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Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric patients.

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.

Anti-Bacterial Agents↗

Time-resolved three-dimensional MR imaging of gastric emptying modified by IV administration of erythromycin.

OBJECTIVE: The aim of our study was to assess the effect of IV erythromycin on gastric emptying and subsequent small-bowel filling using three-dimensional (3D) MR imaging in both healthy subjects and patients with functional dyspepsia. SUBJECTS AND METHODS: Six healthy volunteers and six patients with symptoms of functional dyspepsia ingested 10 mL of gadopentetate dimeglumine mixed into 500 mL of a liquid nutrient. On two separate days, gastric emptying was determined using 3D volume measurements that were obtained every 5 min for as long as 25 min on 3D T1-weighted gradient-echo MR imaging with and without the use of IV erythromycin. Gastric volumes and filling of the small bowel were quantified on the 3D data sets using semiautomatic software. RESULTS: Delineation of the bright gastric lumen proved easy. After 25 min, a significant decrease in gastric volumes could be seen in examinations performed with and without erythromycin. In healthy volunteers, gastric volumes decreased significantly more after the administration of erythromycin. In three patients with functional dyspepsia, MR imaging revealed reduced rates of gastric emptying. The administration of erythromycin resulted in a significantly faster rate of gastric emptying in two of those three patients. CONCLUSION: Three-dimensional MR imaging is a feasible method of assessing gastric volumes and diagnosing delayed gastric emptying. In patients with reduced rates of gastric emptying, 3D MR imaging may be an appropriate tool with which to monitor therapeutic approaches, such as the use of prokinetic agents like erythromycin.

Adult↗

Effects of oral erythromycin on fasting and postprandial antroduodenal motility in patients with type I diabetes, measured with an ambulatory manometric technique.

OBJECTIVE: The aim of this double-blind crossover study was to evaluate the effects of oral erythromycin (250 mg t.i.d.) on fasting and postprandial gastrointestinal motility and gastrointestinal symptoms in patients with type I diabetes. RESEARCH DESIGN AND METHODS: Antroduodenal motility was recorded with an ambulatory manometric technique for a 20-h period, including a high-caloric high-fat dinner and a low-caloric low-fat breakfast and a long fasting period, after 2 weeks erythromycin and placebo treatment in 12 patients with type I diabetes. During the manometric study, plasma glucose concentrations were assessed by frequent self-testing. Gastrointestinal symptoms were scored daily to assess the severity of the symptoms (range 0-3). RESULTS: Oral erythromycin decreased the migrating motor complex cycle length from 118.9 +/- 46.0 to 86.2 +/- 25.3 min (P = 0.03) by shortening phase II from 68.7 +/- 23.5 to 48.5 +/- 19.4 min (P < 0.05). The total number of duodenal phase III increased from 48 to 62 (P = 0.075). However, the degree of antral participation to duodenal phase III did not increase. Erythromycin significantly decreased the duration of the postprandial period after dinner (from 417.0 +/- 137.9 to 348.8 +/- 93.8 min, P = 0.04). During this shorter postprandial period, the number of antral contractions (P < 0.01) and the antral motility index increased (P < 0.03), and early phase III activity at the level of the duodenum was abolished. In diabetic patients with antral hypomotility, after dinner, the mean symptom score improved significantly, from 2.07 +/- 0.86 to 1.52 +/- 0.63 (P = 0.018). CONCLUSIONS: This ambulatory antroduodenal manometric study showed that oral erythromycin (250 mg t.i.d.) improves both fasting and postprandial antroduodenal motor activity after a high-caloric meal in patients with type I diabetes. Furthermore, in diabetic subjects with postprandial antral hypomotility, erythromycin reduces dyspeptic symptoms.

Administration, Oral↗

Increased use of erythromycin causes resistance in Haemophilus influenzae.

The use of erythromycin in Sweden has increased since 1975. An increasing prevalence of Haemophilus influenzae (H.i.) with reduced susceptibility to erythromycin has been noted in our laboratory during the years 1980 to 1985. The largest consumers of erythromycin were found to be children less than 4 years of age. Variations in resistance level of H.i. isolated from patients within this age group and variations in consumption of erythromycin were analysed for each year. The highest prevalence of resistant strains was found during spring and summer. The consumption of the antibiotic was highest during the first quarter of the year, gradually decreasing, and increasing sharply again during the fourth quarter of the year. Judging also from deviations from this pattern there seems to be an association between consumption and resistance. The different levels of resistance reported in the literature may reflect different populations of patients with different consumption of erythromycin, and different levels at different time of the year. Considering the present high level of H.i. with decreased susceptibility to erythromycin the drug is not likely to have clinical effect in H.i. infections.

