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PubMed1979

Intravenous erythromycin in acute chest infections in critically ill patients.

Superinfections with resistant micro-organisms have recently become an increasing problem in hospital patients and are throught to be contributed to by inappropriate use of newer, broad-spectrum antibiotics. Erythromycin exhibits a more limited spectrum of antibacterial activity and was therefore re-evaluated in the treatment of acute chest infections in critically ill patients. Twenty-one patients were given erythromycin in a dose of 1.8 g per day by continuous intravenous infusion for up to five days. A satisfactory clinical response occurred in ten patients, in all of whom erythromycin-sensitive micro-organisms were isolated from sputum. An unsatisfactory response occurred in six patients, all associated with micro-organisms insensitive to erythromycin and requiring alternative antibiotic treatment. No undesirable side-effects were noted. It is concluded that erythromycin is a safe and useful agent in the routine treatment of acute chest infections in critically ill patients.

Acute Disease↗
PubMedDate not supplied

Erythromycin-induced hypoacusis: 11 new cases and literature review.

OBJECTIVE: To report 11 cases of possible erythromycin-induced hearing loss and to review all cases reported in the literature. CASE SUMMARY: In the 11 cases reported, the following are reviewed: age, gender, time to onset of and recovery from hypoacusis in relation to erythromycin administration, presence or absence of renal or hepatic disease, underlying disorders, and concurrent administration of other drugs. Hypoacusis appeared with dosages equal to or higher than 4 g/d in patients with a mean age of 52.5 +/- 19 years, a high percentage of whom (45 percent) presented with renal impairment. The hearing loss was reversible in all cases, and subsided a few days (median = 3) after dosage reduction or drug discontinuation. DISCUSSION: Our patients' characteristics are similar to those of patients reported in the literature. Most data indicate that erythromycin-induced hypoacusis is a dose-dependent effect; however, its occurrence in patients otherwise free from disposing factors suggests that it is idiosyncratic. CONCLUSIONS: Erythromycin administered for appropriate indications and dosage adjustments in patients with impaired renal and/or liver function may prevent or reduce the incidence of erythromycin-induced hypoacusis.

Adult↗
PubMed1995

Erythromycin is ineffective against Listeria monocytogenes in multidrug resistant cells.

Multidrug resistance of tumor cells is a well-known phenomenon in oncology. Among the substances excluded from the cells are not only antineoplastic drugs but also certain antibiotics, e.g. erythromycin. To prove the hypothesis that this might render infections with intracellular bacteria untreatable with these antibiotics we used erythromycin to treat intracellular infection of multidrug resistant (MDR) cells with Listeria monocytogenes. Erythromycin was unable to restrict the growth of L. monocytogenes in KBV-1 MDR cells in concentrations of up to 25 micrograms/ml. In contrast, 0.049 micrograms/ml of erythromycin were sufficient to restrict the growth of the bacteria in nonresistant KB 3-1 cells. When verapamil was added to the supernatant of KBV-1 cells, erythromycin regained its effectivity on L. monocytogenes multiplying in these cells. The fact that MDR cells may render intracellular bacteria inaccessible to certain antibiotics might have important implications for the persistence of these bacteria in the host and for the treatment of patients with genetically engineered MDR cells.

Dose-Response Relationship, Drug↗
PubMed1997

Pulmonary concentrations of dirithromycin and erythromycin during acute exacerbation of mild chronic obstructive pulmonary disease.

