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PubMed1998

Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin.

Torsades de pointes is a potentially life-threatening form of polymorphic ventricular tachyarrhythmia typically seen in the presence of repolarization-prolonging agents. We investigated this particular form of tachyarrhythmia in the isolated, perfused rabbit heart. The experimental model was designed to reproduce conditions that are clinically known to be associated with an increased propensity to the development of torsades de pointes. The class III agent clofilium (1 microM) and d,l-sotalol (10 microM), as well as the antibiotic erythromycin (30-150 microM) were infused in the presence of either normal (5.88 mM) or low (1.5 mM) potassium concentration in sinus-driven or atrioventricular (AV)-blocked hearts. Ventricular tachyarrhythmias spontaneously emerged in the clofilium-, d,l-sotalol-, and erythromycin-treated AV-blocked hearts. The episodes showed typical features of torsades de pointes found in humans. They developed within 4-12 min after the onset of infusion, were normally nonsustained, and only rarely degenerated into ventricular fibrillation. Electrical stimulation at cycle lengths <600 ms and perfusion with MgSO4 suppressed arrhythmic activity. In the d,l-sotalol- and erythromycin-treated hearts, torsades de pointes occurred only in the presence of hypokalemia and bradycardia, whereas, in the presence of clofilium, bradycardia alone caused torsades de pointes. Monophasic action-potential recordings demonstrated early afterdepolarizations in endocardial and epicardial recordings. Thus the isolated AV-blocked rabbit heart represents a model for studying drug-related torsades de pointes and its mechanism.

Animals↗
PubMed1999

Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart.

Tegaserod (HTF 919) is a new drug being developed for gastrointestinal motility disorders. Because other gastrointestinal prokinetic agents, such as cisapride and erythromycin, cause slowing of cardiac repolarization and have been implicated in the development of the potentially fatal ventricular arrhythmia, torsades de pointes, a study was initiated to determine whether tegaserod and its main human metabolite adversely influence cardiac repolarization. By using isolated Langendorff-perfused rabbit hearts, we show that QT intervals remain unchanged at concentrations of tegaserod from 0.5 to 10 microM. It was not until the tegaserod concentration was increased to 50 microM (roughly 500-5,000 times more concentrated than those typically found in human plasma after administration of recommended clinical dosages), that a small, but significant increase in the QT interval (12+/-4%; p < 0.05; n = 4) was observed. No significant changes in QT occurred in the presence of the tegaserod metabolite at any of the concentrations tested (0.5-50 microM). In contrast, cisapride caused QT lengthening at concentrations as low as 0.1 microM, with significant QT increases occurring when 5-50 microM cisapride was used (22+/-4% to >70%, respectively; p < 0.01; n = 4). Erythromycin also caused significant lengthening of QT intervals (11+/-2%; p < 0.001; n = 4), although 100 microM concentrations of this drug were required to achieve this effect. These results demonstrate that both cisapride and erythromycin can slow cardiac repolarization at therapeutic doses and that tegaserod's lack of QT prolongation at therapeutic doses suggests that it has the potential to be a safer alternative to cisapride as a gastrointestinal prokinetic agent.

Animals↗
PubMed1987

Erythromycin in the treatment of pertussis: a study of bacteriologic and clinical effects.

In an open randomized study 17 patients with a positive culture for Bordetella pertussis were treated for 10 days with erythromycin (50 mg/kg/day divided in 2 doses). The bacterium could not be isolated during therapy and in only one patient was it isolated 5 days after cessation of treatment. In comparison B. pertussis was isolated 10 and 15 days after diagnosis from 10 and 4 patients, respectively, of a group of 21 untreated controls. The treated group developed significantly fewer whoops than did the control group, even though most of the individuals had reached the paroxysmal stage at diagnosis. The dose of erythromycin (ethylsuccinate and stearate preparations) gave serum concentrations about 100 times larger than the minimal inhibitory concentration of isolated bacteria and was well-tolerated. Thus adequate erythromycin treatment eliminates B. pertussis from the nasopharynx and reduces symptoms in patients having a history of pertussis of less than 14 days. Adequate dosage and length of treatment might be crucial for these results.

Adolescent↗
PubMed1994

Decline of erythromycin resistance of group A streptococci in Japan.

