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PubMed2002

Comparison of selection for mutants with reduced susceptibility to ABT-773, erythromycin and rifampicin in respiratory tract pathogens.

Attempts were made to select mutants on agar media containing the new ketolide ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not select for mutants in four strains, whereas in eight strains the frequencies at 72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes, clindamycin. The susceptibility profiles indicate that different mutations were selected and that ABT-773 and erythromycin may interact with the ribosome differently.

Anti-Bacterial Agents↗
PubMed2004

Trends of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae in Europe.

OBJECTIVES: To forecast trends in resistance to penicillin and erythromycin among Streptococcus pneumoniae in Europe. METHODS: Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has collected routine antimicrobial susceptibility test results of S. pneumoniae. To observe and predict changes of reduced susceptibility over time, we used a multinomial logistic regression model. RESULTS: Large variations in penicillin and erythromycin non-susceptibility were observed between countries, and reduced susceptibility to erythromycin (17%) has become more frequent than reduced susceptibility to penicillin (10%) in Europe overall. An overall decrease in single penicillin non-susceptibility, but an increase in dual non-susceptibility was observed, indicating a shift of single penicillin to combined non-susceptibility with erythromycin. By 2006, the proportion of single erythromycin and dual non-susceptibility could increase to as much as 20.4% and 8.9%, respectively. CONCLUSIONS: Our results indicate that appropriately dosed beta-lactams for empirical therapy are still the treatment of choice, and that macrolides should be used with prudence.

Adolescent↗
PubMed1983

Cefoxitin versus erythromycin, neomycin, and cefazolin in colorectal operations. Importance of the duration of the surgical procedure.

Perioperative parenteral cefoxitin was compared with oral erythromycin, neomycin and parenteral cefazolin in a prospective, double-blind, randomized evaluation of 119 patients undergoing colorectal operations. Patients receiving cefoxitin had a higher wound infection rate than patients receiving erythromycin-neomycin-cefazolin (12.5% v 3.2%, respectively, p = .06). A direct correlation existed between the duration of the operation and the infection rate. Cefoxitin prophylaxis was as effective as erythromycin-neomycin-cefazolin in patients undergoing surgical procedures of 4 hours or less (infection rates of 4.8% and 4.0%, respectively). However, for surgical procedures lasting more than 4 hours, 5 of 14 patients (37.5%) receiving cefoxitin developed a wound infection v 0 of 13 patients receiving erythromycin-neomycin-cefazolin (p less than .05). It is speculative as to whether frequent two-gram doses of cefoxitin given during the operation would provide prophylaxis equivalent to erythromycin-neomycin-cefazolin.

Cefazolin↗
PubMed2000

Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding.

OBJECTIVE: To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated, critically ill patients with large volume gastric aspirates. DESIGN: Prospective, double-blind, randomized, and placebo-controlled trial. SETTING: General intensive care unit in a university hospital. PATIENTS: Twenty critically ill, mechanically ventilated patients intolerant of nasogastric feeding (indicated by a residual gastric volume of > or =250 mL during feed administration at > or =40 mL/hr). INTERVENTIONS: After a gastric aspirate of > or =250 mL, which was discarded, the enteral feeding was continued at the previous rate for 3 hrs. Intravenous erythromycin (200 mg) or placebo was then administered over 20 mins. The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and -2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion (chi-square p = .05). CONCLUSION: In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding, a single small dose of intravenous erythromycin allows continuation of feed in the short term.

APACHE↗
PubMed1999

Efficacy of prolonged administration of intravenous erythromycin in an ambulatory setting as treatment of severe gastroparesis: one center's experience.

Intravenous erythromycin is a potent gastric prokinetic with demonstrated efficacy in the acute therapy of gastroparesis; long-term oral therapy has been limited by tolerance and modest efficacy. Our aim was to review our experience with prolonged administration of intravenous erythromycin in an ambulatory setting as therapy for severe gastroparesis, refractory to usual dietary and oral prokinetic regimens. We conducted a retrospective analysis of patients with gastroparesis treated with intravenous erythromycin for at least 1 month. Information on demographics; origin of gastroparesis; dosage, duration, and route of administration; clinical outcome in the short- and longer-term; and complications were determined. Eleven patients received a total of 14 courses of intravenous erythromycin for a median of 6.5 months (range, 1 to 19 months) at a median dosage of 300 mg/day (range, 150 to 1,000 mg/day). One patient received no benefit, two had complete responses, and all others reported some benefit. Two had dramatic relapse on cessation of therapy and subsequently improved on its resumption. Parenteral nutrition could be discontinued in one of four patients. There were four episodes of line sepsis; two required catheter removal. A nonocclusive thrombus developed at the site of a central line in one patient. Secondary infections or antibiotic resistance were not encountered. Prolonged administration of intravenous erythromycin in an ambulatory setting is feasible, well tolerated, and effective in patients with severe gastroparesis.

