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1.
BMC Infect Dis ; 24(1): 981, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285366

RESUMO

BACKGROUND: Mycoplasma genitalium (MG), a sexually transmitted infection (STI), has emerged as a common cause of non-gonococcal urethritis and cervicitis worldwide, with documented resistance to commonly used antibiotics including doxycycline and azithromycin. Data in Ghana regarding the prevalence of MG is limited. METHODS: This retrospective study investigated MG presence and macrolide resistance among patients who previously reported to selected clinics for STI symptoms between December 2012 and June 2020. Samples were screened for MG and mutations associated with azithromycin resistance were investigated using Nucleic Acid Amplification Testing (NAAT) including the Resistance Plus MG® kit from SpeeDx and the LightMix® kit for MG, combined with the Modular Mycoplasma Macrolide from TIB Molbiol. RESULTS: A total of 1,015 samples were screened, out of which MG infection rate by TIB Molbiol and SpeeDx were 3.1% and 3.4%, respectively. The mutation responsible for macrolide resistance was detected in one MG positive sample by both assays. Both diagnostic tests revealed no significant association between MG infection and socio-demographic characteristics, clinical symptoms, gonorrhea, and chlamydia infection status. There was no significant difference in the mycoplasma percentage positivity rate detected using SpeeDx (3.4%) and TIB Molbiol (3.1%). CONCLUSIONS: While not commonly tested as a cause of STI symptoms, MG is widespread in Ghana, exhibiting symptoms and prevalence comparable to those in other countries and linked to antimicrobial resistance. Future research using various molecular techniques is essential to monitor resistance trends and guide future antibiotic choices.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Infecções por Mycoplasma , Mycoplasma genitalium , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/genética , Mycoplasma genitalium/isolamento & purificação , Humanos , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/microbiologia , Gana/epidemiologia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Prevalência , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Saúde Sexual , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Mutação , Testes de Sensibilidade Microbiana
2.
AAPS PharmSciTech ; 25(7): 226, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327374

RESUMO

Drug-resin complexes usually form in the aqueous phase. For poorly water-soluble drugs, low drug loading limits the use of resin in drug formulation. In this study, we used a new method to prepare azithromycin resinates, improving the drug loading rate, shortening the preparation time and simplifying the process. We used hydro-alcoholic solution as the drug loading solvent and the ion exchange resin as the carrier, and this method enabled the resin to adsorb both the retardant and the drug. The sustained release effect of retardant Eudragit RL, RS100 was analyzed. Drug loading efficiency, release profiles, morphology, physicochemical characterization and pharmacokinetic study were assessed. Preparation of drug resinate by batch method resulted in 14% higher drug loading of azithromycin and 3.5 h shorter loading time as compared to pure water for hydroalcoholic solution as drug loading solvent. Raman mappings demonstrated that the retardant with higher molecular weight was more likely to adsorb to the outer layer of the resin compared to the drug. The in vitro release and in vivo pharmacokinetic study of azithromycin resinates showed a sustained release profile with few gastrointestinal adverse effects. Therefore, the addition of ethanol not only improved the efficiency of drug loading but also showed sustained-release effect with one-pot preparation of azithromycin resinates.


Assuntos
Azitromicina , Preparações de Ação Retardada , Solubilidade , Azitromicina/farmacocinética , Azitromicina/administração & dosagem , Azitromicina/química , Preparações de Ação Retardada/farmacocinética , Animais , Liberação Controlada de Fármacos , Solventes/química , Portadores de Fármacos/química , Troca Iônica , Química Farmacêutica/métodos , Masculino , Composição de Medicamentos/métodos , Resinas de Troca Iônica/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/química , Resinas Acrílicas/química
3.
Int J Nanomedicine ; 19: 9637-9658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309186

RESUMO

Introduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA. Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated. Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors. Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.