We compared the concentrations of dirithromycin and erythromycin at steady state in serum and the intrapulmonary region in patients suffering from acute exacerbation of mild chronic obstructive pulmonary disease. Twenty patients received dirithromycin, 500 mg given orally once daily for five consecutive days. The other 20 patients were treated with erythromycin base, which was administered orally four times daily at a total daily dose of 1000 mg for seven days. All patients were divided into eight groups, with five subjects in each group, according to sampling times (2, 4, 8, and hrs after the last dose) and treatment. After the erythromycin treatment mean serum concentrations were higher than those of dirithromycin treatment mean serum concentrations were higher than those of dirithromycin for upto 4 hours, but they were undetectable 24 hours after the last dose. At all time periods, the concentrations of dirithromycin in bronchial secretion, bronchial mucosa and epithelial lining fluid were greater than the concentration in serum. Concentrations of erythromycin were always lower than those of dirithromycin in the explored pulmonary sites. Our data demonstrated that a five day course of 500 mg of dirithromycin once daily induced higher concentrations and longer persistence in the various potential sites of pulmonary infection than a seven day course of 250 mg of erythromycin every 6 hrs. The shorter duration of therapy and the once daily dosing with good efficacy against common respiratory pathogens would be advantageous for patients and would be likely to promote better patient compliance and acceptability.

Administration, Oral↗
PubMed1999

A pilot study of low-dose erythromycin in bronchiectasis.

Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p<0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis.

Anti-Bacterial Agents↗
PubMed1984

Spiramycin and erythromycin in the treatment of acute tonsillo-pharyngitis: a comparative study.

A randomized study was carried out in 100 patients with acute tonsillo-pharyngitis to compare the effectiveness and tolerance of treatment with 500 mg spiramycin 3-times daily for 3 days and 500 mg erythromycin 3-times daily for 5 days. Details were recorded on entry of fever, sore throat, difficulty in swallowing, inflammation of the tonsils and/or pharynx, and oedema. Patients in the two groups were re-examined on Days 4 and 6, respectively. Throat swab cultures and blood determinations of haemoglobin, leucocytes and erythrocyte sedimentation rate were made before and after treatment. The results, analyzed in the 95 patients (48 on spiramycin, 47 on erythromycin) who attended for follow-up, indicated that whilst both antibiotics were effective, only 1 patient receiving spiramycin was classified as failing to respond to treatment compared with 8 of those receiving erythromycin. Moreover, significantly fewer patients on erythromycin had complete disappearance of all the signs and symptoms at the end of the treatment period. These findings were supported by the results of the bacteriological cultures. Both treatments reduced leucocyte levels in those patients with high counts initially, but there was no apparent effect on haemoglobin or erythrocyte sedimentation rate. Two patients on spiramycin complained of dry mouth. In the erythromycin group, 2 patients reported dizziness and 5 nausea.

Adolescent↗
PubMed1999

Delivery of erythromycin to subcutaneous tissues in rats by means of a trans-phase delivery system.

Topical administration of antibiotics is associated with reduced risk of systemic side-effects and alteration of gut microflora, and results in higher concentrations of antibiotics at the site of application (and so a lower dose of the drug is required). In conditions such as acne vulgaris, infiltration of the antibiotics into the infected subcutaneous layers is highly desirable. A trans-phase delivery system (TPDS), a mixture of benzyl alcohol, acetone and isopropanol, has been shown to enhance the effective transport of the antibiotic erythromycin across the epidermal barrier and enhance accumulation in the dermis. Two formulations containing N-methyl[14C]erythromycin were compared, a TPDS solution and a propylene glycol solution. They were applied to the dorsal areas of 4-6 week old Fischer rats and tissues were removed for analysis of radioactivity after 2, 4, 8, 12 or 24 h and skin was biopsied and sectioned for autoradiography. The erythromycin dissolved in the TPDS solvent mixture penetrated the stratum corneum and a relatively high concentration was maintained in adjacent tissues for up to 24 h. Penetration was very effective and the erythromycin was detected in significant amounts in the underlying muscle, various organs and later in the urine. In contrast the propylene glycol carrier, probably because of its primarily hydrophilic character, caused the erythromycin to traverse tissue barriers rapidly and appear in the urine. Microautoradiographs qualitatively revealed progressive disappearance of radioactivity from the surface; this correlated with results obtained by direct isotope counting. The route of penetration, in addition to following the interkeratinocyte spaces, seemed to include the perimeter of the pilosebaceous glands and their appendages before diffusion into the capillaries. The propylene glycol solution seemed to traverse the epidermis and the papillary and reticular dermis more rapidly, which might explain its rapid appearance in the urine. These data suggest that the different solutions penetrate the skin by different mechanisms.

