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Effect of erythromycin treatment on antibody responses in pertussis.

The effect of erythromycin treatment on antibody responses to Bordetella pertussis filamentous haemagglutinin (FHA) and pertussis toxin (PT) was investigated in convalescent blood samples from 105 children with pertussis. Erythromycin had been given to 59 children, median age 3.2 years (range 0.3-9.9) on median day 7 (range 11-14) after onset of disease while the remaining 46 children, age 3.45 (0.6-8.1) were untreated. No significant differences in IgG antibody concentration were noted to FHA by ELISA and to PT, neither by NT nor by ELISA, but a tendency towards lower median titers was seen to both antigens and by both type of assays in the erythromycin-treated group. Similarly, early erythromycin treatment i.e. within 7 days of onset of symptoms, did not influence significantly of the development of the antibody responses but tended to lead to lower titer levels. A significant response to PT and FHA was found in about 90% of blood samples, irrespective of treatment. All 56 children with culture-confirmed B. pertussis infection had a significant response to PT. The study has thus shown a slight but not significant effect of erythromycin treatment on antibody responses in pertussis.

Adhesins, Bacterial↗

The interaction between chronic oral slow-release theophylline and single-dose intravenous erythromycin.

Eight volunteers were each given 300 mg of erythromycin lactobionate by i.v. infusion over 15 min in the presence and absence of chronic dosing with slow-release theophylline. Pharmacokinetic profiles were obtained for theophylline in the presence and absence of erythromycin and for erythromycin in the presence and absence of theophylline. A very small, clinically unimportant, but statistically significant increase occurred in mean (+/- S.E.M.) serum theophylline concentration from 4.9 +/- 0.3 mg/l to 5.2 +/- 0.3 mg/l in the presence of erythromycin (P = less than 0.01). The theophylline pharmacokinetic parameters did not change significantly. The only changes in erythromycin pharmacokinetics were an increase in the renal excretion (0-12 h) from 5.5 +/- 4.0 mg to 11.2 +/- 6.0 mg (P less than 0.03) and an increase in renal clearance (0-2 h) from 9.0 +/- 6.0 ml/min to 21.6 +/- 15 ml/min (P less than 0.05) in the presence of theophylline.

Administration, Oral↗

Emergence of the M phenotype of erythromycin-resistant pneumococci in South Africa.

Erythromycin-resistant pneumococci have been isolated in South Africa since 1978; however, from 1987 to 1996, resistance to macrolides was only detected in 270 (2.7%) of 9,868 blood or cerebrospinal fluid (CSF) pneumococcal isolates, most of which were obtained from the public sector. In South Africa, macrolide use in the public sector is estimated at 56% of that in the private sector. Most erythromycin-resistant strains (89%) exhibited resistance to erythromycin and clindamycin (macrolide-lincosamide-streptogramin B phenotype). In the United States, most erythromycin-resistant pneumococci exhibit the newly described M phenotype (resistance to erythromycin alone), associated with the mefE gene. The M phenotype in South Africa increased significantly in the last 10 years, from 1 of 5,115 to 28 of 4,735 of blood and CSF isolates received from 1987 to 1991 compared with 1992 to 1996 (p = 5 x 10(-7)). These data suggest that, although macrolide resistance in pneumococci remains low in the public sector, the mefE gene is rapidly emerging in South Africa.

Anti-Bacterial Agents↗

Antimalarial activity of azithromycin and erythromycin against Plasmodium berghei.

Several antibiotics that inhibit protein synthesis on 70S ribosomes, including the macrolide erythromycin, and the azalides azithromycin (ZITHROMAX) and CP-63,956, demonstrated antimalarial activity against two strains of Plasmodium berghei. In a four-day in vivo test, the azalides were 25-fold more potent than erythromycin against the chloroquine-sensitive P. berghei N strain, and displayed additive effects with chloroquine. This effect was not observed with the erythromycin-chloroquine combination. Against the chloroquine-resistant P. berghei MSU/RC strain, the azalides were 60-fold more potent than erythromycin. Additive effects were observed with azalide-chloroquine combinations against this strain, but these results were not significantly different from the erythromycin-chloroquine combination.

