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PubMed2000

Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae.

Macrolides may influence the inflammatory response to an infection by mechanisms that are unrelated to their antimicrobial effect. Indeed, erythromycin and other macrolides inhibit cytokine production and induce degranulation of neutrophils in vitro. CXC chemokines are small chemotactic cytokines that specifically influence neutrophil functions. To determine the effect of a clinically relevant dose of erythromycin on the production of CXC chemokines and neutrophil degranulation, six healthy humans received a 30 min iv infusion of erythromycin (1000 mg). Whole blood obtained before and at various times after the infusion was stimulated ex vivo with heat-killed Streptococcus pneumoniae. Ex vivo production of the CXC chemokines interleukin 8 (IL-8) and epithelial cell-derived neutrophil attractant 78 (ENA-78), in whole blood obtained after erythromycin infusion, was lower than that in blood drawn before erythromycin infusion (maximum inhibition post-infusion: 32.9 +/- 6.5% and 35.2 +/- 12.6% decrease in production, respectively, expressed as percentage change relative to production before infusion of erythromycin, both P < 0.05). In contrast, infusion of erythromycin was associated with an enhanced capacity of whole blood to release the neutrophil degranulation products bactericidal/permeability increasing protein (BPI), human neutrophil elastase (HNE) and human lactoferrin (HLF) upon stimulation with S. pneumoniae. Effects of erythromycin were greatest 4 h after infusion was stopped, when BPI, HNE and HLF concentrations were increased by +107.6 +/- 33.5%, +134.7 +/- 34.8% and +205.9 +/- 55.9 %, respectively (expressed as percentage change relative to production before infusion of erythromycin) (all P < 0. 05). These results indicate the ability of erythromycin to reduce CXC chemokine production and to enhance neutrophil degranulation in human blood.

Adult↗
PubMed2001

Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy.

OBJECTIVE: To test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Delayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. METHODS: Thirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. RESULTS: Preoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. CONCLUSIONS: Low doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.

Adult↗
PubMed2004

Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea.

Oral wide-spectrum antibiotics are the linchpin of rosacea treatment. Oral and topical metronidazole, topical tretinoin, and topical benzoyl peroxide may also be used in the treatment of rosacea. We aimed to show that benzoyl peroxide-erythromycin gel is efficient in the treatment of acne rosacea. Fifty-six patients with acne rosacea were enrolled in our study. We administered benzoyl peroxide-erythromycin gel to 27 patients and metronidazole gel to 29 patients. In all the patients, the intensities of erythema, telangiectasia, papules/pustules, and nodules were evaluated before, during and after the treatment. The positivity of Demodex folliculorum from skin scratches was compared between the two groups at each visit. At the end of the therapy on the third examination, in the benzoyl peroxide-erythromycin group, 91.7% of the patients showed marked clinical improvement, and 8.3% of them showed complete remission. In the metronidazole group, 73.3% showed marked clinical improvement, and 26.7% of them showed complete remission. Clinical improvement in the papular component was 65.2% for the benzoyl peroxide-erythromycin group, and 81.5% for metronidazole group. In the first examination, the clinical results of the agents were similar. Although both of the drugs were found to be effective in the second and third examinations, metronidazole gel was more effective than benzoyl peroxide-erythromycin. Both of the drugs were found to be significantly effective especially in treating the papular component of rosacea. Demodex folliculorum was found to be positive in 74.1% of the benzoyl peroxide-erythromycin group and in 62.1% of the metronidazole group at the beginning. In the benzoyl peroxide-erythromycin group, 40.7% of Demodex folliculorum positive patients, became negative by the first examination. This was 17.2% for the metronidazole group. In the benzoyl peroxide-erythromycin group, among the patients who were positive for Demodex folliculorum in the first examination, 37.5% of them became negative. This was 36.7% for the metronidazole group. Benzoyl peroxide-erythromycin gel was superior to metronidazole gel in decreasing Demodex folliculorum by the first examination, but the effect of the two drugs on Demodex folliculorum was similar by the second examination. As a result, topically applied combined benzoyl peroxide-erythromycin gel may be an alternative choice of treatment for acne rosacea.

Administration, Cutaneous↗
PubMed2000

The effect of erythromycin on human esophageal motility is mediated by serotonin receptors.

