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Clindamycin, erythromycin, and the newer macrolides.

Clindamycin continues to be an important agent for the management of infections due to gram-positive cocci and anaerobes. Such pathogens are frequently important in skin, soft tissue, and deep infections of the foot. Erythromycin has an impressive safety record and has retained its activity against many organisms, including several that play a role in infections of the foot. Clindamycin and erythromycin are frequently used as alternatives to the penicillins and cephalosporins. Newer macrolides, in comparison to erythromycin, have similar antimicrobial spectra of activity, improved pharmacokinetic parameters, and better tissue penetration. As new microorganisms emerge as clinical problems, newer macrolides may play a therapeutic role.

Anti-Bacterial Agents↗

[Effects of erythromycin on hydrogen peroxide-induced interleukin-8 synthesis and regulation of glutathione in human bronchial epithelial cells].

OBJECTIVE: To study the effects of erythromycin on Hydrogen peroxide (H2O2)-induced interleukin-8 synthesis and regulation of glutathione in human bronchial epithelial cells. METHODS: Human bronchial epithelial (16HBE) growth curve was recorded by MTT, cells were divided into three groups (1) control (incubation for 24, 36, 48) (2) H2O2 (Pre-incubation for 24, 36, 48 h before adding H2O2 (3) H2O2 + EM (Pre-incubation EM for 24, 36, 48 h before adding H2O2). IL-8 levels were measured in culture supernatants by ELISA, activation of transcription factor NF-kappaB and AP-1 in HBE was evaluated by Electrophoretic mobility shift assay (EMSA). Intracellular GSH and Gamma-GCS concentrations were measured by spectrophotometric assay, gamma-GCS-HS protein were determined by Western blot. RESULTS: Erythromycin (1 microg/ml, 10 microg/ml) and H2O2 (0.01 mM, 0.1 mM) have no effects on cell growth, Preincubation with EM (5 microg/ml) for 36 h and 48 h significantly inhibit H2O2 (0.01 mmol/L) induced increase of IL-8 levels in HBE supernatants, in the mean time decrease the expression of NF-kB and AP-1. Preincubation with EM (5 microg/ml) for 48 h significantly inhibit H2O2 (0.01 mmol/L) induced increase of gamma-GCS levels, gamma-GCS-HS protein expression and AP-1 binding of gamma-GCS-HS promoter in HBE. However GSH and gamma-GCS-HS protein expression in EM + H2O2 group significantly higher than those in control group. CONCLUSION: Erythromycin inhibits oxidant-mediated IL-8 levels through down-regulation of NF-kB and AP-1 binding in HBE, which can further influence the synthesis of GSH and expression gamma-GCS in HBE.

Bronchi↗

[Erythromycin improves quality of endoscopy for acute upper gastrointestinal bleeding].

Twenty four patients with acute upper gastrointestinal bleeding undergoing endoscopy were assessed. Thirteen received erythromycin before the examination and 11 did not. The cleansing effect was bad in 2/6, satisfactory in 4/3 and good in 7/2 patients (erythromycin/non erythromycin group respectively). The need for repeat endoscopy was in 3 and 8 patients respectively. In conclusion erythromycin given before endoscopy improves quality of endoscopic examination in patients with upper gastrointestinal bleeding.

Acute Disease↗

[Access of torsades de pointes in Legionnaires' disease: an uncommon adverse effect of erythromycin].

We report the case of a 77-year-old man with legionnaires's disease who, immediately after an intravenous infusion of one gram of erythromycin presented with wave burst arrhythmia with widening of the QT space. The blood level of erythromycin at the time of this adverse reaction was the same as the peak observed in young subjects after intravenous administration of this drug. Fourteen similar cases were found in the literature. In vitro and in vivo studies have shown that erythromycin may exert on the cardiac muscle fibres an electrophysiological effect similar to that of class I antiarrhythmic agents.

Aged↗

[Comparative study of minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) values for tetracycline, monocycline, erythromycin and rokitamycin against eleven strains of Chlamydia trachomatis].

