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PubMed2003

Duodenogastric reflux after biliary surgery: scintigraphic quantification and improvement with erythromycin.

BACKGROUND: Persistence of dyspeptic symptoms after cholecystectomy or choledochoduodenostomy is common. There is -evidence that at least some of these symptoms may be attributed to duodenogastric reflux (DGR). The aim of the study was to quantify DGR before and after cholecystectomy, with or without choledochoduodenostomy, and endoscopic sphincterotomy for common bile duct stones, and to assess the effect of erythromycin on the increased DGR. METHODS: Forty-seven patients before and after cholecystectomy, 26 after cholecystectomy and choledochoduodenostomy and nine after sphincterotomy had postprandial (300 mL of fresh milk, 4% fat) duodenogastric reflux measured by 99mTc-hepatic imino diacetic acid scintigraphy. Patients with a DGR index (DGRi) >20% were considered as having pathological DGR that justifies symptoms, and their DGRi was reassessed after administration of 200 mg of erythromycin intravenously. RESULTS: Twenty-seven patients before cholecystectomy (57%) showed a normal DGRi <7%. In five cases DGRi was greater than 20%. After cholecystectomy, duodenogastric refluxes increased, so that only 16 patients (32%) showed a normal DGRi, while a DGRi >20% was observed in 10 cases. Only eight patients after cholecystectomy and choledochoduodenostomy (23%) presented with a DGRi within the normal range. The remaining 18 had a DGRi >7%. Five of them exhibited a DGRi >20%. Of the nine patients with sphincterotomy, three showed a DGRi >20%. Erythromycin almost completely normalized DGRi in all 18 patients with pathological DGR (P < 0.0001). CONCLUSIONS: Duodenogastric reflux is common after biliary surgery, including endoscopic sphincterotomy. Erythromycin appears to decrease duodenogastric reflux to normal levels.

Adult↗
PubMed2003

The [14C-N-methyl]-erythromycin breath test dosimetry complies with the French regulations for radiation safety.

The [14C-N-methyl]-erythromycin breath test (14C-ERMBT) is one of the most valuable probes for liver cytochrome P450-3A4 activity in humans. In order to extend the use of this test in France, we herein provide safety data regarding either patient dosimetry or worker exposure to [14C-N-methyl]-erythromycin. In order to determine the maximum radiation exposure for patient and nuclear medicine technician following one intravenous 14C-ERMBT [111 kiloBequerel (kBq)], we have used the dosimetric data gathered in animal studies and extrapolated to humans using a weight-based method, approximate data provided by the French Society of Radioprotection and erythromycin pharmacokinetics in humans, considering always the worst conditions for the patient and worker exposure determination. The radioactivity administered to a patient after one 14C-ERMBT was equal to 108.8 kBq (i.e. 98% of the total radioactivity in the 14C-erythromycin vial) leading to a patient effective dose of 20 microsievert (microSv) and a maximum effective dose after 14CO2 inhalation by the exposed worker of 16 microSv compared with a mean individual annual effective dose from natural and artificial radioactivity exposure of 3500 microSv in France. The 14C-ERMBT is safe and complies with the European regulations regarding the administration of 14C-labelled compounds in humans. It can therefore be used in clinical research in France without any particular safety requirement.

Animals↗
PubMed2001

Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans.

