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PubMed2005

Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy.

AIM: To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS: Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS: Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control (16 min vs 70 min, P = 0.005), whereas the small bowel transit time was comparable between the two groups (227 min vs 183 min, P = 0.18). Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION: Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

Body Mass Index↗
PubMed1995

In vivo evaluation of three acid-stable azalide compounds, L-701,677, L-708,299 and L-708,365 compared to erythromycin, azithromycin and clarithromycin.

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Animals↗
PubMed2000

The effects of erythromycin on human peripheral neutrophil apoptosis.

Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in treating chronic inflammatory diseases of the respiratory tract such as diffuse panbronchiolitis (DPB) and chronic sinusitis. The evaluate the anti-inflammatory action of erythromycin, we examined apoptosis of isolated neutrophils incubated with and without erythromycin. As a result, erythromycin augmented neutrophil apoptosis in a dose-dependent manner, with a maximal effect at 10 micrograms/ml and above. The percentage of neutrophil apoptosis at 12 h was 79.2 +/- 2.3% in medium with 10 micrograms/ml of erythromycin compared with 51.2 +/- 4.1% in control medium (p < 0.005). In a manner similar to that of erythromycin, another macrolide antibiotic, roxithromycin, also increased neutrophil apoptosis. However, there was no effect on apoptosis induced by treatment with josamycin (macrolide antibiotic), ampicillin (beta-lactam.) and cefazolin (cephalosporin antibiotic), or gentamycin (aminoglycoside). These findings suggest that erythromycin shortens neutrophil survival by accelerating neutrophil apoptosis.

Ampicillin↗
PubMed2000

[Streptococcus pyogenes: penicillin and erythromycin susceptibility in the cities of Neuquen and Cipolletti].

Penicillin resistance has not yet been detected in Streptococcus pyogenes. However macrolide-resistant streptococci have emerged in several countries. Only low rates of erythromycin-resistant S. pyogenes were reported in Argentina, with the exception of a 11.1% observed in Mendoza. The aim of the present study was to determine the susceptibility to penicillin and to erythromycin of 251 consecutive clinically-significant isolates of S. pyogenes obtained from four centers of Cipolletti and Neuquén during the period April-December 1998. The double disk test with erythromycin and clindamycin disks was employed as a screening method to detect ERY-resistant streptococci and to determine the phenotype of macrolide resistance. Disk diffusion was also employed for determining penicillin susceptibility. Macrolide-resistant isolates were also tested for penicillin, ceftriaxone, erythromycin, clindamycin and azithromycin susceptibility by the agar dilution method. Additionally they were also tested for erythromycin susceptibility by E-test (AB Biodisk, Solna, Sweden). All streptococci studied were susceptible to penicillin and thirty of them (12.0%) were resistant to erythromycin. All these resistant isolates were also resistant to azithromycin but susceptible to ceftriaxone and clindamycin. They showed the phenotype M (probably efflux-mediated mechanism) and the MICs of erythromycin ranged between 8 and 16 micrograms/ml. According to these results we conclude that in spite of universal susceptibility to penicillin in S. pyogenes, macrolide resistance is a matter of concern in Neuquén and Cipolletti. At least in those cities it appears to be necessary to routinely perform macrolide susceptibility tests in beta-hemolytic streptococci.

Anti-Bacterial Agents↗
PubMedDate not supplied

Erythromycin-resistance of cutaneous bacterial flora in acne.

Some studies have raised the problem of an increase of bacterial resistance in acne patients. This study was carried out in France, where no previous studies about resistance to erythromycin has been performed, on 40 patients with mild to moderately severe acne. Microbiological samples were obtained by using Williamson and Kligman method. This study showed that the prevalence of bacterial resistance to erythromycin was 95% for Staphylococcus epidermidis strains and 52% for Propionibacterium acnes strains. Resistant strains were more frequent in patients with predominantly inflammatory lesions (papules and pustules). The influence of previous or current treatment with erythromycin was also studied and showed that even patients without any previous use of erythromycin had resistant strains for Propionibacterium acnes (42%). In addition the minimum inhibitory concentrations (MIC) for zinc were evaluated. All the Propionibacterium acnes strains tested were inhibited at concentrations less or equal to 512 mug/ml of zinc. However, zinc combined with erythromycin in vitro did not modify the erythromycin MIC. This first French study on bacterial resistance to erythromycin in acne patients confirms the results of studies performed in other countries.