Assuntos
Antibacterianos , Azitromicina , Ácido Hialurônico , Staphylococcus aureus Resistente à Meticilina , Micelas , Quercetina , Infecções Estafilocócicas , Animais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Quercetina/farmacologia , Quercetina/química , Quercetina/farmacocinética , Quercetina/administração & dosagem , Células RAW 264.7 , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Azitromicina/química , Azitromicina/farmacologia , Azitromicina/farmacocinética , Azitromicina/administração & dosagem , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Portadores de Fármacos/química , Testes de Sensibilidade Microbiana
4.
Ann Clin Lab Sci ; 54(4): 452-456, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39293830

RESUMO

OBJECTIVE: To observe the effect of low-dose azithromycin on pulmonary ventilation function and inflammatory factors IL-6, IL-13 in children with bronchial asthma. METHODS: A total of 80 children with asthma in Pediatric Medicine affiliated to Taizhou Women and Children's Hospital of Wenzhou Medical University from January 2019 to December 2022 were selected and divided into control group (42 cases) and study group (38 cases). The control group regularly inhaled Salmeterol Xinafoate and Fluticasone Propionate inhalation, while the study group was additionally given low-dose azithromycin. After four weeks of treatment, pulmonary function tests including FEV1, FVC were performed and inflammatory indicators including CRP, FeNO, IL-6, IL-13 were measured. The occurrence of adverse reactions during treatment was recorded. RESULTS: Pulmonary function tests including FEV1%, FEV1/FVC% were improved in all subjects, and the improvement of pulmonary function was more significant in the study group (P<0.05). The levels of CRP, FeNO, IL-6 and IL-13 were decreased in the two groups, especially in the study group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups (P>0.05). CONCLUSION: Low-dose azithromycin can significantly improve the pulmonary function in children with bronchial asthma, reduce the levels of inflammatory factors, control airway mucus secretion and inflammation, and can be used to treat chronic lung diseases such as bronchial asthma.


Assuntos
Asma , Azitromicina , Interleucina-13 , Interleucina-6 , Testes de Função Respiratória , Humanos , Asma/tratamento farmacológico , Asma/fisiopatologia , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Feminino , Interleucina-13/metabolismo , Interleucina-13/sangue , Criança , Masculino , Interleucina-6/sangue , Interleucina-6/metabolismo , Ventilação Pulmonar/efeitos dos fármacos , Adolescente , Pré-Escolar
5.
J Med Case Rep ; 18(1): 433, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243108

RESUMO

BACKGROUND: This case report presents an exceptionally rare and atypical presentation of diphtheria in a 17-year-old female of Hausa ethnicity residing in an area with an elevated incidence within Kano State, Nigeria. By the end of 39th epidemiological week of 2023, only two cases of cutaneous diphtheria have been reported among 5,811 cases managed at MMSH diphtheria treatment center (DTC), representing approximately 0.035% of all diphtheria cases during that time period. CASE PRESENTATION: A 17-year-old Hausa female presented with a 3-day history of throat discomfort, malaise, and muffled speech. Physical examination revealed a pseudomembrane covering the tonsillar pillars, grade 3 tonsillar enlargement, and an unusual genital manifestation characterized by extensive vulval edema, severe pain, and a large, greyish patch extending into the vaginal introitus. Her medical history was significant for recent exposure to diphtheria and the emotional impact of her sibling's death from the same disease. Diagnostic tests, including throat swab culture and histocytology, confirmed diphtheria in the throat and vulvovaginal regions. The patient was promptly initiated on diphtheria antitoxin, Azithromycin, and innovative sitz baths with hydrogen peroxide. After 4 days of Sitz bath therapy, complete pseudomembrane clearance was observed, and the patient's symptoms resolved. CONCLUSION: This case underscores the complexity of diphtheria presentations, particularly with rare pseudomembranes in both throat and vaginal regions. The successful management, combining traditional and innovative therapies, highlights the importance of recognizing and addressing unusual manifestations promptly. The potential role of auto-inoculation and the efficacy of interventions like hydrogen peroxide sitz baths warrant further investigation. Overall, this case contributes to the understanding of diverse diphtheria presentations, guiding future clinical strategies for management of diphtheria cases and emphasizing the imperative of comprehensive vaccination efforts.


Assuntos
Difteria , Humanos , Feminino , Adolescente , Difteria/diagnóstico , Difteria/tratamento farmacológico , Antitoxina Diftérica/uso terapêutico , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Nigéria , Corynebacterium diphtheriae/isolamento & purificação
6.
Nat Commun ; 15(1): 7936, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261449

RESUMO

Traditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics of Escherichia coli after exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days. The results of our experiments provide evidence that bacteria exposed to these drugs replicate, evolve, and generate a sub-population of small colony variants (SCVs) which are resistant to multiple drugs. These SCVs contribute to the evolution of heteroresistance and rapidly revert to a susceptible state once the antibiotic is removed. Stated another way, exposure to bacteriostatic drugs selects for the evolution of heteroresistance in populations previously lacking this trait. More generally, our results question the definition of bacteriostasis as populations exposed to bacteriostatic drugs are replicating despite the lack of net growth.