Adult↗
PubMed2004

Erythromycin in the short- and long-term control of dyspepsia symptoms in patients with gastroparesis.

BACKGROUND: Few prokinetic drugs are available to treat gastroparesis. Data are limited on short-term and long-term efficacy of erythromycin as a prokinetic drug. GOALS: Assess efficacy of low-dose erythromycin suspension to treat gastroparesis. STUDY: Patients with dyspepsia and gastroparesis by gastric emptying study were treated with low-bulk diet and low-dose (50-100 mg 3 times a day and at bedtime) oral erythromycin suspension. Data were collected by retrospective chart review and telephone questionnaire for short- and long-term follow-up, respectively. RESULTS: Of 25 patients, 18 had short-term follow-up, 18 had longterm follow-up, and 14 had both. On short-term follow-up, 15 patients (83%) experienced some or dramatic improvement, while 3 (17%) experienced worsening or no change in symptoms (P = 0.005). Mean duration of long-term use was 11 +/- 7 months. On long-term followup, 12 (67%) patients noticed some or dramatic improvement, while 6 (33%) experienced worsening or no change in symptoms (P = 0.16). Correlation (0.7) between short- and long-term response was significant (P < 0.005). Of the 3 patients with poor short-term response, none did well long term. Of the 11 patients with some or dramatic response in short-term, 7 continued to have some response long term. There was no relation between gastric emptying time and response to erythromycin suspension. CONCLUSIONS: Treatment of gastroparesis with low-dose erythromycin and low-bulk diet results in a dramatic short-term improvement in the majority of patients. Short-term response predicts long-term response. This response may not be as great, possibly due to tachyphylaxis.

Adult↗
PubMed1999

Inhibitory effect of erythromycin on interleukin-8 secretion from exudative cells in the nasal discharge of patients with chronic sinusitis.

OBJECTIVES: The mechanism of the efficacy of long-term low-dose macrolide therapy for chronic sinusitis is not fully understood. The authors studied the inhibitory effect of erythromycin on interleukin-8 (IL-8) secretion from exudative cells in the nasal discharge of patients with chronic sinusitis. STUDY DESIGN AND METHODS: Exudative cells in the nasal discharge were isolated from six patients with nonallergic chronic sinusitis. The cells, more than 90% of which were neutrophils, were incubated with or without erythromycin in the presence of 10 micrograms/mL of lipopolysaccharide. The IL-8 concentrations in the culture supernatants were measured by enzyme-linked immunoassay. RESULTS: The amount of secreted IL-8 in the absence of erythromycin was 682 +/- 226 pg/10(6) cells/24 h. The IL-8 secretion was significantly reduced to 66 +/- 15% and 46 +/- 13% of the control in the presence of 10(-6) and 10(-5) M of erythromycin, respectively. CONCLUSION: Erythromycin may act as a biologic modulator that inhibits IL-8 secretion from exudative cells and thereby blocks the vicious circle of neutrophil recruitment and IL-8 generation in the inflammatory site in chronic sinusitis.

Anti-Bacterial Agents↗
PubMedDate not supplied

Erythromycin resistance in group A beta-hemolytic streptococci.

Recent reports have indicated a high incidence of erythromycin resistance in Group A streptococci isolated from children in Japan. The present study investigated antibiotic susceptibility patterns of 280 pharyngeal isolates from ambulatory patients using the plate dilution technique. The incidences of resistance to erythromycin and tetracycline were 4.3 and 7.8%, respectively. No resistance to penicillin, ampicillin, methicillin, oxacillin, cefaclor or moxalactam was found, and there was no evidence of penicillin tolerance using the standard tube dilution technique. The erythromycin-resistant isolates were of T-pattern 12, M-type 12, and two erythromycin-resistant isolates were also resistant to tetracycline. Data on the source of the isolates suggest that a localized outbreak of erythromycin-resistant streptococcal infection occurred.

Anti-Bacterial Agents↗
PubMedDate not supplied

Microbiological aspects of erythromycin.

Almost 35 years after its discovery, erythromycin remains highly active against most strains of a broad array of clinically important organisms. Many strains of Gram-positive and Gram-negative aerobic, facultative and anaerobic bacteria, as well as Mycoplasma, treponemes and Chlamydia, are susceptible to this agent. Erythromycin acts by binding to the ribosomes of the target organisms, thereby inhibiting protein synthesis. Although a pharmacokinetically superior erythromycin estolate has been shown to be a less potent antibiotic prior to hydrolysis, it appears to contribute significantly to the therapeutic response following administration of erythromycin estolate. Clinical laboratory susceptibility testing or erythromycin may be done using standardized methods, but the laboratorian is cautioned to remember the adverse effect of acidic test conditions on the apparent activity of this antibiotic.

