Erythromycin Treatment Research Articles

Real-time monitoring of immune responses under pathogen invasion and drug interference by integrated microfluidic device coupled with worm-based biosensor

Immune response to environmental pathogen invasion is a complex process to prevent host from further damage. For quantitatively understanding immune responses and revealing the pathogenic environmental information, real-time monitoring of such a whole dynamic process with single-animal resolution in well-defined environments is highly desired. In this work, an integrated microfluidic device coupled with worm-based biosensor was proposed for in vivo studies of dynamic immune responses and antibiotics interference in infected C. elegans. Individual worms housed in chambers were exposed to the various pathogens and discontinuously manipulated for imaging with limited influence on physiological activities. The expression of immune responses gene (irg-1) was time-lapse measured in intact worms during pathogen infection. Results demonstrated that irg-1 gene could be induced in the presence of P. aeruginosa strain PA14 in a dose-dependent manner, and the survival of infected worm could be rescued under gentamicin or erythromycin treatments. We expect it to be a versatile platform to facilitate future studies on pathogenesis researches and rapid drug screen using C. elegans disease model.

The association between erythromycin monotherapy for Mycobacterium avium complex lung disease and cross-resistance to clarithromycin: A retrospective case-series study.

Long-term, low-dose erythromycin monotherapy, based on the anti-inflammatory effects of macrolides, has been reported to have the potential to suppress the exacerbation of Mycobacterium avium complex (MAC) lung disease with less toxicity. It remains unclear whether erythromycin monotherapy induces cross-resistance to clarithromycin, a key drug for MAC. To clarify this point, we conducted a retrospective, single-center, case-series study on patients with MAC lung disease who underwent erythromycin monotherapy for at least 6 months. Drug susceptibility tests, before and after erythromycin treatment initiation, were analyzed. Thirty-three patients were included in our study. All 33 patients showed susceptibility to clarithromycin for MAC both before and after erythromycin monotherapy. There was no significant difference in clarithromycin minimum inhibitory concentrations between before and after erythromycin treatment (median difference=0μg/ml; P=.313, Wilcoxon's signed-rank test). We conclude that erythromycin monotherapy for MAC lung disease may not induce cross-resistance to clarithromycin.

EPIDEMIOLOGICAL INVESTIGATION OF PASTEURELLA MULTOCIDA INFECTION IN POULTRY IN GAZIPUR DISTRICT OF BANGLADESH

The present study was undertaken to determine the present status of fowl cholera (FC) infection of poultry in Gazipur district during September 2016 to February 2017. A total of 282 either dead or sick birds (Layer and Sonali) were taken as sample in which the sick birds were subjected to record clinical data and consequently the dead birds were for post mortem examination. Hence, overall 12.41% prevalence was found for FC and about 87.59% was for mixed other diseases. All the birds were grouped into six named as A1, A2 and up to A6 accordingly their age. The highest incidence (29.79 %) was found in A1 (8-20weeks) group and the lowest was 4.26% in A5 (51-60 weeks) group. Furthermore, six FC infected farms were categorized to treat with six specific antibiotics individually. Thereafter, the highest recovery rate (89.6% and 87.5%) was recorded in two farms using Enrofloxacin and Gentamicin particularly. The lowest recovery rate (60%) was in Erythromycin treatment group. However, the layer birds of six farms lost their body weight almost 11.84%, specifically the highest percentages (16.49%) was in treated with Ampicillin and lowest percentages (5.79%) found in a farm treated with Gentamicin. In brief, FC commonly appears just near to laying age and therapeutic management trivially decreases the body weight that ultimately shoots up the production cost.

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin

BackgroundPreterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown.MethodsWe prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.ResultsIn contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis.ConclusionsOur data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Combination of Erythromycin and Curcumin Alleviates Staphylococcus aureus Induced Osteomyelitis in Rats.

