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1.
Mol Biol Rep ; 51(1): 520, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625436

RESUMO

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.


Assuntos
Azitromicina , Síndrome do QT Longo , Humanos , Azitromicina/efeitos adversos , Células HEK293 , Antibacterianos/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/genética , Mutação
2.
Syst Rev ; 13(1): 108, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627798

RESUMO

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.


Assuntos
Antibacterianos , Leptospirose , Criança , Humanos , Antibacterianos/efeitos adversos , Doxiciclina/uso terapêutico , Azitromicina/efeitos adversos , Metanálise em Rede , Penicilinas/uso terapêutico , Leptospirose/tratamento farmacológico , Leptospirose/induzido quimicamente
3.
AAPS PharmSciTech ; 25(4): 77, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589761

RESUMO

Keratin has the potential to function as the gel matrix in an ophthalmic formulation for the encapsulation of the macrolide antibiotic azithromycin. The quality of this formulation was thoroughly evaluated through various analyses, such as in vitro release assessment, rheological examination, intraocular retention studies in rabbits, assessment of bacteriostatic efficacy, and safety evaluations. It is worth mentioning that the gel demonstrated shear thinning properties and exhibited characteristics of an elastic solid, thereby confirming its structural stability. The gel demonstrated a notable affinity for mucosal surfaces in comparison to traditional azithromycin aqueous solutions. In vitro release testing revealed that drug release transpired via diffusion mechanisms, following a first-order kinetic release pattern. Additionally, the formulated gel exhibited remarkable antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in bacteriostatic evaluations. Lastly, safety assessments confirmed that the gel eye drops induced minimal irritation and displayed no apparent cytotoxicity, indicating their good safety and biocompatibility for ocular application. Thus, these findings indicated that the prepared azithromycin gel eye drops complied with the requisite standards for ophthalmic preparations.


Assuntos
Conjuntivite Bacteriana , Sistemas de Liberação de Medicamentos , Animais , Coelhos , Azitromicina/farmacologia , Queratinas/uso terapêutico , Conjuntivite Bacteriana/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Géis/química , Soluções Oftálmicas/química
4.
Cochrane Database Syst Rev ; 3: CD014959, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483067

RESUMO

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.


Assuntos
Antibioticoprofilaxia , Leptospirose , Humanos , Antibioticoprofilaxia/efeitos adversos , Doxiciclina/efeitos adversos , Azitromicina/efeitos adversos , Qualidade de Vida , Antibacterianos/efeitos adversos , Penicilinas , Leptospirose/prevenção & controle
5.
Cochrane Database Syst Rev ; 3: CD014960, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483092

RESUMO

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.


Assuntos
Infecção Hospitalar , Leptospirose , Humanos , Antibacterianos/efeitos adversos , Doxiciclina/efeitos adversos , Azitromicina , Qualidade de Vida , Cloranfenicol , Penicilinas , Cefalosporinas/efeitos adversos , Cefotaxima , Leptospirose/tratamento farmacológico
6.
Sci Rep ; 14(1): 6947, 2024 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521802

RESUMO

Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.


Assuntos
Disenteria Bacilar , Shigella , Criança , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Disenteria Bacilar/tratamento farmacológico , Disenteria Bacilar/epidemiologia , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Farmacorresistência Bacteriana/genética , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Ceftriaxona/farmacologia , Testes de Sensibilidade Microbiana , Inibidores da Síntese de Proteínas/farmacologia , Plasmídeos/genética
7.
Microbiol Spectr ; 12(4): e0391823, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38441474

RESUMO

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant Escherichia coli T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test, ompC gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of tolA, eptB, lpxP, and opgE and upregulation of ompC gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the mph(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the ompC elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the mph(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene ompC.IMPORTANCEUsually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the ompC gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Azitromicina/farmacologia , Colistina/farmacologia , Regulação para Cima , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Porinas/genética , Porinas/metabolismo , Testes de Sensibilidade Microbiana , Proteínas de Escherichia coli/metabolismo
8.
MMWR Morb Mortal Wkly Rep ; 73(12): 255-259, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38547027

RESUMO

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxone-resistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.


Assuntos
Anti-Infecciosos , Gonorreia , Humanos , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina , Neisseria gonorrhoeae , Azitromicina , Anti-Infecciosos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana
9.
Chest ; 165(3): e71-e74, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38461021

RESUMO

CASE PRESENTATION: An 8-year-old girl presented with a 34-day history of cough, fatigue, and impaired exercise tolerance. She experienced cyanosis on exertion but denied fever, hemoptysis, hematuria, or seizures. Her perinatal and family histories were unremarkable, and she had no history of exposure to TB. A chest radiogram from a local clinic showed diffuse pulmonary lesions. Tuberculin skin test, interferon-γ release assay, and HIV antibody test results were all negative. Immunoglobulin levels and lymphocyte subsets were normal. The patient did not respond to IV azithromycin for 1 week for community-acquired pneumonia. She was transferred to our hospital because of progressive respiratory distress and hypoxemia.