OBJECTIVE: Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibiting agents such as erythromycin and the dopamine agonist alpha-dihydroergocryptine (DHEC). METHODS: The study was carried out as a single-center, controlled, nonblinded, 2-way crossover clinical trial with randomly allocated period-balanced sequences, investigating two treatments of a single oral dose of 10 mg DHEC (on the morning of day 1), once administered alone (reference), once along with a 4-day treatment (days -2 to 1) of 500 mg erythromycin 3 times daily. Periods were separated by a washout of at least 14 days. Nine healthy white male volunteers, 22 to 42 years old, with a body weight range of 58 to 90 kg (body mass index, 20.2-25.1 kg x m(-2)) began the study. One subject discontinued prematurely, and 8 concluded the study in accordance with the study protocol. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by a large variability. Concomitant treatment with erythromycin led to respective increases of 9.5 (95% confidence interval [CI], 6.5 to 13.9) and 16.5 (95% CI, 8.7 to 31.5) times the maximum observed plasma drug concentration and the area under the time course of the plasma concentrations up to the last quantifiable concentration after dosing of unchanged DHEC (determined by radioimmunoassay). The 24-hour urinary excretion was on average 11 times larger (95% CI, 5.9 to 20.7). Qualitatively similar findings were recorded for the total of DHEC plus metabolites (as determined by enzyme immunoassay). CONCLUSIONS: The concomitant use of erythromycin or similarly CYP3A4-inhibiting agents along with direct dopaminergic agonists such as the ergoline DHEC may cause a clinically relevant increase in pharmacokinetic exposure, which may induce exaggerated dopaminergic effects.

Administration, Oral↗
PubMed2002

One-year low-dose erythromycin treatment of persistent chronic sinusitis after sinus surgery: clinical outcome and effects on mucociliary parameters and nasal nitric oxide.

OBJECTIVE: In 17 patients with chronic sinusitis persistent after sinus surgery, long-term, low-dose erythromycin therapy was tested. The aim of the investigation was to study the clinical outcome and effects on nasal nitric oxide (NO), ciliary beat frequency (CBF), and mucociliary transport (saccharine transit time). STUDY DESIGN AND SETTING: We conducted a prospective open study at a tertiary teaching hospital. Symptoms were assessed using visual analog scales. NO was measured using a chemiluminescence analyzer, and mucociliary transport was measured with the saccharine crystal technique. CBF was measured in nasal brush samples using a phase contrast microscope. All patients were treated with erythromycin succinate 250 mg 2x daily or clarithromycin 250 mg 1x daily and were assessed after 3 months. In cases where there was no response, treatment was abandoned. The remaining patients (responders) were reassessed after 12 months of treatment. RESULTS: Of 17 patients, 12 responded to treatment. The 12-month follow-up showed an improvement in saccharine transit time (P < 0.05) but no significant change in CBF. There was a trend toward an increase in NO (P = 0.12). Endoscopic nasal examination scoring improved significantly (P < 0.01). In the visual analog scale scoring, the most pronounced improvements were seen in nasal congestion, sticky secretion, and runny nose at 3 and 12 months (P < 0.01). Improvements were also seen in headache (P < 0.05). CONCLUSION: The present study suggests that long-term, low-dose treatment with erythromycin is effective in persistent chronic sinusitis that does not respond to sinus surgery or systemic steroid/antibiotic treatment. SIGNIFICANCE: Long-term, low-dose erythromycin therapy seems to be a promising alternative when more conventional therapy fails. However, placebo-controlled studies are needed to validate the potential of this treatment.

Adolescent↗
PubMed2002

Erythromycin use during pregnancy in relation to pyloric stenosis.

OBJECTIVE: Newborn infants treated with erythromycin may be at risk for developing pyloric stenosis. Because erythromycin is known to cross the placenta and is a recommended treatment for chlamydia and other infections in pregnancy, we explored whether erythromycin taken during pregnancy might similarly lead to an increase in risk of pyloric stenosis. STUDY DESIGN: We used data collected between 1976 and 1998 as part of an ongoing case-control surveillance program. Cases were 1044 infants with a diagnosis of pyloric stenosis. Two control groups were used: 1704 nonmalformed infants and 15,356 infants with a wide range of other malformations. Odds ratios and 95% CIs were calculated by using data from each control group. RESULTS: All odds ratio estimates are close to 1.0, all CIs include 1, and all upper 95% confidence bounds are less than 2.0. CONCLUSION: We found no evidence of an increased risk of pyloric stenosis among infants born to mothers exposed to erythromycin during pregnancy.

