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1.
PLoS One ; 17(5): e0265229, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35536784

RESUMO

Reports of potential treatment failure have raised particular concerns regarding the efficacy of the single dose azithromycin regimen in the treatment of urogenital and anorectal Chlamydia trachomatis (CT) infections. Several factors have been suggested, including heterotypic resistance. Antimicrobial susceptibility testing in CT requires cell culture with serial dilutions of antibiotics, which is laborious and for which there is no standardized testing methodology. One method to partly overcome these difficulties would be to use a genotypic resistance assay, however most current available assays do still require prior CT culture. In order to facilitate the assessment of genotypic resistance directly from clinical samples, without the need for prior culture, the aim of this study was to develop a CT specific PCR assay for the assessment of resistance associated mutations (RAMs) in the 23S rRNA gene, and to evaluate a sample of clinical cases in which CT PCR's remained positive during follow-up despite azithromycin treatment. Neither the in silico analysis nor the analytical specificity testing demonstrated clinically relevant cross-reactivity with other bacterial species. These results in conjunction with the analytical sensitivity demonstrating consistent CT 23S rRNA gene detection in the range of 10e3 IFU/mL, exemplify the assay's apt performance. Although no known macrolide RAMs were detected in the clinical cases, the described assay allows future culture independent macrolide RAM surveillance in CT, and increases accessibility for other laboratories to engage in screening.


Assuntos
Chlamydia trachomatis , RNA Ribossômico 23S , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Chlamydia trachomatis/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Genes de RNAr , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Mutação , RNA Ribossômico 23S/genética
2.
J Med Microbiol ; 71(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35511246

RESUMO

During this global pandemic of the COVID-19 disease, a lot of information has arisen in the media and online without scientific validation, and among these is the possibility that this disease could be aggravated by a secondary bacterial infection such as Prevotella, as well as the interest or not in using azithromycin, a potentially active antimicrobial agent. The aim of this study was to carry out a systematic literature review, to prove or disprove these allegations by scientific arguments. The search included Medline, PubMed, and Pubtator Central databases for English-language articles published 1999-2021. After removing duplicates, a total of final eligible studies (n=149) were selected. There were more articles showing an increase of Prevotella abundance in the presence of viral infection like that related to Human Immunodeficiency Virus (HIV), Papillomavirus (HPV), Herpesviridae and respiratory virus, highlighting differences according to methodologies and patient groups. The arguments for or against the use of azithromycin are stated in light of the results of the literature, showing the role of intercurrent factors, such as age, drug consumption, the presence of cancer or periodontal diseases. However, clinical trials are lacking to prove the direct link between the presence of Prevotella spp. and a worsening of COVID-19, mainly those using azithromycin alone in this indication.


Assuntos
COVID-19 , Coinfecção , Azitromicina/farmacologia , Humanos , Pandemias , Prevotella , SARS-CoV-2
3.
J Infect Chemother ; 28(7): 948-954, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35440370

RESUMO

INTRODUCTION: Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. METHODS: We investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein. A retrospective cohort study was performed on intensive care COVID-19 patients. RESULTS: Co-incubation of clarithromycin with spike protein-stimulated healthy volunteer PBMCs ex vivo resulted in an increase in CD8+ (p = 0.004) and CD4+ (p = 0.007) IL-2, with a decrease in CD8+ (p = 0.032) and CD4+ (p = 0.007) IL-10. The addition of amoxicillin to clarithromycin resulted in an increase in CD8+ IL-6 (p = 0.010), decrease in CD8+ (p = 0.014) and CD4+ (p = 0.022) TNF-alpha, and decrease in CD8+ IFN-alpha (p = 0.038). Amoxicillin alone had no effect on CD4+ or CD8+ cytokines. Co-incubation of azithromycin resulted in increased CD8+ (p = 0.007) and CD4+ (p = 0.011) IL-2. There were no effects on monocyte phagocytosis. 102 COVID-19 ICU patients received antibiotics on hospital admission; 62 (61%) received clarithromycin. Clarithromycin use was associated with reduction in mortality on univariate analysis (p = 0.023), but not following adjustment for confounders (HR = 0.540; p = 0.076). CONCLUSIONS: Clarithromycin has immunomodulatory properties over and above azithromycin. Amoxicillin in addition to clarithromycin is associated with synergistic ex vivo immunomodulatory properties. The potential benefit of clarithromycin in critically ill patients with COVID-19 and other viral pneumonitis merits further exploration.


