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PubMedDate not supplied

Clonal differences among erythromycin-resistant Streptococcus pyogenes in Spain.

The aim of this study was to determine whether the high levels of erythromycin resistance in Streptococcus pyogenes found in Spain are due to the introduction and spread of one or more clones. Phenotypic and genotypic techniques were used to characterize all erythromycin-resistant S. pyogenes (ErR) isolated in Gipuzkoa, Spain, in the last 10 years and 128 ErR isolated in Vitoria and Madrid during 1996. Of 437 ErR, 97% had the M phenotype; all 283 of the strains studied had the mefA determinant of resistance. After biotyping, T serotyping, emm typing, and genotyping, four major clones were detected. Clones B (biotype I, type T4, emm4, pulsed-field gel electrophoresis [PFGE] II) and D (biotype V, type T8.25, emm75, PFGE IV) comprised 78.8% of all ErR. The resistance of S. pyogenes to erythromycin was mainly due to an efflux mechanism of resistance (M phenotype); few clones were responsible for it.

Anti-Bacterial Agents↗
PubMed1994

[Histopathological studies on paranasal mucosa from patients treated with erythromycin].

Low-dose and long-term administration of erythromycin (EM therapy) has been reported to be very effective for patients with intractable chronic sinusitis including sinobronchial syndrome. However, we sometimes encounter patients whose sinusitis is extremely resistant to EM therapy. Therefore, the present study was carried out to determine the correlation between the clinical efficacy of EM therapy and the histopathological features of the ethmoidal mucosa and nasal polyps of patients treated with erythromycin. Patients with significant lymphocytic infiltration in the submucosal area responded well to EM therapy. Furthermore, patients with neutrophilic infiltration within and beneath the ciliary epithelium tended to show improvement with this therapy. On the other hand, EM therapy was minimally effective in patients whose subepithelial layer showed marked eosinophilic infiltration. In patients showing excellent and good clinical results, histological changes in the paranasal mucosa after therapy were as follows: a decrease in the number of inflammatory cells, reduced interstitial edema, increased fibrosis and normalization of the secretory glands. From these results, we conclude that erythromycin may suppress chronic inflammation except for an allergic reaction characterized by marked eosinophilic infiltration.

Adolescent↗
PubMed1999

The macrolides: erythromycin, clarithromycin, and azithromycin.

In addition to erythromycin, macrolides now available in the United States include azithromycin and clarithromycin. These two new macrolides are more chemically stable and better tolerated than erythromycin, and they have a broader antimicrobial spectrum than erythromycin against Mycobacterium avium complex (MAC), Haemophilus influenzae, nontuberculous mycobacteria, and Chlamydia trachomatis. All three macrolides have excellent activity against the atypical respiratory pathogens (C. pneumoniae and Mycoplasma species) and the Legionella species. Azithromycin and clarithromycin have pharmacokinetics that allow shorter dosing schedules because of prolonged tissue levels. Both azithromycin and clarithromycin are active agents for MAC prophylaxis in patients with late-stage acquired immunodeficiency syndrome (AIDS), although azithromycin may be the preferable agent because of fewer drug-drug interactions. Clarithromycin is the most active MAC antimicrobial agent and should be part of any drug regimen for treating active MAC disease in patients with or without AIDS. Although both azithromycin and clarithromycin are well tolerated by children, azithromycin has the advantage of shorter treatment regimens and improved tolerance, potentially improving compliance in the treatment of respiratory tract and skin or soft tissue infections. Intravenously administered azithromycin has been approved for treatment of adults with mild to moderate community-acquired pneumonia or pelvic inflammatory diseases. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens, particularly Streptococcus pneumoniae, group A streptococci, and H. influenzae. The emergence of macrolide resistance with these common pathogens may limit the clinical usefulness of this class of antimicrobial agents in the future.

Adult↗
PubMed1983

Treatment of acute nonspecific gastroenteritis of infants and young children with erythromycin.