We evaluated the efficacy of tetracycline, minocycline, erythromycin and rokitamycin (rikamycine, TMS-19Q) in controlling in vitro propagation of Chlamydia trachomatis in HeLa 229 cells. Ten recent clinical isolates of Chlamydia trachomatis and one fast-growing strain were tested with inocula of 100-1,000 inclusion forming units per well of a 96-wheel microculture plate. Chlamydia trachomatis inclusions were detected by an immunoperoxidase-antiperoxidase procedure (PAP), including a genus-specific monoclonal antibody. Minimal inhibitory concentration (MIC) geometric means and ranges were respectively 0.128, 0.015-0.25 mg/l tetracycline, 0.001, less than or equal to 0.001-0.004 mg/l minocycline, 0.187, 0.031-0.5 mg/l erythromycin, and 0.005, less than or equal to 0.001-0.062 mg/l rokitamycin; minimal lethal concentration (MLC) geometric means and ranges were 6.79, 0.125-32 mg/l tetracycline, 0.225, 0.062-2 mg/l minocycline, 3.37, 1-32 mg/l erythromycin, and 0.112, 0.031-1 mg/l rokitamycin. Since rokitamycin appears to be the more bactericidal from the four antibiotics tested, clinical studies in sexually transmitted diseases are indicated.

Chlamydia trachomatis↗

[Erythromycin pharmacokinetics in children after rectal and oral administration].

Pharmacokinetics of erythromycin base was studied clinically in children not older than 14 years treated with new children dosage forms of the antibiotic i. e. 0.1 and 0.25 g enteric coated tablets and 0.06 and 0.125 g suppositories. It was noted that the new dosage forms were characterized by higher availability which was 2.5-3 times higher than that after using the erythromycin base tablets without the coating. Systematic increasing of erythromycin availability after the use of the rectal suppositories was observed with increasing of the children age. Absolute absorption in newborns, sucklings and children over 1 year amounted to 28, 36 and 54 per cent respectively.

Administration, Oral↗

Comparison of oral erythromycin ethylsuccinate and ciprofloxacin in the treatment of acute respiratory tract infections.

A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single-blind, multicentre study. The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents. Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group. In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms. This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.

Adolescent↗

Fulminant hepatic failure associated with intravenous erythromycin lactobionate.

Fatal fulminant hepatic failure accompanied by brisk hemolysis developed in an elderly man after intravenous administration of erythromycin lactobionate for a lower respiratory infection. To our knowledge, this is the first case of fatal hepatotoxicity associated with intravenous erythromycin therapy. Erythromycin should be added to the list of drugs that can cause fulminant hepatic failure.

Aged↗

[Study of the effect of protoplast formation on the antibiotic activity of erythromycin producers].

The influence of protoplasting and regeneration on the strains of the erythromycin-producing organism differing by their origin was studied with respect to changes in the antibiotic production property. 223 regenerates of the erythromycin-producing culture were tested in several generations and it was shown that there was a marked change in the range of the variation by that property. 40 to 70 per cent of the variants in the IInd generation increased their levels of erythromycin biosynthesis by 20 to 60 per cent as compared to the intact cultures. However, in the subcultures the antibiotic production level decreased and by the IVth generation only 3 to 6 per cent of the variants preserved its increase by 10 to 20 per cent over the control level because of the culture high instability.

Colony Count, Microbial↗

Comparison of chlamydial culture with Chlamydiazyme assay during erythromycin PCE treatment of Chlamydia genital infections.