Administration, Cutaneous↗
PubMed1997

Effects of erythromycin, clarithromycin and rokitamycin on nifedipine metabolism in rats.

The effects of erythromycin, clarithromycin and rokitamycin on the metabolism of nifedipine were studied in vitro and in situ. Erythromycin, clarithromycin or rokitamycin added to nifedipine did not inhibit the formation of metabolite, M-1, of nifedipine, whereas pretreatment with erythromycin or clarithromycin significantly (p < 0.05) inhibited its formation. Only erythromycin significantly (p < 0.05) inhibited the formation of M-2 from M-1. These observations agreed with the results obtained using an in situ rat intestinal loop technique. As assessed by the concentrations of nifedipine and M-2 in jugular and portal vein blood, the inhibition of nifedipine metabolism by erythromycin was greater after multiple doses than after a single dose. Moreover, our results suggest that rokitamycin is a less potent inhibitor of nifedipine metabolism.

Animals↗
PubMed2001

Centrilobular nodules correlate with air trapping in diffuse panbronchiolitis during erythromycin therapy.

BACKGROUND: Low-dose erythromycin therapy improves airflow limitation and airway inflammation in patients with diffuse panbronchiolitis (DPB). However, to our knowledge there has been no study to determine whether physiologic improvement during erythromycin therapy correlates with radiologic findings. STUDY OBJECTIVE: To clarify whether improvement in pulmonary function correlates with specific changes on chest CT. DESIGN: The relationship between five CT findings and five pulmonary function parameters was evaluated before and 3 months after low-dose erythromycin therapy in 24 patients with DPB retrospectively. RESULTS: After erythromycin therapy, the predicted percentage of vital capacity (%VC; 87.0 +/- 3.07% vs 98.9 +/- 3.39%; p = 0.00006) and 50% of the maximum midexpiratory flow rate of FVC (1.41 +/- 0.26 L/s vs 1.61 +/- 0.27 L/s; p = 0.03) significantly increased, and the residual volume/total lung capacity ratio (RV/TLC%; 44.5 +/- 1.93% vs 40.7 +/- 1.83%; p = 0.0019) significantly decreased, but the FEV(1) to FVC ratio and 25% of the maximum expiratory flow rate of FVC did not. In five CT findings, centrilobular nodules (3.7 +/- 0.4 vs 1.5 +/- 0.3; p = 0.0001), peripheral bronchiolar wall thickness (3.8 +/- 0.3 vs 2.6 +/- 0.4; p = 0.0007), and peripheral bronchiolectasis (2.8 +/- 0.3 vs 2.2 +/- 0.4; p = 0.0058) had significantly improved, whereas low attenuation area and central bronchiectasis had not. There were positive correlations of improved scores of centrilobular nodules with improved %VC (r = 0.58, p = 0.0062) and RV/TLC% (r = 0.64, p = 0.0022). CONCLUSIONS: Decreased air trapping in DPB correlates with an improvement of centrilobular nodules, which reflects the obstructive lesions of bronchioles during the erythromycin therapy.

Bronchiolitis↗
PubMed1982

The effect of erythromycin on theophylline pharmacokinetics at steady state.

We compared steady-state theophylline pharmacokinetics in 13 healthy adults before and immediately after erythromycin therapy. All subjects received a five-day course of oral aminophylline 3 mg/kg every six hours prior to and during a five-day course of oral erythromycin stearate (1 g daily). Each subject acted as his own control. Multiple serum samples were collected over ten hours following the last dose of aminophylline during both the control and experimental phases of the study. Erythromycin did not significantly affect theophylline clearance (P greater than 0.70), elimination (P greater than 0.75), or volume of distribution (P greater than 0.30). We found no evidence of a pharmacokinetic interaction between theophylline and erythromycin at steady state. Worsening pulmonary function may be responsible for altered theophylline pharmacokinetics in patients coincidentally receiving erythromycin.