Assuntos
COVID-19 , Claritromicina , Amoxicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Citocinas , Humanos , Interleucina-2 , Macrolídeos/farmacologia , Estudos Retrospectivos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
4.
Theranostics ; 12(6): 2658-2673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401823

RESUMO

Rationale: Chronic wounds are one of the common complications of diabetes. Due to the physiological conditions of diabetic patients, these wounds are more susceptible to bacterial infections and the formation of bacterial biofilms, leading to the inefficiency of conventional antibiotic treatment. Methods: Here, hollow mesoporous silica nanoparticles (HMSN) were used as the nanocarriers for co-delivery of azithromycin (AZM) and glucose oxidase (GOX), achieving a remarkable synergistic effect in chronic diabetic wounds. GOX possesses the catalytic ability to consume glucose and produce H2O2 in the diabetic wound area. The down-regulation of local glucose could effectively improve the chronic diabetic wound microenvironment. Meanwhile, the generated H2O2 effectively inhibits bacterial growth and eradicates bacterial biofilms with the synergism of antibiotics AZM. Results: In the bacteria-infected diabetic cutaneous wound models, the reduction of glucose, generation of H2O2, and release of AZM could effectively reduce the bacterial infection and promote the wounds healing. Moreover, there is no obvious toxicity behavior after the treatment. Conclusions: Therefore, the designed nanosystem could effectively accelerate the diabetic wound healing process by the amelioration of the hyperglycemia microenvironment and the eradication of bacterial biofilms around the wounds, making them promising candidates for clinical transformation.


Assuntos
Diabetes Mellitus , Infecção dos Ferimentos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Bactérias , Diabetes Mellitus/tratamento farmacológico , Glucose , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
5.
Artigo em Inglês | MEDLINE | ID: mdl-35469554

RESUMO

The National Neisseria Network (NNN), Australia, comprises reference laboratories in each state and territory established in 1979. The NNN has reported data on susceptibility profiles for all Neisseria gonorrhoeae isolated from each jurisdiction for an agreed group of antimicrobial agents for the Australian Gonococcal Surveillance Programme (AGSP) since 1981. The antibiotics reported represent current or potential agents used for the treatment of gonorrhoea and include ceftriaxone; azithromycin; ciprofloxacin; and penicillin. More recently, gentamicin susceptibilities are included in the AGSP Annual Report. Ceftriaxone, combined with azithromycin, is the recommended treatment regimen for gonorrhoea in the majority of Australia. However, there are substantial geographic differences in susceptibility patterns in Australia, with certain remote regions of the Northern Territory and Western Australia having low gonococcal antimicrobial resistance rates. In these regions, an oral treatment regimen comprising amoxycillin, probenecid, and azithromycin is recommended for the treatment of gonorrhoea.


Assuntos
Gonorreia , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Northern Territory
6.
Clin Lab ; 68(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443581

RESUMO

BACKGROUND: The goal of the study was to analyze the clinical characteristics of Legionella cases caused by Legionella micdadei and explore the diagnosis and treatment. METHODS: The pathogen was identified by routine isolation and culture, biochemical identification, serum agglutination test, mass spectrometry identification, and routine PCR. Combined with the related literature review, the clinical diagnosis and treatment of Legionella micdadei were analyzed. RESULTS: The patient suffered from pulmonary infection caused by Legionella micdadei. After treatment with moxi-floxacin for 2 weeks, the body temperature dropped and the shadow of the lung was completely absorbed after 2 months. Combined with literature analysis, 8 cases of Legionella micetidis, including 7 males and 1 female, aged from 27 to 57 years old, 6 cases with basic diseases, which were treated with azithromycin, erythromycin or levofloxacin, and all of them achieved good therapeutic effect. CONCLUSIONS: The detection of Legionella should be strengthened in patients with pneumonia whose symptoms have no obvious improvement after antibiotic treatment. Azithromycin, erythromycin or levofloxacin are effective in the treatment of Legionella spp.