We compared chlamydial culture with the chlamydial antigen detection enzyme immunoassay system (Chlamydiazyme, Abbott Diagnostic Products; Abbott Park, IL) during treatment of Chlamydia genital infections. Participants received 333 mg of erythromycin PCE (Abbott Laboratories; Abbott Park, IL) 3 times per day for 7 days. On days 0, 3, 7, and 14, chlamydial cultures were positive in 30/30 (100%), 5/29 (17.2%), 0/27, and 0/25 participants, respectively. Concurrent Chlamydiazyme assays were positive in 30/30 (100%), 11/30 (37%), 1/28 (4%), and 0/25 participants. Twenty-eight of 28 persons who received erythromycin PCE for at least 3 days had negative test results for both chlamydial culture and Chlamydiazyme at their last clinic visit. Chlamydiazyme assay tended to remain positive longer than chlamydial culture during treatment, but 7 days after therapy was completed, no Chlamydia trachomatis antigens were detectable by this assay. Erythromycin PCE was well tolerated and rapidly eliminated Chlamydia genital infections in 83% of persons showing negative cultures by the third day of therapy.

Antigens, Bacterial↗

[Effect of erythromycin and phosphomycin on the ingestion and destruction capacity of the human polymorphonuclear leukocyte].

The aim of the present study was to evaluate the uptake and intracellular destruction capacity of the human neutrophil. Human neutrophils from healthy individuals not receiving any therapy were incubated during 15, 90 and 180 minutes with the minimal, intermediate and maximal doses achieved in serum during treatment with therapeutic doses of these antibiotics (3, 6.45 and 9.9 micrograms/ml of erythromycin and 30, 45 and 60 micrograms/ml of phosphomycin). After this incubation, the uptake capacity and the intracellular destruction capacity of Candida guillermondii by neutrophils was assessed. Both erythromycin and phosphomycin maintained the baseline levels of both capacities in all the incubations evaluated. In addition, during the incubation with maximal dose erythromycin (15 min) a stimulatory tendency of the uptake and intracellular destruction capacity was observed.

Candida↗

Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy.

Topical antimicrobial therapy has not been effective in the past against cutaneous bacterial infections. In this study, a new topical antibiotic ointment, mupirocin, was compared with oral erythromycin ethylsuccinate in the treatment of impetigo. Seventy-five patients clinically diagnosed as having impetigo and with positive cultures of Staphylococcus aureus, Streptococcus pyogenes, or both were examined in an investigator-blinded study. Patients used topical mupirocin applied three times daily or the usual oral dose of erythromycin ethylsuccinate (30 to 50 mg/kg per day). Patients' lesions were examined clinically and cultured bacteriologically on days 0, 3, and 8, and 1 week after treatment. Susceptibility testing was performed on pathogens isolated to determine antibiotic resistance. Mupirocin treatment produced similar clinical results to oral erythromycin and was superior in the eradication of S aureus, including antibiotic-resistant S aureus. These results show topical mupirocin to be a safe and effective alternative to oral antibiotic therapy in the treatment of impetigo.

Administration, Oral↗

Comparison of oral erythromycin ethylsuccinate and clavulanate-potentiated amoxicillin in the treatment of acute respiratory tract infections.

Seven hundred fifty patients with acute upper or lower respiratory tract infections were randomly assigned to receive 2 gm of erythromycin ethylsuccinate daily or 1.125 gm of clavulanate-potentiated amoxicillin daily in a single-blind, multicenter study. The efficacy of each formulation was similar, with close to 90% of patients in each treatment group being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side effects, their overall incidence being similar in both treatment groups. However, diarrhea occurred more than twice as often in the amoxicillin group than the erythromycin group. In each group, the number of patients failing to complete treatment was similar; the main reasons cited for discontinuation were gastrointestinal symptoms. The results indicate that both erythromycin ethylsuccinate and clavulanate-potentiated amoxicillin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.

Acute Disease↗

[Antibiotic sensitivity of Campylobacter jejuni and Campylobacter coli strains with special reference to sensitivity to erythromycin and neomycin].

166 strains of C. jejuni and 46 strains of C. coli were typed against 14 antibiotics using the agar diffusion test. All strains were resistant against Penicillin G, Oxacillin and Rifampicin. Susceptibility were found against Chloramphenicol, Erythromycin, Neomycin, Oxytetracyclin, Streptomycin and Gentamycin. The minimal inhibition concentration was performed for Erythromycin and Neomycin. All strains tested were inhibited by less than or equal to 2 micrograms/ml Neomycin, one strain was resistant against 4 micrograms/ml Erythromycin.

