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PubMed2004

Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Lemna minor.

Pharmaceutically active substances have recently been recognised as an emerging environmental problem. Human and veterinarian therapeutic agents can contaminate aquatic ecosystems via sewage discharges (human and animal excretion), improper disposal or industrial waste. Very little is known on the effects of pharmaceutical pollutants on aquatic photosynthetic organisms. In this study the effects of erythromycin, tetracycline and ibuprofen on the growth of the cyanobacterium Synechocystis sp. PCC6803 and the duckweed Lemna minor FBR006 were studied at concentrations of 1-1000 microg l(-1). At dosage of 1 mg l(-1), erythromycin affected the growth of both Synechocystis and Lemna with a maximum inhibition of 70 and 20%, respectively. Tetracycline had inhibitory effects (20-22% reduction in growth) on Synechocystis at intermediate dosages. The same aminoglycoside antibiotic promoted growth in Lemna by 26% at 10 microg l(-1), while frond development was reduced at 1 mg l(-1) (tetracycline). The anti-inflammatory ibuprofen strongly stimulated the growth of Synechocystis at all concentrations tested (72% increase at 10 microg l(-1)) although inhibited Lemna in a linear dose-dependent manner with a 25% reduction over control levels at a dosage of 1 mg l(-1). The 7 days effective concentration (EC(50)) calculated for Lemna were 5.6, 1 and 4 g l(-1), respectively, for erythromycin, tetracycline and ibuprofen. Moreover, exposure to the three pharmaceuticals resulted in the production of the stress hormone, abscisic acid (ABA), in Lemna. Erythromycin and tetracycline were more effective in promoting ABA synthesis compared to ibuprofen. The effects shown by the three therapeutic drugs on Synechocystis and Lemna growth may have potential implications in the assessments of residual environmental risks associated with the presence of pharmaceuticals in freshwater ecosystems. Promotion of ABA synthesis in Lemna by the two antibiotics and by copper suggests that the plant hormone could be a suitable (additional) indicator for future evaluation of phytotoxicity that results in plant senescence.

Abscisic Acid↗
PubMed2006

Erythromycin block of the HERG K+ channel: accessibility to F656 and Y652.

The HERG potassium channel might have a non-canonical drug binding site, distinct from the channel's inner cavity, that could be responsible for elements of closed-state pharmacological inhibition of the channel. The macrolide antibiotic erythromycin is a drug that may block unconventionally because of its size. Here we used whole-cell patch-clamp recording at 37 degrees C from heterologously expressed HERG channels in a mammalian cell line to show that erythromycin either produces a rapid open-state-dependent HERG channel inhibition, or components of both open-state-dependent and closed-state-dependent inhibition. Alanine-substitution of HERG's canonical determinants of blockade revealed that Y652 was not important as a molecular determinant of blockade, and that mutation of F656 resulted in only weak attenuation of inhibition. In computer models of the channel, erythromycin could make several direct contacts with F656, but not with Y652, in the open-state model, and erythromycin was unable to fit into a closed-state channel model.

Cell Line↗
PubMed2004

Use of erythromycin for nonsurgical female sterilization in West Bengal, India: a study of 790 cases.

OBJECTIVE: Determine if erythromycin is an effective agent for achieving occlusion of the Fallopian tube for nonsurgical female sterilization. METHODS: Two studies of 100 healthy volunteers requesting sterilization were planned, one in Julpia Andhermanik and the other in Kolkata (Calcutta). A readily available marketed tablet preparation containing 500 mg of the estolate salt of erythromycin was used for the trial. In one study (Bishnupur), the tablet was crushed before placing in a copper-T IUD inserter for placement at the fundus. In the other study (Kolkata), crushed tablets were processed into 50 mg pellets of the same diameter as standard quinacrine pellets and 10 pellets were inserted at the fundus using aseptic precautions. Procedures in each study were repeated at 30 days. Oral contraceptives were prescribed for three cycles following first insertion. No incentive was offered for participation in the trial. Follow-up treatment, including first-trimester abortion for pregnancy due to failure of the sterilization procedure, was assured without charge. Due to extraordinary patient demand, one study (Bishnupur) was expanded to 690 cases for reasons of compassion. RESULTS: At 12 months of use, the failure rate of the sterilization procedure for the crushed 500 mg tablets was 35.8% (SE = 1.8) with 417 women at risk. At 12 months of use, the failure rate for the erythromycin pellets was 28.6% (SE = 5.0) with 43 women at risk. There were no serious complications reported in either trial. All pregnancies resulting from failure of the sterilization procedure were terminated by menstrual regulation within 10 weeks gestation. CONCLUSIONS: The failure rate in this study is unacceptably high for erythromycin to be used as a sterilization method.

