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PubMed1986

An in-vitro study of oral therapeutic doses of co-trimoxazole and erythromycin stearate on abnormal polymorphonuclear leucocyte migration.

The effects of administration for four days of co-trimoxazole (2 X 500 mg tablets daily) and erythromycin stearate (3 X 500 mg tablets daily) on persistently abnormal polymorphonuclear leucocyte (PMNL) migration in six individuals with a history of chronic or recurrent bacterial infections were studied. The effects of co-incubation of PMNL in vitro with both antimicrobial agents at concentrations of 12(-5) and 10(-4) M were also investigated. Two different leucoattractants were used, autologous serum activated with bacterial endotoxin (EAS) and the synthetic chemotactic tripeptide FMLP. In three homosexual males with the acquired immunodeficiency syndrome (AIDS) abnormal PMNL motility was associated with the presence of serum inhibitor(s) of cell migration. In a fourth female subject, with recurrent episodes of acute periodontitis, and intrinsic cellular defect of PMNL migration associated with markedly impaired FMLP-induced degranulation and binding to PMNL was observed. In the remaining two subjects with chronic osteomyelitis, the precise abnormality of PMNL movement was not defined but appeared to be of the cellular intrinsic type. Co-incubation of PMNL with erythromycin, but not cotrimoxazole, at both concentrations tested (10(-5) and 10(-4) M) significantly improved cell migration to EAS, Likewise administration of erythromycin, but not cotrimoxazole, significantly improved PMNL migration to EAS. Improvement or correction of abnormal PMNL motility during antimicrobial chemotherapy with erythromycin may be a useful property of this antimicrobial agent.

Acquired Immunodeficiency Syndrome↗
PubMed1987

In-vitro comparison of roxithromycin and erythromycin against 900 anaerobic bacterial strains.

The in-vitro antibacterial activity of roxithromycin was assessed by an agar dilution method against 900 recent clinical anaerobic isolates by five laboratories in England, France, Germany and Japan. Roxithromycin had similar activity to erythromycin against most anaerobic bacteria, the latter being slightly more active against Gram-negative bacilli. Roxithromycin inhibited 53% of the Bacteroides fragilis group strains; the noticeable exception was Bact. thetaiotaomicron, only 17% of strains of which were inhibited by 4 mg/l roxithromycin. In contrast, all isolates of Bacteroides, other than the Bact. fragilis group, and all Mobiluncus isolates were inhibited by 2 mg/l of roxithromycin or less. This compound was inactive against half the Fusobacterium strains. Roxithromycin and erythromycin inhibited 65 and 72%, respectively, of 436 strains of Gram-negative anaerobes (MIC less than or equal to 4 mg/l). Roxithromycin suppressed 97% of non-sporulating Gram-positive to bacilli, 86% of Peptococcoaceae and 95% of clostridia. Two-thirds of Clostridium difficile strains were susceptible to roxithromycin (MIC less than or equal to 1 mg/l). The activity of roxithromycin against Gram-positive bacilli was identical to that of erythromycin. Overall a concentration of 4 mg/l roxithromycin and erythromycin inhibited 79 and 83%, respectively, of the strains investigated.

Bacteria, Anaerobic↗
PubMed1988

Effects of two erythromycins, doxycycline and phenoxymethylpenicillin on human leucocyte chemotaxis in vitro.

The effect of erythromycin, doxycycline and phenoxymethylpenicillin on human polymorphonuclear leucocyte (PMNL) chemotaxis was studied in vitro with Boyden's filter technique. Both erythromycin base and 2'-acetyl erythromycin stearate increased the PMNL chemotaxis significantly at concentrations greater than or equal to 50 microM, 2'-acetyl erythromycin stearate also at concentrations of 2.5-5 microM. Phenoxymethyl-penicillin reduced migration at 500 microM but lower concentrations had no significant effect. Doxycycline prevented migration significantly at concentrations greater than or equal to 50 microM.

Cell Count↗
PubMed1988

Comparison of spiramycin and erythromycin in the treatment of experimental guinea pig legionellosis.

