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To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE).
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The effect of erythromycin esteolate (EE) on bile flow and bile acid secretion was studied in male Wistar rats in vivo. Daily oral treatment with a dose of up to 100 mg/kg for 1 week increased the bile flow and the bile acid secretion. Increasing the days of treatment to 4 weeks with a dose of 20 mg/kg did not alter the measured parameters significantly. Acute intravenous injection of erythromycin lactobionate (50 mg/kg) also increased bile flow and biliary bile acid secretion temporarily. The increase in bile flow may partly be due to the osmotic effect of the drug and its metabolites in bile. Since EE failed to produce cholestasis in the range of therapeutic doses, rats do not seem to be a suitable experimental model for studying EE-cholestasis.
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To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae.
In a crossover design study, we compared the plasma bactericidal activities of erythromycin estolate (500 mg) and erythromycin ethylsuccinate (600 mg) after administration of a single oral dose to 12 healthy volunteers. Both erythromycin esters displayed very good plasma bactericidal activities against Streptococcus pneumoniae. The median bactericidal titers produced in plasma against Streptococcus pyogenes and Streptococcus pneumoniae were significantly higher with erythromycin estolate than with the ethylsuccinate ester at both 2 and 8 h after dosing (P less than 0.05 by Student's t test). Both erythromycin esters showed rather weak bactericidal activity against Branhamella catarrhalis; a further look at these results indicated that erythromycin estolate presented 50% of the plasma samples at 2 h with bactericidal titers superior or equal to 1:8, versus 11% for the ethylsuccinate ester. Of the 60 plasma bactericidal activity tests performed against Staphylococcus aureus, only 6 (10%) and 3 (5%) exhibited titers of 1:8 or greater for erythromycin estolate and erythromycin ethylsuccinate, respectively. Clinical trials are warranted in which these products are compared in infections other than Streptococcus pyogenes pharyngitis, for which the clinical superiority of erythromycin estolate has been demonstrated.
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One hundred and fourteen Corynebacterium diphtheriae, toxigenic, gravis type, pharyngeal carriers were identified during a diphtheria epidemic in Elgin, Texas. All carriers were treated with erythromycin estolate, 1 g/day in divided doses for 6 days. Serial pharyngeal cultures were obtained in order to monitor the bacteriological response. Seventy-two carriers had positive cultures immediately prior to the start of therapy, and only these individuals were considered in the analysis of the effects of erythromycin. Forty-eight hours after institution of therapy, 96% of the carriers had become culture negative; all were negative by the 4th day of therapy, and all remained culture negative while taking the drug. Two days after cessation of therapy, all but one (99%) were culture negative. However, upon reculture 2 weeks later, 15 (21%) had relapsed to the carrier state. There were no significant differences in the serum diphtheria antitoxin levels, immunization status, age, sex, or socioeconomic status of those who relapsed and those who remained culture negative. This study demonstrates that erythromycin is effective in converting carriers to culture-negative status, but when given for only 6 days it is associated with large numbers of relapses. Because previous studies have not included follow-up cultures 2 weeks after therapy, it is suggested that all C. diphtheriae carriers be treated with either erythromycin or penicillin and that all be recultured at a minimum of 2 weeks after completion of therapy to assure eradication of the diphtheria organisms.
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To determine if it is appropriate to recommend that patients with group A beta-hemolytic streptococcal pharyngitis, who are clinically well by the morning after starting antibiotic treatment, can return to school or day care, or if they should wait until they have completed 24 hours of antibiotics as recommended by the American Academy of Pediatrics Committee on Infectious Diseases.