Six hundred seventy isolates from children with Group A streptococcal infections from 1981 through 1990 were typed serologically and their antibiotic susceptibilities were determined. There were 479 isolates from patients with pharyngitis, 133 from those with scarlet fever, 35 from those with suppurative infection and 23 from those with nonsuppurative disease. The prevalent M serotypes were 12, 4, 1, 3 and 28. None of the 670 isolates were resistant to penicillin G and cephalexin. Resistance rates of isolates to erythromycin and lincomycin was 22.2% in 1981 and 1982, but a marked decrease was noted after 1983 and only one has been resistant since 1986. Nineteen of 21 erythromycin-resistant isolates were M type 12, and two others were M types 4 and 28. Chloramphenicol resistance was similar to that of erythromycin, and the tetracycline resistance rate decreased gradually from 60% to less than 20%.

Adolescent↗
PubMed1995

Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.

We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1996

Detection of Bordetella pertussis by polymerase chain reaction and culture in the nasopharynx of erythromycin-treated infants with pertussis.

BACKGROUND: Pertussis is a highly contagious respiratory disease and the most serious effects occur in young infants. Recently it has been shown that rapid and highly specific PCR can be a useful diagnostic tool for detection of pertussis infection. To our knowledge there are no previous studies concerning the disappearance of Bordetella pertussis DNA from the nasopharynx during antimicrobial treatment. METHODS: We studied prospectively how rapidly live B. pertussis organisms and DNA of these bacteria disappear from the nasopharynx during erythromycin therapy in unvaccinated infants. Eighty-five nasopharyngeal swabs obtained from nine erythromycin-treated infants with pertussis on consecutive days during hospitalization were tested by PCR and culture. The PCR products were further analyzed by Southern hybridization. RESULTS: On the fourth day of treatment 56% of the samples were positive by culture and 89% by PCR, whereas after 7 days the rates were 0 and 56%, respectively. In seven of nine patients PCR remained positive for 1 to 7 days longer than culture. The follow-up study also showed the semiquantitative nature of the PCR assay. The intensity of the PCR products in agarose gel usually weakened with time during erythromycin therapy. CONCLUSIONS: The results of this study show that PCR assay can achieve the specific diagnosis of pertussis infection in a large proportion of infants even when antimicrobial treatment has killed the organisms and culture is no longer positive.

Bacteriological Techniques↗
PubMed1998

Impact of erythromycin on respiratory colonization of Ureaplasma urealyticum and the development of chronic lung disease in extremely low birth weight infants.

BACKGROUND: Chronic lung disease (CLD) is a significant cause of neonatal morbidity and mortality despite advances in neonatal care. Ureaplasma urealyticum colonization of the lower respiratory tract has been associated with CLD, particularly in extremely low birth weight infants. Despite numerous studies demonstrating the pathogenicity of this organism, treatment remains controversial. This study examines neonates colonized with U. urealyticum in the lower respiratory tract and treated with erythromycin, as compared with noncolonized neonates. METHODS: A prospective cohort study of 124 neonates weighing <1000 g at birth, requiring endotracheal intubation and ventilation. Endotracheal aspirates were cultured for U. urealyticum and conventional bacteria twice weekly for the duration of endotracheal intubation. Infants colonized with U. urealyticum were treated with intravenous erythromycin. Maximal ventilatory requirements, CLD at Day 28 and 36 weeks postconception, duration of ventilation, oxygen dependency and hospital stay were documented. RESULTS: Twenty-two infants (18%) were identified as being U. urealyticum colonized in endotracheal aspirates. Colonization was significantly associated with younger maternal age, prolonged rupture of membranes, premature labor and vaginal delivery. Of colonized neonates 14% were delivered by cesarean section, with intact membranes. As compared with noncolonized infants, there were no statistically significant differences in chronic lung disease, duration of oxygen therapy or time to discharge. CONCLUSIONS: Seven published cohort studies of similar high risk populations where U. urealyticum-colonized infants did not receive erythromycin therapy, show a consistent association with CLD (pooled relative risk + 5.21; 95% confidence interval, 2.93 to 9.64). This association was not demonstrated in the current study and adds further weight to the need for a randomized controlled trial to be performed to evaluate this treatment regimen.

Anti-Bacterial Agents↗
PubMedDate not supplied

Treatment of chlamydial urethritis in men and Chlamydia trachomatis-positive female partners: comparison of erythromycin and tetracycline in treatment courses of one week.