Spiramycin was compared with erythromycin in a guinea pig model of severe Legionella pneumophila serogroup 1 infection. Male guinea pigs weighting 264-321 g were infected by the intraperitoneal route with 1.2 x 10(7) virulent L. pneumophila serogroup 1. Forty eight h after infection, animals that had lost greater than or equal to 9% of their body weight were randomly assigned to receive 48, 54 and 72 h after infection intraperitoneal injections of (1) distilled water (n = 20), (2) erythromycin lactobionate, 30 mg/kg per injection, (n = 22) or (3) the injectable form of spiramycin adipate, 30 mg/kg per injection (n = 22). Animals were observed daily for 15 days. All infected animals treated with distilled water died within four days of infection. Of the 22 animals treated with spiramycin, 10 (45.5%) died, and of the 22 animals treated with erythromycin, 11 (50.0%) died of disseminated L. pneumophila infection. In this animal model of very severe L. pneumophila infection, the injectable forms of erythromycin and of spiramycin gave similar results. Spiramycin should therefore be considered for the treatment of Legionnaires' disease in man.

Animals↗
PubMed1990

Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction.

The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students. The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction. Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin. Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin. Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction.

Adult↗
PubMed1991

Erythromycin and the treatment of Coxiella burnetii pneumonia.

Erythromycin is commonly used for the empirical treatment of community-acquired pneumonia, but there is some concern about its usefulness when Q fever is suspected because of in-vitro studies showing a lack of efficacy against Coxiella burnetii. This study was undertaken to assess the clinical value of the antibiotic in this setting. Nineteen patients with Q fever pneumonia treated with a variety of antibiotics considered ineffective against C. burnetii, were reviewed. Eleven patients who received erythromycin had a rapid clinical improvement and each became afebrile by the fourth day of treatment. However, only two of eight patients who received other antibiotics improved (both of them had been treated with beta-lactams). Both groups were comparable regarding to age and previous duration and severity of disease. Those patients who did not respond to other antibiotics improved promptly after erythromycin was started. This study suggests that erythromycin is an adequate treatment for Q fever pneumonia.

Adolescent↗
PubMed1992

Investigation of the in-vitro uptake, intraphagocytic biological activity and effects on neutrophil superoxide generation of dirithromycin compared with erythromycin.

The cellular uptake by human neutrophils and the intraphagocytic biological activity of the new macrolide antimicrobial agent dirithromycin (0.01-2 mg/L) compared with erythromycin was investigated in vitro. Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila were used as the test intracellular microbial pathogens. After coincubation (45 min at 37 degrees C) of neutrophils with a fixed concentration of 2 mg/L of each antibiotic the respective intracellular/extracellular ratios for erythromycin and dirithromycin were 6.1 +/- 2.5 and 10.6 +/- 2 respectively (P < 0.005). Using a combination of techniques (colony counting, radiometry and fluorescence microscopy) both erythromycin and dirithromycin at concentrations of 0.01 and 0.5 mg/L and higher, respectively, were found to possess dose-related intraphagocytic bacteristatic activity for each of the test microbial pathogens. The effects of dirithromycin and erythromycin (1-20 mg/L) on neutrophil chemotaxis and generation of reactive oxidants by these cells were also investigated in vitro. Both antimicrobial agents caused a dose-related stimulation of neutrophil migration which was associated with inhibition of leucoattractant-activated generation of superoxide and activity of the myeloperoxidase/H2O2/halide system. However, superoxide generation by neutrophils activited with opsonized zymosan or phorbol myristate acetate was unaffected by the macrolides. These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis.

Adult↗
PubMed1993

Influence of methylprednisolone on the intracellular antimicrobial activity of erythromycin and clindamycin against Legionella pneumophila.

We have investigated the effect of methylprednisolone on the intracellular activity of erythromycin and clindamycin in vitro. An assay system was developed for the determination of intracellular activity of antibiotics against Legionella pneumophila using guinea pig resident alveolar macrophages. Erythromycin at a concentration of 0.625 mg/L (5 x MIC) and clindamycin at a concentration of 8 mg/L (MIC) inhibited the growth of a single strain of L. pneumophila in macrophages, whilst ceftizoxime at a concentration of 0.625 mg/L (5 x MIC) did not. Methylprednisolone at therapeutic concentrations did not affect the intracellular antibacterial activity of either erythromycin or clindamycin against L. pneumophila. We found no direct effect of methylprednisolone on the intracellular antibacterial activity of either erythromycin or clindamycin.

