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PubMed1994

Effects of oral erythromycin on esophageal pH and pressure profiles in patients with gastroesophageal reflux disease.

Erythromycin, a possible motilin agonist, is a potent gastrokinetic agent that may increase the lower esophageal sphincter pressure. Therefore, we assessed the effects of erythromycin in two dosages (250 and 500 mg per os four times a day) on esophageal pH and pressure profiles in reflux patients using prolonged ambulatory monitoring systems. Studies were blinded, placebo-controlled with randomized crossover design. Patients took each drug for three days prior to studies, with erythromycin serum levels obtained the day of esophageal studies. Erythromycin 250 mg four times a day had no effect on esophageal contraction pressures or peristalsis during the day or meal periods. In the supine position, however, erythromycin significantly (P = 0.012) decreased esophageal contraction velocity and showed a strong trend (P = 0.059) towards increasing the percentage of peristaltic waves. Despite these potentially beneficial effects on esophageal clearance, no significant difference in acid exposure times during 24-hr pH studies were observed between placebo and low-dose erythromycin. High-dose erythromycin (500 mg four times a day) was associated with drug levels in the typical antibiotic efficacy range (normal 1-3 micrograms/ml; patients 1.7-7.0 micrograms/ml), but, here again, there was no significant difference in all acid reflux parameters between placebo and erythromycin phases. Therefore, "standard" doses of erythromycin have no important clinical effects on esophageal pressures or acid reflux parameters.

Administration, Oral↗
PubMed2000

Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study.

PURPOSE: Nausea and vomiting three to seven days after an elective operation on the colon and rectum remain a persistent clinical problem. Erythromycin, a safe, inexpensive drug that stimulates intestinal motilin receptors, has previously been shown to accelerate gastric emptying significantly after upper gastrointestinal surgery. We aimed to evaluate the effect of postoperative intravenous erythromycin on postoperative ileus in patients undergoing elective surgery for primary colorectal cancer. METHODS: Between May 1998 and April 1999, 150 patients undergoing primary resection of colon or rectal cancer were enrolled in this prospective, randomized, placebo-controlled trial. One hundred thirty-four patients completed the study. Patients were excluded if they had extensive metastatic disease, were taking medications known to interact with erythromycin, or if they required an ileostomy. Patients received either 200 mg of intravenous erythromycin or placebo every six hours. Clinical endpoints were recorded and continuous end-points are presented as mean +/- standard deviation. RESULTS: There were no significant complications related to erythromycin. The erythromycin (n = 65) and placebo (n = 69) groups were comparable regarding demographic and operative factors. The erythromycin group had a slightly shorter length of time to passage of flatus (4.1 +/- 1.3 vs. 4.4 +/- 1.1 days; P = 0.03). There was no significant difference between erythromycin and placebo in time to first solid food (5.6 +/- 1.9 vs. 5.4 +/- 1.8 days), time to first bowel movement (5.2 +/- 1.9 vs. 5.4 +/- 1.3 days), or time to discharge from hospital (7.5 +/- 2.0 vs. 7.6 +/- 2.8 days). There was no difference in the rate of clinically significant nausea (26 vs. 26 percent; P = 0.99), vomiting (17 vs. 16 percent; P = 0.88), or nasogastric tube placement (9 vs. 7 percent; P = 0.68). CONCLUSIONS: Erythromycin does not seem to alter clinically important outcomes related to postoperative ileus in patients undergoing resection for colorectal cancer.

Aged↗
PubMed1998

Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine.

