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PubMedDate not supplied

[Modification of intestinal colonization and translocation of Campylobacter jejuni by erythromycin and an extract of Lactobacillus acidophilus in axenic mice].

Erythromycin (15 mg) or lyophylized heat-killed Lactobacillus acidophilus (80 mg) were administered per os daily in germ-free mice infected at day O with 10(7)-10(8) Campylobacter jejuni per os. Bacterial colonization of intestine and bacterial translocation of C. jejuni toward mesenteric lymph nodes, blood and liver were then studied for 5 days. The results were compared with those from an infected untreated control group. Compared to the control group, the numbers of free and mucosa-associated bacteria decreased at day 5 in the erythromycin-treated group and the number of mucosa-associated bacteria was reduced from day 1 to day 5 in the Lactobacillus-treated group. Both treatments reduced the frequency of bacterial translocation toward mesenteric lymph nodes from day 1 to day 5. We concluded that both erythromycin and heat-killed L. acidophilus are effective in treating Campylobacter infection in mice, though probably through different mechanisms.

Animals↗
PubMed1998

Precursor-directed biosynthesis of 12-ethyl erythromycin.

A precursor-directed method for the biosynthesis of novel 6-deoxyerythronolide B derivatives has been extended to allow alteration of the functionality at C-12. We recently described a simple and practical method for harnessing the biosynthetic potential of the erythromycin pathway to generate novel molecules of natural product-like complexity by feeding designed synthetic molecules to an engineered mutant strain having an altered 6-deoxyerythronolide B synthase (DEBS). Our initial applications of this technique focused on alteration of the ethyl side chain of 6-dEB (C14-C15). We now report the extension of this approach to modification of the C-12 substituent. An appropriately designed substrate is shown to incorporate into 6-dEB biosynthesis, yielding a 6-dEB analogue bearing a 12-ethyl group. This 6-dEB analogue is a substrate for post-polyketide tailoring enzymes, and is converted into the corresponding analogue of erythromycin C. These results show that many of the downstream active sites are tolerant of this unnatural functionality and suggest that a wide variety of erythromycin derivatives should be accessible by this approach or by total biosynthesis via genetic engineering.

Anti-Bacterial Agents↗
PubMedDate not supplied

Improvement of esophageal and gastric motility after 2-week treatment of oral erythromycin in patients with non-insulin-dependent diabetes mellitus.

Forty-five patients with non-insulin-dependent diabetes mellitus (NIDDM) were enrolled in the study. Before and after the 2-week treatment course of oral erythromycin, esophageal (the mean transit time, MTT) and gastric motility (the halftime of gastric emptying, GETt1/2) were evaluated by radionuclide labeled liquid and solid meals. Meanwhile, the fasting blood sugar (FBS) levels were monitored. After a 2-week erythromycin treatment, MTT shortened from 9.32+/-1.12 to 6.28+/-0.91 s and GETt1/2 shortened from 210.2+/-24.3 to 128.3+/-30.1 min. Meanwhile, FBS decreased from 198.2+/-30.1 to 121.5+/-21.3 mg/dl (P value <.05). We conclude that a 2-week treatment course of oral erythromycin can significantly improve esophageal and gastric motility which results in a better control of blood sugar in patients with NIDDM.

Administration, Oral↗
PubMed2000

Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase.

BACKGROUND: The macrolide antibiotic erythromycin A, like other complex aliphatic polyketides, is synthesised by a bacterial modular polyketide synthase (PKS). Such PKSs, in contrast to other fatty acid and polyketide synthases which work iteratively, contain a separate set or module of enzyme activities for each successive cycle of polyketide chain extension, and the number and type of modules together determine the structure of the polyketide product. Thus, the six extension modules of the erythromycin PKS (DEBS) together catalyse the production of the specific heptaketide 6-deoxyerythronolide B. RESULTS: A mutant strain of the erythromycin producer Saccharopolyspora erythraea, which accumulates the aglycone intermediate erythronolide B, was found unexpectedly to produce two novel octaketides, both 16-membered macrolides. These compounds were detectable in fermentation broths of wild-type S. erythraea, but not in a strain from which the DEBS genes had been specifically deleted. From their structures, both of these octaketides appear to be aberrant products of DEBS in which module 4 has 'stuttered', that is, has catalysed two successive cycles of chain extension. CONCLUSIONS: The isolation of novel DEBS-derived octaketides provides the first evidence that an extension module in a modular PKS has the potential to catalyse iterative rounds of chain elongation like other type I FAS and PKS systems. The factors governing the extent of such 'stuttering' remain to be determined.

