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PubMed1985

Genetic analysis of erythromycin production in Streptomyces erythreus.

Streptomyces erythreus produces the 14-membered macrolide antibiotic erythromycin A. The properties of erythromycin A nonproducing mutants and their genetic linkage to chromosomal markers were used to establish the rudiments of genetic organization of antibiotic production. Thirty-three Ery- mutants, produced by mutagenesis of S. erythreus NRRL 2338 and affecting the formation of the macrolactone and deoxysugar intermediates of erythromycin A biosynthesis, were classified into four phenotypically different groups based on their cosynthesis behavior, the type of biosynthetic intermediate accumulated, and their ability to biotransform known biochemical intermediates of erythromycin A. Demonstration of the occurrence of natural genetic recombination during conjugal mating in S. erythreus enabled comparison of the genetic linkage relationships of three different ery mutations with seven other markers on a simple chromosome map. This established a chromosomal location for the ery mutations, which appear to be located in at least two positions within one interval of the map.

Chromosome Mapping↗
PubMed1993

Identification of a Saccharopolyspora erythraea gene required for the final hydroxylation step in erythromycin biosynthesis.

In analyzing the region of the Saccharopolyspora erythraea chromosome responsible for the biosynthesis of the macrolide antibiotic erythromycin, we identified a gene, designated eryK, located about 50 kb downstream of the erythromycin resistance gene, ermE. eryK encodes a 44-kDa protein which, on the basis of comparative analysis, belongs to the P450 monooxygenase family. An S. erythraea strain disrupted in eryK no longer produced erythromycin A but accumulated the B and D forms of the antibiotic, indicating that eryK is responsible for the C-12 hydroxylation of the macrolactone ring, one of the last steps in erythromycin biosynthesis.

Amino Acid Sequence↗
PubMed1988

Variability of clarithromycin and erythromycin susceptibility tests with Haemophilus influenzae in four different broth media and correlation with the standard disk diffusion test.

Four separate laboratories performed antimicrobial susceptibility tests with 40 Haemophilus influenzae isolates, each tested in triplicate. Erythromycin and a new macrolide, clarithromycin (A-56268; TE-031), were tested by the disk diffusion method, by the agar dilution procedure in two different media, and by broth microdilution tests in four different media. Erythromycin MICs for 90% of the strains were 16 micrograms/ml in Mueller-Hinton broth with 3% lysed horse blood and NAD, 4.0 micrograms/ml in hemophilus test medium, and 2.0 micrograms/ml in supplemented Schaedler broth or in the fastidious broth medium from Beckman Instruments, Inc. Clarithromycin MICs were generally 1 doubling dilution greater than erythromycin MICs in each of the media. Erythromycin disk tests corresponded best with MICs determined in the fastidious broth medium. In that same medium, clarithromycin MICs were about 1 doubling dilution greater than what would be expected from the results of disk tests. Because there were fewer growth failures, hemophilus test medium is recommended for microdilution tests with H. influenzae. Incubation of all tests for a full 24 h without an increased CO2 atmosphere was needed to achieve maximal precision of the tests. Interlaboratory and intralaboratory reproducibility of all tests was satisfactory.

Clarithromycin↗
PubMed1997

Surveillance and detection of erythromycin resistance in Bordetella pertussis isolates recovered from a pediatric population in the Intermountain West region of the United States.

Forty-seven Bordetella pertussis isolates recovered from January 1985 to June 1997 at Primary Children's Medical Center were tested for erythromycin resistance. Agar dilution MICs were determined on Regan-Lowe agar. Forty-six isolates were found to be erythromycin susceptible (all MICs were less than or equal to 0.12 microg/ml). One isolate was found to be erythromycin resistant (MIC, 32 microg/ml). In addition, we compared Etest MIC results and disk diffusion zone diameter measurements, performed on commercially prepared Regan-Lowe agar, to the agar dilution MIC result. Etest MIC and/or disk diffusion testing on commercial Regan-Lowe agar appears to be an adequate method for erythromycin resistance screening of B. pertussis isolates.

Anti-Bacterial Agents↗
PubMed2002

Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae.

