-
Antimicrobial Agents and Chemotherapy Feb 2010Syphilis is a multistage infectious disease that is usually transmitted through contact with active lesions of a sexual partner or from an infected pregnant woman to her... (Review)
Review
Syphilis is a multistage infectious disease that is usually transmitted through contact with active lesions of a sexual partner or from an infected pregnant woman to her fetus. Despite elimination efforts, syphilis remains endemic in many developing countries and has reemerged in several developed countries, including China, where a widespread epidemic recently occurred. In the absence of a vaccine, syphilis control is largely dependent upon identification of infected individuals and treatment of these individuals and their contacts with antibiotics. Although penicillin is still effective, clinically significant resistance to macrolides, a second-line alternative to penicillin, has emerged. Macrolide-resistant strains of Treponema pallidum are now prevalent in several developed countries. An understanding of the genetic basis of T. pallidum antibiotic resistance is essential to enable molecular surveillance. This review discusses the genetic basis of T. pallidum macrolide resistance and the potential of this spirochete to develop additional antibiotic resistance that could seriously compromise syphilis treatment and control.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Macrolides; Male; Pregnancy; Syphilis; Treponema pallidum
PubMed: 19805553
DOI: 10.1128/AAC.01095-09 -
Respiratory Medicine Oct 2014Macrolide antibiotics have anti-inflammatory and immunomodulatory properties in addition to antibacterial activity. Until recently, only a small number of studies... (Review)
Review
Macrolide antibiotics have anti-inflammatory and immunomodulatory properties in addition to antibacterial activity. Until recently, only a small number of studies evaluating macrolides in patients with non-cystic fibrosis (CF) bronchiectasis had been published. These were open-label, uncontrolled, short-duration studies that included small numbers of patients. However, these studies suggested that macrolides can reduce exacerbation frequency, reduce sputum volume, and improve lung function in patients with non-CF bronchiectasis. Three recently published randomised, double-blind, placebo-controlled studies showed that macrolides (azithromycin or erythromycin) taken for between 6 and 12 months led to significant reductions in exacerbation rate and reduced the decline in lung function. In all studies, macrolides were generally well tolerated. The advantages of macrolide maintenance therapy need to be balanced against the risks, which include emergence of bacterial resistance, cardiotoxicity and ototoxicity. In addition, a key need is the consistent definition of endpoints for studies in non-CF bronchiectasis, particularly the definition of exacerbation, to allow systematic data analysis. Existing studies on the use of low-dose macrolides in non-CF bronchiectasis are encouraging, but further studies are needed to define the optimal agent, dose, duration for treatment, and the patients likely to benefit and long-term safety.
Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Erythromycin; Evidence-Based Medicine; Female; Forced Expiratory Volume; Humans; Macrolides; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiration; Treatment Outcome
PubMed: 25301290
DOI: 10.1016/j.rmed.2014.09.005 -
Revista Espanola de Quimioterapia :... Jun 2023Mycoplasma pneumoniae is a bacterium that lacks a cell wall. It produces infections all It produces infections world-wide, in epidemic outbreaks every 4-7 years, or... (Review)
Review
Mycoplasma pneumoniae is a bacterium that lacks a cell wall. It produces infections all It produces infections world-wide, in epidemic outbreaks every 4-7 years, or endemically. Its clinical manifestations occur mostly in the respiratory tract and it is a common cause of atypical pneumonia. The treatment is with macrolides, tetracyclines or fluoroquinolones. Since 2000, an increase in resistance to macrolides has been detected worldwide, being more frequent in Asia. In Europe the frequency of resistance ranges between 1% and 25%, depending on the country. Molecular techniques and serology techniques provides very high sensitivity in diagnostic confirmation, being very useful for detecting and controlling M. pneumoniae outbreaks. The detection of resistance to macrolides requires a sequencing technique.
Topics: Humans; Mycoplasma pneumoniae; Macrolides; Drug Resistance, Bacterial; Pneumonia, Mycoplasma; Anti-Bacterial Agents; Europe
PubMed: 36966384
DOI: 10.37201/req/118.2022 -
Scientific Reports Apr 2020Macrolactones, macrocyclic lactones with at least twelve atoms within the core ring, include diverse natural products such as macrolides with potent bioactivities (e.g....