Assuntos
Antibacterianos , Cloranfenicol , Escherichia coli , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Azitromicina/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos
7.
Lung ; 202(5): 683-693, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39284999

RESUMO

INTRODUCTION: In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis. METHODS: Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP. RESULTS: Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers. CONCLUSION: Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood. TRIAL REGISTRATION: EudraCT 2019-000580-24 (17 May 2019).


Assuntos
Azitromicina , Citocinas , Sarcoidose Pulmonar , Humanos , Azitromicina/uso terapêutico , Azitromicina/farmacologia , Pessoa de Meia-Idade , Feminino , Masculino , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/sangue , Citocinas/sangue , Citocinas/genética , Adulto , Interleucina-8/sangue , Interleucina-8/genética , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/sangue , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Expressão Gênica/efeitos dos fármacos , Idoso , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo
9.
Trials ; 25(1): 626, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334260

RESUMO

BACKGROUND: Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone. METHODS: The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme. DISCUSSION: The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020.


Assuntos
Antimaláricos , Azitromicina , Mortalidade da Criança , Combinação de Medicamentos , Pirimetamina , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfadoxina , Humanos , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Serra Leoa , Sulfadoxina/administração & dosagem , Sulfadoxina/uso terapêutico , Lactente , Método Duplo-Cego , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Administração Oral , Malária/prevenção & controle , Malária/mortalidade , Ensaios Clínicos Fase III como Assunto , Resultado do Tratamento , Feminino , Masculino , Esquema de Medicação , Fatores de Tempo
11.
PLoS One ; 19(8): e0307548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39172948

RESUMO

The present study assessed the impact of using irrigation water contaminated with Azithromycin (AZM) residues on the biomass and antioxidant compounds of purple corn; for this purpose, the plants were cultivated under ambient conditions, and the substrate used consisted of soil free from AZM residues, mixed with compost in a ratio of 1:1 (v/v). The experiment was completely randomized with four replications, with treatments of 0, 1, 10, and 100 µg/L of AZM. The results indicate that the presence of AZM in irrigation water at doses of 1 and 10 µg/L increases the weight of dry aboveground biomass, while at an amount of 100 µg/L, it decreases. Likewise, this study reveals that by increasing the concentration of AZM from 1 to 10 µg/L, total polyphenols and monomeric anthocyanins double, in contrast, with an increase to 100 µg/L, these decrease by 44 and 53%, respectively. It has been demonstrated that purple corn exposed to the antibiotic AZM at low doses has a notable antioxidant function in terms of DPPH and ORAC. The content of flavonols, phenolic acids, and flavanols increases by 57, 28, and 83%, respectively, when the AZM concentration is from 1 to 10 µg/L. However, with an increase to 100 µg/L, these compounds decrease by 17, 40, and 42%, respectively. On the other hand, stem length, root length, and dry weight of root biomass are not significantly affected by the presence of AZM in irrigation water.


Assuntos
Antioxidantes , Azitromicina , Biomassa , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/efeitos dos fármacos , Azitromicina/farmacologia , Antioxidantes/farmacologia , Antibacterianos/farmacologia , Polifenóis/análise , Polifenóis/farmacologia , Irrigação Agrícola/métodos , Antocianinas/análise
12.
Eye Contact Lens ; 50(10): 455-459, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39133177

RESUMO

OBJECTIVE: We conducted a retrospective evaluation of the long-term prognosis associated with anterior blepharitis subsequent to topical antibiotic intervention. METHODS: Inclusion criteria encompassed 92 eyes of 92 patients who exhibited clinical manifestations of anterior blepharitis and undergone a regimen of topical azithromycin. The follow-up duration extended to a minimum of one year within our medical facility. The diagnostic framework for anterior blepharitis, along with the evaluation of both objective and subjective manifestations, adhered to the Blepharitis Preferred Practice Pattern as promulgated by the American Academy of Ophthalmology. Relapse denoted the resurgence of blepharitis symptoms subsequent to the primary treatment, necessitating the instigation of either topical or oral therapeutic measures. RESULTS: Of 92 cases of anterior blepharitis, 48 showed recurrence, with a recurrence rate of 52.2%. During the follow-up period, 2 patients experienced 5 relapses, 2 patients experienced 4 relapses, 5 patients experienced 3 relapses, 13 patients experienced 2 relapses, and 26 patients experienced 1 relapse. When the patients were divided into three groups: multiple recurrence group (22 patients), single recurrence group (26 patients), and no recurrence group (44 patients), there were no significant differences in the blepharitis finding score before and after the initial treatment among three groups. However, significantly fewer patients in the no recurrence group required further treatment after initial treatment, and the percentage of patients with residual blepharitis during follow-up was significantly lower in the no recurrence group. CONCLUSIONS: Our data suggest that patients with residual findings after blepharitis treatment are at a risk of recurrence.


