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Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci.

OBJECTIVE: Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth. STUDY DESIGN: In a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy. RESULTS: Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance. CONCLUSIONS: In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.

Adult↗

Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones.

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.

Administration, Oral↗

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.

Adult↗

Motilin and erythromycin stimulate pepsinogen secretion by chief cells isolated from guinea pig stomach.

BACKGROUND: Motilin and erythromycin bind the same receptor in the gastrointestinal muscle cells. Motilin stimulates pepsinogen secretion in humans and dogs. However, it is unclear whether it acts directly on gastric chief cells or via other neurotransmitters. METHODS: Isolated gastric chief cells were obtained from guinea pig stomach by collagenase digestion and calcium chelation with ethylene glycol-bis(B-amynomethyl ether)-N,N,N',N'-tetraacetic acid. RESULTS: Significant stimulation of pespinogen secretion induced by motilin occurred at 1 pmol/L, half maximum at 10 pmol/L, and maximum at 100 pmol/L. Erythromycin caused significant stimulation at 1 pmol/L, half maximum at 100 pmol/L, and maximum at 1 nmol/L. Atropine (1 mumol/L) had no effect on either motilin- or erythromycin-induced pepsinogen secretion. Motilin and erythromycin determined a threefold increase in the intracellular calcium concentrations. Pretreatment of isolated chief cells with motilin and erythromycin induced a reversible, dose- and time-dependent desensitization of the pepsinogen secretion stimulated by carbachol and cholecystokinin but not that stimulated by secretin, vasoactive intestinal peptide, or prostaglandin E2. CONCLUSIONS: Motilin and erythromycin directly stimulate pepsinogen secretion in isolated chief cells.

Animals↗

Erythromycin-induced stabilization of ermA messenger RNA in Staphylococcus aureus and Bacillus subtilis.

Erythromycin-induced stabilization of ermA mRNA was studied in Staphylococcus aureus, its original host background, and in Bacillus subtilis, subcloned on plasmid vectors. By RNA blot analysis it was shown that 40 nM-erythromycin specifically increased the chemical half-life of ermA mRNA from 2.5 to 17.5 minutes whereas the half-life of cat-86 mRNA was not increased by erythromycin. While expression of ermA has been shown to be induced by erythromycin at the level of translation, our studies with three ermA constitutive mutants demonstrated that mRNA stabilization in growing cells occurred independently of induced gene expression, suggesting that the stabilized mRNA was not functional for protein synthesis. Studies of ermA/lacZ fusions demonstrated that the 5' end of the mRNA was sufficient to confer stabilization. Translation of specific amino acid codons in a leader peptide located at the extreme 5' end of the mRNA was required for the erythromycin-induced stabilization as a frameshift mutation introduced into the leader peptide determinant abolished stabilization. By S1 mapping, no differences were detected in the length of the 5' or 3' end of ermA mRNA with the addition of erythromycin, indicating that the stabilized transcript was not processed at its ends.

Bacillus subtilis↗

Defining the structural requirements for a helix in 23 S ribosomal RNA that confers erythromycin resistance.

The helix spanning nucleotides 1198 to 1247 (helix 1200-1250) in Escherichia coli 23 S ribosomal RNA (rRNA) is functionally important in protein synthesis, and deletions in this region confer erythromycin resistance. In order to define the structural requirements for resistance, we have dissected this region using in vitro mutagenesis. Erythromycin resistance is established after a minimal deletion of three bases, CAU1231 or AUG1232. The maximum deletion observed to confer resistance is 25 bases. The level of erythromycin resistance conferred by intermediate sized deletions is variable and some deletion mutants show a sensitive phenotype. Deletions that extend into the base-pairing between GCC1208 and GGU1240 result in non-functional 23 S RNAs, which consequently do not confer resistance. A number of phylogenetically conserved nucleotides have been shown to be non-essential for 23 S RNA function. However, removal of either these or non-conserved nucleotides from helix 1200-1250 measurably reduces the efficiency of 23 S RNA in forming functional ribosomes. We have used chemical probing and a modified primer extension method to investigate erythromycin binding to wild-type and resistant ribosomes with a 12-base deletion in 23 S RNA. Erythromycin interacts as strongly with mutant 23 S RNA as with wild-type 23 S RNA. Deletions in the 1200-1250 helix do not therefore confer resistance by reducing erythromycin binding, but by suppressing the effects of the drug at the level of its mechanism of action.