OBJECTIVE: We have studied the possible interaction of erythromycin and itraconazole, both inhibitors of cytochrome P450 3A4 isoenzyme (CYP3A4), with intravenous lignocaine in nine healthy volunteers using a randomized cross-over study design. METHODS: The subjects were given oral placebo, erythromycin (500 mg three times a day) or itraconazole (200 mg once a day) for 4 days. Intravenous lignocaine 1.5 mg x kg(-1) was given with an infusion for 60 min on the fourth day of pretreatment with placebo, erythromycin or itraconazole. Timed plasma samples were collected until 11 h. The concentrations of lignocaine and its metabolite monoethylglycinexylidide (MEGX) were measured by gas chromatography. RESULTS: The area under the lignocaine concentration-time curve was similar during all three phases but erythromycin significantly increased the elimination half-life of lignocaine from 2.5 to 2.9 (0.7) h compared with placebo. Following itraconazole administration, t1/2 was 2.6 h. The values for plasma clearance and volume of distribution at steady state were similar during all the phases. Compared with placebo and itraconazole, erythromycin significantly increased MEGX peak concentrations by approximately 40% and AUC(0-11 h) by 45-60%. CONCLUSION: The plasma decay of lignocaine administered intravenously is virtually unaffected by the concomitant administration of erythromycin and itraconazole. However, erythromycin increases the concentrations of MEGX, which indicates that erythromycin either increases the relative amount of lignocaine metabolized via N-de-ethylation or decreases the further metabolism of MEGX. Further studies are necessary to elucidate the clinical significance of the erythromycin-induced elevated concentrations of MEGX during prolonged intravenous infusions of lignocaine.

Adult↗
PubMed1991

Antimicrobial therapy in preterm premature rupture of membranes: results of a prospective, double-blind, placebo-controlled trial of erythromycin.

This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes. Sixty-five women were randomly assigned to receive double-blind treatment with either erythromycin base or an identical-appearing placebo three times daily for 7 days. Only women between 23 and 34 completed weeks' gestation who did not have an indication for delivery were enrolled in the study. Pretreatment microbiologic tests were obtained and women were followed expectantly. Fifty-five women and their newborns completed the protocol and were fully evaluated. Overall, time from rupture of membranes to onset of labor and to delivery was longer, although not significantly, for erythromycin-treated women. Similarly, there was a trend for reduced neonatal intensive care (level II, p = 0.07). When gestational age at enrollment was controlled, erythromycin treatment of women between 28 to 32 weeks' gestation was associated with a prolonged interval from enrollment to delivery [erythromycin: 292 hours (5 to 679); placebo: 54 (12 to 323); p less than 0.044]. Fifty percent of erythromycin-treated women between 28 to 32 weeks' gestation continued their pregnancies at least 13 days after premature rupture of membranes, whereas 50% of placebo-treated women were delivered of infants within 4 days (p = 0.02). Erythromycin treatment among women less than 28 and between 33 to 34 weeks' gestation was not associated with prolonged latency or other changes. There were no differences between erythromycin- and placebo-treated women in the occurrence of clinically recognized chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. In this double-blind, placebo-controlled trial, erythromycin treatment was well tolerated, safe, and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother-newborn pairs with preterm premature rupture of membranes.

Adolescent↗
PubMed1994

Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease.

Motilin induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean +/- SEM. LES pressure increased from 13.9 +/- 2.9 mm Hg at baseline to 28.9 +/- 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 +/- 0.4 seconds, 3.8 +/- 0.4 seconds, and 4.1 +/- 0.5 seconds to 4.2 +/- 0.2 seconds, 4.6 +/- 0.5 seconds, and 5.6 +/- 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.

Erythromycin↗
PubMed1983

Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats.

