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International Journal of Molecular... May 2023Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for... (Review)
Review
Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.
Topics: Humans; Macrolides; Anti-Bacterial Agents; Sinusitis; Treatment Outcome; Cytokines; Chronic Disease; Rhinitis
PubMed: 37298439
DOI: 10.3390/ijms24119489 -
Journal of Microbiology, Immunology,... Oct 2022Expansion of the single sequence type 3 (ST3) was associated with a high macrolide resistance rate among Mycoplasma pneumoniae in Korea during the 2014-2016 epidemic....
BACKGROUND
Expansion of the single sequence type 3 (ST3) was associated with a high macrolide resistance rate among Mycoplasma pneumoniae in Korea during the 2014-2016 epidemic. This study investigates the macrolide resistance rate and genetic diversity of the subsequent epidemic of M. pneumoniae pneumonia in 2019-2020.
METHODS
The culture for M. pneumoniae was developed from 1228 respiratory samples collected from children with pneumonia in four hospitals in Korea between January 2019 and January 2020. Determination of macrolide resistance and multilocus sequence typing analysis were performed on M. pneumoniae isolates. eBURST analysis was applied to estimate the relationships among strains and to assign strains to a clonal complex.
RESULTS
M. pneumoniae was cultured in 93 (7.6%) of 1228 clinical samples. The overall macrolide resistance rate of M. pneumoniae strains was 78.5% (73/93). Of the nine STs identified, three were novel. The most common ST was ST3 (66 [71.0%]) followed by ST14 (18 [19.4%]) and ST7/ST15 (2 [2.2%] each). Three STs (ST3, ST14, and ST17) exhibited macrolide resistance. The macrolide resistance rates of ST3 and ST14 were 98.5% (65 of 66) and 38.9% (7 of 18), respectively.
CONCLUSION
Compared to the previous outbreak in 2014-2016, the overall macrolide resistance remained high; however, an increasing proportion of macrolide resistance was observed within ST14 strains in 2019-2020.
Topics: Child; Humans; Mycoplasma pneumoniae; Macrolides; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 34475003
DOI: 10.1016/j.jmii.2021.07.011 -
Scientific Reports Nov 2023The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides...
The prevalence of Mycobacterium avium complex-pulmonary disease (MAC-PD) has become a growing concern worldwide, and current treatments involving macrolides (clarithromycin [CLR] or azithromycin), ethambutol, and rifampicin have limited success, highlighting the need for better therapeutic strategies. Recently, oxazolidinone drugs have been identified as novel anti-tuberculosis drugs effective against drug-resistant M. tuberculosis. However, the effects of these drugs against MAC are still controversial due to limited data. Here, we first evaluated the intracellular anti-MAC activities of two oxazolidinone drugs, linezolid (LZD) and delpazolid (DZD), against 10 macrolide-susceptible MAC strains and one macrolide-resistant M. avium strain in murine bone marrow-derived macrophages (BMDMs) and found that both drugs demonstrated similar potential. The synergistic efficacies with CLR were then determined in a chronic progressive MAC-PD murine model by initiating a 4-week treatment at 8 weeks post-infection. Upon assessment of bacterial burdens and inflamed lesions, oxazolidinone drugs exhibited no anti-MAC effect, and there was no significant difference in the synergistic effect of CLR between LZD and DZD. These findings suggest that oxazolidinone drugs inhibit intracellular bacterial growth, even against macrolide-resistant MAC, but their clinical application requires further consideration.
Topics: Humans; Mice; Animals; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Oxazolidinones; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Macrolides; Lung Diseases
PubMed: 37996500
DOI: 10.1038/s41598-023-48001-y -
MSphere Oct 2022Escherichia coli is intrinsically resistant to macrolides due to outer membrane impermeability, but may also acquire macrolide resistance genes by horizontal transfer....
