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PubMed1985

Penetration of erythromycin into tonsillar tissue.

A study was carried out to investigate serum levels and tonsillar tissue penetration of erythromycin in 80 children suffering from chronic tonsillitis who had to undergo tonsillectomy. Oral erythromycin ethyl succinate (1 g twice daily) was given for the 2 days preceding surgery, the last dose scheduled for 2, 3, 4 or 6 hours before the start of the operation and the withdrawal of blood and tissue samples. The results showed that erythromycin penetrated quickly into tonsillar tissue and the levels were higher in tissue than in serum at all time points. Mean levels of erythromycin were consistently greater than the minimum inhibitory concentrations for most common Gram-positive oro-pharyngeal pathogens and H. influenzae.

Administration, Oral↗
PubMed1989

Acute and chronic Legionnaires' disease and co-existent tuberculosis: a trial of erythromycin.

To assess the prevalence of Legionnaires' disease, 115 patients with 'difficult-to-treat' chest infections were screened for Legionnella pneumophila. The results were positive in 10 (37%) of 27 patients with pulmonary tuberculosis, 15 (22%) of 68 with a recent onset acute respiratory infection, and 7 (35%) of 20 patients with history of a chronic respiratory infection. These 32 patients were enrolled in an open therapeutic trial of erythromycin. Less severe cases (17 of 32) received erythromycin stearate orally (500 mg 4-times daily) for up to 28 days, while severe cases were treated for the first few days with intravenous erythromycin lactobionate (4 g/day). Weekly chest X-ray examinations revealed prompt resolution. Most patients had no signs and symptoms detectable after 7 days, and none persisted up to 28 days. There were no therapeutic failures and microbiological tests on Day 28 were negative for Legionella pneumophila. It is suggested that the possibility of co-existing legionellosis should be considered in all patients with difficult to treat acute and chronic chest infections, particularly in developing countries where tuberculosis is very common, and treatment instituted or supplemented with erythromycin as the drug of choice.

Acute Disease↗
PubMed2006

Impact of ibuprofen therapy in the outcome of experimental pneumococcal acute otitis media treated with amoxicillin or erythromycin.

The impact of ibuprofen combined with amoxicillin or erythromycin for therapy of penicillin-resistant pneumococcal acute otitis media (AOM) was evaluated in a gerbil model. Ibuprofen (at 2.5 or 7.5 mg/kg, orally) and/or amoxicillin or erythromycin (5 mg/kg each, s.c.) were administered at 5 h (early therapy, as single-dose regimen) or at 18 h (delayed therapy, five doses) postinoculation (PI). Each antibiotic alone and combined with ibuprofen was more effective administered as early regimen than as delayed treatment when evaluating the presence of otorrhea, otoscopic aspect, culture-positive and bacterial counts in middle ear (ME) samples, and loss of body weight. There was a trend for a better bacteriological outcome in animals receiving amoxicillin or erythromycin and ibuprofen, especially with the high dose. Such a dose of ibuprofen, associated with each antibiotic regimen, also preserved the animal well-being, avoiding a great weight loss in comparison to those receiving the antibiotic alone but a statistically significant difference was only observed for animals receiving delayed therapy with erythromycin and high-dose ibuprofen. In conclusion, ibuprofen combined with antibiotics seemed to improve the outcome of this experimental pneumococcal AOM.

Amoxicillin↗
PubMed2005

The effect of erythromycin and fluvoxamine on the pharmacokinetics of intravenous lidocaine.

