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Erythromycin-induced dynamic ileus?

A 39-year-old man and a 79-year-old woman developed dynamic ileus soon after erythromycin stearate was administered for a respiratory tract infection. Both had had prior uncomplicated abdominal operations: the man, vagotomy and pyloroplasty for bleeding duodenal ulcer, 3 years earlier; and the woman, an appendectomy some 44 years before. The temporal association with erythromycin therapy, resolution of signs and symptoms when the drug was stopped, an uneventful recovery, and the absence of other causes, suggest a possible role of erythromycin in the pathogenesis of dynamic ileus in these patients. Disturbed gastrointestinal motility patterns caused by erythromycin, in the presence of structural changes of the alimentary tract due to prior surgical procedures, may have contributed and we review these events.

Adult↗

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.

Adolescent↗

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome (CVS) is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 24 children (10 boys, 14 girls). Many patients had mild associated abdominal pain with their vomiting. Fourteen patients had previously been given metoclopramide but none responded. Two patients were mildly developmentally delayed. Twenty-four patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in two to four divided doses for 7 days. This dose was repeated as needed when symptoms reappeared. Eighteen of 24 patients reported total resolution of symptoms when re-evaluated at 2 and 6 months. All males responded, eight of 18 responders were female, and all six with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of CVS in childhood. Because the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in CVS.

Adolescent↗

Erythromycin reduces delayed gastric emptying in critically ill trauma patients: a randomized, controlled trial.

BACKGROUND: Early enteral feeding has been shown to be beneficial in improving outcome in critically injured trauma patients. Delayed gastric emptying occurs frequently in trauma patients, increasing the time to achieve nutritional goals, and limiting the benefit of early enteral feedings. Intravenous erythromycin is an effective agent for improving gastric motility in diabetics and postgastrectomy patients. The purpose of this study is to determine the effectiveness of erythromycin for improving gastric motility in critically injured trauma patients. METHODS: All critically injured patients who received gastric feedings within 72 hours of admission were candidates for the study. Those patients who failed to tolerate feedings at 48 hours (gastric residual > 150 mL) were eligible for enrollment. Patients were prospectively assigned to two treatment groups by randomization to receive either erythromycin (ERY) or placebo (PLA). Treatment was continued in patients who tolerated gastric feedings until the feedings were no longer required. Patients with continued intolerance for 48 hours after randomization were considered failures of therapy and given metoclopramide. RESULTS: Sixty-eight patients were enrolled and were well matched for age, sex, and Injury Severity Score. Mortality, intensive care unit length of stay, hospital length of stay, number of ventilator days, and rate of nosocomial infections were similar in each group. There was a significant difference between the ERY group and the PLA group in the amount of feedings tolerated at 48 hours (58% vs. 44%, p = 0.001). There was no difference in the amount of feedings tolerated (as a percentage of target goal volume) throughout the entire duration of the study (ERY [65% of target] vs. PLA [59%], p = 0.061). Overall success of therapy at 48 hours was 56% in the ERY group versus 39% in the PLA group, but this also did not reach statistical significance (p = 0.22). CONCLUSION: Intravenous erythromycin improves gastric motility and enhances early nutritional intake in critically injured patients.

Adult↗

Effects of oral erythromycin on upper gastrointestinal motility in patients with non-insulin-dependent diabetes mellitus.

Twenty patients (18 males, 2 females) with type II (non-insulin-dependent) diabetes mellitus were enrolled in the study. They were aged 49-72 years (mean age 65 years). Radionuclide-labelled water was used to measure oesophageal motility, expressed as the oesophageal mean transit time (MTT). A radionuclide-labelled solid meal was used to measure gastric motility, expressed as the half-time of gastric emptying (T1/2GET). A baseline study was performed before oral erythromycin therapy. After a 2-week course of treatment, the subjects underwent a second study. Fasting blood sugar (FBS) was also monitored in each study. In the baseline study, MTT was 8.88 +/- 2.00 s and T1/2GET was 198.0 +/- 58.9 min. After treatment with erythromycin, MTT decreased to 7.48 +/- 2.24 s (P < 0.01) and T1/2GET decreased to 137.1 +/- 71.2 min (P < 0.01). In addition, the FBS decreased from 159.0 +/- 40.2 mg dl-1 at baseline to 139.2 +/- 39.8 mg dl-1 after 2 weeks of erythromycin treatment (P < 0.05). We conclude that erythromycin is an effective prokinetic agent for diabetic gastroparesis, and that improved oesophageal transit and gastric emptying may improve glycaemic control.

