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PubMed2001

Erythromycin enhances oesophageal motility in patients with gastro-oesophageal reflux.

BACKGROUND: Intravenous (i.v.) erythromycin enhances gastric emptying and oesophageal motility in both healthy and disease situations, acting either as a motilin or acetylcholine agonist. The purpose of the present paper was to investigate any possible effect of i.v. erythromycin on oesophageal motility in patients with gastro-oesophageal reflux (GOR). METHODS: In 15 patients with GOR (proven on 24-h ambulatory oesophageal pH measurement), standard oesophageal manometry was performed after i.v. injection of placebo and 200 mg erythromycin, in a random blind fashion. RESULTS: Erythromycin significantly increased lower oesophageal sphincter (LOS) pressure from 17 +/- 5 to 41 +/- 10 mmHg (P < 0.001), without affecting the postdeglutition relaxation of LOS. Erythromycin also increased the amplitude (from 79 +/- 34 to 97 +/- 40 mmHg; P < 0.001), duration (from 3.4 +/- 0.6 to 3.8 +/- 0.6 s; P = 0.005), velocity (from 3.1 +/- 0.8 to 3.5 +/- 1.15 cm/s; P = 0.0047) and strength (from 149 +/- 84 to 201 +/- 103 mmHg.s; P < 0.001) of peristalsis at 5 cm proximal to the LOS. Similarly, the drug increased the amplitude of peristalsis at 10 and 15 cm proximal to the LOS (from 70 +/- 39 to 77.4 +/- 37 mmHg; P = 0.049 and from 36 +/- 20 to 49 +/- 36 mmHg; P = 0.004, respectively) and the duration of peristalsis at the same levels (from 3.1 +/- 0.6 to 3.3 +/- 0.5 s; P = 0.011, and from 2.7 +/- 0.6 to 3 +/- 0.5 s; P = 0.003, respectively). CONCLUSION: Intravenously administered erythromycin improves impaired oesophageal motility in patients with GOR. This observation might be of clinical use.

Adult↗

PubMed2003

Predominance of two M-types among erythromycin-resistant group A Streptococci from Greek children.

In order to investigate the potential relationship between erythromycin resistance and specific M-serotypes among clinical isolates of Streptococcus pyogenes from children in Greece, we randomly selected a total of 49 erythromycin-resistant (EryR) and 21 erythromycin-susceptible (EryS) isolates from the 1158 S. pyogenes isolates from the two main children's hospitals of Athens during the period October 1997 to October 1998. The isolates were further characterized by M-serotyping, examined for their susceptibility to penicillin, vancomycin and clindamycin, and categorized into resistance phenotypes. A total of 248 (21%) S. pyogenes isolates in the two main children's hospitals of Athens during the study period were resistant to erythromycin. All 49 EryR and 21 EryS isolates were susceptible to penicillin and vancomycin. With respect to erythromycin and clindamycin resistance, phenotypes M and IR MLSB dominated, with 30 and 17 isolates, respectively, two isolates belonged to the CR MLSB phenotype. Among the erythromycin resistant isolates, two M serotypes were dominant: M22 (30%) and M84 (41%). More specifically, M22 and M84 were most prevalent in resistance phenotypes IR MLSB (65%) and M (63%), respectively. In the susceptible group, no isolate belonged to these two M-serotypes, nor was a predominant serotype found. In contrast to susceptible isolates, two distinct M-serotypes were highly represented among EryR S. pyogenes isolates and predominantly associated with two distinct phenotypes.

Anti-Bacterial Agents↗

PubMed1997

The efficacy of prophylactic erythromycin in preventing vertical transmission of Ureaplasma urealyticum.