Animals↗
PubMed1994

Pharmacokinetics of azithromycin and erythromycin in human endometrial epithelial cells and in cells infected with Chlamydia trachomatis.

The pharmacokinetics of azithromycin and erythromycin were examined in uninfected and Chlamydia trachomatis infected human endometrial epithelial cells in vitro. Cells which were grown in a polarized orientation showed a three-fold higher quantity of azithromycin uptake than did non-polarized cells. Cellular penetration profiles of azithromycin exceeded erythromycin by as much as eight-fold. In addition, approximately 20% of azithromycin remained cell-associated after 24 h in drug-free medium whereas erythromycin was not retained beyond 3 h. Hormone-responsive primary human endometrial gland epithelial cells, cultured directly after hysterectomy, showed enhanced uptake of both antimicrobials compared with laboratory adapted epithelial cell lines. Cells infected with a genital serovariant of C. trachomatis showed no significant difference in antibiotic uptake during the early stages of the chlamydial developmental cycle, and only a slight decrease in azithromycin uptake in the late stage of infection compared with non-infected cells. Morphological evidence of the bactericidal activity of azithromycin was evident in infected cells at most stages of the chlamydial developmental cycle, whereas the same concentration of erythromycin produced less evidence of marked bactericidal activity as observed by transmission electron microscopy.

Azithromycin↗
PubMed2000

High prevalence of erythromycin-resistant, clindamycin/miocamycin-susceptible (M phenotype) Streptococcus pyogenes: results of a Spanish multicentre study in 1998. Spanish Group for the Study of Infection in the Primary Health Care Setting.

Using the standard agar dilution method we studied the prevalence of susceptibility to 14-, 15- and 16-membered ring macrolides and clindamycin in Streptococcus pyogenes isolated in 1998 from 21 laboratories in Spain. The number of strains admitted to the study was proportional to the numbers of inhabitants in each geographical area. We also determined the susceptibility phenotypes and the genetic basis for the antibiotic resistance. A total of 486 unduplicated isolates of S. pyogenes were used. Throat swab samples provided 359 (73.9%) isolates, and the remaining 127 isolates were from other sources. One hundred and fourteen (23.5%) isolates were resistant to erythromycin, a 14-membered ring macrolide, and azithromycin, a 15-membered macrolide, whereas only 1% of isolates were resistant to miocamycin, a 16-membered macrolide and 0.8% were resistant to clindamycin. Of the 114 erythromycin-resistant strains, 109 (95.6%) were susceptible to clindamycin and miocamycin. Since induction with erythromycin did not modify susceptibility to the latter antibiotics, these 109 strains were considered to have the M phenotype. Twenty strains with the M phenotype, one per laboratory, were assayed by PCR and showed the presence of the mef gene, which is responsible for antibiotic resistance by an efflux system. Among comparable studies covering entire countries, ours demonstrates one of the highest rates of S. pyogenes erythromycin resistance and clindamycin and miocamycin susceptibility in the world. Strains with the M phenotype account for the great majority of these isolates.

Adult↗
PubMed2000

Streptococcus pneumoniae resistance to erythromycin and penicillin in relation to macrolide and beta-lactam consumption in Spain (1979-1997).

Streptococcus pneumoniae resistance to penicillin and erythromycin in relation to beta-lactam and macrolide consumption in Spain over 19 years (1979-1997) was studied from resistance data collected by a search of the literature. Antibiotic consumption was expressed in defined daily dosage (DDD)/1000 inhabitants/day. A significant relationship (P: < 0.001) between erythromycin resistance (MIC >/= 1 mg/L) and global macrolide consumption (r = 0.942), as well as between high-level penicillin resistance (MIC >/= 2 mg/L) and global beta-lactam consumption (r = 0.948) was observed. The relationship between erythromycin resistance and macrolide consumption was due mainly to consumption of macrolides taken twice a day (adjusted r(2) = 0.886). Prevalence of high-level penicillin resistance correlated with consumption of oral cephalosporins (adjusted r(2) = 0.877); however, there appeared to be no correlation of consumption of oral or parenteral aminopenicillins, narrow-spectrum penicillins or cephalosporins with intermediate-level penicillin resistance (MIC 0. 12-1 mg/L). The prevalence of high-level penicillin and of erythromycin resistance were also strongly correlated with each other (r = 0.903, P: < 0.001). In addition to global consumption, different categories of resistance (high or intermediate), and the differential capability of antibiotics to select resistance, must be taken into account when studying antibiotic impact on bacterial populations. Although this ecological analysis is not able to demonstrate a causal relationship between antibiotic consumption and development of resistance, it suggests that overuse of certain specific antibiotics is more likely to be related to the increase in drug-resistant strains of S. pneumoniae.

