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PubMed1995

Erythromycin inhibits the assembly of the large ribosomal subunit in growing Escherichia coli cells.

Erythromycin and other macrolide antibiotics have been examined for their effects on ribosome assembly in growing Escherichia coli cells. Formation of the 50S ribosomal subunit was specifically inhibited by erythromycin and azithromycin. Other related compounds tested, including oleandomycin, clarithromycin, spiramycin, and virginiamycin M1, did not influence assembly. Erythromycin did not promote the breakdown of ribosomes formed in the absence of the drug. Two erythromycin-resistant mutants with alterations in ribosomal proteins L4 and L22 were also examined for an effect on assembly. Subunit assembly was affected in the mutant containing the L22 alteration only at erythromycin concentrations fourfold greater than those needed to stop assembly in wild-type cells. Ribosomal subunit assembly was only marginally affected at the highest drug concentration tested in the cells that contained the altered L4 protein. These novel results indicate that erythromycin has two effects on translation, preventing elongation of the polypeptide chain and also inhibiting the formation of the large ribosomal subunit.

Anti-Bacterial Agents↗
PubMed1990

Effect of erythromycin on the oro-caecal transit time in man.

Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility. 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial. The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon. t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication. It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.

Adult↗
PubMed1984

Lack of clinically important interaction between erythromycin and theophylline.

In 11 healthy volunteers the kinetics of theophylline and the plasma levels and the urinary excretion of its metabolites were studied before and after treatment with erythromycin for 10 days. Theophylline was administered as an intravenous bolus injection (280 mg) followed by a constant intravenous infusion (23.8 +/- 4.1 mg/h) for 6 hours. The total clearance of theophylline at steady-state (63.4 +/- 9.9 vs 63.8 +/- 14.4 ml/min, before vs after erythromycin treatment) and the elimination half-life after cessation of the infusion (6.7 +/- 2.6 vs 7.5 +/- 1.8 h, before vs after treatment) did not change during the treatment with erythromycin. No difference in the formation of metabolites before and after treatment with erythromycin was detected; the findings in urine were 40.4 +/- 5.0 vs 42.1 +/- 5.4% 1,3-dimethyluric acid, 29.6 +/- 4.6 vs 30.1 +/- 5.9% 1-methyluric acid and 13.4 +/- 3.5 vs 12.5 +/- 2.2% 3-methylxanthine before and after erythromycin treatment, respectively. It is concluded that a clinically relevant interaction between erythromycin and theophylline does not occur.

Adult↗
PubMed1992

Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin.

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 micrograms/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean +/- SE) of 45.3 +/- 8.2% and 37.3 +/- 5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5 +/- 14.5 pmol/liter in diabetic patients and 63.3 +/- 6.0 pmol/liter in healthy subjects (P < 0.01). However, patients with AN had higher (130.0 +/- 11.9 pmol/liter) motilin plasma levels than patients without (74.0 +/- 9.4 pmol/liter, P < 0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients without AN, but did not stimulate motilin release in neuropathic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Erythromycin stimulates gallbladder emptying and motilin release by atropine-sensitive pathways.

The effect of administering different doses of erythromycin on gallbladder emptying and plasma concentrations of immunoreactive motilin was investigated in healthy volunteers. Erythromycin was infused for 30 min at four different doses: 20, 50, 100, and 1000 mg/hr. Gallbladder volume was determined by ultrasound scanning every 10 min for 60 min. All doses, except 20 mg/hr, provoked a significant reduction in gallbladder volume (P < 0.01). The gallbladder emptying peak occurred after 20 min infusion. It was approximately 40-45% of basal volume and 60-70% of the emptying observed after a standard meal. At 100 mg/hr, erythromycin caused a 2.5-fold increase in plasma motilin concentration, which reached a peak after 30 min infusion. Plasma motilin peaked following maximum gallbladder emptying in all subjects. To evaluate whether cholinergic pathways were implicated in the action of erythromycin, 100 mg/hr erythromycin was infused together with 6 micrograms/kg/hr atropine. Atropine inhibited both gallbladder emptying and motilin release (P < 0.001). Infusion of 1 microgram/kg/hr somatostatin had the same inhibitory effects (P < 0.001). Our results suggest that atropine acts by inhibiting an erythromycin-activated cholinergic neural mechanism. Somatostatin could exert its inhibitory effect by blocking the release of acetylcholine from neural terminations.

Adult↗
PubMed1986

Erythromycin induces migrating motor complex in human gastrointestinal tract.