Anti-Bacterial Agents↗
PubMed1996

Coprescription of terfenadine and erythromycin or ketaconazole: an assessment of potential harm.

PURPOSE: In a retrospective study, the authors used a pharmacy claims database to analyze the rate of coprescription of terfenadine and erythromycin or ketaconazole. STUDY PERIOD: The investigators reviewed claims filed for these drugs between January 1, 1990, and June 30, 1993. The time period allowed for comparison of coprescription rates before and after the Food and Drug Administration (FDA) required the manufacturer of terfenadine to inform the medical community of potentially serious adverse interactions. RESULTS: There were 5,802 coprescription events for terfenadine and erythromycin and 150 coprescription events for terfenadine and ketaconazole. Rates per 100,000 terfenadine users demonstrated large declines about 18 months after initial regulatory action. Coprescription events of terfenadine with either erythromycin or ketaconazole continued to occur despite regulatory action. CONCLUSIONS: Results of this study suggest important roles for the pharmacist as a risk manager, disseminating information about newly published drug interactions. Both health providers and patients are audiences for the pharmacist's drug expertise. The delay in physician reaction to new information from pharmaceutical companies and the federal government suggests an early, strong role for the pharmacist in changing prescribing behavior.

Anti-Allergic Agents↗
PubMed2003

Analysis of erythromycin and benzoylperoxide in topical gels by liquid chromatography.

Gels containing a combination of erythromycin and benzoylperoxide are frequently used in the treatment of acne vulgaris. A method was developed to determine the content of both erythromycin and benzoylperoxide in these gels. Erythromycin was extracted from the gel in conditions where the oxidative power of benzoylperoxide was neutralised by addition of ascorbic acid and this extract was analysed on an Xterra RP(18) column, with a mobile phase containing acetonitrile-0.2 M K2HPO4-water (35:5:60, v/v/v). The detection wavelength was 215 nm. A second extraction procedure was developed for the analysis of benzoylperoxide. The extraction solution was analysed on a Hypersil C(18) BDS column and a mobile phase containing acetonitrile-water (58:42, v/v). Detection was performed at 254 nm. The flow rate was 1.0 ml/min in both methods. The selectivity, repeatability, linearity and recovery of both methods were examined. Special attention was given to determination of the recovery and the uncertainty on the recovery. This allowed evaluation of the bias of the extraction method. The method developed was used to examine the stability of a gel for topical use.

Administration, Topical↗
PubMed1989

A community outbreak of group A beta haemolytic streptococci with transferable resistance to erythromycin.

Erythromycin resistance amongst group A streptococci (GAS) in Great Britain is a relatively rare occurrence and outbreaks have been sporadically reported. Over an 8-month period in 1986 ten associated cases occurred in the town of Bridgewater in Somerset. Isolates were group A, type M4 and resistant to erythromycin (MIC 8 mg/l) but sensitive to lincomycin and clindamycin. Erythromycin resistance was transferable from all isolates to a group A recipient strain. No plasmid DNA could be detected in the original isolates or transconjugants.

Adult↗
PubMed2000

Kinetic studies on the interaction between a ribosomal complex active in peptide bond formation and the macrolide antibiotics tylosin and erythromycin.