Osteomyelitis is commonly caused by Staphylococcus aureus. Both erythromycin and curcumin can suppress S. aureus growth, but their roles in osteomyelitis are barely studied. We aim to explore the activities of erythromycin and curcumin against chronical osteomyelitis induced by methicillin-resistant S. aureus (MRSA). Chronicle implant-induced osteomyelitis was established by MRSA infection in male Wistar rats. Four weeks after bacterial inoculation, rats received no treatment, erythromycin monotherapy, curcumin monotherapy, or erythromycin plus curcumin twice daily for 2 weeks. Bacterial levels, bone infection status, inflammatory signals and side effects were evaluated. Rats tolerated all treatments well, with no death or side effects such as, diarrhea and weight loss. Two days after treatment completion, erythromycin monotherapy did not suppress bacterial growth and had no effect in bone infection, although it reduced serum pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. Curcumin monotherapy slightly suppressed bacterial growth, alleviated bone infection and reduced TNF-α and IL-6. Erythromycin and curcumin combined treatment markedly suppressed bacterial growth, substantially alleviated bone infection and reduced TNF-α and IL-6. Combination of erythromycin and curcumin lead a much stronger efficiency against MRSA induced osteomyelitis in rats than monotherapy. Our study suggests that erythromycin and curcumin could be a new combination for treating MRSA induced osteomyelitis.

Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

An important problem in management of the case with myasthenia gravis (MG) is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

Chemopreventive effects of a low-side-effect antibiotic drug, erythromycin, on mouse intestinal tumors.

It is important to establish effective methods for preventing colorectal cancer because the number of colorectal cancer deaths is increasing. Erythromycin one of the macrolide antibiotics, has been shown to exert pleiotropic effects, such as anti-inflammatory and anti-oxidative effects, on mammalian cells. In the present study, we aimed to evaluate the preventive effects of erythromycin on intestinal carcinogenesis. We first confirmed that erythromycin suppresses the transcriptional activity of nuclear factor-κB and activator protein-1 and the expression of its downstream targets, interleukin-6 and cyclooxygenase-2 in human colon cancer cells. Next, we fed 5-week-old male Apc mutant Min mice with diets containing 500 ppm erythromycin for 15 weeks. Erythromycin treatment significantly reduced the number of proximal intestinal polyps to 70.9% of the untreated control value. Moreover, erythromycin reduced the levels of interleukin-6 and cyclooxygenase-2 mRNA expression in intestinal polyps. Although the levels of hepatic NADPH oxidase mRNA were decreased, erythromycin treatment did not affect the levels of oxidative stress markers, reactive carbonyl species, in the liver of Min mice. Our results suggest that erythromycin suppresses intestinal polyp development in Min mice, in part by attenuating local inflammation, and indicate that erythromycin is useful as a chemopreventive agent.

Erythromycin or Clindamycin - is it Still an Empirical Therapy against Streptococcus agalactiae in Patients Allergic to Penicillin?

Retrospective analysis of Streptococcus agalactiae antibiotic susceptibility isolated in 2010-2013 was performed. Penicillin was still the first-line antibiotic. Due to the high percentage of strains resistant to erythromycin and clindamycin empirical treatment with these antibiotics may not be effective. Lower resistance rate to erythromycin and clindamycin among strains isolated from infected pregnant women and newborns were observed than among strains isolated from samples from patients hospitalized in other departments (29% and 47% v. 46% and 63%). The increasing resistance rate might give a rise to a new epidemiological situation.

The Chondroprotective Role of Erythromycin in a Murine Joint Destruction Model

Inflammation is a major player in the joint destruction process. Macrolide antibiotics have recently been found to have a novel anti-inflammatory function, but their effects on the joint are unknown. Our objective was to investigate the effect of macrolide antibiotic erythromycin on cartilage gene expression under inflammatory conditions as well as on joint pathology in an in vivo inflammatory joint destruction model. In our in vivo studies, mouse knee joints were injected with monosodium iodoacetate (MIA), a chemical that inhibits glycolysis and causes joint inflammation and matrix loss. Erythromycin was administered by daily intraperitoneal injection. Changes in joint cartilage and synovium were evaluated by histological analysis. In our in vitro studies, primary bovine articular chondrocytes were treated with erythromycin in the presence of pro-inflammatory cytokine IL-1β or lipopolysaccharide (LPS), and cartilage gene expression analysis was performed. Regional differences in cartilage matrix destruction along the medial-lateral axis were observed in joints of MIA-injected mice. Erythromycin treatment inhibited cartilage matrix loss and synovitis in these joints. In addition, erythromycin inhibited IL-1β and LPS-induced expression of MMPs and iNOS, as well as the positive regulatory loop between IL-1β and Toll-like receptor 4 (TLR4) in articular chondrocytes. Furthermore, erythromycin prevented LPS-induced NF-κB activation, a key mediator of TLR4-mediated cartilage destruction process. Erythromycin has the ability to inhibit catabolic gene expression mediated by IL-1β and TLR4 in chondrocytes in vitro and maintains cartilage matrix levels in experimental inflammatory joint destruction in vivo, suggesting that it possesses a chondroprotective activity.

