Efficacy and tolerance of erythromycin acistrate in the treatment of acute exacerbations of chronic bronchitis in the elderly.

This randomized, investigator-blind, parallel-group trial compared erythromycin acistrate (EA) and erythromycin base (EB) in the treatment of elderly patients with acute exacerbations of chronic bronchitis. In total, 57 hospitalized patients were included, of whom 28 received EA 400 mg three times daily, and 29 EB 500 mg three times daily for 10-21 days. The mean age of the patients was 70 and 68 years in the EA and EB groups, respectively. The patients underwent medical examination before the onset of the study, at the 7th day during the treatment and 3-5 days after termination of the treatment. The efficacy assessment was based on clinical signs and symptoms of infection as well as on bacteriological culture from sputum samples. 55% of the patients in the EA group and 61% in the EB group were totally cured, 23 and 29%, respectively, had only mild symptoms at the end of the therapy and 14 versus 11% of the patients did not respond at all. The predominant pathogens isolated from sputum were Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae. 60% of the patients in the EA group and 46% in the EB group from whom a sample was taken had normal flora in the posttreatment culture. In the EA group, 8 patients and in the EB group 7 patients complained of gastrointestinal side effects and 4 and 1, respectively, discontinued the treatment prematurely. Slight, reversible elevations of one or more liver parenchymal enzyme activities during and after treatment were seen at the same frequency in both treatment groups. The results show that EA is as effective and well tolerated as EB in the treatment of exacerbations of chronic bronchitis in elderly patients.

Erythromycin and 2'-acetyl erythromycin concentrations in plasma and pelvic tissues after repeated doses of erythromycin acistrate.

The concentrations of erythromycin (E) and 2'-acetyl erythromycin (2'-AE) in female pelvic organs, i.e. endometrium, myometrium, ovary and Fallopian tube, as well as in plasma, were determined after oral dosing of erythromycin acistrate (EA, CAS 96128-89-1), a erythromycin prodrug. Ten patients undergoing selective gynecological operation were given three doses of EA (400 mg) at 8-h intervals immediately before the operation. Tissue samples were taken 75-205 min after the intake of the last dose. Blood samples were collected immediately prior to and up to 8 h after the intake of the last dose. High total antibiotic (erythromycin + 2'-acetyl erythromycin) concentration in plasma were measured throughout the dose interval after the last dose. The concentrations of E in plasma were over the MICs for most of the erythromycin-sensitive bacteria (0.5 micrograms/ml) in 7 out of 10 patients (mean 0.66 micrograms/ml) at the end of the third dose interval. The drug concentrations in tissues were lower than in plasma (due to short treatment time of totally 24 h). The mean percentage of penetration (tissue/plasma ratios) for erythromycin ranged from 63 to 95% in various pelvic tissues. However, rather extensive interindividual variation was observed. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 29-39% in plasma and 42-73% in tissue samples. There were negligible amounts of inactive anhydro forms in plasma after EA and their concentrations in tissue samples were low, as well.

Penetration of erythromycin into periapical lesions after repeated doses of erythromycin acistrate and erythromycin stearate: a pilot study.

In 26 patients who had undergone apicectomy and extirpation of granulomas (n = 9) or radicular cysts (n = 17), concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms were determined with a novel chemical method in plasma and periapical lesions after at least 2 days of treatment with erythromycin acistrate (EA) (400 mg three times daily, n = 11) or erythromycin stearate (ES) (500 mg three times daily, n = 15). Oral surgery was performed 2 1/2 to 3 hours after the last dose. Blood samples were collected at the time of operation, and immediately before antibiotic treatment, and 1, 2, and 6 hours after treatment. At all time points EA produced at least twice the total antibiotic (2'-acetyl erythromycin plus erythromycin) concentrations in plasma as ES. Erythromycin levels in plasma were at least as high after EA treatment as after ES. In periapical lesions erythromycin concentration after EA was three times higher (1.34 +/- 0.28 micrograms/gm) than after ES treatment (0.40 +/- 0.17 micrograms/gm). Although the total drug concentration in periapical lesions was about the same after EA (2.64 micrograms/ml) and ES (3.41 micrograms/ml), most of the drug recovered after ES was antimicrobially inactive anhydroerythromycin (3.01 micrograms/gm). The concentration of anhydroerythromycin in plasma was approximately the same as that of erythromycin after ES throughout the dose interval. After EA treatment both plasma and the periapical lesion samples contained hardly detectable amounts of anhydroerythromycin. Hence EA has a good bioavailability essential for treatment and prophylaxis of bacterial infections in dentistry.

Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections.

Erythromycin acistrate is a new 2'-acetyl esther prodrug of erythromycin, whose structure resembles that of erythromycin estolate. However, in toxicological studies, it does not have the problems of hepatotoxicity. To assess its effects on hepatic functions in clinical practice, the liver parameters of patients with respiratory tract or skin infections were monitored during therapy. In total 1549 patients were treated for 7-14 days. In addition, 127 patients with suspected viral infections served as controls. There were no significant differences in serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (gamma-GT) or alkaline phosphatase (APHOS) values between the erythromycin acistrate or control groups at the beginning or end of therapy. ASAT values increased moderately in 2.4% and clearly in 0.3% of patients treated, but also decreased in 2.0%. ALAT values were moderately increased in 9.9%, clearly increased in 0.6% and normalized in 3.5% of the patients. gamma-GT values increased moderately in 3.5% and and clearly in 0.3%, but decreased to normal in 3.3% of the patients. APHOS was moderately elevated in 1.0% of the patients and normalized in 1.3%. The correlation of changes between the different liver enzymes was poor. Only ten patients (0.6%) had two or more clearly elevated liver enzyme values by the end of the therapy, of whom five had increased liver enzyme activities before the treatment, two had underlying disease explaining the changes and in only three patients out of 1549 (0.2%) could hepatic changes be attributed to erythromycin acistrate therapy. These changes were reversible. The results demonstrate the hepatic safety of erythromycin acistrate in clinical practice. Concomitant food intake did not affect the safety profile.

Effect of Lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea.

The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied. Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week. The volunteers were randomly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment. Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt. Other side effects of erythromycin, such as abdominal distress, stomach pain and flatulence, were less common in the GG yoghurt group than in the placebo yoghurt group. The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG. No Lactobacillus GG was found in the faecal samples of volunteers in the group taking pasteurized yoghurt.

Effect of erythromycin on the oro-caecal transit time in man.

Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.