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PubMed1994

The effect of erythromycin on the pharmacokinetics and pharmacodynamics of zopiclone.

1. The effect of erythromycin on the pharmacokinetics and pharmacodynamics of oral zopiclone, a non-benzodiazepine hypnotic, was investigated in a double-blind, cross-over study. 2. Ten healthy volunteers were given placebo or 500 mg erythromycin orally three times a day for 6 days followed by an oral dose of 7.5 mg zopiclone. 3. Erythromycin increased plasma zopiclone concentration by 4-fold at 0.5 h (P < 0.05) and by 2-fold at 1 h (P < 0.05). There were increases of 3- and 2-fold in the AUC(0,1 h) and AUC(0,2 h) values (P < 0.05). The total AUC of zopiclone increased by 80% (P < 0.05) but the peak concentration by only 40% (P < 0.05). The peak time of zopiclone concentration was reduced from 2 to 1 h (P < 0.001). 4. Significant pharmacodynamic differences between the treatments were observed from 0.5 h to 2 h with respect to saccadic latency and digit symbol substitution tests. 5. The interaction between erythromycin and zopiclone resulted mainly in accelerated absorption which may lead to a faster hypnotic effect in patients.

Administration, Oral↗
PubMed1983

Pharmacokinetics of erythromycin in foals and in adult horses.

The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10-12-week-old foals given 20.0 mg/kg intravenously. The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10-12 weeks) was 1.0-1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h. No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally. Peak levels in foals given the drug orally were 0.42 micrograms/ml at 120 min after administration. Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later; the peak level achieved was 1.44 micrograms/ml serum 90 min after administration and concentrations exceeded 0.25 micrograms/ml for 6 h. In the mares the milk concentrations were approximately twice those in serum. Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals.

Administration, Oral↗
PubMed1992

Effect of erythromycin on L-threonine transport in rabbit jejunum in vitro.

Several antibiotics characterized by different molecular structures are known to affect some intestinal activities. Some of them have been described as inhibitors of the intestinal sugar and amino acid transport with different mechanisms. Erythromycin (EM) is a macrolide antibiotic acting as a motilin agonist and thus stimulating the gastrointestinal motor activity. Since several substances which increase the motor activity of the gastrointestinal tract may produce effects on the intestinal absorption of nutrients, the present study has been carried out to determine whether erythromycin affects the L-threonine intestinal absorption. The results obtained indicate that erythromycin diminishes the L-threonine intestinal transport, probably at the mucosal border level. Two groups of experiments carried out, with Na(+)-deprived medium and ouabain-enriched medium, might indicate that erythromycin action could be due to either a direct or an indirect action on the Na(+)-dependent L-threonine transport located in the brush border.

Animals↗
PubMed1975

Interaction of bile with erythromycin Lactobionate in vitro.

An interaction of bile with erythromycin lactobionate in vitro has been demonstrated. The major bile components involved in this interaction have been shown to be the bile salts. The nature of the bile salt-erythromycin interaction has been investigated. The way in which an interaction between bile salts and erythromycin in vivo might lead to the hepatic dysfunction and cholestasis associated with some instances of erythromycin therapy is discussed.

Bile↗
PubMed1994

Comparative study of erythromycin, troleandomycin and tylosin on the rabbit intestine.

The macrolide antimicrobial agents, erythromycin, troleandomycin and tylosin were tested for their effect on isolated whole segments of the rabbit duodenum, jejunum, ileum and ascending colon, as well as on strips of the circular and longitudinal smooth muscle of the ascending colon. The 14-membered macrolides erythromycin and troleandomycin were found to possess a concentration-dependent contractile effect on the intestinal smooth muscle. The order of potency was: erythromycin > troleandomycin. The 16-membered macrolide tylosin was found to have a much weaker potency than erythromycin and troleandomycin. In addition, the circular smooth muscle of the ascending colon was found to be more sensitive to the compounds tested than the longitudinal smooth muscle.

Animals↗
PubMed1991

The cyclosporin-erythromycin interaction: impaired first pass metabolism in the pig.