A double-blind placebo-controlled trial of erythromycin ethylsuccinate was conducted in 65 infants and young children hospitalized with acute nonspecific gastroenteritis. Etiologic agents included rotaviruses (29%), Campylobacter jejuni (17%), "classical" enteropathogenic Escherichia coli (12%), enterotoxigenic E. coli (11%), Salmonella (9%), Shigella (2%), and Giardia lamblia (2%). No pathogens were obtained from 25 (38%) children. Treatment with erythromycin had no effect on the course of the illness in terms of the time required for hydration, stool frequency and temperature to return to normal, or for vomiting to be abolished. Children treated with erythromycin, however, experienced a marginally, but significantly (P less than 0.05), shorter period of abnormal stool consistency compared with control subjects. This effect was most pronounced in children from whom no enteropathogens were isolated.

Acute Disease↗
PubMed1978

HPLC as a rapid means of monitoring erythromycin and tetracycline fermentation processes.

Reverse phase high performance liquid chromatography (HPLC) was used as a rapid means of monitoring the erythromycin and the tetracycline fermentation processes. The sample preparation process for tetracycline in the fermentation broth includes simple dilution and filtration through a Millipore filter prior to injection into the HPLC column. Fermentation growth samples showed no interference, and excellent separation for selective determination of tetracycline, 4-epitetracycline, anhydrotetracycline, chlortetracycline, and 4-epianhydrotetracycline was obtained. The relative standard deviation for the HPLC analysis for tetracycline is about one percent and the correlation coefficient between the HPLC and the spectrophotometric assay methods is better than 0.994. The sample preparation procedure for erythromycin determination in fermentation broth requires solvent cleanup and extraction processes. The chromatographic analysis takes approximately 25 minutes, and the HPLC method is capable of separating and quantifying erythromycins A, B, C, and various epimers and degradation compounds. The correlation coefficient between the HPLC and the microbiological assay method is 0.970.

Biological Assay↗
PubMed1982

Plasmid DNA in the erythromycin producing microorganism, Streptomyces erythreus NRRL 2338.

Streptomyces erythreus NRRL 2338, the erythromycin producing microorganism, contains extrachromosomal (plasmid) DNA. Four different plasmids, pSE1, pSE2, pSE4 and pSE6 present in the wild-type strain have characteristic mobilities on agarose gel electrophoresis, molecular weight and restriction endonuclease digestion patterns. Treatment of the wild-type strain with ethidium bromide or acridine orange gave two variants, one that could not convert erythronolide B to 3 (alpha)-mycarosylerythronolide B and another than produced 2 approximately 3 times more erythromycin A than the parental strain. Although the plasmid DNA profile of these two variants is different from the wild-type strain, it is not possible to conclude that any of the structural genes for erythromycin biosynthesis are located on the plasmids of S. erythreus NRRL 2338.

DNA Restriction Enzymes↗
PubMed1984

Enzymic hydrolysis of erythromycin by a strain of Escherichia coli. A new mechanism of resistance.

Escherichia coli BM2195 is highly resistant to erythromycin by inactivation of the antibiotic. We have determined the structure of the modified antibiotic by physico-chemical techniques including mass spectrometry, infrared spectrophotometry, 13C nuclear magnetic resonance, and circular dichroism. The results obtained indicate that E. coli BM2195 resists erythromycin by the production of an erythromycin esterase which hydrolyzes the lactone ring of the antibiotic.

Circular Dichroism↗
PubMed1988

Effects of roxithromycin, a new semisynthetic macrolide, and two erythromycins on drug metabolizing enzymes in rat liver.