Administration, Oral↗
PubMed2003

Drug interaction between mosapride and erythromycin without electrocardiographic changes.

QT prolongation and torsades de pointes have been documented in patients administered cisapride and its blocking of potassium channels in myocytes has been suggested as the mechanism. An interaction with cytochrome P450 CYP3A4 inhibitor drugs like macrolide and azole antifungals is also thought to be a possible mechanism. Since mosapride has characteristics similar to cisapride, we examined the effects of mosapride on the electrocardiogram and pharmacokinetics before and after its coadministration with erythromycin. Ten healthy male volunteers were repeatedly administered mosapride 15 mg/day for 7 days followed by coadministration with erythromycin 1200 mg/day for 7 days. Coadministration with erythromycin resulted in a 1.6-fold increase in the Cmax of mosapride and prolongation of t(1/2) from 1.6 to 2.4 hours, indicating the inhibition of mosapride metabolism. However, there were no significant differences in the QT interval and QTc between mosapride alone and concomitant use with erythromycin. There was no correlation between the electrocardiographic parameters and plasma mosapride concentrations, and no case exceeded the upper limit of the normal range of QTc. Although there was a certain pharmacokinetic interaction between mosapride and erythromycin, their coadministration did not affect the electrocardiogram at all, indicating a reduced likelihood of severe clinical adverse events like QT prolongation and torsades de pointes.

Adult↗
PubMed2002

Lack of clinically relevant interaction between desloratadine and erythromycin.

OBJECTIVE: To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin. DESIGN: A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study. PARTICIPANTS: 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years. INTERVENTIONS: Oral desloratadine 7.5mg daily in combination with either placebo (n = 24) or erythromycin 500mg every 8 hours (n = 24) for 10 days. After a minimum 7-day washout period, participants crossed over to the alternative regimen. MAIN OUTCOME MEASURES: ECG parameters. RESULTS: Desloratadine/erythromycin did not induce clinically or statistically significant changes in any ECG parameter. The maximum corrected QT (QT(c)) interval was 445 msec for both treatments. The peak plasma concentration and area under the plasma concentration-time curve from 0 to 24 hours of desloratadine were slightly increased by 1.2- and 1.1-fold by concomitant administration of erythromycin compared with desloratadine/placebo. Gastrointestinal adverse events were more frequent after desloratadine/erythromycin than desloratadine/placebo (46 vs 4%), reflecting the poor gastrointestinal tolerability of erythromycin. There were no reports of syncope. CONCLUSION: Combined desloratadine/erythromycin therapy was well tolerated and had no clinically relevant electrocardiographic effects at a dose that was 50% higher than the recommended dose of 5mg. Although coadministration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with any prolongation of the QT(c) interval, and no toxicity was observed clinically.

Adult↗
PubMed2000

In vitro effects of erythromycin, lidocaine, and metoclopramide on smooth muscle from the pyloric antrum, proximal portion of the duodenum, and middle portion of the jejunum of horses.

OBJECTIVE: To evaluate effects of erythromycin, lidocaine, and metoclopramide on smooth muscle of the pyloric antrum (PA), proximal portion of the duodenum (PD), and middle portion of the jejunum (MJ) of horses. Sample Population-Strips of smooth muscle from 7 horses. PROCEDURE: Isolated muscle strips were suspended in a bath and attached to isometric force transducers. Once stable spontaneous contractions were observed, agents were added. Isometric stress responses were compared with the amplitude of spontaneous contractions. RESULTS: A single dose of erythromycin to the PA increased contractile amplitude (CA) for the longitudinal smooth muscle (mean +/- SEM, 76+/-16 g/cm2) but decreased CA for circular smooth muscle (-79+/-23 g/cm2). The inhibitory effect was decreased by tetrodotoxin, N(G)-nitro-L-arginine methyl ester, and a vasoactive intestinal peptide antagonist. Erythromycin increased CA for the MJ, which was maximal at 10(-4)M (171+/-36 g/cm2). Lidocaine increased CA for the PD, which was maximal at 10(-4) M (60+/-5 g/cm2). Metoclopramide increased the CA, which was maximal at 10(-4) M for the PA (75+/-26 g/cm2), PD (279+/-33 g/cm2), and MJ (456+/-59 g/cm2). CONCLUSIONS: Regional differences in responses to erythromycin, lidocaine, and metoclopramide were evident in the gastrointestinal tract of horses. Metoclopramide increased CA in all tissues used, whereas erythromycin inhibited CA in circular smooth muscle but stimulated CA in longitudinal smooth muscle from the PA. Inhibition is caused by stimulation of inhibitory nerves and is mediated, in part, by nitric oxide and vasoactive intestinal peptide.