A geographical analysis of how commonly prescribed oral antibiotics are quantitatively and qualitatively responsible for the different local rates of erythromycin and penicillin resistance in Streptococcus pneumoniae in Spain is presented. From 1998 to 1999 a multicenter surveillance study yielded 1,684 consecutive S. pneumoniae isolates from community-acquired respiratory infections. Data on antibiotic sales in the retail market for the same period were gathered, and the corresponding defined doses per 1,000 inhabitants per day were calculated. Macrolides and beta-lactams were considered separately. Macrolides were subdivided into thrice-, twice-, and once-a-day macrolides, and beta-lactams were split into aminopenicillins and cephalosporins. Univariate Spearman nonparametric coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were entered into several multiple lineal regression models. Ample variation in both resistance rates and antibiotic consumption was seen. Multivariate analyses showed that integrated consumption of both macrolides and beta-lactams accounted well for erythromycin (R(2) = 0.722; P = 0.002) and penicillin (R(2) = 0.706; P = 0.002) resistance. Macrolides were more important drivers for local differences in both erythromycin and penicillin resistance than beta-lactams were. Consumption of once-a-day macrolides was key for local erythromycin resistance variations. Cephalosporins were slightly more important penicillin resistance drivers than aminopenicillins were.

Anti-Bacterial Agents↗
PubMed2003

Survey of emm gene sequences from pharyngeal Streptococcus pyogenes isolates collected in Spain and their relationship with erythromycin susceptibility.

We conducted a nationwide survey of the variable 5' emm (M protein gene) sequences from 614 pharyngeal Streptococcus pyogenes isolates susceptible (299 isolates) and resistant (315 isolates) to erythromycin that were isolated in Spain from 1996 to 1999. Almost 98% of these isolates had emm sequences in agreement with previously recorded M antigen association. We only identified a new 5' emm sequence in 17 isolates. Nine different emm types accounted for 85% of the S. pyogenes isolates susceptible to erythromycin. By contrast, only 3 emm types accounted for 70% of the erythromycin-resistant isolates. Further characterization of these isolates by ribotyping and pulsed-field gel electrophoresis indicated that high frequency of erythromycin resistance in Spain is due to few clones.

Anti-Bacterial Agents↗
PubMed1982

Nuclear inheritance of erythromycin resistance in human cells: new class of mitochondrial protein synthesis mutants.

The characterization of two new erythromycin-resistant mutants of HeLa cells is described. The strains ERY2305 and ERY2309 both exhibited resistance to erythromycin in growth assays and cell-free mitochondrial protein synthesis assays. The erythromycin resistance phenotype could not be transferred by cybridization. The mutation appeared to be encoded in the nucleus and inherited as a recessive trait. These two mutants, therefore, represent a new class of erythromycin-resistant mutants in human cells that is distinct from the cytoplasmically inherited mutation in strain ERY2301 described previously.

Cell Division↗
PubMed1989

Untreated asymptomatic bacteriuria in girls: II--Effect of phenoxymethylpenicillin and erythromycin given for intercurrent infections.

OBJECTIVE: To investigate the effects of phenoxymethylpenicillin and erythromycin on urinary isolates from patients with untreated asymptomatic bacteriuria. DESIGN: Retrospective study of subgroup of patients from cohort followed up till the end of 1986. SETTING: Outpatient clinic for children with urinary tract infections. PATIENTS: 51 Girls aged under 15 with untreated asymptomatic bacteriuria. INTERVENTIONS: Before 1982 intercurrent infections (mostly tonsillitis or otitis) were treated with phenoxymethylpenicillin; after 1982 erythromycin treatment was preferred. END POINTS: Change of bacterial strain in urinary tract and symptomatic recurrences of disease. MEASUREMENTS AND MAIN RESULTS: Bacteria identified by serotype and electrophoretic type and compared before and after antibiotic treatment. Bacteriuria eradicated and replaced by new strains in most patients treated with phenoxymethylpenicillin, leading to symptomatic recurrences in about 15%. Conversely, patients given erythromycin rarely showed change in bacteriuria and none suffered symptomatic recurrence. CONCLUSIONS: In girls with untreated asymptomatic bacteriuria the use of phenoxymethylpenicillin for intercurrent infections may lead to a change of urinary bacteria and leave them at substantial risk of acute pyelonephritis. With erythromycin this risk is small (2/20 courses in this series).

Adolescent↗
PubMed1998

Randomised trial of erythromycin on the development of chronic lung disease in preterm infants.

AIMS: To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease. METHODS: Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interleukins IL-1 beta and IL-8, and tumour necrosis factor alpha (TNF-alpha) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation. RESULTS: Nine infants (13%) were positive for U urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non-treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1 beta and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD. CONCLUSIONS: U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.

Anti-Bacterial Agents↗
PubMed1998

Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin.