Animals↗

The emergence of erythromycin resistance in Streptococcus pyogenes in Fremantle, Western Australia.

Erythromycin resistance in Streptococcus pyogenes is unusual except in Japan. Since January 1, 1985, a dramatic increase has occurred in the prevalence of erythromycin-resistant Strept. pyogenes infections in the outpatients who have presented to Fremantle Hospital, Western Australia. In 1985, 1% of isolates of Strept. pyogenes was erythromycin-resistant. This had risen to 9.1% of isolates in 1986 and to 17.6% of isolates in 1987. Several M- and T-types of Strept. pyogenes were involved. Treatment failure now can be expected when erythromycin is prescribed for the treatment of common infections in outpatients at this hospital. Laboratories that use disc methods of antimicrobial susceptibility testing may not detect erythromycin resistance in these organisms.

Adolescent↗

Erythromycin-associated cholestatic hepatitis.

OBJECTIVE: To estimate the risk of cholestatic hepatitis of uncertain origin in patients who had recently received erythromycin, a drug which is known to cause this disorder. DESIGN: A retrospective cohort study using data automatically recorded on general practitioners' office computers. SETTING: Some 600 general practices in the United Kingdom. SUBJECTS: 366,064 people who received erythromycin. MAIN OUTCOME MEASURE: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for erythromycin. RESULTS: There were 13 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving erythromycin which were either characteristic of or consistent with a syndrome previously described as being associated with this drug. CONCLUSION: The risk of cholestatic jaundice associated with erythromycin is estimated to be in the range of 3.6 per 100,000 users (95% confidence interval, 1.9-6.1).

Adolescent↗

Microbial degradation of erythromycins A and B.

Growing cultures, as well as broken and lyophilized cells of pseudomonas 56 were found to degrade erythromycin A, and lyophilized cells inactivated erythromycins A and B. The enzyme system involved in this degradation was constitutive and the enzyme level in the cells could be increased about 8-fold when oleandomycin or erythromycin B was added to the growth medium. The ability of whole or broken cells to inactivate erythromycin A was completely lost when these preparations were boiled, and the erythromycin A-inactivating activity was localized in the cell membrane fraction. The lyophilized cells did not degrade oleandomycin, methymycin, tylosin, a mixture of leucomycins, josamycin, or maridomycin III.

Anti-Bacterial Agents↗

3-Keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis and in vitro activity.

A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A were prepared with a novel synthetic route, which include 6 reaction steps--oximation, protection, hydrolysis, oxidation, deprotection and addition. The antibacterial activity of these compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms. Several of these derivatives showed improved antibacterial activity against some erythromycin-resistant organisms as compared to erythromycin A.

Anti-Bacterial Agents↗

Erythromycin coadministration increases plasma atorvastatin concentrations.

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhibitor of HMG-CoA reductase, was investigated in 12 healthy volunteers. Each subject received a single 10 mg dose of atorvastatin on two separate occasions, separated by 2 weeks. Erythromycin (500 mg qid) was given from 7 days before through 4 days after the second atorvastatin dose. Atorvastatin concentrations were determined by an enzyme inhibition assay, which measured both atorvastatin and active metabolites. When erythromycin was coadministered with atorvastatin, mean Cmax and AUC(0-infinity) increased by 37.7% and 32.5%, respectively. Mean terminal half-life was similar following each atorvastatin dose. Possible mechanisms for this interaction include erythromycin inhibition of first-pass conversion of atorvastatin to inactive metabolites and erythromycin inhibition of P-glycoprotein-mediated intestinal or biliary secretion.

Adolescent↗

Can prophylactic oral erythromycin reduce time to full enteral feeds in preterm neonates?

Efficacy of oral, prophylactic erythromycin in reducing the time to establish full enteral feeds (150 ml/kg/day) was assessed in neonates < 32 weeks, ready for enteral feeds. Seventy-three consecutive neonates were randomised to receive oral erythromycin ethyl succinate (n = 36) or placebo (n = 37) in a double-blind trial until full enteral feeds or 14 days of therapy were reached. A prospectively designed feeding regimen, including plan of action for signs of feed intolerance, was common for all enrolled neonates. The median gestational age, birth weight and postnatal age at start of feeds were 29 versus 30 weeks (p = 0.40), 1232 versus 1280 g (p = 0.96) and 5 versus 5 days (p = 0.84) for erythromycin and placebo group, respectively. Time to achieve full feeds was not significantly different in the two groups. (median times: erythromycin 93.5 versus placebo 104 hours, p = 0.60). Erythromycin-related side-effects did not occur.

