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PubMed2002

The influence of magnesium on the electrophysiological effects of erythromycin in the isolated Guinea pig heart.

There have been several case reports that erythromycin can prolong the QT interval, resulting in torsades de pointes. As magnesium is well established in the treatment of torsades de pointes, we aimed to investigate how this trace element influences the electrophysiological effects of erythromycin. The effects of erythromycin and magnesium on cardiac conduction and refractoriness were evaluated in isolated guinea pig hearts perfused by the method of Langendorff. Erythromycin was given in concentrations of 10, 30 and 100 microM. In the magnesium group MgSO4 was elevated to 3.4 mM. Magnesium at a concentration of 3.4 mM did not affect cardiac conduction and refractoriness. Erythromycin prolongs the QT interval in a dose-dependent manner. The prolongation of the QT interval by erythromycin was diminished by the elevated magnesium concentration (3.4 mM) at high rates (pacing cycle length 180 vs. 220 ms). The most pronounced effect of erythromycin (100 microM) was the prolongation of the atrial effective refractory period. This effect was nearly abolished by the elevated magnesium concentration (129.0 +/- 8.3% vs. 41.9 +/- 10.6%, P < 0.01, n = 6, x +/- SEM). In summary, magnesium minimizes the effects of erythromycin on the repolarization period in the ventricle and on the effective refractory period of the atrium.

Animals↗
PubMed1992

The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease.

There are significant interpatient differences in the activity of a major drug metabolizing enzyme termed P450IIIA. Because P450IIIA uniquely catalyzes the N-demethylation of erythromycin, we have proposed that the P450IIIA activity of a patient may be determined from the rate of 14CO2 production in the breath after an intravenous infusion of a test dose of [14C-N-methyl]erythromycin. However, direct evidence that this erythromycin breath test selectively measures P450IIIA and not other major human liver P450s in patients has been lacking. We therefore administered the erythromycin breath test to nine patients with severe liver disease who were awaiting liver transplantation. Microsomes were prepared from liver samples obtained during surgery and the concentration of P450IA2, P450IIC8, P450IIC9, P450IIE1, and P450IIIA were determined immunochemically. We found a significant correlation between patients' erythromycin breath test results and their liver P450IIIA levels (r2 = 0.56, p = 0.02). In contrast, there was no correlation at all between the erythromycin breath test result and the microsomal levels of any of the other four P450s assayed. The correlation of the erythromycin breath test and P450IIIA did not appear related to the extent of liver disease because neither correlated with prothrombin time or albumin or bilirubin levels. These data provide the best evidence to date that the erythromycin breath test is a specific assay of in vivo P450IIIA activity in patients.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression.

1. Macrolides have long been used as anti-bacterial agents; however, there is some evidence that may exert anti-inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti-inflammatory activity. 2. Erythromycin pretreatment (30 mg kg(-1) day(-1) for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg(-1))-induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor-alpha and macrophage-inflammatory protein-2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA upregulation in response to airway challenge with LPS. 3. Mesentery superfusion with LPS (1 mug ml(-1)) induced a significant increase in leukocyte-endothelial cell interactions at 60 min. Erythromycin pretreatment abolished the increases in these parameters. 4. LPS exposure of the mesentery for 4 h caused a significant increase in leukocyte rolling flux, adhesion and emigration, which were inhibited by erythromycin by 100, 93 and 95%, respectively. 5. Immunohistochemical analysis showed that LPS exposure of the mesentery for 4 h caused a significant enhancement in P-selectin, E-selectin, ICAM-1 and VCAM-1 expression that was downregulated by erythromycin pretreatment. 6. Flow cytometry analysis indicated that erythromycin pretreatment inhibited LPS-induced CD11b augmented expression in rat neutrophils. 7. In conclusion, erythromycin inhibits leukocyte recruitment in the lung and this effect appears mediated through downregulation of CAM expression. Therefore, macrolides may be useful in the control of neutrophilic pulmonary diseases.

Animals↗
PubMed2000

Low-dose intravenous erythromycin: effects on postprandial and fasting motility of the small bowel.