Base Sequence↗

Amoxicillin or erythromycin for the treatment of antenatal chlamydial infection: a meta-analysis.

OBJECTIVE: To compare the effectiveness of amoxicillin and erythromycin for the treatment of antenatal Chlamydia trachomatis infection by meta-analysis of available trials involving random assignment of subjects. DATA SOURCES: A computer search of English-language abstracts using MEDLINE and the Cochrane Pregnancy and Childbirth Database (medical subject heading terms: pregnancy, chlamydia, erythromycin, amoxicillin, antenatal antibiotics) was supplemented with a review of the bibliographies of the relevant articles generated by the computer search. METHODS OF STUDY SELECTION: Five trials were identified, four of which met our inclusion criteria for the meta-analysis. DATA EXTRACTION AND SYNTHESIS: Trials to be included in this meta-analysis underwent trial quality evaluation and data abstraction. An estimate of the relative risk (RR) was calculated for the dichotomous outcomes using a fixed-effects model. The pooled RR for the effectiveness of amoxicillin compared with erythromycin was 1.11 (95% confidence interval [CI] 1.05-1.18), and the pooled RR for gastrointestinal side effects of amoxicillin compared with erythromycin was 0.29 (95% CI 0.20-0.42). The pooled RR for gastrointestinal side effects that resulted in discontinuation of therapy of amoxicillin compared with erythromycin was 0.14 (95% CI 0.06-0.36). CONCLUSION: The available data suggest that amoxicillin is more effective than erythromycin for the treatment of antenatal C trachomatis infection and has fewer gastrointestinal side effects, leading to better compliance.

Amoxicillin↗

Distribution of intramuscularly administered erythromycin into subcutaneous tissue chambers before and after inoculation with Pasteurella haemolytica.

Distribution of erythromycin into subcutaneous tissue chambers was characterised pharmacokinetically and the effect of Pasteurella haemolytica infection on the extent of penetration was studied. Thermoplastic tissue chambers were implanted subcutaneously in the paralumbar fossae of six calves. Thirty-five days after implantation, the tissue chamber distribution of intramuscularly administered erythromycin (30 mg kg-1) was studied. Chambers were then inoculated with P haemolytica and the tissue chamber pharmacokinetics of erythromycin were again studied. Diffusion of erythromycin into tissue chambers was best described using a two-compartment model with tissue chambers representing a relatively inaccessible compartment. Despite changes in chamber fluid pH, the extent of erythromycin penetration into chambers was not affected by P haemolytica inoculation. Comparison of computer simulated concentration-time curves resulting from different routes of administration revealed that penetration of erythromycin into less accessible sites was more likely to be higher after intravenous administration than after intramuscular administration.

Animals↗

Comparative trial of erythromycin and sulphatrimethoprim in the treatment of tetracycline-resistant Vibrio cholerae O1.

The efficacy of the 2 antimicrobial compounds, erythromycin and trimethoprim-sulphamethoxazole, were compared in the treatment of the clinical symptoms of cholera and the eradication of Vibrio cholerae O1 organisms from the stools of patients infected with tetracycline-resistant strains. 47 patients with a clinical diagnosis of cholera, without prior antibiotic therapy, were included in the trial and received either erythromycin, trimethoprim-sulphamethoxazole, or a placebo twice daily. The mean number of vibrios per gram of stool decreased from 5.2 x 10(8) +/- 0.3 per ml to 0 within 36 h of admission following either erythromycin or trimethoprim-sulphamethoxazole therapy, while organisms persisted in placebo-treated controls for more than 7 d. Clinically there was a significant reduction in the number of diarrhoeal stools per day and duration of diarrhoea in the erythromycin-treated group compared with the placebo-treated controls. During the study an isolate resistant to trimethoprim-sulphamethoxazole but sensitive to erythromycin was obtained. As an adjunct to oral rehydration therapy, erythromycin may serve as an effective alternative treatment for cholera, especially in areas where trimethoprim-sulphamethoxazole resistance may be emerging.