OBJECTIVE: Erythromycin exhibits prokinetic properties. The drug enhances esophageal and gastric motility by acting as a motilin agonist and promoting acetylocholine release. 5-HT3 receptors are involved in the spontaneously occurring migrating motor complex and the effect of erythromycin on antral motility in dogs. The aim of the study was to investigate the hypothesis that 5-HT3 receptors are also involved in the action of erythromycin on the human esophagus. METHODS: A total of 18 healthy volunteers underwent standard esophageal manometry on three different occasions in a double-blind, placebo-controlled, randomized manner, as follows: 1) after placebo, 2) after 200 mg of erythromycin i.v., and 3) after 200 mg of i.v. erythromycin subsequent to pretreatment with either 4 mg of i. v. ondansetron (serotonin receptor antagonist) (10 subjects) or 12 microg/kg of i.v. atropine (8 subjects). RESULTS: Erythromycin significantly increased a) the amplitude of peristalsis at 5 cm (from 87 +/- 19 mm Hg to 108 +/- 26 mm Hg; p = 0.0007), 10 cm (from 72 +/- 24 mm Hg to 81 +/- 26 mm Hg; p = 0.016), and 15 cm (from 47 +/- 15 mm Hg to 55 +/- 17 mm Hg; p = 0.014) proximal to LES, b) the duration of peristalsis at 5 cm (from 4.5 +/- 0.9 s to 5.7 +/- 1.2 s; p < 0.0001) and 10 cm (from 4.1 +/- 1 s to 4.9 +/- 1 s; p < 0.0001) proximal to the LES and c) the strength of peristalsis at 5 cm proximal to the LES (from 180 +/- 49 mm Hg x s to 276 +/- 100 mm Hg x s; p < 0.0001), and decreased the velocity of peristalsis at distal esophagus (from 4.1 +/- 1 cm/s to 3.8 +/- 0.9 cm/s; p = 0.03). In addition, erythromycin significantly increased the resting pressure of the LES (from 36 +/- 10 mm Hg to 44 +/- 12 mm Hg; p = 0.002). Pretreatment with ondansetron totally reversed all of the effects of erythromycin to the placebo state. Pretreatment with atropine not only prevented the effects of erythromycin, but it reduced the amplitude and strength of peristalsis at the distal esophagus at significantly lower levels than after placebo. CONCLUSIONS: Erythromycin exerts its prokinetic action on the lower esophagus by stimulating cholinergic pathways. This action includes not only an increase in LES pressure, but significant increases in the amplitude and duration of esophageal peristalsis, as well. 5-HT3 receptors are also involved in this process.

Adult↗
PubMed1997

Inhibition of nifedipine metabolism in dogs by erythromycin: difference between the gut wall and the liver.

The purpose of this study was to evaluate possible interaction of nifedipine with erythromycin or rokitamycin in the intestinal mucosa. Male beagle dogs were orally administered nifedipine (10 mg), with or without oral pre-medication with erythromycin (300 mg), and 300 mg erythromycin or rokitamycin twice a day for 3 days. The experiments were of randomized cross-over design with a two-week wash-out period between dosing regimens. Erythromycin pre-medication for 3 days resulted in a significant increase in the area under the serum nifedipine concentration-time curve (AUC), whereas the curve for one nifedipine metabolite (M-2) decreased significantly. When the effects of erythromycin on the metabolism of nifedipine were studied using dog liver microsomes it was found that erythromycin significantly inhibited formation of M-2 but not of the metabolite M-1. These results indicate that formation of M-2 from M-1 in the liver might be reduced by erythromycin pre-medication. To avoid possible metabolism in the gut, the dogs were then administered 8 mg nifedipine into the peritoneal cavity, with or without multiple dose pre-treatment with erythromycin for 3 days. After intraperitoneal administration of nifedipine, the maximum concentration (Cmax) of nifedipine increased significantly. After pre-administration of erythromycin the relative bioavailability of nifedipine after oral administration was increased compared with injection into the peritoneal cavity. In-vitro study using rat intestinal microsomes and the in-vivo rat intestinal loop technique also showed that pre-administration of erythromycin inhibits nifedipine metabolism in the small intestine.