A randomised controlled feasibility and proof-of-concept trial in delayed gastric emptying when metoclopramide fails: We should revisit nasointestinal feeding versus dual prokinetic treatment: Achieving goal nutrition in critical illness and delayed gastric emptying: Trial of nasointestinal feeding versus nasogastric feeding plus prokinetics

Delayed gastric emptying (DGE) commonly limits the use of enteral nutrition (EN) and may increase ventilator-associated pneumonia. Nasointestinal feeding has not been tested against dual prokinetic treatment (Metoclopramide and Erythromycin) in DGE refractory to metoclopramide. This trial tests the feasibility of recruiting this 'treatment-failed' population and the proof of concept that nasointestinal (NI) feeding can increase the amount of feed tolerated (% goal) when compared to nasogastric (NG) feeding plus metoclopramide and erythromycin treatment. Eligible patients were those who were mechanically ventilated and over 20 years old, with delayed gastric emptying (DGE), defined as a gastric residual volume ≥250ml or vomiting, and who failed to respond to first-line prokinetic treatment of 3 doses of 10mg IV metoclopramide over 24h. When assent was obtained, patients were randomised to receive immediate nasointestinal tube placement and feeding or nasogastric feeding plus metoclopramide and erythromycin (prokinetic) treatment. Of 208 patients with DGE, 77 were eligible, 2 refused assent, 25 had contraindications to intervention, almost exclusively prokinetic treatment, and it was feasible to recruit 50. Compared to patients receiving prokinetics (n=25) those randomised to nasointestinal feeding (n=25) tolerated more of their feed goal over 5 days (87-95% vs 50-89%) and had a greater area under the curve (median [IQR] 432 [253-464]% vs 350 [213-381]%, p=0.026) demonstrating proof of concept. However, nasointestinally fed patients also had a larger gastric loss (not feed) associated with the NI route but not with the fluid volume or energy delivered. This is first study showing that in DGE refractory to metoclopramide NI feeding can increase the feed goal tolerated when compared to dual prokinetic treatment. Future studies should investigate the effect on clinical outcomes. EudraCT number: 2012-001374-29.

Role of the vaginal microbiome in preterm prelabour rupture of the membranes: an observational study

BackgroundAround 30% of preterm births are preceded by prelabour rupture of the membranes, and pathobionts ascending from the vagina are implicated in 40% of cases. A detailed understanding of the vaginal microbiome in preterm prelabour rupture of the membranes (PPROM) is pivotal for the development of predictive, preventive, and therapeutic strategies. We aimed to assess the vaginal microbiome of women with PPROM and the effect of erythromycin treatment. MethodsVaginal swabs were taken from pregnant women at four antenatal timepoints and following PPROM before and after erythromycin treatment. A subset of those women sampled antenatally subsequently developed PPROM whereas the remainder delivered at term, forming the control group from which gestational age-matched (27–30 weeks') samples were drawn. Swabs were immediately frozen and stored at −80°C, and bacterial DNA was extracted by enzymatic and mechanical disruption. Bacterial species composition and structure of resident communities were examined by next generation sequencing of 16S rRNA gene amplicons, V1-V3 (Illumina MiSeq, San Diego, CA, USA). Findings91 pregnant women were examined. Women who went on to develop PPROM (n=12) had a vaginal microbiome before membrane rupture that was dominated by Lactobacillus iners (7, 58%), L jenseni (1, 8%), and L crispatus (1, 8%); three women (25%) had a vaginal microbiome low in Lactobacillus spp and enriched with Gram-negative bacteria such as Prevotella spp (dysbiotic). Control women (n=39) had a vaginal microbiome dominated by L crispatus (17, 43%), L iners (12, 31%), L jenseni (5, 13%), and L gasseri (5, 13%), with no samples displaying dysbiosis. After membrane rupture but before erythromycin treatment (n=17), the vaginal microbiome was dominated by L iners (8, 47%), dysbiosis (5, 29%), L crispatus (3, 18%), and L iners plus L crispatus (1, 6%). After 48 h of erythromycin treatment (n=23), dysbiosis increased to become the dominant state in 18 women (74%). InterpretationOur finding that a vaginal microbiome devoid of L crispatus before membrane rupture is a feature of pregnancies complicated by PPROM supports a protective role for L crispatus in the prevention of this complication of pregnancy. Dysbiosis rises after PPROM and becomes the dominant community state after erythromycin treatment. This finding suggests that environmental perturbations of membrane rupture, in combination with erythromycin treatment, promotes dysbiosis and a community state that harbours bacteria implicated in maternal and neonatal sepsis. FundingMedical Research Council.

