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A placebo-controlled trial of low-dose erythromycin to promote feed tolerance in preterm infants.

UNLABELLED: The aim of this study was to assess the efficacy of erythromycin, a motilin agonist, in promoting enteral feed tolerance in preterm infants of < or = 32 wk gestation. Eligible infants were randomized to receive either low-dose (2.5 mg kg(-1) per dose 6 hourly) oral erythromycin ethylsuccinate or placebo for 10 d from the time of the first oral feed. The data from 22 erythromycin and 21 placebo infants were analysed. Birthweights (erythromycin 1,216 +/- 380 g, placebo 1,355 +/- 228 g, p = 0.25), gestation (erythromycin 28.6 +/- 2.2 wk, placebo 29.3 +/- 1.7 wk, p = 0.24) and other clinical variables were not different between the groups. Almost all infants were fed expressed breast milk. Erythromycin infants had significantly fewer episodes of large residual gastric aspirates (>30% of the previous 6 h worth of feeds) over 10 d (erythromycin 1.1 +/- 1.9, placebo 3.6 +/- 2.2 episodes, p = 0.0007). Infants in the erythromycin group achieved full oral feeds more quickly (6.0 +/- 2.3 vs 7.9 +/- 3.5 d, p = 0.04). There were no significant differences between the groups with regard to the number of days on total parenteral nutrition or to the time needed to regain birthweight. One enrolled infant from each group died of necrotizing enterocolitis. CONCLUSION: Low-dose erythromycin promoted gastric emptying and feed tolerance in premature infants at a lower gestational age than previously reported. Increased exposure to broad-spectrum antibiotics may not be free of risk. Further studies are recommended to assess its efficacy in premature infants with established feed intolerance.

Double-Blind Method↗

[The effects of erythromycin on the secretion of tumor necrosis factor-alpha and transforming growth factor-beta1 and expression of connexin 43 in human pleural mesothelial cells].

OBJECTIVES: To investigate the effects of erythromycin on secretion of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)), and the level of connexin 43 in human pleural mesothelial cells (HPMC), and to explore the mechanism of pleurodesis. METHODS: HPMC was incubated with erythromycin at concentrations of 100 mg/L or 25 mg/L. The levels of TNF-alpha and TGF-beta(1) in the supernatants were measured by ELISA method, and levels of connexin 43 were detected by Western blot. RESULTS: The secretion of TNF-alpha by HMPC increased after incubation with 100 mg/L erythromycin for 3 or 5 days, and the secretion of TGF-beta(1) increased markedly after incubation with lower or higher concentrations of erythromycin. The levels of connexin 43 in HPMC decreased after stimulation with 100 mg/L erythromycin, but no relationship was observed between the levels and the stimulation time. CONCLUSIONS: HPMC incubated with erythromycin showed increased secretion of TNF-alpha and TGF-beta(1), which may be one of the mechanisms for erythromycin pleurodesis. Erythromycin decreased the level of connexin 43 in HPMC, and this effect may be a response of the cells to the stimulus. A high concentration of erythromycin is suggested for clinical pleurodesis based on the results from this study.

Cells, Cultured↗

Absorption of various erythromycin esters and salts in mice after intragastric intubation.

Erythromycin base and its different salts and esters were given intragastrically to mice. Serum concentrations of erythromycin and its 2'-esters were determined by the bacterial growth inhibition method. Acetyl and propionyl erythromycin were the best absorbed 2'-esters, and differed significantly from butyryl erythromycin and erythromycin base. Erythromycin estolate yielded a larger area under the concentration curve than acistrate or stearate. Among the syrup preparations, erythromycin acistrate was significantly better absorbed than 2'-ethylsuccinyl erythromycin. Absorption of 2'-esters decreased with increasing number of esterified carbon atoms and increasing hydrophobicity and increasing log P value (the logarithm of octanol-water partition coefficient). In addition to sufficient lipophilicity, the optimum absorption of erythromycin esters seems to require a high hydrophilicity.

Animals↗

erm genes in erythromycin-resistant Staphylococcus aureus and coagulase-negative staphylococci.