To determine if prophylactic erythromycin alters the vertical transmission rate of Ureaplasma urealyticum. Randomized prospective study of 51 singleton pregnancies between 22 and 35 weeks' gestation with preterm premature rupture of membranes or preterm labor. Patients received oral erythromycin for 7 days in addition to routine prophylactic intravenous ampicillin or ampicillin alone. Lower genital colonization with U. urealyticum was 33 of 51 (65%). Vertical transmission of U. urealyticum was 25% (3 of 12) in the erythromycin group and 4 of 17 (24%) for the controls. The average interval from randomization to delivery was 303.5 hr in the erythromycin group and 70.9 hr for controls (p = 0.04). Although not statistically significant, histologic chorioamnionitis in patients colonized with Ureaplasma was lower in the erythromycin group (3 of 12, 25%) compared to the controls (10 of 17, 59%). Prophylactic erythromycin does not decrease vertical transmission of Ureaplasma. It may decrease the incidence of histologic chorioamnionitis and increase the latency period.

Administration, Oral↗

PubMed2002

Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh.

BACKGROUND: Resistance to erythromycin has been very uncommon among group A streptococci in the United States. METHODS: As part of a longitudinal study, we obtained surveillance throat cultures twice monthly and with each new respiratory tract illness from children in kindergarten through grade 8 at one school in Pittsburgh. Screening for resistance to erythromycin and clindamycin was initially accomplished with use of the Kirby-Bauer disk-diffusion test. The minimal inhibitory concentration of resistant isolates was determined by the E test. A double disk-diffusion test was used to characterize the resistance phenotype, and the polymerase-chain-reaction assay was used to identify the resistance gene. The molecular relatedness of strains was determined by field-inversion gel electrophoresis. RESULTS: A total of 1794 throat cultures were obtained from 100 children between October 2000 and May 2001, of which 318 cultures (18 percent) from 60 of the children were positive for group A streptococci. Forty-eight percent of these isolates (153 of 318) were resistant to erythromycin. None were resistant to clindamycin. Results of the double disk-diffusion test indicated the presence of the M phenotype of erythromycin resistance. Molecular typing indicated that the outbreak was due to a single strain of group A streptococci. Of 100 randomly selected isolates of group A streptococci obtained from the community between April and June 2001, 38 were resistant to erythromycin. CONCLUSIONS: In January 2001, during a longitudinal study of schoolchildren, we detected the emergence of erythromycin resistance in pharyngeal isolates of group A streptococci. This clonal outbreak also affected the wider community.

Adolescent↗

PubMed2002

Cytochrome P450 3A4 and P-glycoprotein mediate the interaction between an oral erythromycin breath test and rifampin.

BACKGROUND: The intravenous (14)C-erythromycin breath test (ERMBT(IV)) does not measure aggregate liver and intestinal cytochrome P450 (CYP) 3A4 activity. Accordingly, we evaluated an oral stable-labeled ((13)C) formulation of the test (ERMBT(oral)) as an alternative CYP3A4 phenotyping probe. METHODS: After an overnight fast, 14 young healthy volunteers (5 women and 9 men) received the ERMBT(IV) (0.07 micromol, 3 muCi), followed by the ERMBT(oral) (500 mg). The next morning, the CYP3A4 inhibitor troleandomycin (500 mg) was given, and both ERMBTs were repeated. After at least 24 hours, the CYP3A4 and P-glycoprotein inducer rifampin (600 mg; INN, rifampicin) was given daily for 7 days, and both ERMBTs were repeated 24 hours after the last dose of rifampin. Plasma samples were collected for 10 hours with each administration of the ERMBT(oral), and erythromycin levels were measured by liquid chromatography-mass spectrometry. Finally, the effect of troleandomycin on erythromycin transport was examined in Caco-2 cell monolayers. RESULTS: Compared with baseline values, the median ERMBT(IV) and ERMBT(oral) results and erythromycin apparent oral clearance (CL/F) all significantly decreased, by at least 70%, with troleandomycin treatment (P =.001 for each comparison). With rifampin treatment, the median ERMBT(IV) result and CL/F increased 2-fold (P < or =.01), but the median ERMBT(oral) result was unchanged (P =.30). There were no rank-order correlations between the ERMBT(IV) and ERMBT(oral) results or between either ERMBT result and CL/F within each treatment group (P > or =.07). In addition, troleandomycin had no effect on erythromycin transport in Caco-2 cells (P > or =.20). CONCLUSIONS: The ERMBT(oral) was influenced by processes in addition to intestinal and hepatic CYP3A4 activity and therefore did not provide a straightforward measure of aggregate CYP3A4 phenotype. The erythromycin-rifampin interaction cannot be attributed to CYP3A4 induction alone and probably also reflected intestinal P-glycoprotein induction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Erythromycin induces pyloric relaxation accompanied by a contraction of the gastric body after pylorus-preserving gastrectomy.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery; however, long-term retention of food in the residual stomach is a frequent complication during the early postoperative period. We reported that gastric stasis after PPG was attributable to the delayed recovery of gastric phase III, in which pyloric relaxation accompanied a contraction of the gastric body. The objective of the present study is to determine whether erythromycin can induce phase III with pyloric relaxation after PPG. METHODS: We studied gastrointestinal motility in dogs after PPG by using strain gauge force transducer. After randomized administration of either erythromycin or saline, interdigestive gastropyloroduodenal motility was recorded. RESULTS: Erythromycin induced phase III with pyloric relaxation in the early postoperative period. Pyloric relaxation accompanied a contraction of the gastric body. Compared with the saline group (body: 87.2 +/- 16.7 mmHg x min, antrum: 69.7 +/- 13.7 mmHg x min, pylorus: 91.7 +/- 22.1 mmHg x min), the erythromycin group showed significantly increased gastropyloric motility indexes (body: 506.2 +/- 33.5 mmHg x min, antrum: 430.9 +/- 53.7 mmHg x min, pylorus: 589.5 +/- 59.5 mmHg x min). CONCLUSIONS: Erythromycin can induce phase III, in which pyloric relaxation accompanied a contraction of the gastric body in the early postoperative period after PPG. Erythromycin might be used as a prokinetic agent for the treatment of early gastric stasis after PPG.