Adult↗
PubMed1982

Erythromycin resistance due to a mutation in a ribosomal RNA operon of Escherichia coli.

There are seven ribosomal RNA operons (rrn operons) in Escherichia coli. A single rrn operon was amplified by use of a multicopy recombinant plasmid containing a complete rrnH operon. rrnH thereby has the potential to contribute a greater fraction of the rRNA found in ribosomes. Erythromycin-resistant mutants were isolated from cells containing the plasmid, and at least one mutation to resistance was shown to reside in rrnH on the plasmid. Erythromycin resistance was retained when a major deletion was introduced into the 16S rRNA gene and was abolished by deletions that affect the 16S and 23S rRNA genes but do not alter the 5S rRNA gene or non-rrnH DNA. Cell-free S30 protein-synthesizing extracts from cells containing the mutant plasmid have an increased resistance to erythromycin. The selection procedure used to isolate erythromycin-resistance mutations in rrnH may allow, with minor modifications, the isolation of mutations in rrn operons that change resistance of the ribosome to other antibiotics or that alter other properties of ribosomes.

DNA, Recombinant↗
PubMed2002

Bacterial resistance and therapeutic outcome following three months of topical acne therapy with 2% erythromycin gel versus its vehicle.

Two-hundred-and-eight acne vulgaris patients were enrolled in a 24-week study to determine the bacterial resistance issues associated with the use of a topical 2% erythromycin gel. It consisted of a 12-week randomized, double-blind, parallel-group treatment phase comparing the active gel versus its vehicle followed by a 12-week single-blind regression phase with gel vehicle only. Bacteriological samples were taken from the face, back and nares for quantification by species and antibiotic resistance characteristics. Acne efficacy was assessed through week 12. The prevalence of erythromycin-resistant coagulase-negative Staphylococci on the face was extremely high (87%) at baseline, increased to 98% by week 12 in the erythromycin-treated group and did not change during regression. The density of these resistant organisms also significantly increased with erythromycin treatment with no change during regression. Similar prevalence and density patterns were also observed on the untreated back and in the nares. Nearly all of the resistant isolates were highly resistant (minimal inhibitory concentrations > 128 microg/ml). Resistance development was confined to the macrolide class of antibiotics. No anti-acne efficacy was observed.

Acne Vulgaris↗
PubMed1993

Activity of erythromycin and clindamycin in an experimental Staphylococcus aureus infection in normal and granulocytopenic mice. A comparative in vivo and in vitro study.

The activity of 2 bacteriostatic antibiotics, erythromycin and clindamycin, against Staphylococcus aureus was studied in vitro and in an experimental infection in granulocytopenic as well as normal mice. In vivo, on the basis of dosage, erythromycin was 2.20 times more potent than clindamycin in normal mice and 1.95 times more potent in irradiated granulocytopenic mice. Tissue concentrations were calculated from the plasma concentrations, taking plasma protein and tissue binding into account. On the basis of the area under the curve for the free tissue concentrations, clindamycin was 1.48 times more potent than erythromycin in normal mice and 1.64 times more potent in irradiated mice, which is somewhat less than expected from the comparison in vitro. It is concluded that the relative antistaphylococcal efficacies of erythromycin and clindamycin in vivo can be predicted from the in-vitro values if the relevant pharmacokinetics are taken into account. Irradiation decreased the efficacy of both antibiotics such that an about 8-fold increase in dose led to an antibacterial effect similar to that in non-irradiated animals. This could imply that these drugs will not be sufficiently effective against staphylococcal infections in granulocytopenic patients.

Agranulocytosis↗
PubMed1998

Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates.

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [n = 155; median GA 26 (23-29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40 mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs 12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks' postconceptual age (p < 0.05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants (n = 14) and those not treated (n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.

Anti-Bacterial Agents↗
PubMed1992

Clinical comparative study of azithromycin versus erythromycin in the treatment of acute respiratory tract infections in children.