Acne Vulgaris↗
PubMed2001

Bioavailability and stability of erythromycin delayed release tablets.

BACKGROUND: Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. OBJECTIVES: To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. METHODS: Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. RESULTS: Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% CONCLUSION: The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

Administration, Oral↗
PubMed2003

Involvement of dopamine D3 and neuropeptide Y Y5 receptors in diabetic gastroparetic rats without response to erythromycin.

Erythromycin may accelerate gastric emptying in animals and human probably as an motilin agonist, but its prokinetic effects show obvious individual disparity. This study was to find the mechanism of this phenomenon. Microarray analysis was used to screen genes that might be involved in the response of diabetic gastroparesis rats to erythromycin. It was found that erythromycin accelerated gastric emptying of diabetic rats with great individual disparity. Through microarray analysis we screened differential expression genes that might be involved in the effect of erythromycin. Among 10 genes screened out, dopamine D3 receptor (DRD3) and neuropeptide Y Y5 receptor (NPYY5) genes were submitted to RT-PCR quantification and showed consistent results with microarray. It can be concluded that erythromycin promote gastric emptying of gastroparetic rats; DRD3 and NPYY5 may be involved in prokinetic action of erythromycin; and targets other than motilin receptor of erythromycin might exist as prokinetics.

Animals↗
PubMed1992

Effect of food on absorption and hydrolysis of erythromycin acistrate.

Effect of food on absorption of erythromycin acistrate (2'-acetyl erythromycin stearate, Erasis; CAS 96128-89-1) was studied in 14 healthy volunteers in a randomized cross-over design. The subjects were given 400 mg erythromycin acistrate enteric coated tablets b.i.d. for 4 days. On the 1st and 4th days the tablets were taken after an overnight fast or immediately after a light or a heavy breakfast. Erythromycin (E), 2'-acetyl-erythromycin (2AE), anhydroerythromycin and anhydro-2'-acetyl-erythromycin concentrations in plasma were analyzed chemically by HPLC. After a single dose the lag time of absorption (tlag) was significantly longer after both types of breakfasts as compared to fast. The tmax of E and 2AE were also somewhat delayed by food although tmax of 2AE after a heavy breakfast only differed statistically significantly from that of the fasting state. Food significantly delayed the absorption especially in some subjects since no drug was observed during the 12-h observation period in 2 and 5 of the subjects after a light and heavy breakfast, respectively. At steady state the delaying effect of food on absorption had almost disappeared. No significant differences were observed in Cmax- or AUC0-12-values between the fasting and the fed states both after a single dose or at steady state. It is concluded, that food does not affect the mean bioavailability of erythromycin acistrate neither the mean rate of absorption but in some subjects the absorption from enteric coated tablets might be significantly delayed.

Adult↗
PubMed2005

Effect of erythromycin on gastric dysmotility and neuroendocrine peptides in rats with diabetes mellitus.

OBJECTIVE: To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin (SS), vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP) in plasma and isolated gastric antrum tissue of diabetes mellitus (DM) rat models. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: control group (n = 10), DM group (n = 10), and erythromycin group (DM models with erythromycin treatment, n = 10). A single dose of streptozotocin (100 mg/kg, dissolved in 0.1 mol/L citric acid buffer, pH4.5) was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be (+++) to (++++) over one week were considered successful DM models. The resting tension, mean contractile amplitude and frequency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. RESULTS: (1) In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile frequency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension (P < 0.01). (2) Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control (P < 0.05), while the SP level decreased (P < 0.05). In the gastric antrum, SS of DM group was significantly higher than that of control group (P < 0.01), while SP and MTL levels were lower than those of control group (P < 0.05 and P < 0.01, respectively). However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group (P < 0.05). (3) The blood glucose was lower in erythromycin group than DM group (P < 0.01). CONCLUSIONS: Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

Animals↗
PubMed1990

Prospective comparison of patient tolerance to enteric-coated vs nonenteric-coated erythromycin.