Diffuse panbronchiolitis-The response and recurrence after erythromycin therapy.

Diffuse panbronchiolitis (DPB) is a rare clinicopathological entity. To date, no cohort study of DPB has been conducted in Taiwan. Erythromycin treatment improves the clinical outcome of DPB; however, whether relapse will occur or not is unclear. Herein, we report the first retrospective cohort of DPB patients in one medical center in Taiwan, including their clinical presentation and outcomes of erythromycin treatment. The study comprised a retrospective cohort analysis of 27 patients with a confirmed diagnosis of DPB. Clinical, radiological, and laboratory parameters were analyzed, and the course and outcome of erythromycin treatment were examined. The mean age at symptom onset was 56.6±18.5 years, and the time between symptom onset and a correct diagnosis was 4.3±4.2 years. The percentages of patients with centrilobular micronodules on chest computed tomography, obstructive ventilator impairment with hypoxemia, and an elevated cold agglutinin titer were 72%, 37%, and 78%, respectively. After erythromycin treatment, 22 of the 27 (81.5%) patients showed clinical improvement, of whom six suffered a relapse. Four of these six patients clinically improved after a second course of erythromycin treatment. Erythromycin therapy was suitable for DPB in our experience. In this study cohort, 27% experienced a relapse, of which two-thirds of the patients improved after a second course of erythromycin treatment.

Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is caused by the expansion of a CTG repeat in the 3' untranslated region of DMPK. The transcripts containing an expanded CUG repeat (CUG (exp)) result in a toxic gain-of-function by forming ribonuclear foci that sequester the alternative splicing factor muscleblind-like 1 (MBNL1). Although several small molecules reportedly ameliorate RNA toxicity, none are ready for clinical use because of the lack of safety data. Here, we undertook a drug-repositioning screen to identify a safe and effective small molecule for upcoming clinical trials of DM1. We examined the potency of small molecules in inhibiting the interaction between CUG (exp) and MBNL1 by in vitro sequestration and fluorescent titration assays. We studied the effect of lead compounds in DM1 model cells by evaluating foci reduction and splicing rescue. We also tested their effects on missplicing and myotonia in DM1 model mice. Of the 20 FDA-approved small molecules tested, erythromycin showed the highest affinity to CUG (exp) and a capacity to inhibit its binding to MBNL1. Erythromycin decreased foci formation and rescued missplicing in DM1 cell models. Both systemic and oral administration of erythromycin in the DM1 model mice showed splicing reversal and improvement of myotonia with no toxicity. Long-term oral administration of erythromycin at the dose used in humans also improved the splicing abnormality in the DM1 model mice. Oral erythromycin treatment, which has been widely used in humans with excellent tolerability, may be a promising therapy for DM1.

Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan.

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Macrolide-induced hyperthermia in foals: Role of impaired sweat responses.

The mechanism of hyperthermia, a potentially fatal adverse effect of erythromycin treatment of foals, is unknown. To determine the cause of erythromycin-associated hyperthermia. It was hypothesised that the normal sweat response of foals is impaired by treatment with erythromycin. Blinded, crossover study in 10 healthy pony foals. Foals kept in stalls were given either erythromycin (25mg/kg bwt orally, 3 times daily) or control for 10days then turned out for a further 10days. Quantitative intradermal terbutaline sweat tests were performed on Days 1 (baseline), 3, 10 and 20. The effects on terbutaline-induced sweating of erythromycin, terbutaline concentration and treatment day were analysed by repeated-measures ANOVA with Bonferroni-corrected pairwise post hoc comparisons. Peak temperatures were compared by Wilcoxon's signed rank test and proportions by McNemar's related samples test. Significance was set at P<0.05. There were significant 2-factor interactions for treatment × terbutaline after baseline, treatment × day at every terbutaline concentration, and day × terbutaline for erythromycin (P<0.001) but not control (P=0.9) treatment. Sweating was significantly reduced from baseline in erythromycin-treated foals at all subsequent days. Erythromycin-treated foals produced less sweat at all time-points than did control-treated foals (P<0.05). Peak rectal temperatures of erythromycin-treated foals were significantly higher (P=0.02) than those of controls. During the first 3days outside more erythromycin-treated than control-treated foals required treatment for hyperthermia (6 vs. 0; P=0.03). We believe drug-induced anhidrosis is the likely cause of hyperthermia in some foals treated with erythromycin.