The efficacy and tolerability of azithromycin and erythromycin in the treatment of acute respiratory tract infections in children were compared in an open, multicenter, randomized trial. A total of 151 children, aged from 2 months to 14 years, suffering from upper airways infections (60), or lower respiratory tract infections (91), were randomized to be treated either with azithromycin, 10 mg/Kg/day per os once daily for 3 or 10 mg/Kg/day 1 and 5 mg/Kg/days 2-5 (77 patients) or with erythromycin, 50 mg/Kg/day thrice daily for at least 7 days (74 patients). The two treatment groups did not significantly differ as to sex, age, weight, type and severity of infection, and infecting pathogens. Clinical evaluation was performed prior to therapy, on treatment days 1, 3, 5 and 7, and on day 10. Microbiological and laboratory assessment were carried out at baseline and after the end of therapeutic course. Chest X-ray and serologic assays for Mycoplasma pneumoniae infection were obtained in patients suspected to have lower respiratory tract infections. At the end of therapy, clinical cure was achieved in 73 out of 77 patients (94.8%) in the azithromycin group, and in 60/72 evaluable subjects (83.3%) in the erythromycin group. A significantly more rapid remission of several illness-related signs and symptoms was observed in patients treated with azithromycin. A total of 75 bacterial pathogens were isolated at baseline microbiological examination; at the end of the therapeutic course bacteriological eradication was obtained in 34/34 cases (100%) treated with azithromycin, and in 40/41 children (97.5%) treated with erythromycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1996

In vitro susceptibilities of 176 clinical isolates of Streptococcus pneumoniae to 11 beta-lactams, erythromycin, and tetracycline.

One hundred seventy six consecutive, non-duplicate pneumococcal isolates from clinical specimens collected from November 1994 through February 1995 in nine general hospitals throughout Belgium were tested for their in vitro susceptibilities to penicillin, ampicillin, amoxycillin with and without clavulanate, cefaclor, cefuroxime, cefonicid, cefprozil, cefpodoxime, cefotaxime, imipenem, tetracycline, and erythromycin by means of the NCCLS microdilution test. The overall rate of decreased susceptibility to penicillin was 12.5%, including 6.3% of intermediately and 6.3% of fully resistant isolates. Penicillin, ampicillin amoxycillin, amoxycillin/clavulanate, cefuroxime, cefotaxime and imipenem had the highest activity on a weight basis (MIC50 < or = 0.008 microgram/ml), followed by cefpodoxime and erythromycin (MIC50 of 0.015 microgram/ml), cefprozil and tetracycline (MIC50 of 0.12 microgram/ml), and eventually, cefaclor and cefonicid (MIC50 of 0.5 microgram/ml). Aggregate rates of susceptible plus intermediately resistant isolates at NCCLS-recommended breakpoints, i.e. overall percentages of isolates likely to respond to increased antibiotic doses in vivo (except for meningitis), were 100.0% for imipenem and cefotaxime, 98.9% for amoxycillin with and without clavulanate, 93.8% for penicillin, and 90.9% for cefuroxime. Overall rates of susceptibility to erythromycin and tetracycline amounted to 78.4% and 72.7%, respectively. MIC values of all beta-lactams increased with those of penicillin. Ampicillin was equally active as penicillin against isolates with reduced susceptibility to the latter (MIC90 of 2 micrograms/ml); imipenem, cefotaxime, and amoxycillin with and without clavulanate however, were more active (MIC90 3, 1, and 1 doubling dilution, respectively, below that of penicillin), while cefpodoxime, cefuroxime, cefprozil, cefonicid, and cefaclor on the other hand, were less active (MIC90, 1, 1, 2, 5, and 5 doubling dilutions, respectively, above that of penicillin). In conclusion, the present data confirm that pneumococcal resistance to penicillin has increased in Belgium, suggest that resistance to erythromycin may have stabilised, and reveal an unexpectedly high rate of resistance to tetracycline. Imipenem was the most active antibiotic tested overall, and amoxycillin with or without clavulanate the most active oral antibiotic, with activity almost similar to that of cefotaxime.