Erythromycin base and its salts are frequently used in clinical practice. The most frequent side effects of oral erythromycin preparations are gastrointestinal. Various salts and enteric coatings have been developed without adequate comparison in regard to gastrointestinal side effects. The overall incidence of gastrointestinal side effects (abdominal pain and cramps, nausea, vomiting, diarrhea, and gas) of two common erythromycin base formulations, Erythromycin Base Filmtab (Abbott), a nonenteric-coated base tablet, and Eryc (Parke-Davis), a pelletized, encapsulated, enteric-coated base capsule, were compared in 368 adults at two dosage levels (1 g/d and 2 g/d). Minimal differences were found when target symptoms were compared by preparation coating. In contrast, subjects receiving erythromycin at the 2-g/d dosage level reported higher incidence rates for each of the target symptoms, regardless of product coating, than did those patients treated at the 1-g/d dosage level. Enteric coating of erythromycin base offers little protection from the common dose-related gastrointestinal adverse effects of oral erythromycin.

Administration, Oral↗
PubMed1990

Occurrence of Ureaplasma urealyticus and Mycoplasma hominis in non-gonococcal urethritis before and after treatment in a double-blind trial of ofloxacin versus erythromycin.

The efficacy of ofloxacin, a new quinolone derivate, was tested against that of erythromycin in a prospective double-blind trial in patients with non-gonococcal urethritis (NGU) with special reference to the occurrence of Mycoplasma hominis and Ureaplasma urealyticum. 188 male NGU patients were randomized to treatment with either ofloxacin 200 mg b.i.d. or erythromycin 500 mg b.i.d. for seven days. Before treatment eight (4.3%) patients, five in the erythromycin group and three in the ofloxacin group, were M. hominis positive. At follow-up day 8 and 15 after start of treatment all five in the erythromycin group and two in the ofloxacin group were still positive. U. urealyticum was recovered in 16 patients (8.5%) before treatment. One patient was still positive in the erythromycin group when examined day 15, whereas all patients were negative in the ofloxacin group at both follow-up controls. Clinically, the efficacy of treatment day 15 was 77.4% in the erythromycin group and 84.3% in the ofloxacin group. The difference was not significant. Side-effects occurred in 38.5% in the erythromycin group and in 21.3% in the ofloxacin group. This difference is significant. Ofloxacin is effective in the treatment of NGU in males and is an alternative to conventional antibiotic treatment.

Double-Blind Method↗
PubMed1990

[The in vivo penetration of erythromycin into alveolar macrophages].

In order to appreciate the in vivo penetration of erythromycin the alveolar spaces a broncho-alveolar lavage was carried out in 24 guinea pigs, 30 minutes, 1 hour 30 minutes and three hours after a single intraperitoneal injection of 50 mgms. of erythromycin. The erythromycin dose was assessed by a microbiological method in the alveolar macrophages and the supernatant of the broncho-alveolar lavage liquid. The intramacrophage concentrations of erythromycin were 3.9, 11.5 and 12 times higher than the serum concentrations at 30 minutes, 1 hour 30 and three hours respectively. The concentrations in the broncho-alveolar lavage liquid was always higher than the serum concentrations tacking account of the different dilutions estimated with relation to the glucose concentrations. At 30 minutes, 1 hour 30 minutes and three hours the alveolar macrophages contained 1.9; 7.6 and 6 times more erythromycin respectively than the lavage supernatant. From the first half hour of its administration the erythromycin was concentrated in the alveolar spaces, in particular within the macrophages. Already noted in vitro, this rapidity of erythromycin concentration in vivo in alveolar macrophages appears to be one of the reasons to explain its activity against micro-organisms developing within macrophages.

Absorption↗
PubMed1988

Effect of dosing intervals on efficacy of clarithromycin and erythromycin in mouse infection models.