Administration, Oral↗

Treatment of chancroid with erythromycin.

Chancroid is a sexually transmitted disease that is not often recognized in the United States. It has traditionally been treated with sulfonamides and/or tetracyclines. Recently, 14 active-duty U. S. Army personnel who acquired chancroid in the Far East were seen at the Madigan Army Medical Center, Tacoma, Wash. All of the organisms were isolated from clinical material on solid media without the use of a blood-clot tube. Because of dissatisfaction with conventional treatment and the demonstration of in vitro sensitivity of the organism to erythromycin, seven of the last eight patients were treated with erythromycin. All patients treated with erythromycin had rapid and favorable responses and none suffered recurrences. The results of this study led to three conclusions: chancroid is a relatively common disease in the Far East, the causative organism can be isolated by most clinical microbiology laboratories with proper technique, and erythromycin is an effective drug in the treatment of chancroid.

Adult↗

Treatment of gonococcal urethritis in men with a rifampicin-erythromycin combination.

A group of men with uncomplicated gonococcal urethritis were treated with a single oral dose of rifampicin (900 mg) and erythromycin stearate (1 g). Neisseria gonorrhoeae was isolated from four of 108 men at the first follow-up examination, and from none of 68 who attended a second follow-up examination. It is concluded that this rifampicin-erythromycin combination may be useful for the therapy of gonorrhea. It may be of particular value in the treatment of infections due to penicillin-resistant N. gonorrhoeae, since in vitro studies showed that both rifampicin and erythromycin were active against 20 strains of beta-lactamase-producing N. gonorrhoeae. The effect of this rifampicin-erythromycin combination against associated infections with Chlamydia trachomatis was disappointing. This organism was isolated from five of nine patients who had yielded isolates of C. trachomatis before treatment.

Administration, Oral↗

Comparison of rosaramicin and erythromycin stearate for treatment of cervical infection with Chlamydia trachomatis.

The macrolide antibiotic rosaramicin inhibits in vitro growth of Chlamydia trachomatis. Rosaramicin (1 g daily given to 18 patients for seven days) and erythromycin stearate (2 g daily given to 19 patients for seven days) were compared in the treatment of chlamydial cervicitis. Cultures of cervical specimens obtained nine to 11 days and 24-32 days after commencement of therapy were negative for all rosaramicin-treated patients seen at follow-up. The first follow-up culture of one erythromycin recipient was positive. The extent of cervicitis decreased in all patients after treatment, but the only patients to achieve a completely normal cervical appearance were those with minimal-to-moderate lesions before treatment. Gastrointestinal side effects, including nausea, vomiting, and abdominal pain, occurred in ten of 19 patients given erythromycin and in 13 of 18 given rosaramicin. Minimally elevated levels of alanine aminotransferase in serum occurred in four (22.2%) of 18 rosaramicin recipients. It is concluded that rosaramicin and erythromycin stearate both eradicate C. trachomatis cervical infection but frequently cause adverse gastrointestinal effects.

Adolescent↗

Treatment of nongonococcal urethritis: comparison of ofloxacin and erythromycin.

Ofloxacin, a new quinolone carboxylic acid derivative, has been reported to be effective and safe in the treatment of nongonococcal urethritis (NGU). In the present investigation 188 male outpatients with NGU were randomized to double-blind treatment with either erythromycin (500 mg twice a day) or ofloxacin (200 mg twice a day) for seven days. Before therapy Chlamydia trachomatis was isolated from 43.6% of the patients. One relapse and one reinfection occurred in the erythromycin-treated group, whereas all patients in the group given ofloxacin were culture-negative at follow-up. Among the C. trachomatis-positive group of patients, the clinical efficacy of ofloxacin was 83.7%, and that of erythromycin, 77.4% at the final follow-up. In the C. trachomatis-negative group, the efficacy of ofloxacin was 93%, and that of erythromycin, 84.3%. The differences are not significant. No serious adverse effects were demonstrated. The results indicate that ofloxacin might be a valuable alternative for the treatment of NGU in men.