Anti-Bacterial Agents↗
PubMed2000

Antimicrobial use and colonization with erythromycin-resistant Streptococcus pneumoniae in Greece during the first 2 years of life.

We evaluated nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae during the first 2 years of life in central and southern Greece. Of 2448 children studied from February 1997 to February 1999, 766 (31%) carried 781 pneumococcal isolates. Ninety-five (3.9%) of the children attended day care centers. Eighteen percent of the pneumococci were resistant to erythromycin (minimal inhibitory concentration 1 to >128 microg/mL), with 67.9% of them carrying the erm(B) gene and 29.2% mef(A) gene products. Four strains possessed neither the erm(B) nor the mef(A) gene. Multidrug resistance occurred in 97% and 40% of isolates carrying the erm(B) and mef(A) gene, respectively. An association was found between the erm(B) gene and serotypes 6B and 23F and between the mef(A) gene and serotypes 14 and 19F. A significant relationship existed between carriage of erythromycin-resistant pneumococci and use of macrolides or beta-lactams in the previous 3 months; the association was strongest when macrolide therapy was administered during the last month (odds ratio, 5.92; P=.0001). The findings indicate the necessity of a judicious use of both macrolides and beta-lactams in young children to reduce the colonization with erythromycin-resistant pneumococci and the subsequent spread of such strains to the community.

Anti-Bacterial Agents↗
PubMed1998

Resistance of Streptococcus pyogenes to erythromycin and related antibiotics in Italy. The Italian Surveillance Group for Antimicrobial Resistance.

A survey of antimicrobial resistance in Streptococcus pyogenes, performed within the framework of a national surveillance program, has revealed a dramatic increase in resistance of S. pyogenes to erythromycin in most areas of Italy. In virtually all the centers that provided data for 3 consecutive years, the incidence of erythromycin-resistant strains increased twofold to 20-fold from 1993 to 1995 and was greater than 30% in five of the 14 centers participating in the study. The clonality of erythromycin-resistant isolates was studied in 15 strains isolated from different patients at the Institute of Microbiology of Verona University (Verona). The features of the Verona isolates and the substantially different rates of erythromycin and clindamycin resistance observed in most centers suggest that the spread of different resistance genes in multiple clones might be occurring throughout the country.

Anti-Bacterial Agents↗
PubMed1998

Penicillin vs. erythromycin in the treatment of diphtheria.

In an open-label, randomized trial, 44 Vietnamese children with diphtheria were given penicillin therapy (intramuscular benzylpenicillin, 50,000 U/[kg.d] for 5 days and then oral penicillin, 50 mg/[kg.d] for 5 days), and 42 were given erythromycin therapy (50 mg/[kg.d] orally for 10 days). There were no differences in times to membrane clearance or bacteriologic clearance, but median times to fever clearance were 27 hours (95% confidence interval [CI], 19-30; range, 0-124 hours) for penicillin recipients and 46 hours (95% CI, 34-54; range, 0-148 hours) for erythromycin recipients (P = .0004). In the penicillin group, acute treatment failed for one patient, and one patient relapsed. Three patients in the penicillin group developed diphtheritic myocarditis as evidenced by abnormal electrocardiograms. Erythromycin did not cause prolongation of the QT interval corrected for heart rate. Cultures of specimens from 15 patients (17.4%) were positive for toxigenic Corynebacterium diphtheriae. All isolates were susceptible to penicillin, but for isolates (27%), all of which were from patients who received penicillin treatment, were resistant to erythromycin (minimum inhibitory concentrations, > 64 mg/L). Penicillin is recommended as first-line treatment for diphtheria in Vietnam.