DNA Transposable Elements↗
PubMed1991

Comparative efficacy of erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for otitis media with effusion in children.

We randomly assigned children with otitis media with effusion to receive either erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for a 2-week period, primarily to determine whether either erythromycin-sulfisoxazole or cefaclor would have greater short term efficacy than that found previously for amoxicillin, and secondarily to supplement earlier data on outcomes in placebo-treated subjects. Interim analyses showed no statistically significant (P less than 0.05) differences between the three antimicrobial treatment groups in the primary outcome measures, i.e. the prevalence of middle-ear effusion 2 and 4 weeks after entry, and indicated that postulated differences favoring the erythromycin-sulfisoxazole and cefaclor groups over the amoxicillin group were unlikely to be found even if the originally calculated sample size were attained. Subject accrual was therefore terminated. Final analysis showed no significant between-group differences in other outcome measures as well. In antimicrobial vs. placebo comparisons neither erythromycin-sulfisoxazole nor cefaclor gave more favorable outcomes than placebo, whereas more children were effusion-free in the amoxicillin group than in the placebo group at 2 weeks (31.6% vs. 14.1%, P = 0.007), but not at 4 weeks. We conclude that when antimicrobial treatment for otitis media with effusion is deemed advisable, neither erythromycin-sulfisoxazole nor cefaclor should replace amoxicillin as first line treatment.

Amoxicillin↗
PubMed1998

A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin, and cotrimoxazole.

BACKGROUND AND OBJECTIVES: Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India. With reports of increasing resistance to the drug, this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500 mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim 160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. STUDY DESIGN: Forty-six patients with a clinical diagnosis of chancroid were randomly divided into 3 groups. Sixteen patients received ciprofloxacin, whereas 15 each received erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed day 21. Clinical response was noted in terms of cure, improvement, or failure. RESULTS: Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was observed in 6.7% cases in both groups. There were no failures with either ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was observed with 53.3% cure rates and a high failure rate of 46.7%. CONCLUSION: Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin is better in terms of dosage schedule, duration of treatment, and low cost. Cotrimoxazole should be discontinued as drug of choice because of high failure rates.

Adult↗
PubMed1989

Erythromycin effects on multiple-dose carbamazepine kinetics.

To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.

Absorption↗
PubMed1989

Enhanced secretion of Escherichia coli beta-lactamase by a spontaneous erythromycin-resistant mutant of Bacillus subtilis.

An extracellular-protease-deficient mutant, ME142, was isolated from Bacillus subtilis as a spontaneous erythromycin-resistant (Eryr) clone. This mutant showed conditional sporulation and only sporulated normally in the absence of erythromycin. In the presence of the antibiotic, sporulation was greatly reduced. Production of extracellular proteases by ME142 also exhibited conditional deficiency, possibly due to pleiotropic effects of the sporulation deficiency. The production of protease was 2-10% that of the wild-type level in the presence of erythromycin. ME142 showed poor competence for transformation even in the absence of erythromycin; however, derivatives of ME142 were isolated which had the same Eryr phenotype but which exhibited normal competence. One such mutant, ME162, was used as a host for the secretion of Escherichia coli beta-lactamase. The amount of beta-lactamase in the culture supernatants of ME162 increased significantly when the cells were cultured with erythromycin, suggesting that proteolysis of the beta-lactamase in the supernatants of ME162 was greatly reduced as compared to that in the supernatants of the wild-type strain.

Bacillus subtilis↗
PubMed1985

Morphological response and growth characteristics of Legionella pneumophila exposed to ampicillin and erythromycin.

The morphological response of two strains of Legionella pneumophila to ampicillin 10 micrograms/ml and erythromycin 10 micrograms/ml in vitro was studied by electronmicroscopy, MIC estimations and viable counts. In the presence of ampicillin, discrete lesions appeared in the bacterial cell walls through which cytoplasmic contents extruded and lysis occurred. A few spheroplasts, together with minicells of 0.15-micron diameter, and apparently normal cells were present after exposure to ampicillin for several hours. Conversely, erythromycin initially resulted in inhibition of division and the formation of filamentous organisms. The cell walls of these filaments were eventually disrupted with numerous small membranous vesicles appearing on their surfaces. On further erythromycin treatment, breakage of the cell wall at a restricted number of sites occurred, leading to cell lysis. In the presence of erythromycin, a few morphologically normal cells were present but no spheroplasts or minicells were observed. Viable counts demonstrated that ampicillin killed the bacteria faster than erythromycin. Regrowth did not occur in the continued presence of either antibiotic, but after their removal regrowth was observed.

Ampicillin↗
PubMed1996

Effect of erythromycin on human biliary motility.