Animals↗

PubMed1971

Altered methylation of ribosomal RNA in an erythromycin-resistant strain of Staphylococcus aureus.

In certain strains of Staphylococcus aureus, a concentration of erythromycin between 10(-8) and 10(-7) M can induce resistance to concentrations of this drug as high as 10(-4) M. In one such strain studied, S. aureus (1206), N(6)-dimethyladenine is not normally present in 23S rRNA; however, a compound presumptively identified (on the basis of paper chromatography in three different solvents) as N(6)-dimethyladenine appears in the 23S rRNA of growing cells that have been incubated in a medium containing 10(-7) M erythromycin. It has been shown previously that the induction of the erythromycin-resistant phenotype that occurs under these conditions requires 10(-8)-10(-7) M erythromycin for maximal expression within 1 hr and that induction results in modified 50S ribosomal subunits, which are then unable to bind erythromycin or lincomycin. Methylated adenine is also found in the 16S rRNA from the strain of S. aureus studied; however, in contrast to the situation with 23S rRNA, the amount in 16S rRNA is not affected by erythromycin. These findings provide the first example of a correlation between the methylation of rRNA and altered ribosomal function.

Adenine↗

PubMed2004

Kinetics of macrolide action: the josamycin and erythromycin cases.

Members of the macrolide class of antibiotics inhibit peptide elongation on the ribosome by binding close to the peptidyltransferase center and blocking the peptide exit tunnel in the large ribosomal subunit. We have studied the modes of action of the macrolides josamycin, with a 16-membered lactone ring, and erythromycin, with a 14-membered lactone ring, in a cell-free mRNA translation system with pure components from Escherichia coli. We have found that the average lifetime on the ribosome is 3 h for josamycin and less than 2 min for erythromycin and that the dissociation constants for josamycin and erythromycin binding to the ribosome are 5.5 and 11 nM, respectively. Josamycin slows down formation of the first peptide bond of a nascent peptide in an amino acid-dependent way and completely inhibits formation of the second or third peptide bond, depending on peptide sequence. Erythromycin allows formation of longer peptide chains before the onset of inhibition. Both drugs stimulate the rate constants for drop-off of peptidyl-tRNA from the ribosome. In the josamycin case, drop-off is much faster than drug dissociation, whereas these rate constants are comparable in the erythromycin case. Therefore, at a saturating drug concentration, synthesis of full-length proteins is completely shut down by josamycin but not by erythromycin. It is likely that the bacterio-toxic effects of the drugs are caused by a combination of inhibition of protein elongation, on the one hand, and depletion of the intracellular pools of aminoacyl-tRNAs available for protein synthesis by drop-off and incomplete peptidyl-tRNA hydrolase activity, on the other hand.