Animals↗
PubMed1998

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents.

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.

Anti-Bacterial Agents↗
PubMed1997

In vivo characterization of the colonic prokinetic effect of erythromycin in the rabbit.

The motor effect of erythromycin was characterized in conscious rabbits chronically fitted with electrodes and strain-guage force transducers implanted along the proximal and distal colon. Fecal pellet output was also evaluated as an index of propulsive activity. In order to get an insight into the pathways involved in mediating the effect of erythromycin, the macrolide was also administered after pretreatment with atropine, nifedipine or ondansetron. Furthermore, in vitro experiments with erythromycin alone and in the presence of atropine, nifedipine, tetrodotoxin or ondansetron were carried out with circular muscle strips taken from rabbit distal colon. In vivo, erythromycin (0.087-5.6 mg/kg i.v. bolus) dose-dependently stimulated spike and mechanical activities at both colonic levels, with a more marked effect on the distal colon. Erythromycin also dose-dependently increased the number of aborally migrating long spike bursts and fecal pellet output. The reproducibility of the response to erythromycin was confirmed by experiments with the dose of 2.8 mg/kg i.v. bolus, repeated in five consecutive experiments at 48-hour intervals. Nifedipine, but not atropine or ondansetron, significantly reduced the colonic motor response to erythromycin. In vitro experiments gave results in line with the in vivo data: the concentration-dependent contractile effect of erythromycin was almost suppressed by nifedipine, but resistant to atropine, tetrodotoxin or ondansetron. In conclusion, this study provides evidence that: (1) erythromycin is a prokinetic drug at the colonic level in rabbits, and (2) both in vivo and in vitro, the effects of erythromycin are exerted at the smooth muscle level by mechanisms depending on influx of extracellular calcium, while muscarinic and 5-HT3 receptors are not involved, at least in this model.

Animals↗
PubMed1993

A mechanism of erythromycin treatment in patients with diffuse panbronchiolitis.

Recently, "low-dose and long-term" erythromycin treatment has been reported as effective on diffuse panbronchiolitis (DPB), but its mechanism is still obscure. Patients with DPB were found to have significantly higher percentages of neutrophils in the pre-erythromycin treatment bronchoalveolar lavage fluid (BALF) than healthy nonsmoking volunteers (p < 0.001). They showed a significant reduction in BALF neutrophil percentages after erythromycin treatment (p < 0.01). The neutrophil chemotactic activity (NCA) was significantly elevated in BALF obtained from 19 patients with DPB compared with that from healthy volunteers (p < 0.001). A significant reduction in the NCA was observed in post-erythromycin treatment BALF of 11 patients with DPB (p < 0.001). Additionally, there was a significant correlation between the reduction of NCA and neutrophil percentage in pre- and post-erythromycin treatment BALF (r = 0.726, p < 0.05). Finally, we investigated the effect of erythromycin on the intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS) and interleukin-8 (IL-8) in mice. The intrapulmonary influx of neutrophils was significantly suppressed (p < 0.001) in mice intraperitoneally injected with erythromycin at 5 mg per animal 2 h before intratracheal injection of LPS (control group: 6.5 +/- 1.6 x 10(5) versus erythromycin-treated group: 1.7 +/- 0.5 x 10(5)), but not 10 h before lung challenge. This inhibition was observed at 6 h after lung challenge and became maximal with 84% suppression at 24 h. Week-long administration of erythromycin did not alter the intrapulmonary influx of neutrophils. The number of neutrophils in the peripheral blood was not affected by erythromycin, indicating that the drug was not toxic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

A randomized, placebo-controlled trial of erythromycin estolate chemoprophylaxis for household contacts of children with culture-positive bordetella pertussis infection.

CONTEXT: Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis. OBJECTIVE: To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Community based. SUBJECTS: All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment. PRIMARY OUTCOME: Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis. RESULTS: There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients. CONCLUSIONS: Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.

Adolescent↗
PubMed2002

The association of erythromycin and infantile hypertrophic pyloric stenosis: causal or coincidental?

