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PubMed1985

Topical sulfacetamide vs oral erythromycin for neonatal chlamydial conjunctivitis.

Conjunctival and nasopharyngeal cultures for Chlamydia trachomatis were obtained from infants 30 days of age or younger with purulent conjunctivitis. Conjunctival specimens were also tested for other bacterial pathogens and for viruses. Most of the infants studied were black and came from a low-income, urban population. By random assignment infants received either topical treatment with 10% sulfacetamide sodium ophthalmic solution or systemic treatment with oral erythromycin estolate (50 mg/kg/day). Treatment was continued for 14 days if C trachomatis was isolated from the conjunctivae. Treatment was considered to be effective if conjunctivitis resolved and if follow-up chlamydial cultures of the conjunctivae and nasopharynx were negative at completion of therapy and two to four weeks later. Chlamydia trachomatis was isolated in the absence of other pathogens from the eyes of 37 (73%) of 51 infants with conjunctivitis. Other bacterial pathogens were isolated from four infants (8%) and viruses from none. Chlamydial infection was eradicated from 14 (93%) of 15 infants treated orally. In contrast, persistent conjunctival infection was detected in eight infants (57%) and nasopharyngeal colonization in three (21%) of 14 infants after topical treatment. It was concluded that C trachomatis is the most frequent cause of neonatal conjunctivitis in the low-income, urban population studied; that erythromycin estolate administered orally for 14 days eradicates chlamydial conjunctival and nasopharyngeal infection; and that topical sulfacetamide therapy may result in persistent conjunctival infection and nasopharyngeal colonization.

Administration, Oral↗
PubMed1993

Effect of tauroursodeoxycholate on actin filament alteration induced by cholestatic agents. A study in isolated rat hepatocyte couplets.

The mechanism of the protective effect of ursodeoxycholic acid in cholestatic liver diseases remains unclear. Since there is evidence that alterations in the pericanalicular actin microfilament network play a major role in cholestasis, the aims of this study were (a) to determine the effect of the cholestatic agents, taurolithocholate (TLC) and erythromycin estolate (ERY), on F-actin distribution in isolated rat hepatocyte couplets and (b) to assess the effect of tauroursodeoxycholate (TUDC) and taurocholate on the modifications induced by these two compounds. F-actin was stained with fluorescein-isothiocyanate phalloidin and fluorimetric measurements were performed using a scanning laser cytometer ACAS 570. F-actin distribution was assessed in the couplets by the ratio of the pericanalicular area fluorescence/total couplet fluorescence (CF/TF). At non-cytotoxic concentrations, TLC (50, 100 microM) and ERY (10, 50, 100 microM) induced a significant accumulation of F-actin around the bile canaliculus as indicated by increased fluorescence in the pericanalicular area and by the increased CF/TF ratio compared with the controls. Electron microscopy studies showed significant alterations in bile canaliculi microvilli in couplets treated with 100 microM TLC. Only a few canaliculi showed an increase in pericanalicular microfilaments after treatment with 100 microM ERY. As assessed by scanning laser cytometry, TUDC prevented changes in F-actin distribution when it was added to the medium with taurolithocholate or erythromycin estolate at equimolar concentrations. However, the morphological changes observed by electron microscopy after treatment with TLC were not modified by co-treatment with TUDC. Taurocholate was ineffective. We conclude that (a) abnormalities of pericanalicular F-actin microfilaments occur in two different models of cholestasis, (b) tauroursodeoxycholate prevents the accumulation of pericanalicular F-actin detected by scanning laser cytometry but not the morphological changes of the canaliculus observed by electronic microscopy. Therefore, in these experimental conditions, the protective effect of TUDC appears to be partial.

Actins↗
PubMed1979

Effect of chlorpromazine and erythromycin on bile salt-induced cholestasis in the rat.