The effects of some macrolides (4 mmoles . kg-1 p.o. daily for 4 days in vivo; 0.3 mM in vitro) on hepatic drug-metabolizing enzymes in rats were compared. One group of macrolides including previously studied compounds (oleandomycin, erythromycin and troleandomycin), as well as several other erythromycin derivatives, showed induction of microsomal enzymes and formation of inactive cytochrome P-450-metabolite complexes in vivo; this formation increased in the order: oleandomycin, erythromycin ethylsuccinate, erythromycin stearate, erythromycin itself, erythromycin propionate, erythromycin estolate and troleandomycin. Troleandomycin and, to a lesser extent, erythromycin and oleandomycin formed cytochrome P-450-metabolite complexes when incubated in vitro with 1 mM NADPH and microsomes from rats pretreated with troleandomycin or phenobarbital, but not with microsomes from control rats or rats treated with 3-methylcholanthrene. In contrast, two other macrolides, josamycin and midecamycin, showed no induction of microsomal enzymes and no detectable formation of cytochrome P-450-metabolite complexes in vivo. In vitro, these macrolides failed to form detectable complexes even with microsomes from rats pretreated with troleandomycin or phenobarbital. Hexobarbital sleeping time was unaffected by preadministration of josamycin or midecamycin (4 mmoles . kg-1 p.o.) 2 hr earlier; the in vitro activity of hexobarbital hydroxylase was not inhibited by 0.3 mM josamycin or midecamycin. We conclude that, unlike several erythromycin derivatives, josamycin and midecamycin do not form inactive cytochrome P-450-metabolite complexes in rats.

Animals↗
PubMed2005

Exaggerated block of hERG (KCNH2) and prolongation of action potential duration by erythromycin at temperatures between 37 degrees C and 42 degrees C.

BACKGROUND: Environmental and genetic factors interact to define susceptibility to drug-induced long QT syndrome. Although erythromycin induces long QT syndrome, substantial variability exists with regard to its incidence. OBJECTIVES: Because fever frequently results in empiric antibiotic usage, we assessed whether temperatures over the range from 36 degrees to 42 degrees C determined responsiveness to erythromycin (100 micromol/L). METHODS: I(hERG) was recorded in mammalian cells, and action potentials were recorded in neonatal ventricular mouse myocytes. RESULTS: Erythromycin (100 micromol/L) produced no block of I(hERG) at 22 degrees C but produced significant block at 37 degrees C. Extent of block of I(hERG) increased linearly (r = 0.46, P < .01) as temperature increased between 36 degrees C and 42 degrees C. To assess physiologic relevance, action potential duration (APD) was recorded at temperatures between 36 degrees C and 42 degrees C in neonatal ventricular myocytes. Significantly greater prolongation of APD by erythromycin was observed at 42 degrees C compared with 37 degrees C. To assess whether transmembrane diffusion of erythromycin was the rate-limiting step for block of I(hERG) at 22 degrees C, erythromycin was applied within the patch pipette. Under these conditions, erythromycin rapidly blocked I(hERG) even at 22 degrees C. The F656C mutation in the distal S6 of KCNH2 completely abrogated block of I(hERG) measured at 37 degrees C. CONCLUSION: Progressively greater block of hERG and prolongation of APD by erythromycin was observed at temperatures between 36 and 42 degrees C. Temperature-dependent block of I(hERG) is explained by temperature-dependent access of erythromycin to the intracellular binding site at F656.

Action Potentials↗
PubMed2004

Investigating the potential of erythromycin and derivatives as chiral selector in capillary electrophoresis.

Macrocyclic antibiotics are present in an increasing number of chiral separation applications. In this study, erythromycin and some derivatives, belonging to the group of macrolide antibiotics, were investigated for their potential as chiral selector. Erythromycin A itself and five related substances namely erythromycin A N-oxide, anhydroerythromycin A, anhydroerythromycin A N-oxide, erythralosamine and erythralosamine N-oxide were included. Twenty-one chiral compounds with a wide difference in physico-chemical properties were used to test the chiral activity of the erythromycins. The chiral compounds were analysed using capillary zone electrophoresis with the erythromycins dissolved in the running buffer at different concentrations ranging from 0.1 to 10mM, with three different BGEs: sodium phosphate pHs 3.0 and 7.0 and sodium borate pH 9.2. The erythromycins showed more interactions with the acidic compounds (as observed with leucovorin, dopa, carbidopa, ketoprofen, indoprofen and warfarin) than with the neutral or weakly basic ones, especially in acidic medium. Unfortunately, no chiral separations were obtained for any of the 21 racemic mixtures. The complexation constants were calculated for the compounds showing interaction, based on the variation of electrophoretic mobility of the compounds in the presence of different concentrations of erythromycins. Finally, the size of erythromycin A was calculated using computational modelling. It was shown that the aglycone ring is only half as big as the beta-cyclodextrin cavity, giving a possible explanation for the negative response of erythromycin in this study.