Clarithromycin is a new macrolide with a serum half-life which is at least twice that of erythromycin. In order to select the appropriate dosing intervals, the in vitro post-antibiotic effect (PAE) of clarithromycin and erythromycin were compared and the efficacies of clarithromycin and erythromycin when administered once (q.d.), twice (b.i.d.) and three (t.i.d.) times a day in mouse protection tests were measured. The doses were selected from achievable peak serum concentrations in man and were 18 mg/kg for clarithromycin which gave a peak blood level of 2.0 micrograms/ml and a serum half-life of 0.82 h, and 10 mg/kg for erythromycin which gave a peak blood level of 0.9 microgram/ml and a serum half-life of 0.46 h. The PAE of clarithromycin for Staph. aureus is 6.25 h compared to 2.35 h for erythromycin. Clarithromycin was effective against Staph. aureus, Strep. pyogenes and Strep. pneumoniae when administered q.d., b.i.d. and t.i.d. and there was no difference in the cumulative mortalities in the three treatment groups. For erythromycin, there was also no difference in the survival of Strep. pyogenes and Strep. pneumoniae-infected mice, but when tested against Staph. aureus it was more effective when administered t.i.d. than b.i.d., and b.i.d. was more effective than q.d. Clarithromycin administered q.d. was more effective than erythromycin administered t.i.d. against Staph. aureus.

Animals↗
PubMed1987

Influence of theophylline on the renal clearance of erythromycin.

The influence of theophylline on the kinetics of erythromycin was studied in 11 healthy subjects who received both drugs intravenously in therapeutic doses. Total clearance, terminal half-life and volume of distribution of erythromycin were not altered by concomitant theophylline treatment. However, renal clearance of erythromycin was enhanced by theophylline treatment (86.0 +/- 81.1 ml/min vs. 32.5 +/- 15.9 ml/min, with vs. without theophylline). Theophylline also altered urinary flow rate (4.7 +/- 1.6 ml/min vs. 1.9 +/- 1.2 ml/min, with vs. without theophylline) whereas fluid intake was identical (125 ml/h) as well as the pH of the urine (pH 6.5). The possible explanation that theophylline is acting via enhancing urinary flow rate, which reduced tubular reabsorption of erythromycin, has been ruled out by the findings of an additional trial done in 6 out of the 11 subjects. In this trial, renal clearance of erythromycin was not influenced by enhanced urinary flow rate (7.2 +/- 1.9 ml/min) which was due to high fluid intake (500 ml/h) whereas the pH of the urine was kept at 6.5 as in the first part of the study. When other mechanisms to explain the observed interaction were discussed taking into account our published results on theophylline kinetics influenced by concomitant erythromycin administration, the most likely explanation for our finding seems to be the interaction between erythromycin and 1-methyluric acid, one of the theophylline metabolites.

Adult↗
PubMed1978

Bioavailability and effect of food on the gastrointestinal absorption of two erythromycin derivatives.

The concentrations of erythromycin in the serum were comparable after a single 500 mg oral dose of two brands of erythromycin stearate (Resibion and Erythrocin) in six healthy fasting volunteers. There was no significant difference in their pharmacokinetics. Over a period of 24 hours, 4 and 5% of the 500 mg dose of each preparations was excreted in the urine. Analysis of serum erythromycin concentration data were performed according to a one-compartment open model. The short half-life in the serum (1.43-1.78 hours), small portion of the dose excreted in the urine (4-5%), and the low renal clearance value (0.43-0.51 ml/min/kg) indicate that the majority of erythromycin is extensively cleared by extrarenal mechanisms. In addition, serum concentrations of erythromycin were measured during continuous treatment (250 mg base every 6th hour) with erythromycin stearate (Resibion) or enteric-coated erythromycin base (Etromycin) in ten healthy volunteers, in both fasting and non-fasting conditions. Again in the fasting state the serum levels were comparable and those from both the stearate and base were markedly reduced by food.