Adult↗

Suspected interaction: warfarin and erythromycin.

The patient described had a markedly enhanced response to warfarin when he was given erythromycin concomitantly. Before the initiation of erythromycin, his warfarin anticoagulation had been well controlled. After withdrawal of erythromycin, his response to warfarin returned to normal. These findings and previously reported clinical and laboratory data lead to the conclusion that, at least in some patients, a potentially serious interaction between erythromycin and warfarin can occur.

Adult↗

Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment.

Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

Adult↗

Persistence of erythromycin-resistant group a streptococci in cultured respiratory cells.

BACKGROUND: A significant association between erythromycin resistance and ability of bacteria to enter human respiratory cells has been documented in group A streptococci (GAS) isolated in Italy from children with pharyngitis. The occurrence of strains combining cell invasiveness with erythromycin resistance raised serious concern because they could escape penicillin by virtue of intracellular location and macrolides by virtue of resistance, resulting in difficulty in eradication. METHODS: Thirty-one pharyngeal cell-invasive, erythromycin-resistant (ER) GAS, representing that many clones recently identified among Italian GAS carrying the internalization-related gene prtF1, were investigated for intracellular persistence inside cultured respiratory cells (A549) by means of a survival assay and by staining and polymerase chain reaction assays on infected cells. RESULTS: All tested ER GAS could be recovered in culture from infected cells 24 hours from infection with logarithms exceeding 4.0 (4 strains). The highest survival rate (>5.0) was exhibited by strain SP1900 [erm(A)/iMLS-B; high-level erythromycin resistance [minimum inhibitory concentration, > or =128 microg/mL)], the most widespread clone, which was cultivable from infected cells up to day 5. As long as SP1900-infected cells could be maintained in culture, the presence of multiple cocci inside cells was consistently revealed by microscopy. During the same time, DNA sequences internal to both genes prtF1 and erm(A) continued to be amplified by polymerase chain reaction. CONCLUSIONS: These results suggest that the ER GAS are capable of persisting in human respiratory cells. This might contribute to clinical problems such as relapsing infection and persistent carriage despite antibiotic treatment and might have facilitated the widespread diffusion of ER GAS in Italy.

Adhesins, Bacterial↗

Transient repression of erythromycin formation in Streptomyces erythraeus.

The effect of a D-glucose on growth and erythromycin production by Streptomyces erythraeus was investigated. D-Glucose stimulated growth and caused a strong but temporary suppression of antibiotic formation. Maximum specific suppression of erythromycin formation occurred at a carbohydrate concentration of 20 mg ml-1. A non-metabolizable analogue of glucose, 2-deoxy-D-glucose, also suppressed antibiotic formation. Since glucose caused a decrease in erythromycin formation only when added before the stage of antibiotic production, we conclude that this sugar exerted a transient repressive effect on erythromycin biosynthesis.

Deoxyglucose↗

Loss of cytochrome oxidase in Saccharomyces cerevisiae during inhibition of mitochondrial protein synthesis by erythromycin and chloramphenicol.

There is a major reduction in respiratory competence, and inhibitionof growth, several hours after the addition of erythromycin or chloramphenicol to Saccharomyces cerevisiae growing in medium containing a non-fermentable carbon source. Spectrographic evidence is presented for a loss of cytochrome oxidase as a consequence of the antibiotic treatment. This loss is prevented by cyanide or oligomycin. When glucose is added, however, the loss occurs irrespective of the presence of the respiratory inhibitors. Cycloheximide does not affect respiratory competence or cause loss of cytochrome oxidase, and it prevents the loss elicited by erythromycin if both compounds are added together. However, if cycloheximide is added some time after the addition of erythromycin, it fails to block the response to the latter drug. The results cannot be accounted for on the basis of the segregation of a finite number of mitochondria into an increasing number of progeny cells but, rather, suggest that the mitochondria are modified during growth in chloramphenicol or erythromycin.