Assuntos
Antibacterianos , Azitromicina , Blefarite , Soluções Oftálmicas , Recidiva , Humanos , Blefarite/tratamento farmacológico , Blefarite/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Idoso , Adulto , Prognóstico , Seguimentos , Idoso de 80 Anos ou mais , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Adulto Jovem
13.
Viral Immunol ; 37(6): 298-307, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39096169

RESUMO

The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).


Assuntos
Antivirais , Azitromicina , Tratamento Farmacológico da COVID-19 , COVID-19 , Reposicionamento de Medicamentos , Hidroxicloroquina , Ivermectina , Lopinavir , Ritonavir , SARS-CoV-2 , Humanos , Antivirais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Ivermectina/uso terapêutico , Ritonavir/uso terapêutico , Azitromicina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Quimioterapia Combinada , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Pessoa de Meia-Idade , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Idoso , Pregnenodionas/uso terapêutico
14.
Medicine (Baltimore) ; 103(32): e39039, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121326

RESUMO

Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.


Assuntos
Azitromicina , Tratamento Farmacológico da COVID-19 , Eletrocardiografia , Hidroxicloroquina , Síndrome do QT Longo , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/administração & dosagem , Eletrocardiografia/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Azitromicina/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/administração & dosagem , Síndrome do QT Longo/induzido quimicamente , Idoso , Síndrome de Sjogren/tratamento farmacológico , Quimioterapia Combinada , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Levofloxacino/efeitos adversos , Adulto , SARS-CoV-2 , COVID-19
16.
J Microbiol Methods ; 224: 107009, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39098402

RESUMO

The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.


Assuntos
Babesia , Babesiose , Clindamicina , Doenças do Cão , Carga Parasitária , Parasitemia , Reação em Cadeia da Polimerase em Tempo Real , Animais , Cães , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Babesia/genética , Babesia/isolamento & purificação , Parasitemia/parasitologia , Parasitemia/veterinária , Babesiose/parasitologia , Babesiose/diagnóstico , Clindamicina/uso terapêutico , Carga Parasitária/métodos , Doxiciclina/uso terapêutico , Azitromicina/uso terapêutico , Metronidazol/uso terapêutico , Antiprotozoários/uso terapêutico , Naftoquinonas
17.
N Engl J Med ; 391(8): 699-709, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39167806

RESUMO

BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested. METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison. RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group. CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).


Assuntos
Antibacterianos , Azitromicina , Infecções Bacterianas , Mortalidade da Criança , Mortalidade Infantil , Administração Massiva de Medicamentos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Infecções Bacterianas/mortalidade , Infecções Bacterianas/prevenção & controle , Quimioprevenção/efeitos adversos , Quimioprevenção/estatística & dados numéricos , Farmacorresistência Bacteriana , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/estatística & dados numéricos , Níger/epidemiologia , População Rural/estatística & dados numéricos
18.
Front Immunol ; 15: 1447625, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211048

RESUMO

Macrolide antibiotic azithromycin is widely used in clinical practice to treat respiratory tract infections and inflammatory diseases. However, its mechanism of action is not fully understood. Given the involvement of the CD27 pathway in the pathophysiology of various T-lymphocyte-mediated inflammatory, autoimmune, and lymphoproliferative diseases, we examined the impact of AZM on CD27 regulation and potential consequences on CD4+ and CD8+ T-cell phenotypes. Using cellular immunology approaches on healthy donors' peripheral blood mononuclear cells, we demonstrate AZM-mediated downregulation of surface CD27 expression as well as its extracellular release as soluble CD27. Notably, AZM-exposed CD27high (hi) cells were defective in their ability to expand compared to CD27intermediate (Int) and CD27low (lo) subsets. The defective CD27hi subset expansion was found to be associated with impaired cell proliferation and cell division. At the molecular level, the CD27hi subset exhibited lower mTOR activity than other subsets. Functionally, AZM treatment resulted in marked depletion of helper CD4+ (Th1) and cytotoxic CD8+ T-lymphocyte (Tc1)-associated CXCR3+CD27hi effector cells and inhibition of inflammatory cytokine IFN-γ production. These findings provide mechanistic insights on immunomodulatory features of AZM on T-lymphocyte by altering the CD27 pathway. From a clinical perspective, this study also sheds light on potential clinical benefits observed in patients on prophylactic AZM regimens against various respiratory diseases and opens avenues for future adjunct therapy against Th1- and Tc1-dominated inflammatory and autoimmune diseases.