Assuntos
Azitromicina , Tosse , Humanos , Feminino , Criança , Tosse/etiologia , Hemoptise , Dispneia , Hipóxia/complicações
10.
Sci Rep ; 14(1): 6883, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519558

RESUMO

We developed a reporter system based on simultaneous expression of two fluorescent proteins: GFP as a reporter of the capacity of protein synthesis and mutated mScarlet-I as a reporter of translational errors. Because of the unique stop codons or frameshift mutations introduced into the mScarlet-I gene, red fluorescence was produced only after a mistranslation event. These reporters allowed us to estimate mistranslation at a single cell level using either flow cytometry or fluorescence microscopy. We found that laboratory strains of Escherichia coli are more prone to mistranslation compared to the clinical isolates. As relevant for uropathogenic E. coli, growth in human urine elevated translational frameshifting compared to standard laboratory media, whereas different standard media had a small effect on translational fidelity. Antibiotic-induced mistranslation was studied by using amikacin (aminoglycoside family) and azithromycin (macrolide family). Bactericidal amikacin induced preferably stop-codon readthrough at a moderate level. Bacteriostatic azithromycin on the other hand induced both frameshifting and stop-codon readthrough at much higher level. Single cell analysis revealed that fluorescent reporter-protein signal can be lost due to leakage from a fraction of bacteria in the presence of antibiotics, demonstrating the complexity of the antimicrobial activity.


Assuntos
Antibacterianos , Mutação da Fase de Leitura , Humanos , Antibacterianos/farmacologia , Azitromicina/farmacologia , Amicacina , Escherichia coli/genética , Códon de Terminação/genética , Biossíntese de Proteínas
11.
Chemosphere ; 353: 141542, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428535

RESUMO

The escalating global concern regarding antibiotic pollution necessitates the development of advanced water treatment strategies. This study presents an innovative approach through the fabrication and evaluation of a Polyethersulfone (PES) membrane adorned with GO-TiO2 nanocomposites. The objective is to enhance the removal efficiency of various antibiotics, addressing the challenge of emerging organic compounds (EOCs) in water systems. The nanocomposite membranes, synthesized via the phase inversion method, incorporate hydrophilic agents, specifically GO-TiO2 nanocomposites and Polyvinylpyrrolidone (PVP). The resultant membranes underwent comprehensive characterization employing AFM, EDS, tensile strength testing, water contact angle measurements, and FESEM to elucidate their properties. Analysis revealed a substantial improvement in the hydrophilicity of the modified membranes attributed to the presence of hydroxyl groups within the GO-TiO2 structure. AFM images demonstrated an augmentation in surface roughness with increasing nanocomposite content. FESEM images unveiled structural modifications, leading to enhanced porosity and augmented water flux. The pure water flux elevated from 0.980 L/m2.h-1 for unmodified membranes to approximately 6.85 L/m2.h-1 for membranes modified with 2 wt% nanocomposites. Membrane performance analysis indicated a direct correlation between nanocomposite content and antibiotic removal efficiency, ranging from 66.52% to 89.81% with 4 wt% nanocomposite content. Furthermore, the nanocomposite-modified membrane exhibited heightened resistance to fouling. The efficacy of the membrane extended to displaying potent antibacterial properties against microbial strains, including S. aureus, E. coli, and Candida. This study underscores the immense potential of GO-TiO2 decorated PES membranes as a sustainable and efficient solution for mitigating antibiotic contamination in water systems. The utilization of nanocomposite membranes emerges as a promising technique to combat the presence of EOC pollutants, particularly antibiotics, in water bodies, thus addressing a critical environmental concern.


Assuntos
Nanocompostos , Polímeros , Povidona , Sulfonas , Antibacterianos/farmacologia , Azitromicina , Amoxicilina , Ciprofloxacina , Escherichia coli , Staphylococcus aureus , Nanocompostos/química , Membranas Artificiais
12.
BMC Pregnancy Childbirth ; 24(1): 200, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486177

RESUMO

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.


