surgery results in decreased numbers of intestinal bacteria. Intraluminal levels of these agents are reported to be very high, but systemic availability is still debated. The systemic levels were studied in 8 patients undergoing colon surgery. Each patient received neomycin sulfate and erythromycin base, 1 g each, 19, 18 and 9 hours preoperatively. Twelve samples from serum, one from wound muscle and one from the intestinal wall were obtained from each patient in the 26 hours after the initial dose. Considerable variation was observed among levels. The following means were calculated: peak serum levels were 3.4 and 0.59 micrograms/ml, muscle levels were 1.68 and 0.23 micrograms/g and intestinal wall levels were 6.4 and 12.9 micrograms/g for erythromycin and neomycin respectively. Observed times to peak levels were 19 and 12 hours after the initial dose for erythromycin and neomycin respectively. The detectable systemic concentrations that result when these agents are given orally for bowel preparation before colon surgery may contribute to the drugs' efficacy.

Adult↗
PubMed1976

Gastric acid inactivation of erythromycin stearate in solid dosage forms.

The effect of hydrochloric acid at pH 1.2-3.2 ON ERYTHROMYCIN STEARATE AND COMMERCIAL DOSAGE FORMS OF ERYTHROMYCIN STEARATE WAS STUDIED. Under all conditions examined, erythromycin was readily dissolved from the stearate as hydrochloride, and rapidly lost its biological activity in solution. The inclusion of pepsin in the test systems did not affect the results. Although formulation differences somewhat affected the rate of destruction, acid lability was exhibited by all products examined, except enteric-coated tablets. Amounts of acid considered to be normal in the fasting stomach contents of adults during the time likely for a dose to remain in the stomach caused 70-90% destruction within 15 min after the shells started to rupture. Amounts of hydrochloric acid appreciably less than 1 mEq, representing abnormally small quantities even in the fasting state, caused destruction ranging from 30 to 70% of the doses in 15 min. These results are not reconcilable with published statements that the sensitivity of erythromycin to gastric acid is overcome by providing the antibiotic in the form of stearate salt.

Capsules↗
PubMed1993

Erythromycin binding is reduced in ribosomes with conformational alterations in the 23 S rRNA peptidyl transferase loop.

The antibiotic erythromycin inhibits protein synthesis by binding to the 50 S ribosomal subunit, where the drug interacts with the unpaired bases 2058A and 2059A in the peptidyl transferase loop of 23 S rRNA. We used a chemical modification approach to analyse conformational changes that are induced by mutations in the peptidyl transferase loop, and to determine how these changes affect drug interaction. Mutations at positions 2057 (G-->A) and 2058 (A-->G, or -->U), all of which confer drug resistance, induce a more open conformation in the peptidyl transferase loop. Erythromycin still protects against chemical modification in the mutant peptidyl transferase loops, but the affinity of the drug interaction is reduced 20-fold in the 2057A mutant, 10(3)-fold in the 2058U mutant and 10(4)-fold in the 2058G mutant. Single mutations at position 2032 in the adjacent hairpin loop, which have previously been shown to alter drug tolerances, gave no detectable effects on the structure of the peptidyl transferase loop or on erythromycin binding. Dual mutations at positions 2032 and 2058, however, induce a marked change in the rRNA conformation with opening of the phylogenetically conserved base-pair 2063C.2447G, and confer a slow growth, drug-sensitive phenotype. The data suggest that the target site of erythromycin lies within the peptidyl transferase loop, and that limited disruption of the conformation of this site reduces drug binding, and consequently confers resistance. In addition, there is structurally and functionally important interaction between the drug target site in the peptidyl transferase loop and position 2032.

Base Sequence↗
PubMed1995

The erythromycin resistance gene of the Corynebacterium xerosis R-plasmid pTP10 also carrying chloramphenicol, kanamycin, and tetracycline resistances is capable of transposition in Corynebacterium glutamicum.

The clinical isolate Corynebacterium xerosis M82B carries the 50-kb R-plasmid pTP10 that confers resistance to the antibiotics chloramphenicol, kanamycin, erythromycin, and tetracycline. A detailed restriction map of pTP10 was constructed by cloning and analyzing restriction fragments of pTP10 in Escherichia coli. The resistance determinants of pTP10 were located by studying the phenotype of the recombinant plasmids in E. coli and Corynebacterium glutamicum. Restriction patterns of fragments encoding the kanamycin and erythromycin resistances revealed striking similarity to the kanamycin resistance of transposon Tn903 and the erythromycin resistance on plasmid pNG2 from Corynebacterium diphtheriae, respectively. Expression of the resistance determinants in E. coli and C. glutamicum ATCC 13032 led to high resistance levels in both strains, with the exception of the tetracycline resistance gene, which could be expressed only in C. glutamicum. Furthermore, the erythromycin resistance gene was found to be located on a transposable element which is functional in C. glutamicum strains.