Erythromycin↗
PubMed2004

In vivo activity of amoxicillin/clavulanic acid and erythromycin in experimental otitis media caused by Streptococcus pneumoniae plus Haemophilus influenzae.

A gerbil model of acute otitis media induced by Streptococcus pneumoniae plus Haemophilus influenzae was used to assess the efficacy of amoxicillin/clavulanic acid (A/C) (1.5/0.3, 2.5/0.5 and 10/2 mg/kg) and erythromycin (2.5, 10, 20 and 50 mg/kg) with or without acetaminophen. The amoxicillin/clavulanic acid MIC was 1/0.5 mg/l for both organisms and the erythromycin MICs were 0.12 and 4 mg/l for S. pneumoniae and H. influenzae, respectively. The organisms were inoculated directly into the middle ear (ME) and antibiotic treatment started 2 h post-inoculation and continued at 8h intervals for three doses. Acetaminophen was administered at 50 mg/kg. Samples for bacterial counting were obtained from the ME on day 2. Amoxicillin/clavulanic acid peri-MIC concentrations in ME were effective in eradicating both organisms. Despite the inflammation induced by S. pneumoniae, erythromycin did not eradicate H. influenzae at ME concentrations (2.4 mg/l for erythromycin 50 mg/kg) higher than those obtained in humans but lower than the MIC.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2004

Relative contribution of target gene mutation and efflux to fluoroquinolone and erythromycin resistance, in French poultry and pig isolates of Campylobacter coli.

Thirty-eight avian and swine French isolates of Campylobacter coli were studied for their mechanisms of co-resistance to fluoroquinolones and erythromycin. A Thr86Ile modification of GyrA, responsible for fluoroquinolone resistance, was found in all the strains. Two different levels of resistance to erythromycin (MIC of 8-16 or >/=256 mg/l) were observed. A A2075G mutation in the 23S rRNA genes was found only in the highly-resistant strains. Phe-Arg-beta-naphthylamide, an efflux pump inhibitor, potentiated erythromycin in all the strains examined but restored susceptibility only in the strains with a low-level of resistance. This suggests the involvement of efflux in intrinsic and in acquired low-level of resistance to erythromycin in C. coli.

Amino Acid Substitution↗
PubMed2005

Erythromycin resistance in the commensal throat flora of patients visiting the general practitioner: a reservoir for resistance genes for potential pathogenic bacteria.

The prevalence and mechanism of erythromycin resistance in commensal throat streptococci was determined from October 2000 until December 2002 as part of an ongoing study of the NIVEL in general practice patients (N=678). Resistance prevalence for 1mg/L and 16 mg/L erythromycin was 57% and 20%, respectively. The percentage of total commensal flora resistant within each patient ranged from 1% to 100% (median, 1%). mefA was predominantly found among isolates on the 1mg/L plates, and ermB was found in 64% of the isolates on the 16 mg/L plates. Erythromycin resistance was transferred from a commensal isolate to Streptococcus pneumoniae with a frequency of 1 x 10(-9). Commensal streptococci of general practice patients in The Netherlands form a large reservoir of transferable erythromycin resistance (genes) for potential pathogenic microorganisms.

Anti-Bacterial Agents↗
PubMed2005

Investigation of erythromycin and tetracycline resistance genes in methicillin-resistant staphylococci.