Buffers↗
PubMed1997

Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole.

BACKGROUND: The oral bioavailability of buspirone is very low as a result of extensive first-pass metabolism. Erythromycin and itraconazole are potent inhibitors of CYP3A4, and they increase plasma concentrations and effects of certain drugs, for example, oral midazolam and triazolam. The possible interactions of buspirone with erythromycin and itraconazole have not been studied before. METHODS: The pharmacokinetics and pharmacodynamics of buspirone were investigated in a randomized, double-blind, double-dummy crossover study with three phases. Eight young healthy volunteers took either 1.5 gm/day erythromycin, 200 mg/day itraconazole, or placebo orally for 4 days. On day 4, 10 mg buspirone was administered orally. Timed blood samples were collected up to 18 hours, and the effects of buspirone were measured with four psychomotor tests up to 8 hours. RESULTS: Erythromycin and itraconazole increased the mean area under the plasma concentration-time curve from time zero to infinity [AUC(0-infinity] of buspirone about sixfold (p < 0.05) and 19-fold (p < 0.01), respectively, compared with placebo. The mean peak plasma concentration (Cmax) of buspirone was increased about fivefold (p < 0.01) and 13-fold (p < 0.01) by erythromycin and itraconazole, respectively. These interactions were evident in each subject, although a striking interindividual variability in the extent of both interactions was observed. The elimination half-life of buspirone did not seem to be prolonged by either erythromycin or itraconazole. The effect of itraconazole on the Cmax and AUC(0-infinity) of buspirone was significantly (p < 0.01) greater than that of erythromycin. The greatly elevated plasma buspirone concentrations resulted in increased (p < 0.05) pharmacodynamic effects (as measured by the Digit Symbol Substitution test and the Critical Flicker Fusion test) and in side effects of buspirone. CONCLUSIONS: Both erythromycin and itraconazole greatly increased plasma buspirone concentrations, obviously by inhibiting its CYP3A4-mediated first-pass metabolism. These pharmacokinetic interactions were accompanied by impairment of psychomotor performance and side effects of buspirone. The dose of buspirone should be greatly reduced during concomitant treatment with erythromycin, itraconazole, or other potent inhibitors of CYP3A4.

Administration, Oral↗
PubMed2001

Association between erythromycin resistance and ability to enter human respiratory cells in group A streptococci.

BACKGROUND: An increase in erythromycin resistance rates among group A streptococci has been reported in some European countries. These bacteria, long thought to be extracellular pathogens, can be efficiently internalised by, and survive within, human cells of respiratory-tract origin. Macrolide antibiotics enter eukaryotic cells, whereas beta-lactams are essentially confined to the extracellular fluid. A protein encoded by gene prtF1 is required for efficient entry of group A streptococci into epithelial cells. We investigated isolates of group A streptococci from children with pharyngitis in Italy for the presence of prtF1 and cell-invasion efficiency. METHODS: We investigated 74 erythromycin-resistant and 52 erythromycin-susceptible isolates collected throughout Italy in 1997-98 from children with pharyngitis. Erythromycin-resistance phenotypes (constitutive, inducible, and M) were assessed by the triple-disc test and resistance determinants (ermB, ermTR, and mefA) by PCR. All strains were examined for the presence of prtF1 by PCR and for their ability to enter cultured human respiratory cells. FINDINGS: The proportion of prtF1-positive strains was significantly higher among erythromycin-resistant than susceptible strains (66 [89%] vs 11 [21%]; difference 68% [95% CI 52-84]). All erythromycin-resistant strains without prtF1 were of the M phenotype. The proportion of highly cell-invasive isolates (invasion efficiency >10%) was significantly higher among erythromycin-resistant than among susceptible strains (59 [80%] vs five [10%]; difference 70% [57-83]). INTERPRETATIONS: The unsuspected association between erythromycin resistance and cell invasiveness in group A streptococci raises serious concern. Strains combining erythromycin resistance and ability to enter human respiratory-tract cells may be able to escape both beta-lactams by virtue of intracellular location and macrolides by virtue of resistance.