Adolescent↗

A clinical trial comparing the safety and efficacy of a topical erythromycin-zinc formulation with a topical clindamycin formulation.

One hundred three patients with acne vulgaris were randomly designated to receive either a topical formulation of erythromycin plus zinc or a topical solution of 1% clindamycin phosphate (Cleocin-T). The patients treated themselves twice daily and were examined at 3, 6, 9, and 12 weeks after the start of therapy. By week 6 the overall severity grade was consistently lower and the percent reduction of severity, papules, pustules, and total comedones was higher in the erythromycin-zinc-treated group than in the clindamycin-treated group. In the 92 patients who completed this study (48 receiving erythromycin-zinc and 44 receiving clindamycin), no serious topical or systemic side effects were reported. Two patients, one from each treatment group, suffered mild irritation. One patient was withdrawn from the erythromycin-zinc-treated group. Results of patch tests were negative. The superiority of the erythromycin-zinc formulation may be due to the increased (4%) erythromycin concentration and/or the ability of 1.2% zinc acetate to enhance the product's activity.

Acne Vulgaris↗

Drug resistance of Enterococcus faecium clinical isolates and the conjugative transfer of gentamicin and erythromycin resistance traits.

Drug resistance and the transferability of resistance were examined in 218 Enterococcus faecium clinical isolates obtained from in-patients of a Japanese university hospital between 1990 and 1999. One hundred and sixty one isolates (73.9%) were drug-resistant and 127 (58.2%) isolates were resistant to two or more drugs. Vancomycin resistant E. faecium (VRE) was not isolated. The transferability of drug-resistance to an E. faecium strain was examined by broth or filter mating. Six (12.5%) of the 48 gentamicin resistance traits, and fifty (50%) of the 101 erythromycin resistance traits were transferred by filter mating. The gentamicin resistance traits of five isolates and the erythromycin resistance traits of four isolates were transferred to the recipient strains by both broth mating and filter mating at a frequency of about 10(-6) and 10(-5) per donor cell, respectively. The five gentamicin resistant strains were shown to harbor pMG1-like plasmids on the basis of their Southern hybridization with pMG1 (65.1 kbp, Gm(r)), which transfers efficiently between enterococci by broth mating. Each of the four erythromycin resistant transconjugants obtained by broth mating harbored a large conjugative plasmid (more than 100 kbp). The plasmids showed no homology with well-characterized enterococcal conjugative plasmids such as pAD1, pPD1, pAM(beta)1, pIP501 and pMG1 by Southern hybridization. Of the erythromycin resistance traits that transferred only by filter mating, it was found that the erythromycin resistance trait was conferred by a 47-kbp transposable element that transferred from the chromosome of the donor strain to different sites within the pheromone responsive plasmid pAD1 (60 kbp) of the recipient strain, suggesting that the erythromycin resistance trait was encoded on a conjugative transposon, which was named Tn950.

Anti-Bacterial Agents↗

The effect of intravenous erythromycin on esophageal motility in healthy subjects.

