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Chlamydia trachomatis is an obligate intracellular parasite responsible for many clinical syndromes, including neonatal conjunctivitis and pneumonia. The gold standard of diagnosis has been isolation in cell culture. However, this requires days of processing. Several rapid diagnostic tests are available. Giemsa staining of conjunctival smears, enzyme immunoassay, and the fluorescein-conjugated monoclonal antibody test. Both the EIA and the FA tests show promise as ideal rapid diagnostic tests. Treatment of chlamydial conjunctivitis must focus upon the eradication of nasopharyngeal carriage as well as cure of ophthalmic symptoms. The need for nasopharyngeal eradication is underscored by the fact that it is the source for chlamydial pneumonia as well as for conjunctival re-infection. Clinical studies have shown that oral erythromycin estolate or ethylsuccinate suspension 50 mg/kg/day twice-daily or four times a day for 14 to 21 days are the therapeutic regimens of choice. Neonatal ocular prophylaxis is currently under study. One per cent silver nitrate does not prevent chlamydial conjunctivitis but preliminary studies do show favorable results with topical erythromycin. Nevertheless, neither 1 per cent silver nitrate nor topical erythromycin eradicate nasopharyngeal carriage, elimination of which is necessary for the prevention of neonatal chlamydial pneumonia.
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The hepatotoxicity of a new erythromycin derivative, erythromycin acistrate (EA, 2'-acetyl erythromycin stearate), was compared with that of erythromycin stearate (ES), erythromycin estolate (EE) and erythromycin-11,12 cyclic carbonate (EC) in 4-5-day, 28-day and 6-month oral toxicity studies in rats and dogs. In the 4-day rat study, EC caused fatty metamorphosis in the liver. ES caused similar, but milder changes at a dose nearly five times higher. The 5-day dog study revealed markedly increased serum alanine aminotransferase (S-ALAT), serum aspartate aminotransferase (S-ASAT), serum alkaline phosphatase (S-APHOS) and serum gamma-glutamyl transpeptidase (S-gamma-GT) values in the EC- and EE-groups, and slightly elevated S-ALAT values also in the EA- and ES-groups. Microscopy revealed cholangitis, pericholangitis and phlebitis in the portal areas in the EC-group at all doses. Epithelial hyperplasia was observed also in the bile ducts. EE caused similar but milder changes. The changes in the EA-group were small, but mildly atypical bile duct epithelium was seen in female dogs receiving 2 x 200 mg/kg of EA. The ES-group was practically without changes and very much like the EA-group. Thus the dog proved to be a more sensitive model for assessing the hepatotoxicity of erythromycin derivatives. In the 28-day studies, only EA and ES were investigated. In the rat study, slightly elevated serum enzyme levels within the normal range were measured in the high-dose regimens of both drugs. In the dog study, 300 mg/kg of EA caused slightly elevated S-ALAT in males, but the values returned to normal after a 2-week off-dose period. Only EA was studied in the 6-month study. In male rats, 400 mg/kg of EA caused slightly elevated enzyme levels and neutral fat droplets in centrilobular hepatocytes. In male dogs given 150 mg/kg of EA, S-ALAT, S-APHOS, and S-gamma-GT values were elevated after four weeks of treatment but returned to normal thereafter. No severe changes were seen in the liver histopathology. In conclusion, EC and EE were clearly hepatotoxic in dogs, and EC also in rats. EA, and to a somewhat lesser extent ES, showed signs of mild hepatotoxicity only at high doses. This evidently reversible effect was considered a common characteristic of erythromycins.
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The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10-12-week-old foals given 20.0 mg/kg intravenously. The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10-12 weeks) was 1.0-1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h. No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally. Peak levels in foals given the drug orally were 0.42 micrograms/ml at 120 min after administration. Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later; the peak level achieved was 1.44 micrograms/ml serum 90 min after administration and concentrations exceeded 0.25 micrograms/ml for 6 h. In the mares the milk concentrations were approximately twice those in serum. Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals.
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Twelve trials with 1,720 participants met the inclusion criteria. Ten trials investigated treatment regimens and two investigated prophylaxis regimens. The quality of the trials was variable. Results showed that short-term antibiotics (azithromycin for three days, clarithromycin for seven days, or erythromycin estolate for seven days) were equally effective with long-term antibiotic treatment (erythromycin estolate or erythromycin for 14 days) in the microbiological eradication of Bordetella pertussis (B. pertussis) from the nasopharynx. The relative risk (RR) was 1.02 (95% confidence interval (CI) 0.98 to 1.05). Side effects were fewer with short-term treatment (RR 0.66; 95% CI 0.52 to 0.83). There were no differences in clinical improvement or microbiological relapse between short and long-term treatment regimens. Contact prophylaxis (of contacts older than six months of age) with antibiotics did not significantly improve clinical symptoms or the number of cases that developed culture positive B. pertussis.
