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1.
J Environ Manage ; 329: 117022, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549062

RESUMO

In this study, a ternary ZnO@spinel cobalt ferrite@carbon nanotube magnetic photocatalyst (ZSCF@CNT) was successfully synthesized and used to activate peroxymonosulfate (PMS) for Cefixime (CFX) antibiotic degradation under UVC irradiation. The morphology, optical, structural, and physicochemical properties of ZSCF@CNT were characterized and analyzed by XPS, XRD, FESEM-EDX, TEM, BET, VSM, UV-vis DRS and PL analysis. The results indicated that the ternary ZSCF@CNT photocatalyst exhibited superior catalytic activity on CFX elimination than that of individual components and binary composite catalysts, in which CFX with was rapidly removed under UVC irradiation and PMS. The effect of operational parameters including initial PMS, catalyst, and CFX concentrations and solution pH on the catalytic activity was investigated in detail; the optimal conditions were: pH: 7.0, catalyst: 0.3 g/L, PMS: 3.0 mM, leading to total CFX (10 mg/L) elimination in ∼20 min. Based on the radical scavenger tests, various radicals and non-radical species including sulfate, hydroxyl and superoxide radicals, singlet oxygen and electrons were involved in the ZSCF@CNT/PMS/UVC system. The high surface area, reduced agglomeration formation and excellent separation of photogenerated electron-hole pairs embodied in ZSCF@CNT photocatalyst conferred its superior catalytic activity and stability. The results from the tests in real water matrices revealed that ZSCF@CNT could be a promising photocatalyst to activate PMS for actual aqueous matrices' treatment.


Assuntos
Nanotubos de Carbono , Óxido de Zinco , Cefixima , Peróxidos/química
2.
Chemosphere ; 314: 137516, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36521743

RESUMO

The study reports an innovative approach on sunlit driven heterostructure photocatalytic generation of H2O2 and removal of cefixime. In the present work, we have fabricated Mn/Mg doped CoFe2O4 modified CaCr2O4 decorated by Ag3PO4 quantum dots (Ag3PO4 QDs), a p-n-p nano heterojunction. The study promotes the photocatalytic production of H2O2 and self-Fenton photocatalytic degradation of cefixime. Egg white-assisted synthesis of Mn-doped CoFe2O4 causes the lattice oxygen defect, which enhances the photocatalytic activity. Lattice oxygen defect enable the adsorption of O2, which enable the conversion of •O2 in the valence band of CoFe2O4 for the endogenous production of H2O2. The higher in the surface area enhance the photocatalytic activity under visible light irradiation. Mn-CoFe2O4-CaCr2O4-Ag3PO4 QDs enables the complete photocatalytic degradation of cefixime (99.9%) and the complete removal was determined by total organic carbon (TOC) removal and it was around 99.4%. Meanwhile the photocatalytic degradation pathway of cefixime was determined by LC-MS/MS. Reusability of the nano heterojunction was determined by six cycle test, and the reusability of the nano heterojunction was 99.8%. Further, the toxicity of the nanomaterial was studied in maize plant and the results shows that the nanoheterojunction enhances the maize growth. The study systematically reveals the robust activity of nano heterojunction for sustainable water treatment.


Assuntos
Peróxido de Hidrogênio , Pontos Quânticos , Cefixima , Cromatografia Líquida , Espectrometria de Massas em Tandem , Pontos Quânticos/química
3.
BMC Infect Dis ; 22(1): 939, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36513989

RESUMO

BACKGROUND: Indiscriminate and widespread use of antibiotics has resulted in emergence of many antibiotic-resistant organisms. Antibiotic administration during pregnancy is mostly avoided, unless there is compelling medical condition. We hypothesized that the uropathogens isolated from pregnant women would be more susceptible to antibiotics compared to those isolated from nonpregnant women, thus will be helpful in formulating separate empiric guideline for pregnant women based on the resistance pattern. METHODS: This was a prospective cross-sectional study conducted over a period of 2 years in which females with the clinical diagnosis of either cystitis or asymptomatic bacteriuria during pregnancy were included from the community settings. Uropathogen species and their antimicrobial resistance pattern were compared between the pregnant and nonpregnant groups. After accounting for centre-to-centre variation and adjusting for age and socio-economic status, the adjusted odds ratio for antibiotic resistance was calculated and compared between pregnant and nonpregnant women using logistic regression analysis. RESULTS: A total of 1758 women (pregnant: 43.3%; nonpregnant: 56.6%) were screened in the study over a period of 2 years, out of which 9.3% (163/1758) were having significant bacteriuria. Escherichia coli and Klebsiella pneumoniae were the two commonest uropathogen in both the groups; their prevalence being 83.6% in pregnant women and 85.2% in nonpregnant women, respectively. Resistance against ampicillin, cefixime, cefoxitin, ceftazidime, ceftriaxone and amoxicillin-clavulanic acid were found significantly lower in the pregnant women compared to nonpregnant. After adjusting the age and socio-economic status accounting for centre-to-centre variation, the odds of resistance for cefixime, amoxicillin-clavulanic acid and co-trimoxazole were found lower and statistically significant among the pregnant women group. CONCLUSIONS: The antimicrobial resistance was significantly higher among the community-dwelling nonpregnant women compared to pregnant women in case of few antibiotics. The study highlighted the need of building local antibiogram that could help to initiate the empirical treatment and thus prevent emergence of antimicrobial resistance.