BACKGROUND: Erythromycin is a motilin agonist and its effects on gastrointestinal motility are dependent on both dose and whether it is administered during the postprandial or fasting state. AIM: To study the motility response of the small bowel to a low dose of intravenous erythromycin after meal intake and during fasting. METHODS: Eighteen healthy subjects with mean age of 25 years were studied by small bowel manometry. Erythromycin was administered intravenously (0.75 mg per kg body weight) during 20 min in the postprandial (n=9) and the fasting state (n=9), and the motility response was recorded. RESULTS: Erythromycin significantly reduced the frequency of propagated contractions (P < 0.001) and the amplitude of contractions (P < 0.02) in the small bowel during established postprandial motility. During the fasting state, erythromycin invariably initiated a phase III-like activity, which was similar to the spontaneous nocturnal phase III and migrated significantly more slowly than the diurnal phase III (P < 0.01). CONCLUSIONS: A low dose of erythromycin administered intravenously during the postprandial state significantly inhibits small bowel motility, whereas administration during the fasting state initiates a phase III resembling the nocturnal rather than the diurnal phase III. These effects of erythromycin may indicate interference with vagal pathways. Due to its inhibitory effects, the clinical use of erythromycin in patients with hypomotility should be reconsidered, and the potential usefulness of these effects in patients with exaggerated intestinal motility deserves further attention.

Adult↗
PubMed2003

No clinically significant effect of erythromycin or azithromycin on the pharmacokinetics of voriconazole in healthy male volunteers.

AIMS: The antibiotic erythromycin is a potent inhibitor of cytochrome P450 CYP3A4 metabolism. As CYP isozymes, including CYP3A4, are involved in the metabolism of the new triazole voriconazole, this study investigated the effects of multiple-dose erythromycin or azithromycin on the steady-state pharmacokinetics of voriconazole in healthy male subjects. METHODS: In an open, randomized, parallel-group, single-centre study, 30 healthy male subjects aged 20-41 years received oral voriconazole 200 mg twice daily for 14 days plus either erythromycin (1 g twice daily on days 8-14), azithromycin (500 mg once daily on days 12-14) or placebo (twice daily on days 8-14). Only morning doses were administered on day 14. Plasma concentrations of voriconazole were measured up to 12 h postdose on days 7 and 14, and plasma pharmacokinetic parameters were calculated. Adverse events and standard laboratory test results were recorded before and throughout the study. RESULTS: Comparison of the voriconazole Cmax day 14/day 7 ratio for the voriconazole + erythromycin group with that of the voriconazole + placebo group yielded a ratio of 107.7%[90% confidence interval (CI) 90.6, 128.0]; for the voriconazole + azithromycin group, the ratio was 117.5% (90% CI 98.8, 139.7). Comparison of the voriconazole AUCtau day 14/day 7 ratios of the voriconazole + erythromycin and voriconazole + azithromycin groups with that of the voriconazole + placebo group showed ratios of 101.2% (90% CI 89.1, 114.8) and 107.9% (90% CI 95.1, 122.4), respectively. For voriconazole tmax, the differences between the day 14-day 7 calculations for the voriconazole + erythromycin or the voriconazole + azithromycin groups and that of the voriconazole + placebo group were - 0.2 h (90% CI - 0.8, 0.3) and - 0.1 h (90% CI - 0.7, 0.5), respectively. None of these changes was considered clinically relevant. The study drugs were well tolerated by subjects in all groups; the most common study drug-related adverse events were visual disturbances, reported in all groups, and abdominal pain, present in the voriconazole + erythromycin group. CONCLUSIONS: Coadministration of erythromycin or azithromycin does not affect the steady-state pharmacokinetics of voriconazole in a clinically relevant manner in healthy male subjects.

Adult↗
PubMed1999

Effects of erythromycin on experimental extrinsic allergic alveolitis.