The effects of subacute administration of chlorpromazine HCI (CPZ), erythromycine base and erythromycin estolate on the cholestatic response to intravenous taurolithocholate (TLC) and taurochenodeoxycholate (TCDC) in the rat were investigated. All three enhanced the recovery of bile flow after TCDC but not after TLC. Erythromycin base and estolate enhanced bile flow recovery after TCDC and potentiated the increase of plasma 5'-nucleotidase, as did CPZ. Neither erythromycin estolate nor CPZ precipitated a cholestatic response in rat maintained for 9-13 days on a diet supplemented with 0.05% lithocholic acid. It is concluded that the interaction of CPZ and erythromycins with bile salts is not based on the cholestatic properties of the drugs, and hence is not a practical way of distinguishing cholestatic from non-cholestatic drugs.

Alanine Transaminase↗
PubMed1999

Etiology and treatment of community-acquired pneumonia in ambulatory children.

OBJECTIVES: To determine the etiology of community-acquired pneumonia in ambulatory children and to compare responses to treatment with azithromycin, amoxicillin-clavulanate or erythromycin estolate. METHODS: Ambulatory patients with pneumonia were identified at the Children's Medical Center of Dallas, TX. Children age 6 months to 16 years with radiographic and clinical evidence of pneumonia were enrolled and randomized to receive either azithromycin suspension for 5 days or a 10-day course of amoxicillin-clavulanate for those <5 years or erythromycin estolate suspension for those > or = 5 years. Blood culture was obtained in all patients and we obtained nasopharyngeal and pharyngeal swabs for culture and polymerase chain reaction (PCR) testing for Chlamydia pneumoniae and Mycoplasma pneumoniae and nasopharyngeal swabs for viral direct fluorescent antibody and culture. Acute and convalescent serum specimens were tested for antibodies to C. pneumoniae, M. pneumoniae and Streptococcus pneumoniae. Patients were evaluated 10 to 37 days later when repeat specimens for serology, PCR and culture were obtained. For comparative purposes healthy children attending the well-child clinic had nasopharyngeal and pharyngeal swabs obtained for PCR and culture for C. pneumoniae and M. pneumoniae. RESULTS: Between February, 1996, and December, 1997, we enrolled 174 patients, 168 of whom fulfilled protocol criteria for evaluation. There were 55% males and 63% were <5 years of age. All blood cultures were sterile and there was no correlation between the white blood cell and differential counts and etiology of pneumonia. Etiologic agents were identified in 73 (43%) of 168 patients. Infection was attributed to M. pneumoniae in 7% (12 of 168), C. pneumoniae in 6% (10 of 168), S. pneumoniae in 27% (35 of 129) and viruses in 20% (31 of 157). None of the swab specimens from 75 healthy control children was positive for C. pneumoniae or M. pneumoniae. Clinical response to therapy was similar for the three antibiotic regimens evaluated, including those with infection attributed to bacterial agents. CONCLUSION: Although a possible microbial etiology was identified in 43% of the evaluable patients, clinical findings and results of blood cultures, chest radiographs and white blood cell and differential counts did not distinguish patients with a defined etiology from those without a known cause for pneumonia. There were no differences in the clinical responses of patients to the antimicrobial regimens studied.

Adolescent↗
PubMed1999

Compliance of pediatric patients with treatment involving antibiotic suspensions: a pilot study.

In collaboration with 11 German pediatricians in private practice, this pilot study assessed the treatment compliance of 289 pediatric patients (56.1% male: mean age, 53.9+/-35.6 months) who were given antibiotic suspensions (selection and duration determined by the pediatrician) to treat the following bacterial infections: acute otitis media, 34.6%; group A streptococcal tonsillopharyngitis/scarlet fever, 28.7%; lower respiratory tract infection, 18.3%; sinusitis/sinobronchitis, 9.3%; and other infections, 9.0%. The most frequently used antibiotics were amoxicillin (26.3%), erythromycin estolate (19.0%), penicillin V benzathine (14.2%), and cefaclor (13.5%). Compliance was assessed by means of a standardized telephone interview and a urine test that detects antibacterial activity using a Bacillus subtilis spore suspension. Overall compliance (positive urine test result at the end of the planned treatment period) was 79.6% (230 of 289 patients). Compliance was highest with erythromycin estolate (94.5%), followed by penicillin V benzathine (85.4%), cefaclor (76.9%), and amoxicillin (71.1%). Good compliance was also significantly associated with a patient age of > or =3 years and a treatment duration of > or =7 days. Compliance was not significantly influenced by the underlying bacterial infection. In summary, 20.4% of patients were noncompliant when treated with antibiotic suspensions.