Assuntos
Gestão de Antimicrobianos , Bacteriúria , Infecções Urinárias , Feminino , Humanos , Gravidez , Bacteriúria/diagnóstico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Cefixima/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Estudos Transversais , Estudos Prospectivos , Vida Independente , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli
4.
BMJ Open ; 12(11): e064782, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368750

RESUMO

INTRODUCTION: Neisseria gonorrhoeae infections are common and incidence increasing. Oropharyngeal infections are associated with greater treatment failure compared with other sites and drive transmission to anogenital sites through saliva. Gonococcal resistance is increasing and new treatments are scarce, therefore, clinicians must optimise currently available and emerging treatments in order to have efficacious therapeutic options. This requires pharmacokinetic data from the oral cavity/oropharynx, however, availability of such information is currently limited. METHODS AND ANALYSIS: Healthy male volunteers (participants) recruited into the study will receive single doses of either ceftriaxone 1 g, cefixime 400 mg or ceftriaxone 500 mg plus 2 g azithromycin. Participants will provide samples at 6-8 time points (treatment regimen dependent) from four oral sites, two oral fluids, one anorectal swab and blood. Participants will complete online questionnaires about their medical history, sexual practices and any side effects experienced up to days 5-7. Saliva/oral mucosal pH and oral microbiome analysis will be undertaken. Bioanalysis will be conducted by liquid chromatography-mass spectrometry. Drug concentrations over time will be used to develop mathematical models for optimisation of drug dosing regimens and to estimate pharmacodynamic targets of efficacy. ETHICS AND DISSEMINATION: This study was approved by Royal Melbourne Hospital Human Research Ethics Committee (60370/MH-2021). The study results will be submitted for publication in peer-reviewed journals and reported at conferences. Summary results will be sent to participants requesting them. All data relevant to the study will be included in the article or uploaded as supplementary information. TRIAL REGISTRATION NUMBER: ACTRN12621000339853.


Assuntos
Gonorreia , Masculino , Humanos , Gonorreia/tratamento farmacológico , Ceftriaxona/uso terapêutico , Antibacterianos , Cefixima/uso terapêutico , Neisseria gonorrhoeae
5.
Chemotherapy ; 67(4): 261-268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417841

RESUMO

INTRODUCTION: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs. METHODS: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 µg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. RESULTS: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Humanos , Cefixima/farmacologia , Cefixima/uso terapêutico , Escherichia coli , beta-Lactamases , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções por Escherichia coli/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico
6.
Cochrane Database Syst Rev ; 11: CD010452, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36420914

RESUMO

BACKGROUND: Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. OBJECTIVES: To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. MAIN RESULTS: We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones.  We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.


Assuntos
Anti-Infecciosos , Febre Paratifoide , Febre Tifoide , Criança , Adulto , Humanos , Adolescente , Febre Paratifoide/tratamento farmacológico , Febre Tifoide/tratamento farmacológico , Cefalosporinas/uso terapêutico , Azitromicina/efeitos adversos , Ceftriaxona/uso terapêutico , Cefixima/uso terapêutico , Fluoroquinolonas/uso terapêutico , Antibacterianos/uso terapêutico , Cloranfenicol/uso terapêutico , Anti-Infecciosos/uso terapêutico , Monobactamas/uso terapêutico , Ciprofloxacina/uso terapêutico , Ofloxacino/uso terapêutico , Recidiva , Paquistão
7.
PLoS One ; 17(10): e0276625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36269734