Erythromycin-resistant S. aureus from general practice and a dermatology ward with a very high consumption of erythromycin was studied for ermA and ermC content by Southern blot analysis. The prevalence of these erm genes was also studied in coagulase-negative staphylococci from the same dermatology ward and in a collection of 15 S. aureus and 18 coagulase-negative staphylococci found in the same specimen from 15 different patients. ermA was only found as a chromosomal insert and ermC only on small plasmids. In erythromycin-resistant S. aureus from general practice ermC was responsible for 84% of erythromycin resistance, while 16% of the strains contained ermA. In 17 of 18 S. aureus strains from the dermatology ward a 2.5 kb plasmid contained ermC. Among 58 erythromycin-resistant coagulase-negative staphylococci only 2 (3%) had ermA, whereas 44 strains (76%) had ermC. ermA or ermC genes were common in S. epidermidis (36/38). However, in 20 isolates of erythromycin-resistant coagulase-negative staphylococci of other species, 10 had neither ermA nor ermC. ermC was the most common erm gene in both coagulase-negative staphylococci and S. aureus. In 11 of 15 patients with erythromycin-resistant S. aureus the co-isolated erythromycin-resistant coagulase-negative staphylococcus had another resistance mechanism, either another gene or a different phenotypic expression of the same gene. Resistance to pristinamycin, a streptogramin antibiotic only used in animals, was not found in S. aureus but was found in 14% of erythromycin-resistant coagulase-negative staphylococci.

Animals↗

Effect of erythromycin on gallbladder emptying in patients with antrectomy or truncal vagotomy.

OBJECTIVES: Erythromycin, a motilin-like agent, stimulates gallbladder contraction in healthy control subjects. Because the action of erythromycin is cholinergic dependent and possibly related to premature phase III migrating motor complex activity in the antrum, we investigated the effect of erythromycin on gallbladder volume in six patients with truncal vagotomy without gastric resection and 14 patients with antrectomy (6 with Billroth I anastomosis, 8 with Billroth II anastomosis), and we compared the results obtained with those in eight healthy controls. In addition, the effect of meal ingestion on gallbladder volume was studied. METHODS: Gallbladder volumes, measured with ultrasonography, were determined every 15 min for 180 min after erythromycin infusion (3 mg/kg i.v.), as well as 30 and 60 min after meal ingestion. RESULTS: Basal gallbladder volumes were not significantly different among the four groups. Erythromycin induced a significant (p < 0.01-0.05) gallbladder contraction of maximal 46 +/- 6% in the controls, 49 +/- 9% in the patients with truncal vagotomy, and 38 +/- 7% in the patients with antrectomy and Billroth I anastomosis. In the patients with antrectomy and Billroth II anastomosis, no significant reduction in gallbladder volume after erythromycin was observed. Meal-induced gallbladder contraction was normal in all patients, including those with Billroth II anastomosis. CONCLUSIONS: These results indicate that neither the long vagus nerve nor the antrum is essential for erythromycin-induced effects on the gallbladder. Because no significant reduction in gallbladder volume in response to erythromycin was observed in the patients with antrectomy and Billroth II anastomosis, we suggest that duodenojejunal anatomical integrity is essential for erythromycin-induced gallbladder contraction.

Adult↗

Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects.

The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa.

Adult↗

The relationship between erythromycin consumption and resistance in Finland. Finnish Study Group for Antimicrobial Resistance.

Because the discovery of new antimicrobial agents cannot be expected in the near future, we will have to manage with the antimicrobials currently available at least for the next decade or two. Therefore, attempts to prevent development of antimicrobial resistance are of major importance. The relationship of local antimicrobial consumption and antimicrobial resistance has been shown in many hospital studies but not in the community, even though this is where most antibiotics are used. At the beginning of 1990s, erythromycin resistance in group A streptococci increased rapidly in Finland. The geographical variations found led to a nationwide study of the possible relation between local erythromycin consumption and variations in erythromycin resistance in the community. Erythromycin resistance was found to be significantly (P = 0.006) linked to local consumption of erythromycin. In further experiments, we found that a new erythromycin resistance phenotype belonging to the T4 serotype was spread over the whole country; 83% of the erythromycin-resistant isolates were of this new phenotype in 1994. In 1991, recommendations were given to reduce use of erythromycin in Finland. Following these recommendations, macrolide consumption decreased by 40% from 1991-1994. Studies are now in progress to evaluate the effect of this reduction on erythromycin resistance of group A streptococci.