Adhesins, Bacterial↗
PubMedDate not supplied

Erythromycin, clarithromycin, and azithromycin: are the differences real?

Erythromycin, clarithromycin, and azithromycin are clinically effective for the treatment of common respiratory and skin/skin-structure infections. Erythromycin and azithromycin are also effective for treatment of nongonococcal urethritis and cervicitis due to Chlamydia trachomatis. Compared with erythromycin, clarithromycin and azithromycin offer improved tolerability. Clarithromycin, however, is more similar to erythromycin in pharmacokinetic measures such as half-life, tissue distribution, and drug interactions. Misunderstandings about differences among the macrolides (erythromycin and clarithromycin) and the azalide (azithromycin) in terms of pharmacokinetics and pharmacodynamics, spectrum of activity, safety, and cost are common. The uptake and release of these compounds by white blood cells and fibroblasts account for differences in tissue half-life, volume of distribution, intracellular:extracellular ratio, and in vivo potency. Although microbiologic studies reveal that gram-positive pathogens are equally susceptible to these agents, significantly more isolates of Haemophilus influenzae are susceptible to azithromycin than to erythromycin or clarithromycin. Concentrations achieved at the infection site and duration above the minimum inhibitory concentration are as important as in vitro activity in determining in vivo activity against bacterial pathogens. Analysis of safety data indicates differences among these agents in drug interactions and use in pregnancy. Analysis of safety data reveals pharmacokinetic drug interactions for erythromycin and clarithromycin with theophylline, terfenadine, and carbamazepine that are not found with azithromycin. Both erythromycin and azithromycin are pregnancy category B drugs; clarithromycin is a category C drug. The numerous differences in pharmacokinetics, microbiology, safety, and costs among erythromycin, clarithromycin, and azithromycin can be used in the judicious selection of treatment for indicated infections.

Anti-Bacterial Agents↗
PubMed2003

Analysis of erythromycin and tylosin in bovine muscle using disposable screen printed electrodes.

A disposable electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of two macrolides (erythromycin and tylosin) in bovine muscle was developed using a screen printed electrode (SPE) system as a differential pulse voltammetry (DPV) transducer with mouse anti-erythromycin (and anti-tylosin) monoclonal antibodies (MAb) serving as molecular recognition elements. The immunochemical system makes use of the competition assay principle, and employs an erythromycin (or tylosin)-BSA conjugate as coating molecule. After competition between free and coated analyte for the antibodies, the activity of the alkaline phosphatase labelled antiglobulins was measured electrochemically using 1-naphthylphosphate as substrate. Using standard solutions of erythromycin and tylosin, the detection limit of the assay was 0.2 ng mL(-1) determined to be for erythromycin and 2.0 ng mL(-1) for tylosin, while the sensitivity (25% inhibition concentration) was 1.0 ng mL(-1) for erythromycin and 3.0 ng mL(-1) for tylosin. The suitability of the assay for quantification of erythromycin and tylosin in bovine muscle was also studied. Spiked and real samples were analysed using the immunosensor system developed here. The ELISA showed precision values (relative standard deviation, RSD%) ranging from 4 to 9% for erythromycin and from 8 to 15% for tylosin; the accuracy (relative error, RE%) ranged from -11 to 6% and from -4 to 12% for erythromycin and tylosin, respectively. Results obtained on real samples were confirmed by micro-liquid chromatography coupled on line with tandem mass spectrometry (micro-LC-MS-MS), using an atmospheric pressure ionisation (API) source and an ionspray (IS) interface. The latter provides unequivocal identification and quantification of the analytes at the level of interest.