Blotting, Southern↗
PubMed1990

Effect of age on single- and multiple-dose pharmacokinetics of erythromycin.

The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d. for 7 doses. The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses. Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively). The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h). No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution. The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults. Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance. The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people.

Adult↗
PubMed1993

5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin.

In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.

Adult↗
PubMed1982

[Concentrations of erythromycin and amoxicillin in tonsil and sinus tissues of patients with tonsillitis and sinusitis. A comparison (author's transl)].

Thirty male patients with chronic tonsillitis and 30 male patients with chronic Sinusitis maxillaris were pre-treated for four days with either 2 X 1 g erythromycin daily per os or 3 X 0.75 g amoxicillin daily per os in an open and randomised comparative study. MIC values for the relevant bacteria were determined beforehand. The intended tonsillectomy or radical operation was performed on the third day of pre-treatment, circa 1.5 h after the final administration of antibiotics. The tonsils or the sinus membrane were examined bacteriologically; the concentrations of erythromycin or amoxicillin were determined. At the same time, the concentration of the antibiotic administered was determined in the serum. The average concentration of erythromycin in the tonsil tissue was 1.24 micrograms/g; it was 1.21 micrograms/g in the sinus membrane. Amoxicillin was found at a concentration of 0.17 microgram/g in the tonsil tissue, and 0.1 microgram/g in the sinus membrane. While the levels of erythromycin in the tissue generally equalled or exceeded the MIC value for the pathogen in question, the levels of amoxicillin only reached the relevant MIC value for the given pathogen in a few cases since the concentration in the tissue was insufficient. The clinical tolerance of both antibiotics was good.

Administration, Oral↗
PubMed1979

[Erythromycin determination in organ tissues (author's transl)].

The recovery rates of erythromycin after in vitro and in vivo administration were studied comparatively in liver, lung, and kidney. Using buffer standards the recovery rate in homogenates of in vitro administered erythromycin decreased with increasing protein concentration. At constant protein concentration the erythromycin administered recovered correlated linearly. Mincing the tissues with scissors was not found to be adequate, even when followed by a diffusion period of up to 24 hours. Similarly, shock freezing resulted in lower values. Even and optimal breaking down of tissues was found after homogenisation or ultrasonics. The recovery rates were not raised by treating the tissue with trypsin. There was no evidence of enzymatical erythromycin degradation in liver homogenates under the assay conditions.

Animals↗
PubMed1988

Comparative in-vitro activity of erythromycin, vancomycin and pristinamycin.

We have studied the in-vitro activity of erythromycin, vancomycin and pristinamycin against 1,006 clinical isolates comprising streptococci, staphylococci, Neisseria gonorrhoeae, Haemophilus influenzae and anaerobes. In-vitro studies show pristinamycin to inhibit staphylococci and streptococci, including erythromycin highly-resistant organisms, at a concentration of less than or equal to 0.78 mg/l. Although pristinamycin's mean MIC for streptococci is higher than that of erythromycin, pristinamycin is bactericidal, whereas erythromycin is bacteristatic against Streptococcus agalactiae and oral streptococci. Enterococci were less uniformly susceptible to pristinamycin: 58 of the 94 Enterococcus faecalis tested were resistant (MIC greater than or equal to 3.12 mg/l). 14 of the 15 isolates of Enterococcus faecium were inhibited by less than or equal to 1.56 mg/l pristinamycin. Pristinamycin showed poor activity against Haemophilus influenzae (mode MIC 1.56 and MIC90 of 3.12 mg/l) but all except two of the 100 Neisseria gonorrhoeae tested were inhibited by less than or equal to 0.78 mg/l pristinamycin. Pristinamycin inhibited all nine Clostridium spp. at less than or equal to 0.39 mg/l and 38 of 40 strains of anaerobic gram-positive cocci at less than or equal to 0.78 mg/l. It was less effective against the Bacteroides fragilis group: (MIC90 3.12 mg/l). Pristinamycin had poor bactericidal activity against the anaerobes tested.

Bacteria↗
PubMed1996

The frequency of resistance to erythromycin in group A streptococci in Ankara.

UNLABELLED: The frequency of resistance to erythromycin of group A beta-haemolytic streptococci in the last 7 years was determined in three medical centres in Ankara. While all group A beta-haemolytic streptococci strains were susceptible to penicillin, a gradual increase in resistance to erythromycin until 1992 was observed. However, a substantial increase in erythromycin resistance occurred in 1993 when newer macrolides became available and were widely used in the latter part of 1992. CONCLUSION: The data show that frequent testing for resistance to erythromycin of group A beta-haemolytic streptococci is required for the use of this antibiotic in our country.