Fifteen healthy subjects, fasted at least 8 hr, were studied by means of an infused manometric method. Twenty minutes after termination of the natural phase III activity in the duodenum, erythromycin or normal saline was administered intravenously for 15 min. When normal saline (N = 5) was infused, the next migrating motor complex (MMC) was initiated 151.2 +/- 42.1 min after the infusion. On the other hand, when erythromycin was infused at a rate of 1.0 mg/kg/hr (N = 5) or 3.0 mg/kg/hr (N = 5), MMC-like contractions were initiated at shorter intervals, ie, 47.8 +/- 40.9 min (P less than 0.005) or 23.0 +/- 13.0 min (P less than 0.001) respectively. The duration, frequency, amplitude, and migrating velocity of the naturally occurring MMC (N-MMC) were not significantly different from those of the erythromycin-induced contractions except for the duration of the phase III contractions in the stomach; the duration (5.3 +/- 2.2 min) of the erythromycin-induced contractions being significantly (P less than 0.05) longer than that (3.2 +/- 0.9 min) of the naturally occurring MMC. The immunoreactive motilin (IRM) concentration did not increase significantly after the infusion of erythromycin, when compared to that after infusion of normal saline. It is concluded that erythromycin at a dose of 1-3 mg/kg/hr for 15 min during the interdigestive state, similar to motilin, has a significant influence upon the initiation of MMC in the human gastrointestinal tract, but further investigations are required to confirm whether endogenous motilin is involved or not.

Adult↗
PubMed1982

Erythromycin (2 X 1 g) as a Regimen for community-acquired pneumonia.

Erythromycin is regarded more and more as the primary therapy for community-acquired pneumonia. In a prospective study, treatment with erythromycin was evaluated in cases of community-acquired pneumonia requiring hospitalisation. Therapy was started intravenously with 1 g erythromycin lactobionate b. i. d., followed by 1 g erythromycin ethylsuccinate b. i. d., administered orally, until the patient had definitely recovered. Twenty-four patients with documented pneumonia were admitted to the study; five were excluded since the infections were caused by bacteria which were not susceptible to erythromycin. Nineteen patients responded well to therapy. No severe side-effects could be observed. Erythromycin (1 g b. i. d.) appears to be an effective, well-tolerated regimen for severe community-acquired pneumonia.

Erythromycin↗
PubMed1982

The penetration of erythromycin into the middle ear.

The penetration of erythromycin was studied in 108 cases of secretory otitis media. Erythromycin ethylsuccinate was given orally in a dosage of 30-60 mg/kg/day and samples of middle ear effusion were obtained at different intervals. The concentration of erythromycin in the middle ear effusions reached the plasma level (1.1-1.2 mg/l) after 26 hours. The plateau levels were maintained during the steady state. Elimination was slow; 14 hours after the last dose of a ten-day treatment, the concentration of erythromycin in the middle ear effusions was still as high as 0.9 mg/l, compared to 0.2 mg/l in plasma. The concentration of erythromycin in the middle ear effusions surpassed the MICs of most respiratory pathogens. Erythromycin can thus be regarded as a suitable drug in the treatment of otitis media. Furthermore, since the respiratory mucosa reacts in a uniform manner to an inflammatory stimulus, the result of this penetration study is valid for inflammatory diseases in any area lined with respiratory epithelium.

Adolescent↗
PubMedDate not supplied

Side-effects due to the intravenous infusion of erythromycin lactobionate.

A double-blind study was designed to test the hypothesis that local side-effects during i. v. administration of erythromycin lactobionate depend on the drug concentration and that they can therefore be minimized by dissolving erythromycin in a larger infusion volume. Forty healthy students were assigned in a randomized sequence to four 30 min infusions: 120 and 250 ml of erythromycin lactobionate (1 g in 0.9% NaCl) and 120 and 250 ml of placebo (0.9% NaCl). An unexpectedly high incidence (95% and 80% for the infusion volumes of 120 and 250 ml, respectively) of severe systemic side-effects was observed during the first 79 infusions. Because all of these systemic side-effects were associated with the infusion of erythromycin, the study was terminated at this point. Side-effects included abdominal cramps, nausea, vomiting, dizziness and profuse sweating. The postulated positive effect of lower erythromycin concentrations in the infusion on local side-effects (pain at the infusion site, erythema) was marginal (63% vs. 45%). Compared to the systemic side-effects, the problem of local tolerance is less important. In young adults, 30 min infusions of 1 g erythromycin lactobionate are associated with a high incidence of systemic side-effects which may be due to an age-dependent effect of the drug on smooth muscle.