Seventy-one consecutive men who had Chlamydia trachomatis-positive nongonococcal urethritis were assigned randomly to treatment for one week with either tetracycline or erythromycin (1g daily). Seventy men completed the study. At follow-up, there were two therapeutic failures among 36 patients treated with erythromycin, and two failures among 34 patients treated with tetracycline. Twenty-four C. trachomatis-positive female contacts were randomly assigned to treatment regimens similar to those of the men. There was one treatment failure among 12 women treated with erythromycin, and no failure among 12 treated with tetracycline. In this study the urethral smears contained fewer than five leukocytes per high-power field in 16% of the C. trachomatis-positive men with symptoms suggestive of urethritis.

Adolescent↗
PubMedDate not supplied

Suboptimal efficacy of erythromycin and tetracycline against vaginal Ureaplasma urealyticum.

Female sexual contacts of men with nongonococcal urethritis (NGU) are often treated with either tetracycline or erythromycin because these antimicrobial agents are active in vitro against most strains of both Chlamydia trachomatis and Ureaplasma urealyticum, the major identified causes of NGU. Both drugs are known to be active against genital C. trachomatis infections in women. In this study, tetracycline and erythromycin base were evaluated for efficacy against U. urealyticum in the vagina. U. urealyticum was isolated from 400 (85%) of 473 women. Among women whose cultures for U. urealyticum were initially positive, cultures were negative at follow-up for one (1%) of 95 receiving no treatment, four (6%) of 71 receiving erythromycin base (250 mg four times daily for seven to ten days), and 59 (42%) of 142 receiving tetracycline (500 mg four times daily for five to ten days). Thus, none of the regimens is reliable for eradication of U. urealyticum from the vagina.

Chlamydia trachomatis↗
PubMedDate not supplied

Comparison of ophthalmic silver nitrate solution and erythromycin ointment for prevention of natally acquired Chlamydia trachomatis.

During prospective studies of infants born vaginally to women with cervical Chlamydia trachomatis infection, we evaluated 27 infants given 0.5% erythromycin ointment and 93 given 1% silver nitrate solution as eye prophylaxis, according to the preference of the parents or delivery room personnel. The cumulative proportion of infants developing chlamydial conjunctivitis was 25% for both groups (P = 0.37, Mantel-Cox test). The cumulative proportion of infants developing chlamydial infection at any anatomic site was 74% for those given erythromycin and 70% for those given silver nitrate (P = 0.93). The two groups did not differ significantly in cumulative proportions developing nonchlamydial conjunctivitis. These results indicate that, as it is routinely used in our hospital, erythromycin ointment was not more effective than silver nitrate as prophylaxis against chlamydial conjunctivitis. The influence of delayed administration on efficacy of prophylaxis requires further evaluation.

Chlamydia Infections↗
PubMedDate not supplied

Single dose azithromycin for the treatment of chancroid: a randomized comparison with erythromycin.

BACKGROUND AND OBJECTIVES: Chancroid is endemic in sub-Saharan Africa and enhances the sexual transmission of the human immunodeficiency virus Type 1 (HIV-1). Azithromycin is an orally absorbed macrolide antibiotic that is active against Haemophilus ducreyi, the causative agent of chancroid, and has pharmacokinetic properties that are suitable for single dosing. STUDY DESIGN: In a randomized single-blinded study of 127 men presenting to a referral STD clinic with culture proven chancroid, we compared the efficacy of azithromycin, administered as a single 1 g dose, with erythromycin 500 mg given 4 times daily for 7 days. RESULTS: Cure rates were 89% (73 of 82) in the azithromycin group and 91% (41 of 45) in the erythromycin group. A failure to respond to treatment was associated with HIV-1 seropositivity and a lack of circumcision. Both regimens were well tolerated. CONCLUSIONS: Azithromycin, given as a single 1 g oral dose, is an effective treatment for chancroid in men, and offers major prescribing advantages over erythromycin.

AIDS-Related Opportunistic Infections↗
PubMed1991

Erythromycin ototoxicity: a call to heighten recognition.

Bilateral sensorineural hearing loss developed in a 64-year-old woman treated with intravenous erythromycin lactobionate for bacteremic pneumococcal pneumonia. Discontinuance of the antibiotic led to prompt correction of the hearing deficit. Reversible hearing loss is an infrequently described adverse effect attributed to high-dose erythromycin therapy. Possible risk factors, including age, gender, and hepatic and renal function, may contribute to the development of erythromycin ototoxicity.

Erythromycin↗
PubMed1992

Erythromycin therapy for gastroparesis.

Gastroparesis from numerous causes has been treated with a number of prokinetic agents. We report the successful use of erythromycin as a prokinetic agent in the treatment of two cases of idiopathic gastroparesis in which treatment with metoclopramide or domperidone or both had failed. We also review information about erythromycin's mechanism of action, previous therapeutic uses, administration (doses, duration, and route), and role as an alternative to other prokinetic agents. When treatment with other agents is unsuccessful, erythromycin is a viable alternative therapy for gastroparesis.