Anti-Bacterial Agents↗
PubMed2001

Erythromycin inhibits Pseudomonas aeruginosa-induced tumour necrosis factor-alpha production in human whole blood.

Erythromycin has been shown to be beneficial for panbronchiolitis, a disorder linked to infection with Pseudomonas aeruginosa. Erythromycin, but not the anti-Pseudomonas antibiotics imipenem, ceftazidime, gentamicin and ciprofloxacin, caused a dose-dependent decrease in the production of tumour necrosis factor (TNF)-alpha by whole blood stimulated with heat-killed P. aeruginosa. The release of interleukin (IL)-10, IL-6, interferon-gamma and IL-8 was inhibited only at the highest erythromycin concentration. Inhibition of TNF-alpha production by erythromycin may, at least in part, explain the efficacy of this macrolide during panbronchiolitis despite its lack of activity for P. aeruginosa.

Anti-Bacterial Agents↗
PubMed2002

Endothelial cell compatibility of azithromycin and erythromycin.

Phlebitis is a severe local adverse event related to the use of parenteral macrolides. In order to evaluate the effect of azithromycin and erythromycin on human venous endothelial cells, we set up an in vitro model. The intracellular levels of purine nucleotides, as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and guanosine 5'-triphosphate (GTP), were measured by means of high-performance liquid chromatography. Incubation of cells with 2 mg/mL azithromycin and erythromycin resulted in a rapid decline of intracellular ATP from 12.5 +/- 0.9 nmol/million cells to 4.1 +/- 0.3 and 2.6 +/- 0.4 nmol/million cells, respectively, after 60 min. In addition, ADP was extensively depleted from 2.1 +/- 0.17 nmol/million cells to 0.8 +/- 0.09 and 0.8 +/- 0.13 nmol/million cells after 60 min. After exposure of 0.5 mg/mL azithromycin and erythromycin, no significant decline of intracellular high-energy phosphate levels occurred after 20 and 60 min. Based on these results, solutions of azithromycin and erythromycin may not be well tolerated and may cause local adverse reactions even if diluted according to the manufacturer's recommendation.

Anti-Bacterial Agents↗
PubMed2003

Clonal diversity among erythromycin-resistant beta-haemolytic Streptococcus isolates in La Rioja, Spain.

OBJECTIVE: To analyse clonal diversity in 72 erythromycin-resistant beta-haemolytic streptococci. METHODS: Clonal relationships were studied for streptococci of groups A (GAS, n = 30), B (GBS, n = 34), C (GCS, n = 4) and G (GGS, n = 4) by means of PFGE. Streptococcal isolates were obtained from a 450-bed hospital in Spain during the following periods: GAS (1996-2001), GBS (1999-2001), GCS and GGS (1997-2000). RESULTS: Twenty-two of the 30 GAS isolates showed the M resistance phenotype and harboured the mef(A) gene. Five unrelated PFGE patterns were identified among these 22 GAS isolates. Sixteen of them, obtained during four different years of the study, showed one of the two predominant PFGE patterns. The remaining eight GAS isolates showed the MLSB resistance phenotype, and four unrelated PFGE patterns were detected. All but one erythromycin-resistant GBS showed the MLSB resistance phenotype, and an erm gene was identified in all cases [erm(B) or erm(A)]. Twenty-two unrelated PFGE patterns were demonstrated among 25 GBS with the MLSB resistance phenotype; the remaining eight MLSB GBS isolates could not be typed by PFGE. The eight erythromycin-resistant GGS and GCS isolates of this study presented seven unrelated PFGE patterns. GGS and GCS strains showed an MLSB resistance phenotype and had the erm(A) gene. CONCLUSIONS: High clonal diversity was detected in this series of erythromycin-resistant GBS, whereas lower diversity was seen in the GAS isolates.