BACKGROUND: Recent clinical studies have demonstrated the efficacy of erythromycin for treating patients with chronic lower respiratory tract inflammation. Mechanisms related to the anti-inflammatory action are yet to be determined. OBJECTIVES: The therapeutic efficacy of erythromycin in experimental extrinsic allergic alveolitis (EAA) was evaluated. METHODS: A murine model of EAA was developed by intratracheal inoculations with particulate Trichosporon mucoides followed by erythromycin or josamycin treatment. Cell populations, specific antibodies, chemotactic activities, TNF-alpha, IL-1beta, MIP-2 and KC of bronchoalveolar lavage fluid (BALF); histopathology of the lung and footpad reaction; myeloperoxidase of the whole lung; and immunohistochemistry of intercellular adhesion molecule- (ICAM-1), at 6 and 96 h after the challenge, were examined. RESULTS: There was a marked neutrophilic alveolitis and bronchiolitis at 6 h, and lymphocytic alveolitis and perivenule cuffing at 96 h after the challenge. Increase in total inflammatory cells and neutrophils in BALF at 6h was significantly suppressed by pretreatment with 5 mg/kg/day of erythromycin intraperitoneally for 5 days (P<0.01), with no apparent effect on specific antibodies, chemotactic activity or cytokines. Erythromycin also suppressed the Arthus-type reaction in the footpad (P<0.01). Histopathological studies revealed that erythromycin markedly decreased neutrophils in the lung and skin lesions and myeloperoxidase in the lung, simultaneously with inhibiting ICAM-1 expression. The therapy has no remarkable effects on lymphocytes or 96 h response. Josamycin had no effects on the model. CONCLUSIONS: The therapeutic dosage of erythromycin significantly suppressed acute neutrophil influx into the lung, intradermal Arthus reaction and the expression of ICAM-1 in the lesions of experimental EAA. Erythromycin may be effective for treating subjects with acute EAA.

Alveolitis, Extrinsic Allergic↗
PubMed1990

Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies.

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

Adult↗
PubMed2001

Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis.

OBJECTIVES: To evaluate the risk for infantile hypertrophic pyloric stenosis (IHPS) among infants prescribed systemic erythromycin, infants prescribed a course of erythromycin ophthalmic ointment, and infants whose mothers were prescribed a macrolide antibiotic during pregnancy. STUDY DESIGN: Retrospective cohort study of infants born at an urban hospital from June 1993 through December 1999. RESULTS: Of 14,876 eligible infants, 43 (0.29%) developed IHPS. Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66). Erythromycin ophthalmic ointment for conjunctivitis was not associated with increased risk of IHPS. Maternal macrolide antibiotics within 10 weeks of delivery may have been associated with higher risk of IHPS but the data were not conclusive. CONCLUSIONS: This study confirms an association between systemic erythromycin in infants and subsequent IHPS, with the highest risk in the first 2 weeks of age. No association was found with erythromycin ophthalmic ointment. A possible association with maternal macrolide therapy in late pregnancy requires further study. Systemic erythromycin should be used with prudence in early infancy.

Anti-Bacterial Agents↗
PubMed1999

Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis.

BACKGROUND: Erythromycin has recently been found to be a gastrointestinal prokinetic agent in humans. Acute hyperglycaemia has been associated with delayed gastric emptying in both healthy controls and diabetic patients. Our aim was to investigate in gastroparetic patients (diabetics and idiopathics) whether hyperglycaemia, per se, reduces gastric motility during erythromycin-induced acceleration of gastric emptying of solids. METHODS: In 12 gastroparetic patients, 6 diabetics and 6 idiopathics, gastric emptying of solids was measured scintigraphically after giving placebo in normoglycaemia (5-8.9 mmol/l glucose) or 200 mg erythromycin lactobionate intravenously in normo- or hyperglycaemia (16-19 mmol/l glucose) induced by intravenous glucose infusion in random order on separate days. RESULTS: Erythromycin in normoglycaemia accelerated solids gastric emptying compared with placebo in all patients by abolishing the lag-phase duration and by decreasing the retained percentage of a meal in the stomach at 120 and 150 min (14.5% +/- 5.3% versus 88.4% +/- 10.6% and 3.5% +/- 2.1% versus 70.1% +/- 15.4%, respectively) (P < 0.001). The retained isotopic percentage in the stomach after erythromycin in induced hyperglycaemia compared with erythromycin in normoglycaemia, at 120 and 150 min, was increased (51.9% +/- 9.8% versus 14.5% +/- 5.3%, and 24.5% +/- 5.9% versus 3.5% +/- 2.1%, respectively) (P < 0.001) but was decreased in comparison with placebo (P < 0.001). A significantly increased percentage of isotope was retained in the stomach of the diabetic patients at 120 and 150 min, compared with the idiopathics, only after giving erythromycin in the hyperglycaemic condition (57.6% +/- 8.7% versus 46.1% +/- 7.6% (P = 0.036) and 27.8% +/- 5.7% versus 21.1 +/- 4.4% (P = 0.040), respectively). CONCLUSIONS: Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis and increases the retained isotopic meal in the stomach. Hyperglycaemia reduces gastric motility more in the diabetic patients with gastroparesis than in idiopathic patients.