In this study, erythromycin [erm(A) and erm(C)] and tetracycline [tet(K) and tet(M)] resistance genes were investigated by multiplex polymerase chain reaction (PCR) in a total of 56 methicillin-resistant (mecA+) staphylococcal hospital isolates, 28 of which were determined to be Staphylococcus aureus (MRSA) and the other 28 were coagulase-negative staphylococci (MRCNS). Internal control primers amplifying a specific fragment of 16S rDNA of staphylococci were included in the multiplex PCR protocol to ensure the efficacy of amplification and to determine any PCR inhibition. No resistance genes were detected in 5 of 56 (8.9%) isolates in the study. In the study, tet(K) genes were detected widely (42.9%) in MRCNS, whilst tet(M) genes were detected in MRSA (50.0%). Regarding the erythromycin resistance genes, whilst erm(A) genes were detected in most (71.4%) MRSA isolates, detection rates of erm(C) genes were the same (64.3%) both in MRCNS and MRSA. The resistance rates for tetracycline and erythromycin were 57.1% and 78.6%, respectively, in MRSA isolates. In conclusion, in this study, the multiplex PCR technique including an internal control is shown to be a fast, sensitive, reliable, practical, reproducible and economic technique for the detection of erythromycin and tetracycline resistance in staphylococcal isolates.

Bacterial Proteins↗
PubMed2005

Investigation of degradation products in a topical gel containing erythromycin and benzoyl peroxide by liquid chromatography-mass spectrometry.

Benzamycin, combining benzoyl peroxide and erythromycin, is a topical gel used in the treatment of acne vulgaris. Because of the reactivity of benzoyl peroxide, preparations containing both erythromycin and benzoyl peroxide might be unstable and degradation products could be formed. To investigate and identify these latter products, a gradient-based liquid chromatographic method using volatile mobile phase constituents was developed. Mass spectrometry data were acquired on solutions containing erythromycin and benzoyl peroxide and on freshly prepared, 2-month-old and 18-month-old samples of Benzamycin. With the reference spectra as interpretative templates, it was concluded that erythromycin undergoes oxidation, followed by benzoylation.

Benzoyl Peroxide↗
PubMed2004

A multicenter, randomized, double-blind, placebo-controlled trial of the prokinetic agent erythromycin in the postoperative recovery of infants with gastroschisis.

BACKGROUND/PURPOSE: The recovery of gut function after repair of gastroschisis is frequently prolonged, and these infants are prone to complications associated with parenteral nutrition. This trial was designed to investigate the effect of the prokinetic agent, erythromycin, on the attainment of full enteral feeding in infants after primary repair of uncomplicated gastroschisis. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was used to investigate the effect of enteral erythromycin (3 mg/kg/dose 4 times daily) compared with placebo on the attainment of full enteral feeding tolerance after primary repair of uncomplicated gastroschisis. Eleven neonatal surgical units in the United Kingdom participated in the study. The primary end-point was the time taken to achieve continuous enteral feeding at 150 mL/kg/24 hours sustained for 48 hours. RESULTS: Of 70 eligible infants, 62 were recruited and randomly divided. There were 30 patients in group I (placebo) and 32 in group II (erythromycin). The groups were comparable in terms of mean gestational age, mean birth weight, extent of evisceration, and degree of intestinal peel. There was no statistically significant difference between the 2 groups in the time taken to achieve full enteral feeding (27.2 v 28.7 days; P =.75). Similarly, no significant differences were found in the incidence of catheter-related sepsis, duration of parenteral nutrition, or time to discharge between the 2 groups. CONCLUSIONS: Enterally administered erythromycin at a dose of 3 mg/kg 4 times daily conferred no advantage in the time taken to achieve full enteral feeding after primary repair of uncomplicated gastroschisis.

Double-Blind Method↗
PubMed2005

MAMA-PCR assay for the detection of point mutations associated with high-level erythromycin resistance in Campylobacter jejuni and Campylobacter coli strains.