BACKGROUND: The ground squirrel on a high cholesterol diet exhibits prolonged intestinal transit, a pathogenetic factor in cholesterol gallstone formation. AIMS: To examine the effect of a high cholesterol diet on the characteristics of the migrating myoelectrical complex (MMC) and the potential benefit of erythromycin. METHODS: Twenty four animals received either a trace (controls) or a 1% (high) cholesterol diet. After four weeks, five bipolar jejunal and terminal ileal electrodes were implanted. Seven days later, myoelectric activity was measured in conscious, fasted animals before and after treatment with erythromycin. Biliary lipid composition was assessed. RESULTS: Compared with controls, animals fed the high cholesterol diet exhibited a prolonged MMC cycle period (70 (6) versus 83 (3) minutes; p<0.05), whereas MMC migration velocity and the proportions of the MMC represented by phases I, II, and III were unchanged. Oral erythromycin significantly shortened the MMC cycle period in animals on the control and high cholesterol diet by 59% and 54% respectively, and increased the proportion of the cycle period occupied by phase III of the MMC in both dietary groups. Gall bladder bile became saturated with cholesterol and crystals developed in nine of 12 animals on the high cholesterol diet; controls had none. CONCLUSION: Animals fed a high cholesterol diet had a prolonged MMC cycle period. This, along with diminished gall bladder motility, impairs the enterohepatic cycling of bile salts and reduces their hepatic secretion, contributing to the formation of abnormal bile. Erythromycin initiated more frequent cycling of the MMC. Its therapeutic value in cholesterol gallstone formation warrants further evaluation.

Animals↗
PubMed1977

A new look at erythromycin.

This article reviews the current place of erythromycin in antibiotic therapy. Overall, erythromycin is thought to be underused because: (1) the fear of resistance has been exaggerated; (2) significant toxicity has been associated with only one derivative (the estolate); (3) newer antibiotics have very rarely been demonstrated to be superior to erythromycin. Erythromycin has an important place in treating acute upper and lower respiratory tract infections, acute otitis media, sinusitis, skin and soft tissue, osteomyelitis, prostatitis, infections due to Mycoplasma spp. and Chlamydia organisms, and infections due to anaerobes.

Bacterial Infections↗
PubMed1981

Fluorimetric and microbiological assays of erythromycin concentrations in plasma and vaginal washings.

Using a microbiological and a fluorimetric assay to determine penetration of erythromycin into vaginal fluids, concentrations were measured in plasma from nine men one hour after a single oral dose of erythromycin stearate 2 g and in vaginal washings and plasma samples taken simultaneously from 11 women two hours after the last dose of a 10-day course of erythromycin stearate (250 mg four times daily). Both assay methods gave accurate and reproducible results in plasma but only the fluorimetric method was capable of measuring concentrations of erythromycin in vaginal washings. The latter method had many advantages in estimating drug concentrations in body fluids such as vaginal washings and the results from it may provide an index of tissue penetration and of patient compliance in adhering to drug regimens.

Adolescent↗
PubMed1983

Treatment of chancroid with erythromycin. A clinical and microbiological appraisal.

One hundred and thirty seven patients presenting with genital ulcerations from which Haemophilus ducreyi was isolated were treated with erythromycin stearate 500 mg every six hours for seven days. Of these, 91 (66%) had associated inguinal lymphadenopathy. Only two of the 100 patients who returned after one week showed no clinical improvement. Despite decrease in size H ducreyi was reisolated from the ulcers of three patients, two of whom had not complied with treatment. The patients were treated for a further week either with erythromycin or with a placebo preparation and on day 14 no discernible difference in clinical response was evident. H ducreyi was not reisolated from any lesion. In contrast, the natural course of development of associated lymphadenopathy was not modified by treatment. H ducreyi was not, however, isolated from any gland after the start of treatment. Side effects attributable to erythromycin were minimal and treatment had to be discontinued in only two patients. This study clearly indicates that treatment with erythromycin for one week results in rapid healing of lesions and the elimination of H ducreyi from both ulcers and associated lymph glands.

Chancroid↗
PubMed1995

Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection.