Diabetes Mellitus, Type 1↗
PubMed2005

Antiangiogenic effect of erythromycin: an in vitro model of Bartonella quintana infection.

BACKGROUND: Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. METHODS: The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. RESULTS: We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. CONCLUSION: The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.

Amino Acid Sequence↗
PubMed1996

Erythromycin interaction with risperidone or clomipramine in an adolescent.

An adverse event is described which appeared when the macrolide antibiotic erythromycin was added to a regimen of risperidone 0.5 mg bid and clomipramine 50 mg tid in a 15-year-old male being treated for Tourette's, obsessive-compulsive, and attention-deficit hyperactivity disorders. An acute onset of behavioral symptoms, including agitation, labile mood, incessant talking, and argumentativeness, began within 24 h of starting the erythromycin and persisted for 9 days after its discontinuation. It was followed by a return to stable functioning on the prior risperidone-clomipramine regimen. Erythromycin, risperidone, and clomipramine are all metabolized by the hepatic cytochrome P450 system. It is postulated that the addition of erythromycin, a known inhibitor of CYP3A and CYP1A2, resulted in alterations in the metabolism of clomipramine and risperidone. Clomipramine metabolism is dependent upon the isoenzymes CYP2D6 and CYP1A2, and risperidone is a substrate for CYP2D6. Erythromycin would inhibit demethylation of clomipramine at the 1A2 isoenzyme and lead to a dual interaction between risperidone and clomipramine at the CYP2D6 isoenzyme. The subsequent increases in plasma levels of clomipramine, risperidone, their metabolites, or a combination of these agents could explain the adverse effects noted in this patient. In the absence of risperidone, clomipramine could have been metabolically cleared by CYP2D6. In the absence of clomipramine, risperidone clearance would not be affected by erythromycin. So the proposed mechanism requires an interaction involving all three agents: erythromycin, clomipramine, and risperidone. Alterations in plasma protein binding may also have played a role, because all three agents are extensively protein bound. Caution is urged when prescribing erythromycin with psychotropic drugs that are highly protein bound and/or are metabolized by the same P450 isoenzymes.

Acne Vulgaris↗
PubMed1995

Infections caused by erythromycin-resistant Streptococcus pneumoniae: incidence, risk factors, and response to therapy in a prospective study.

To evaluate the incidence and the significance of resistance to erythromycin among clinical isolates of Streptococcus pneumoniae, we identified and prospectively followed all hospitalized patients in a 27-month period who had the organism isolated from any clinical sample. Patients who had an infection caused by pneumococci resistant to erythromycin (minimum inhibitory concentration, > 1 microgram/mL) were compared to those with infections caused by erythromycin-susceptible organisms. The incidence of erythromycin resistance among pneumococci doubled over the study period (from 7.6% in 1988 to 15.2% in 1992). Most strains (94%) showed resistance to multiple antibiotics, including other macrolides. By multivariate analysis, an age of < 5 years and nosocomial acquisition of the infection were independent risk factors for erythromycin resistance. Among patients with pneumococcal pneumonia caused by erythromycin-resistant organisms, 9 patients treated with third-generation cephalosporins were cured, while therapy with erythromycin failed for 2 of the 6 patients to whom it was administered. The rapid and significant increase of erythromycin resistance among clinical isolates of S. pneumoniae points to the need for routine surveillance of pneumococcal resistance.

Adolescent↗
PubMed1985

Erythromycin stearate, 1.5 g, for the oral prophylaxis of streptococcal bacteraemia in patients undergoing dental extraction: efficacy and tolerance.