The inhibition of peptide bond formation by tylosin, a 16-membered ring macrolide, was studied in a model system derived from Escherichia coli. In this cell-free system, a peptide bond is formed between puromycin (acceptor substrate) and AcPhe-tRNA (donor substrate) bound at the P-site of poly(U)-programmed ribosomes. It is shown that tylosin inhibits puromycin reaction as a slow-binding, slowly reversible inhibitor. Detailed kinetic analysis reveals that tylosin (I) reacts rapidly with complex C, i.e., the AcPhe-tRNA. poly(U).70S ribosome complex, to form the encounter complex CI, which then undergoes a slow isomerization and is converted to a tight complex, CI, inactive toward puromycin. These events are described by the scheme C + I <==> (K(i)) CI <==> (k(4), k(5)) CI. The K(i), k(4), and k(5) values are equal to 3 microM, 1.5 min(-1), and 2.5 x 10(-3) min(-1), respectively. The extremely low value of k(5) implies that the inactivation of complex C by tylosin is almost irreversible. The irreversibility of the tylosin effect on peptide bond formation is significant for the interpretation of this antibiotic's therapeutic properties; it also renders the tylosin reaction a useful tool in the study of other macrolides failing to inhibit the puromycin reaction but competing with tylosin for common binding sites on the ribosome. Thus, the tylosin reaction, in conjunction with the puromycin reaction, was applied to investigate the erythromycin mode of action. It is shown that erythromycin (Er), like tylosin, interacts with complex C according to the kinetic scheme C + Er <==> (K(er)) CEr <==> (k(6), k(7)) C*Er and forms a tight complex, CEr, which remains active toward puromycin. The determination of K(er), k(6), and k(7) enables us to classify erythromycin as a slow-binding ligand of ribosomes.

Anti-Bacterial Agents↗
PubMed2005

Accelerated transformation and deactivation of erythromycin in superheated water. 2. Transformation reactions and bioassays.

The work presented in this second part of a two-part series on the accelerated transformation of erythromycin in superheated water focuses on the chemical nature and resultant antimicrobial implications of the overall reaction observed. Analyses of reactor effluents employing infrared spectroscopy and liquid chromatography/mass spectrometry indicated that the initial step in the decomposition pathway is one of dehydration. Subsequent hydrolysis in the presence of an acetate buffer appeared to result in the loss of the sugar cladinose. Chemical transformation under superheated conditions was tied to the loss of antibiotic function by an agar dilution test. The sensitivity of this test was verified by determination of the minimum inhibitory concentration (MIC) of erythromycin corresponding to each of two test microorganisms. MIC values for the selected strains of Escherichia coli and Bacillus subtilis were 35 and 0.5 mg/L, respectively. To relate the loss of antimicrobial activity to increased reaction temperature and thus to increased extent of parent compound transformation to microbially benign intermediates, bioassays using E. coli as test microorganism were performed on flow reactor effluents resulting from reaction of initial erythromycin concentrations of 75-150 mg/L.

Amino Sugars↗
PubMed2002

Vitamin A metabolism is altered in brown Norway and long-Evans rats infused with naftidrofuryl or erythromycin intravenously.

Enzymatic retinyl ester hydrolysis is a key reaction for maintaining cellular retinol homeostasis. The ability of naftidrofuryl and erythromycin to inhibit retinol liberation by retinyl ester hydrolase (REH) in vitro suggests an ability to interfere with vitamin A metabolism in vivo, particularly during hepatic processing. To address this question, systemic and local response to these agents were studied in Brown Norway (BN) and Long-Evans (LE) rats. The study was conducted in two parts: a drug-loading phase and a washout phase. Analysis of variance of the time course changes in plasma retinol during the post-treatment period (Days 10-18) showed rat strain (p < 0.04) and time (p < 0.001; strain-by-time interactive effect, p < 0.001) to be significant factors, but drug exposure (p = 0.19) was not significant. Endpoints included hepatic REH activity, size and composition of the liver vitamin A stores, and retinoid content of the kidneys. Rats recovering from naftidrofuryl dosing demonstrated a lower REH activity than did animals recovering from erythromycin treatment (p < 0.009). The major side effect of erythromycin is vitamin A accumulation in the liver (p < 0.001) and reductions in retinol reserves (p < 0.02) were among the consequences of naftidrofuryl treatment. In the kidney of LE rats, there were higher concentrations of vitamin A (p < 0.003) secondary to naftidrofuryl exposure. Together our data suggest that clinically achievable concentrations of the drugs, given as a continuous infusion, produce aberrations in vitamin A metabolism.