Anti-Bacterial Agents↗

Clinical use of erythromycin in children with gastrointestinal dysmotility.

Intolerant feeding is a common symptom in gastrointestinal disorders which is commonly found in systemic diseases. Prokinetic drugs play a role in management. A low dose of erythromycin has an effect on improvement of antroduodenal motility and gastric emptying in children and adults. The objective of this study was to evaluate the efficacy of intravenous erythromycin in the treatment of GI dysmotility in children. Retrospective studies were performed in the Department of Pediatrics, Siriraj Hospital, Mahidol University between 1996 and 2000 in 22 patients with intolerance of feeding due to GI dysmotility. Their ages ranged from 11 days to 12 years (42.1 +/- 48.1 months). The patients were divided into 2 groups: 12 critically ill and 10 non-critically ill patients. Dosages of intravenous erythromycin were 1-3 mg/kg/dose every 6 hours. The result of treatment was evaluated as: good (tolerant feeding), fair (tolerant feeding but needing erythromycin for longer than 1 month) and failed (intolerant feeding). All non-critically ill patients had improved symptoms with 9 +/- 4.3 days duration of treatment. In the other group, 8 patients had good results with 10.9 +/- 6 days of treatment. Two patients needed the drug for longer than 1 month and the other 2 patients did not respond and died due to severe infection. Low dose intravenous erythromycin had good efficacy in the treatment of intolerant feeding related to GI dysmotility in children.

Child↗

[Effect of erythromycin on apoptosis of eosinophils in nasal polyps in vitro].

OBJECTIVE: To study the effect of erythromycin on apoptosis of eosinophils in nasal polyps in vitro. METHODS: Fifteen nasal polyp biopsies were collected during nasal polypectomy. The specimens were cultured with erythromycin in RPMI1640, and cultured without erythromycin as control group. The explants in both groups were taken out at 1, 3, 5 day after culture. The apoptosis of cells was detected by terminal deoxynucleotidyl transferasemediated dUTP nick endlabeling(TUNEL), eosinophils were identified by morphology and serial sections stained with HE, then the apoptosis index (AI) of eosinophils was calculated. RESULTS: The AI of eosinophils in nasal polyps after cultured for 1,3,5 days with erythromycin were (31.77 +/- 9.52)%, (32.67 +/- 9.44)% and (50.34 +/- 8.78)% respectively. In control group, the AI of eosinophils were (29.18 +/- 7.31)%, (29.82 +/- 12.03)% and (42.25 +/- 8.08)% respectively. There were significant difference between two groups at 5 day after culture(P < 0.05). CONCLUSION: Erythromycin promoted apoptosis of eosinophils in nasal polyps in vitro.

Adolescent↗

Comparative efficacy of spiramycin and erythromycin in acute exudative tonsillitis in adults: a randomized controlled trial.

A randomized control trial was designed to compare the efficacies of spiramycin given one gram twice daily and erythromycin given 500 mg thrice or four times daily in the treatment of acute exudative tonsillitis in adults whose ages were over 13 years old from January 1989 to January 1991 at a community clinic. A total of 120 cases were enrolled in the study. Fifty-three patients received spiramycin while 67 received erythromycin. Group A beta-hemolytic streptococci (GABHS), S. aureus, and positive titer of Mycoplasma pneumoniae were detected in 19, 47 and 8 per cent in spiramycin group and 21, 36 and 11 per cent in erythromycin group respectively. GABHS were totally eradicated on day 3 of treatment in both groups through eradication of S. aureus was slightly slower initially in the spiramycin group. Marked improvement was similarly achieved in both groups after 3 days of therapy. Dyspepsia was felt in 34.4 and 8.2 per cent of erythromycin and spiramycin groups respectively but was tolerable by most patients. We concluded that spiramycin given twice daily was as effectively as conventional erythromycin but spiramycin is more convenient to administer and causes much less gastro-intestinal side-effect.