Child, Preschool↗

Economic analysis of treatment with roxithromycin in comparison with erythromycin in patients with lower respiratory tract infections.

A number of new antibiotics have lately become available for treatment of lower respiratory tract infections in out-patients. The new drugs are generally more expensive than the older ones, which might be justified by better effects, improved safety, or by other advantages. In this study, a retrospective economic analysis has been made using data from a previous trial comparing a new macrolide, roxithromycin, with an older 1, erythromycin stearate in the treatment of lower respiratory tract infections. The trial was multicentre, double blind, randomized and comparative. There were no significant differences in efficacy between treatments, although the cure rate was higher for roxithromycin, 85% vs 79% for erythromycin. 20/39 of the erythromycin-treated patients reported adverse events, vs 7/40 roxithromycin-treated subjects, a highly significant difference. More detailed information was obtained by reviewing the medical records of the participants, and from questionnaires distributed to the 3 centres that had included patients in the trial. Additional visits were found necessary for 4 patients treated with erythromycin and for 1 using roxithromycin. Using the healing rates in the present investigation, and including costs for initial drug treatments, second consultations, and failed therapy, average cost-effectiveness (SEK/patient cured) was 409 for roxithromycin-treated patients, and 488 for erythromycin-treated. Roxithromycin should then be cheaper than erythromycin stearate. With the same healing rate, roxithromycin would be less cost-effective, but indirect costs and effects on quality of life are not then taken into account.

Anti-Bacterial Agents↗

A comparative efficacy and safety study of clarithromycin, roxithromycin and erythromycin stearate in mild pneumonia.

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↗

[Effect of erythromycin and clarithromycin on ion transport across dissected canine tracheal epithelium].

Since erythromycin was shown to be effective in the treatment of patients with diffuse panbronchiolitits, newly discovered effects of macrolide antibiotics have attracted much attention. It was reported that erythromycin inhibits Cl secretion across cultured canine tracheal epithelial cells. Erythromycin may decrease the movement of water toward the lumen, thus reducing sputum volume. We tested the hypothesis that erythromycin and clarithromycin have a similar effect on the dissected canine tracheal epithelium, by measuring the short circuit current using Ussing chambers. Addition of erythromycin or clarithromycin did not change the short circuit current within 20 minutes when applied on either the mucosal side or the submucosal side. No changes in the short circuit current were observed after pretreatment of the epithelium with amiloride, an Na channel blocker, or bumetanide, a Cl transport inhibitor, and subsequent addition of the macrolide antibiotics. These data indicate that neither erythromycin nor clarithromycin has any short term effect on ion transport in the dissected canine tracheal epithelium.

Animals↗

Effect of erythromycin on the absorption of fexofenadine in the jejunum, ileum and colon determined using local intubation in healthy volunteers.

OBJECTIVE: To investigate the in vivo intestinal absorption mechanism(s) and systemic availability of fexofenadine in the jejunum, ileum and colon in humans. METHOD: A single dose of fexofenadine hydrochloride (60 mg as solution) was applied under fasting conditions, either alone or directly after a solution of erythromycin lactobionate (corresponding to a dose of 250 mg erythromycin), to the jejunum, ileum and colon in 6 healthy volunteers (3 male and 3 female) using a regional intubation dosing technology (Bioperm AB, Lund, Sweden). A total of 36 fexofenadine administrations were performed. The administration of fexofenadine to the specified location either alone or in combination with erythromycin was conducted in a randomized manner on 2 consecutive days with a 5-day washout period between doses. RESULTS: The plasma AUC for fexofenadine (mean +/- SEM) was higher (2.7-to 2.3-fold, p < 0.001) after application to the jejunum (1090 +/- 134 h x ng/ml) than to the ileum (404 +/- 102 h x ng/ml) or colon (476 +/- 212 h x ng/ml). No significant differences were found between application to the ileum and colon. The administration of erythromycin affected the absorption rate after jejunal application with a prolonged tmax from a median of 40 min (range 10-90 min) to a median of 3 hours (range 10-180 min) (p = 0.009). A change in tmax was not observed with application to the ileum and colon. The concomitant administration of erythromycin in the jejunum tended to increase the plasma AUC of fexofenadine from 1090 +/- 134 to 1750 +/- 305 h x ng/ml (p = 0.069). CONCLUSIONS: The systemic availability of fexofenadine was significantly higher after jejunal administration in accordance with a low permeability compound. The effects of erythromycin suggest that absorption of fexofenadine involves an uptake transport in addition to passive diffusion in the jejunum and predominantly passive diffusion in the ileum and colon.

Administration, Oral↗

Activity of erythromycin against Haemophilus influenzae from respiratory tract infections.

Ampicillin and amoxycillin are very frequently used for treating respiratory infections due to Haemophilis influenzae, but the emergence of beta-lactamase producing strains of this organism may limit their use. Erythromycin would be a suitable alternative but to date variable absorptions and reported minimal inhibitory concentrations (MICs) outside the range of achievable blood levels of erythromycin have prevented its use. The purpose of this study was to determine the MICs of erythromycin for strains of H. influenzae isolated from patients with lower respiratory tract infection and the frequency of beta-lactamase production in these strains. Eighty-five of 100 strains were sensitive to erythromycin (MIC much less than 2.00 mg/L). Eleven strains were resistant to ampicillin and 10 of these produced beta-lactamase. Nine beta-lactamase producing strains had MICs to erythromycin of 2.0 mg/L or less. With the blood levels of erythromycin obtainable with new formulations, this antibiotic should prove of use in the treatment of respiratory infections due to H. influenzae.

Adolescent↗

Biological properties of ER 42859, a novel erythromycin derivative.

The antimicrobial activity of a new semi-synthetic oral erythromycin derivative, ER 42859, was evaluated in vitro and in vivo in comparison with erythromycin, spiramycin, josamycin, oleandomycin and the newer semi-synthetic derivatives flurithromycin, roxithromycin and A-56268. MIC values of ER 42859 were superior to those of roxithromycin, oleandomycin, josamycin and spiramycin but generally 2-fold poorer than those of erythromycin. The activity equalled that of erythromycin against Haemophilus influenzae and was superior to that of roxithromycin and A-56268 against this organism. MIC values of the compound were greatly influenced by pH due to the dibasic nature of the molecule. ER 42859 had markedly superior activity to erythromycin, spiramycin, josamycin, oleandomycin and flurithromycin against experimental infections in mice and similar activity to roxithromycin and A-56268. Blood and tissue levels were high and prolonged in rodents. In volunteers, blood levels were prolonged but inferior to those of erythromycin.

Animals↗

Isolation and structure of a new macrolide antibiotic, erythromycin G, and a related biosynthetic intermediate from a culture of Saccharopolyspora erythraea.

The new naturally occurring erythromycin G (4), formally derived from erythromycin B by hydroxylation of the C-16 methyl group, and 3-O-mycarosylerythronolide B (5), an erythromycin biosynthetic intermediate previously obtained only from microorganisms blocked in erythromycin biosynthesis, were isolated from a concentrate of mother liquors derived from a culture of Saccharopolyspora erythraea. The structure of erythromycin G was defined by spectroscopic data and X-ray crystallographic analysis. Theoretical calculation of 4 has been performed at MM2 level, and the low-energy conformations have been compared with X-ray data: both theoretical and experimental approaches give similar three-dimensional shapes. Antibacterial activity of 4 against both gram-positive and gram-negative organisms has been evaluated. A simple method for the isolation of large amounts of erythromycins B (2) and D is provided as well.

Anti-Bacterial Agents↗

Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines.

OBJECTIVE: To determine whether erythromycins, sulfonamides, and tetracyclines are associated with an increased risk for acute hepatitis. DESIGN: Case-control study. SETTING: Medicaid billing data from Michigan and Florida between 1980 and 1987. PATIENTS: The 107 cases included patients hospitalized with acute symptomatic hepatitis without an identifiable cause of liver disease noted in the medical record. Four controls per case were randomly selected and were matched for age, sex, and state. RESULTS: Five cases (4.7%) and four controls (0.9%) were exposed to erythromycins, yielding an odds ratio of 5.2 (95% Cl, 1.1 to 26.6). No case or control was exposed to erythromycin estolate. Eight cases (7.5%) and three controls (0.7%) were exposed to oral sulfonamides, yielding an odds ratio of 11.4 (Cl, 2.7 to 67.8). All (except one control) had received trimethoprimsulfamethoxazole. Five cases (4.7%) and four controls (0.9%) were exposed to tetracyclines, yielding an odds ratio of 5.2 (Cl, 1.4 to 19.7). The results did not change substantively for erythromycin or sulfonamides after adjustment using multiple logistic regression for age, sex, state, and use of other hepatotoxic drugs. With tetracyclines, however, the odds ratio decreased to 3.6 (Cl, 0.9 to 14.3). Associations were also seen with isoniazid (P = 0.008) and rifampicin (P = 0.04). The number of patients developing acute symptomatic liver disease resulting in hospitalization for each million patients treated with a 10-day course of erythromycin was 2.28 cases; for sulfonamides, this figure was 4.8 cases; and for tetracycline, the figure was 1.56 cases. CONCLUSION: Erythromycin, sulfonamides, and tetracyclines are associated with acute symptomatic hepatitis resulting in hospitalization. Given the widespread use of these drugs, they will be among the more common drugs associated with hepatitis.