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All splenectomized individuals are at risk of developing pneumococcal sepsis, but most reports fail to mention how many patients are given prophylactic penicillin therapy. Fourteen reported cases of postsplenectomy bacterial sepsis in patients receiving prophylactic penicillin therapy are reviewed. In only five cases, the patients had penicillin-sensitive pneumococcal infection. Hence, the exact frequency of the failure of penicillin prophylaxis cannot be calculated, but it appears to be very rare. Continuous antibiotic prophylaxis used indefinitely and pneumococcal vaccine are both strongly recommended for all children and adults undergoing splenectomy.
Randomised controlled trials comparing any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina.
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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.
The GETt1/2 decreased from 198.0 +/- 58.9 minutes at baseline to 139.1 +/- 67.6 minutes following one day of erythromycin therapy (p < 0.01), and to 137.1 +/- 71.2 minutes after two weeks of treatment (vs. baseline p < 0.01). The FBS decreased from 159.0 +/- 40.2 mg/dl at baseline to 149.0 +/- 38.5 mg/dl following one day of therapy (p = 0.12, NS), and to 139.2 +/- 39.8 mg/dl after two weeks of treatment (vs. baseline p < 0.02).
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Because of the lack of a UV chromophore and their much smaller abundances in comparison with the major component, the minor components in erythromycin estolate preparations are difficult to analyze by high performance liquid chromatography ultraviolet (HPLC-UV). Tentative assignment of the major and minor components can be achieved with the combination of full scan and ZoomScan using an ion trap mass spectrometer. Tandem mass spectrometry (MS/MS) provided an effective method to quickly identify most components without chromatographic separation, and all the related compounds, except the isobaric pair ECE and PdMeEA, could be identified in this way. The best result was obtained by using liquid chromatography/tandem mass spectrometry (LC/MS/MS) operated in selected reaction monitoring mode. The major compound, the estolate of erythromycin A (EAE), and seven other minor components, could be separated and identified, with semiquantitative estimates of relative concentrations.
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We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2003).
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A high-performance liquid chromatographic analysis of erythromycin and its esters in plasma, urine and saliva is presented. A diethyl ether extract of sample was chromatographed on a reversed-phase column and components of the column effluent were monitored by electrochemical detection at +0.9 V (vs. Ag/AgCl). The method sensitivity limit was 10 ng with inter-day coefficients of variation from 3.2 to 10.3%. In order to assess precisely the relative concentrations of erythromycin esters (ethylsuccinate or estolate) and their active by-product erythromycin base, it is necessary to adopt measures preventing their continuous hydrolysis in biological fluids and during sample preparation.
Suitable antimicrobials given during the catarrhal stage of whooping cough can attenuate the course of the disease. The efficacy of antibiotics administered prophylactically during the incubation period remains controversial but appears to be beneficial. Currently, erythromycin given for two weeks is the antibiotic of choice for pertussis. No treatment failures were observed with erythromycin estolate. Erythromycin ethylsuccinate and stearate must be given at high dosages (50-60 mg/kg/day) in order to achieve sufficient concentrations in the respiratory secretions. With ampicillin and amoxicillin treatment failures have been observed. The role of josamycin and co-trimoxazole in pertussis remains open.
Tetracyclines are active in vitro against most urinary tract pathogens, Chlamydia, Mycoplasma pneumoniae, Brucella, rickettsiae, and Nocardia. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and infections due to Salmonella typhi. Erythromycin is active in vitro against M. pneumoniae, Streptococcus pneumoniae, and group A beta-hemolytic streptococci. Erythromycin may be used as prophylactic therapy for subacute bacterial endocarditis and for recurrence of acute rheumatic fever in patients who are allergic to penicillin. Clindamycin should be used only for the treatment of anaerobic infections. Tetracycline may cause gastrointestinal upset; phototoxic dermatitis; hepatitis, especially in pregnant females; discoloration of teeth and bone dysplasia in the human fetus and children; and suprainfections, especially oral and anogenital candidiasis. Tetracycline should be used with caution in patients with renal insufficiency. The most important toxic effect of chloramphenicol is bone marrow suppression, which is dose related and idiosyncratic. The incidence of undesirable side effects associated with the use of erythromycin is low. Gastrointestinal irritation is the most common; cholestatic hepatitis may occur with erythromycin estolate. Pseudomembranous colitis is the most important toxic effect associated with clindamycin.
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In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.