BACKGROUND: To investigate the effects of intravenous erythromycin on human gall-bladder and sphincter of Oddi motor function. METHODS: Twelve consecutive patients with suspected sphincter of Oddi dysfunction were studied. Gall-bladder function was assessed by ultrasonography, and sphincter of Oddi motility was evaluated by means of endoscopic manometry. RESULTS: All patients were found to have normal gall-bladder function. The percentage of maximal gall-bladder emptying following a standardized, liquid test meal was significantly increased by erythromycin, whereas the postprandial residual gall-bladder volume was significantly decreased after erythromycin (P < 0.01). Endoscopic manometry revealed the presence of sphincter of Oddi dysfunction in two of the 12 patients. Erythromycin significantly decreased the basal sphincter of Oddi pressure and slowed the sphincter of Oddi phasic contraction frequency in all patients (P < 0.01). However, the mean duration of the sphincter phasic contractions (P < 0.05) and their amplitude (P = 0.05) were increased by the compound. CONCLUSIONS: Erythromycin stimulates gall-bladder motility but induces varying effects on human sphincter of Oddi motility.

Adult↗
PubMed2004

Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response.

BACKGROUND: Chronic intestinal pseudo-obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy. AIM: To determine the value of erythromycin treatment in chronic intestinal pseudo-obstruction. METHODS: All patients with proven chronic intestinal pseudo-obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non-responders to identify the factors associated with benefit. RESULTS: Fifteen consecutive patients (nine females; median age, 37 years; median follow-up, 41 months) were treated with oral erythromycin, 1.5-2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non-responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non-responders to be taking long-term opiates. CONCLUSIONS: Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo-obstruction.

Adult↗
PubMed1982

Dose-related pharmacokinetics after oral administration of a new formulation of erythromycin base.

1 Erythromycin concentrations in serum and urine were determined in 24 healthy male, fasting subjects after oral administration of 250, 500, or 1000 mg of erythromycin base (250 mg capsules containing enteric-coated pellets). The subjects also received a film-coated erythromycin stearate tablet (equivalent to 500 mg base). 2 The mean +/- s.d. maximal serum erythromycin concentrations were 1.9 +/- 0.8, 3.8 +/- 1.4, 6.5 +/- 2.9 and 2.9 +/- 1.7 mg/l for 250, 500, or 1000 mg base and 500 mg stearate, respectively. The serum peaks usually occurred after 2 h irrespective of dosage form given. 3 The mean +/- s.d. areas under the serum concentration v time curves (AUC0-infinity) were 4.5 +/- 1.7, 11.2 +/- 4.3, 27.2 +/- 10.6 and 7.5 +/- 3.4 mg l -1 . h after 250, 500, or 1000 mg base, and 500 mg stearate, respectively. 4 The urinary recoveries were 5.0, 6.7, 8.6% of the base doses given and 4.4% of the stearate dose given. 5 Dose-dependent excretion of erythromycin occurred. The increase in AUC was larger than multiples of the lowest base dose.

Administration, Oral↗
PubMed1987

Pharmacokinetics of erythromycin in patients with severe cirrhosis. Respective influence of decreased serum binding and impaired liver metabolic capacity.

Pharmacokinetic parameters were studied after i.v. infusion of erythromycin (500 mg) in five patients with alcoholic cirrhosis and six normal subjects. Serum AAG levels were 4.7 +/- 2.4 mumol l-1 in cirrhotics and 10.3 +/- 2.1 +/- mumol l-1 in normals. The unbound fraction (fu) of erythromycin was significantly higher in cirrhotic patients (58.3 +/- 17.7%) than in normal subjects (30.5 +/- 2.8%, P less than 0.01), and a negative correlation was found between fu values and serum AAG (r = -0.867, P less than 0.01). Due to increase in fu, volume of distribution (Vss) was significantly augmented in cirrhotics (85.5 +/- 23.8 l vs 57.6 +/- 14.8 l, P less than 0.05). Serum clearance of unbound erythromycin (CLu) was significantly reduced in cirrhotic patients (42.2 +/- 10.1 l h-1 vs 113.2 +/- 44.2 l h-1 in normal subjects, P less than 0.01). This led to marked elevation of serum concentrations of unbound drug and was entirely explained by the decrease of non renal (i.e. hepatic intrinsic) clearance (31.6 +/- 7.5 l h-1 in cirrhotics, 98.6 +/- 41.5 l h-1 in normals, P less than 0.02); renal clearance remained unchanged. It is concluded that in cirrhotic patients, low serum AAG levels and reduced liver metabolic capacity may lead to marked changes in pharmacokinetics of erythromycin, and that similar results might be expected for drugs which exhibit the same serum binding and pharmacokinetic behaviour as erythromycin.

Adult↗