Assuntos
Legionella , Legionelose , Pneumonia , Adulto , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Eritromicina/farmacologia , Feminino , Humanos , Legionellaceae , Legionelose/complicações , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico
7.
J Healthc Eng ; 2022: 5288148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35388320

RESUMO

Objective: The objective is to explore the efficacy of azithromycin combined with glucocorticoids in the treatment of children with pneumonia and its effect on the inflammatory response. Methods: A total of 86 children with pneumonia were divided into the experimental group (EG) and the control group (CG). Both groups received conventional treatment, the CG was treated with azithromycin and the EG was additionally treated with glucocorticoid methylprednisolone. The therapeutic effect, disappearance time of clinical symptoms, pulmonary function, inflammatory factors, immune function, quality of life, and adverse reactions were measured in the two groups. Results: After treatment, compared with CG, the total effective rate was significantly elevated, the disappearance time of various clinical symptoms was earlier, and various pulmonary function indexes were increased in the EG. The interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C reactive protein (CRP), and CD8+ levels were reduced, and CD3+ and CD4+ levels were increased in the EG. The quality-of-life scores were upregulated in the EG. Moreover, there was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: The combined use of azithromycin and glucocorticoids in the treatment of children with Mycoplasma pneumoniae infection has a good curative effect, can significantly improve lung function, restore pulmonary inflammatory indexes to normal, and enhance patients' immune function and improve their quality of life, with fewer adverse reactions and safety.


Assuntos
Glucocorticoides , Pneumonia por Mycoplasma , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Criança , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Pulmão , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Qualidade de Vida
8.
Emerg Microbes Infect ; 11(1): 1049-1057, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35333699

RESUMO

With the development of multidrug resistance in Salmonella spp. in recent years, ciprofloxacin, ceftriaxone, and azithromycin have become the principal antimicrobial agents used for the treatment of Salmonella infections. The underlying mechanisms of plasmid-mediated ciprofloxacin and ceftriaxone resistance have attracted extensive research interest, but not much is focused on azithromycin resistance in Salmonella. In this study, we investigated the genetic features of two conjugative plasmids and a non-transferable virulence plasmid that encode azithromycin resistance in food-borne Salmonella strains. We showed that the azithromycin resistance phenotype of these strains was conferred by erm(B) gene and/or the complete genetic structure IS26-mph(A)-mrx-mphR-IS6100. Comparative genetic analysis showed that these conjugative plasmids might originate from Escherichia coli and play a role in the rapid dissemination of azithromycin resistance in Salmonella. These conjugative plasmids may also serve as a reservoir of antimicrobial resistance (AMR) genes in Salmonella in which these AMR genes may be acquired by the virulence plasmids of Salmonella via genetic transposition events. Importantly, the formation of a novel macrolide-resistance and virulence-encoding plasmid, namely pS1380-118 kb, was observed in this study. This plasmid was found to exhibit transmission potential and pose a serious health threat as the extensive transmission of azithromycin resistant and virulent Salmonella strains would further compromise the effectiveness of treatment for salmonellosis. Further surveillance and research on the dissemination and evolution routes of pS1380-118kb-like plasmids in potential human pathogens of the family of Enterobacteriaceae are necessary.