Twenty Campylobacter jejuni and 16 Campylobacter coli strains isolated from humans and food/animals, including 17 isolates resistant to erythromycin, were analyzed. A combined mismatch amplification mutation assay-PCR technique was developed to detect the mutations A 2074 C and A 2075 G in the 23S rRNA gene associated with erythromycin resistance. All high-level erythromycin-resistant strains examined by DNA sequencing carried the transition mutation A 2075 G, whereas no isolate carried the A 2074 C mutation. No mutations were found among the susceptible and low-level erythromycin-resistant strains.

Animals↗
PubMed2004

Protective role of tetrahydrocurcumin against erythromycin estolate-induced hepatotoxicity.

Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, was investigated for its possible hepatoprotective effect in Wistar rats against erythromycin estolate-induced toxicity. Oral administration of THC significantly prevented the occurrence of erythromycin estolate-induced liver damage. The increased level of serum enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)), bilirubin, cholesterol, triglycerides, phospholipids, free fatty acids and plasma thiobarbituric acid reactive substances (TBARS) and hydroperoxides observed in rats treated with erythromycin estolate were very much reduced in rats treated with THC and erythromycin estolate. This biochemical observation were supplemented by histopathological examination of liver section. Results of this study revealed that THC could afford a significant protection against erthromycin estolate-induced hepatocellular damage. Tetrahydrocurcumin had a better protective effect when compared with Silymarin, a reference drug.

Administration, Oral↗
PubMedDate not supplied

Is erythromycin therapy teratogenic in humans?

The possible teratogenic effect of erythromycin therapy, noted previously, was studied. Women who had taken erythromycin or penicillin V in early pregnancy and their infants were studied, using the Swedish Medical Birth Register where information on drug use during pregnancy was recorded based on interviews in early pregnancy. The risk for any congenital malformation after erythromycin therapy (but not after penicillin V therapy) was increased (odds ratio 1.24, 95% confidence interval: 1.01-1.51) and this was due to an effect on cardiovascular malformations (odds ratio 1.92, 95% CI: 1.37-2.68). There was also an indicated increased risk for pyloric stenosis (risk ratio 3.0, 95% CI: 1.1-8.5 after exposure in early pregnancy). Various explanations to the finding are discussed, one of them linked to the fact that erythromycin inhibits a specific cardiac potassium channel (IKr) which seems to play a major role in cardiac rhythm regulation in the early embryo. Potent blocking drugs cause as a class effect cardiac defects in animal experiments.

Adult↗
PubMed2006

Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: a pharmacodynamic drug interaction.

Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists.

Animals↗
PubMed1996

The effects of menopause and hormone replacement therapies on prednisolone and erythromycin pharmacokinetics.

The pharmacokinetics of oral and intravenous prednisolone and intravenous erythromycin were examined in premenopausal women, postmenopausal women not undergoing hormone replacement therapy, postmenopausal women undergoing estrogen replacement therapy, and postmenopausal women undergoing estrogen and progestin replacement therapy. The unbound clearance of prednisolone was significantly lower in postmenopausal women (11.6 +/- 2.3 ml/min/kg) than in premenopausal women (16.6 +/- 3.5 ml/min/kg). A comparable difference was also observed in total clearance and in half-life. The bioavailability and volume of distribution of prednisolone were unaffected by menopausal status. Hormone replacement therapies did not significantly affect prednisolone pharmacokinetics. In contrast to prednisolone elimination, erythromycin elimination, as measured by the erythromycin breath test, was not significantly affected by either menopausal status or hormone replacement therapy. In addition, there was no correlation between prednisolone clearance and the erythromycin breath test result. Although cytochrome P450 3A4 (CYP3A4) has been implicated in steroid hormone metabolism, these results suggest that another enzyme system, which is decreased in menopause (rather than simply an age effect), is also involved in prednisolone metabolism.

Adult↗
PubMed2002

Limited induction of torsade de pointes by terikalant and erythromycin in an in vivo model.