Erythromycin stearate, 1.5 g, was effective in reducing the prevalence of streptococcal bacteraemia following dental extraction when administered orally under supervision 1 h before extraction. Blood samples were collected from adult patients for culture and erythromycin assay 1 to 2 min after the dental procedure. High dilution techniques involving the use of 1 litre bottles of broth were used to inactivate erythromycin present in blood cultures. Viridans streptococci were isolated from 6 of 40 patients receiving erythromycin (15%) compared with 18 of 42 control patients (43%). The mean serum erythromycin concentration at the time of extraction was 3.7 mg/l for 34 patients receiving erythromycin who had negative blood cultures compared with 1.8 mg/l for the six patients given erythromycin who had viridans streptococci isolated from the blood. Both the 1.5 g erythromycin stearate and placebo oral doses were well tolerated in a double blind comparative study which included 109 adult dental patients.

Administration, Oral↗
PubMed1988

Comparative liver toxicity of various erythromycin derivatives in animals.

The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs. In the 4-day rat study, EC caused fatty metamorphosis in the liver. ES caused similar, but milder changes at a dose nearly five times higher. The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups. Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses. Epithelial hyperplasia was observed also in the bile ducts. EE caused similar but milder changes. The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA. The ES-group was practically without changes and very much like the EA-group. Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives. In the 28-day studies, only EA and ES were investigated. In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs. In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period. Only EA was studied in the 6-month study. In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes. In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter. No severe changes were seen in the liver histopathology. In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats. EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses. This evidently reversible effect was considered a common characteristic of erythromycins.

Animals↗
PubMed1990

Comparative in-vitro activity of azithromycin and erythromycin against Gram-positive cocci, Haemophilus influenzae and anaerobes.

The in-vitro activities of azithromycin and erythromycin were compared against 689 clinical isolates, including Gram-positive cocci, Haemophilus influenzae, and anaerobes. Of the 100 methicillin-susceptible isolates of Staphylococcus aureus tested, 77% were susceptible to 1 mg/l azithromycin and 0.5 mg/l erythromycin, whereas 22% were resistant to 32 mg/l of both compounds. All methicillin-resistant S. aureus isolates were highly resistant to both macrolides (MIC greater than 64 mg/l). Coagulase-negative staphylococci showed a wide range of susceptibilities to both compounds; MIC50 values for azithromycin and erythromycin for all isolates were 0.5 and 0.25 mg/l, respectively. With the exception of enterococci, both macrolides showed similar activity against streptococci; MIC90 values for both group A and group B streptococci were 0.03 and 0.06 mg/l for erythromycin and azithromycin, respectively. Azithromycin was less active than erythromycin against enterococci, with mode MICs of 4.0 and 1.0 mg/l, respectively; about 20% of isolates were highly resistant to both compounds. Azithromycin was substantially more active than erythromycin against H. influenzae; 41% of isolates were inhibited by 0.5 mg/l azithromycin and all isolates were inhibited by 2 mg/l. The MIC90 for erythromycin was 8 mg/l; 36% of isolates required concentrations of greater than or equal to 4 mg/l for inhibition. The anaerobic bacteria tested showed similar susceptibility to both azithromycin and erythromycin.

Azithromycin↗
PubMed1991

Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin.

The effects of erythromycin stearate over a concentration range of 0.1-10 mg/l on production of elastase, protease and leucocidin by clinical isolates of Pseudomonas aeruginosa were investigated. Growth of P. aeruginosa N42 in broth was not affected significantly during 24 h culture with erythromycin (0.1-10 mg/l), although extracellular protein contents were reduced by erythromycin at concentrations of 0.1-1.0 mg/l. Production of elastase and protease by strain N42 was significantly suppressed by erythromycin with a maximum inhibition at 0.5 mg/l, but the complete inhibition of enzyme production was not achieved. In contrast, leucocidin production by strain N42 was completely impaired by erythromycin at concentrations of 0.1-5.0 mg/l. Although the leucotoxic activity, as determined by vital staining, was not detected, the leucocidin fraction prepared from the autolysate of strain N42 cultured with 10 mg/l of erythromycin induced morphological changes in human leucocytes, resulting in release of elastase. Erythromycin exerted similar effects on other clinical isolates of P. aeruginosa. These findings indicate that erythromycin might have a role in P. aeruginosa infection, although it has no direct antibacterial activity.