Anti-Bacterial Agents↗

PubMed1990

Unconsciousness associated with midazolam and erythromycin.

An 8-yr-old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy. Sixty minutes after premedication with oral midazolam 0.5 mg kg-1 and oral atropine 0.03 mg kg-1, an infusion of erythromycin 400 mg was started. When 200 mg of erythromycin had been infused, the patient lost consciousness, but other vital functions remained normal. After 45 min, he awakened spontaneously. At the time the plasma concentration of midazolam was 134 ng ml-1. In order to investigate possible interactions between midazolam and erythromycin, we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery. The plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin. The altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug, erythromycin.

Adenoidectomy↗

PubMed1995

Legionella bozemanii cavitary pneumonia poorly responsive to erythromycin: case report and review.

A case of pneumonia due to Legionella bozemanii--only the 20th culture-proven case reported so far--progressed with cavitation 9 days after the initiation of intravenous therapy with erythromycin. Review of all 20 reported cases revealed a similar propensity toward radiographic progression (25%) and cavitation (25%) during therapy. A slow response to long courses of erythromycin was the rule (35% of cases). In two instances, long courses of intravenous erythromycin failed and the patient died. Pleural effusion was reported in 60% of patients, including two with empyema. Overall mortality was high (40%). Although mortality was only 21% among patients who lived long enough to receive adequate courses of erythromycin, all three such patients who died had received erythromycin alone. Combination therapy with erythromycin and rifampin proved more effective in terms of survival. Infections due to non-pneumophila Legionella may be overlooked because of the organisms' special serological and culture requirements.

Adult↗

PubMed1997

Effect of erythromycin on postprandial gastroesophageal reflux in reflux esophagitis.

UNLABELLED: The macrolide antibiotic erythromycin has recently been reported to exert profound prokinetic properties. The aim of the study was to investigate the effect of erythromycin on postprandial gastroesophageal reflux in patients with reflux esophagitis. METHODS: In 16 patients with reflux esophagitis (according to Savary and Miller: grade I, n = 8; grade II, n = 4; grade III/IV, n = 4) two pH measurements, with and without erythromycin, were performed for three postprandial hours after lunch. Erythromycin was administered in a dose of 3.5 mg/kg intravenously just prior to lunch. RESULTS: With erythromycin, the median fraction time esophageal pH < 4 was significantly decreased (7.6% versus 18.1%; P < 0.05). This decrease was the result of a diminished frequency of reflux episodes (19 vs 25; P < 0.05) and a shortening of the median reflux duration (0.7 min vs 1.1 min; P < 0.05). CONCLUSIONS: Intravenous administration of erythromycin decreases postprandial gastroesophageal reflux in patients with reflux esophagitis.

Adult↗

PubMed1976

Relative efficacy of clindamycin, erythromycin, and penicillin in treatment of Treponema pallidum in skin syphilomas of rabbits.

The currently recommended antibiotic for treatment of fetal syphilis in pregnant women who are allergic to penicillin is erythromycin. However, clindamycin crosses the placenta more effectively than erythromycin. Therefore, an in vivo rabbit model of intradermal syphilomas was used to determine the effect of clindamycin compared with the effects of erythromycin and penicillin on the growth of virulent Treponema pallidum. The average number of motile treponemes in two, paired, mature lesions was determined before and after therapy in groups of four rabbits per dosage. Single intramuscular doses of clindamycin (15 and 40 mg/kg) and erythromycin (12 and 40 mg/kg) did not decrease treponeme counts significantly. Single injections of penicillin (10,000 units/kg) reduced treponemal counts by more than 250-fold. Multiple intramuscular injections of clindamycin reduced counts by five- to sevenfold, whereas multiple doses of erythromycin and penicillin decreased treponeme counts by greater than 300-fold. These studies indicate that clindamycin is far less active than erythromycin or penicillin in treatment of established syphilitic lesions in rabbits.