1. The pharmacokinetic interaction between cyclosporin (CsA) and erythromycin has been studied in the weanling pig model. 2. Blood CsA and metabolite-1 (M1) concentrations were monitored by high performance liquid chromatography in portal, hepatic and jugular venus blood before and after treatment with erythromycin stearate for 7 days. 3. Erythromycin significantly increased maximum concentration (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC) of CsA in the peripheral circulation. This was accompanied by a significant reduction in the hepatic extraction ratio calculated from portal and hepatic Cmax and AUC data. 4. The extraction ratio appears to be concentration-dependent in that values derived from Cmax (high concentrations) were greater than those from AUC (average concentrations). 5. Time to Cmax (tmax) and t1/2 of CsA were essentially unchanged and no significant changes were observed in peripheral M1 kinetics apart from a small increase in tmax. 6. The pharmacokinetic changes observed in the pig suggest that the CsA-erythromycin interaction is caused by inhibition of hepatic metabolism and the impact of inhibition is greatest during first-pass when CsA concentrations are at their highest.

Animals↗
PubMed1995

The frequency of erythromycin-resistant Staphylococcus aureus in impetiginized dermatoses.

A trend toward increasing resistance of Staphylococcus aureus to standard antibiotic therapy has been reported. Specimens were taken from 98 patients in our outpatient staff clinic who had clinical signs of superficial skin infections. Patients with erythromycin-resistant S. aureus were contacted by telephone or seen in clinic. The organism was found in 87% of patients. Twenty-two (26%) of the 85 cultures that grew S. aureus were resistant to erythromycin. Treatment failure occurred in one of these patients. We conclude that S. aureus is the most common causative organism in secondary skin infections and impetigo in our patient population. Despite significant erythromycin resistance, there was a low frequency of treatment failure in this group. Erythromycin may still be a reasonable agent in the treatment of uncomplicated superficial skin infections in our community at this time.

Adolescent↗
PubMed2000

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study.

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.

Administration, Oral↗
PubMed2001

Effects of low doses of erythromycin on the 13C Spirulina platensis gastric emptying breath test and electrogastrogram: a controlled study in healthy volunteers.

OBJECTIVE: Electrogastrography and stable isotope gastric emptying breath tests (GEBTs) are relatively simple, noninvasive tests of gastric motor function that may be useful in monitoring the effects of therapeutic interventions. It was our primary objective to examine the effects of low dose i.v. erythromycin on the results of the 13C Spirulina platensis GEBT and electrogastrography. We were also interested in evaluating the reproducibility of these tests. METHODS: In 10 healthy subjects (five female, ages 23-37 yr), we simultaneously performed the GEBT, using a prepackaged meal (340 kcal), and electrogastrography on each of four different occasions separated by at least 1 wk. After performance of baseline studies, they were repeated in random order after the infusion of 50 mg of erythromycin (Er50), 100 mg erythromycin (Er100), and a placebo (saline). Breath samples were obtained at baseline and at 75, 90, and 180 min after the meal and T1/2 and Tlag calculated. Electrogastrography recordings began 30 min before the test meal and continued for 2 h after the meal. RESULTS: Baseline and placebo T1/2 and Tlag were similar. Er50 resulted in a modest acceleration of gastric emptying (T1/2 Er50 vs baseline vs placebo = 104.0 vs 132.7 vs 125.5 min) and reduction in lag time (Tlag Er50 vs baseline vs placebo = 47.2 vs 61.5 vs 56.2 min). A similar decrease was seen in response to Er100. The baseline and placebo fasting and fed electrogastrography parameters were similar. After infusion of Er100, the percentage of normal slow waves in the first postprandial hour decreased relative to baseline and placebo (percent normogastria Er100 vs baseline vs placebo = 64.1+/-7.5 vs 82.4+/-6.4 vs 79.7+/-5.5). This corresponded with an increase in percent tachygastria during the same period and an overall decrease in the mean dominant frequency. Similar but less striking changes were seen after administration of Er50. Replicate GEBTs showed a high degree of reproducibility both within and between individuals for T1/2 and Tlag. In contrast, replicate electrogastrograms revealed moderate to high variability for all parameters except the dominant frequency. CONCLUSION: The stable isotope GEBT utilizing 13C S. platensis demonstrates responsiveness to the prokinetic effects of low dose i.v. erythromycin and good reproducibility.