Inhibitors of CYP3A4 (cytochrome P450 3A4) have a minor effect on lidocaine pharmacokinetics. We studied the effect of coadministration of the antidepressant fluvoxamine (CYP1A2 inhibitor) and antimicrobial drug erythromycin (CYP3A4 inhibitor) on lidocaine pharmacokinetics in a double-blind, randomized, three-way crossover study. Nine volunteers ingested daily 100 mg fluvoxamine and placebo, 100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos for 5 days. On day 6, 1.5 mg/kg lidocaine was administered IV over 60 min. Concentrations of lidocaine and its major metabolite monoethylglycinexylidide were measured for 10 h. Fluvoxamine alone decreased the clearance of lidocaine by 41% (P < 0.001) and prolonged its elimination half-life from 2.6 to 3.5 h (P < 0.01). During the combination of fluvoxamine and erythromycin, lidocaine clearance was 53% smaller than during placebo (P < 0.001) and 21% smaller than during fluvoxamine alone (P < 0.05). During the combination phase the half-life of lidocaine (4.3 h) was longer than during the placebo (2.6 h; P < 0.001) or fluvoxamine (3.5 h; P < 0.01). We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of lidocaine and may increase the risk of lidocaine toxicity. Concomitant use of both fluvoxamine and a CYP3A4 inhibitor such as erythromycin can further increase plasma lidocaine concentrations by decreasing its clearance.

Adult↗
PubMed2001

Studies on macrolide antibiotics I. Synthesis and antibacterial activity of erythromycin A 9-O-substituted oxime ether derivatives against Mycobacterium avium complex.

A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics.

Anti-Bacterial Agents↗
PubMed2004

Anti-inflammatory effect of erythromycin on histamine-induced otitis media with effusion in guinea pigs.

In this study, the anti-inflammatory effect of erythromycin was investigated in a model of histamine-induced otitis media with effusion (OME). OME was induced in guinea pigs by the transtympanic injection of histamine solution into the middle-ear cavity. Guinea pigs were randomly assigned to one of three groups: control, erythromycin treatment, or methylprednisolone treatment. After histamine injection, the animals were treated with intraperitoneal medication for five days consecutively. Afterwards, the animals were sacrificed and the temporal bones were removed. The samples were examined stereologically. In the erythromycin-treated group, it was observed that neutrophil infiltration was significantly inhibited when compared to the control group. This result shows that erythromycin may produce a significant anti-inflammatory effect in this model of OME.

Animals↗
PubMed1997

Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin.

A pre-treatment and a 3-week post-treatment isolate of Neisseria gonorrhoeae from a 13-year-old boy treated with azithromycin in a single 1 g oral dose were characterized microbiologically. Both isolates were of the same serovar/auxotype (1B6/non-requiring) and had similar antibiograms apart from erythromycin and azithromycin: the pre- and post-treatment MICs (minimum inhibitory concentrations) were: 1 mg/L and 32 mg/L to erythromycin and 0.125 mg/L and 3 mg/L to azithromycin. The finding that both isolates were 1B6/NR, had similar antibiograms (other than azithromycin and erythromycin), and no other 1B6/NR isolates were resistant to erythromycin supports the view that macrolide resistance developed following treatment. A high overall level of azithromycin susceptibility was confirmed by testing 67 clinical isolates: MIC90 0.5 mg/L (range 0.023-0.75 mg/L). We conclude that the long half-life of azithromycin which is beneficial in treating chlamydial infection may result in increased selective pressure for resistance in gonococci. This report also highlights the importance of antibiotic susceptibility surveillance of gonococci and stresses the need for appropriate treatment of gonococcal infection, particularly when it is prescribed outwith departments of genitourinary medicine.

Adolescent↗
PubMed2005

Ribosomes containing mutants of L4 ribosomal protein from Thermus thermophilus display multiple defects in ribosomal functions and sensitivity against erythromycin.

Protein L4 from Thermus thermophilus (TthL4) was heterologously overproduced in Escherichia coli cells. To study the implication of the extended loop of TthL4 in the exit-tunnel and peptidyltransferase functions, the highly conserved E56 was replaced by D or Q, while the semiconserved G55 was changed to E or S. Moreover, the sequence -G55E56- was inverted to -E55G56-. When we incorporated these mutants into E. coli ribosomes and investigated their impact on poly(Phe) synthesis, high variations in the synthetic activity and response to erythromycin of the resulting ribosomes were observed. In the absence of erythromycin, ribosomes harboring mutations G55E and E56D in TthL4 protein were characterized by low activity in synthesizing poly(Phe) and decreased capability in binding tRNA at the A site. On the other hand, ribosomes possessing mutations G55E, G55S, G55E-E56G, or E56Q in TthL4 protein were unexpectedly more sensitive to erythromycin. Evidence in support of these findings was drawn by in vivo experiments, assessing the erythromycin sensitivity of E. coli cells expressing wild-type or mutant TthL4 proteins. Our results emphasize the role of the extended loop of L4 ribosomal protein in the exit-tunnel and peptidyltransferase center functions.