Animals↗
PubMed1983

Effect of erythromycin on carbamazepine kinetics.

Two recent reports of carbamazepine-induced intoxication during concurrent therapy with macrolide antibiotics prompted us to perform a carefully controlled two-way cross-over study in eight healthy male nonsmokers. Treatment A was 250 mg erythromycin every 6 hr for 5 days before and 3 days after 400 mg carbamazepine. Treatment B was 400 mg of carbamazepine alone. One half of the subjects received treatment A, then B, while the other half received treatment B, then A. There was a 4-wk washout period between treatments. Plasma samples obtained at various times up to 72 hr after the carbamazepine dose were assayed in duplicate by HPLC. The data were fit to a one-compartment open model with first-order absorption and elimination. Clearance of oral carbamazepine was lower in the presence of erythromycin (mean +/- SD, 0.290 +/- 0.074 and 0.360 +/- 0.072 1 X kg-1 X day-1). There were no differences in apparent volume of distribution (1.01 +/- 0.20 and 1.04 +/- 0.12 1 X kg-1), elimination rate constant (0.302 +/- 0.113 and 0.348 +/- 0.079 day-1), or absorption rate constant (14.5 +/- 8.7 and 15.5 +/- 16.6 day-1) between the two treatment groups. The decrease in clearance of oral carbamazepine secondary to erythromycin indicates that further clinical studies are warranted.

Adult↗
PubMed2000

Improvement in bronchiolitis obliterans organizing pneumonia in a child after allogeneic bone marrow transplantation by a combination of oral prednisolone and low dose erythromycin.

We report a 13-year-old boy who developed dyspnea at rest 1 year after the occurrence of cGVHD following an allogeneic bone marrow transplant (BMT). Pulmonary function data, imaging studies, lung biopsy, and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). Although reports suggest that oral methylprednisolone or methylprednisolone pulse therapies improve BOOP after BMT, we treated our patient with a combination of oral prednisolone (1 mg/kg) and low dose erythromycin (10 mg/kg) to avoid the side-effects of high-dose steroids. With this therapy, our patient showed clinical and radiological improvements within 1 week. The steroids were tapered off 12 months later and erythromycin was given for 14 months. We conclude that therapy consisting of a combination of oral prednisolone and low-dose erythromycin for BOOP after BMT may minimize the dose and duration of steroid use.

Administration, Oral↗
PubMed2006

Erythromycin and feeding intolerance in premature infants: a randomized trial.

OBJECTIVES: To evaluate the effectiveness of low-dose oral erythromycin to treat feeding intolerance in preterm infants. DESIGN: This study was a prospective, double-blind, randomized, placebo-controlled trial on 60 premature infants suffering from feeding intolerance. Thirty infants were given oral erythromycin 1 mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization was stratified on enrollment according to gestational age whether >32 weeks or 32 weeks, the erythromycin group achieved full enteral feeding earlier than placebo group (10.5+/-4.1 vs 16.3+/-5.7 days, respectively; P=0.01) had fewer episodes of gastric residuals (P<0.05) and shorter duration of parenteral nutrition (PN) (P<0.05). On the other hand, in infants with gestational age 32 weeks gestation. A similar effect on younger preterm infants was not demonstrable.

Anti-Bacterial Agents↗
PubMed2006

Determination of the stereochemistry of anhydroerythromycin A, the principal degradation product of the antibiotic erythromycin A.