Assuntos
Corioamnionite , Endometrite , Sepse Neonatal , Infecção Puerperal , Sepse , Infecções Urinárias , Recém-Nascido , Gravidez , Feminino , Humanos , Azitromicina/uso terapêutico , Sepse Neonatal/epidemiologia , Sepse Neonatal/prevenção & controle , Cesárea , Corioamnionite/tratamento farmacológico , Corioamnionite/epidemiologia , Corioamnionite/prevenção & controle , Endometrite/epidemiologia , Endometrite/prevenção & controle , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/epidemiologia , Sepse/prevenção & controle , Infecção Puerperal/epidemiologia , Infecção Puerperal/prevenção & controle , Infecção da Ferida Cirúrgica , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controle
13.
ACS Nano ; 18(12): 8934-8951, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483284

RESUMO

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Ratos , Humanos , Animais , Hidrogéis/farmacologia , Azitromicina/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Anti-Inflamatórios/farmacologia
14.
Ital J Pediatr ; 50(1): 38, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38439015

RESUMO

BACKGROUND: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. METHODS: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis. RESULTS: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment. CONCLUSIONS: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients.


Assuntos
Doxiciclina , Pneumonia por Mycoplasma , Criança , Humanos , Doxiciclina/uso terapêutico , Mycoplasma pneumoniae , Macrolídeos/uso terapêutico , Azitromicina , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Pneumonia por Mycoplasma/tratamento farmacológico
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 198-203, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322510

RESUMO

Objective: To establish and evaluate a microbial sensitivity test method for Neisseria gonorrhoeae based on resazurin coloration. Methods: Based on the broth microdilution method, resazurin was added as a live bacteria indicator. WHO G, a WHO gonococcal reference strain, was used to optimize the incubation time for resazurin-stained bacteria and the color change was visually observed to obtain the results. Agar dilution method (the gold standard) and resazurin-based microdilution assay were used to determine the minimum inhibitory concentration (MIC) of azithromycin, ceftriaxone, and spectinomycin for 3 reference strains and 32 isolates of Neisseria gonorrhoeae. The results were analyzed based on essential agreement (EA), which reflected the consistency of the MIC values, category agreement (CA), which reflected the consistency in the determination of drug resistance, intermediary, and sensitivity, very major error (VME), which reflected false sensitivity, and major error (ME), which reflected pseudo drug resistance, to evaluate the accuracy of resazurin-based microdilution assay as a microbial sensitivity test of of Neisseria gonorrhoeae. CA and EA rates≥90% and VME and ME rates≤3% were found to be the acceptable performance rates. Results: The results obtained 6 hours after resazurin was added were consistent with those of the agar dilution method and the resazurin-based microdilution assay was established accordingly based on this parameter. The EA of resazurin-based microdilution assay for measuring the MIC results of azithromycin, ceftriaxone, and spectinomycin was 97.1%, 91.5%, and 94.3%, respectively, and the CA was 88.6%, 94.3%, and 94.3%, respectively. The VME was 0% for all three antibiotics, while the ME was 11.4%, 5.7%, and 5.7%, respectively. Conclusion: The resazurin-based microdilution assay established in this study showed good agreement with agar dilution method for measuring the MIC of antibiotics against Neisseria gonorrhoeae. Moreover, the sensitivity results of this method were highly reliable and could be easily obtained through naked eye observation. Nonetheless, the results of drug resistance should be treated with caution and the optimization of parameters should be continued.


Assuntos
Azitromicina , Neisseria gonorrhoeae , Oxazinas , Xantenos , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Espectinomicina , Ágar , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
16.
Stat Med ; 43(6): 1170-1193, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38386367

RESUMO

This research introduces a multivariate τ $$ \tau $$ -inflated beta regression ( τ $$ \tau $$ -IBR) modeling approach for the analysis of censored recurrent event data that is particularly useful when there is a mixture of (a) individuals who are generally less susceptible to recurrent events and (b) heterogeneity in duration of event-free periods amongst those who experience events. The modeling approach is applied to a restructured version of the recurrent event data that consists of censored longitudinal times-to-first-event in τ $$ \tau $$ length follow-up windows that potentially overlap. Multiple imputation (MI) and expectation-solution (ES) approaches appropriate for censored data are developed as part of the model fitting process. A suite of useful analysis outputs are provided from the τ $$ \tau $$ -IBR model that include parameter estimates to help interpret the (a) and (b) mixture of event times in the data, estimates of mean τ $$ \tau $$ -restricted event-free duration in a τ $$ \tau $$ -length follow-up window based on a patient's covariate profile, and heat maps of raw τ $$ \tau $$ -restricted event-free durations observed in the data with censored observations augmented via averages across MI datasets. Simulations indicate good statistical performance of the proposed τ $$ \tau $$ -IBR approach to modeling censored recurrent event data. An example is given based on the Azithromycin for Prevention of COPD Exacerbations Trial.


Assuntos
Azitromicina , Doença Pulmonar Obstrutiva Crônica , Humanos
18.
JAMA ; 331(6): 482-490, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349371

RESUMO

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.