Acute Disease↗

Pharmacokinetic interpretation of erythromycin and tylosin activity in serum after intravenous administration of a single dose to cows.

The distribution and elimination kinetics of erythromycin and tylosin, which are macrolide antibiotics, were studied in healthy cows. A single dose (12-5 mg/kg) of drug was administered as an intravenous bolus, and blood samples were collected at precisely timed intervals. The standard cylinder plate bioassay method using Sarcina lutea as test organism was employed to determine antibiotic activity in the serum. The results suggested that these drugs are distributed in at least two kinetically distinct body compartments. By use of established mathematical techniques, values were assigned to the individual rate constants controlling distribution between the central and peripheral compartments and to the rate constant controlling overall elimination (beta) of each drug from the body. The calculated overall tissue to serum drug level ratios (k12/k21) after apparent distribution equilibrium was attained were 2-28 and 2-05 for erythromycin and tylosin, respectively. The half-life (mean+/-SD) of erythromycin was 3-16 h+/-0-44, while that of tylosin was 1-62 h+/-0-17. The total body clearance (ml/kg/min) values were 2-88+/-0-47 for erythromycin and 7-8+/-2-95 for tylosin. Analogue computer simulated curves of the antibiotic levels in the central and tissue compartments as wel as an elimination curve were generated. The tissue level of erythromycin reached a peak of 43 per cent of the dose at 67 min. At 6 h, the percentages of the dose of erythromycin in the central and tissue compartments and eliminated were 6, 19 and 75, respectively. The peak level of tylosin in the tissue compartment (26-5 per cent of the dose) was present at 30 min. At 4 h, 1 and 5 per cent of the dose were contained in the central and peripheral compartments, respectively, while 94 per cent had been eliminated. This single dose study provides information which is essential for the design of a satisfactory dosage regimen.

Animals↗

Oral erythromycin for treatment of feeding intolerance in preterm infants: a preliminary report.

UNLABELLED: Feeding intolerance is a common problem in preterm infants resulting in a prolonged hyperalimentation which is associated with an increased risk of serious and sometimes even life threatening complications, including cholestasis jaundice, liver impairment, nutritional deficiency, biochemical rickets and catheter-related septicaemia. Erythromycin, a commonly used macrolide antibiotic, has been reported as having potent prokinetic properties and enhancing gastrointestinal motor activity. The authors, therefore, conducted a preliminary study of oral erythromycin for the treatment of feeding intolerance in preterm infants to evaluate the safety and efficacy of this drug. AIM: To evaluate the safety and efficacy of oral erythromycin as a prokinetic agent in promoting enteral feeding in preterm infants with feeding intolerance. METHOD: Preterm infants, gestational age (GA) < or = 36 wk, who met the feeding intolerance criteria, were enrolled in the study. Inclusion criteria included infants who received enteral feeding less than half of full feeding or less than 75 ml/kg/day by day 14 post-natal age or gastric residual > or = 50 per cent of a given amount of feeding, more than 2 consecutive feeds by day 7 post-natal age. All patients received oral erythromycin ethylsuccinate 12 mg/kg every six hours for 2 days, then 3 mg/kg every six hours for 5 days. The times taken to establish full enteral feeding after the drug treatment and time to stop hyperalimentation were recorded. Potential adverse effects of erythromycin were assessed. Response to treatment was defined as decreased gastric residual < 30 per cent of a similar amount of the previous feed and was able to continue to full feeding. RESULTS: Ten preterm infants were enrolled in this study with a mean GA of 30.8 weeks (26-35), mean birth weight of 1,489 g (range 900-2,560 g) and mean age at entry of 9.2 days (range 7-12 days). Nine of 10 infants responded to treatment within 24 hours. The average time to establish full enteral feeding after the drug treatment was 6.6 days (range 4-10 days). None of the infants developed adverse effects such as vomiting, diarrhea, or pyloric stenosis. CONCLUSION: The preliminary data indicates that oral erythromycin is effective and safe in facilitating enteral feeding in preterm infants with feeding intolerance. Infants can achieve full feeding within a week after treatment, and this may shorten the course of hyperalimentaiton. Further randomized controlled trials are warranted.