Acute Disease↗

Prophylaxis of ophthalmia neonatorum: comparison of silver nitrate, tetracycline, erythromycin and no prophylaxis.

From November, 1989, to October, 1991, 4544 neonates were born at our hospital. Neonatal ocular prophylaxis immediately after birth was used with 1% tetracycline ophthalmic ointment in 1156 neonates, 0.5% erythromycin ophthalmic ointment in 1163 neonates and 1% silver nitrate drops in 1082 neonates. No prophylaxis for neonatal conjunctivitis was given to 1143 neonates. A total of 302 infants (6.7%) developed conjunctivitis during the first 4 weeks of life. Between December, 1991, and January, 1992, 425 neonates were born at our hospital and all were given 0.5% erythromycin ophthalmic ointment twice in the first 24 hours after birth for ocular prophylaxis. Thirty-one (7.3%) infants developed conjunctivitis during the neonatal period. The incidence rates of neonatal chlamydial conjuctivitis in the tetracycline, erythromycin, silver nitrate, no prophylaxis and erythromycin twice groups were 1.3, 1.5, 1.7, 1.6 and 1.4%, respectively. We conclude that neonatal ocular prophylaxis with erythromycin (one or two doses) or tetracycline or silver nitrate does not significantly reduce the incidence of neonatal chlamydial conjunctivitis compared with that in those given no prophylaxis.

Conjunctivitis, Bacterial↗

Pharmacokinetics and tissue residue profiles of erythromycin in broiler chickens after different routes of administration.

This study investigated the disposition kinetics and plasma availability of erythromycin in broiler chickens after single intravenous (i.v.), intramuscular (i.m.), subcutaneous (s.c.) and oral administrations (p.o.) of 30 mg kg(-1) b. wt. Tissue residue profiles were also studied after multiple intramuscular, subcutaneous, and oral administration of 30 mg kg(-1) b. wt., twice daily for three consecutive days. Plasma and tissue concentrations of erythromycin were determined using microbiological assay methods with Micrococcus luteus as the test organism. Following intravenous injection, plasma concentration-vs-time curves were best described by a two compartment open model. The decline in plasma drug concentration was bi-exponential with half-lives of (t(1/2alpha)) 0.19 h and (t(1/2beta)) 5.3 h for distribution and elimination phases, respectively. After intramuscular, subcutaneous and oral administration erythromycin at the same dose was detected in plasma at 10 min and reached its minimum level 8 h post-administration. The peak plasma concentration (Cmax) were 5.0, 5.3, and 6.9 microg x ml(-1) and were attained at 1.7, 1.4, and 1.3 h (Tmax), respectively. The elimination half-lives (T(1/2el)) were 3.9, 2.6, and 4.1 h and the mean residence times (MRT) were 3.5, 3.2, and 3.6 h, respectively. The systemic bioavailabilities were 92.5, 68.8, and 109.3%, respectively. In vitro protein binding percent of erythromycin in broiler plasma was ranged from 21 to 31%. The limit of quantification (LOQ) for the assay was 0.03 microg x ml(-1) in plasma and tissues. The tissue level concentrations were highest in the liver, and decreased in the following order: plasma > kidney > lung > muscle and heart. No erythromycin residues were detected in tissues and plasma after 24 h except in liver and kidney where it persisted during 48 h following intramuscular and oral administrations.

Administration, Oral↗

[Biogenesis and regulation of biosynthesis of erythromycins in Saccharopolyspora erythraea: a review].

Data on the structure and stages of biosynthesis of erythromycins, relating to (1) successive addition of L-mycarose and D-desosamine to the lactones erythronolide B and mycarosyl-erythronolide B, respectively, and (2) biotransformation of erythromycin D to erythromycin A, are presented. Pathways of biosynthesis of L-mycarose, D-desosamine, and methylmalonyl-CoA and methylpropionyl-CoA precursors of erythronolide B are reviewed, along with the properties of genes coding the enzymes involved. Possible mechanisms of biochemical and gene regulation of erythromycin biosynthesis in Saccharopolyspora erythraea are discussed, including the role of factors ensuring predominant formation of the target product, erythromycin A.