Chloramphenicol↗

Post-antibiotic effect of azithromycin and erythromycin on streptococcal susceptibility to phagocytosis.

The effect of azithromycin and erythromycin on growth, cell surface hydrophobicity and the susceptibility to the bactericidal activity of human polymorphonuclear leucocytes (PMNL) was examined in four Streptococcus species. Exposure to either 10 x MIC azithromycin or erythromycin induced a post-antibiotic effect (PAE) of between 2.4 and 4.3 h. Erythromycin caused a longer PAE for S. sanguis than azithromycin under the same conditions. The cell surface charge (hydrophobic or hydrophilic) of the streptococci was altered significantly during PAE; loss of hydrophobicity was induced by both macrolides, and this effect was variable amongst the species. The decrease in hydrophobicity was not related to inhibition of growth. The effect of each drug during PAE on the interaction of opsonised suspensions of the streptococci with human PMNL revealed that erythromycin, and to a lesser extent azithromycin, increased susceptibility to the bactericidal activity of human PMNL; this effect was abolished following PAE. The present study clearly showed that PAE should not only be considered as delayed bacterial growth, but also as modulation of bacterial susceptibility to phagocytosis which may influence the outcome of the host-parasite relationship.

Azithromycin↗

Intersubject and dose-related variability after intravenous administration of erythromycin.

1 It is well-known that considerable variability and unpredictability in serum concentrations results from orally administered erythromycin. 2 Disposition kinetics and their variability were studies in 24 healthy subjects after a single dose of erythromycin lactobionate and four doses were studied to evaluate dose-related variability in five other subjects. 3 Erythromycin kinetics were adequately described by a classical two compartment open model with little intersubject variability. 4 Dose-related variability occurred. Clearance was independent of dose but T1/2 beta and Vdss increased with dose. 5 Data are presented to show that non-invasive sampling of urine and saliva are of limited value in studying erythromycin pharmacokinetics.

Adolescent↗

Pharmacokinetic interaction between theophylline and erythromycin.

1 The pharmacokinetics of a single intravenous dose of theophylline alone and during the fifth day of treatment with 500 mg erythromycin every 8 h was studied in six healthy subjects. 2 At the same time the pharmacokinetics of erythromycin at steady-state on the fourth day of the treatment (alone) and the fifth day (during the theophylline co-administration) were also studied. 3 Mean +/- s.d. theophylline clearance was decreased from 62 +/- 15.4 to 53 +/- 10.3 ml min-1 (P less than 0.05) and elimination half-life rose from 7.1 +/- 1.9 to 7.7 +/- 2 h (P less than 0.05) when erythromycin was co-administered. 4 Mean +/- s.d. erythromycin area under the curves (0-8 h) and (0-oc) were reduced from 6.09 +/- 3.2 to 3.8 +/- 2.5 micrograms ml-1 h and 7.2 +/- 3.6 to 5.0 +/- 2.9 micrograms ml-1 h (P less than 0.05) in the presence of theophylline. Mean steady state and maximum steady state concentrations were also reduced from 0.75 +/- 0.4 to 0.47 +/- 0.3 microgram ml-1 (P less than 0.05) and 1.45 +/- 0.87 to 0.85 +/- 0.51 microgram ml-1 (P less than 0.05) respectively. 5 The potential clinical implications of this indication should be considered.

Adult↗

Enprofylline disposition in the presence and absence of amoxycillin or erythromycin.

1 The kinetic disposition of a novel xanthine bronchodilator, enprofylline, was determined in young healthy male volunteers in the presence and absence of amoxycillin or erythromycin. These data were compared to those derived from a similar study of theophylline disposition in the presence and absence of erythromycin. 2 Erythromycin inhibited theophylline disposition only in those subjects in whom the control kinetic study was done after antibiotic ingestion, but the effect was modest. Erythromycin had no effect on enprofylline disposition. 3 Amoxycillin reduced the renal clearance of enprofylline, but the change was not statistically significant.

Adult↗