The absorptions of 6 erythromycin preparations were compared in a cross-over study in healthy humans. In a single-dose study, 500 mg of each preparation was, after an overnight fast, given to 10 volunteers. The two enterosoluble preparations of erythromycin base studied were absorbed slowly, and the peak serum concentration (1.5-2 mg/l) was achieved only at 4 h. The absorption of the stearates was quick, but especially one of them was poorly absorbed, the serum concentration being always below 1 mg/l. Both of the two estolates gave highest apparent concentrations, and the maximum serum level (2-2.5 mg/l) was achieved at 2 h, but the concentration of active erythromycin remains unknown. In the second part of the study, two erythromycin stearates and one base preparation were given at 6-h interval in a cross-over fashion, each for 4 days. On the 4th day, blood samples were analyzed. The erythromycin base gave higher serum concentrations than did the two stearates, which were equivalent. It seems doubtful that the erythromycin stearate at the dose of 250 mg every 6th hour would give satisfactory serum levels of erythromycin which would be effective against most bacteria during the whole treatment.
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Antibiotics are effective in eliminating B. pertussis from patients with the disease, rendering them non-infectious, but do not alter the subsequent clinical course of the illness. Effective regimens include: three days of azithromycin, seven days of clarithromycin, seven or 14 days of erythromycin estolate, and 14 days of erythromycin ethylsuccinate. Considering microbiological clearance and side effects, three days of azithromycin or seven days of clarithromycin are the best regimens. Seven days of trimethoprim/sulfamethoxazole also appeared to be effective for the eradication of B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who cannot tolerate a macrolide. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.
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All randomised controlled trials that compared any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina.
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Erythromycin taurate, a new derivative of erythromycin, was prepared by reacting erythromycin base with tauric acid and its physico-chemical and biological properties were evaluated. The derivative has reasonably good solubility in organic solvents. The partition coefficient values in chloroform/water 1.17 and octanol/water 1.16 systems indicate its good distribution in various tissues in vivo. The in vitro antimicrobial potency of the derivative (833.33 microg mg(-1)) is higher than that of the existing derivatives such as erythromycin estolate, erythromycin stearate, erythromycin ethyl succinate, erythromycin gluceptate, erythromycin lactobionate. The antimicrobial spectrum is comparable to that of the parent compound. Our results indicate that erythromycin taurate has a high potential for possible clinical application and is more efficient against Escherichia coli and Klebsiella pneumoniae than the parent base.
All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment.
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In a 6-volunteer cross-over study the pharmacokinetics of 3 erythromycin preparations were compared. A single oral dose of 500 mg of each preparation was administered at each occasion and the levels measured in timed samples of plasma and saliva. Markedly higher blood concentrations of the estolate and propionate were obtained compared to the stearate. Comparison of serum and plasma concentration of the drugs from each split sample showed no significant differences. Plasma concentrations always exceeded those in saliva but for any one preparation a similar ratio was obtained at different times. This may be useful to ascertain compliance and to measure concentration of the compounds where direct measurement in plasma is not practicable.
At 12 months of use, the failure rate of the sterilization procedure for the crushed 500 mg tablets was 35.8% (SE = 1.8) with 417 women at risk. At 12 months of use, the failure rate for the erythromycin pellets was 28.6% (SE = 5.0) with 43 women at risk. There were no serious complications reported in either trial. All pregnancies resulting from failure of the sterilization procedure were terminated by menstrual regulation within 10 weeks gestation.
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We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007).
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Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.
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Erythromycin has been used as an antibiotic for more than four decades, but only in the last 10 years have other therapeutic benefits of this agent been exploited. Animal and human studies have demonstrated a prokinetic effect on the gastrointestinal tract at sub-antimicrobial doses (typically a quarter or less of the antibiotic dose). A limited number of studies have been performed in children to investigate this action. A review of this literature is particularly pertinent given the frequency of clinical problems related to gastrointestinal dysmotility in children and the limited availability of prokinetic agents in paediatric practice, compounded by the recent withdrawal of cisapride. The prokinetic effects of erythromycin have been investigated in infants with dysmotility associated with prematurity, in low birth-weight infants recovering from abdominal surgery, and in older children with a variety of other gastrointestinal disorders. Only one randomized placebo-controlled trial has been conducted. All except one of these studies have shown a beneficial effect of erythromycin in either promoting tolerance of enteral feeds or enhancing a measured index of gastrointestinal motility. Erythromycin appears to be equally effective when given orally (as ethylsuccinate or estolate) or intravenously (as lactobionate). Significantly, no serious adverse effects have been reported in studies in which erythromycin has been used for its prokinetic effects, although fatal reactions have followed the intravenous administration of erythromycin to neonates in antibiotic doses.
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Food was withheld from foals overnight before intragastric administration of erythromycin estolate (25 mg/kg of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals received both drugs with 2 weeks between treatments. Plasma erythromycin concentrations were determined at various times after drug administration by use of high-performance liquid chromatography. Maximum plasma peak concentrations, time to maximum concentrations, area under plasma concentration versus time curves, half-life of elimination, and mean residence times were determined from concentration versus time curves.
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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.
Although 14 days of erythromycin is recommended for the treatment of Bordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact.
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The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.