Assuntos
Azitromicina , Infecções por Salmonella , Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona , Ciprofloxacina/farmacologia , Escherichia coli/genética , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Salmonella/genética
9.
Am J Physiol Lung Cell Mol Physiol ; 322(5): L683-L698, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35348023

RESUMO

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma. The current study investigated these nonantibiotic activities of azithromycin in mice exposed daily to intranasal house dust mite (HDM) extract for 10 days. HDM-exposed mice exhibited airways hyperresponsiveness to aerosolized methacholine, a pronounced mixed eosinophilic and neutrophilic inflammatory response, increased airway smooth muscle (ASM) thickness, and elevated levels of epithelial mucin staining. Azithromycin (50 mg/kg sc, 2 h before each HDM exposure) attenuated HDM-induced airways hyperresponsiveness to methacholine, airways inflammation (bronchoalveolar lavage eosinophil and neutrophils numbers, and IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, and RANTES levels), and epithelial mucin staining (mucous metaplasia) by at least 50% (compared with HDM-exposed mice, P < 0.05). Isolated tracheal segments of HDM-exposed mice secreted Muc5ac and Muc5b (above baseline levels) in response to exogenous ATP. Moreover, ATP-induced secretion of mucins was attenuated in segments obtained from azithromycin-treated, HDM-exposed mice (P < 0.05). In additional ex vivo studies, ATP-induced secretion of Muc5ac (but not muc5b) from HDM-exposed tracheal segments was inhibited by in vitro exposure to azithromycin. In vitro azithromycin also inhibited ATP-induced secretion of Muc5ac and Muc5b in tracheal segments from IL-13-exposed mice. In summary, azithromycin inhibited ATP-induced mucin secretion and airways inflammation in HDM-exposed mice, both of which are likely to contribute to suppression of airways hyperresponsiveness.


Assuntos
Asma , Pyroglyphidae , Trifosfato de Adenosina , Alérgenos , Animais , Asma/patologia , Azitromicina/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Interleucina-13 , Metaplasia , Cloreto de Metacolina , Camundongos , Mucinas , Muco
10.
Antimicrob Agents Chemother ; 66(4): e0229421, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35345891

RESUMO

The emergence of multidrug resistance in Neisseria gonorrhoeae is concerning, especially the cooccurrence of azithromycin resistance and decreased susceptibility to extended-spectrum cephalosporin. This study aimed to confirm the antibiotic resistance trends and provide a solution for N. gonorrhoeae treatment in Guangdong, China. A total of 5,808 strains were collected for assessment of antibiotic MICs. High resistance to penicillin (53.80 to 82%), tetracycline (88.30 to 100%), ciprofloxacin (96 to 99.8%), cefixime (6.81 to 46%), and azithromycin (8.60 to 20.03%) was observed. Remarkably, spectinomycin and ceftriaxone seemed to be the effective choices, with resistance rates of 0 to 7.63% and 2.00 to 16.18%, respectively. Moreover, the rates of azithromycin resistance combined with decreased susceptibility to ceftriaxone and cefixime reached 9.28% and 8.64%, respectively. Furthermore, genotyping identified NG-STAR-ST501, NG-MAST-ST2268, and MLST-ST7363 as the sequence types among representative multidrug-resistant isolates. Evolutionary analysis showed that FC428-related clones have spread to Guangdong, China, which might be a cause of the rapid increase in extended-spectrum cephalosporin resistance currently. Among these strains, the prevalence of N. gonorrhoeae was extremely high, and single-dose ceftriaxone treatment might be a challenge in the future. To partially relieve the treatment pressure, a susceptibility test for susceptibility to azithromycin plus extended-spectrum cephalosporin dual therapy was performed. The results showed that all the representative isolates could be effectively killed with the coadministration of less than 1 mg/liter azithromycin and 0.125 mg/liter extended-spectrum cephalosporin, with a synergistic effect according to a fractional inhibitory concentration (FIC) of <0.5. In conclusion, dual therapy might be a powerful measure to treat refractory N. gonorrhoeae in the context of increasing antibiotic resistance in Guangdong, China.