Drug Resistance, Microbial↗
PubMed1993

Anti-inflammatory action of erythromycin. Its inhibitory effect on neutrophil NADPH oxidase activity.

The effects of erythromycin on the NADPH oxidase activity in the neutrophils of normal subjects and patients with bronchiolitis were investigated. In the patients receiving erythromycin, NADPH oxidase activity was significantly lower in a whole-cell system than that before therapy. Erythromycin was also found to inhibit the superoxide generation of neutrophils exposed to phorbol myristate acetate in a whole-cell system and the activation of superoxide-generating NADPH oxidase by sodium lauryl sulfate (sodium dodecyl sulfate) in a cell-free system. The concentration of the drug required for 50 percent inhibition of the oxidase was 0.7 mM in the whole-cell system and 0.2 mM in the cell-free system. These results suggest that erythromycin, an antibiotic which penetrates well into human neutrophils, may exhibit an anti-inflammatory action due to inhibiting of neutrophil NADPH oxidase activation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma.

It has been demonstrated that bronchial hyperresponsiveness is a characteristic feature of bronchial asthma, and airway inflammation plays an important role in bronchial hyperresponsiveness. Erythromycin is an antibiotic extensively used worldwide which is also reported to have anti-inflammatory action. This study was designed to clarify whether erythromycin could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, histamine challenge was performed in 23 patients with bronchial asthma (atopic type, 11; nonatopic type, 12). All patients were treated for ten weeks with erythromycin, 200 mg three times daily, orally. After ten weeks' treatment, PC20, an index of bronchial sensitivity, was increased significantly. There was no difference between atopic and nonatopic patients in the improvement of PC20. It was concluded that erythromycin reduces the severity of bronchial responsiveness in patients with bronchial asthma.

Adult↗
PubMed1996

Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes.

Roxithromycin and erythromycin were incubated with rat and human liver microsomal or reconstituted cytochrome P450 (P450 or CYP) monooxygenase systems in the presence of an NADPH-generating system, and the effects of these chemicals on testosterone 6 beta-hydroxylation and nifedipine oxidation activities were compared with those of typical CYP3A4 inhibitors including ketoconazole, troleandomycin, and gestodene. Roxithromycin and erythromycin were found to be relatively weak inhibitors of testosterone 6 beta-hydroxylation and nifedipine oxidation activities by rat and human liver microsomes or by reconstituted systems containing CYP3A4/5. Formation of an inhibitory P450-metabolite complex was determined spectrally by incubating troleandomycin with human liver microsomes; the extents of the complex formation were lesser in liver microsomes of humans than those of rats treated with dexamethasone. Erythromycin and roxithromycin were also activated slightly by rat liver microsomes to form P450.Fe(II)-metabolite complex, although these chemicals caused very little or undetectable levels, respectively, of spectral changes by human liver microsomes even when a human sample which contained relatively high levels of CYP3A4 was used. These results suggested that roxithromycin and erythromycin were relatively less potent to inhibit CYP3A4-catalytic activities in human liver microsomes, because of their low capabilities to form P450.Fe(II)-metabolite complex.

Animals↗
PubMed2001

Role of erythromycin for treatment of incipient chronic lung disease in preterm infants colonised with Ureaplasma urealyticum.