Erythromycin↗

[Demonstration of a mechanism of anti-inflammatory effect of erythromycin on allergic airway inflammation in rat].

OBJECTIVE: To investigate whether erythromycin exerts anti-inflammatory effect on allergic airway inflammation and whether erythromycin modulate allergic airway inflammation by inhibiting nuclear factor kappa B (NF-kappa B) activation. METHODS: Ovalbumin (OVA) together with aluminum hydroxide and Bordetella Pertussis was injected intraperitoneally to immunize SD rats and two weeks later 1% OVA was inhaled to challenge them for consecutive 7 days to mimic allergic airway inflammation. In treatment group, erythromycin was given orally (180 mg/kg.d) during the course of allergen exposure. WBC counts in bronchoalveolar lavage fluid (BALF) and lung specimen analysis were used to describe lung tissue inflammation. The expression of NF-kappa B subunit p65 in cell nucleus of lung tissue was measured by immunohistochemistry and NF-kappa B binding activation in lung tissue by electrophoresis mobility shift assay (EMSA). RESULTS: Lung tissue specimen analysis indicated that the severity of allergic inflammation was reduced in treatment group. The number of total WBC in BALF (x 10(8)/L) (31 +/- 22) was lower than that in model group animals (66 +/- 28), P < 0.01. The number (x 10(3)/mm(2)) of cells with nuclear staining of NF-kappa B per square millimeter of submucosal region around large bronchus (1.4 +/- 0.4) was lower than that in model group animals (2.6 +/- 0.6), P < 0.01. NF-kappa B binding activity (32 +/- 14) was lower than that of model group (46 +/- 17), P < 0.05. CONCLUSION: Erythromycin had an obvious protective role in allergic airway inflammation. Erythromycin inhibited NF-kappa B transcriptional activity to exert anti-inflammatory effect.

Animals↗

[Relation of pbp2B, ermB, ermA/B, mefA genes with resistance to penicillin and erythromycin among Streptococcus pneumoniae isolates from children].

OBJECTIVE: To investigate the relation of pbp2B, ermB, ermA/B and mefA genes to penicillin and erythromycin resistance among isolated Streptococcus pneumoniae (Sp) in children. METHODS: Twenty-six strains of Sp were collected from September 2002 to April 2003 at the Children Hospital of Suzhou University. (1) Twenty-six pneumococcal isolates were obtained from respiratory tract secretions of children with respiratory diseases. (2) Susceptibility of the isolates to penicillin, cefuroxime, ceftriaxone, cefotaxime and erythromycin was determined by E-test. (3) The genes pbp2B, ermB, ermA/B and mefA of the isolates were detected with PCR. (4) The PCR product of pbp2B gene was sequenced. (5) DNA sequences of pbp2B of pneumococcal isolates were compared with those of SpR6 [penicillin sensitive (www.ncbi.nlm.gov/nucleotide, NC-003098)]. RESULTS: Among the 26 isolates studied, pbp2B gene mutation was found in 15(58%) isolates, all were point mutation of A, B, C and D genotypes which were seen in 11(73%), 2(13%), 1(7%) and 1(7%), respectively. The numbers of isolates susceptible to penicillin, cefuroxime, ceftriaxone and cefotaxime were 9(82%), 10(91%), 11(100%) and 11(100%), of 11 non-mutation isolates;numbers of isolates resistant to penicillin, cefuroxime, ceftriaxone, and cefotaxime were 13(87%), 11(73%), 1(7%) and 1(7%) out of 15 isolates with mutation.ErmB, ermA/B, mefA and erm/mef genes were positive in 9(35%), 16(62%), 7(27%) and 21(81%)isolates. MIC of erythromycin was 2 to > 256 mg/L among pneumococcal isolates with erm/mef genes. CONCLUSION: Among antibiotic resistant pneumococcal isolates in the area, the main basis of penicillin resistance was the mutation of pbp2B genes. Genotype A mutation had the highest rate among the isolates with mutation and manifested as resistance to penicillin and cefuroxime. Expression of either all or any of the ermA, ermB and mef genes led to erythromycin resistance. Antibiotics resistant Sp strains in this area are forming a challenge to efficacy of penicillin and erythromycin.

Aminoacyltransferases↗