The effects of a new semisynthetic macrolide, roxithromycin, on drug metabolizing enzymes of rat liver were compared with two erythromycins, the base (EB) and the estolate (EE), after 7 days' treatment with high oral doses (400 and 800 mg/kg daily). Dose-related higher concentrations of roxithromycin were reached in serum and liver than after EB or EE. The two reference erythromycins induced the synthesis of microsomal enzymes and formed inactive cytochrome P-450-metabolite complexes. N-Demethylation of erythromycin itself and aminopyrine was increased by the treatment. Liver microsomal enzyme activities were not induced and the inactive cytochrome P-450-metabolite complex was not formed after 400 mg/kg of roxithromycin and only to a very limited extent after 800 mg/kg (10% vs. 50% after EE). At the higher dose microsomal activities were not changed by roxithromycin and only aminopyrine N-demethylation was reduced.

Animals↗
PubMed1996

Preparation and in vitro antibacterial activity of 9-O-glycosyloxime derivatives of erythromycin A, a new class of macrolide antibiotics.

9-O-Glycosyloxime derivatives of erythromycin A have been synthesized and their in vitro antibacterial activity compared with that of erythromycin A (1). This new class of macrolide antibiotics showed reduced antibacterial spectrum. However, some derivatives were as or more active than erythromycin A (1) against strains, responsible for respiratory track infections, such as Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Anti-Bacterial Agents↗
PubMed1999

A direct inhibitory effect of erythromycin on rat urinary bladder smooth muscle.

Erythromycin (EM) exerts a dual effect on the contractility of smooth muscle. An excitatory effect mediated via motilin receptors is expressed mainly in the smooth muscle of the stomach and duodenum. The other, a direct inhibitory effect mediated via an unknown mechanism, has been described in guinea-pig and human gallbladder, in the longitudinal smooth muscle of the guinea-pig small intestine and in bronchial smooth muscle. In the present study, the effect of EM on the isolated urinary bladder of the rat was examined using isometric force measurements. The muscarinic agonist carbachol evoked contractions that were reduced by EM in a concentration-dependent manner; at 5 x 10(4) M by 46% [from 1.04+/-0.42 gm. to 0.56+/-0.22 gm., (p <0.001)] and at 10(-3) M by 57% [from 1.04+/-0.42 gm. to 0.45+/-0.20 gm., (p <0.001)]. The inhibitory effect of EM was not altered by the nerve blocker tetrodotoxin. Electric field stimulation of 0.5 Hz, 1 Hz, and 2 Hz contracted the urinary bladder. Erythromycin at 5 x 10(-4) M reduced the contractions evoked at 0.5 Hz by 15% [from 0.60+/-0.22 gm. to 0.51+/-0.20 gm., (p = 0.004)] and at 10(-3) M by 23% [from 0.60+/-0.22 gm. to 0.46+/-0.12 gm., (p <0.001)]. Erythromycin failed to affect the contractions evoked by bradykinin, phenylephrine or substance P. It is concluded that EM has a direct inhibitory effect on the rat urinary bladder smooth muscle.

Animals↗
PubMed1999

Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban.

Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers in an open-label, crossover study with a 5-day washout between regimens. Argatroban 1 microgram/kg/min was infused alone for 5 hours (regimen A) and again on day 6 of a 7-day oral regimen of 500 mg erythromycin four times daily (regimen B). Serial blood samples for the determination of activated partial thromboplastin time (aPTT) and argatroban concentrations were collected for up to 48 hours following infusion. Mean values for argatroban area under the concentration-time curves (AUC0-inf), maximum concentration (Cmax), and half-life (t1/2) were similar between regimens. Mean aPTT values were not affected significantly by the concomitant administration of argatroban and erythromycin compared to argatroban alone. No serious adverse events or bleeding episodes occurred during the study. These results suggest that oxidative metabolism by CYP3A4/5 is unlikely to be an important in vivo elimination pathway for argatroban. Therefore, coadministration of CYP3A4/5 inhibitors should not require a modification in the dosage of argatroban.

Adolescent↗
PubMed1976

[Passage into normal salivary, lacrimal and nasal secretions of ampicillin and erythromycin administered intramuscularly].