Adult↗
PubMed1993

Selective digestive decontamination by erythromycin-base in a polyvalent intensive care unit.

OBJECTIVE: To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MR Enterobacteriaceae producing an extended spectrum beta-lactamase (ESB). DESIGN: After a 10-week prospective survey to ascertain the baseline incidence in two bays (1 and 3) of the same ICU, bay 1 was compared with bay 3 during a further survey of 6 months. The patients in bay 1 received erythromycin-base. SETTING: Two non-contiguous bays, 1 and 3, of 4 beds, in the same polyvalent ICU of a university hospital. PATIENT: Consecutive patients with unit stay longer than 2 days; 34 patients were included during the control period, 43 in bay 1 (decontamination) and 46 in bay 3 (control) during the trial period. INTERVENTION: Erythromycin-base, 1 g t.i.d. in powder form administered by gastric tube to patients in bay 1 from admission to discharge. MEASUREMENTS AND RESULTS: Digestive tract carriage was monitored by cultures of gastric and rectal swab specimens, sampled twice a week. Enterobacteriaceae were isolated on Drigalski agar with incorporated ceftazidime (4 mg/l). In bay 1 there was a decrease in ESB producing Enterobacteriaceae (23% vs 10%, p = 0.0004) from rectal swab, especially in K. pneumoniae (15% vs 2%, p = 10(-5)), during the decontamination period in comparison to the control period. During the trial period the only differences observed between bays 1 and 3 were in the gastric samples: K. pneumoniae were less often isolated in bay 1 than in bay 3 (0% vs 3%, p = 0.03). Intestinal carriage with multiresistant Enterobacteriaceae occurred in 28% patients in bay 1 and 30% patients in bay 3 during the trial period (p = 0.79). Erythromycin-base did not delay the carriage by patients in bay 1 (log rank test p = 0.42). CONCLUSION: Erythromycin-base was not effective in preventing digestive tract carriage due to Enterobacteriaceae resistant to third generation cephalosporin by production of chromosomal cephalosporinase. The decrease in isolates containing K. pneumoniae in bay 1 cannot be definitively attributed to erythromycin-base, since the number of this species in bay 3 was low.

Adult↗
PubMedDate not supplied

Antimicrobial activity of josamycin against erythromycin-resistant staphylococci as compared to roxythromycin and clarithromycin.

In an in vitro study 246 clinical isolates of erythromycin-resistant staphylococci from six hospitals in Austria were investigated for susceptibility to josamycin and other, newer macrolide antibiotics, e.g. roxithromycin and clarithromycin. 71 strains of Staphylococcus aureus showed an MIC > or = 4 mg/l and 100 strains of S. aureus showed an MIC > or = 256 mg/l. In addition, 25 strains of coagulase-negative staphylococci resistant to erythromycin at an MIC of > or = 4 mg/l were investigated. At an MIC of 2 mg/l 57% of the erythromycin-resistant strains of S. aureus were inhibited by josamycin, 25% by clarithromycin and 11.6% by roxithromycin. At an MIC of 2 mg/l 13.3% of erythromycin-resistant coagulase-negative staphylococci were inhibited by josamycin, 10.7% by clarithromycin and 9.3% by roxithromycin. This study suggests that josamycin is still active in vitro against more than 50% of erythromycin-resistant strains of S. aureus. This drug is also more active than roxithromycin and clarithromycin against erythromycin-resistant S. aureus.

Clarithromycin↗
PubMed1986

In vitro killing of erythromycin-exposed group A streptococci by polymorphonuclear leukocytes.

After exposure to erythromycin, group A streptococci were tested for susceptibility to the antimicrobial activity of human peripheral blood neutrophils in the absence of the antibiotic. Bacterial susceptibility to phagocytic killing increased after prior exposure to supra-inhibitory levels of erythromycin for even as brief as three minutes. Extended exposure and higher concentrations of erythromycin increased phagocytic killing. Although the degree of sensitization varied in different strains of streptococci, all strains tested were significantly more susceptible to phagocytic killing after erythromycin exposure. Killing of erythromycin-treated bacteria that occurred in the absence of antibiotic was dependent upon internalization of the bacteria. Thus, the brief exposure of group A streptococci to inhibitory levels of erythromycin increases their susceptibility to phagocytic killing by peripheral blood neutrophils.

Erythromycin↗
PubMed1994

Erythromycin accelerates solid emptying at the expense of gastric sieving.