Anti-Bacterial Agents↗
PubMed1978

Prophylaxis against tetanus in non-immune patients with wounds: the role of antibiotics and of human antitetanus globulin.

The potential value of oral erythromycin for antitetanus prophylaxis in non-immune patients with open wounds was assessed. Serum obtained by venepuncture from health persons 2 h after an oral dose of an erythromycin preparation was used as a culture medium rendered anaerobic by addition of cooked meat. Strains of Clostridium tetani inoculated into these sera failed to multiply when the donor had taken 500 mg of erythromycin estolate before a meal; other erythromycin preparations and the estolate at a dosage of 250 mg were ineffective or inconsistent in their inhibition of the growth of Cl. tetani. Human antitetanus globulin (ATG) was given to 12 patients, 9 with severe injuries and 3 with extensive burns, all of whom were judged, from their history, to be non-immune (or with expired immunity); all except one had received large intravenous infusions of blood and/or other fluids. Serum antitoxin assays by a mouse protection technique on days 0, 1--2, 3--5, 6--10 and 14+ showed no detectable antitoxin (less than 0.01) unit/ml) in the initial (pre-ATG) sample from three patients with severe injuries and in one with extensive burns. All the patients in the severely injured group showed an early appearance or increase in tetanus antitoxin to protective titres. Two of the three severely burned patients showed, respectively, a delayed appearance or an increase in antitoxin; the other burned patients showed a reduction from the initial pre-ATG titre, followed by a return to that titre after day 5.

Blood Transfusion↗
PubMed1976

Erythromycin therapy for streptococcal pharyngitis.

Streptococcal eradication rates of 86% were demonstrated in 97 patients seen on day 14 and in 73 patients seen on both days 14 and 28 after a ten-day course of erythromycin estolate therapy given at a dosage of 20 mg/kg/day, administered in two equal doses. The efficacy of this regimen compares favorably with other results in which this and other erythromycin preparations have been employed at higher doses, usually in the range of 30 to 50 mg/kg/day. Our reported effectiveness at a lower than usual dose of erythromycin is probably explained by the following factors: the known susceptibility of group A streptococci to low concentrations of erythromycin, the uniform absorption of the estolate formulation of erythromycin, and adequate compliance in adhering to the treatment regimen by the majority of our patients. This dosage schedule of erythromycin is simple to administer; and a reduction by half of the total dose usually recommended provides an economical advantage for patients.

Erythromycin↗
PubMed1981

Cefadroxil monohydrate versus erythromycin in paediatric patients.

Cefadroxil monohydrate, an oral cephalosporin with a long half-life, was compared to erythromycin estolate for efficacy in treating upper respiratory tract infections in children. The study was carried out on forty patients, twenty receiving cefadroxil and twenty receiving erythromycin. Each drug was dosed at 50 mg/kg/day and was given every 12 hours in two equally divided doses. The complete cure rate was 95% for the cefadroxil group and 80% for the erythromycin group. Two patients originally in the erythromycin test group showed no improvement either bacteriologically or clinically after 3 days of treatment. It was found that these patients harboured S. aureus which had become resistant to erythromycin during the course of therapy. Both patients were shifted to cefadroxil treatment and achieved complete cures. Two patients in the erythromycin group and one in the cefadroxil group were diagnosed as having scarlet fever. All three responded clinically, yet cultures from the two treated with erythromycin showed persistence of bacteria while the one treated with cefadroxil proved to be cured both clinically and bacteriologically.

Cefadroxil↗
PubMed2000

Equine proliferative enteropathy: a cause of weight loss, colic, diarrhoea and hypoproteinaemia in foals on three breeding farms in Canada.