Aged↗
PubMed1998

Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy.

A patient who had taken lovastatin for 7 years received erythromycin before dental procedures. Multiple organ toxicity developed, manifested as rhabdomyolysis, acute renal failure, pancreatitis, ileus, livedo reticularis, and elevated aminotransferase values, without liver injury. No previous reports have identified multiple organ injury of this magnitude. A computer literature search identified only three other reported instances of erythromycin and lovastatin interaction. Manifestations in these previous cases consisted of rhabdomyolysis in all three, as well as elevated aminotransferase values and acute renal failure in two cases. In all the cases, the clinical presentation of organ toxicity occurred after the cessation of erythromycin therapy between day 1 and day 5. Advanced age and chronic renal insufficiency were identified as potential risk factors for drug interaction. Health care professionals should be aware of the potential interaction between these two commonly prescribed drugs, which can mimic sepsis.

Acute Kidney Injury↗
PubMed1998

T wave alternans associated with HIV cardiomyopathy, erythromycin therapy, and electrolyte disturbances.

We report a case of T wave alternans in a patient with HIV cardiomyopathy. T wave alternans is an unusual electrocardiographic finding in acquired long QT syndromes that can precede the development of torsades de pointes. Our patient had multiple risk factors for the development of the acquired long QT syndrome, including HIV cardiomyopathy, electrolyte disturbances, and erythromycin therapy. T wave alternans has not been described previously with HIV cardiomyopathy and only rarely with erythromycin therapy. Patients who have HIV cardiomyopathy and who receive intravenous erythromycin may benefit from monitoring for QT prolongation and electrolyte disturbances to avoid the development of torsades de pointes.

Adult↗
PubMed1997

Interaction between tacrolimus and erythromycin.

A 40-year-old Asian man, 6 months post renal transplant and receiving tacrolimus therapy, presented to the emergency department with a complaint of sudden-onset left eye pain with blurred vision, headache on the left side, and nausea and vomiting. On being admitted, the patient was intubated for respiratory depression, and erythromycin was initiated for suspected atypical pneumonia. Tacrolimus concentrations (whole blood) drawn on the 3rd day of hospitalization were reported to be > 60.0 ng/ml. Before hospitalization, tacrolimus concentrations were reported to be 9.8 ng/ml on a maintenance dose of 7 mg twice daily. Six days after discontinuation of erythromycin and a decrease in tacrolimus dose, the concentration decreased to 11.5 ng/ml and the original dose of tacrolimus was restarted. It is recommended that concurrent administration of erythromycin and tacrolimus be avoided. However, if concomitant therapy is necessary, tacrolimus concentrations, serum creatinine, blood urea nitrogen, and urine output should be monitored.

Adult↗
PubMed1998

Erythromycin treatment in diffuse panbronchiolitis.

Diffuse panbronchiolitis is a chronic infectious airway disease that mainly occurs in the Far East. The prognosis for diffuse panbronchiolitis has dramatically improved over the past 10 years with the use of low-dose long-term erythromycin treatment. The beneficial effect of erythromycin and other 14-membered-ring macrolides in this condition is considered to be due to an anti-inflammatory rather than anti-infective mechanism. Recent investigations have revealed many new actions to the airway epithelial and inflammatory cells, e.g., neutrophils, lymphocytes, and macrophages. Furthermore, erythromycin treatment of diffuse panbronchiolitis provides a new understanding of the pathophysiology and the treatment of chronic infectious airway disease.

Anti-Bacterial Agents↗
PubMed2005

Acute pancreatitis due to erythromycin overdose.

BACKGROUND: Antibiotic overdose is typically regarded as a benign event. We report a 15-year-old girl who developed pancreatitis after an overdose of erythromycin. CASE: A 15-year-old girl presented for care because of severe epigastric pain after an overdose of 5.3 g (16 x 333 mg tablets) of erythromycin base. Her physical examination was normal except for epigastric tenderness. Her serum lipase was 2024 U/L (normal, <60). She was treated with intravenous fluids and an opiate analgesic. Her serum lipase declined to 1834 and 73 U/L at 17 and 36 hours, respectively, after the initial measurement at which time she was asymptomatic. CONCLUSION: Our case supports transient pancreatitis as a potential consequence of erythromycin overdose.

Abdominal Pain↗