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Microbiology Spectrum Feb 2022To investigate the presence and location of (T) in clinical Streptococcus suis isolates and explore the transmission ability and fitness cost of (T)-carrying mobile...
To investigate the presence and location of (T) in clinical Streptococcus suis isolates and explore the transmission ability and fitness cost of (T)-carrying mobile genetic elements among S. suis isolates, MICs were determined by broth microdilution. The presence of (T) in S. suis was detected by PCR. The genetic environment of (T) in S. suis was explored by whole-genome sequencing (WGS) analysis. Intraspecies and interspecies transmission were examined by electrotransformation. The fitness cost associated with the carriage of an (T)-harboring plasmid or an integrative and conjugative element (ICE) was examined by competition experiments. Of 237 nonduplicate strains, (T) was detected in 2 S. suis strains (SC262-ST954 and SC117-ST1314), with its location on a 5,125-bp plasmid in S. suis SC262 and on a 64,013-bp ICESC117 in S. suis SC117, respectively. Both the (T)-carrying plasmid pSC262 and the ICESC117 were transmissible by transformation. Plasmid pSC262 can replicate and express macrolide-lincosamide resistance in heterologous hosts, including S. aureus and S. pneumoniae. Both the (T)-carrying plasmid and the ICE posed a fitness cost to the host S. suis isolate. To the best of our knowledge, this is the first report of the macrolide-lincosamide-streptogramin B resistance gene (T) in S. suis. Its location on a plasmid or an ICE will aid in its transmission. The low detection rate of (T) gene among the S. suis population might be due to the fitness cost of the (T)-carrying plasmid and ICE. Macrolide and lincosamide resistance due to the presence of (T) have posed a challenge for the treatment of Gram-positive pathogens. Although the low detection rate of (T) gene among the S. suis population due to the fitness cost of the (T)-carrying plasmid and ICE, the presence of (T) in S. suis and its potential transmission to other Gram-positive pathogens will be of important significance.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Humans; Lincosamides; Macrolides; Microbial Sensitivity Tests; Staphylococcus aureus; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus suis
PubMed: 35019703
DOI: 10.1128/spectrum.01657-21 -
Frontiers in Cellular and Infection... 2023Traditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of when cultured . Sanger sequencing is the...
BACKGROUND
Traditional drug susceptibility testing cannot be performed in clinical laboratories due to the slow-growing characteristics of when cultured . Sanger sequencing is the standard method for detecting drug resistance-associated mutations. It has been used in some laboratories to guide the choice of macrolide antibiotics for infected patients. Furthermore, resistance to fluoroquinolone has become another emerging clinical challenge.
OBJECTIVE
Sequencing analysis can detect unknown mutations, but it is time-consuming, requires professional analytical skills and the appropriate testing equipment. The main objective of this study was to establish a nested real-time PCR method for the simultaneous detection of and genotypes in relation to the macrolide and fluoroquinolone resistance.
RESULTS
105 MG-positive samples and 27 samples containing other pathogens were used for validation. The limit of the nested real-time PCR detection was 500 copies/reaction and there was no cross-reaction with , , , , , , and , but the assay cross-reacted with . Compared with sequencing results, the sensitivity of was 100% (95% CI; 93.3 -100), the specificity was 94.3% (95% CI; 79.4 - 99.0), the overall consistency was 98% (95% CI; 92.5 - 99.7) and value was 0.96 ( < 0.001); the sensitivity of was 100% (95% CI; 93.4 - 100), the specificity was 89.7% (95% CI; 71.5 - 97.3) and the overall consistency was 96.9% (95% CI; 90.7 - 99.2) with a value of 0.92 ( < 0.001).
CONCLUSIONS
The results of this sensitive and rapid alternative for identifying resistant genotypes of are intuitive and easy to interpret, especially for mixed MG populations. Although the relevant primers need further adjustment, this reliable method would provide an effective diagnostic tool for the selection of antibiotics in clinical practice.
Topics: Humans; Fluoroquinolones; Mycoplasma genitalium; RNA, Ribosomal, 23S; Real-Time Polymerase Chain Reaction; Macrolides; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Mycoplasma Infections; Mycobacterium tuberculosis; Anti-Bacterial Agents; Mutation
PubMed: 37928183
DOI: 10.3389/fcimb.2023.1271392 -
Emerging Infectious Diseases Jan 2023Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in...