Anti-Bacterial Agents↗

Effect of erythromycin on feeding intolerance in very low birth weight infants: a preliminary observation.

To investigate the effect of erythromycin on feeding intolerance in very low birth weight infants, from February 1997 to December 1997 twenty infants weighing less than 1500 g, with prolonged intolerance of enteral feeding, were enrolled in this study. The protocol for erythromycin treatment was: a loading dose of 30 mg/kg/day, divided into three portions given every eight hours intravenously for 1 hour over a three day period; then a maintenance dose of 3-5 mg/kg intravenously for one hour once a day was given until full feeding was well established. The assessment of erythromycin effect was the daily net orogastric balance (volume of orogastric tube feeding minus volume of orogastric aspirates). The mean gestational age was 27.1 +/- 2.0 weeks (mean +/- SD) and the mean birth weight was 1025 +/- 196 g. The mean age when erythromycin started was 19.5 +/- 14 days; the mean days after the initiation of erythromycin when orogastric tube feeding could be started and full feeding established were 2.4 +/- 1.1 days and 15.1 +/- 2.2 days, respectively. At the beginning of erythromycin treatment, the net balance of tube aspirates was -4.8 +/- 4.1 ml. The net balance rose significantly to 30.6 +/- 15.3 ml, 92.6 +/- 25.4 ml and 125.3 +/- 18.1 ml at 7, 14 and 21 days after erythromycin treatment, respectively. In conclusion, erythromycin treatment is a safe method to improve intolerance of enteral feeding in very low birth weight infants. It is suggested that the effect of erythromycin on gastrointestinal motility in these infants should be further investigated in the context of a randomized, controlled trial before widespread clinical implementation of this treatment.

Anti-Bacterial Agents↗

Human cytochrome P450 3A4-catalyzed testosterone 6 beta-hydroxylation and erythromycin N-demethylation. Competition during catalysis.

Cytochrome P450 3A4 is known to catalyze the metabolism of both endogenous substrates (such as the 6 beta-hydroxylation of testosterone) and many important therapeutic agents, including the N-demethylation of erythromycin. However, erythromycin and testosterone have been reported to have little or no effect on the metabolism of each other by recombinant CYP3A4. In an effort to understand the basis of these observations, we studied the N-demethylation of erythromycin and the 6 beta-hydroxylation of testosterone in human liver microsomes and in microsomes from cells containing recombinant human CYP3A4 and P450 reductase under a variety of experimental conditions. In both human liver microsomal and recombinant CYP3A4 systems, erythromycin inhibited testosterone 6 beta-hydroxylation in a concentration dependent manner, and vice versa. However, the inhibition mechanism was complex. At low substrate concentrations, testosterone and erythromycin acted as competitive inhibitors to each other. Under these experimental conditions, an apparent competitive inhibition of testosterone 6 beta-hydroxylation by erythromycin was observed, with Ki values similar to that of the K(m) values for erythromycin. When the rates of testosterone 6 beta-hydroxylation and erythromycin N-demethylation were determined in microsomal incubations containing both substrates at lower concentrations, the observed rates for each reaction were in good agreement with the calculated rates based on the rate equation describing simultaneous metabolism of two substrates by a single enzyme. However, at high substrate concentrations, the kinetic results could be best explained by a mechanism involving partial competitive inhibition. We conclude from these studies that testosterone and erythromycin mutually inhibit the metabolism of each other, consistent with the fact that CYP 3A4 catalyzes the metabolism of both substrates.

Aryl Hydrocarbon Hydroxylases↗

Variability in the absorption and disposition of erythromycin estolate in humans.

