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PubMed2005

Utilisation of macrolides and the development of Streptococcus pyogenes resistance to erythromycin.

OBJECTIVES: The aim of the study was to evaluate the relationship between the development of the resistance of Streptococcus pyogenes strains to erythromycin and the utilisation of macrolides in the Olomouc region, Czech Republic. METHOD: During the period 1997-2001, data for utilisation of macrolides was obtained from the database of the regional General Health Insurance Company and expressed indefined daily doses per 1,000 patients per day. S. pyogenes strains were isolated from community patients suffering from acute bacterial tonsillitis. Their susceptibility to antibiotics was assessed by the disk diffusion method. RESULTS: Utilisation of macrolides increased by 13% in the period 1997-2001; their utilisation represented 11.40% of total antibiotic prescription in 1997 and 15.48% in 2001. Occurrence of erythromycin-resistant S. pyogenes strains increased significantly from 14% in 1997 to 32% in the year 2001 (P < 0.01). In 2000, macrolides consumption decreased non-significantly, but with no concomitant decrease in erythromycin-resistant S. pyogenes strains occurrence. Absolute susceptibility of S. pyogenes, the most important bacterial pathogen in community-acquired bacterial tonsillitis, to penicillin contrasts with increasing macrolide resistance. CONCLUSIONS: The study documents the influence of increased utilisation of macrolides on bacterial resistance. Penicillin should be a first-choice antibiotic in acute bacterial tornsillitis; macrolides should only be reserved for patients allergic to penicillins.

Anti-Bacterial Agents↗
PubMed1981

Successful treatment of Legionella micdadei (Pittsburgh pneumonia agent) pneumonia with erythromycin.

Optimal treatment of Legionella micdadei pneumonia has not been established, although in vitro studies have shown the pathogen to be sensitive to erythromycin. At our institution, L. micdadei pneumonia was diagnosed in six patients over a one and one-half year period. All patients were immunocompromised and had a typical clinical syndrome; in four of six, diagnosis was made by isolation of the pathogen. All patients received erythromycin (2 to 4 g daily) for 12 to 27 days, and five of six recovered completely. One patient improved initially but died four weeks later from Serratia marcescens pneumonia and septicemia. Although L. micdadei may cause life-threatening pneumonia in immunocompromised hosts, prompt diagnosis and institution of erythromycin therapy can result in a favorable outcome.

Adult↗
PubMed1991

A randomized placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group.

Ureaplasma urealyticum has been associated with low birth weight and histologic chorioamnionitis and it is a frequent isolate from the chorioamnion of patients who are delivered prematurely. In prior clinical trials using antibiotics active against U. urealyticum, antibiotic treatment was associated with reduced prematurity and increased mean birth weight. In this multicenter, randomized, double-blind clinical trial, pregnant women with U. urealyticum were treated with 333 mg of erythromycin base or placebo three times daily, starting between 26 and 30 weeks' gestation and continuing through 35 completed weeks of pregnancy. Women with urinary tract infection or Neisseria gonorrhoeae infection were excluded from the trial, and women with Chlamydia trachomatis or group B streptococci were excluded from these analyses. Erythromycin did not eliminate U. urealyticum from the lower genital tract. There were no significant differences between erythromycin- and placebo-treated women in infant birth weight or gestational age at delivery, in frequency of premature rupture of membranes, or in neonatal outcome.

Adult↗
PubMed1981

Competition between erythromycin and virginiamycin for in vitro binding to the large ribosomal subunit.

When the S component of virginiamycin binds in vitro to the 50 S ribosomal subunit, a change of fluorescence intensity proportional to the amount of complex formed occurs. Erythromycin competes with virginiamycin S for attachment to ribosomes, and removes previously bound virginiamycin S from its target, as revealed by spectrofluorimetric analysis. The 50 S subunits which are incubated with the M component of virginiamycin (50 S*) have an increased affinity for virginiamycin S (the association constants of virginiamycin S with ribosomes are 2.5 x 10(6) M-1 in the absence of virginiamycin M, and 15 x 10(6) M-1 in its presence). Erythromycin does not compete with virginiamycin S for attachment to 50 S* subunits nor is it able to remove virginiamycin S previously bound to the 50 S* subunit. Thus, virginiamycin M produces a change in ribosomes, which results in a tighter complex virginiamycin S-50 S* subunit. Such change does not require the presence of virginiamycin M, however, as shown by the observation that ribosomes to which labeled virginiamycin M is transiently linked bind virginiamycin S in a form that cannot be removed by erythromycin.