Adult↗
PubMed1989

[The effect of erythromycin treatment on natural killer (NK) cell activity in patients with chronic lower respiratory tract infections].

We measured NK activity before and after administration of erythromycin in 7 cases of chronic respiratory infection, and investigated the relationship between NK activity and improvement of the clinical syndrome. 1) We saw a significant rise in NK activity after treatment of erythromycin. Values before and after ranged from 40.0 +/- 21/2% to 62.0 +/- 32.7%. 2) There was no correlation between treatment period of erythromycin and the rate of rise in NK activity in the various cases such as rapidly rising cases or slowly rising cases, etc. 3) We saw a rise in NK activity before improvement of the clinical syndrome. Therefore it is suggested that treatment of erythromycin affects a rise in NK activity.

Adult↗
PubMed1991

An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea.

Derivatives of erythromycin with modifications at their C-6 position are generally sought for their increased stability at acid pH, which in turn may confer improved pharmacological properties. A recombinant mutant of the erythromycin-producing bacterium, Saccharopolyspora erythraea, produced an erythromycin derivative, 6-deoxyerythromycin A, that could not be obtained readily by chemical synthesis. This product resulted from targeted disruption of the gene, designated eryF (systematic nomenclature, CYP107), that apparently codes for the cytochrome P450, 6-deoxyerythronolide B (DEB) hydroxylase, which converts DEB to erythronolide B (EB). Enzymes normally acting on EB can process the alternative substrate DEB to form the biologically active erythromycin derivative lacking the C-6 hydroxyl group.

Amino Acid Sequence↗
PubMed2006

Orally administered erythromycin in rainbow trout (Oncorhynchus mykiss): residues in edible tissues and withdrawal time.

Aquaculture production has notably increased in the last decades, mainly thanks to intensive farming. Together with market globalization, this gives rise to the spreading of several fish diseases, thus increasing the demand for veterinary drugs for aquatic species. Nonetheless, very few chemicals are registered for use in aquaculture, and fish farmers are often forced to resort to off-label use of drugs authorized for other food-producing animal species. Rainbow trout is the major farmed fish species in Italy and the second one in Europe. Erythromycin is the antibiotic of choice against gram-positive cocci, the major concern for trout farming, but it is not yet registered for aquaculture use in most European countries. The aim of this study was to follow the depletion of erythromycin in rainbow trout (Oncorhynchus mykiss), after its administration at 100 mg kg(-1) trout body weight day(-1) for 21 days through medicated feed (water temperature, 11.5 degrees C). Erythromycin residues in fish muscle plus skin in natural proportion were determined by a validated liquid chromatography-electrospray ionization-tandem mass spectrometry method. Interpolation of our data, following European Agency for the Evaluation of Medicinal Products guidelines, gives a withdrawal time of 255 degrees C-days ( degrees C-day = water temperature x days), thus showing that the general value (500 degrees C-day) recommended by the Council Directive (EEC) no. 82/2001 for off-label drug use in aquaculture would be too conservative in this case, with excessive costs for the farmers. Our study provides preliminary data for a more prudent use of erythromycin in rainbow trout, suggesting a possible withdrawal time after treatment.

Animals↗
PubMed1978

Susceptibility of skin and throat strains of group A streptococci to rosamicin and erythromycin.

The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 mug of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 mug of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.

Aminoglycosides↗
PubMed1981

Effect of carbon dioxide on in vitro susceptibility of anaerobic bacteria to erythromycin.

The activity of erythromycin against 317 strains of anaerobic bacteria, including 133 strains of the Bacteroides fragilis group, was tested by the agar dilution method in an anaerobic atmosphere with two different concentrations of carbon dioxide and without CO2. The effect of the atmosphere of incubation on the agar surface pH was also determined. All strains grew well in the GasPak (GP) environment. However, 3.5 and 30.3% of strains failed to grow in the 2 and 0% CO2 environments, respectively. The quality of growth was best in the GP environment and poorest in the 0% CO2 environment. Minimal inhibitory concentrations in the GP and 2% CO2 environments were frequently the same or one dilution lower in the 0% than in the GP environment. In the 0% CO2 atmosphere, minimal inhibitory concentrations were usually two to three dilutions lower than in the GP environment. Consequently, only 24% of B. fragilis strains were susceptible to erythromycin in the GP environment, whereas 77% were susceptible in the 0% CO2 environment. For Fusobacterium species, 12% were susceptible to erythromycin in the GP environment, and 73% were susceptible in the 0% CO2 environment. There was a comparable decrease in pH in all three atmospheres tested. In vitro susceptibility testing of erythromycin against anaerobic bacteria should be performed in an atmosphere containing carbon dioxide.