Administration, Oral↗
PubMed1986

The effect of the combination of erythromycin with new beta-lactam antibiotics against gram-negative aerobic respiratory pathogens.

The effect of erythromycin on the in vitro activity of cefotaxime, ceftizoxime, cefoperazone, moxalactam, ceftazidime, cefmenoxime, aztreonam, imipenem, piperacillin, and gentamicin against 89 bacteria isolated from sputum and tracheal aspirates of patients admitted to intensive care units was evaluated. There were 30 Pseudomonas aeruginosa, 27 Klebsiella pneumoniae, 9 Enterobacter cloacae, 5 Escherichia coli, 4 Enterobacter aerogenes, 3 each of Klebsiella oxytoca, Pseudomonas maltophilia, Serratia marcescens, 2 each of Morganella morganii, Acinetobacter anitratus; 1 Proteus mirabilis. All isolates were resistant to erythromycin. Organisms were screened for synergy by fixed erythromycin concentration at 1, 8 and 16 micrograms/ml. There were 16 isolates that showed a greater than four-fold difference in MICs. These strains were analyzed by the checkerboard broth method. No antagonism was seen for any drug combination with erythromycin. One Enterobacter cloacae showed synergy of ceftizoxime and erythromycin, and 1 E. cloacae showed synergy with cefotaxime. Addition was found for 2 P. aeruginosa, 1 each E. aerogenes, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. At concentrations of erythromycin achievable in blood or pulmonary tissue, the activity of newer beta-lactams and gentamicin is not altered by erythromycin.

Anti-Bacterial Agents↗
PubMed1977

[Component composition and admixtures of related compounds in commercial preparations with an erythromycin base].

Chromatographic purity of erythromycin base preparations manufactured in the USSR with various technological procedures and those of 4 foreign firms was studied. All the preparations studied in addition to the main component of erythromycin A contained 5 to 7 per cent of erythromycin C and about 1.5 to 3.5 per cent of a non-identified component possessing a somewhat lower chromatographic mobility than erythromycin C. The admixture of 0.5--1 per cent of anhydroerythmycin was found in many erythromycin preparations. The preparations of some foreign firms contained also a number of additional substances. It was shown that the antimicrobial activity of anhydroerythromycin was 50-60 times lower than that of erythromycin. Direct correla;ion between the level of the antimicrobial activity of the market prepaetions of erythromycin and the level of its chemical purity was noted.

Animals↗
PubMed1982

[Cooperative functioning of 2 systems of protection against its own antibiotic in Str. erythreus 1571, a superproducer of erythromycin].

Protein synthesis in the mycelium of various ages and the protoplasts of Str. erythreus 1571 was slightly sensitive even to high concentrations of erythromycin and lincomycin. Oxytetracycline and neomycin in low concentrations induced marked inhibition of the protein synthesis. 14C-Erythromycin was binding with the mycelium of the organism producing it in much lower amounts than with the mycelium of Str. roseolus, a lincomycin-producing culture. No products of erythromycin biotransformation by the cell-free preparations of Str. erythreus containing cofactors for enzymatic phosphorylation and demethylation were detected with the methods of microbiological titration and radiochromatography. Enzymatic N-demethylation of lincomycin was observed in the cell-free preparations of Str. erythreus. Erythromycin and lincomycin had practically no effect on polylysine synthesis in the cell-free system of Str. erythreus with poly-A and inhibited the synthesis of this polypeptide in the cell-free systems of E. coli MRE 600 and B. subtilis ATCC 6633. These antibiotics had either no effect on the fragment (puromycin) reaction with the ribosomes of Str. erythreus. In case of the ribosomes of E. coli MRE 600 the fragment reaction was sensitive to lincomycin but not to erythromycin. The ribosomes isolated from Str. erythreus and their 50S subunits bound 14C-erythromycin in much lower amounts than those isolated from E. coli and their 50S subunits. The data are indicative of the presence of 2 systems protecting the culture from erythromycin in Str. erythreus 1571, i.e. at the level of ribosomes and at the level of the cytoplasmic membrane.

Biotransformation↗