The safety profile of erythromycin is notable for the frequent occurrence of intolerable gastrointestinal effects. One of the more serious of these is infantile hypertrophic pyloric stenosis (IHPS). A recent cluster of IHPS cases prompted an epidemiological investigation which identified oral erythromycin chemoprophylaxis of pertussis as the major risk factor. Evidence suggests an association between early postnatal erythromycin exposure and IHPS. There is no substantive evidence of a risk associated with prenatal exposure, with the single published case-control study to date producing negative findings. The epidemiological investigations of the association with early postnatal exposure have reported significantly elevated odds ratios but have a variety of methodological limitations that prevent definitive conclusions being made. Nevertheless, the concordance of findings across studies increases the strength of evidence favouring an association. The prominent gastrokinetic properties of erythromycin have been postulated as the mechanism behind this phenomenon. A comprehensive assessment of this potential adverse effect should consider its biological plausibility in light of known gastrointestinal physiology, its modulation by erythromycin, and the known pathophysiology of IHPS. Gastrointestinal motor activity in the fasted mammal consists of three phases, phase III being large amplitude contractions called migrating motor complexes (MMC) that can be initiated by motilin and erythromycin. The gastrokinetic effects of erythromycin are variable and complex and include effects on the timing, duration, amplitude and distribution of MMCs. It has been speculated that the motilinomimetic effects of erythromycin on antral smooth muscle function, such as the MMC, may mediate the effect via work hypertrophy. Although intuitively plausible and consistent with hypertrophic obstructive changes similar to IHPS observed in hyperplastic rat ileum after artificially induced mechanical obstruction, there is no direct evidence of this phenomenon. Further complicating the association is the limitations of our knowledge about the pathophysiology of IHPS, including numerous genetic abnormalities, increased parietal cell mass, and gastric hyperacidity. The implications of the reported findings with erythromycin on the benefit-risk profiles of newer macrolides and azalides must be considered. The available data on the comparative gastrokinetic properties of macrolides are significant for the potent gastrokinetic properties and its acid degradation products, the marked variation in gastrokinetic properties associated with macrolide ring size, and the requirement for specific glycosidic linkages at the C-3 and C-5 carbons of the macrolide ring. The variation in gastrokinetic properties associated with variations in molecular structure suggests that if the association between erythromycin and IHPS is causal it may not be a class effect.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Comparison between physiologic and erythromycin-induced interdigestive motility.

BACKGROUND: The last part of duodenal phase III of the migrating motor complex behaves as a retroperistaltic pump. We have compared the phase-III-like gastroduodenojejunal activity induced by erythromycin with the naturally occurring phase III, focusing on peristaltic patterns. The effect of two doses of erythromycin, 3 mg/kg/h and 12 mg/kg/h (in four subjects), or saline, given intravenously for 15 min, was studied in nine fasting healthy subjects (five men and four women). METHODS: Motility was recorded on three different days. On one day standard 5-h eight-channel antroduodenojejunal manometry was performed and saline infused 30 min after the first phase III. On the other two study days, erythromycin in the low or the high dose was infused and recording performed for another 2-h period. RESULTS: The low dose of erythromycin induced a phase III in the stomach in all subjects within 12.8 +/- 1.4 min. In contrast, the higher dose did not induce phase-III activity within the 1st h after infusion but induced marked antral pressure waves. The duration of the erythromycin-induced phase III and the naturally occurring antral phase III was 4.7 +/- 1.7 and 1.9 +/- 0.3 min, respectively (p < 0.01). The duration of the erythromycin-induced phase III in the proximal jejunum was 44% shorter than the spontaneous one (p < 0.01). The propagation velocity, from the proximal duodenum to the proximal jejunum, of the erythromycin-induced phase III was slower than that of the spontaneous phase III: 5.7 +/- 0.9 and 15.9 +/- 3.9 cm/min, respectively (p < 0.01). In the proximal duodenum the proportion of retrograde pressure waves (of all propagating waves) was about 10% in early phase III, increasing to about 85% in late phase III in both the spontaneous and erythromycin-induced phase III. In the proximal jejunum retrograde pressure waves were not observed in phase III. CONCLUSIONS: Erythromycin given in a low dose is very effective in inducing phase-III-like motility. The last part of duodenal phase III is characterized by retroperistalsis also when this motility phase is induced by erythromycin.