Proliferative enteropathy (PE) is a transmissible enteric disease caused by Lawsonia intracellularis. An outbreak of equine PE was diagnosed in foals from 3 breeding farms. Most foals had been weaned prior to the appearance of clinical signs, which included depression, rapid and marked weight loss, subcutaneous oedema, diarrhoea and colic. Poor body condition with a rough haircoat and a potbellied appearance were common findings in affected foals. Respiratory tract infection, dermatitis and intestinal parasitism were also found in some foals. Haematological and plasma biochemical abnormalities included hypoproteinaemia, transient leucocytosis, anaemia and increased serum creatinine kinase concentration. Postmortem diagnosis of PE was confirmed on 4 foals based on the presence of characteristic intracellular bacteria within the apical cytoplasm of proliferating crypt epithelial cells of the intestinal mucosa, using silver stains, and by results of PCR analysis and immunohistochemistry. Antemortem diagnosis of equine PE was based on the clinical signs, hypoproteinaemia and the exclusion of common enteric infections. Faecal PCR analysis was positive for the presence of L. intracellularis in 6 of 18 foals tested while the serum of all 7 foals with PE serologically evaluated had antibodies against L. intracellularis. Most foals were treated with erythromycin estolate alone or combined with rifampin for a minimum of 21 days. Additional symptomatic treatments were administered when indicated. All but one foal treated with erythromycin survived the infection. This study indicates that equine PE should be included in the differential diagnosis of outbreaks of rapid weight loss, diarrhoea, colic and hypoproteinaemia in weanling foals.

Animal Husbandry↗
PubMed1979

Use of antibiotics in the outpatient setting.

Antibiotics with small but definable mortality, such as chloramphenicol, should not be used when safer drugs will suffice. Antibiotics with a low (1 to 5 per cent) morbidity should not be used when safer drugs are available. Therefore, cleocin, minocycline, or oral erythromycin estolate should rarely be used and regular erythromycin base is almost always preferable. Fever should not be treated with antibiotics since they are not antipyretics. "Colds" should not be treated with antibiotics, but antibiotics should be administered to patients with a history of chronic bronchitis, sinusitis, and recurrent otitis as soon as any symptoms begin. Intramuscular antibiotics should not be given except for benzathine penicillin. Use placebos instead of antibiotics when the patient's psyche demands an intramuscular injection. Make certain that the needle, syringe, and solution are sterile. Agents other than penicillin or cephalosporins should be used in patients with a definite history of penicillin allergy. Combination antibiotics or broad spectrum antibiotics like cephelosporins or tetracyclines should not be used when narrow spectrum antibiotics of known efficacy are available for specific syndromes such as streptococcal pharyngitis.

Ambulatory Care↗
PubMed2003

Use of erythromycin for the treatment of severe chronic constipation in children.

The efficacy of erythromycin was assessed in the treatment of 14 children aged 4 to 13 years with refractory chronic constipation, and presenting megarectum and fecal impaction. A double-blind, placebo- controlled, crossover study was conducted at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital. The patients were randomized to receive placebo for 4 weeks followed by erythromycin estolate, 20 mg kg-1 day-1, divided into four oral doses for another 4 weeks, or vice versa. Patient outcome was assessed according to a clinical score from 12 (most severe clinical condition) to 0 (complete recovery). At enrollment in the study and on the occasion of follow-up medical visits at two-week intervals, patient score and laxative requirements were recorded. During the first 30 days, the mean SD clinical score for the erythromycin group (N = 6) decreased from 8.2+/-2.3 to 2.2+/-1.0 while the score for the placebo group (N = 8) decreased from 7.8+/-2.1 to 2.9+/-2.8. During the second crossover phase, the score for patients on erythromycin ranged from 2.9+/-2.8 to 2.4+/-2.1 and the score for the patients on placebo worsened from 2.2+/-1.0 to 4.3+/-2.3. There was a significant improvement in score when patients were on erythromycin (P < 0.01). Mean laxative requirement was lower when patients ingested erythromycin (P < 0.05). No erythromycin-related side effects occurred. Erythromycin was useful in this group of severely constipated children. A larger trial is needed to fully ascertain the prokinetic efficacy of this drug as an adjunct in the treatment of severe constipation in children.