The inter- and intrapersonal variability in the absorption and disposition of erythromycin estolate in humans was assessed by comparing total erythromycin serum concentrations in five subjects who each received a single erythromycin estolate tablet on three separate occasions under identical experimental conditions. Coefficients of variation for the pharmacokinetic parameters Cmax, Tmax, AUC0-12, MRT, and t1/2 were of a similar magnitude when calculated between subjects in any one administration phase or between phases. In addition, serum concentrations of both erythromycin base (active component) and erythromycin propionate were selectively determined in the same subjects only during the final two phases of the study. Comparison of AUC0-12 values showed that the percentage of the total area (base and ester components) present as erythromycin base remained relatively constant between administrations (mean values of 14.5 and 11.2%), with low coefficients of variation between subjects (10.8 and 11.6%). Discrepancy value calculations revealed that the variability in serum concentration-time profiles between the three phases of the study fell into the "small"-to-"moderate" classification. From these data it is apparent that intrapersonal variations in the absorption and disposition of erythromycin estolate are of a similar magnitude to interpersonal variations and should be borne in mind in the design and interpretation of comparative bioavailability studies involving similar formulations of this compound. The relative proportions of erythromycin base and propionate did, however, remain fairly constant both between treatments and between subjects.

Adult↗

Toxicity, uptake, and subcellular distribution in rat hepatocytes of roxithromycin, a new semisynthetic macrolide, and erythromycin base.

Rat hepatocytes were used to study the toxicity of a new semisynthetic macrolide, roxithromycin, in comparison with erythromycin base and erythromycin estolate. Roxithromycin caused lactate dehydrogenase leakage close to that of erythromycin estolate and higher than erythromycin base after 21 h of exposure to the drugs. This effect was, at least in part, explained by the higher uptake: roxithromycin was two to three times more concentrated by liver cells than erythromycin base. For both roxithromycin and erythromycin base, the uptake depended on time, temperature, and extracellular antibiotic concentration. The accumulated macrolides egressed rapidly when cells were incubated in antibiotic-free medium. No uptake and no loss of accumulated drugs were observed at 4 degrees C. After accumulation by hepatocytes, roxithromycin and erythromycin base underwent similar subcellular distribution, mostly concentrating in cytosol and lysosomes. The small amount accumulated in the other particulate fractions followed the order mitochondria much greater than nuclei greater than microsomes. Roxithromycin, however, was less concentrated than erythromycin base in the microsomes.

Animals↗

Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450.

Erythromycin and some other macrolide antibiotics can first induce a cytochrome P-450 isozyme similar to the one induced in rats by pregnenolone-16 alpha-carbonitrile and then inhibit it by forming a stable cytochrome P-450-metabolite complex. The purpose of this study was to compare azithromycin, a novel 15-membered ring azalide, and erythromycin estolate for the potential to cause hepatic microsomal enzyme induction and inhibition in Sprague-Dawley rats. The daily oral administration of 800 mg of erythromycin estolate per kg for 7 days resulted in statistically significant elevations of NADPH-cytochrome c reductase, erythromycin N-demethylase (3.2-fold), and total cytochrome P-450 content. Approximately 40% of cytochrome P-450 was complexed with erythromycin metabolite. In contrast, the daily administration of 200 mg of azithromycin per kg for 7 days caused significant elevations of N-demethylase (2.5-fold) only and did not produce any increases in total cytochrome P-450 content or NADPH-cytochrome c reductase. No complexed cytochrome P-450 was detected in the azithromycin-dosed rats despite liver concentrations of azithromycin that were 118 times greater than the liver concentrations of erythromycin estolate in erythromycin estolate-dosed rats. Although the short-term oral administration of azithromycin produced hepatic accumulation of the drug and elevated azithromycin demethylase activity, there was no other evidence of hepatic cytochrome P-450 induction or inactivation via cytochrome-metabolite complex formation. In contrast to erythromycin estolate, azithromycin is not expected to inhibit its own metabolism or that of other drugs via this pathway.

Animals↗

A comparison of the gastrointestinal side effects of two forms of erythromycin.

BACKGROUND: The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. METHODS: This was a multicenter, prospective, single-blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. RESULTS: There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI-related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). CONCLUSIONS: Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI-symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less.

Adult↗

Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum.

BACKGROUND: Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants. OBJECTIVES: To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity. SEARCH STRATEGY: Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction. DATA COLLECTION AND ANALYSIS: Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals. MAIN RESULTS: Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study. REVIEWER'S CONCLUSIONS: Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.

Anti-Bacterial Agents↗

Oral erythromycin improves gastrointestinal motility and transit after subtotal but not total gastrectomy for cancer.