Anhydroerythromycin A arises from the acid-catalysed degradation of erythromycin A both in vitro and in vivo. It has negligible antibacterial activity, but inhibits drug oxidation in the liver, and is responsible for unwanted drug-drug interactions. Its structure has 18 chiral centres common with erythromycin A, but C-9 (the spiro carbon) is also chiral in anhydroerythromycin and its stereochemistry has not previously been reported; both 9R- and 9S-anhydroerythromycin A are plausible structures. An understanding of the chirality at C-9 was expected to throw light on the mechanism of acid-catalysed degradation of erythromycin A, a subject that has been debated in the literature over several decades. We now report a determination of the three-dimensional structure of anhydroerythromycin A, including the stereochemistry at C-9, by NMR and molecular modelling. In parallel, the relative stereochemistry of anhydroerythromycin A 2'-acetate was determined by X-ray crystallography. Both compounds were shown to have 9R stereochemistry, and anhydroerythromycin A exhibited considerable conformational flexibility in solution.

Erythromycin↗
PubMed1999

Erythromycin derivatives ABT 229 and GM 611 act on motilin receptors in the rabbit duodenum.

1. The present study was undertaken to determine whether the macrolide antibiotic erythromycin, its stable motilide derivatives ABT 229 and GM 611 and motilin act at the same receptors on intestinal muscle 2. Each compound contracted the longitudinal muscle of the rabbit duodenum in a concentration-dependent manner that was unaffected by 1 mumol/L tetrodotoxin. The potency order (pEC50 values in brackets) was motilin (8.4), ABT 229 (7.6), GM 611 (7.5) and erythromycin (6.0). 3. The motilin receptor antagonists GM 109 and [phe3, leu13]-motilin, both shifted the concentration-response curves for each agonist to the right, but did not affect concentration-response relationships for the muscarinic agonist carbachol. Schild regression analysis yielded similar pA2 values for GM 109 (in the range 7.2-7.5) for all agonists. This analysis was not done for [phe3, leu13]motilin, which was a non-competitive antagonist and partial agonist. 4. It is concluded that erythromycin, the motilides and motilin act at the same (motilin) receptor on rabbit duodenal muscle and do not have any detectable actions at other receptors in this preparation.

Animals↗
PubMed2001

Risk of torsades de pointes from oral erythromycin with concomitant carbimazole (methimazole) administration.

There are many reports of intravenous erythromycin causing QT prolongation and torsades de pointes, but this complication is seldom ascribed to orally administered erythromycin, which is by far the most commonly prescribed route. This report describes a case of torsades de pointes associated with oral erythromycin as a result of a previously undescribed interaction with carbimazole, an antithyroid drug that is metabolized to the active drug methimazole, and the potential pharmacokinetic and pharmacodynamic mechanisms are highlighted.

Administration, Oral↗
PubMed2002

Erythromycin susceptibility of viridans streptococci from the normal throat flora of patients treated with azithromycin or clarithromycin.

OBJECTIVE: To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin. METHODS: Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance. RESULTS: There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mefA/E in isolates with low-level resistance and ermA/M in isolates with high-level resistance. CONCLUSIONS: There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.

Anti-Bacterial Agents↗
PubMed1996

[Treatment of radiotherapy-induced gastroparesis with erythromycin].

HISTORY: A 75-year-old woman who had undergone a hysterectomy with adnexectomy followed by radiotherapy for endometrial carcinoma complained of postprandial nausea with vomiting after eating solid foods and of cramp-like abdominal pain, but her appetite was good. She had lost 25 kg in weight over 13 months. EXAMINATION: Physical examination, laboratory tests, radiology and gastroscopy were unremarkable. Gastric scintigraphy showed abnormally prolonged emptying. TREATMENT AND COURSE: Nausea and vomiting stopped at once after erythromycin (a motilin agonist) had been administered. It was at first given intravenously after meals (50 mg three times daily for 5 days), then orally for 10 weeks (250 mg three times daily before meals). Subsequent examination revealed normal gastric emptying. The symptoms did not recur after erythromycin had been discontinued. CONCLUSION: Erythromycin is an effective drug against gastroparesis caused by radiotherapy, because it acts even when the enteric nerves are damaged.

Aged↗