Anaerobiosis↗
PubMed1985

Antibacterial activities of erythromycins A, B, C, and D and some of their derivatives.

The MICs of erythromycins A, B, C, and D and some of their derivatives were determined against 21 gram-positive and 15 gram-negative microorganisms. Antibacterial activity was confined to gram-positive and very few gram-negative bacteria. Erythromycin B was somewhat less active than erythromycin A, and erythromycin C and D showed about half that activity or even less. Most other derivatives had negligible activity. Determination of potency by diffusion and turbidimetric assays were in line with MICs. The examination of the results of these assays, however, revealed that there are differences between the data of different laboratories, depending on the microorganisms and conditions used.

Bacteria↗
PubMed1986

Contribution of two different mechanisms to erythromycin resistance in Escherichia coli.

Escherichia coli BM2570 was resistant to high levels of erythromycin by two different mechanisms. The two genes conferring resistance to erythromycin in BM2570 were carried by a 150-kilobase self-transferable plasmid, pIP1527, and were cloned separately in E. coli. A single polypeptide with an Mr of 27,000 was encoded by the gene erxA and conferred high-level resistance to macrolide, lincosamide, and streptogramin B-type antibiotics by a mechanism other than drug inactivation. This resistance phenotype, not previously reported for a clinical isolate of enterobacteria, was probably due to modification of the ribosomes. The gene ereB encoded an enzyme with an Mr of 51,000 which inactivated erythromycin and oleandomycin. The two different mechanisms specified by erxA and ereB contributed in more than an additive fashion to the high level of resistance to erythromycin conferred by plasmid pIP1527 to E. coli BM2570.

Bacterial Proteins↗
PubMed1988

In vitro assay to demonstrate high-level erythromycin resistance of a clinical isolate of Treponema pallidum.

We have previously demonstrated that cells of Treponema pallidum freshly extracted from infected rabbit testes can be intrinsically radiolabeled with [35 S]methionine to very high specific activities. In this study we used the inhibition of [35 S]methionine incorporation into trichloroacetic acid-precipitable protein in vitro as an assay to test the susceptibilities of three different pathogenic treponemal strains to various antibiotics. In general, the results correlated very well with the known efficacies of these antibiotics in treating human patients with syphilis. One of the strains tested, however, a clinical isolate of T. pallidum designated street strain 14, was found to exhibit high-level resistance to erythromycin and a closely related macrolide, roxithromycin (RU 965). Street strain 14 was originally isolated from a human patient with active secondary syphilis who failed to respond to erythromycin therapy. Thus, our results indicate that an erythromycin-resistant strain of T. pallidum can be responsible for erythromycin treatment failure. In addition, street strain 14 treponemes were found to be generally less susceptible by this assay to a variety of antibiotics than were treponemes of the T. pallidum Nichols strain. These findings suggest that the outer envelope of street strain 14 treponemes may be generally less permeable to antibiotics than is that of Nichols strain treponemes.

Animals↗
PubMed1994

Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia.

We tested in vitro 49 isolates of Chlamydia pneumoniae obtained from 35 children with community-acquired pneumonia against clarithromycin and erythromycin. The children were part of a treatment study comparing the two drugs. Clarithromycin was 2- to 10-fold more active than erythromycin, with a MIC for 90% of strains tested and minimal chlamydiacidal concentration for 90% of strains tested of 0.031 microgram/ml compared with 0.125 microgram/ml for erythromycin. Eight of these children, two of whom were treated with erythromycin and six of whom received clarithromycin, remained culture positive after treatment. We were able to test 21 isolates from these children. All were susceptible to both drugs, and the MICs did not change after therapy.

Child↗