Animals↗
PubMed2002

Binding of radiolabeled porcine motilin and erythromycin lactobionate to smooth muscle membranes in various segments of the equine gastrointestinal tract.

OBJECTIVE: To identify and characterize motilin receptors in equine duodenum, jejunum, cecum, and large colon and to determine whether erythromycin lactobionate competes with porcine motilin for binding to these receptors. SAMPLE POPULATION: Specimens of various segments of the intestinal tracts of 4 adult horses euthanatized for reasons unrelated to gastrointestinal tract disease. PROCEDURE: Cellular membranes were prepared from smooth muscle tissues of the duodenum, jejunum, pelvic flexure, and cecum. Affinity and distribution of motilin binding on membrane preparations were determined by use of 125I-labeled synthetic porcine motilin. Displacement studies were used to investigate competition between 125I-labeled synthetic porcine motilin and erythromycin lactobionate for binding to motilin receptors in various segments of bowel. RESULTS: Affinity of 125I-labeled synthetic porcine motilin for the equine motilin receptor was estimated to be 6.1nM. A significantly higher number of motilin receptors was found in the duodenum than in the pelvic flexure and cecum. The jejunum had a significantly higher number of motilin receptors than the cecum. Erythromycin lactobionate displacement of 125I-labeled porcine motilin from the equine motilin receptor did not differ significantly among various segments of bowel. CONCLUSIONS AND CLINICAL RELEVANCE: Motilin receptors were found in the duodenum, jejunum, pelvic flexure, and cecum of horses. The highest number of motilin receptors was in the duodenum, and it decreased in more distal segments of bowel. Erythromycin lactobionate competed with motilin binding in the equine gastrointestinal tract. This suggests that 1 of the prokinetic actions of erythromycin in horses is likely to be secondary to binding on motilin receptors.

Animals↗
PubMed1996

Neutrophil chemotactic activity in cryptogenic organizing pneumonia and the response to erythromycin.

The present study was aimed at elucidating the role of inflammatory cells in the pathogenesis of cryptogenic organizing pneumonia, and the mode of action of erythromycin in inhibiting the progression of the disease. Bronchoalveolar lavage fluid was obtained from 16 patients with cryptogenic organizing pneumonia and 4 control subjects. Neutrophil chemotactic activity was determined in relation to the concentration of two cytokines, interleukin-8 and tumor necrosis factor-alpha. Eight patients with cryptogenic organizing pneumonia, 4 with bronchoalveolar lavage fluid neutrophilia and 4 without, received low dose oral erythromycin daily (600 mg) for 2 to 3 months. Bronchoalveolar lavage fluid was obtained before and after treatment. In the bronchoalveolar lavage fluid of cryptogenic organizing pneumonia patients with bronchoalveolar lavage fluid neutrophilia, the levels of neutrophil chemotactic activity, interleukin-8, and tumor necrosis factor-alpha were significantly increased compared with levels measured in control subjects and in cryptogenic organizing pneumonia patients without bronchoalveolar lavage fluid neutrophilia. The level of interleukin-8 correlated with the percent of neutrophils and neutrophil chemotactic activity of bronchoalveolar lavage fluid, while the level of tumor necrosis factor-alpha did not. Furthermore, the levels of interleukin-8 and neutrophil chemotactic activity in the bronchoalveolar lavage fluid of cryptogenic organizing pneumonia patients with bronchoalveolar lavage fluid neutrophilia were significantly decreased following treatment with erythromycin. In contrast, the level of tumor necrosis factor-alpha was not affected by treatment with erythromycin. It is possible that cryptogenic organizing pneumonia is caused by neutrophil-mediated inflammation, and that the favorable clinical effect of erythromycin is due to inhibition of neutrophil accumulation in the peripheral airways through a biological activity other than bacteriostasis, e.g., local suppression of interleukin-8 production.