RESUMO

Thermophilic Campylobacter species are common cause of animal and human bacterial diseases with growing resistance to antimicrobials. The aim of this study was to determine the prevalence and antimicrobial susceptibility pattern of Campylobacter species from bovine, knives and personnel in Jimma Town, Ethiopia. Faecal samples and carcasses swabs were collected from cattle systematically selected from the annual plan of Jimma Municipal Abattoir. Personnel hand and knife swabs were collected after slaughtering each selected cattle. A cross-sectional study with systematic sampling method was conducted from October 2019 to September 2020 for the isolation, identification and antimicrobial susceptibility pattern of thermophilic Campylobacter species. Isolation and identification of Campylobacter species were performed according to the techniques recommended by the International Organization for Standardization, and in vitro antibiotic susceptibility testing was screened using the standard agar disc diffusion method as recommended by Clinical and Laboratory Standards Institutions. A total of 684 samples (171 samples from faeces, carcasses, knives and personnel hands, were collected independently). The overall prevalence of thermophilic Campylobacterspecies was 5.6% (38/684). Majority of the isolates were from faecal samples (12.9%, n = 22) followed by carcass swabs(4.1% n = 7), knife swabs(3.5% n = 6) and personnel hand swabs(1.8% n = 3). Isolated and identified species of C.jejuni, C. coli and C. lari accounted for 63.2%, 23.7% and 13.2%, respectively. The isolated Campylobacter species were found to be resistant to Cephalothin (100%), Ampicillin (60.5%), Cefotaxime (60.5%), Chloramphenicol (47.4%) and Tetracycline (42.1%). On the other hand, the isolates were susceptible to Nalidixic acid (86.8%), Ciprofloxacin (86.8%), Sulphamethazole (84.2%), Ceftriaxone (78.9%), Clindamycin (68.4%) and Cefixime (65.8%). 84.2% of the isolates showed multi-drug resistance for three-to-six drug classes. All the C. lari isolates were multidrug resistant. All the three isolated species of Campylobacter were resistant to Cephalothin, and most were multidrug resistant. Isolation of Campylobacter species from faecal, carcass, knife and hand swabs revealed possible risk of contamination and exposure to Campylobacter infection of those who consume raw meat. Therefore, enactment of hygienic practices during the slaughtering process, proper handling and cooking of meat and awareness creation on jurisdictional antibiotic usage are required to avoid Campylobacter infection.


Assuntos
Infecções por Campylobacter , Campylobacter , Bovinos , Animais , Humanos , Infecções por Campylobacter/microbiologia , Matadouros , Ácido Nalidíxico , Cefalotina , Estudos Transversais , Cefixima , Ceftriaxona , Clindamicina , Ágar , Etiópia/epidemiologia , Resistência Microbiana a Medicamentos , Antibacterianos/farmacologia , Tetraciclina , Ciprofloxacina , Cloranfenicol/farmacologia , Ampicilina , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana
8.
Foodborne Pathog Dis ; 19(10): 704-712, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36264103

RESUMO

Escherichia albertii is an emerging pathogen causing foodborne infections with diarrhea, abdominal pain, and fever. E. albertii has been isolated from various food sources, such as chicken and pork. Although many foodborne outbreaks of E. albertii have been reported, the causative food has not been identified. It is necessary to develop effective detection methods for E. albertii. Because enrichment procedure as the first step of food test is important for growing pathogens, this study aimed to develop a novel effective enrichment for E. albertii detection in food. In this study, we investigated the optimal concentration and combination of cefixime and tellurite for supplementing modified EC broth (mEC) to effectively isolate E. albertii from chicken meat. The results showed that mEC supplemented with 50 µg/L cefixime and 2.5 mg/L tellurite (CT-mEC) inhibited the growth of competitive bacteria in chicken meat but not that of E. albertii. Therefore, it was indicated that CT-mEC had strong potential to selectively grow E. albertii. In an E. albertii foodborne outbreak, CT-mEC was evaluated. E. albertii was successfully isolated from a food sample, a kind of salad, by enrichment with CT-mEC but not buffered peptone water and mEC. In this study, CT-mEC as a selective enrichment broth has been developed to detect E. albertii in chicken meat. It was demonstrated that the selective enrichment broth was effective for the efficient detection of E. albertii in food.