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Two studies of 100 healthy volunteers requesting sterilization were planned, one in Julpia Andhermanik and the other in Kolkata (Calcutta). A readily available marketed tablet preparation containing 500 mg of the estolate salt of erythromycin was used for the trial. In one study (Bishnupur), the tablet was crushed before placing in a copper-T IUD inserter for placement at the fundus. In the other study (Kolkata), crushed tablets were processed into 50 mg pellets of the same diameter as standard quinacrine pellets and 10 pellets were inserted at the fundus using aseptic precautions. Procedures in each study were repeated at 30 days. Oral contraceptives were prescribed for three cycles following first insertion. No incentive was offered for participation in the trial. Follow-up treatment, including first-trimester abortion for pregnancy due to failure of the sterilization procedure, was assured without charge. Due to extraordinary patient demand, one study (Bishnupur) was expanded to 690 cases for reasons of compassion.
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PL is not an uncommon disease in childhood, with age peaks in the preschool and early school-age years. It is usually recurrent, and shows a seasonal variation with onset most often in the fall or winter. In childhood PL, erythromycin is an effective initial treatment choice.
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Three to four review authors independently extracted data and assessed the quality of each trial.
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Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result.
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Using primary cultures of parenchymal hepatocytes as a model system, the cytotoxic potential of dantrolene sodium (DS) was compared with that of erythromycin estolate (EE)--a known hepatotoxin. Parallel morphological and functional comparisons were made, following 4-, 8-, or 24-h exposures of hepatocyte cultures, using phase contrast microscopy and lactate dehydrogenase (LDH) leakage, respectively. Four-hour exposures of cultures to rather low concentrations of EE (i.e. 50 microM) resulted in cellular necrosis and significantly elevated LDH release. As the concentration of this hepatotoxin was increased, the changes were more pronounced. However, even 4- or 8-h exposures of cultures to a maximum of 100 microM DS did not affect LDH leakage or morphological integrity, although marginally detectable morphological changes did not occur at the highest concentration after 24-h. The value of using primary parenchymal hepatocyte cultures as a model system for the assessment of xenobiotic-induced hepatotoxicity was confirmed.
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We examined the duration of positivity of the throat culture after antibiotics were begun as a means of assessing the potential risk of transmission to close school contacts. Forty-seven children (4 to 17 years of age) with pharyngitis and a positive throat culture for group A streptococci in an outpatient, staff model health maintenance organization clinic were enrolled and were randomly selected to receive therapy with either oral penicillin V, intramuscular benzathine penicillin G, or oral erythromycin estolate. Additional throat cultures were obtained and clinical findings were recorded for each child during three home visits in the 24 hours after their initial clinic visit. Acute and convalescent sera were obtained for determination of anti-streptolysin O and anti-DNase B titers.
In the field of gene expression analysis, DNA microarray technology is having a major impact on many different areas including toxicology. For instance, a number of studies have shown that transcription profiling can generate the information needed to assign a compound to a mode-of-action class. In this study, we investigated whether compounds inducing similar toxicological endpoints produce similar changes in gene expression. In vitro primary rat hepatocytes were exposed to 11 different hepatotoxicants: acetaminophen, amiodarone, clofibrate, erythromycin estolate, isoniazid, alpha-naphtylylisothiocyanate, beta-naphtoflavone, 4-pentenoic acid, phenobarbital, tetracycline, and zileuton. These molecules were selected on the basis of their variety of hepatocellular effects observed such as necrosis, cholestasis, steatosis, and induction of CYP P450 enzymes. We used a low-density DNA microarray containing 59 genes chosen as relevant toxic and metabolic markers. The in vitro gene expression data generated in this study were generally in good agreement with the literature, which mainly concerns in vivo data. Furthermore, gene expression profiles observed in this study have been confirmed for several genes by real-time PCR assays. All the tested drugs generated a specific gene expression profile. Our results show that even with a relatively limited gene set, gene expression profiling allows a certain degree of classification of compounds with similar hepatocellular toxicities such as cholestasis, necrosis. The clustering analysis revealed that the compounds known to cause steatosis were linked, suggesting that they functionally regulate similar genes and possibly act through the same mechanisms of action. On the other hand, the drugs inducing necrosis and cholestasis were pooled in the same cluster. The drugs arbitrarily classified as the CYP450 inducers formed individual clusters. In conclusion, this study suggests that low-density microarrays could be useful in toxicological studies.