Macrolactones, macrocyclic lactones with at least twelve atoms within the core ring, include diverse natural products such as macrolides with potent bioactivities (e.g. antibiotics) and useful drug-like characteristics. We have developed MacrolactoneDB, which integrates nearly 14,000 existing macrolactones and their bioactivity information from different public databases, and new molecular descriptors to better characterize macrolide structures. The chemical distribution of MacrolactoneDB was analyzed in terms of important molecular properties and we have utilized three targets of interest (Plasmodium falciparum, Hepatitis C virus and T-cells) to demonstrate the value of compiling this data. Regression machine learning models were generated to predict biological endpoints using seven molecular descriptor sets and eight machine learning algorithms. Our results show that merging descriptors yields the best predictive power with Random Forest models, often boosted by consensus or hybrid modeling approaches. Our study provides cheminformatics insights into this privileged, underexplored structural class of compounds with high therapeutic potential.
Topics: Biological Products; Cheminformatics; Databases, Chemical; Machine Learning; Macrolides; Models, Chemical; Quantitative Structure-Activity Relationship; Software
PubMed: 32286395
DOI: 10.1038/s41598-020-63192-4 -
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 -
PloS One 2017Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date,...
BACKGROUND AND OBJECTIVE
Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013-2016.
MATERIALS AND METHODS
Consecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively.
RESULTS
In total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7-6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%).
CONCLUSIONS
The prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance surveillance and testing for resistance-associated mutations in M. genitalium positive cases would be valuable.
Topics: DNA, Bacterial; Drug Resistance, Bacterial; Estonia; Female; Fluoroquinolones; Humans; Macrolides; Male; Mutation; Mycoplasma Infections; Mycoplasma genitalium; Population Surveillance; Prevalence; RNA, Ribosomal, 23S; Russia; Sequence Analysis, DNA
PubMed: 28407014
DOI: 10.1371/journal.pone.0175763 -
British Journal of Cancer May 2023Autophagy plays an important role in tumour cell growth and survival and also promotes resistance to chemotherapy. Hence, autophagy has been targeted for cancer therapy....
BACKGROUND
Autophagy plays an important role in tumour cell growth and survival and also promotes resistance to chemotherapy. Hence, autophagy has been targeted for cancer therapy. We previously reported that macrolide antibiotics including azithromycin (AZM) inhibit autophagy in various types of cancer cells in vitro. However, the underlying molecular mechanism for autophagy inhibition remains unclear. Here, we aimed to identify the molecular target of AZM for inhibiting autophagy.
METHODS
We identified the AZM-binding proteins using AZM-conjugated magnetic nanobeads for high-throughput affinity purification. Autophagy inhibitory mechanism of AZM was analysed by confocal microscopic and transmission electron microscopic observation. The anti-tumour effect with autophagy inhibition by oral AZM administration was assessed in the xenografted mice model.
RESULTS
We elucidated that keratin-18 (KRT18) and α/β-tubulin specifically bind to AZM. Treatment of the cells with AZM disrupts intracellular KRT18 dynamics, and KRT18 knockdown resulted in autophagy inhibition. Additionally, AZM treatment suppresses intracellular lysosomal trafficking along the microtubules for blocking autophagic flux. Oral AZM administration suppressed tumour growth while inhibiting autophagy in tumour tissue.
CONCLUSIONS
As drug-repurposing, our results indicate that AZM is a potent autophagy inhibitor for cancer treatment, which acts by directly interacting with cytoskeletal proteins and perturbing their dynamics.
Topics: Animals; Mice; Azithromycin; Anti-Bacterial Agents; Macrolides; Disease Models, Animal; Cytoskeletal Proteins; Autophagy; Neoplasms
PubMed: 36871041
DOI: 10.1038/s41416-023-02210-4 -
Jornal Brasileiro de Pneumologia :... 2012Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have... (Review)
Review
Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.
Topics: Anti-Inflammatory Agents; Asthma; Bronchiolitis; Child; Clinical Trials as Topic; Cystic Fibrosis; Humans; Immunologic Factors; Immunomodulation; Lung Diseases; Macrolides
PubMed: 23288126
DOI: 10.1590/s1806-37132012000600016 -
Emerging Infectious Diseases Oct 2020Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a...
Macrolide-resistant Bordetella pertussis emerged in Vietnam during 2016-2017. Direct analyses of swab samples from 10 patients with pertussis revealed a macrolide-resistant mutation, A2047G, in the 23S rRNA. We identified the MT104 genotype of macrolide-resistant B. pertussis (which is prevalent in mainland China) and its variants in these patients.
Topics: Anti-Bacterial Agents; Bordetella pertussis; China; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; RNA, Ribosomal, 23S; Vietnam
PubMed: 32946738
DOI: 10.3201/eid2610.201035 -
PloS One 2023Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying... (Review)
Review
Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.
Topics: Humans; Macrolides; Common Cold; Retrospective Studies; Japan; Anti-Bacterial Agents; Anti-Infective Agents; Prescriptions; Hypersensitivity; Observational Studies as Topic
PubMed: 37347735
DOI: 10.1371/journal.pone.0287297