Anti-Bacterial Agents↗
PubMed2005

Enhanced resistance to erythromycin is conferred by the enterococcal msrC determinant in Staphylococcus aureus.

OBJECTIVES: The msrC gene, found on the chromosome of Enterococcus faecium, shares a high degree of similarity with the staphylococcal erythromycin resistance determinant msr(A). The enterococcal determinant was cloned into Staphylococcus aureus to determine whether msrC could confer antibiotic resistance in staphylococci. METHODS: A shuttle vector comprising pBluescript and pSK265 was used to introduce multiple copies of msrC into S. aureus RN4220. The integration vector pCL84 was employed to insert a single copy of msrC into the S. aureus chromosome. MICs were determined by the broth microdilution method. RESULTS: Expression of msrC from both chromosomal and plasmid loci in erythromycin-susceptible S. aureus RN4220 (MIC 0.25 mg/L) gave rise to enhanced protection against erythromycin, with an MIC of 32-64 mg/L for S. aureus RN4220 containing msrC in multiple copies and an MIC of 16-64 mg/L with msrC inserted as a single copy in the S. aureus chromosome. CONCLUSIONS: MsrC mediates high-level resistance to erythromycin in S. aureus.

Bacterial Proteins↗
PubMed2005

Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae.

OBJECTIVE: To evaluate the effect of delayed administration of erythromycin in the course of acute otitis media caused by an erythromycin-susceptible Streptococcus pneumoniae strain in the gerbil model. METHODS: The bacterium was inoculated by transbullar challenge in the middle ear (ME) and antibiotic treatment at different doses was administered at various times thereafter. RESULTS: When 2.5 mg/kg of erythromycin was administered as a single dose 2, 5, 18 or 21 h post-inoculation (pi) the bacterial eradication rate was 55, 40, 0 and 0%, respectively. A higher dose (5 mg/kg) administered also as a single dose 2, 5, 18 and 21 h pi achieved bacterial eradication rates of 62.5, 43.8, 0 and 0%, respectively. Using a very high dose (50 mg/kg) repeated three times at 3 h intervals (total dose 150 mg/kg) and starting the treatment 21 h pi only achieved bacterial eradication in 25% of cases. The concentration of erythromycin achieved in the ME 90 min after administration of 5 mg/kg 5 or 21 h pi was very similar (0.74 and 0.79 mg/L) but the ME half-life was longer (98.2 min) with the early administration as compared with the delayed form (47.5 min), which could partially explain the different results. Further experiments showed that the failures observed with the delayed administration were not related to the time elapsed from antibiotic administration to ME sampling or selection of antibiotic-resistant mutants. CONCLUSION: Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.

Animals↗
PubMed2002

UK guidelines for use of erythromycin chemoprophylaxis in persons exposed to pertussis.

Pertussis is well controlled in the UK as a result of an effective vaccination programme. Nevertheless, the disease has not been eliminated, and cases still occur in the most vulnerable group of young infants. Erythromycin chemoprophylaxis has been advocated for use in contacts to prevent secondary cases but the evidence for its use is weak. These guidelines are based on a review of the evidence and aim to help clinicians make more rational decisions on the use of erythromycin chemoprophylaxis for pertussis. Erythromycin has well-established side effects and so its use should be limited to situations where it is likely to be of greatest benefit. If a clinically suspected or confirmed case of pertussis is identified who is also in household contact with someone at greatest risk from pertussis--young infants, especially neonates--then erythromycin chemoprophylaxis should be considered. The aim is to protect those at greatest risk from pertussis by offering chemoprophylaxis to them, to all their household contacts who are unimmunized and to contacts who are 5 years or older if they did not receive a pre-school pertussis booster (not given to those born before 1996 in the United Kingdom). There is no evidence of any benefit from chemoprophylaxis given more than 21 days from the date of onset of the primary case. Unimmunized or partially immunized cases and contacts should complete their course of vaccine.

Antibiotic Prophylaxis↗
PubMed2000

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Acetaminophen↗