Assuntos
Azitromicina , Transdução de Sinais , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Azitromicina/farmacologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fenótipo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Antibacterianos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos
19.
J Mater Chem B ; 12(34): 8465-8476, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39109448

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) pneumonia can have serious physiological consequences, particularly when P. aeruginosa biofilms are formed. Although inhaled therapy is preferred, inhaled drugs tend to get trapped by pulmonary mucus, which hinders efficient antibiotic permeability through mucus and biofilms. In this study, we prepare poly[2-(pentamethyleneimino)ethyl methacrylate]-block-poly[2-(N-oxide-pentamethyleneimino)ethyl methacrylate] (PPEMA-b-PPOEMA) micelles loaded with azithromycin (AZM) using reversible addition-fragmentation chain transfer (RAFT) polymerization to achieve effective treatment of P. aeruginosa pneumonia. The zwitterionic structure on the surface of the micelle facilitates the successful traversal of the mucus and optimal concentration within the biofilm. Furthermore, the protonation of piperidine in the polymer enables the micelles to exhibit a positive charge in the acidic environment of a bacterial infection, enhancing AZM's interaction with the bacterium. Both in vivo and in vitro experiments demonstrate that this transmucosal zwitterionic polymer, in combination with a charge reversal strategy, effectively promotes the enrichment of micelles at the site of bacterial infection, thereby increasing the number of antibiotics reaching the bacterial interior and demonstrating remarkable antibacterial synergy. Overall, this work offers a promising approach for trans-airway drug delivery in the treatment of pneumonia.


Assuntos
Antibacterianos , Micelas , Pseudomonas aeruginosa , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Mucinas/química , Mucinas/metabolismo , Camundongos , Administração por Inalação , Azitromicina/química , Azitromicina/farmacologia , Azitromicina/administração & dosagem , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Pneumonia/tratamento farmacológico , Doença Crônica , Portadores de Fármacos/química
20.
PLoS Negl Trop Dis ; 18(8): e0012398, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39146379

RESUMO

Haemophilus ducreyi (HD) is an important cause of cutaneous ulcers in several endemic regions, including the Western Pacific Region, especially among children. An HD sequence typing on swab samples taken from 1,081 ulcers in the Namatanai district of Papua New Guinea, during the pilot study for treatment of yaws, has been performed using the Grant typing system. Of the 363 samples that tested positive for the 16S rDNA of HD, the dsrA sequences of 270 samples were determined. Altogether they revealed 8 HD strain types circulating in Namatanai, including seven strain types of Class I (I.3, I.4, I.5, I.9, I.10, I.11, I.12) and one strain of Class II (II.3); four Class I types (I.9, I.10, I.11, I.12) were novel. The southern region of Namatanai (Matalai Rural) was identified as the region with the lowest genotype diversity and with most infections caused by HD Class II. The middle and northern subdistricts were affected mainly by HD Class I. Analysis of patient characteristics revealed that Class II HD infections were more often represented by longer-lasting ulcers than Class I HD infections. An increase in the prevalence of the I.10 strain was found after azithromycin administration compared to the untreated population at baseline likely reflecting higher infectivity of HD Class I, and more specifically strain type I.10.


Assuntos
Antibacterianos , Azitromicina , Cancroide , Genótipo , Haemophilus ducreyi , Humanos , Haemophilus ducreyi/genética , Haemophilus ducreyi/isolamento & purificação , Haemophilus ducreyi/efeitos dos fármacos , Azitromicina/uso terapêutico , Papua Nova Guiné/epidemiologia , Feminino , Masculino , Criança , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adolescente , Cancroide/microbiologia , Cancroide/epidemiologia , Cancroide/tratamento farmacológico , Adulto , Pré-Escolar , Adulto Jovem , RNA Ribossômico 16S/genética , Bouba/microbiologia , Bouba/epidemiologia , Bouba/tratamento farmacológico , Pessoa de Meia-Idade , Análise de Sequência de DNA , DNA Bacteriano/genética , Projetos Piloto , Filogenia
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