Assuntos
Gonorreia , Neisseria gonorrhoeae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Cefixima/farmacologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Resistência às Cefalosporinas , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , China/epidemiologia , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus
11.
Antimicrob Agents Chemother ; 66(4): e0224621, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35293783

RESUMO

While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and macrolide resistance, and the potential for onward transmission of resistance to close contacts are poorly understood. We determined the effects of long-term exposure to azithromycin or erythromycin on phenotypic and genotypic macrolide resistance within the oropharyngeal microbiome of healthy adults and their close contacts in a randomized, single-blinded, parallel-group trial of 4 weeks of twice-daily oral 400 mg erythromycin ethylsuccinate or twice-daily oral 125 mg azithromycin. Using oropharyngeal swabs collected from 20 index healthy adults and 20 paired close contacts, the oropharyngeal microbial composition and macrolide resistance in streptococci were assessed by 16S rRNA sequencing and antibiotic susceptibility testing of oropharyngeal cultures, respectively, at baseline and weeks 4 and 8 (washout). Targeted quantitative PCR of antibiotic resistance genes was performed to evaluate paired changes in resistance gene levels in index patients and close contacts and to relate the potential transmission of antibiotic resistance. Neither azithromycin nor erythromycin altered oropharyngeal microbiota characteristics significantly. Proportional macrolide resistance in oropharyngeal streptococci increased with both erythromycin and azithromycin, remaining above baseline levels for the azithromycin group at washout. Levels of resistance genes increased significantly with azithromycin[erm(B) and mef] and erythromycin (mef), returning to baseline levels at washout only for the erythromycin group. We found no evidence of onward transmission of resistance to close contacts, as indicated by the lack of concomitant changes in resistance gene levels detected in close contacts. (This study has been registered with the Australian and New Zealand Clinical Trials Registry under identifier ACTRN12617000278336.).


Assuntos
Antibacterianos , Microbiota , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Austrália , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Eritromicina/farmacologia , Humanos , Macrolídeos/farmacologia , RNA Ribossômico 16S/genética , Streptococcus
12.
Antimicrob Agents Chemother ; 66(4): e0239221, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35311521

RESUMO

Recent mutations in RND efflux pumps in clinical strains have further increased multidrug resistance. We show that R717L and R717Q substitutions (found in azithromycin-resistant Salmonella enterica spp.) in the Escherichia coli efflux pump AcrB dramatically increase macrolide, as well as fluoroquinolone, resistance. On the other hand, cells became more susceptible to novobiocin and ß-lactam cloxacillin. We urge the control of, and adjustments to, treatments with antibiotics and the need for novel antibiotics and efflux pump inhibitors.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Antibacterianos/química , Azitromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
13.
PLoS One ; 17(3): e0264737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35235608

RESUMO

Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.


Assuntos
Anti-Infecciosos , Gonorreia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Ceftriaxona/farmacologia , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Mitomicina/farmacologia , Neisseria gonorrhoeae , Catar/epidemiologia , Tetraciclina/farmacologia
14.
Bioresour Technol ; 350: 126944, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35247561

RESUMO

The long-term stable operation of the mixed culture polyhydroxyalkanoate (PHA) enrichment stage is the guarantee for the continuous synthesis of PHA, however extracellular polymeric substances (EPS) sludge bulking occurred from time to time may cause the operation fail. In order to solve this problem, as a quencher of signal molecules and antibiotic, azithromycin (AZM) was used in the two systems with different modes to recover the sedimentation capacity of the sludge. The results showed that AZM addition resulted in the reduction of polysaccharide /protein (PS/PN) ratio in EPS and significant improvement of the sedimentation capacity of the sludge. Quorum quenching of AZM or aiiA gene maintained the sedimentation ability of the sludge in a relay mode. By adding AZM, the growth of Thauera and Flavobacterium, which caused sludge bulking, was inhibited. Paracoccus, a strong PHA producer, has been enriched to ensure that the maximum PHA synthesis of the system.


Assuntos
Matriz Extracelular de Substâncias Poliméricas , Poli-Hidroxialcanoatos , Azitromicina/farmacologia , Reatores Biológicos , Esgotos
15.
Theranostics ; 12(3): 1187-1203, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154482

RESUMO

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. Methods: 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. Results: 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. Conclusions: Taken together, this work highlights the possible role of azithromycin in obesity epidemic and presents strategies for safe applications of antibiotics in the future.