Adolescent↗
PubMed1988

Aetiology of acute pharyngitis and clinical response to empirical therapy with erythromycin versus amoxicillin.

One hundred and eighty-nine adults with acute pharyngitis had culture and serological evaluation for group A beta haemolytic streptococci (GABHS), Mycoplasma pneumoniae, and Branhamella catarrhalis. Sixteen patients had evidence for infection with GABHS, none for M. pneumoniae, and one for B. catarrhalis. For those with GABHS, there was no significant difference between empirical treatment by erythromycin or amoxicillin. For those without GABHS, empirical treatment with erythromycin appeared to result in a statistically significant reduction in cough and a noticeable but less than significant reduction of other symptoms when compared to empirical treatment with amoxicillin. The new formulation of erythromycin utilized in this study (PCE) may be associated with a reduction in gastrointestinal intolerance from that reported with other erythromycin products.

Amoxicillin↗
PubMed2002

Erythromycin slows aging of Saccharomyces cerevisiae.

Life span was measured by counting budding cycles in cohorts of yeast cells treated with erythromycin, paraquat, or geneticin. Paraquat treatment increases oxidative stress; geneticin treatment increases errors during cytoplasmic protein synthesis. Treating with either or both compounds resulted in shorter life spans. Saccharomyces cerevisiae strain K65-3D grown in 16 microg/ml erythromycin, a treatment that results in more accurate protein synthesis by bacteria, had a mean life span that was significantly longer (27%) than that of untreated yeast cells. The life spans of petite variants with no detectable respiratory activity or extranuclear DNA were not affected by this dose of erythromycin, which appeared, therefore, to exert its effect on aging by means of mitochondria. Fitting the data to Weibull and Gompertz distributions allowed calculation of an accelerated life model that relates life span to dose of erythromycin.

Anti-Bacterial Agents↗
PubMed1992

Oral erythromycin prophylaxis against Streptococcus pyogenes infection in penicillin-allergic military recruits: a randomized clinical trial.

Historically, military recruits have required benzathine penicillin G to prevent epidemics of Streptococcus pyogenes. In this randomized clinical trial, low-dose oral erythromycin was evaluated as an alternative for prophylaxis against group A beta-hemolytic streptococci in penicillin-allergic recruits. US Marine Corps recruits (186) reporting penicillin allergy were randomly given either oral erythromycin (250 mg twice a day) or a vitamin (one tablet daily) for 60 days. Evidence of infection was defined as a two-dilution rise in anti-streptolysin O titer. The erythromycin group had a significantly lower risk of S. pyogenes infection than did the vitamin group (relative risk 0.44; 95% confidence interval, 0.22-0.89). There was no significant difference among the treatment groups in isolation of group A beta-hemolytic streptococci from throat cultures. Low-dose oral erythromycin appears as effective as benzanthine penicillin G in preventing S. pyogenes infection.

Administration, Oral↗
PubMed1984

Erythromycin compared with a combination of ampicillin plus flucloxacillin for the treatment of community acquired pneumonia in adults.

Erythromycin was compared with a combination of ampicillin plus flucloxacillin for treating adults admitted to hospital with community acquired pneumonia. A satisfactory clinical response to a seven day course of antibiotics was observed in 29 of 36 patients (81%) in the erythromycin group and 35 of 39 patients (90%) treated with ampicillin plus flucloxacillin, as judged by a fall in temperature, improvement in the general condition, diminution of respiratory symptoms and radiographic improvement. Streptococcus pneumoniae was the causative organism most commonly detected and a satisfactory outcome of treatment of diagnosed pneumococcal pneumonia cases was observed in 16 of 18 patients (89%) treated with erythromycin compared with 20 of 22 patients (91%) treated with ampicillin plus flucloxacillin. These results indicate that erythromycin has similar clinical efficacy to ampicillin plus flucloxacillin, given as a seven day course, for the treatment of community acquired pneumonia in adults.

Adult↗