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We sought to study the clinical features of PL in children followed up at our institution.
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The activities of 11 5-nitroimidazole compounds have been compared against Giardia intestinalis in vitro using a 3H-thymidine incorporation assay. All the compounds were at least equipotent to, or more active than metronidazole with the exception of panidazole. Satranidazole, ronidazole and S75 0400 A were all about five times more active than metronidazole and warrant further study as potential chemotherapeutic agents for man. No major differences in the response to these compounds was found between two stocks of Giard. intestinalis with the exception of flunidazole. Several other antiprotozoal drugs showed activity against Giard. intestinalis. Berberine sulphate, paromomycin sulphate, erythromycin estolate and sulphasalazine, all of which have been used to treat human patients, showed no activity in vitro.
A randomized crossover study in 16 healthy volunteers given multiple doses of erythromycin base enteric-coated tablets or erythromycin estolate capsules revealed essentially no difference in the resultant plasma concentration of bioactive erythromycin. This similarity in bioactivity persisted despite the fact that total eryghromycin levels (bioactive erythromycin base plus bioinactive erythromycin propionate) were at least three times higher after administration of the estolate than after administration of the base.
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Streptococcal eradication rates of 86% were demonstrated in 97 patients seen on day 14 and in 73 patients seen on both days 14 and 28 after a ten-day course of erythromycin estolate therapy given at a dosage of 20 mg/kg/day, administered in two equal doses. The efficacy of this regimen compares favorably with other results in which this and other erythromycin preparations have been employed at higher doses, usually in the range of 30 to 50 mg/kg/day. Our reported effectiveness at a lower than usual dose of erythromycin is probably explained by the following factors: the known susceptibility of group A streptococci to low concentrations of erythromycin, the uniform absorption of the estolate formulation of erythromycin, and adequate compliance in adhering to the treatment regimen by the majority of our patients. This dosage schedule of erythromycin is simple to administer; and a reduction by half of the total dose usually recommended provides an economical advantage for patients.
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The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.
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During a 24-month period, throat-swab cultures were obtained on 1,362 well children who were 3 months to 14 years of age. The overall incidence of positive cultures for group-A beta-hemolytic Streptococcus was 3.3%; in those children older than 1 year, it was 4.4%. The largest incidence of positive cultures occurred in the 5- to 7-year-old (8.3%) and 8- to 10-year-old (4.5%) age groups. No positive cultures were obtained from 339 infants younger than 1 year of age. There was no relation between positive cultures and the month of the year. There were no significant differences between the age, sex, presence of tonsils, previous group-A streptococcal infections, or the presence in a daycare center or school of children with positive cultures compared with those children with negative cultures. Follow-ups were obtained on 29 of 45 children with positive throat cultures; all of the children were asymptomatic and had normal results of physical examinations. Group-A streptococci of the same serotype as the original isolate were isolated from 19 of these children. Three to four days after a ten-day course of erythromycin estolate, five of 19 children again had positive cultures. Twenty-six of the 29 children had a total of 43 siblings residing in the home. Serotypically identical group-A streptococci were isolated from five siblings (11%). Only one of 29 patients from whom paired serum samples were obtained showed a fourfold rise or fall in the Streptozyme titers.
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Capillary electrophoresis was utilized in the study of the macrolide antibiotics (i.e. pharmaceutical glycoconjugates) clarithromycin, erythromycin, oleandomycin, troleandomycin, and spiramycin. In order to assist in analyte solubilization, two buffer systems using acetonitrile were developed. The first system involved 30 mM sodium cholate and 20% acetonitrile in 80 mM sodium phosphate, pH 6. This buffer permitted the baseline resolution of all five glycoconjugated antibiotics. In addition, erythromycin was separated from its derivatives estolate and ethylsuccinate. In the absence of surfactants, a higher acetonitrile quantity, 65%, was used in the second buffer system, with 35 mM sodium phosphate, pH 6. Selectivity between oleandomycin and clarithromycin was reversed in this system compared to the cholate buffer, indicating solute interaction with the cholate micelles in the previous system. Calibration linearity and detection sensitivity were improved in the high acetonitrile buffer, due to decreased background absorbance. It was demonstrated that both buffer systems can be utilized for the visualization of minor components that may be present in bulk pharmaceuticals.
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Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.
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The effects of erythromycin estolate, a well known hepatotoxic macrolide antibiotic, on isolated rat hepatocyte viability and on subcellular Ca2+ transport have been investigated. Erythromycin estolate (0.5 mM), but not erythromycin base and erythromycin ethylsuccinate, induced 100% cell death after 60 min incubation, and caused maximal inhibition of mitochondrial and microsomal Ca2+ sequestration activities at 0.1 mM concentration. Sodium lauryl sulphate, which is the surfactant moiety of the erythromycin estolate molecule, caused effects similar to those exhibited by erythromycin estolate. Disorders of the intracellular calcium homeostasis seem to play a role in the lauryl sulphate-mediated hepatotoxic action of erythromycin estolate.
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One hundred two children with group A streptococcal pharyngitis were treated on a randomized basis with either 15 mg/kg of erythromycin estolate or 25 mg/kg of erythromycin ethylsuccinate given twice daily for ten days. Twelve patients, including 11 erythromycin ethylsuccinate-treated patients and one erythromycin estolate-treated patient, were dropped from the study at the request of their parents because of abdominal cramping and/or nausea and vomiting that occurred 15 to 45 minutes after ingestion of drug. Eighteen other patients (12 treated with erythromycin ethylsuccinate and six treated with erythromycin estolate) had similar gastrointestinal (GI) tract symptoms that resolved or abated. Excluding patients with reinfections with new streptococcal serotypes and those with resistant strains, the bacteriologic failure rates were 4.3% and 17.5%, and the total failure rates were 6.4% and 35.3% with erythromycin estolate therapy and with erythromycin ethylsuccinate therapy, respectively. The high rate of GI tract intolerance associated with the erythromycin ethylsuccinate appears to be dose related.
Thirty-nine pregnant women admitted for therapeutic abortions during early or mid pregnancy were given erythromycin estolate, erythromycin base, or clindamycin hydrochloride orally in single or multiple doses. Peak serum levels of clindamycin were 3.4 to 9.0 mug/ml following a single dose of 450 mg, whereas peak serum levels of erythromycin were 0.29 to 7.2 mug/ml following 500 mg in a single dose. The individual variability of serum concentrations of erythromycin was greater than that reported in normal men and nonpregnant women, whereas the serum levels of clindamycin were rather uniform, and similar to what has been reported in nonpregnant individuals. Following multiple doses of each antibiotic, high serum levels were obtained in virtually all subjects, and urine levels were also higher. Following single doses the mean urinary recovery was 2% for erythromycin and 16.8% for clindamycin.