Adult↗
PubMedDate not supplied

Inhibitory effect of erythromycin on P-glycoprotein-mediated biliary excretion of doxorubicin in rats.

The macrolide antibiotic erythromycin has recently been shown to overcome the resistance to anticancer drugs that results from overexpression of P-glycoprotein. The present study, using erythromycin lactobionic acid as a model drug, investigated the inhibitory effects of erythromycin on the efflux of doxorubicin from P388/ADR cells expressing P-glycoprotein and on the biliary excretion mechanism of doxorubicin in rats, which is primarily mediated by P-glycoprotein. Erythromycin lactobionic acid was found to inhibit the efflux of doxorubicin (5 microM) from P388/ADR cells in a concentration-dependent manner. In rats receiving constant-rate infusion of doxorubicin (30 micrograms/min), both the biliary and renal clearance of this drug dramatically decreased and its plasma concentrations increased after an intravenous injection of erythromycin lactobionic acid (100 mg/kg as erythromycin). These results suggest that erythromycin competitively inhibits P-glycoprotein-mediated biliary and renal excretion of doxorubicin. The effect of erythromycin on the biliary secretion of doxorubicin was also analyzed quantitatively by the competitive inhibition model. The computer-estimated values of Vmax/Km, Km and Ki were 8.79 ml/minute, 0.82 microgram/ml and 0.41 microgram/ml, respectively. The findings of these experiments suggest that the inhibitory effect of erythromycin on the P-glycoprotein-mediated biliary excretion of doxorubicin is competitive and that combination chemotherapy of doxorubicin with erythromycin may induce toxicity as a result of increased plasma concentrations of doxorubicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Metabolism of cyclosporin A. III. Interaction of the macrolide antibiotic, erythromycin, using rabbit hepatocytes and microsomal fractions.

The interaction between cyclosporin A (CsA) and the macrolide antibiotic, erythromycin, has been studied in freshly isolated rabbit hepatocytes and in rabbit liver microsomal fractions. In hepatocytes, CsA was rapidly accumulated inside the cells and metabolized to its different groups of derivatives (mono- and/or dihydroxylated and/or N-demethylated metabolites) [Fabre, Bertault-Peres, Fabre, Maurel, Just, and Cano: Drug Metab. Dispos. 15, 384 (1987)]. In the presence of erythromycin in the extracellular compartment, CsA metabolism was inhibited in a concentration-dependent manner. However, erythromycin did not affect intracellular CsA accumulation and binding of CsA to its intracellular protein binding site(s). Since CsA was specifically metabolized by the cytochrome P-450 LM3c isozyme [Bertault-Peres, Bonfils, Fabre, Just, Cano, and Maurel: Drug Metab. Dispos. 15, 391 (1987)], we further studied the effect of erythromycin on CsA metabolism by liver microsomal fractions. In the presence of erythromycin, CsA metabolism was also decreased. Lineweaver-Burk analysis of erythromycin-CsA interaction demonstrated that erythromycin was a competitive inhibitor (Ki = 156 microM) of CsA metabolism (Km = 0.43 microM; Vmax = 4.8 nmol/min). In agreement with these data, CsA inhibited (i) erythromycin N-demethylation to a large extent and (ii) the appearance of the erythromycin-cytochrome P-450 LM3c complex. We could conclude that the interaction between CsA and erythromycin most likely results from the fact that both drugs are extensively metabolized by the same cytochrome P-450 form: P-450 LM3c or P-450 III A4 according to the new nomenclature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Erythromycin therapy for group A streptococcal pharyngitis. Results of a comparative study of the estolate and ethylsuccinate formulations.

One hundred two children with group A streptococcal pharyngitis were treated on a randomized basis with either 15 mg/kg of erythromycin estolate or 25 mg/kg of erythromycin ethylsuccinate given twice daily for ten days. Twelve patients, including 11 erythromycin ethylsuccinate-treated patients and one erythromycin estolate-treated patient, were dropped from the study at the request of their parents because of abdominal cramping and/or nausea and vomiting that occurred 15 to 45 minutes after ingestion of drug. Eighteen other patients (12 treated with erythromycin ethylsuccinate and six treated with erythromycin estolate) had similar gastrointestinal (GI) tract symptoms that resolved or abated. Excluding patients with reinfections with new streptococcal serotypes and those with resistant strains, the bacteriologic failure rates were 4.3% and 17.5%, and the total failure rates were 6.4% and 35.3% with erythromycin estolate therapy and with erythromycin ethylsuccinate therapy, respectively. The high rate of GI tract intolerance associated with the erythromycin ethylsuccinate appears to be dose related.