Ureaplasma urealyticum is frequently isolated from tracheal aspirates of very low birthweight infants who go on to develop chronic lung disease. The use of erythromycin has been advocated in ventilated very low birthweight infants who are colonised with U. urealyticum, although the association between U. urealyticum and chronic lung disease remains controversial. There are only two randomised, controlled trials involving a total of 37 U. urealyticum-positive very low birthweight infants. Both trials failed to demonstrate a reduction in the incidence of chronic lung disease after 7 or 10 days of erythromycin. On the other hand, there are reports of rare but serious adverse effects of erythromycin in newborn infants including sudden cardiovascular compromise and hypertrophic pyloric stenosis. We conclude that, at present, there is insufficient evidence to support the use of erythromycin for the treatment of incipient chronic lung disease in very low birthweight infants colonised with U. urealyticum.

Anti-Bacterial Agents↗
PubMed2000

Effects of prior feeding on pharmacokinetics and estimated bioavailability after oral administration of a single dose of microencapsulated erythromycin base in healthy foals.

OBJECTIVE: To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals. ANIMALS: 6 healthy foals, 3 to 5 months old. PROCEDURE: Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of erythromycin A and anhydroerythromycin A in plasma were determined, using high-performance liquid chromatography. Results pharmacokinetic analysis of plasma concentration-time data for food-withheld and fed conditions were compared. RESULTS: Plasma concentrations of erythromycin A for foals were lower after feeding than concentrations when food was withheld. Area under the plasma concentration-time curve, maximum plasma concentration, and estimated bioavailability were greater in foals when food was withheld than when foals were fed. Anhydroerythromycin A was detected in plasma after administration of MEB in all foals. CONCLUSIONS AND CLINICAL RELEVANCE: Foals should be given MEB before they are fed hay. Administration of MEB to foals from which food was withheld overnight apparently provides plasma concentrations of erythromycin A that exceed the minimum inhibitory concentration of Rhodococcus equi for approximately 5 hours. The dosage of 25 mg/kg every 8 hours, PO, appears appropriate.

Administration, Oral↗
PubMed2000

Characterization of erythromycin-resistant methylase genes from multiple antibiotic resistant Staphylococcus spp isolated from milk samples of lactating cows.

OBJECTIVE: To isolate and characterize erythromycin-resistant methylase genes in multiple-antibiotic resistant staphylococci isolated from milk samples. ANIMALS: 300 lactating cows. PROCEDURE: 23 erythromycin-resistant staphylococci were isolated from milk samples of 300 lactating cows. The prevalence of erythromycin-resistant methylase (erm) genes, ermC and ermA genes, and the multicomponent macrolide efflux pump in staphylococci msrA genes were identified and characterized by use of multiplex polymerase chain reaction (PCR), Southern hybridization, restricted fragment length polymorphism (RFLP) analysis, and dot-blot hybridization. RESULTS: Biochemical characterization indicated that 3 of 23 (13%) isolates were coagulase-positive Staphylococcus aureus, and the rest were coagulase-negative. Multiplex PCR resulted in amplification of a 520-base pair (bp) region of the ermC gene from the cell lysates of a strain of S simulans M-21 and S sciuri M-28. The ermC gene in both isolates was found on a 3-kilobase plasmid. The ermA gene was found on the chromosome of 21 isolates, and 6 RFLP patterns were observed. None of the isolates harbored the msrA gene. CONCLUSIONS: Erythromycin-resistant Staphylococcus spp isolated from milk samples of lactating cows may serve as reservoirs of erm genes homologous to those described in human isolates. However, the chromosomal insert patterns and prevalence of these genes, the sizes of plasmids harboring the genes, and the number of inserts of the genes (copy number) may differ from that of human isolates.

Animals↗
PubMed2006

Effect of intraluminal distension or ischemic strangulation obstruction of the equine jejunum on jejunal motilin receptors and binding of erythromycin lactobionate.