Effects of Erythromycin on Neutrophil Chemotaxis in Rats

Background: Erythromycin showed an inhibitory effect on neutrophil exudation to the middle ear cavity in a rat model of otitis media. Methods: Erythromycin (EM) was administered intraperitoneally into male Splague-Dawley rats at 10 mg/kg once daily for 7 or 14 days. A purified neutrophil suspension was employed in the neutrophil chemotaxis experiment using the Boyden chamber method. Results: A significant increase in migration was observed at 50 and 100 ng/ml growth-related gene product (GRO) as compared to the assay with the addition of serum alone. Strong migration activity was also seen in the presence of zymosanactivated C5a in the assay medium. Treatment with EM for both 7 and 14 days suppressed the enhanced migration of neutrophils induced by 50 and 100 ng/ml GRO. In contrast, C5a significantly enhanced neutrophil migration under the treatment of EM for both 7 and 14 days. Conclusion: The present study first revealed that EM administration to animals selectively inhibited the GRO-induced migration of neutrophils, which may contribute to its antiinflammatory effect on the upper respiratory mucosa.

Erythromycin as a Safe and Effective Treatment Option for Erythema Annulare Centrifugum.

Background:Erythema annulare centrifugum (EAC) is an inflammatory dermatosis with unknown etiology. It is usually self-limited, but chronic disease may be difficult to treat. We observed incidentally the therapeutic effect of erythromycin for EAC among patients taking erythromycin for other diseases.Aim:To evaluate the treatment response of erythromycin for EAC.Materials and Methods:During the study period, from July 2007 to February 2011, all patients with EAC were assigned to erythromycin stearate tablet 1000 mg per day for two weeks. EAC was diagnosed by a constellation of clinical and pathological findings. The efficacy (before and after the treatment) was assessed clinically by one dermatologist and photographically by two blinded dermatologists. Secondary outcomes included adverse drug effects and recurrence.Results:Eight patients were enrolled in this study. Most patients had chronic relapsing disease with poor response to previous treatment. All the patients showed rapid response with profound reduction in the size of lesion and erythema two weeks after initiation of erythromycin treatment. The response was so obvious and complete that a coincidental response was less likely. Three patients had recurrence of disease and they tended to have more extensive lesions. Readministration of erythromycin was effective. All patients tolerated the treatment well.Conclusion:Our study documented erythromycin as a safe and cost-effective treatment for EAC.

Scallop larval survival from erythromycin treated broodstock after conditioning without sediment

Abstract Pathogenic bacteria are known to be one of the main factors affecting Pecten maximus larval survival in hatcheries. As a result, juvenile production often relies on the use of antibiotics during larval culture. However, limitations of the usage of chemicals such as chloramphenicol in aquaculture have been reinforced due to their negative environmental impact and alternatives are accordingly needed. Thus, the importance of bacterial transfer from oocytes to larvae has been studied here as well as procedures to limit larval mortality in P. maximus. In order to reduce bacterial contamination during larval development, we focused on two periods, broodstock conditioning and post-fertilization. The animals were conditioned for 2 months with two erythromycin treatments of 6 days, with (SA) or without sandy-bottom (NSA). The absence of sediment strongly reduced contamination by Vibrios of oocytes (NSA: 0.003 ± 0.002 CFU oocyte− 1 SA: 0.57 ± 0.17 CFU oocyte− 1) and D-larvae (NSA: 0.14 ± 0.05 CFU D-larva− 1 SA: 0.51 ± 0.002 CFU D-larva− 1). It also enhanced survival by 52% at 15 days post fertilization, whereas a two day antibiotic treatment of D-larvae did not improve subsequent survival, regardless of broodstock conditioning method. Furthermore, both treatments led to similar fatty acid profiles of oocytes and resulting larvae, suggesting that broodstock conditioning was physiologically similar with or without sediment. This work has shown that gamete contamination could be reduced when sandy-bottom was removed during broodstock conditioning under bacterial control with erythromycin. The present results contribute to a reduced utilization of antimicrobial agents for great scallop larval rearing in controlled condition.

Controlled trial for long-term low-dose erythromycin after sinus surgery for chronic rhinosinusitis.