Assuntos
Antibacterianos , Azitromicina , Mortalidade da Criança , Malária , Humanos , Azitromicina/provisão & distribuição , Azitromicina/uso terapêutico , Burkina Faso/epidemiologia , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , Mortalidade da Criança/tendências , Malária/epidemiologia , Malária/mortalidade , Malária/prevenção & controle , Antibacterianos/provisão & distribuição , Antibacterianos/uso terapêutico , Estações do Ano , Lactente , Pré-Escolar
19.
Medicine (Baltimore) ; 103(5): e37007, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306553

RESUMO

BACKGROUND: Nontuberculous mycobacteria (NTM), an extremely rare pathogen causing cervicofacial infections, may result in permanent hearing impairment or intracranial complications. Due to the lack of specific manifestations during the initial onset of NTM otomastoiditis, physicians may misdiagnose it as cholesteatoma or other common bacterial infections. PATIENT CONCERNS: A 44-year-old male who complained of left-sided aural fullness, otalgia, and dizziness for 2 months. DIAGNOSIS: The initial diagnosis was hypothesized to be cholesteatoma based on a whitish mass with mucoid discharge filling the entire outer ear canal on otoscopy and left-sided mixed hearing loss. However, NTM was identified by microbial culture at the 2-month follow-up after surgery. INTERVENTIONS: The patient underwent a left-sided exploratory tympanotomy. Because NTM otomastoiditis was diagnosed, 3 weeks of starting therapies were administered with azithromycin (500 mg/day, oral administration), cefoxitin (3 g/day, intravenous drip), and amikacin (750 mg/day, intravenous drip). The maintenance therapies were azithromycin (500 mg/day, oral administration) and doxycycline (200 mg/day, oral administration) for 7 months. OUTCOMES: The patient's clinical condition improved initially after surgery, but the otomastoiditis gradually worsened, combined with subtle meningitis, 2 months after surgery. The external auditory canal became swollen and obstructed, making it difficult to monitor the treatment efficacy through otoscopy. Thus, we used regular vestibular function tests, including static posturography, cervical vestibular evoked myogenic potentials, and video Head Impulse Test, to assess recovery outcomes. After antibiotic treatment, the infectious symptoms subsided significantly, and there was no evidence of infection recurrence 7 months after treatment. Improvements in static posturography and cervical vestibular evoked myogenic potentials were compatible with the clinical manifestations, but video Head Impulse Test showed an unremarkable correlation. LESSONS: The clinical condition of NTM otomastoiditis may be evaluated using vestibular tests if patients have symptoms of dizziness.


Assuntos
Colesteatoma , Potenciais Evocados Miogênicos Vestibulares , Masculino , Humanos , Adulto , Tontura/diagnóstico , Micobactérias não Tuberculosas , Azitromicina , Testes de Função Vestibular , Vertigem/diagnóstico , Potenciais Evocados Miogênicos Vestibulares/fisiologia
20.
Sex Transm Dis ; 51(5): 305-312, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301622

RESUMO

BACKGROUND: In 2021, national Chlamydia trachomatis (CT) treatment guidelines changed from recommending either azithromycin (1 g; single dose) or doxycycline (100 mg twice daily for 7 days) to recommending only doxycycline as first-line treatment. The distribution and trends in CT prescribing practices before the guidelines change is largely unknown. METHODS: We conducted a trends analysis using Washington STD surveillance data. We included all female cases of urogenital CT 15 years or older who resided in King County and were diagnosed between 2010 and 2018. Surveillance data included information on demographics, sexual history, clinical features, diagnosing facility (eg, emergency department, family planning), and treatment regimen. We conducted descriptive analyses to examine trends in prescribing practices over time and by facility type. We used Poisson regression to examine the association between CT case characteristics and receipt of receipt of azithromycin. RESULTS: There were 36,830 cases of female urogenital CT during the study period. The percent of cases receiving azithromycin increased significantly from 86% in 2010 to 94% in 2018; the percent receiving doxycycline decreased from 13% to 5%. Five of the 8 facility types prescribed azithromycin to >95% of CT cases by 2018. Cases who were younger or cases of color were more likely to receive azithromycin (versus doxycycline) compared with older and White cases, respectively. CONCLUSIONS: A substantial shift in CT prescribing practices will be needed to adhere to new CT treatment guidelines. Our findings highlight the need for targeted provider education and training to encourage the transition to doxycycline use.


Assuntos
Azitromicina , Infecções por Chlamydia , Feminino , Humanos , Azitromicina/uso terapêutico , Doxiciclina/uso terapêutico , Antibacterianos/uso terapêutico , Chlamydia trachomatis , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/epidemiologia , Washington/epidemiologia
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