The authors have measured, with the agar diffusion technique, the antibiotic concentrations in the serum as well as in the normal nasal, lachrymal and salivary secretions, after an intramuscular injection of 500 mg of ampicillin and of 200 mg of erythromycin. Bacillus subtilis is used as test germ for dosage of ampicillin and Sarcina lutea for the dosage of erythromycin. An important quantity of ampicillin (0.5 to 2.5 microgram/ml) passes into the nasal secretion. Its passage into the saliva is very irregular and is usually very slight. Bacillus subtilis is not suitable for systematically studying the ampicillin concentration in the lachrymal secretion, which displays a strong, inherent inhibitory effect on this micro-organism. Important concentrations of erythromycin are found in the three secretions: 0.5 to 3.25 microgram/ml in the nasal mucus and in the lachrymal secretion, 0.3 to 4.5 microgram/ml in saliva.

Ampicillin↗
PubMed1999

[The mechanism and effect of erythromycin in development of pulmonary fibrosis].

OBJECTIVE: To observe the effect of erythromycin on the development of pulmonary fibrosis and explore the new therapy in pulmonary fibrosis. METHODS: By evaluating the pathologic changes, the synthesis of collagen protein, the level of activity and expression of tumor necrosis factor-alpha (TNF-alpha), the effect of erythromycin was investigated on the rat model of pulmonary fibrosis induced by bleomycin. RESULTS: The alveolitis alleviated in the first week in treatment group comparing with the control group (142.5 +/- 13.9 mg/g), the synthesis of collagen protein decreased in the fourth week treatment group (96.8 +/- 4.8 mg/g) (q Test P < 0.01). CONCLUSION: Erythromycin may alleviate the process of rat pulmonary fibrosis induced by bleomycin.

Animals↗
PubMedDate not supplied

Effect of erythromycin and cisapride on emptying of the vagally denervated intrathoracic stomach.

BACKGROUND: Subsequent to esophagectomy and reconstruction among patients with esophageal cancers, the intrathoracic denervated stomach acts as a passive conduit without peristalsis. OBJECTIVE: The study was designed to assess the impact of two prokinetic drugs viz. erythromycin and cisapride on the emptying of vagally denervated intrathoracic stomach. METHODS: Twenty consecutive patients of carcinoma esophagus, who had undergone one stage transhiatal oesophagectomy with cervical esophagogastrostomy and were disease free at three months postoperative follow-up, were included in the study. These patients were randomised into two groups of ten each. The patients in group A received erythromycin, while patients in group B received cisapride. The gastric emptying was studied by scintigraphy, using a standard test meal containing 99m Tc sulphur colloid labelled 'IDLIS' [rice based radio labelled food] before and after the drug treatment. RESULTS: The pre and post treatment mean gastric half emptying time of the patients in the erythromycin group was 52.6 min and 49.7 min (p > 0.1) and in cisapride group it was 53.76 and 26.4 min respectively (p < 0.05). Intergroup comparison of the difference was not statistically significant. CONCLUSION: Cisapride is an effective prokinetic agent in the treatment of gastric stasis of the vagally denervated intrathoracic stomach.

Adult↗
PubMed2003

[Prognosticating the region-selectivity in the O-methylation reaction of erythromycins by conformational search model].