The proarrhythmic activities of the selective I(Kr) blocker erythromycin and the less selective K(+) channel blockers, terikalant and clofilium, have been compared in an alpha(1)-adrenoceptor-stimulated, anaesthetized rabbit model. Terikalant (2.5, 7.5 and 25 nmol kg(-1) min(-1); n = 10), erythromycin (133, 400 and 1330 nmol kg(-1) min(-1); n = 8), clofilium (20, 60 and 200 nmol kg(-1) min(-1); n=10) or vehicle (n = 8) was infused intravenously over 19 min and there was a 15-min interval between each infusion [corrected]. QT and QTc intervals, and epicardial monophasic action potential duration were prolonged significantly (and to a similar extent) only by clofilium and terikalant. The total incidences of torsade de pointes were 60%*, 20%, 0% and 0% in clofilium-, terikalant-, erythromycin- and vehicle-treated animals, respectively (*P < 0.05 compared to vehicle control). In conclusion, terikalant exerted mild proarrhythmic activity though it prolonged repolarisation markedly. Despite being given in high doses, erythromycin neither prolonged repolarisation nor induced proarrhythmia.

Action Potentials↗
PubMed2003

Synthesis of two and antibacterial activity of one novel oxime ether derivatives of erythromycin A.

The synthesis of novel erythromycin A 9-O-(2-ethenesulfony-ethyl)-oxime and erythromycin A 9-O-(3-oxo-butyl)-oxime from erythromycin A (EA) by the Michael reaction is described and to describe the effects of transformation of ketone in position 9 of EA to an oxime ether. This transformation occurred in a single step without protecting of any functional moiety of erythromycin oxime and zero waste manner in good yield. The antibacterial screen of EA 9-O-(2-ethenesulfony-ethyl)-oxime is also reported.

Anti-Bacterial Agents↗
PubMed1998

Effect of motilin and erythromycin on calcium-activated potassium channels in rabbit colonic myocytes.

BACKGROUND & AIMS: Motilin and erythromycin are prokinetic agents that act on the same receptor in gastrointestinal smooth muscle to cause contraction. Both agonists may also cause an increase in outward current. The aim of this study was to determine whether motilin and erythromycin activate calcium-activated potassium (KCa) channels. METHODS: Freshly dispersed longitudinal smooth muscle cells of the rabbit colon were used to measure whole-cell outward current and single-channel activity using patch clamp recording methods. RESULTS: Erythromycin and motilin increased a calcium-dependent outward potassium current and increased the open probability of KCa channels of cell- attached patches. CONCLUSIONS: Erythromycin and motilin activate KCa channels via an intracellular second messenger system. This effect may modulate the increase in contractility caused by these agonists.

Animals↗
PubMed2002

L22 ribosomal protein and effect of its mutation on ribosome resistance to erythromycin.

The ribosomal protein L22 is a core protein of the large ribosomal subunit interacting with all domains of the 23S rRNA. The triplet Met82-Lys83-Arg84 deletion in L22 from Escherichia coli renders cells resistant to erythromycin which is known as an inhibitor of the nascent peptide chain elongation. The crystal structure of the Thermus thermophilus L22 mutant with equivalent triplet Leu82-Lys83-Arg84 deletion has been determined at 1.8A resolution. The superpositions of the mutant and the wild-type L22 structures within the 50S subunits from Haloarcula marismortui and Deinococcus radiodurans show that the mutant beta-hairpin is bent inward the ribosome tunnel modifying the shape of its narrowest part and affecting the interaction between L22 and 23S rRNA. 23S rRNA nucleotides of domain V participating in erythromycin binding are located on the opposite sides of the tunnel and are brought to those positions by the interaction of the 23S rRNA with the L22 beta-hairpin. The mutation in the L22 beta-hairpin affects the orientation and distances between those nucleotides. This destabilizes the erythromycin-binding "pocket" formed by 23S rRNA nucleotides exposed at the tunnel surface. It seems that erythromycin, while still being able to interact with one side of the tunnel but not reaching the other, is therefore unable to block the polypeptide growth in the drug-resistant ribosome.

Crystallography, X-Ray↗