Adolescent↗
PubMed1997

Erythromycin prolongs the QTc interval among patients with pneumonia.

Erythromycin is commonly used to treat simple community-acquired pneumonia. We measured the prolongation in QT(c) intervals in EKGs associated with intravenous erythromycin administration among patients hospitalized for simple pneumonia (DRGs 89 and 90). We reviewed the medical records of 50 patients who received at least 5 days of intravenous erythromycin, and found 15 with readable paired EKGs, at least one taken during the period of erythromycin administration and at least one other obtained when the patient had no erythromycin. The mean QT(c) interval in lead II for EKGs taken without erythromycin was 0.422 s and the average prolongation of the QT(c) interval associated with erythromycin administration was 0.046 s (P<0.01). The administration of erythromycin was thus associated with an increase in QT(c) intervals to a mean of 0.468 s, a value considered to be abnormally prolonged. We conclude that erythromycin prolongs the QT(c) interval among patients hospitalized with pneumonia in the same manner previously reported for healthy volunteers in an experimental setting. The magnitude of this erythromycin-induced QT(c) prolongation raises QT(c) intervals into the abnormal range. Although no patient in this small study suffered an adverse effect from the QT(c) prolongation, the magnitude of this effect is sufficiently large to raise clinical concerns.

Journal Article↗
PubMedDate not supplied

Erythromycin in the treatment of streptococcal infections.

In a number of well-designed comparison studies since 1958, erythromycin has proved highly effective in the treatment of both streptococcal pharyngitis and skin infections. Of the two formulations most often prescribed, the estolate salt is better absorbed and achieves higher tissue concentrations than does the ethylsuccinate salt. For these reasons and based on results of the published clinical studies, the appropriate daily dosage for erythromycin estolate is 20 to 30 mg/kg/day and that for erythromycin ethylsuccinate is 40 mg/kg/day. Erythromycin estolate may be given in two, three or four daily doses in the treatment of streptococcal pharyngitis with efficacy rates equal to or better than that achieved with penicillin V. Erythromycin ethylsuccinate is as efficacious as penicillin V when given in three or four daily doses. Treatment of streptococcal pharyngitis should be for 10 days. Recent studies in the treatment of streptococcal skin infections have shown erythromycin to be superior to penicillin. This superiority may be due to increasing numbers of penicillin-resistant staphylococci found in these streptococcal skin lesions. Dosage and frequency of administration of erythromycin in the treatment of streptococcal skin infections is similar to that for the treatment for streptococcal pharyngitis. However, b.i.d. administration has not been well-established in the skin infection studies. Treatment should be given for 7 to 10 days. In conclusion erythromycin is a safe and effective antibiotic for the treatment of streptococcal pharyngitis. Penicillin remains the antibiotic of choice for these infections, but erythromycin is an effective alternate when penicillin allergy is suspected. The appropriate therapy for streptococcal skin infections is less clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1977

Erythromycin jaundice: diagnosis by an in vitro challenge test.

A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base. Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base. This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge. Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms.

Drug Hypersensitivity↗
PubMed1980

Selection of an oral erythromycin product.

The chemistry, bioavailability, and adverse effects of erythromycin base, stearate, estolate, and ethylsuccinate are reviewed. Criteria for the evaluation of erythromycin bioavailability studies include study design, patient population, meal composition and timing, and assay methodology. Based on these criteria, the bioavailability of individual erythromycin products are evaluated in this paper. Compared with other antibiotics, the erythromycins have a good safety record. However, both the estolate and ethylsuccinate forms of erythromycin may cause hepatotoxity. Considering bioavailability and adverse effect data, a specific brand of enteric-coated erythromycin base tablets is recommended for erythromycin-sensitive infections in adults. For pediatric patients, a liquid formulation of erythromycin estolate or erythromycin ethylsuccinate is recommended.

Administration, Oral↗