Assuntos
Azitromicina , Doenças Metabólicas , Tecido Adiposo Bege/metabolismo , Animais , Antibacterianos/farmacologia , Azitromicina/farmacologia , Humanos , Camundongos , Obesidade/metabolismo , Roedores
16.
J Vet Intern Med ; 36(2): 508-514, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35150012

RESUMO

BACKGROUND: Erythromycin, a macrolide antibiotic with motilin agonist properties, shortens gastric emptying (GE) time in healthy cats. Azithromycin, another macrolide antibiotic, is effective for treatment of gastric paresis in people. OBJECTIVES: To evaluate the effects of azithromycin on GE and gastric motility in healthy cats in comparison with erythromycin (positive control) and placebo. ANIMALS: Eight healthy purpose-bred cats. METHODS: Prospective, blinded, crossover study. Cats received either azithromycin (3.5 mg/kg PO q24h), erythromycin (1 mg/kg PO q8h), or placebo for 24 hours before and during evaluation of GE. A validated method using ultrasound for sequential measurements of antral area as well as amplitude and frequency of contractions was used to assess GE and evaluate gastric antral motility postprandially over an 8-hour period. RESULTS: GE was significantly faster (P < .05) after administration of azithromycin and erythromycin when compared to placebo in the late phase of fractional emptying from 75% (mean ± SD: 327 ± 51 minutes, 327 ± 22 minutes, and 367 ± 29 minutes, respectively), to 95% fractional emptying (399 ± 52 minutes, 404 ± 11 minutes, and 444 ± 24 minutes, respectively). The drugs had no significant effect on antral motility variables at any time point. CONCLUSIONS AND CLINICAL IMPORTANCE: Azithromycin and erythromycin shorten GE time in a comparable manner in healthy cats. Evaluation of their efficacy in cats with gastric dysmotility is warranted.


Assuntos
Azitromicina , Esvaziamento Gástrico , Animais , Azitromicina/farmacologia , Gatos , Estudos Cross-Over , Motilidade Gastrointestinal , Estudos Prospectivos
17.
Molecules ; 27(3)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35164298

RESUMO

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton-McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Azitromicina/análogos & derivados , Azitromicina/farmacologia , Animais , Antibacterianos/síntese química , Anti-Inflamatórios/síntese química , Azitromicina/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Células Cultivadas , Humanos , Macrolídeos/síntese química , Macrolídeos/química , Macrolídeos/farmacologia , Camundongos Endogâmicos BALB C , Modelos Moleculares , Oxirredução , Pneumonia/tratamento farmacológico
18.
Biomed Pharmacother ; 147: 112682, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35131658

RESUMO

Viral infections have a great impact on human health. The urgent need to find a cure against different viruses led us to investigations in a vast range of drugs. Azithromycin (AZT), classified as a macrolide, showed various effects on different known viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Zika, Ebola, Enterovirus (EVs) and Rhinoviruses (RVs), and Influenza A previously; namely, these viruses, which caused global concerns, are considered as targets for AZT different actions. Due to AZT background in the treatment of known viral infections mentioned above (which is described in this study), in the early stages of COVID-19 (a new zoonotic disease caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) development, AZT drew attention to itself due to its antiviral and immunomodulatory effects as a valuable candidate for COVID-19 treatment. AZT usage instructions for treating different viral infections have always been under observation, and COVID-19 is no exception. There are still debates about the use of AZT in COVID-19 treatment. However, eventually, novel researches convinced WHO to announce the discontinuation of AZT use (alone or in combination with hydroxychloroquine) in treating SARS-CoV-2 infection. This research aims to study the structure of all of the viruses mentioned above and the molecular and clinical effects of AZT against the virus.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Antibacterianos , Antivirais/farmacologia , Azitromicina/farmacologia , Ebolavirus/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da SARS/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Zika virus/efeitos dos fármacos
19.
Sci Rep ; 12(1): 1075, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058480