The efficacy of macrolides in chronic rhinosinusitis (CRS) is still under controversy. To date, only two double-blind, placebo-controlled studies have been published with differing results. None of these studies investigated the possible benefit of macrolides in the postoperative period. We conducted an investigator-initiated clinical trial using 250-mg erythromycin once a day over a period of 3 months, beginning the administration of either erythromycin or placebo 2 weeks after a surgical intervention for CRS. Randomized double-blind, placebo-controlled trial. The concentrations of eosinophilic cationic protein (ECP) and myeloperoxidase in nasal secretion were chosen as primary outcome measures. Additionally, as a secondary outcome measure, changes in the Sino-Nasal Outcome Test-20 score, olfaction, saccharin transit time, nasal endoscopy score, and self-rating of nasal health using a visual analogue scale were evaluated. Sixty-seven patients after surgery for CRS with or without nasal polyps were screened, and 58 patients were randomized to the study groups. For the primary outcomes, the concentrations of ECP changed from 176.4 µl/l ± 79.0 to 226.1 µl/l ± 200.6 in the erythromycin group and from 186.9 µl/l ± 36.0 to 192.9 µl/l ± 189.2 in the placebo group; no statistical differences were found. Of the secondary outcomes, only the nasal endoscopy score showed a statistically significant improvement in the erythromycin group (from 2.6 ± 1.4 to 1.9 ± 1.5 points) compared to the placebo group (from 2.5 ± 1.3 to 2.6 ± 1.5 points). The subgroup of patients without nasal polyps in the erythromycin group showed a tendency to improvement in some secondary outcome criteria. A general recommendation for long-term, low-dose erythromycin treatment after surgery for CRS cannot be given. In patients with CRS without nasal polyps, a tendency to improved parameters was detected. Ib.

The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial

Long-term macrolide treatment has proven benefit in inflammatory airways diseases, but whether it leads to changes in the composition of respiratory microbiota is unknown. We aimed to assess whether long-term, low-dose erythromycin treatment changes the composition of respiratory microbiota in people with non-cystic fibrosis bronchiectasis. Microbiota composition was determined by 16S rRNA gene sequencing of sputum samples from participants in the BLESS trial, a 12-month, double-blind, placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg) in adult patients with non-cystic fibrosis bronchiectasis and at least two infective exacerbations in the preceding year. The primary outcome was within-patient change in respiratory microbiota composition (assessed by Bray-Curtis index) between baseline and week 48, comparing erythromycin with placebo. The BLESS trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000460303. The BLESS trial took place between Oct 15, 2008, and Dec 14, 2011. Paired sputum samples were available from 86 randomly assigned patients, 42 in the placebo group and 44 in the erythromycin group. The change in microbiota composition between baseline and week 48 was significantly greater with erythromycin than with placebo (median Bray-Curtis score 0·52 [IQR 0·14-0·78] vs 0·68 [0·46-0·93]; median difference 0·16, 95% CI 0·01-0·33; p=0·03). In patients with baseline airway infection dominated by Pseudomonas aeruginosa, erythromycin did not change microbiota composition significantly. In those with infection dominated by organisms other than P. aeruginosa, erythromycin caused a significant change in microbiota composition (p=0·03 [by analysis of similarity]), representing a reduced relative abundance of Haemophilus influenzae (35·3% [5·5-91·6] vs 6·7% [0·8-74·8]; median difference 12·6%, 95% CI 0·4-28·3; p=0·04; interaction p=0·02) and an increased relative abundance of P aeruginosa (0·02% [0·00-0·33] vs 0·13% [0·01-39·58]; median difference 6·6%, 95% CI 0·1-37·1; p=0·002; interaction p=0·45). Compared with placebo, erythromycin reduced the rate of pulmonary exacerbations over the 48 weeks of the study in patients with P. aeruginosa-dominated infection (median 1 [IQR 0-3] vs 3 [2-5]; median difference -2, 95% CI -4 to -1; p=0·01), but not in those without P. aeruginosa-dominated infection (1 [0-2] vs 1 [0-3]; median difference 0, -1 to 0; p=0·41; interaction p=0·04). Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis. In patients without P. aeruginosa airway infection, erythromycin did not significantly reduce exacerbations and promoted displacement of H. influenzae by more macrolide-tolerant pathogens including P. aeruginosa. These findings argue for a cautious approach to chronic macrolide use in patients without P. aeruginosa airway infection. Mater Adult Respiratory Research Trust Fund.