BACKGROUND: It has been confirmed that erythromycin has gastrokinetic properties of enhancing gastric emptying both in health and disease. The objective of the present study was to investigate any possible effect of erythromycin on esophageal motility. METHODS: In 14 healthy subjects, standard esophageal manometry was performed before and after the intravenous administration of 200 mg of erythromycin. The calculated manometric parameters of esophageal motility were the lower esophageal sphincter (LES) pressure; the amplitude and duration of peristalsis at 5, 10, and 15 cm proximal to the LES; and the velocity and strength of peristalsis at 5 cm proximal to the LES. RESULTS: Erythromycin significantly increased the LES pressure (P<0.001), and the amplitude (P=0.002), duration (P=0.003), strength (P=0.014) and velocity (P=0.008) of peristalsis at 5 cm proximal to LES. Erythromycin also increased the amplitude of peristalsis at 10 cm proximal to the LES (P=0.035). CONCLUSION: Erythromycin affects the motility of the distal esophagus.

Adult↗

Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine.

INTRODUCTION: Cytochrome P4503A (CYP3A) is primarily responsible for the metabolism of cyclosporine and that of many other drugs. Several substrates of CYP3A have been investigated for use as pharmacologic probes to predict the CYP3A-metabolizing capacity of an individual and, therefore, the disposition of other CYP3A substrate drugs. One such measure of CYP3A activity is the 14C erythromycin breath test, which has been applied to the prediction of cyclosporine disposition. However, the test has practical limitations. Because of this, the 0- to 8-hour urinary dapsone recovery ratio has been studied as an alternative and more practical probe of CYP3A activity. METHODS: The dapsone recovery ratio and the 14C erythromycin breath test were correlated with cyclosporine concentrations in 16 patients with rheumatoid arthritis to determine the usefulness of the dapsone recovery ratio as an alternative to the 14C erythromycin breath test. The erythromycin breath test showed a fourfold variation between subjects and correlated weakly with trough cyclosporine concentrations (r = -0.50, p < 0.05), whereas the dapsone recovery ratio varied only approximately twofold between subjects and did not correlate with trough cyclosporine concentrations (r = 0.02, p = 0.94). The correlation between the dapsone recovery ratio and the erythromycin breath test (r = 0.22, p = 0.41) was not significant. CONCLUSIONS: These data suggest that results obtained with one probe in vivo may not apply to another CYP3A substrate. The poor quantitative relationship between cyclosporine concentrations and the erythromycin breath test limits its usefulness in the prediction of an individual's cyclosporine dose requirement.

Adult↗

Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.

The effect of cytochrome P-450 3A (CYP3A) substrates (erythromycin, midazolam) and an inhibitor (ketoconazole) on P-glycoprotein-mediated transport was studied in Caco-2, the human colon adenocarcinoma cell line expressing various functions of differentiated intestinal epithelial cells. The involvement of P-glycoprotein in the transport of these drugs was also examined. The basal-to-apical transport of rhodamine 123, a P-glycoprotein substrate, was inhibited by erythromycin, midazolam and ketoconazole, as well as by P-glycoprotein inhibitors such as verapamil. The apical-to-basal transport of rhodamine 123 was increased by these drugs. The transepithelial transport of erythromycin and midazolam, but not of ketoconazole, was much greater from the basal to apical side than from the apical to basal side. The inhibitory effect of verapamil was observed on the basal to apical transport of erythromycin, but not on midazolam and ketoconazole transport. In conclusion, erythromycin, midazolam and ketoconazole could interact with P-glycoprotein-mediated transport, and P-glycoprotein could be, at least in part, involved in the transport of erythromycin, but not of midazolam and ketoconazole, in the intestinal epithelia.

ATP Binding Cassette Transporter, Subfamily B↗

High-performance liquid chromatographic determination of erythromycin.

An isocratic, reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the determination of erythromycin. The method uses a muBondapak C18 reversed-phase column with a mobile phase composed of acetonitrile-methanol-0.2 M ammonium acetate-water (45:10:10:35). The relative standard deviation of the method for quantification of erythromycin is about 0.6%, and the method is capable of selectively quantifying erythromycins A, B, C and at least nine other erythromycin epimers and degradation compounds in 15 min of chromatographic time. The bio-equivalent potencies of erythromycin powders calculated from the HPLC data agreed well with those of the microbiological assay method. The HPLC method developed is also applicable for the analysis of various derivatives of erythromycin.