Erythromycin accelerates gastric emptying by inducing antral contractions similar to phase III of interdigestive MMC. These powerful contractions are capable of forcing coin-sized indigestibles out of the stomach. In contrast, fed motility is associated with submaximal contractions that fragment (trituration) and propel solids while retaining large (> 0.5 mm) pieces for further size reduction (gastric sieving). In this study, using dogs with duodenal fistulas, we tested the hypothesis that erythromycin-induced acceleration of gastric emptying resulted in the passage of inadequately triturated (> 0.05 mm) chunks of solids into the duodenum. We found that gastric emptying was accelerated by erythromycin (vs 0.15 M NaCl control, P < 0.05). However, the percentage of chyme collected in the > 0.5-mm fraction was much greater (P < 0.01) in the erythromycin-treated experiments (63 +/- 9%) than the controls (7 +/- 1%). Correspondingly, while a fine gruel was passed during controls, under erythromycin infusion, most of the solids were emptied as large chunks virtually unchanged from the swallowed pieces. We conclude that erythromycin accelerates gastric emptying at the expense of gastric sieving.

Animals↗
PubMed1995

Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction.

Treatment of chronic intestinal pseudoobstruction with prokinetic agents has been disappointing. Our study was designed to determine if octreotide and erythromycin would provide sustained relief from nausea, abdominal pain, and bloating in pseudoobstruction. Using gastrointestinal manometry, quantitative parameters of the activity front of the migrating motor complex at baseline and after prokinetic therapy with erythromycin and octreotide were determined in 14 patients with intestinal pseudoobstruction who had nausea, abdominal pain, and bloating. Patients were treated with erythromycin and octreotide for 20-33 weeks. Octreotide increased the frequency, duration, and motility index of activity fronts (AFs) from 1.2 +/- 0.3 AFs/4 hr, 2.7 +/- 0.7 min, and 85 +/- 23 min mm Hg to 4.1 +/- 0.8 AFs/4 hr, 5.5 +/- 0.7 min, and 152 +/- 24 min mm Hg, respectively (P < 0.05). Antral activity was decreased from 63 +/- 14 to 23 +/- 8% by octreotide (P < 0.05). Erythromycin induced antral activity; however, small intestinal motor activity was suppressed. While on erythromycin and octreotide, five patients had long-term improvement of nausea and abdominal pain. All responders had at least 5 AFs/4 hr induced by octreotide. We conclude that octreotide and erythromycin relieve abdominal pain and nausea in pseudoobstruction. Patients who have at least 5 AFs/4 hr after octreotide administration are most likely to clinically respond.

Adult↗
PubMedDate not supplied

Erythromycin lactobionate: pharmacokinetics and uterine tissue levels.

Erythromycin is well-known for its properties of tissular diffusion. An estimation of its concentration in uterine tissue seemed worthwhile, in order to justify the use of erythromycin lactobionate in uterine infections by sensitive micro-organisms. The authors studied the uterine levels of this macrolid, after perfusion of 1g of erythromycin lactobionate, over a period of one hour. The protocol involved a group of 15 women, who were to undergo a hysterectomy for benign non-inflammatory pathology. The uterine specimens and plasmatic pharmacokinetics of the antibiotic constitute the data. The concentrations of antibiotic were determined by microbiological methods. 2 sets of results emerge: during perfusion, the uterine erythromycin levels are equal or inferior to simultaneous serum levels. after perfusion, the uterine levels are superior to serum levels. A bicompartmental linear model was used, which simulated the tissular levels in standard treatment with erythromycin lactobionate. If the erythromycin 4 micrograms/ml critical concentration is compared with uterine tissue concentration, the antibiotic may be expected to be active against a uterine affected by sensitive micro-organisms during a period of approximately 5 hours. This result must be confirmed by a clinical study.

Adult↗
PubMed2004

Enhancing of erythromycin production by Saccharopolyspora erythraea with common and uncommon oils.