Campylobacter↗

Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro. 1. Uptake of 3H-macrolides by human macrophages.

The degree of penetration of roxithromycin in human macrophages was evaluated and compared with that of erythromycin. The results indicated that both macrolides at concentrations of 2, 10 and 20 micrograms/ml were concentrated by macrophages, even if roxithromycin was consistently and significantly more accumulated than erythromycin. Comparison of the degree of penetration of the two drugs into dead, resident and stimulated phagocytes indicated that the process of transfer through the macrophage wall was of an active nature, related to the metabolic state of the cells. Analysis of the binding of the two macrolides to intracellular proteins showed that more binding sites were available for erythromycin than for roxithromycin.

Analysis of Variance↗

[Comparison of the in vitro post-antibiotic effect of C14 macrolides (erythromycin and roxithromycin) and C16 macrolides (josamycin and spiramycin) against Staphylococcus aureus].

In vitro post-antibiotic effect (PAE) induced by erythromycin, roxithromycin, josamycin and spiramycin has been compared on Staphylococcus aureus. Three MLSB sensitive and three MLSB inducible resistant S. aureus strains have been used. delta t was the time required for culture to increase by 1 log10 after drug removal in comparison with controls. For erythromycin and roxithromycin delta t ranged from 6 minutes at 1 x MIC to 48 minutes at 4 x MIC (average of the six strains at 4 x MIC: 33 minutes). For josamycin and spiramycin, delta t ranged from 36 at 1/2 x MIC to 138 minutes at 4 x MIC (average at 4 x MIC: 101 minutes). No difference was observed between MLSB sensitive and MLSB inducible resistant S. aureus strains. In our experimental conditions, PAEs observed with josamycin and spiramycin (16-membered-ring macrolides) were 2.5 to 3 times longer than those observed with erythromycin and roxithromycin (14-membered-ring macrolides). These results added to biological differences previously observed between 14-membered-ring and 16-membered-ring macrolides.

Erythromycin↗

[Comparative in vitro bacteriostatic and bactericidal effect of 5 macrolides: roxithromycin, erythromycin, oleandomycin, josamycin and spiramycin against 284 hospital bacterial strains].

The bacteriostatic and bactericidal activities of five macrolides (roxithromycin, erythromycin, troleandomycin, josamycin and spiramycin) were tested against 284 bacterial strains belonging to various species of Gram positive (staphylococci, streptococci, pneumococci, Listeria sp, Corynebacterium sp, Bacillus sp) and Gram negative bacteria (Neisseria sp, H. influenzae, P. multocida). The activity of these compounds on the whole strains showed near results: 71.8% of susceptible strains to erythromycin and spiramycin, 70% to josamycin, 67.6% to roxithromycin, 65.5% to troleandomycin. Resisting strains were MLSB resistant cocci Gram positive, H. influenzae and P. multocida strains. Species usually less studied (nongroupable streptococci, Corynebacterium sp, Bacillus sp) were very susceptible to macrolides with MICS equal or inferior to 1 mg/l for the two last genus. A bactericidal effect was observed for 38.8% of 72 tested strains (erythromycin), 36.1% (josamycin), 34.7% (spiramycin), 31.9% (roxithromycin), 20.8% (troleandomycin). Among various tested species, this bactericidal effect concerned especially group A streptococci, N. meningitidis and Corynebacterium (except D2 and JK species).

Cross Infection↗

[Pharmacodynamics of erythromycin lactobionate during tonsillectomy in children].

In 22 children serum levels and concentration of erythromycin in the tonsil tissue after intravenous injection were measured. The concentration of erythromycin in the tonsils one hour after injection was four times the serum level. Two hours after injection the ratio was reduced significantly to 1.2. From the results it is concluded that perioperative antibiotic therapy with erythromycin has pharmacodynamic advantages.

Child↗