AIM: In order to find a way to prognosticate the region-selectivity in the O-methylation reaction of erythromycin and its derivatives, conformation search model of Hyperchem Pro 6.0 used in personal computer was used to establish it. METHODS: The results of O-methylation reaction of compound 1, 2 and 3 showed the difference between 6-OH and 11-OH. Using the conformational search model of hyperchem, 1,000 conformations of compound 4, 5 and 6 were found with the parameter of dihedral angle. The 14-membered lactone ring was defined as a "plane". The position of carbonyl of 1- or 9- and hydroxyl of 6- or 11- is different, either "up-plane" or "down-plane". A statistic analysis of low-energy conformation clusters was used to sort these clusters by the parameter of the dihedral angle. The data is in accord with the results of the experiments. RESULTS: Conformation numbers, energy minimum, energy average and position of the active groups of compounds 4, 5 and 6, the simplified structures of compound 1, 2 and 3, were given in Table 1. by sorting the dihedral angle. CONCLUSION: The interaction of the hydroxyl and carbonyl were analysed and found that O-methylation reactions of erythromycin and its derivatives were impacted by the space factor. The clusters of energy minimum, maximum number and "outside" were discussed. The selectivity of the O-methylation reaction of erythromycin and its derivatives can be prognosticated by analysing the parameter of the dihedral angle.

Electronic Data Processing↗
PubMed1992

Erythromycin associated hearing loss in a patient with prior cis-platinum induced ototoxicity.

A case is reported of reversible sensorineural hearing loss associated with intravenous erythromycin treatment. Cis-platinum induced high frequency hearing loss developed nine months previously during treatment for stage IV papillary cystadenocarcinoma. Renal and hepatic function were normal; however, serum erythromycin levels were elevated. Clinical recovery promptly followed discontinuation of erythromycin.

Cisplatin↗
PubMed2004

Evaluation of the degree of susceptibility of Streptococcus pyogenes erythromycin-resistant strains to rokitamycin (a 16-membered macrolide) using the Epsilometer test.

Routine hospital screening of the resistance of Streptococcus pyogenes to macrolides is usually done using the erythromycin, clarithromycin or azithromycin disk diffusion technique. When a strain is found to be resistant to one of these macrolides, it is generally assumed to be resistant to the whole class. However this approach gives only partial qualitative information because S. pyogenes strains with inducible and M phenotype resistance are still susceptible to 16-membered ring macrolides such as rokitamycin. Seventy-four erythromycin-resistant (22 inducible and 52 M phenotype) strains of S. pyogenes were tested for their susceptibility to rokitamycin and clindamycin (control) by means of the agar disk diffusion test and the results were compared with those obtained using the Epsilometer test, a quantitative technique for measuring bacterial susceptibility and minimal inhibitory concentrations (MIC). Epsilometer testing of erythromycin in comparison with rokitamycin is useful for measuring the real degree of susceptibility of macrolide-resistant strains quickly and simply. This is important because strains with the same disk diffusion diameter do not necessarily have the same MIC, but a scattered distribution of susceptibility.

Anti-Bacterial Agents↗
PubMed2004

Erythromycin-resistant Streptococcus pyogenes in Argentina.

Erythromycin (ERY) resistance in Streptococcus pyogenes has recently emerged as a problem of growing concern all through the world. We are presenting the comparison of results of the continuous surveillance of erythromycin resistance in S. pyogenes performed since 1989 in the Hospital de Pediatría J.P. Garrahan of Buenos Aires City, with independently observed rates in other five centers of Buenos Aires and seven centers of six other Argentinian cities, obtained between 1999 and 2001. A significant increase of erythromycin resistance was observed among S. pyogenes isolated in the Hospital Garrahan (6.6% in 1998-1999 to 9.9% in 2000). Similar trends were also detected in other centers of other Argentinian cities when recent data were compared to results of a multicenter study performed in 1995. However, lower rates of resistance were recorded in Mendoza, Cipolletti and Neuquén in comparison with data of 1995, 1998 and 1998 respectively. The reason of such decreasing resistance rates deserves to be investigated. The average of ERY-resistance rates obtained in the surveyed centers was 6.7% (range 0.5-14.1%). Control of antimicrobial use should be performed to warrant the future effectiveness of macrolide antibiotics regarding the positive association between use and resistance. These results also suggest that susceptibility tests for macrolides should be performed whenever S. pyogenes is isolated in Argentina.

Anti-Bacterial Agents↗