Administration, Oral↗

The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.

Bronchial Diseases↗

Erythromycin inhibits Cl secretion across canine tracheal epithelial cells.

We studied the effect of the macrolide antibiotic erythromycin on bioelectrical properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of erythromycin to the submucosal but not to the mucosal side dose-dependently decreased short-circuit current (Isc), the maximal decrease from the baseline value and the concentration required to produce a half-maximal effect (IC50) being 5.6 +/- 1.0 microA.cm-2 (mean +/- SE, p less than 0.001) and 18 microM, respectively. In contrast, other antibiotics including ampicillin, cephazolin and tetracycline were without effect. The erythromycin-induced decrease in Isc was not altered by amiloride, but it was abolished by bumetanide, diphenylamine-2-carboxylate2, and substitution of Cl in the bathing medium with gluconate (p less than 0.001, in each case). The effect of erythromycin on epithelial Isc was attenuated by pretreatment of cells with indomethacin but not with AA-861 a lipoxygenase inhibitor. Incubation of cells with erythromycin inhibited the release of prostaglandins E2 and F2 alpha from tracheal epithelial cells. These results indicate that erythromycin may selectively inhibit Cl secretion across airway epithelium through the inhibition of prostaglandin synthesis and suggest that this action possibly reflects its clinical efficacy in the treatment of airway hypersecretion.

Animals↗

Effect of zinc gluconate on propionibacterium acnes resistance to erythromycin in patients with inflammatory acne: in vitro and in vivo study.

Tetracyclines and macrolide antibiotics have been in use for acne treatment for more than 20 years. Since 1992 increasing resistance to these antibiotics, and especially to erythromycin, is reported with Propionibacterium acnes. Zinc salts have demonstrated their efficacy in inflammatory acne treatment as well as their bacteriostatic activity against Propionibacterium acnes. The objective of our work was firstly to determine whether the clinical anti-inflammatory efficacy of zinc salts was altered in the presence of erythromycin resistant strains in vivo, and secondly to study the in vitro and in vivo effect of zinc on the sensitivity of Propionibacterium acnes strains to erythromycin. Thirty patients with inflammatory acne were treated by zinc gluconate with a daily dose of 30 mg for two months and bacteriologic samples were taken at D0, D30 and D60. In vivo, this study displayed a reduction in the number of inflammatory lesions after a 2-month treatment whether or not Propionibacterium acnes carriage was present. Concurrently, in vitro addition of zinc salts in the culture media of Propionibacterium acnes reduced resistance of Propionibacterium acnes strains to erythromycin. Thus, association of zinc salts via a systemic route and topical erythromycin treatment seems an interesting option in the light of an increasing number of patients carrying erythromycin resistant Propionibacterium acnes strains.

Acne Vulgaris↗

Effect of erythromycin on homocysteine-induced extracellular matrix metalloproteinase-2 production in cultured rat vascular smooth muscle cells.

BACKGROUND & OBJECTIVE: Several lines of evidence have shown an association between Chlamydia infection and atherosclerosis, but clinical trials of preventive antibiotic (erythromycin) treatment in patients with coronary artery disease have shown conflicting results. Hyperhomocysteinaemia is an independent risk factor of coronary artery disease and causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. In the present study we investigated the effects of erythromycin on the production of homocysteineinduced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells (VSMCs). METHODS: Effects of different concentration of homocysteine (Hcy) (0-5000 micromol/l) on MMP-2 production, and the effects of different erythromycin concentrations (0-10 mmol/l) on homocysteine-induced MMP-2 production in cultured rat VSMCs were studied using gelatin zymography and Western blotting. The changes of MMP-2 under various treatments for 1, 3 and 5 days were also compared. RESULTS: Homocysteine (50-1000 mu mol/l) increased the production of MMP-2 significantly in a dose-dependent manner and reduced the production of MMP-2 at a high level (5000 mu mol/l). Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added erythromycin in a dose-dependent manner. INTERPRETATION & CONCLUSION: Homocysteine increased the production of MMP-2 significantly in a dose-dependent manner. Extracellularly added erythromycin decreased homocysteine-induced MMP-2 secretion. The findings of the present study suggested that the beneficial effect of erythromycin on vascular disease processes might be due to its inhibitory effect on the Hcyinduced production of MMP-2 in VSMCs.

Animals↗