Animals↗

PubMed1986

Kinetics of erythromycin uptake and release by human lymphocytes and polymorphonuclear leucocytes.

The uptake of 14C-labelled erythromycin by human lymphocytes and polymorphonuclear leucocytes was studied. Erythromycin was concentrated by the cells. The amount of accumulated erythromycin was correlated with the cell count and was found to increase with alkaline pH and with increasing temperature of the incubation medium. The uptake of erythromycin could be reduced by compounds which inhibit cell respiration, glycolysis and (Na+-K+)membrane ATPase. Furthermore, the uptake was saturable and followed Michaelis-Menten kinetics (Km = 0.7 and 1.6 mM for lymphocytes and polymorphonuclear leucocytes, respectively). The intracellular concentrations cannot be explained by the principle of non ionic diffusion. It is suggested that erythromycin is actively transported via the nucleoside transport system. The accumulated erythromycin was rapidly released when the cells were washed and re-incubated in antibiotic-free medium. Probably, no strong intracellular binding takes place.

Erythromycin↗

PubMed1990

In-vitro activity of azithromycin, erythromycin, ciprofloxacin and norfloxacin against Neisseria gonorrhoeae, Haemophilus ducreyi, and Chlamydia trachomatis.

The minimum inhibitory concentrations (MICs) of azithromycin, erythromycin, ciprofloxacin and norfloxacin for 300 strains of Neisseria gonorrhoeae, 100 strains of Haemophilus ducreyi and six strains of Chlamydia trachomatis were determined. The two quinolones were more active against gonococcal strains than were the two macrolides. Azithromycin was approximately eight-fold more active against N. gonorrhoeae than was erythromycin (MIC90: 0.25 mg/l azithromycin, 2.0 mg/l erythromycin). The Mtr phenotype of gonococci increased azithromycin MICs approximately four fold. Azithromycin was less active than erythromycin against C. trachomatis. Azithromycin had considerable activity against H. ducreyi and was ten-fold more active than was erythromycin (MIC90: 0.004 mg/l azithromycin, 0.03 mg/l erythromycin). Clinical trials of azithromycin in the treatment of chlamydial infection and genital ulcer disease are indicated.

Azithromycin↗

PubMed1991

Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections.

Erythromycin acistrate is a new 2'-acetyl esther prodrug of erythromycin, whose structure resembles that of erythromycin estolate. However, in toxicological studies, it does not have the problems of hepatotoxicity. To assess its effects on hepatic functions in clinical practice, the liver parameters of patients with respiratory tract or skin infections were monitored during therapy. In total 1549 patients were treated for 7-14 days. In addition, 127 patients with suspected viral infections served as controls. There were no significant differences in serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyltransferase (gamma-GT) or alkaline phosphatase (APHOS) values between the erythromycin acistrate or control groups at the beginning or end of therapy. ASAT values increased moderately in 2.4% and clearly in 0.3% of patients treated, but also decreased in 2.0%. ALAT values were moderately increased in 9.9%, clearly increased in 0.6% and normalized in 3.5% of the patients. gamma-GT values increased moderately in 3.5% and and clearly in 0.3%, but decreased to normal in 3.3% of the patients. APHOS was moderately elevated in 1.0% of the patients and normalized in 1.3%. The correlation of changes between the different liver enzymes was poor. Only ten patients (0.6%) had two or more clearly elevated liver enzyme values by the end of the therapy, of whom five had increased liver enzyme activities before the treatment, two had underlying disease explaining the changes and in only three patients out of 1549 (0.2%) could hepatic changes be attributed to erythromycin acistrate therapy. These changes were reversible. The results demonstrate the hepatic safety of erythromycin acistrate in clinical practice. Concomitant food intake did not affect the safety profile.

Adolescent↗

PubMed1992

Comparative in-vitro activity of azithromycin, macrolides (erythromycin, clarithromycin and spiramycin) and streptogramin RP 59500 against oral organisms.