Bacterial Proteins↗
PubMed1993

A multicentre study comparing the safety and efficacy of dirithromycin with erythromycin in the treatment of bronchitis.

This European multicentre (110 centres), double-blind, randomized clinical trial compared the safety and efficacy of dirithromycin (500 mg orally once daily) and erythromycin (250 mg orally qds) in the treatment of either acute bacterial bronchitis or acute bacterial exacerbations of chronic bronchitis. From January 1989 to September 1990, 1222 patients (529 with acute bronchitis and 693 with acute exacerbations of chronic bronchitis) were included in the trial. Clinical and bacteriological evaluations were performed on 135 evaluable patients with acute bronchitis (72 in the dirithromycin group and 63 in the erythromycin group) and in 202 patients with acute exacerbations of chronic bronchitis (89 treated with dirithromycin and 113 treated with erythromycin). Evaluations were performed during treatment (days 3-5), post-therapy (three to five days after therapy completion), and late post-therapy (10-14 days following the end of therapy). In acute bronchitis, both drugs were effective with clinical success rates of 93.0% and 95.2% at post-therapy, and 96.9% and 100% at late post-therapy for dirithromycin and erythromycin, respectively. Pathogen eradication rates at post-therapy were 83.3% for the dirithromycin group and 85.7% for the erythromycin group. In acute exacerbations of chronic bronchitis, the drugs were also effective with 89.9% and 92.1% cure or improvement at post-therapy and 98.7% and 95.0% at late post-therapy for dirithromycin and erythromycin, respectively. Pathogen eradication rates were 75.3% in both treatment groups. There were no statistically significant differences in clinical and bacteriological results between treatments in patients with acute bronchitis or acute exacerbations of chronic bronchitis. Of the 1222 patients included, no significant differences in the number of patients reporting adverse events were observed. There were nine early discontinuations due to adverse events in the dirithromycin group and 14 in the erythromycin group. Dirithromycin (500 mg once daily for seven days) was as effective and as safe as erythromycin (250 mg qid for seven days) in the treatment of acute bacterial bronchitis and acute bacterial exacerbations of chronic bronchitis.

Adolescent↗
PubMed1997

Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes.

Opsonophagocytic killing of some bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) by phagocytes is enhanced by previous brief exposure of the organism to antibiotics. We studied the regrowth of Legionella pneumophila previously pretreated with levofloxacin, erythromycin and/or rifampicin in human monocytes. The MIC for the L. pneumophila isolate of levofloxacin, erythromycin and rifampicin was 0.03, 0.5 and 0.001 mg/L, respectively. Growth of L. pneumophila from buffered charcoal yeast extract (BCYE) agar for 24 h was subcultured into BYE broth containing from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin. After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms were washed and opsonized with 20% heat inactivated pooled normal human serum. Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio) previously adhered to wells in tissue culture plates containing RPMI and 10% fetal calf serum. After 0, 24, 48 and 72 h of incubation, quantitative cultures of lysed human monocytes were done on BCYE agar. Our results indicate effective inhibition on L. pneumophila at 0 h regardless of the antibiotic (levofloxacin, rifampicin or erythromycin) or their concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, recovery and regrowth of L. pneumophila were both antibiotic- and concentration-dependent. In comparison with controls (no antibiotic pretreatment), peak regrowth of L. pneumophila pretreated with either 1x MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and reduced (30% of control peak regrowth). Regrowth of L. pneumophila pretreated with 1x MIC of rifampicin continued beyond 72 h. Pretreatment with levofloxacin at 4x MIC caused the greatest degree of growth inhibition (2 log10). In contrast, at 72 h, regrowth of organisms pretreated with 4x MIC of erythromycin or rifampicin was less than peak control (P < 0.01) but greater than that seen with levofloxacin (P < 0.01). The rate and degree of regrowth of L. pneumophila pretreated with combinations of levofloxacin or erythromycin with rifampicin, or levofloxacin with erythromycin (all at 1x MIC) was similar to that seen with single drugs. Thus, significant delay and reduction of regrowth in this phagocytic system occurred with levofloxacin only. Prolonged exposure of the organism at 4x MIC levofloxacin concentrations was effective in suppressing regrowth of pretreated L. pneumophila in human monocytes.

Anti-Bacterial Agents↗