Erythromycin lactobionate

The antibiotic erythromycin lactobionate given intravenously acts almost exclusively on Gram-positive bacteria. Even at high plasma and tissue concentrations there is an almost total absence of side-effects. It could be considered, therefore, as first choice in the treatment of patients with infectious respiratory diseases. Most of the 40 patients admitted to the present study were elderly and all had either acute or chronic and becoming acute respiratory disease. Their clinical symptoms and levels of phlogosis improved on treatment with erythromycin lactobionate without any interruption of therapy due to side-effects and toxicity. The absence of unfavourable pharmacological interactions further enhances the usefulness of the drug. In view of the excellent response to monotherapy with erythromycin lactobionate and the few groups of resistant bacteria found in those cases when it was possible to check, it was not considered necessary to investigate any synergistic association with other antibiotics. It can be concluded, therefore, that therapy with erythromycin lactobionate in patients with infective respiratory disease is favourable and patients show excellent tolerability.

Importance:Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties.Objective:To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery.Design, setting, and participants:The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis.Interventions:Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours.Main outcomes and measures:The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content.Results:A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia.Conclusions and relevance:In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery.Trial registration:ClinicalTrials.gov identifier:NCT00827216.

As the pharmacokinetics after a slow infusion had not previously been evaluated in the doses used in this study, it was decided to measure the plasma concentration/time curve after a twelve-hour intravenous infusion of 2·0 g of erythromycin lactobionate in 2 litres of 0·9% normal saline. Six healthy medical students with no past history of cardiovascular, renal, hepatic, metabolic or gastrointestinal disease and no past drug allergy participated. The concentration of erythromycin base in venous blood was measured by small plate microbiological assay. Venous blood was taken at zero, 15, 30, 45, 60 min and at 2, 3, 4, 6, 8, 12, 16, 20 and 24 hr after starting the infusions. Duplicate assays were performed on all plasma samples at Guy's and at the manufacturer's laboratories. A full haematological and biochemical screening profile was performed before and after the study.The mean ± s.e. plasma erythromycin base concentration rose from 0·7 ± 0·2 μg/ml at 15 min to 6·06 ± 1·6 μg/ml at 1 hr. The peak plasma concentration was between 1·48 ± 0·25 μg/ml at 30 min and 7·21 ± 0·93 μg/ml at 4 hr. The plasma concentration at 12 hr was 6·17 ± 0·33 μg/ml, and fell to 0·37 ± 0·05 μg/ml at 24 hr.These findings suggest that therapeutically effective plasma concentrations follow a slow intravenous infusion of erythromycin lactobionate. There was no evidence of adverse haematological or biochemical function in the tests of blood, hepatic or renal function, apart from two volunteers who vomited after the infusions were discontinued.

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.

Background:The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment.Methods:Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection.Results:Erythromycin passes across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to approximately equal to 28 cm2 should provide therapeutic levels of drug within 3 h.Conclusions:Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

Objective:To identify and characterize motilin receptors in equine duodenum, jejunum, cecum, and large colon and to determine whether erythromycin lactobionate competes with porcine motilin for binding to these receptors.Sample population:Specimens of various segments of the intestinal tracts of 4 adult horses euthanatized for reasons unrelated to gastrointestinal tract disease.Procedure:Cellular membranes were prepared from smooth muscle tissues of the duodenum, jejunum, pelvic flexure, and cecum. Affinity and distribution of motilin binding on membrane preparations were determined by use of 125I-labeled synthetic porcine motilin. Displacement studies were used to investigate competition between 125I-labeled synthetic porcine motilin and erythromycin lactobionate for binding to motilin receptors in various segments of bowel.Results:Affinity of 125I-labeled synthetic porcine motilin for the equine motilin receptor was estimated to be 6.1nM. A significantly higher number of motilin receptors was found in the duodenum than in the pelvic flexure and cecum. The jejunum had a significantly higher number of motilin receptors than the cecum. Erythromycin lactobionate displacement of 125I-labeled porcine motilin from the equine motilin receptor did not differ significantly among various segments of bowel.Conclusions and clinical relevance:Motilin receptors were found in the duodenum, jejunum, pelvic flexure, and cecum of horses. The highest number of motilin receptors was in the duodenum, and it decreased in more distal segments of bowel. Erythromycin lactobionate competed with motilin binding in the equine gastrointestinal tract. This suggests that 1 of the prokinetic actions of erythromycin in horses is likely to be secondary to binding on motilin receptors.

Intravenous erythromycin has recently been associated with significant QTc interval prolongation, torsades de pointes, and sudden cardiac death. The prolonged the QTc interval attributed to erythromycin typically is associated with rapid infusion rates in excess of 10 mg/minute. We prospectively assessed the relationship between QTc interval prolongation and erythromycin administration by slow intravenous infusion (mean rate 8.9 +/- 3.5 mg/minute, range 3.9-16.7 mg/minute). Electrocardiographic (ECG) rhythm strips were prospectively obtained in 44 critically ill patients receiving intravenous antibiotics (22 received erythromycin and 22 ceftazidime, cefuroxime, cefotaxime, ceftriaxone, or ampicillin-sulbactam as controls). The ECG recordings were obtained immediately before and within 15 minutes after drug infusions. Only the first available set of ECG strips were evaluated. Two controls had evidence of hepatic dysfunction; no patients receiving erythromycin did. The QTc interval was calculated using Bazett's formula by two blinded investigators. For controls, mean +/- 1 SD (range) QTc intervals were 423 +/- 96 (300-550) msec at baseline and 419 +/- 96 (280-610) msec after infusion (p = 0.712). In contrast, in the erythromycin group, the interval was significantly prolonged from 524 +/- 105 (360-810) msec at baseline to 555 +/- 134 (400-980) msec after infusion (p = 0.034). No patients experienced a dysrhythmia as a consequence of erythromycin infusion. Despite slow rates of infusion, QTc interval prolongation was significant. The clinical importance of this finding remains to be determined.

Ten healthy normal volunteers received an intravenous infusion of erythromycin lactobionate over 60 min to a total dose of 800 mg (n = 9), and 524 mg (n = 1). Blood samples were collected at 10 min intervals for 100 min and gastric contents aspirated, via a nasogastric tube, from pre-dose to 105 min after start of infusion. Incidence and severity of three gastrointestinal symptoms (nausea, stomach discomfort and feelings of hunger), two CNS symptoms (dizziness and faintness) and a 'control' symptom (back pain) were measured using 100 mm visual analogue scales. Rate of infusion and plasma erythromycin concentration correlated with nausea (P less than 0.001) and stomach discomfort (P less than 0.001); plasma erythromycin concentration was also correlated with dizziness (P less than 0.05). Concentrations of active erythromycin in the aspirate were pH dependent. In one subject the concentration of erythromycin in the aspirate exceeded that in the plasma by 100 fold. Bile staining of samples containing the highest levels of microbiologically active erythromycin makes the origin of the erythromycin in these samples uncertain.

Intravenous erythromycin lactobionate has been used for several years to treat various infectious diseases. Several cases of severe nausea and vomiting associated with its use have been reported in Europe but only a few cases have been reported in the U.S. The official product information does not refer to severe nausea and vomiting associated with its intravenous use; however, we report six additional cases of severe nausea and vomiting associated with rapid administration of erythromycin lactobionate, and review the current literature on the characteristics of this adverse effect.