The in-vitro activities of azithromycin, clarithromycin, spiramycin and RP 59500 were compared with erythromycin against a wide range of oral organisms which have been implicated in oral infections and/or endocarditis (clindamycin was included for oral streptococci). All compounds tested showed good activity against many of these organisms, although some variation was observed with different species. Clarithromycin was the most active of the antibiotics tested against Gram-positive anaerobes, including Actinomyces spp., Propionibacterium spp., Lactobacillus spp. and Bifidobacterium dentium. Azithromycin was slightly less active than erythromycin against these species. In general, RP 59500 had higher MICs than the macrolides, other than spiramycin, against these organisms, but was superior in activity against Peptostreptococcus spp., inhibiting all isolates at 2 mg/L. Azithromycin was, in general, the most active antibiotic tested against the Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp., Wolinella spp., Actinobacillus actinomycetemcomitans, Selenomonas spp. and Mitsuokella multiacida, including those isolates which were insusceptible to erythromycin. Clarithromycin showed similar activity to erythromycin against most Gram-negative species, but was superior against Capnocytophaga ochraceus and Eikenella corrodens. RP 59500 was less active than the macrolides against most Gram-negative anaerobes, but was superior to erythromycin and clarithromycin against Fusobacterium spp. and Leptotrichia buccalis, some strains of which were moderately resistant to erythromycin. The macrolides and clindamycin were about equally active against the oral streptococci, whereas RP 59500 showed lower inhibitory activity. The in-vitro results suggest that azithromycin and clarithromycin may be of value in the treatment of dental sepsis and the prophylaxis of endocarditis. RP 59500 showed useful activity against Gram-positive anaerobes and, because of its bactericidal activity against oral streptococci, may also prove to have a role in these areas.

Anti-Bacterial Agents↗

PubMed1998

Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status.

The in-vitro activity of the novel ketolide HMR 3647 was compared with four other macrolides against 335 strains of staphylococci, pneumococci and enterococci with predetermined susceptibility status to erythromycin. HMR 3647 was the most active agent against staphylococci (irrespective of methicillin resistance) of sensitive (MIC90 = 0.25 mg/L) or inducibly resistant phenotype (MIC90 = 2 mg/L), but was inactive against constitutively resistant strains. HMR 3647 was very active against erythromycin-sensitive enterococci (MIC90 = 0.06 mg/L), irrespective of vancomycin resistance, but less active against strains that were resistant to erythromycin (MIC90 = 32 mg/L). The ketolide was highly active against pneumococci (irrespective of penicillin resistance), both erythromycin sensitive (MIC90 = 0.03 mg/L) and erythromycin resistant (MIC90 = 0.25 mg/L). A bactericidal action was found against some erythromycin-sensitive staphylococci, pneumococci and Enterococcus faecium. The microbiological properties of HMR 3647 are thus superior to those of other macrolides.

Anti-Bacterial Agents↗

PubMed1998

Increased activity of 16-membered lactone ring macrolides against erythromycin-resistant Streptococcus pyogenes and Streptococcus pneumoniae: characterization of South African isolates.

The susceptibility of 40 erythromycin-resistant isolates of Streptococcus pyogenes and 40 multiply-resistant isolates of Streptococcus pneumoniae to six macrolide antibiotics, representing 14-, 15- and 16-membered lactone ring structures, was tested. The genetic basis for macrolide resistance in the strains was also determined. Both erm and mef determinants were encountered in the 36 S. pneumoniae isolates tested, but only mef in the five S. pyogenes isolates tested. All isolates showed cross-resistance among the 14-membered macrolides erythromycin, clarithromycin and roxithromycin and the 15-membered macrolide, azithromycin. However, the erythromycin-resistant S. pyogenes isolates retained full susceptibility to spiramycin and josamycin (16-membered agents). These latter two antibiotics were also more active than the other macrolides against erythromycin-resistant S. pneumoniae isolates, especially josamycin which was 8-64 times more active than erythromycin; spiramycin was only two to eight times more active than erythromycin.

Anti-Bacterial Agents↗