Binding Sites↗
PubMed1988

Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle.

Erythromycin, one of the macrolide antibiotics, and its derivatives had been found to mimic actions of exogenous motilin, a gastrointestinal peptide hormone. We found that some of the macrolide compounds inhibited the specific binding of 125I-motilin to rabbit duodenum muscle at 15 C in a dose-dependent fashion. The inhibitory activity of several macrolides examined did not relate to their antibacterial activity but to their motilin-like activity. A 50% inhibition by EM536, a non-antibacterial erythromycin derivative with the highest motilin-like activity, was obtained at 3-40 nM and little higher than that of non-radioactive motilin (5-6 nM) under the present conditions. The results suggest that erythromycin and its derivatives mimic physiological actions of motilin by acting as agonists for a motilin receptor.

Animals↗
PubMed1982

Erythromycin binding to human serum.

Erythromycin binding to human serum was measured under conditions of binding equilibrium. The binding is sensitive to pH changes, decreasing at acid pH. Over a great range of serum dilution, the bound fraction is semilogarithmically related to serum concentration. Binding is shown to be completely reversible. With increasing erythromycin concentration a specific part of binding is saturable and specifically displaceable by erythromycin is specifically bound to a single class of noninteracting binding sites with an apparent dissociation constant Kd = 5.9 microM (38 degrees C). The kinetic and thermodynamic parameters at 25 degrees are: Kd = 8.4 microM, delta H degrees = +4.4 X 10(3) cal per mole, delta G degrees = 6.9 X 10(3) cal per mole, delta S degrees = +38 e.u.

Blood Proteins↗
PubMed1986

In vitro [3H]-erythromycin binding to Staphylococcus aureus.

Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organelles where erythromycin exerts its action. This good agreement shows that the dissociation constant of erythromycin determined with intact bacteria is a good reflect of specific bacterial receptors of macrolides, i.e. ribosomes. In addition, mechanism of uptake of the antibiotic by Staphylococcus aureus was investigated. Passive diffusion process was shown to be mainly responsible for this phenomenon.

Erythromycin↗
PubMed1990

A repeated decapeptide motif in the C-terminal domain of the ribosomal RNA methyltransferase from the erythromycin producer Saccharopolyspora erythraea.

Re-analysis of the primary structure of the ribosomal RNA N-methyltransferase that confers self-resistance on the erythromycin-producing bacterium Saccharopolyspora erythraea has confirmed the presence of a C-terminal domain containing extensive repeat sequences. Nine tandem repeats can be discerned, with a decapeptide consensus sequence GGRx(H/R)GDRRT, although no single residue is wholly invariant. This highly polar, potentially flexible domain, which is predicted to adopt either a random coil or a structure with beta turns, has a counterpart in the erythromycin methyltransferase of an erythromycin-producing species of Arthrobacter. It also significantly resembles a portion of the C-terminal region of the eukaryotic protein nucleolin, which is unusually rich in dimethylarginine and glycine, and which is also predicted to behave as a random coil in solution. This resemblance, despite the very different roles of these proteins in ribosome biogenesis, strengthens the idea that in both rRNA methyltransferases and nucleolin these C-terminal sequences might contribute to rRNA binding.

Amino Acid Sequence↗
PubMed1990

Development of motilin receptors and of motilin- and erythromycin-induced contractility in rabbits.

The development of the motilin receptor was studied through contraction and binding studies of groups of three rabbits aged between 2 and 289 days. The contractility of small intestinal smooth muscle strips was measured isotonically. The aborally decreasing gradient in response to motilin, known to exist in adult rabbits, was already present at day 8 (maximum contractile responses expressed as a percent of the maximal response to acetylcholine were 77% +/- 9%, 34% +/- 10%, and 25% +/- 8% for duodenal, jejunal, and ileal strips, respectively). Throughout the observation period, the doses of motilin and its agonist erythromycin that were required to induce 50% of the response remained constant and were not significantly different from doses required for adults (their negative logarithms were 8.55 +/- 0.35 and 5.70 +/- 0.25, respectively). The correlation between the maximum contractile response toward motilin and erythromycin was almost perfect (r2 = 0.82). Binding studies with iodinated norleucine13-porcine motilin were performed using antral smooth muscle tissue homogenates. The maximum number of binding sites increased rapidly after 8 days (3.3 +/- 0.4 fmol/mg protein) and reached a peak at 21 days (20.7 +/- 1.4 fmol/mg protein), but decreased at that point toward the adult value (40 days, 10.6 +/- 1.3; 289 days, 9.8 +/- 1.1 fmol/mg protein). The dissociation constant, however, remained unchanged. The peak value of receptor density occurred at about the time that the rate of increase of the length of the intestine and of the weight of the antrum were at maximum levels (at 18 and 27 days, respectively). Motilin receptors are expressed early postnatally, and the regional gradient in sensitivity towards motilin is also established soon after birth. If applicable to humans, an early response to erythromycin may have therapeutic value.