OBJECTIVE: To determine whether inflammation of the jejunum of horses decreases the number of motilin receptors and amounts of motilin receptor mRNA and alters erythromycin lactobionate binding affinity to the motilin receptor in jejunal tissues. SAMPLE POPULATION: Jejunal segments in 6 adult horses. PROCEDURE: Each horse was anesthetized, and a ventral median celiotomy was performed; 2 segments of jejunum underwent a sham operation, 2 segments underwent ischemic strangulation obstruction (ISO), and 2 segments underwent intraluminal distension (ILD). Treatments were maintained for 120 minutes. From each segment, full-thickness biopsy samples were collected and smooth-muscle homogenates were prepared. Affinity and distribution of motilin binding to these preparations were determined by use of iodine 125 (125I)-labeled synthetic porcine motilin. Via displacement experiments, competition between 125I-labeled motilin and erythromycin lactobionate for binding to motilin receptors in the different segments was investigated. A quantitative real-time PCR technique was used to assess motilin receptor mRNA content in the muscle preparations. RESULTS: Compared with the ISO or ILD segments, the number of motilin receptors was significantly higher in the sham-operated segments; ILD segments contained the lowest number of motilin receptors. The expression of motilin receptor mRNA was significantly decreased in ILD segments but not in ISO segments. Erythromycin lactobionate displacement of 125I-labeled motilin from motilin receptors did not differ significantly among the jejunal segments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that downregulation and decreased production of motilin receptors in inflamed jejunal tissue contribute to the altered prokinetic response to erythromycin in horses with gastrointestinal disease.

Animals↗
PubMed2000

Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996).

OBJECTIVE: To determine whether foals with pneumonia that were treated with erythromycin, alone or in combination with rifampin or gentamicin, had a higher risk of developing adverse effects, compared with foals treated with trimethoprim-sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and PGP (control foals). DESIGN: Retrospective study. ANIMALS: 143 foals < 240 days old. PROCEDURE: Information on age, sex, breed, primary drug treatment, total days of treatment with the primary drug, and whether the foal developed diarrhea, hyperthermia, or respiratory distress was obtained from the medical records. Relative risk (RR) and attributable risk (AR) were calculated to compare risk of adverse reactions between foals treated with erythromycin and control foals. RESULTS: Only 3 (4.3%) control foals developed diarrhea; none developed hyperthermia or respiratory distress. Foals treated with erythromycin had an 8-fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of erythromycin to treat foals with pneumonia was associated with an increased risk of diarrhea, hyperthermia, and respiratory distress, compared with use of TMS or PGP.

Animals↗
PubMedDate not supplied

Protective effect of Sesbania grandiflora against erythromycin estolate-induced hepatotoxicity.

Sesbania grandiflora, commonly known as 'sesbania', is widely used in Indian folk medicine for the treatment of liver disorders. Oral administration of an ethanolic extract of S. grandiflora leaves (200 mg/kg/day) for 15 days produced significant hepatoprotection against erythromycin estolate (800 mg/kg/day)-induced hepatotoxicity in rats. The increased level of serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase), bilirubin, cholesterol, triglycerides, phospholipids, free fatty acids, plasma thiobarbituric acid reactive substances and hydroperoxides observed in rats treated with erythromycin estolate were significantly decreased in rats treated concomitantly with sesbania extract and erythromycin estolate. The sesbania extract also restored the depressed levels of antioxidants to near normal. The results of the study reveal that sesbania could afford a significant protective effect against erythromycin estolate-induced hepatotoxicity. The effect of sesbania was compared with that of silymarin, a reference hepatoprotective drug.

Administration, Oral↗
PubMed1979

Penetration of erythromycin through respiratory mucosa. A study using secretory otitis media as a model.

This study is based upon the concept that the respiratory mucosa reacts in a uniform manner to an inflammatory stimulus. Secretory Otitis Media (SOM) may be used as a model to disclose some aspects of antibiotic penetration. Erythromycin was given for different periods of time to 108 cases of SOM where myringotomy was indicated. The middle ear effusion was aspirated and blood samples were obtained simultaneously. The concentration of erythromycin was determined by microbiological procedures. Erythromycin penetrated into the middle ear effusion. After the fourth dose the concentration was at the same level as the plasma peak level. The elimination of the drug from the middle ear secretion was considerably prolonged compared with the rapid elimination from plasma. This implies that erythromycin attains a steady state in the middle ear effusion with concentrations equal to the plasma peak level.

Adolescent↗