All splenectomized individuals are at risk of developing pneumococcal sepsis, but most reports fail to mention how many patients are given prophylactic penicillin therapy. Fourteen reported cases of postsplenectomy bacterial sepsis in patients receiving prophylactic penicillin therapy are reviewed. In only five cases, the patients had penicillin-sensitive pneumococcal infection. Hence, the exact frequency of the failure of penicillin prophylaxis cannot be calculated, but it appears to be very rare. Continuous antibiotic prophylaxis used indefinitely and pneumococcal vaccine are both strongly recommended for all children and adults undergoing splenectomy.
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There is insufficient evidence to show whether giving antibiotics to women with ureaplasma in the vagina will prevent preterm birth.
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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.
A combined cholestatic and hepatocellular injury occurred in nine patients, following therapy with erythromycin estolate (EE) or other erythromycin derivatives. Eight of the nine patients developed jaundice within three weeks after initiation of treatment; pain was one of the main symptoms in five patients while fever and itching were noted in four patients. Symptoms and signs subsided and abnormal tests of liver function returned to normal after withdrawal of the drug. The major histologic finding was cholestasis, but the majority of cases also had evidence of hepatocellular injury of variable severity; one biopsy specimen showed centrilobular necrosis. Ultrastructural findings in one case included changes related to cholestasis as well as hepatocellular injury with striking mitochondrial abnormalities. Our data are compared with those of the literature, with special reference to morphologic features.
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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.
The chemistry, bioavailability, and adverse effects of erythromycin base, stearate, estolate, and ethylsuccinate are reviewed. Criteria for the evaluation of erythromycin bioavailability studies include study design, patient population, meal composition and timing, and assay methodology. Based on these criteria, the bioavailability of individual erythromycin products are evaluated in this paper. Compared with other antibiotics, the erythromycins have a good safety record. However, both the estolate and ethylsuccinate forms of erythromycin may cause hepatotoxity. Considering bioavailability and adverse effect data, a specific brand of enteric-coated erythromycin base tablets is recommended for erythromycin-sensitive infections in adults. For pediatric patients, a liquid formulation of erythromycin estolate or erythromycin ethylsuccinate is recommended.
The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays.
We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection.
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The clinical pharmacology of orally administered antibiotics was investigated in 106 infants and children. The antibiotic suspensions studied were ampicillin, cephalexin, erythromycin estolate, erythromycin ethylsuccinate, penicillin G, and penicillin V. The feeding status of the patients was evaluated in relation to the concentrations of drugs in serum, saliva, and tears. Peak concentrations and area-under-the-curve values of cephalexin, penicillin V, and penicillin G were reduced 40% to 60% in patients given milk and drug concurrently. Absorption was enhanced when erythromycin ethylsuccinate was given milk. After administration of both erythromycin formulations, penicillin V and ampicillin, salivary concentrations exceeded the minimal inhibitory concentrations for most pneumococci and group A streptococci and for many meningococci. The clinical implications of these pharmacokinetic data are discussed.
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One trial involving 1071 women was included. Of these, 644 randomly received antibiotic treatment (174 erythromycin estolate, 224 erythromycin sterate, and 246 clindamycin hydrochloride) and 427 received placebo. This trial did not report data on preterm birth. Incidence of low birthweight less than 2500 grams was only evaluated for erythromycin (combined) (n = 398 ) compared to placebo (n = 427) and there was no statistically significant difference between those treated and those not treated (relative risk (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). In regards to side-effects sufficient to stop treatment, data were available for all women, and there were no statistically significant differences between any antibiotic (combined) and the placebo group (RR 1.25, 95% CI 0.85 to 1.85).
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Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit.
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The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner.