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PubMed1986

Comparison of the side effects and gastrointestinal motility observed after administration of erythromycin and josamycin to dogs.

The effects of intravenous erythromycin and josamycin on gastrointestinal motility in dogs have been compared. Erythromycin interrupted the basal motility pattern in the fasted state and induced irregular bursts of spikes in both the fasted and fed states. Emesis occurred in all the dogs in the fasted state experiments and in four out of six dogs in the fed state experiments. Josamycin did not disturb gastrointestinal motility and no dog showed signs of discomfort. The difference in the chemical structure of erythromycin and josamycin is the main reason for their differential effect on the gastrointestinal tract.

Animals↗
PubMed1987

Influence of amoxycillin, erythromycin and roxithromycin on colonization resistance and on appearance of secondary colonization in healthy volunteers.

We investigated the influence of oral administration of amoxycillin, erythromycin and roxithromycin on colonization resistance in healthy volunteers. Antibiotics were administered in a randomized cross-over design. No effect on the colonization resistance of the oropharynx could be demonstrated. Amoxycillin decreased the colonization resistance of the bowel against Enterobacteriaceae and yeasts, whose median concentration in faeces increased 100-fold and 30-fold respectively. Roxithromycin and erythromycin decreased the concentration of Enterobacteriaceae in faeces. Secondary colonization with Enterobacteriaceae was detected as often following roxithromycin as following amoxycillin, but the level of colonization with these bacteria was much higher following amoxycillin. Following roxithromycin and erythromycin the level of secondary colonization did not exceed the original concentration of Enterobacteriaceae, showing that these antibiotics did not decrease the colonization resistance against Enterobacteriaceae. The appearance of secondary colonization in faeces at levels equal to or lower than the concentration of Enterobacteriaceae before administration of antibiotics, should not be regarded as proof of disturbance of colonization resistance.

Adult↗
PubMed1987

Cellular uptake and subcellular distribution of roxithromycin and erythromycin in phagocytic cells.

The intracellular accumulation and subcellular distribution of 14C-labelled roxithromycin and erythromycin has been studied in macrophages and polymorphonuclear neutrophils of both human and animal origin. Roxithromycin was consistently and significantly more accumulated than erythromycin, reaching intracellular/extracellular concentration ratios between 14 (in polymorphonuclear neutrophils) and 190 (in alveolar macrophages from smokers). Uptake was reversible, insensitive to anaerobiosis and to the presence of an aminoglycoside, but inhibited by acid pH. Upon subcellular fractionation by isopycnic centrifugation in sucrose gradients., half the roxithromycin or erythromycin recovered in cell homogenates was found associated with the lysosomes in macrophages, and about one third with azurophil granules in polymorphonuclear leucocytes. Inasmuch as cellular uptake is a necessary, albeit not sufficient, condition for antimicrobials to kill or inhibit the growth of intracellular bacteria the properties of roxithromycin may give it a distinct advantage over other antimicrobial agents.

Animals↗
PubMed1987

An in-vitro comparison of the intraphagocytic bioactivity of erythromycin and roxithromycin.

The binding to human polymorphonuclear leucocytes and the intracellular bioactivity of the macrolide antibiotics erythromycin and roxithromycin on Legionella micdadei, Listeria monocytogenes and Staphylococcus aureus were investigated in vitro by the combination of a fluorochrome microassay and a radioassay. Polymorphs with intact or absent membrane-associated oxidative metabolism were used to investigate the interactions which may occur between the intrinsic oxygen-dependent antimicrobial systems of human polymorphs and the test antibiotics, in the elimination of intracellular microbial pathogens. Elimination of O2-dependent antimicrobial systems with retention of phagocytic activity was achieved by using polymorphs from children with chronic granulomatous disease NaF-pulsed normal polymorphs. Both antimicrobial agents were actively concentrated by polymorphs. Erythromycin was concentrated ten-fold and roxithromycin approximately thirty-fold above extra cellular levels. Both agents possessed intracellular bacteriostatic activity for all three test microbial pathogens. Depletion of polymorph O2-dependent intrinsic antimicrobial systems interfered with the intracellular bioactivity of both antibiotics. This emphasizes the importance of interactions between cell-associated antibiotics and phagocyte antimicrobial systems in the elimination of intracellular microbial pathogens. Like erythromycin, roxithromycin is concentrated by human phagocytes and is bioactive intracellularly.

Bacteria↗
PubMed1988

Uptake of erythromycin by McCoy and HEp2 cells: its dependence on cellular pH gradients.

The accumulation of erythromycin, a weak lipophilic base, was studied in two mammalian cell lines. Uptake was similar in both cell types, being highly pH dependent and not saturated even at external concentrations of 1000 mg/l. At pH 6.7 the ratio of cellular:extracellular erythromycin concentrations (C/E) was only 2.0, whereas at pH 7.5 it was as high as 7.0. Carbonylcyanide-m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation which was used to collapse cellular pH gradients, caused a 50% reduction in C/E ratio within five minutes when the external pH was greater than 6.9 but had no effect at or below pH 6.7. These results suggest that ion-trapping plays a major role in the accumulation of erythromycin by these cells.

Cell Line↗
PubMed1988

Comparison of spiramycin with erythromycin for lower respiratory tract infections.

The efficacy and safety of 2 g oral spiramycin daily were compared with those of 2 g of oral erythromycin daily in a multicentre open prospective trial, involving 198 patients, with a mean age of 61.75 years, with a clinical and radiological diagnosis of acute lower respiratory tract infection. The diagnoses were: acute bronchitis (96), acute superinfection of chronic bronchitis (60) and pneumonia (42). The patients were assessed before therapy and after three and ten days of therapy. Seventy-four (76.3%) of the patients were cured in the spiramycin group and 64 (63.4%) were cured in the erythromycin group (P less than 0.05). Significantly more patients complained of side effects in the erythromycin group (41.4%) than in the spiramycin group (11.8%) P less than 0.001.

Acute Disease↗
PubMed1990

A comparative study of spectinomycin and erythromycin in the treatment of chancroid.

In a randomized, controlled study, 55 patients with genital ulcerations, culture-positive for Haemophilus ducreyi, were treated with a single intramuscular injection of 2 g spectinomycin. A further 61 patients were treated with a five-day oral course of erythromycin base (500 mg, three times daily). Treatment failure occurred in seven patients who received spectinomycin (13%), whilst no treatment failures were recorded among patients who received erythromycin. This difference in efficacy was statistically significant. In contrast, spectinomycin proved significantly more effective than erythromycin in the treatment of the lymphadenopathy associated with primary chancroid lesions.

Administration, Oral↗
PubMed1990

Predominance of resistant oral streptococci in saliva and the effect of a single course of josamycin or erythromycin.

We have investigated the influence of the macrolides erythromycin and josamycin on the selection of resistant oral streptococci by sampling saliva of volunteers before and after oral administration of 1.5 g of either agent followed by a further 0.5 g of the same drug after 6 h, as in routine prophylaxis for oral or dental procedures. The small proportion of resistant organisms present before antibiotic administration increased substantially 48 h after the macrolides were given. After antibiotic administration mean counts of oral streptococci resistant to 1, 4 and 64 mg/l erythromycin were 23%, 17% and 6%, respectively, of the total numbers of streptococci isolated; after josamycin, the values were 13%, 6% and 4% respectively. The proportion of resistant streptococci then declined gradually but remained above pre-antibiotic levels three months later. Streptococci isolated on media containing 64 mg/l of macrolides were mainly Streptococcus sanguis and S. mitis with one isolate of S. salivarius; the majority were resistant to 256 mg/l erythromycin, josamycin, all other macrolides tested and clindamycin. Amoxycillin and pristinamycin were the only compounds tested that were inhibitory to these organisms at therapeutically attainable concentrations.

Adolescent↗
PubMed1996

Mobile rRNA methylase genes coding for erythromycin resistance in Actinobacillus actinomycetemcomitans.

We found that 17 (68%) of 25 Actinobacillus actinomycetemcomitans isolated from periodontally diseased sites had MICs of erythromycin > or = 8 mg/L. The isolates were hybridized with five rRNA methylase genes and gene mobility was determined. Twenty-four (96%) of 25 isolates hybridized with one or more rRNA methylase genes. Representative isolates were able to transfer erythromycin resistance to Haemophilus influenzae and Enterococcus faecalis recipients. The transconjugants were shown to carry rRNA methylase genes by DNA probe hybridization and had MICs of erythromycin 32 to 256 mg/L.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

Comparative in-vitro activity of levofloxacin, other fluoroquinolones, doxycycline and erythromycin against Ureaplasma urealyticum and Mycoplasma hominis.

The susceptibility of 56 Ureaplasma urealyticum and 57 Mycoplasma hominis strains to levofloxacin, ofloxacin, ciprofloxacin, fleroxacin, doxycycline and erythromycin was determined by an agar dilution method. The reference strain used was M. hominis PG 21. Agar plates containing serial dilutions of antibiotics (range 0.03-16 mg/L), and control plates (without antibiotics) were inoculated with bacteria suspended in modified Shepard's broth using a multipoint inoculator. Levofloxacin showed greater activity against all U. urealyticum and M. hominis strains compared with all other antibiotics tested. The MIC90 values for U. urealyticum were as follows: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 1 mg/L; erythromycin, 8 mg/L. The MIC90s for M. hominis were: levofloxacin, 1 mg/L; ofloxacin, 2 mg/L; ciprofloxacin, 4 mg/L; fleroxacin, 4 mg/L; doxycycline, 4 mg/L; erythromycin, > or = 16 mg/L. In conclusion, the results of this study suggest that levofloxacin may be useful in the treatment of mycoplasma genital infections.

Anti-Bacterial Agents↗
PubMed2002

Differences in the susceptibility of Streptococcus pyogenes to rokitamycin and erythromycin A revealed by morphostructural atomic force microscopy.

The aim of this study was to use atomic force microscopy (AFM), an innovative type of microscopy, to investigate the different behaviours of erythromycin A (a 14-membered ring) and rokitamycin (a 16-membered ring) in disrupting the morphology of Streptococcus pyogenes with the M phenotype. AFM scanning and sensing of the topography of a sample makes it possible to obtain simultaneous high-resolution digital measurements of the x, y and z coordinates at any point on the bacteria surface. The images obtained before and 2, 4 and 6 h after incubation with erythromycin A (32 mg/L) and rokitamycin (2 mg/L) clearly show that not even high concentrations of erythromycin A interfere with the M phenotype of S. pyogenes, whereas rokitamycin has a progressive action that leads to the formation of abnormally large cells, the loosening of chain structure and the formation of clusters.

Drug Resistance, Bacterial↗
PubMed2003

Significant increase in the prevalence of erythromycin-resistant, clindamycin- and miocamycin-susceptible (M phenotype) Streptococcus pyogenes in Spain.

In 1998 we conducted a multicentre study in Spain on the susceptibility of Streptococcus pyogenes isolates to different 14-, 15- and 16-membered macrolides and clindamycin, in which the number of strains examined was proportional to the number of inhabitants in each geographical area. The aim of the present work was to re-examine the antimicrobial susceptibility of S. pyogenes in 2001, using the same methodology and centres as in 1998, to determine the different susceptibility phenotypes to macrolides-lincosamides, and to compare the results from the 2 years by statistical tests. A total of 529 unique isolates of S. pyogenes, collected in 21 laboratories, were studied. Throat swabs provided 417 isolates (78.8%), and the remaining 112 were from other sources. Four hundred and thirty-five (82.2%) were isolated from children and 94 (17.8%) from adults. One hundred and fifty-seven (29.7%) of the isolates were resistant to erythromycin and azithromycin, whereas resistance to miocamycin, a 16-membered macrolide, was 1.5%. The prevalence of resistance to clindamycin was 1.3%. The majority (98.7%) of the 157 erythromycin-resistant strains presented the M phenotype. When we compared the results obtained in 1998 and 2001, we observed a statistically significant increase in resistance to erythromycin and azithromycin (P = 0.02, chi(2) test), but not to clindamycin or miocamycin (P = 0.47, chi(2) test with Yates' correction). The significant increase in the prevalence of resistance to some macrolides of S. pyogenes in Spain underscores the need for continuous surveillance of antimicrobial resistance in this species.