Animals↗
PubMed2002

Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects.

BACKGROUND: Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting. AIM: : To assess: (i) the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying; and (ii) any modification of the gastrokinetic action of erythromycin induced by octreotide. SUBJECTS AND METHODS: Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in a double-blind, placebo-controlled manner and in random order: (i) after placebo; (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of intravenous erythromycin following pre-treatment with either 4 mg of intravenous ondansetron (10 subjects) or 50 micro g octreotide. RESULTS: Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pre-treatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post-lag phases of gastric emptying. CONCLUSIONS: Serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying. This effect seems to be enhanced by pre-treatment with octreotide, possibly as a result of the modification of the gastrointestinal hormonal environment.

Adult↗
PubMed1996

Erythromycin inhibits rabbit pyloric smooth muscle through neuronal motilin receptors.

BACKGROUND & AIMS: Erythromycin's effect in accelerating gastric emptying is attributed primarily to increased antral contractility. The aim of this study was to characterize erythromycin's effect on pyloric muscle. METHODS: Rabbit pyloric muscle strips were studied in vitro. RESULTS: Pyloric muscle strips developed spontaneous phasic contractions with a frequency of 1.9 +/- 0.1 contractions per minute. Erythromycin and motilin had dose-dependent inhibitory effects on pyloric muscle. At the maximal effective dose (50 mumol/L), erythromycin caused cessation of spontaneous contractions for 1.8 +/- 0.2 minutes, decreasing the initial 2-minute motility index to 35% +/- 9% (P < 0.01) of basal. In the presence of tetrodotoxin, both erythromycin and motilin increased pyloric contractility. Motilin tachyphylaxis both in the presence or absence of tetrodotoxin abolished the effects of erythromycin. The inhibitory effect of erythromycin was decreased by NG-nitro-L-arginine methyl ester and the vasoactive intestinal peptide antagonist [4-Chloro-D-Phe6, Leu17]vasoactive intestinal peptide. CONCLUSIONS: These studies suggest that motilin receptors are present on both pyloric muscle and inhibitory neurons to pyloric muscle, that the primary effect of erythromycin on the pylorus is mediated by activating motilin receptors on inhibitory motor neurons, and that both nitric oxide and vasoactive intestinal peptide may mediate the inhibitory effect of erythromycin.

Animals↗
PubMed2004

Oral erythromycin and the risk of sudden death from cardiac causes.

BACKGROUND: Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A. METHODS: We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time-concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication. RESULTS: The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors. CONCLUSIONS: The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided.

Administration, Oral↗
PubMed1991

A comparative safety and efficacy study of clarithromycin and erythromycin stearate in community-acquired pneumonia.

The efficacy and tolerance of clarithromycin and erythromycin stearate in the treatment of community-acquired pneumonia were compared in a multicentre, double-blind randomized trial. Two hundred and eight adult patients were randomized to receive either clarithromycin 250 mg 12-hourly (96 patients) or erythromycin stearate 500 mg 6-hourly (112 patients), each for 14 days. One hundred and eight patients were evaluable for efficacy, 64 receiving clarithromycin and 44 erythromycin stearate. There was no significant difference between the two groups in terms of clinical cure (52% for clarithromycin, 40% for erythromycin) or clinical success (clinical cure and improvement; 89% for clarithromycin, 98% for erythromycin stearate), or radiological response (90% for both groups). An intention-to-treat analysis, including all patients entering the study revealed significant differences in favour of clarithromycin. The clinical cure rate after two weeks of treatment was 45% in those who received clarithromycin compared with 25% in the erythromycin stearate group (P = 0.003), whilst improvement in cough was observed in 97% and 80% of patients receiving clarithromycin and erythromycin stearate, respectively (P = 0.07). Adverse effects, mainly gastrointestinal, caused discontinuation of treatment in 4% (4/96) patients in the clarithromycin group in comparison with 19% (21/112) treated with erythromycin stearate (P less than 0.01). These results demonstrate that clarithromycin twice daily is at least as effective as four times daily erythromycin stearate for the treatment of community-acquired pneumonia and is better tolerated.