Chromatography, High Pressure Liquid↗

Erythromycin: a microbial and clinical perspective after 30 years of clinical use (2).

Erythromycin, first introduced for clinical use 30 years ago, was found to be effective for the treatment of gram-positive bacterial infections. Emergence of resistance and the advent of penicillinase-resistant penicillins limited the use of erythromycin for serious staphylococcal infections; however, erythromycin remains among the drugs of choice for the treatment of acne, infections of the skin and soft tissues, streptococcal pharyngitis, bronchitis, pneumonitis, diphtheria, carriers of pertussis, and, when administered with a sulfonamide, otitis media. Erythromycin is the drug of choice for the empiric treatment of outpatients with pneumonitis. Erythromycin is also the drug of choice for the treatment of Legionella pneumonia and is effective therapy for Chlamydia infections. Other uses of erythromycin include prophylaxis for elective colon operations and treatment of Campylobacter enteritis, genitourinary infections, and some sexually transmitted diseases.

Animals↗

A randomized clinical trial to compare the efficacy of erythromycin, ampicillin and tetracycline for the treatment of cholera in children.

To compare the clinical outcome of treatment of cholera in children with ampicillin, erythromycin or tetracycline, a double-'blind' randomized four-cell trial was carried out in Bangladesh. Ampicillin was chosen as additional therapy for acute respiratory tract infection, present in many subjects with diarrhoea. One hundred and eighty-four children aged 1-5 years who were not wasted, with diarrhoea of duration < 48 h, signs of some or severe dehydration, dark-field stool microscopy demonstrating Vibrio cholerae, and a baseline purging rate > 4 mL/kg/h over 6 h were enrolled in the study. Ampicillin, tetracycline, erythromycin or placebo were given orally every 6 h for 3 d. After 3 d of antibiotic treatment, diarrhoeal stool volume was significantly reduced in all antibiotic groups, with mean volumes per kg body weight as follows: tetracycline, 318 mL (SEM = 50), ampicillin, 335 mL (SEM = 30); erythromycin, 323 mL (SEM = 25); placebo, 498 mL (SEM = 37). Compared to tetracycline, the clinical recovery rates by 96 h were 75% with placebo, 91.3% with ampicillin, and 95.7% with eythromycin. Compared to tetracycline, the total mean times to recovery were increased by 66% with placebo (P < 0.001), 25% with ampicillin (P < 0.017), and 9% with erythromycin (P = 0.37). These results indicated comparable clinical efficacy of tetracycline, ampicillin and erythromycin. We therefore recommend that, unless V. cholerae is resistant, ampicillin should be used as a cost-effective alternative to erythromycin for paediatric cholera, especially in children with concomitant acute respiratory infection.

Ampicillin↗

In vitro detection of specific IgE antibodies to erythromycin.

BACKGROUND: In vitro tests for detecting drug-specific IgE would be useful in identifying patients at risk for immediate hypersensitivity reactions to therapeutic doses of a drug. OBJECTIVE: We attempted to verify that IgE-mediated reactions to erythromycin occur and to identify IgE antibodies specific for erythromycin in serum from a patient who had urticaria immediately after administration of the drug. METHODS: Skin prick testing was performed on the patient and five control subjects. Serum from the patient, pooled sera from nonatopic subjects allergic to common aeroallergens, and cord blood controls were analyzed for erythromycin-specific IgE by radioimmunoassay. Sepharose (Pharmacia, Uppsala, Sweden) was used as solid phase covalently linked to erythromycin. RESULTS: We were able to detect erythromycin-specific IgE antibodies in serum from the patient who had an allergic reaction to this antibiotic, but specific IgE could not be detected in control sera. CONCLUSION: Immunologic IgE-mediated reactions to erythromycin do occur, and in vitro diagnosis of such reactions can be made by using Sepharose as a solid phase covalently linked to this drug.

Adult↗