Escherichia coli is intrinsically resistant to macrolides due to outer membrane impermeability, but may also acquire macrolide resistance genes by horizontal transfer. We evaluated the prevalence and types of acquired macrolide resistance determinants in pig clinical E. coli, and we assessed the ability of peptidomimetics to potentiate different macrolide subclasses against strains resistant to neomycin, a first-line antibiotic in the treatment of pig-enteric infections. The erythromycin MIC distribution was determined in 324 pig clinical E. coli isolates, and 62 neomycin-resistant isolates were further characterized by genome sequencing and MIC testing of azithromycin, spiramycin, tilmicosin, and tylosin. The impact on potency achieved by combining these macrolides with three selected peptidomimetic compounds was determined by checkerboard assays in six strains representing different genetic lineages and macrolide resistance gene profiles. Erythromycin MICs ranged from 16 to >1,024 μg/mL. Azithromycin showed the highest potency in wild-type strains (1 to 8 μg/mL), followed by erythromycin (16 to 128 μg/mL), tilmicosin (32 to 256 μg/mL), and spiramycin (128 to 256 μg/mL). Isolates with elevated MIC mainly carried (B), either alone or in combination with other acquired macrolide resistance genes, including (42), (C), (A), (B), and (G). All peptidomimetic-macrolide combinations exhibited synergy (fractional inhibitory concentration index [FICI] < 0.5) with a 4- to 32-fold decrease in the MICs of macrolides. Interestingly, the MICs of tilmicosin in wild-type strains were reduced to concentrations (4 to 16 μg/mL) that can be achieved in the pig intestinal tract after oral administration, indicating that peptidomimetics can potentially be employed for repurposing tilmicosin in the management of E. coli enteritis in pigs. Acquired macrolide resistance is poorly studied in Escherichia coli because of intrinsic resistance and limited antimicrobial activity in Gram-negative bacteria. This study reveals new information on the prevalence and distribution of macrolide resistance determinants in a comprehensive collection of porcine clinical E. coli from Denmark. Our results contribute to understanding the correlation between genotypic and phenotypic macrolide resistance in E. coli. From a clinical standpoint, our study provides an initial proof of concept that peptidomimetics can resensitize E. coli to macrolide concentrations that may be achieved in the pig intestinal tract after oral administration. The latter result has implications for animal health and potential applications in veterinary antimicrobial drug development in view of the high rates of antimicrobial-resistant E. coli isolated from enteric infections in pigs and the lack of viable alternatives for treating these infections.
Topics: Swine; Animals; Escherichia coli; Anti-Bacterial Agents; Azithromycin; Peptidomimetics; Macrolides; Tylosin; Drug Resistance, Bacterial; Spiramycin; Erythromycin; Escherichia coli Infections; Neomycin
PubMed: 36154672
DOI: 10.1128/msphere.00402-22 -
International Journal of Nanomedicine 2023Macrolide drugs are among the broad-spectrum antibiotics that are considered as "miracle drugs" against infectious diseases that lead to higher morbidity and mortality... (Review)
Review
Macrolide drugs are among the broad-spectrum antibiotics that are considered as "miracle drugs" against infectious diseases that lead to higher morbidity and mortality rates. Nevertheless, their effectiveness is currently at risk owing to the presence of devastating, antimicrobial-resistant microbes. In view of this challenge, nanotechnology-driven innovations are currently being anticipated for promising approaches to overcome antimicrobial resistance. Nowadays, various nanostructures are being developed for the delivery of antimicrobials to counter drug-resistant microbial strains through different mechanisms. Metallic nanoparticle-based delivery of macrolides, particularly using silver and gold nanoparticles (AgNPs & AuNPs), demonstrated a promising outcome with worthy stability, oxidation resistance, and biocompatibility. Similarly, macrolide-conjugated magnetic NPs resulted in an augmented antimicrobial activity and reduced bacterial cell viability against resistant microbes. Liposomal delivery of macrolides also showed favorable synergistic antimicrobial activities in vitro against resistant strains. Loading macrolide drugs into various polymeric nanomaterials resulted in an enhanced zone of inhibition. Intercalated nanomaterials also conveyed an outstanding macrolide delivery characteristic with efficient targeting and controlled drug release against infectious microbes. This review abridges several nano-based delivery approaches for macrolide drugs along with their recent achievements, challenges, and future perspectives.
Topics: Gold; Macrolides; Metal Nanoparticles; Anti-Bacterial Agents; Nanostructures
PubMed: 37732155
DOI: 10.2147/IJN.S418588 -
BMC Pulmonary Medicine Apr 2023Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and...
BACKGROUND
Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity.
METHODS
During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants.
RESULTS
At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV < 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 - 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 - 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients.
CONCLUSION
One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.
Topics: Humans; Azithromycin; Tumor Necrosis Factor-alpha; Sputum; Bronchiectasis; Anti-Bacterial Agents; Macrolides; Bronchi; Inflammation; Interleukin-1
PubMed: 37118704
DOI: 10.1186/s12890-023-02444-1 -
The Cochrane Database of Systematic... Jan 2015Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children.... (Meta-Analysis)
Meta-Analysis Review
Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, are view of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children.Objectives To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.Search methods We searched CENTRAL (2014, Issue 3), MEDLINE (1966 to July week 4, 2014), EMBASE (1980 to July, 2014), and both WHOICTRP and ClinicalTrials.gov (13 August 2014).Selection criteria Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community acquired LRTI secondary to M. pneumoniae.Data collection and analysis The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately and resolved disagreements by consensus.Main results A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. Authors' conclusions There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.
Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Community-Acquired Infections; Erythromycin; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Randomized Controlled Trials as Topic
PubMed: 25566754
DOI: 10.1002/14651858.CD004875.pub5 -
Annals of Agricultural and... Jun 2017An excessive use of antimicrobial agents poses a risk for the selection of resistant bacteria. Of particular interest are antibiotics that have large consumption rates... (Review)
Review
An excessive use of antimicrobial agents poses a risk for the selection of resistant bacteria. Of particular interest are antibiotics that have large consumption rates in both veterinary and human medicine, such as the tetracyclines and macrolide-lincosamide-streptogramin (MLS) group of antibiotics. A high load of these agents increases the risk of transmission of resistant bacteria and/or resistance determinants to humans, leading to a subsequent therapeutic failure. An increasing incidence of bacteria resistant to both tetracyclines and MLS antibiotics has been recently observed. This review summarizes the current knowledge on different tetracycline and MLS resistance genes that can be linked together on transposable elements.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Lincosamides; Macrolides; Streptogramins; Tetracyclines
PubMed: 28664720
DOI: 10.26444/aaem/74718 -
BMC Nephrology Nov 2022Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal disorders such as peptic ulcer disease and dyspepsia. However, several studies have...
BACKGROUND
Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal disorders such as peptic ulcer disease and dyspepsia. However, several studies have suggested that PPI use increases the risk of acute kidney injury (AKI). PPIs are often concomitantly used with antibiotics, such as macrolides and penicillins for Helicobacter pylori eradication. Although macrolide antibiotics are considered to have relatively low nephrotoxicity, they are well known to increase the risk of AKI due to drug-drug interactions. In this study, we aimed to investigate the association between PPI use and the development of AKI. We also evaluated the effect of concomitant use of PPIs and macrolide antibiotics on the risk of AKI.
METHODS
This self-controlled case series study was conducted using electronic medical records at Kyoto University Hospital. We identified patients who were prescribed at least one PPI and macrolide antibiotic between January 2014 and December 2019 and underwent blood examinations at least once a year. An adjusted incident rate ratio (aIRR) of AKI with PPI use or concomitant use macrolide antibiotics with PPIs was estimated using a conditional Poisson regression model controlled for the estimated glomerular filtration rate at the beginning of observation and use of potentially nephrotoxic antibiotics.
RESULTS
Of the 3,685 individuals who received PPIs and macrolide antibiotics, 766 patients with episodes of stage 1 or higher AKI were identified. Any stage of AKI was associated with PPI use (aIRR, 1.80 (95% confidence interval (CI) 1.60 to 2.04)). Stage 2 or higher AKI was observed in 279 cases, with an estimated aIRR of 2.01 (95% CI 1.57 to 2.58, for PPI use). For the period of concomitant use of macrolide antibiotics with PPIs compared with the period of PPIs alone, an aIRR of stage 1 or higher AKI was estimated as 0.82 (95% CI 0.60 to 1.13).
CONCLUSIONS
Our findings added epidemiological information for the association between PPI use and an increased risk of stage 1 or higher AKI. However, we did not detect an association between the concomitant use of macrolide antibiotics and an increased risk of AKI in PPI users.
Topics: Humans; Proton Pump Inhibitors; Macrolides; Acute Kidney Injury; Research Design; Anti-Bacterial Agents
PubMed: 36451129
DOI: 10.1186/s12882-022-03008-x -
Theranostics 2022Obesity, a metabolic disease caused by multiple factors, has become a global health problem. In addition to nutrient intake and sedentary lifestyle, environmental...
Obesity, a metabolic disease caused by multiple factors, has become a global health problem. In addition to nutrient intake and sedentary lifestyle, environmental pollutants exposure has been shown to be involved in obesity epidemics. Antibiotics, a new type of environmental pollutant, have been widely used in animal husbandry, aquaculture and microorganism. However, the effects of antibiotics exposure on fat metabolism and metabolic diseases are largely unknown. We screened major types of antibiotics to examine their effects on the differentiation capacity and thermogenic functionality of brown and beige adipocytes, and found that azithromycin, one major kind of macrolide antibiotics suppressed brown and beige adipocyte functionality. We thus examined azithromycin accretion in adipose tissues of obese patients that correlates with BMI by high performance liquid chromatography-tandem mass spectrometry and systematically explore the influences of azithromycin on adiposity and metabolic performance in mice under high diet. Azithromycin (macrolides) inhibits the mitochondrial and thermogenic gene programs of brown and beige adipocytes, thus disrupting their mitochondrial function and thermogenic response. Consistently, azithromycin treatment are more prone to diet-induced obesity in mice, and this was associated with impaired energy expenditure. Importantly, azithromycin is more accumulated in adipose tissue of obese patients and correlates with BMI and body weight. Mechanistically, we found that azithromycin inhibits mitochondria respiratory complex I protein levels and increases reactive oxidative species (ROS) levels, which causes damage of mitochondrial function in brown and beige adipocytes. The deleterious effects of azithromycin can be ameliorated by antioxidant N-acetyl-L-cysteine. Taken together, this work highlights the possible role of azithromycin in obesity epidemic and presents strategies for safe applications of antibiotics in the future.
Topics: Adipose Tissue, Beige; Animals; Anti-Bacterial Agents; Azithromycin; Humans; Metabolic Diseases; Mice; Obesity; Rodentia
PubMed: 35154482
DOI: 10.7150/thno.63067