Adult↗
PubMed2000

Subinhibitory concentrations of erythromycin reduce pneumococcal adherence to respiratory epithelial cells in vitro.

We have investigated the influence of subinhibitory concentrations of erythromycin on the interaction between Streptococcus pneumoniae and human respiratory epithelial cells. Confluent in vitro cell cultures were inoculated with erythromycin-resistant S. pneumoniae and incubated for 24 h. Erythromycin significantly reduced adherence of the pneumococci after 4 h and 24 h: 4.0% +/- 0.7% (mean +/- S.E.M. ) of the pneumococci adhered to the epithelial cells in medium with erythromycin, compared with 7.7% +/- 0.8% in medium without erythromycin (P: = 0.002) after 4 h, and the corresponding values after 24 h were 24.2% +/- 5.3% and 38.4% +/- 5.0%, respectively (P: = 0.038). Disruption of epithelial integrity by S. pneumoniae, measured as the decrease in transepithelial electrical resistance, was delayed in the presence of erythromycin. Neither addition of erythromycin to the culture medium nor infection of the cell cultures with pneumococci significantly affected secretion of interleukin-8 by the epithelial cells. Addition of erythromycin to a pneumococcal suspension in cell culture medium without respiratory epithelial cells almost completely prevented the release of pneumolysin. We conclude that erythromycin at subinhibitory concentrations reduces the adherence to and disruption of respiratory epithelial cells by S. pneumoniae, possibly by interfering with pneumolysin release.

Anti-Bacterial Agents↗
PubMed2001

Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial.

BACKGROUND: Pertussis is still a prevalent public health problem, and antibiotic therapy may decrease disease severity and limit communicability. Erythromycin is the recommended antibiotic for treatment and prophylaxis of pertussis; however, side effects of erythromycin limit its usefulness in some patients. Clarithromycin, a newer macrolide, has good in vitro activity against Bordetella pertussis and a better side effect profile. GOALS OF THE STUDY: To compare the microbiologic and clinical efficacy and the clinical safety of a 7-day course of clarithromycin vs. a 14-day course of erythromycin in children with pertussis. DESIGN: Prospective, randomized, single blind (investigator), parallel group trial. METHODS: Children from 1 month to 16 years of age presenting with a clinically defined pertussis syndrome were eligible for the study. After obtaining informed written consent, we randomized patients to receive either clarithromycin (7.5 mg/kg/dose twice a day for 7 days) or erythromycin (13.3 mg/kg/dose three times a day for 14 days). Nasopharyngeal cultures for B. pertussis were performed at enrollment and after end of treatment. Clinical assessments were performed at enrollment, at end of treatment and at a 1-month follow-up visit. Adverse event data were collected throughout the study. RESULTS: The clarithromycin (n = 76) and erythromycin (n = 77) groups were well-matched for age and previous pertussis immunization. Microbiologic eradication and clinical cure rates were 100% (31 of 31) for clarithromycin and 96% (22 of 23) for erythromycin. The clarithromycin group had significantly fewer adverse events [45% (34 of 76) for clarithromycin vs. 62% (48 of 77) for erythromycin; P = 0.035], and compliance with the medication regimen was significantly higher in these patients. CONCLUSIONS: A 7-day regimen of clarithromycin and a 14-day course of erythromycin were equally effective for treatment of pertussis. Clarithromycin was better tolerated than conventional erythromycin therapy.

Anti-Bacterial Agents↗