Adolescent↗
PubMedDate not supplied

Erythromycin toxicity in primary cultures of rat hepatocytes.

Cultured rat hepatocytes were used to study the toxicity of erythromycin base (EB), erythromycin estolate (EE) and a new fluorinated derivative, (8S)-8-fluoroerythromycin A (EF). EF was not cytotoxic after 18 h incubation at concentrations up to 8 X 10(-4) M and EE was much more toxic than EB at all concentrations studied. EE toxicity was greater in a serum-free medium and was not increased by induction of cytochrome P-450 with phenobarbitone. In hepatocytes co-cultured with rat-liver epithelial cells EE, but not EF, raised the cytochrome P-450 content and formed stable cytochrome P-450 complexes with about 40% of the haemoprotein. The lack of correlation between cytochrome P-450 content and cytotoxicity suggests that some of the parent erythromycin drugs and not their metabolites are the toxic entities.

Animals↗
PubMed1983

In vivo evaluation of ocular inserts of hydrogel impregnated with antibiotics for trachoma therapy.

Sustained release of antibiotics from hydrogel matrices in the eye was studied for the purpose of developing a new method for trachoma therapy. Copolymers of N-vinylpyrrolidone were moulded into an ocular insert and impregnated with erythromycin or erythromycin estolate. The antibiotic-hydrogel inserts completely suppressed the chlamydia trachomatis infection in the owl monkey eyes. The drug elution rates were a little lower in vivo than in vitro. By comparison of the drug elution rate in the human eye with that in the owl monkey eye, similar therapeutic effect is expected in the treatment of human trachoma.

Animals↗
PubMed1985

Seroepidemiology of the group-A streptococcal carriage state in a private pediatric practice.

During a 24-month period, throat-swab cultures were obtained on 1,362 well children who were 3 months to 14 years of age. The overall incidence of positive cultures for group-A beta-hemolytic Streptococcus was 3.3%; in those children older than 1 year, it was 4.4%. The largest incidence of positive cultures occurred in the 5- to 7-year-old (8.3%) and 8- to 10-year-old (4.5%) age groups. No positive cultures were obtained from 339 infants younger than 1 year of age. There was no relation between positive cultures and the month of the year. There were no significant differences between the age, sex, presence of tonsils, previous group-A streptococcal infections, or the presence in a daycare center or school of children with positive cultures compared with those children with negative cultures. Follow-ups were obtained on 29 of 45 children with positive throat cultures; all of the children were asymptomatic and had normal results of physical examinations. Group-A streptococci of the same serotype as the original isolate were isolated from 19 of these children. Three to four days after a ten-day course of erythromycin estolate, five of 19 children again had positive cultures. Twenty-six of the 29 children had a total of 43 siblings residing in the home. Serotypically identical group-A streptococci were isolated from five siblings (11%). Only one of 29 patients from whom paired serum samples were obtained showed a fourfold rise or fall in the Streptozyme titers.

Antibodies, Bacterial↗
PubMed1993

Duration of positive throat cultures for group A streptococci after initiation of antibiotic therapy.

OBJECTIVE: To determine if it is appropriate to recommend that patients with group A beta-hemolytic streptococcal pharyngitis, who are clinically well by the morning after starting antibiotic treatment, can return to school or day care, or if they should wait until they have completed 24 hours of antibiotics as recommended by the American Academy of Pediatrics Committee on Infectious Diseases. METHODS: We examined the duration of positivity of the throat culture after antibiotics were begun as a means of assessing the potential risk of transmission to close school contacts. Forty-seven children (4 to 17 years of age) with pharyngitis and a positive throat culture for group A streptococci in an outpatient, staff model health maintenance organization clinic were enrolled and were randomly selected to receive therapy with either oral penicillin V, intramuscular benzathine penicillin G, or oral erythromycin estolate. Additional throat cultures were obtained and clinical findings were recorded for each child during three home visits in the 24 hours after their initial clinic visit. Acute and convalescent sera were obtained for determination of anti-streptolysin O and anti-DNase B titers. RESULTS: Seventeen (36.2%) of the 47 patients had a positive culture the morning after initiating antibiotic therapy. However, thirty-nine (83%) of the patients became "culture negative" within the first 24 hours. Neither the time interval to the first negative culture nor the presence or absence of group A streptococcal organisms on any single convalescent culture could be predicted by clinical findings. Six of the eight children who failed to convert to a "negative" throat culture within 24 hours of initiating therapy were receiving erythromycin. We could detect no difference in either time to conversion to a negative culture or the presence of a positive culture 24 hours after starting antibiotics between those who demonstrated a significant antibody increase and those who did not. CONCLUSION: The data from this study strongly suggest that children with group A beta-hemolytic streptococcal pharyngitis should complete a full 24 hours of antibiotics before returning to school or daycare.