Resurgence and spread of macrolide-resistant Bordetella pertussis (MRBP) threaten global public health. We collected 283 B. pertussis isolates during 2016-2022 in Shanghai, China, and conducted 23S rRNA gene A2047G mutation detection, multilocus variable-number tandem-repeat analysis, and virulence genotyping analysis. We performed whole-genome sequencing on representative strains. We detected pertussis primarily in infants (0-1 years of age) before 2020 and older children (>5-10 years of age) after 2020. The major genotypes were ptxP1/prn1/fhaB3/ptxA1/ptxC1/fim2-1/fim3-1 (48.7%) and ptxP3/prn2/fhaB1/ptxA1/ptxC2/fim2-1/fim3-1 (47.7%). MRBP increased remarkably from 2016 (36.4%) to 2022 (97.2%). All MRBPs before 2020 harbored ptxP1, and 51.4% belonged to multilocus variable-number tandem-repeat analysis type (MT) 195, whereas ptxP3-MRBP increased from 0% before 2020 to 66.7% after 2020, and all belonged to MT28. MT28 ptxP3-MRBP emerged only after 2020 and replaced the resident MT195 ptxP1-MRBP, revealing that 2020 was a watershed in the transformation of MRBP.
Topics: Child; Infant; Humans; Adolescent; Child, Preschool; Bordetella pertussis; Whooping Cough; China; Anti-Bacterial Agents; Drug Resistance, Bacterial; Macrolides; Evolution, Molecular
PubMed: 38146984
DOI: 10.3201/eid3001.221588 -
Tuberkuloz Ve Toraks Dec 2021Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial... (Review)
Review
Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such as doses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines.
Topics: Anti-Bacterial Agents; Asthma; Azithromycin; Humans; Macrolides; Quality of Life
PubMed: 34957746
DOI: 10.5578/tt.20219610 -
The Journal of International Medical... Feb 2022To analyse macrolide resistance and molecular characteristics of clinical isolates from western China, and to explore the relationship between macrolide-resistance and...
OBJECTIVE
To analyse macrolide resistance and molecular characteristics of clinical isolates from western China, and to explore the relationship between macrolide-resistance and genotypes.
METHODS
Susceptibilities of clinical isolates to erythromycin, azithromycin and clarithromycin were determined by epsilometer test (E-test). Isolated strains were sequenced to ascertain the presence of the 23S rRNA gene A2047G mutation. Strains were typed using multilocus antigen sequence typing, multilocus variable-number tandem-repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE).
RESULTS
Of 58 strains isolated in this study, 46 were macrolide-resistant and 12 were macrolide sensitive. All macrolide-resistant strains carried the A2047G mutation and were the //// genotype; the MLVA types were MT195 (19/58), MT55 (13/58) and MT104 (14/58), and the PFGE profiles were classified into BpSR23 (17/58) and BpFINR9 (29/58) types. None of the macrolide-sensitive strains carried the A2047G mutation; genotypes were ( or )////, and all were MT27. PFGE profiles differed from the macrolide-resistant strains.
CONCLUSIONS
clinical isolates from western China were severely resistant to macrolides. Genotypes differed between macrolide-resistant and macrolide-sensitive strains, and there may be a correlation between acquisition of macrolide resistance and changes in specific molecular types.
Topics: Anti-Bacterial Agents; Bordetella pertussis; Drug Resistance, Bacterial; Genotype; Humans; Macrolides; Whooping Cough
PubMed: 35225710
DOI: 10.1177/03000605221078782 -
The Lancet. Microbe Dec 2023The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy,...
BACKGROUND
The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria.
METHODS
Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment.
FINDINGS
Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance.
INTERPRETATION
Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy.
FUNDING
European Research Council.
Topics: Animals; Infant, Newborn; Humans; Treponema pallidum; Anti-Bacterial Agents; Azithromycin; Syphilis; Macrolides; Linezolid; Ceftriaxone; Globus Pallidus; Drug Resistance, Bacterial; Amoxicillin; Treponema
PubMed: 37827185
DOI: 10.1016/S2666-5247(23)00219-7 -
Biomolecules Oct 2023Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range,... (Review)
Review
Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range, inadequate safety profiles, and low oral bioavailability. Consequently, there is an urgent imperative to develop novel antifungal medications for clinical application. This comprehensive review provides a summary of the antifungal properties and mechanisms exhibited by natural polyketides, encompassing macrolide polyethers, polyether polyketides, xanthone polyketides, linear polyketides, hybrid polyketide non-ribosomal peptides, and pyridine derivatives. Investigating natural polyketide compounds and their derivatives has demonstrated their remarkable efficacy and promising clinical application as antifungal agents.
Topics: Humans; Antifungal Agents; Polyketides; Macrolides; Peptides
PubMed: 38002254
DOI: 10.3390/biom13111572 -
Clinical Infectious Diseases : An... Nov 2023Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
BACKGROUND
Mycoplasma genitalium (MG) is on the CDC Watch List of Antimicrobial Resistance Threats, yet there is no systematic surveillance to monitor change.