Anti-Bacterial Agents↗
PubMed2004

Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis.

OBJECTIVES: Antimicrobial agents are important risk factors for infusion phlebitis, but the risk varies between different antibiotics. Erythromycin and dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic effects on cultured endothelial cells. The pathogenesis of infusion phlebitis is unclear, but chemical toxicity is thought to lead to inflammation and subsequent thrombosis. In the present study, endothelial cells were exposed to antibiotics at the range of concentrations used for intravenous administration, followed by analysis of pro-inflammatory and pro-coagulant surface molecules. METHODS: Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing. After 5 or 24 h additional incubation, cells were analysed for E-selectin (CD62E), tissue factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow cytometry. RESULTS: Despite constitutive expression of ICAM-1 (34%) in HUVEC, 6250 mg/L of dicloxacillin or erythromycin significantly increased the number of cells with ICAM-1 expression by 37% and 30%, respectively. In contrast, cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background levels. A similar pattern was seen with the endothelial cell line EaHy926. The E-selectin and TF density were not affected by the antibiotics examined. CONCLUSIONS: The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1. This is a novel finding in the pathogenesis of infusion phlebitis.

Anti-Bacterial Agents↗
PubMed2005

Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin, moxifloxacin and erythromycin against intracellular Legionella pneumophila and Legionella micdadei in human monocytes.

OBJECTIVES: The antibacterial activity of a new fluoroquinolone, gemifloxacin, was tested against intracellular Legionella pneumophila and Legionella micdadei and was compared with the activities of levofloxacin, gatifloxacin, moxifloxacin and erythromycin. METHODS: For intracellular assays, bacteria were used to infect human monocyte-derived macrophages prepared from heparinized blood of healthy volunteers. Antibiotics were added following phagocytosis. Numbers of viable bacteria were determined at 0, 24, 48, 72 and 96 h. RESULTS: The intracellular antibacterial activity of gemifloxacin was concentration- and time-dependent. All of the quinolones had similar activities against L. pneumophila and L. micdadei at 10 x MIC, but there were minor differences: at 24 h moxifloxacin was significantly more active than the other quinolones against L. pneumophila, while gemifloxacin was more active against L. micdadei (P < 0.01). All of the quinolones were markedly more active than erythromycin (P < 0.01). The antibacterial effect of gemifloxacin against L. pneumophila following drug removal at 24 h persisted for 72 h at 20 x MIC but not at 10 x MIC, while for L. micdadei the antibacterial effect persisted for 24 h at 10 x MIC. CONCLUSIONS: All of the quinolones had similar activities against intracellular L. pneumophila and L. micdadei and were markedly more effective than erythromycin.

Anti-Bacterial Agents↗
PubMed2006

Emergence of a 23S rRNA mutation in Mycoplasma hominis associated with a loss of the intrinsic resistance to erythromycin and azithromycin.

OBJECTIVES: Mycoplasma hominis is intrinsically resistant to 14- and 15-membered macrolides and to the ketolide telithromycin but is susceptible to josamycin, a 16-membered macrolide, and lincosamides. The aim of our study was to investigate the in vitro development of macrolide resistance in M. hominis and to study the impact of ribosomal mutations on MICs of various macrolides and related antibiotics. METHODS: Selection of macrolide-resistant mutants was performed by serial passages of M. hominis PG21 in broth medium containing subinhibitory concentrations of clindamycin, pristinamycin, quinupristin/dalfopristin and telithromycin. Stepwise selection of josamycin-resistant mutants was performed onto agar medium containing increasing inhibitory concentrations of josamycin. Resistant mutants were characterized by PCR amplification and DNA sequencing of 23S rRNA, L4 and L22 ribosomal protein genes. RESULTS: Various mutations in domain II or V of 23S rRNA were selected in the presence of each selector antibiotic and were associated with several resistance phenotypes. Josamycin was the sole antibiotic that selected for single amino acid changes in ribosomal proteins L4 and L22. Unexpectedly, the C2611U transition selected in the presence of clindamycin and the quinupristin/dalfopristin combination was associated with decreased MICs of erythromycin, azithromycin and telithromycin, leading to a loss of the intrinsic resistance of M. hominis to erythromycin and azithromycin. CONCLUSIONS: Ribosomal mutations were associated with resistance to macrolides and related antibiotics in M. hominis. Some mutants showed a loss of the intrinsic resistance to erythromycin and azithromycin.