BACKGROUND: Erythromycin has been shown to be a powerful prokinetic of the gastrointestinal tract. Little is known about its value to improve motility and transit in gastrectomized patients. METHODS: Thirteen disease-free patients subjected to subtotal gastrectomy and 11 subjected to total gastrectomy for gastric cancer entered the study. Gastrointestinal transit of a standard 99mTc-labelled meal and fasting motility were studied before and after oral erythromycin. RESULTS: In patients who had subtotal gastrectomy mean(s.d.) gastric half-emptying time was 42(14) min before and 26(11) min after erythromycin (P = 0.011). Before erythromycin prolonged rhythmical contractions (3 per min) were recorded in eight patients, sporadic non-organized contractions in two and prolonged bursts of waves in one. After erythromycin, clustered waves resembling a migrating motor complex (MMC) appeared in eight patients, while rhythmic motor activity was unchanged in three. In patients who had total gastrectomy jejunal half-emptying time was 39(18) min before and 45(12) min after erythromycin. In eight patients, frequent MMCs were recorded, peristaltic in four, synchronous in one, antiperistaltic in two, with clusters of non-propagated waves in one. After erythromycin, longer peristaltic MMCs were recorded in three, antiperistaltic MMCs persisted in two, synchronous in one and clusters of non-propagated waves in two. CONCLUSION: Oral erythromycin improves gastrointestinal transit and motility after subtotal gastrectomy. The findings after total gastrectomy are controversial.

Administration, Oral↗

Improved high-pressure liquid chromatographic method for the analysis of erythromycin in solid dosage forms.

A stability-indicating high-pressure liquid chromatographic (HPLC) method for the assay of erythromycin in enteric film-coated tablets was developed. The method used a reversed-phase column at 70 degrees with a mobile phase of acetonitrile-methanol-0.2 M ammonium acetate-water (45:10:10:35) at pH 7.0. The column were evaluated for the analysis of erythromycin. The HPLC method was also applicable for the analysis of salts and esters of erythromycin. The linearity and precision of the HPLC assay method for erythromycin in the solid dosage form were examined by spiking erythromycin into a tablet placebo a 60-120% of the label. The recovery of erythromycin was 99.9% with a relative standard deviation of less than 1%. The correction factors to express the results of HPLC in terms of antimicrobial bioequivalency against Staphylococcus aureus TCC 6538P for erythromycins A, B, and C were determined to be 1.0, 0.92, and 0.48, respectively. Eight lots of tablets were assayed by the HPLC method, and the results, expressed in terms of erythromycin bioequivalency, showed no statistically significant difference from those of the microbiological assay method.

Bacteria↗

Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.

Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children.

Adolescent↗

Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian brush-tailed possum.

Erythromycin has been shown to interact with gastrointestinal smooth muscle in a similar manner to motilin, and has been postulated as a motilin receptor agonist. We report that in isolated preparations from the biliary tract of thirty one Australian Brush-tailed Possums (Trichosurus vulpecula) erythromycin acts in a similar manner to motilin. In all muscle strips from the sphincter of Oddi, prepared in both the circular and longitudinal orientation, both synthetic porcine motilin (10(-10) M-10(-6) M) and erythromycin (lactobionate) (10(-8) M-10(-4) M) stimulated contractile activity in a concentration dependent manner, via a direct effect on the smooth muscle (the response was unaffected by tetrodotoxin, omega conotoxin GVIA or atropine). In strips prepared from the gallbladder neither agonist affected the contractile activity in 7 of 8 animals. Motilin was approximately 1000 fold more potent in stimulating contractile activity than erythromycin in both sphincter of Oddi circular strips [pD2 for peak response to motilin 8.67 (mean) +/- 0.06 (SEM) compared with erythromycin 5.67 +/- 0.09] and sphincter of Oddi longitudinal strips [pD2 for peak response to motilin 8.64 (mean) +/- 0.28 (SEM) compared with erythromycin 5.45 +/- 0.23]. The concentration response curves for motilin and erythromycin were similar and both agonists required the presence of extracellular calcium to elicit responses (responses were diminished by verapamil and abolished in calcium free Krebs solution). Our results support the hypothesis that erythromycin mimics the action of motilin in stimulating the sphincter of Oddi in vitro.

Animals↗