Anti-Bacterial Agents↗
PubMed1982

Effect of erythromycin and clindamycin on the indigenous human anaerobic flora and new colonization of the gastrointestinal tract.

Erythromycin and clindamycin were given orally to ten subjects in recommended doses for seven days in order to study the effects of these antibiotics on human flora. Saliva and faecal specimens were collected for up to 29 days after administration of the antibiotics. Erythromycin caused only minor changes in the saliva flora while the aerobic and anaerobic colon flora were considerably disturbed. Clindamycin depressed both the anaerobic saliva and colon flora. Both erythromycin and clindamycin induced new colonization of the oral cavity and colon. The levels of free volatile fatty acids sank in saliva and faeces when erythromycin and clindamycin were given. The ecological disturbances caused by antibiotics require further investigation and should be taken into consideration in therapy.

Administration, Oral↗
PubMed1995

Effect of oral erythromycin on colonic transit in patients with idiopathic constipation. A pilot study.

Erythromycin, a motilin receptor agonist has been shown to have prokinetic effects on the upper gastrointestinal tract and gallbladder. Colonic effects of the drug are controversial, and it is debated whether human colon contains motilin receptors. In this study we evaluated the effects of erythromycin on colonic transit and stool frequency in 11 patients with idiopathic constipation over a 1-month period in an open study. The dose used was 1 g/day for two weeks followed by 500 mg/day for another two weeks. The mean (SE) total and segmental colonic transit was measured before and seven days after therapy in seven of these patients. A daily record of stool frequency was maintained in all 11 patients. Erythromycin shortened the total colonic transit from 86.2 (14.6) to 44.8 (8.99) hr (P < 0.01); however, segmental transit studies revealed a significant effect (P < 0.01) only in the right colon and rectosigmoid region. No significant side effects were observed with short-term therapy. These preliminary results suggest that erythromycin is of therapeutic value in patients with idiopathic constipation.

Administration, Oral↗
PubMed1994

Effect of single dose of oral erythromycin on gastric and gallbladder emptying. Simultaneous assessment by ultrasound.

To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double-blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects.

Administration, Oral↗
PubMed1996

Antral axial forces postprandially and after erythromycin in organic and functional dysmotilities.

Our aims were to measure antral axial forces in patients with suspected upper gut dysmotilities and to compare the number of antral contractions detected by an axial force catheter and by manometric sensors in the distal antrum and pylorus. Fifteen patients (2 men, 13 women; mean age 42 years) underwent studies for 3 hr fasting, 2 hr postprandially, and up to 60 min after intravenous erythromycin (3mg/kg). Seven patients had gastroparesis or chronic intestinal pseudoobstruction, five functional disease, and three subacute obstruction. Postprandially, the number of peaks detected by the two methods was not significantly different; however, after erythromycin, the axial catheter detected more contractions (P = 0.02). Erythromycin significantly increased the number of postprandial axial forces (from 1.2 +/- 0.3/min to 2.5 +/- 0.3/min, P < or = 0.01) in the whole group and in the organic dysmotility group (P = 0.01). Erythromycin significantly increases the number of axial forces in functional and organic upper gut dysmotilities, but the axial force catheter is not advantageous over manometry for postprandial measurements of antral motility.

Adult↗
PubMed1993

Interactions of pre-operative erythromycin administration with general anaesthesia.

Previous reports have demonstrated a gastric emptying effect of erythromycin due to a motilin-like mechanism. We studied 50 patients, scheduled for daycase laparoscopy, randomly assigned to one of two groups: Group P patients received 30 min before induction of anaesthesia, in a double-blind manner an infusion of 250 ml dextrose 5% while patients in Group E (n = 25) received 500 mg of erythromycin diluted in 250 ml dextrose 5%. An orogastric tube was inserted to measure both gastric pH using a pHmeter and residual gastric volume (RGV) using the phenol red dilutional technique. Six patients were excluded for surgical reasons. More patients in Group P (6/22) than in Group E (0/22) had RGV > 25 ml and more patients in Group P (17/22) presented with a gastric pH < 2.5 than in Group E (5/22), P < 0.05. Since coma and respiratory depression have been reported recently after midazolam and alfentanil administration in patients having received erythromycin, recovery conditions were assessed and were found to be comparable between groups. In conclusion, the administration of iv erythromycin before outpatient laparoscopy decreased residual gastric volume and increased gastric pH without affecting recovery from general anaesthesia.

Adult↗