Anti-Bacterial Agents↗
PubMed1986

Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II.

We have determined the nucleotide sequence of the ereB gene of plasmid pIP1527 which confers high-level resistance to erythromycin by inactivation in Escherichia coli. The open reading frame of the ereB gene, 1257-bp, was defined by initiation and termination codons and by cloning in vitro. The corresponding protein has a calculated Mr of 48,118 in close agreement with a previous estimation, 51,000, by electrophoresis of minicell extracts in SDS-polyacrylamide gels. The structure of the modified erythromycin was determined by physico-chemical techniques including mass spectrometry, infrared spectrophotometry and 13C nuclear magnetic resonance. The data obtained indicated that like ereA (Ounissi and Courvalin, 1985) ereB encodes an erythromycin esterase. Comparison of the amino acid sequences of the two isozymes did not reveal any statistically significant homology. Analysis of the nucleotide sequence of the ereB gene suggests that this resistance determinant should be exogenous to E. coli.

Amino Acid Sequence↗
PubMed2001

Gastric feeding with erythromycin is equivalent to transpyloric feeding in the critically ill.

OBJECTIVE: To determine whether adding erythromycin to a gastric feeding regimen could render it as effective in meeting nutritional needs as transpyloric feeding. DESIGN: Randomized, controlled study. SETTING: University hospital medical, surgical, and neurologic care intensive care units. PATIENTS: Critically ill patients, requiring a projected 96 hrs of enteral feeding, who had no specific indication for tube location (gastric or transpyloric). Eighty patients were randomized. INTERVENTIONS: Patients were randomized to gastric feeding with erythromycin (200 mg iv) given every 8 hrs or feeding through a transpylorically placed feeding tube. Goal rate and feeding advancement were determined by protocol. MEASUREMENTS AND MAIN RESULTS: During the 96-hr period, the gastric group received 74% of their goal calories and the transpyloric group received 67%. The only day on which gastric feedings were superior was the first study day, where the gastric group attained 55% of their goal, compared with 44% in the transpyloric group. This 1-day difference was the result of an initial failure of tube placement in some subjects. Exclusion of these patients did not change overall results. Nutritional indexes, length of stay in the intensive care unit, ventilator dependence, and survival were not different between the two groups. CONCLUSIONS: Gastric feeding with erythromycin as a prokinetic is equivalent to transpyloric feeding in meeting the nutritional goals of the critically ill.

Chi-Square Distribution↗
PubMed1992

Effects of erythromycin on gut transit in pseudo-obstruction due to hereditary coproporphyria.

We studied gastrointestinal transit in a 57-year-old man with chronic intestinal pseudo-obstruction along with peripheral and autonomic neuropathy due to hereditary coproporphyria and we evaluated the effects of acute and chronic therapy with erythromycin. Noninvasive scintigraphic studies of regional transit of solid residue through the gut were obtained before treatment, during the acute i.v. administration of 500 mg, every-8-h doses of erythromycin for 24 h and after 15 weeks of oral therapy (500 mg, three times daily). During acute i.v. administration, symptoms and transit measurements dramatically improved; however, all parameters and symptoms returned to pretreatment levels during chronic oral therapy. We conclude that hereditary coproporphyria with associated autonomic neuropathy results in significant delay in small bowel and colonic transit; chronic administration of 500 mg three times a day oral erythromycin was not associated with maintenance of the improvement in regional transit and symptoms observed following acute i.v. administration of the drug at the same dose.

Administration, Oral↗