The enhancing effect of various concentrations of 18 oils and a silicon antifoam agent on erythromycin production by Saccharopolyspora erythraea was evaluated in a complex medium containing soybean flour and dextrin as the main substrates. The oils used consisted of sunflower, pistachio, cottonseed, melon seed, water melon seed, lard, corn, olive, soybean, hazelnut, rapeseed, sesame, shark, safflower, coconut, walnut, black cherry kernel and grape seed oils. The biomass, erythromycin, dextrin and oil concentrations and the pH value were measured. Also, the kinds and frequencies of fatty acids in the oils were determined. The productivity of erythromycin in the oil-containing media was higher than that of the control medium. However, oil was not suitable as a main carbon source for erythromycin production by S. erythraea. The highest titer of erythromycin was produced in medium containing 55 g/l black cherry kernel oil (4.5 g/l). The titers of erythromycin in the other media were also recorded, with this result: black cherry kernel > water melon seed > melon seed > walnut > rapeseed > soybean > (corn = sesame) > (olive = pistachio = lard = sunflower) > (hazelnut = cotton seed) > grape seed > (shark = safflower = coconut). In media containing various oils, the hyphae of S. erythraea were longer and remained in a vegetative form after 8 days, while in the control medium, spores were formed and hyphae were lysed.

Anti-Bacterial Agents↗
PubMed1992

Gastrointestinal side effects of intravenous erythromycin: incidence and reduction with prolonged infusion time and glycopyrrolate pretreatment.

OBJECTIVE: To determine the frequency of gastrointestinal toxicity due to intravenous (IV) erythromycin and to attempt to decrease this toxicity by prolonging the infusion time of erythromycin and/or pretreating with the peripheral anticholinergic, glycopyrrolate 0.1 mg IV. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General medical wards of a tertiary medical center. PATIENTS: A total of 51 hospitalized patients 18 years of age or older who were prescribed IV erythromycin lactobionate (EMLB) 500 mg every 6 hours by their attending physicians. INTERVENTIONS: Each of eight consecutive infusions of EMLB was randomly assigned to one of four groups: control--30-minute infusion/placebo pretreatment; 60/P--60-minute infusion/placebo pretreatment; 30/G--30-minute infusion/glycopyrrolate pretreatment; and 60/G--60-minute infusion/glycopyrrolate pretreatment. MAIN OUTCOME MEASURES: Each infusion was accompanied by a questionnaire in which patients rated the magnitude of nausea and vomiting on a scale of 1 (no toxicity) to 9 (severe toxicity). Scores for both nausea and vomiting were added together for a total toxicity score ranging from 2 to 18. A total score of greater than 8 was defined as clinically important. RESULTS: The 51 patients received a total of 356 infusions with gastrointestinal toxicity occurring in 27 of 51 (53%) patients. Among patients under the age of 40, 22 of 33 (67%) experienced toxicity compared with only five of 18 patients (28%) over the age of 40 (p = 0.018). Clinically important toxicity was seen in 19 of 51 patients (37%), including five who withdrew during the study because of severe nausea and vomiting. In this group, the combination of a 60-minute erythromycin infusion and glycopyrrolate pretreatment decreased clinically important toxicity by 79% from 47% to 10%, a statistically and clinically significant 37% (95% CI, 14% to 60%) difference (p = 0.007). CONCLUSIONS: Gastrointestinal toxicity associated with the IV infusion of erythromycin is common and is more likely to occur in younger patients. A 1-hour infusion of erythromycin combined with pretreatment with glycopyrrolate, 0.1 mg IV, is effective in reducing this toxicity.

Adolescent↗
PubMed1986

Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial.

Pathogenesis and optimal treatment and prevention of preterm labor remain incompletely understood. Entry of cervical/vaginal microorganisms into lower uterine tissues has been implicated in preterm labor and may be amenable to specific therapy. Fifty-eight women with less than 34 completed weeks of gestation and without other obstetric complications, who were receiving intravenous tocolytics because of uterine contractions and who had cervical alteration (less than 5 cm dilated), were enrolled in a prospective randomized, double-blinded evaluation of 7 days of adjunctive therapy with enteric-coated erythromycin base (333 mg three times daily by mouth) versus placebo. Microbiologic examination included cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and group B streptococcus. Fifty-eight women with singleton pregnancies (29 erythromycin; 29 placebo) completed the protocol. Among women with cervical dilatation greater than or equal to 1 cm at the beginning of treatment, mean time until delivery was 32.5 days with erythromycin and 22.4 days with placebo treatment (p = 0.027). Of the erythromycin-treated women, seven of eight were delivered at greater than or equal to 37 weeks and only three of nine placebo-treated women were delivered at greater than or equal to 37 weeks (p = 0.035). Orally administered enteric-coated erythromycin as adjunctive treatment of pregnant women in labor less than or equal to 34 weeks is well tolerated. Adjunctive erythromycin given to women treated for preterm labor less than or equal to 34 weeks is associated with prolongation of pregnancy and delivery at 37 weeks only in women with cervical dilatation at the beginning of treatment.

Amniotic Fluid↗