Aged↗
PubMed1993

Erythromycin versus metronidazole in the treatment of bacterial vaginosis.

Of 101 women, 15-50 years of age, presenting with vaginal discharge, 34 had bacterial vaginosis and were randomly assigned to a seven-day course of oral treatment with either erythromycin (0.5 g b.i.d.) or metronidazole (0.4 g b.i.d.) in a single-blind, cross-over study. Treatment failure (> or = three clinical signs of bacterial vaginosis) occurred in 13 (81%) of 16 patients given erythromycin, as compared with three (17%) of 18 women treated with metronidazole (p < 0.001). Persistence of Gardnerella vaginalis, Mobiluncus species and/or Mycoplasma hominis was found in 14 of 16 patients treated with erythromycin, and in four of 16 patients treated with metronidazole. Treatment with metronidazole was successful (< or = two clinical signs of bacterial vaginosis) in eight of 10 cases of erythromycin treatment failure. Neither of two cases of metronidazole treatment failure was cured with erythromycin. At three-month follow-up of 31 women, persistence or recurrence of bacterial vaginosis was diagnosed in 11 cases (36%).

Administration, Oral↗
PubMed1996

Inhibitory effect of erythromycin on ion transport by stria vascularis and vestibular dark cells.

A previous study showed that systemic administration of erythromycin caused a reversible decline in the endocochlear and cochlear microphonic potentials. Those data were thought to suggest that erythromycin caused hearing loss by interference with ion transport processes in the stria vascularis. The present study was undertaken to test this hypothesis by measuring the effects of erythromycin perfused on either the apical or basolateral side on the transepithelial short circuit current (Isc), a measure of the K+ secretion rate. Isc was measured from preparations of strial marginal cells and the homologous vestibular dark cells in vitro with a micro-Ussing chamber. Erythromycin was found to have no effect when perfused on the apical side but to cause a reversible decrease in Isc when perfused on the basolateral side for both epithelia. These data are consistent with the notion that at least one ototoxic effect of erythromycin is the inhibition of K+ secretion in the inner ear.

Animals↗
PubMed1994

Effect of erythromycin administration on upper gastrointestinal motility in scleroderma patients.

BACKGROUND: Gastrointestinal involvement is frequent in patients with scleroderma. Erythromycin, a macrolide antibiotic, has been shown to accelerate gastric emptying in normal subjects and diabetic patients. The present study investigated the effects of acute erythromycin administration on gastric and gallbladder motility in patients with scleroderma and gastrointestinal involvement. METHODS: Twelve scleroderma patients and 14 healthy subjects were investigated. Each subject was investigated on 4 different days. Gastric and gallbladder emptying and gastric motility were determined by sonography and manometry, and the effect of 2 mg/kg/h erythromycin in fasted patients or after semisolid meal evaluated. RESULTS: The half-time of gastric emptying in response to semisolid meal was 121.3 +/- 14.0 min (SE) in scleroderma patients and 45.7 +/- 10.4 min in healthy subjects (P < 0.01). The peak of gallbladder emptying occurred later in scleroderma patients (95.0 +/- 5.0 min) than in healthy subjects (45.0 +/- 8.0 min) (P < 0.01). Erythromycin stimulated gastric and gallbladder motility in fasted subjects, as shown by manometry and sonography, and accelerated gastric and gallbladder emptying when administered immediately before the meal (P < 0.01). CONCLUSIONS: Erythromycin accelerates gastric and gallbladder emptying in scleroderma patients and might be helpful in the treatment of gastrointestinal motor abnormalities in these patients.

Adult↗