METHODS
We initiated surveillance in sexual health clinics in 6 cities, selecting a quota sample of urogenital specimens tested for gonorrhea and/or chlamydia. We abstracted patient data from medical records and detected MG and macrolide-resistance mutations (MRMs) by nucleic acid amplification testing. We used Poisson regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs, adjusting for sampling criteria (site, birth sex, symptom status).
RESULTS
From October-December 2020 we tested 1743 urogenital specimens: 57.0% from males, 46.1% from non-Hispanic Black persons, and 43.8% from symptomatic patients. MG prevalence was 16.6% (95% CI: 14.9-18.5%; site-specific range: 9.9-23.5%) and higher in St Louis (aPR: 1.9; 1.27-2.85), Greensboro (aPR: 1.8; 1.18-2.79), and Denver (aPR: 1.7; 1.12-2.44) than Seattle. Prevalence was highest in persons <18 years (30.4%) and declined 3% per each additional year of age (aPR: .97; .955-.982). MG was detected in 26.8%, 21.1%, 11.8%, and 15.4% of urethritis, vaginitis, cervicitis, and pelvic inflammatory disease (PID), respectively. It was present in 9% of asymptomatic males and 15.4% of asymptomatic females, and associated with male urethritis (aPR: 1.7; 1.22-2.50) and chlamydia (aPR: 1.7; 1.13-2.53). MRM prevalence was 59.1% (95% CI: 53.1-64.8%; site-specific range: 51.3-70.6%). MRMs were associated with vaginitis (aPR: 1.8; 1.14-2.85), cervicitis (aPR: 3.5; 1.69-7.30), and PID cervicitis (aPR: 1.8; 1.09-3.08).
CONCLUSIONS
MG infection is common in persons at high risk of sexually transmitted infections; testing symptomatic patients would facilitate appropriate therapy. Macrolide resistance is high and azithromycin should not be used without resistance testing.
Topics: Female; Humans; Male; Anti-Bacterial Agents; Urethritis; Mycoplasma genitalium; Uterine Cervicitis; Sexual Health; Macrolides; Drug Resistance, Bacterial; Pelvic Inflammatory Disease; Vaginitis; Mycoplasma Infections; Prevalence
PubMed: 37402645
DOI: 10.1093/cid/ciad405 -
Pediatric Research Apr 2022Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they... (Review)
Review
Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they have non-anti-infective effects, including anti-inflammatory, regulating airway secretion, immune regulation, and other effects. A growing number of studies have shown that the non-anti-infective effects of macrolides have important and potential value in the treatment of pediatric chronic airway diseases; the therapy was described as "long-term, low-dose usage"; unfortunately, there is no guideline or consensus that applies to children. To better carry out the mechanism and clinical research of non-anti-infective effect and promote its rational use in children, the authors summarize the evidence of the usage of long-term, low-dose macrolide antibiotic therapy (LLMAT) in the treatment of chronic airway diseases in children and the progress in recent years. IMPACT: This review summarizes the evidence (mostly in recent 5 years) of the usage of long-term, low-dose macrolide antibiotic therapy in the treatment of chronic airway diseases. The recent studies and guidelines support and enrich the point that long-term, low-dose macrolide antibiotic therapy has potential benefit for children with severe asthma, CF, non-CF bronchiectasis, and BO, which provides clinical references and is of clinical interest. Long-term, low-dose macrolide antibiotic therapy has good safety, and no serious events have been reported; however, potential cardiac side effects and macrolide resistance should be clinically noted.
Topics: Anti-Bacterial Agents; Asthma; Bronchiectasis; Child; Drug Resistance, Bacterial; Humans; Macrolides; Pulmonary Disease, Chronic Obstructive
PubMed: 34120139
DOI: 10.1038/s41390-021-01613-4 -
Respiratory Medicine Oct 2023Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by...
BACKGROUND
Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices.
METHODS
Patients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands. Clinical consultation reports were extracted from the database to assess the cause of macrolide resistance.
RESULTS
Sixteen patients with macrolide-resistant MAC disease were included, from a total of 815 patients with MAC isolates (2%); Macrolide monotherapy in bronchiectasis or CF was the most frequent cause of development of macrolide-resistance MAC disease (n = 8; 50%). Short (n = 3; mean duration 9 months, range 6-12) or guideline non-compliant (n = 2) treatment regimens and patient non-adherence (n = 2) were other key causes of macrolide-resistance.
CONCLUSIONS
Macrolide monotherapy after inappropriate screening is the most frequent cause of macrolide-resistant Mycobacterium avium complex disease in the Netherlands. Educational efforts are needed to prevent this.
Topics: Humans; Mycobacterium avium Complex; Anti-Bacterial Agents; Macrolides; Mycobacterium avium-intracellulare Infection; Drug Resistance, Bacterial; Lung Diseases
PubMed: 37481170
DOI: 10.1016/j.rmed.2023.107366