Adolescent↗
PubMed1989

Protective effect of flavonoids on drug-induced hepatotoxicity in vitro.

Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins. Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH). Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity. Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period. These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups. NT was less toxic than its parent compound, AT. Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis. As the concentration of hepatotoxins was increased, the changes were more pronounced. Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins. The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.

Alanine Transaminase↗
PubMed1992

Protective effect of diosmetin on in vitro cell membrane damage and oxidative stress in cultured rat hepatocytes.

Primary cultures of rat hepatocytes were used to study the effects of the flavonoids diosmin and its main metabolite diosmetin on the cell membrane damage caused by erythromycin estolate (EE) and oxidative stress caused by tert-butylhydroperoxide (TBHP). The damage was evaluated by the leakage of intracellular enzymes lactate dehydrogenase, aspartate-aminotransferase and the residual cell content of a lysosomal marker acid phosphatase (AP). After treating the cells for 40 h with diosmetin EE induced less enzyme leakage. The content of AP was kept higher by diosmetin pretreatment after 6 h exposure to EE. Diosmin at the same concentrations had barely any effect. Diosmetin, but not diosmin, also protected against TBHP toxicity and this was related to lower lipid peroxidation and higher glutathione content caused by pretreatment with the flavonoid. When the cells were treated simultaneously with TBHP and diosmetin after 21 h of culture, the protection by the flavonoid was even higher. In fact the antioxidant activity of diosmetin was considerably greater than that of diosmin. After 40 h exposure to both flavonoids diosmin but not diosmetin was detectable in the cell membrane fraction, suggesting that the latter's protective effect is associated with its metabolites.

Acid Phosphatase↗
PubMed1983

Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats.

The effects of some macrolides (4 mmoles . kg-1 p.o. daily for 4 days in vivo; 0.3 mM in vitro) on hepatic drug-metabolizing enzymes in rats were compared. One group of macrolides including previously studied compounds (oleandomycin, erythromycin and troleandomycin), as well as several other erythromycin derivatives, showed induction of microsomal enzymes and formation of inactive cytochrome P-450-metabolite complexes in vivo; this formation increased in the order: oleandomycin, erythromycin ethylsuccinate, erythromycin stearate, erythromycin itself, erythromycin propionate, erythromycin estolate and troleandomycin. Troleandomycin and, to a lesser extent, erythromycin and oleandomycin formed cytochrome P-450-metabolite complexes when incubated in vitro with 1 mM NADPH and microsomes from rats pretreated with troleandomycin or phenobarbital, but not with microsomes from control rats or rats treated with 3-methylcholanthrene. In contrast, two other macrolides, josamycin and midecamycin, showed no induction of microsomal enzymes and no detectable formation of cytochrome P-450-metabolite complexes in vivo. In vitro, these macrolides failed to form detectable complexes even with microsomes from rats pretreated with troleandomycin or phenobarbital. Hexobarbital sleeping time was unaffected by preadministration of josamycin or midecamycin (4 mmoles . kg-1 p.o.) 2 hr earlier; the in vitro activity of hexobarbital hydroxylase was not inhibited by 0.3 mM josamycin or midecamycin. We conclude that, unlike several erythromycin derivatives, josamycin and midecamycin do not form inactive cytochrome P-450-metabolite complexes in rats.

Animals↗