Acetylcholine↗
PubMed1984

Semi-automated preparation of a 11C-labelled antibiotic--[N-methyl-11C]erythromycin A lactobionate.

A fast semi-automated method is described for labeling the antibiotic, erythromycin A (1), with the short-lived positron-emitting radionuclide, 11C (t 1/2 = 20.4 min), in order to permit the non-invasive study of its tissue uptake in vivo. Labelling was achieved by the fast reductive methylation of N-demethylerythromycin A (2) with [11C]formaldehyde, itself prepared from cyclotron-produced [11C]-carbon dioxide. Rapid chemical and radiochemical purification of the [N-methyl-11C]erythromycin A (3) were achieved by HPLC and verified by TLC with autoradiography. The purified material was formulated for human i.v. injection as a sterile apyrogenic solution of the lactobionate salt. The preparation takes 42 min from the end of radionuclide production and from [11C]carbon dioxide produces [N-methyl-C11]erythromycin A lactobionate in 1-12% radiochemical yield, corrected for radioactive decay.

Carbon Radioisotopes↗
PubMed1985

Ribosomal RNA methylation in Staphylococcus aureus and Escherichia coli: effect of the "MLS" (erythromycin resistance) methylase.

Classical acquired resistance to erythromycin in Staphylococcus aureus ("MLS," or macrolide-lincosamide-streptogramin, resistance) was shown by Weisblum and colleagues to be a direct consequence of the conversion of one or more adenosine residues of 23S rRNA, within the subsequence(s) GA3G, to N6-dimethyladenosine (m62A). The methylation reaction is effected by a class of methylase, whose genes are typically plasmid- or transposon-associated, and whose synthesis is inducible by erythromycin. Using a recently obtained clinical MLS isolate of S. aureus, we have further defined the methylation locus as YGG X m62A X AAGAC; and have shown that this subsequence occurs once in the 23S RNA and that it is essentially completely methylated in all copies of 23S RNA that accumulate in induced cultures. Similar findings were obtained with laboratory S. aureus strains containing two well-characterized evolutionary variants (ermB, ermC) of MLS methylase genes. Analyses of a strain of E. coli containing the ermC gene indicated that the specificity of the methylase gene was unchanged, but that its expression was muted. Even after prolonged periods of induction, the strain manifested only partial resistance to erythromycin, and only about one-third of the copies of the MLS subsequence were methylated in such "induced" cultures. Since the E. coli 23S RNA sequence is known in its entirety, localization of the MLS subsequence is in this case unambiguous; as inferred by homology arguments applied earlier to the S. aureus data, the subsequence is in a highly conserved region of 23S RNA considered to contribute to the peptidyl transferase center of the ribosome.

Base Sequence↗
PubMed1988

Identification and cloning of a plasmid-encoded erythromycin resistance determinant from Lactobacillus reuteri.

Plasmid analysis, plasmid curing, cloning, and hybridization experiments were used to study four Lactobacillus reuteri strains showing high resistance to erythromycin. Plasmid curing with acriflavine resulted in a loss of erythromycin resistance in a frequency of 1-10%. For three of the strains this was accompanied by a loss of a 6.9-MDa plasmid, which was shown to be identical for the different strains and designated pLUL631. The erythromycin (erm) gene was located on a 5.5-MDa plasmid in the fourth strain. A restriction map of pLUL631 was constructed and the location of the erm gene on the plasmid was identified by cloning in Escherichia coli. By using a Streptococcus lactis-E. coli shuttle vector, the erm gene was also transformed to S. lactis and expressed. The erm gene from L. reuteri was shown to be related to the erm gene from pIP501 (Streptococcus agalactiae) by DNA-DNA hybridization.

Cloning, Molecular↗
PubMed1990

Topical erythromycin and zinc therapy for acne.