RESUMO

Inflammatory diseases including COVID-19 are associated with a cytokine storm characterized by high interleukin-6 (IL-6) titers. In particular, while recent studies examined COVID-19 associated arrhythmic risks from cardiac injury and/or from pharmacotherapy such as the combination of azithromycin (AZM) and hydroxychloroquine (HCQ), the role of IL-6 per se in increasing the arrhythmic risk remains poorly understood. The objective is to elucidate the electrophysiological basis of inflammation-associated arrhythmic risk in the presence of AZM and HCQ. IL-6, AZM and HCQ were concomitantly administered to guinea pigs in-vivo and in-vitro. Electrocardiograms, action potentials and ion-currents were analyzed. IL-6 alone or the combination AZM + HCQ induced mild to moderate reduction in heart rate, PR-interval and corrected QT (QTc) in-vivo and in-vitro. Notably, IL-6 alone was more potent than the combination of the two drugs in reducing heart rate, increasing PR-interval and QTc. In addition, the in-vivo or in-vitro combination of IL-6 + AZM + HCQ caused severe bradycardia, conduction abnormalities, QTc prolongation and asystole. These electrocardiographic abnormalities were attenuated in-vivo by tocilizumab (TCZ), a monoclonal antibody against IL-6 receptor, and are due in part to the prolongation of action potential duration and selective inhibition of Na+, Ca2+ and K+ currents. Inflammation confers greater risk for arrhythmia than the drug combination therapy. As such, in the setting of elevated IL-6 during inflammation caution must be taken when co-administering drugs known to predispose to fatal arrhythmias and TCZ could be an important player as a novel anti-arrhythmic agent. Thus, identifying inflammation as a critical culprit is essential for proper management.


Assuntos
Arritmias Cardíacas , Azitromicina/farmacologia , COVID-19 , Hidroxicloroquina/farmacologia , Interleucina-6/metabolismo , SARS-CoV-2/metabolismo , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/metabolismo , COVID-19/fisiopatologia , Feminino , Cobaias , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/fisiopatologia , Interleucina-6/antagonistas & inibidores , Masculino
20.
Emerg Microbes Infect ; 11(1): 344-350, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34994305

RESUMO

Background: After Neisseria gonorrhoeae FC428 was first found in Japan, ceftriaxone-resistant strains disseminated globally, and the gonococcal resistance rate increased remarkably. Epidemiological investigations are greatly significant for the analysis of antimicrobial resistance (AMR) trends, molecular features and evolution. Objectives: To clarify the AMR trend from 2016-2019 and reveal the molecular characteristics and evolution of ceftriaxone-resistant penA 60.001 isolates. Methods: The minimum inhibitory concentrations (MICs) of antibiotics against 4113 isolates were detected by the agar dilution method. N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were used to identify the sequence types. Genome analysis was conducted to analyze resistance genes, virulence factors, and evolutionary sources. Results: Isolates with decreased ceftriaxone susceptibility have increased from 2.05% (2016) to 16.18% (2019). Six ceftriaxone-resistant isolates possessing penA 60.001 appeared in Guangdong Province, and were resistant to ceftriaxone, penicillin, tetracycline, ciprofloxacin and cefixime, but susceptible to azithromycin and spectinomycin. Single-nucleotide polymorphisms (SNPs) in the porB gene were the major cause of different NG-MAST types. ST1903 was the main NG-STAR genotype and only strain-ZH545 was ST7365, with molecular features consistent with the MICs. Furthermore, different MLSTs suggested diverse evolutionary sources. Genome analysis revealed a set of virulence factors along with the resistance genes "penA" and "blaTEM-1B". Half of penA 60.001 strains were fully mixed with global FC428-related strains. Conclusions: Global FC428-related clones have disseminated across Guangdong, possibly causing decreased ceftriaxone susceptibility. Enhanced gonococcal surveillance will help elucidate the trajectory of transmission and curb further dissemination.


Assuntos
Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Azitromicina/farmacologia , China/epidemiologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Genoma Bacteriano , Gonorreia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Espectinomicina/farmacologia
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