BACKGROUND: Diffuse panbronchiolitis is a chronic infection of the lower respiratory tract common among the Japanese people, with a persistent Pseudomonas aeruginosa infection in the late stage and sustained neutrophil retention in the airways. The long term effect of erythromycin was examined retrospectively in a group of patients with diffuse panbronchiolitis, with and without P aeruginosa infection, and the relationship between drug-induced bacterial clearance and clinical improvement was investigated. METHODS: The history, daily volume of sputum, type of organisms in sputum cultures, pulmonary function tests, arterial blood gas tensions, and chest radiographs were compared in 16 patients with diffuse panbronchiolitis with P aeruginosa infection and 12 without. The total and differential cell counts in the bronchoalveolar lavage (BAL) fluid were compared in 14 of the 28 patients (five of whom were infected with P aeruginosa) before and after 1-12 months of treatment with erythromycin (600 mg/day). The outcome of treatment in patients showing clearance of organisms on repeated sputum cultures was compared with that in those demonstrating persistence of bacteria in the sputum and patients with normal flora. RESULTS: Erythromycin improved respiratory function and arterial blood gas tensions irrespective of the presence or absence of P aeruginosa in the sputum. Treatment also resulted in a reduction in the BAL fluid total cell count and the percentage of neutrophils in both groups of patients. There were no differences between patients in whom the bacteria cleared and those with persistent bacteria or patients with a normal flora with regard to the degree of improvement of respiratory function, arterial blood gas tensions, and BAL fluid cell composition. CONCLUSION: The results suggest that the efficacy of erythromycin in diffuse pan-bronchiolitis may be due to anti-inflammatory effect, independent of P aeruginosa infection or bacterial clearance.

Adolescent↗
PubMed1990

Influence of sex and inducer treatment on the high- and low-affinity forms of hepatic microsomal erythromycin N-demethylase in rats.

To study the regulation of the multiple forms of erythromycin N-demethylase, we determined the influence of sex and inducer treatment on this mixed-function oxidase activity in adult Wistar rats injected intraperitoneally once daily for 4 days with dexamethasone, pregnenolone-16 alpha-carbonitrile, phenobarbital, or 2% Tween 80 (control). Based on the results from a computer curve-fitting procedure (ENZFITTER) as well as Eadie-Hofstee and Lineweaver-Burk plots, at least two forms of erythromycin N-demethylase were present in control, dexamethasone, pregnenolone-16 alpha-carbonitrile, and phenobarbital-treated male rats and in control and dexamethasone-treated female rats. Only a high-affinity form was apparent in pregnenolone-16 alpha-carbonitrile and phenobarbital-treated female rats. Therefore, more than one form of erythromycin N-demethylase exists in hepatic microsomes from adult rats, depending on sex and inducer treatment. As well, at a substrate concentration commonly used in the erythromycin N-demethylase assay, the relative contribution of the high- and low-affinity forms to the enzyme activity varies with sex and inducer treatment.

Animals↗
PubMed1979

Collagenase activity of rat kidney with glomerulonephritis is inhibited by erythromycin.

Collagenolytic activity of rat kidney with glomerulonephritis (GN) of Masugi's type was determined by a series of biological experiments. The determination was carried out during the heterologous phase of the disease together with inhibition studies in vivo and in vitro. Erythromycin has been tested in vivo for its inhibitory activity and an activity of collagenase was found in untreated rats with GN only, the panel treated with erythromycin did not show any collagenolysis. Statistical calculations indicate the significance of the inhibition (p less than 0.001). In addition, kidneys of test animals with GN have been investigated for their enzymatic activity and the inhibition by erythromycin in vitro where the kidneys failed to show collagenolytic activity. It can be concluded that erythromycin is able to inhibit in vivo and in vitro the activity of the collagenolytic enzyme produced by polymorphonuclear leukocytes during the heterologous phase of the nephritis, an effect which leads to the recovery of the physiological equilibrium of the protease and its inhibitor.

Animals↗
PubMed1996

Evaluation of the effect of zinc acetate on the stratum corneum penetration kinetics of erythromycin in healthy male volunteers.

Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 +/- 19 to 56 +/- 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 +/- 7 to 18 +/- 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.

Acetates↗
PubMed1979

Clinical and pharmacological evaluation of different preparations of oral erythromycin.

The activity of erythromycin stearate in respiratory tract infections was evaluated. This study involved 269 out-patients. Of these, 76 satisfied the strict criteria for detailed bacteriological study with positive cultures of a known pathogen before treatment and bacteriological follow-up after treatment. The results of erythromycin stearate were good against the haemolytic streptococcal infections. The activity of this antibiotic was shown to be insufficient against Haemophilus influenzae. A second clinical trial with 20 patients with acute exacerbations of chronic bronchitis demonstrated quite good activity from erythromycin ethylsuccinate and no intolerance when administered in a dose of 1 g q.i.d. The administration of 1 g of the ethylsuccinate immediately after a meal gave a peak serum concentration after 60 min of 3.36 micrograms/ml. Blood levels on the fourth day of this treatment showed some accumulation, concentrations of greater than 4 micrograms/ml being found at 30, 60 and 90 min after the dose. With its good absorption, its lack of toxicity and its reputation for good diffusion into bronchial secretions, we consider that erythromycin ethylsuccinate should have a major place in the treatment of respiratory tract infections.

Administration, Oral↗