A double-blind, 12-week study was undertaken to determine the safety and efficacy of a formulation of 4% erythromycin plus 1.2% zinc acetate compared with its vehicle. The study was continued for 40 weeks after the 12-week double-blind phase by switching vehicle-treated patients to active treatment and continuing to give patients treated with active drug the same treatment. Seventy-three female patients started the study; 39 completed 1 full year of study. In the first 12 weeks statistically significant differences were noted in the efficacy of the erythromycin-zinc compared with vehicle for acne severity grades (global assessment) and for papule, pustule, and comedo counts. After crossover, the vehicle-treated group receiving active therapy duplicated the improvement of the group initially treated with erythromycin-zinc. No clinical problems with superinfection or secondary infection occurred during 1 year of treatment in 39 patients.

Acne Vulgaris↗
PubMed1990

A bacteriologically controlled, randomized study comparing the efficacy of 2% mupirocin ointment (Bactroban) with oral erythromycin in the treatment of patients with impetigo.

Sixty patients participated in a bacteriologically controlled, randomized, parallel group comparison of 2% mupirocin ointment (Bactroban) and oral erythromycin ethylsuccinate for the treatment of impetigo. The trial included clinical and bacteriologic evidence and safety assessments. The Investigator's Global Evaluation, which compared the overall efficacy and safety of the trial drugs, demonstrated a more favorable performance for the mupirocin regimen. This difference was statistically and clinically significant. There were no significant differences between the trial regimens for any of the other efficacy variables examined. The bacteriologic success rate was 100% for both treatment groups. There was a clinically significant difference in adverse experience rates between treatment groups, with four (13%) of the erythromycin-treated patients reporting six adverse experiences versus none of the mupirocin-treated patients. The results of the trial indicate that 2% mupirocin ointment is as safe and effective as oral erythromycin ethylsuccinate in the treatment of patients with impetigo.

Erythromycin↗
PubMed1992

A therapeutic trial of the use of penicillin V or erythromycin with or without rifampin in the treatment of psoriasis.

BACKGROUND: After the publication of an uncontrolled trial of nine patients with streptococcus-associated psoriasis who appeared to benefit from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days, we wished to confirm or refute the validity of this observation. OBJECTIVE: Our purpose was to confirm the effectiveness of antibiotics in the treatment of streptococcus-associated psoriasis. METHODS: Twenty patients were placed randomly into two groups. One group was given penicillin or erythromycin for 14 days with a placebo added during the last 5 of the 14 days. The other group received the same medication with the addition of rifampin in the last 5 days. RESULTS: Although all the patients studied met the criteria of the reported preliminary study, we were unable to detect any evidence of improvement in their psoriasis. CONCLUSION: There was no apparent benefit for patients with streptococcus-associated psoriasis from a course of oral penicillin or erythromycin with the addition of rifampin in the last 5 days in a 14-day trial.

Adolescent↗
PubMed1987

Elongating ribosomes in vivo are refractory to erythromycin.

We have studied the kinetics of erythromycin inhibition of translation in growing bacteria. In order to simplify the interpretation of our data, we have used a mutant (envA), known to have an increased permeability to several antibiotics, including erythromycin. The data clearly show that an initial stage of translation is sensitive to erythromycin, but that the elongating ribosome is insensitive to the antibiotic.

Enzyme Induction↗
PubMed1994

Effect of erythromycin on different parts of the rabbit intestine: comparison with motilin.

1. The effect of erythromycin on the rabbit intestinal smooth muscle was investigated and was compared to that of motilin. 2. Whole isolated segments from the duodenum, jejunum, ileum and ascending colon, as well as strips from the circular and longitudinal smooth muscle of the ascending colon were used. 3. Erythromycin was found to possess a concentration-dependent contractile effect on the above intestinal parts but in different degree of intensity. 4. The order of the sensitivity of the intestinal parts to erythromycin was duodenum = jejunum > ascending colon > ileum. 5. The circular smooth muscle of the ascending colon was found to be more sensitive than the longitudinal smooth muscle. 6. A similar contractile effect, but at lower concentrations, and the same regional specificity were observed with motilin.

Animals↗
PubMed1989

Identification of a gene required for the terminal step in erythromycin A biosynthesis in Saccharopolyspora erythraea (Streptomyces erythreus).

We have identified a transcription unit in the ermE region of the chromosome of the erythromycin (Er)-producing bacterium Saccharopolyspora erythraea (Streptomyces erythreus) that is briefly switched on at about the time that macrolide production commences. Disruption of the transcription unit, herein designated eryG, by insertion of an integrational plasmid vector, caused a block at the terminal step in the biosynthesis of erythromycin, the conversion of erythromycin C to A by O-methylation.

Blotting, Northern↗