Assuntos
Peptonas , Água , Cefixima , Microbiologia de Alimentos , Meios de Cultura
9.
BMJ Open ; 12(10): e062401, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253043

RESUMO

OBJECTIVES: To estimate the antibiotic prescription rates for typhoid in India. DESIGN: Cross-sectional study. SETTING: Private sector primary care clinicians in India. PARTICIPANTS: The data came from prescriptions of a panel of 4600 private sector primary care clinicians selected through a multistage stratified random sampling accounting for the region, specialty type and patient turnover. The data had 671 million prescriptions for antibiotics extracted from the IQVIA database for the years 2013, 2014 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean annual antibiotic prescription rates; sex-specific and age-specific prescription rates; distribution of antibiotic class. RESULTS: There were 8.98 million antibiotic prescriptions per year for typhoid, accounting for 714 prescriptions per 100 000 population. Children 10-19 years of age represented 18.6% of the total burden in the country in absolute numbers, 20-29 year age group had the highest age-specific rate, and males had a higher average rate (844/100 000) compared with females (627/100 000). Ten different antibiotics accounted for 72.4% of all prescriptions. Cefixime-ofloxacin combination was the preferred drug of choice for typhoid across all regions except the south. Combination antibiotics are the preferred choice of prescribers for adult patients, while cephalosporins are the preferred choice for children and young age. Quinolones were prescribed as monotherapy in 23.0% of cases. CONCLUSIONS: Nationally representative private sector antibiotic prescription data during 2013-2015 indicate a higher disease burden of typhoid in India than previously estimated. The total prescription rate shows a declining trend. Young adult patients account for close to one-third of the cases and children less than 10 years account for more than a million cases annually.


Assuntos
Quinolonas , Febre Tifoide , Antibacterianos/uso terapêutico , Cefixima , Cefalosporinas/uso terapêutico , Criança , Estudos Transversais , Prescrições de Medicamentos , Feminino , Humanos , Índia/epidemiologia , Masculino , Auditoria Médica , Ofloxacino , Padrões de Prática Médica , Setor Privado , Quinolonas/uso terapêutico , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Adulto Jovem
10.
Curr Microbiol ; 79(11): 338, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36201048

RESUMO

Owing to the resistance of nosocomial pathogens to antibiotics, the need for herbal medicines is felt. The aim of this study was to identify the chemical composition of bark essential oils of Campsis radicans and the effect of its free and encapsulated form on resistant nosocomial pathogens. This plant is a native of Northern Iran. The Bark essential oils of Campsis radicans was first extracted and its antimicrobial effects were investigated. Then, its phytochemical compounds were determined using Gas Chromatography-Mass Spectrometry (GC/MS). Guaiacol (2-methoxy phenol) was selected as the active ingredient among 32 compounds (2.40%). It was encapsulated and the encapsulation efficiency (EE), the particle size, polydispersity index (pdi), Fourier transform infrared (FTIR), release, and stability were determined. Then, the antimicrobial effect of both free and encapsulated forms was evaluated on cotrimoxazole-resistant Pseudomonas aeruginosa, cefixime-resistant Escherichia coli, and fluconazole-resistant Candida albicans. It was observed that both free and encapsulated forms of Guaiacol had an antimicrobial effect on the studied resistant strains, but the encapsulated form had a more antimicrobial effect due to more stability and a more targeted effect. MBC (MFC) ranged from 0.270 to 0.439 µg/ml in the free form and from 0.055 to 0.133 µg/ml in the encapsulated form, EE was 86%, particle size, and pdi were 138 nm and 0.26, respectively. This study showed that this plant can be a suitable alternative to chemical drugs due to its antimicrobial effects.


Assuntos
Anti-Infecciosos , Infecção Hospitalar , Óleos Voláteis , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias , Cefixima/farmacologia , Fluconazol/farmacologia , Guaiacol , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Óleos Vegetais/farmacologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia
11.
Front Cell Infect Microbiol ; 12: 997368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093187

RESUMO

Antibiotic abuse is growing more severe in clinic, and even short-term antibiotic treatment can cause long-term gut dysbiosis, which may promote the development and aggravation of diseases. Cephalosporins as the broad-spectrum antibiotics are widely used for prevention and treatment of community-acquired respiratory tract infection in children. However, their potential consequences in health and disease have not been fully elaborated. In this study, the effects of cefaclor, cefdinir and cefixime on intestinal microbiota and lung injury were investigated in Streptococcus pneumoniae (Spn)-infected mice. The results showed that the proportion of coccus and bacillus in intestinal microbiota were changed after oral administration with cefaclor, cefdinir and cefixime twice for 10 days, respectively. Compared with the Spn-infected group, the proportion of Bifidobacterium and Lactobacillus in intestine were significantly reduced, while Enterococcus and Candida was increased after cephalosporin treatment. Furthermore, 3 cephalosporins could obviously increase the number of total cells, neutrophils and lymphocytes in BALF as well as the serum levels of endotoxin, IL-2, IL-1ß, IL-6 and TNF-α. Mechanically, cephalosporins accelerated Spn-induced pulmonary barrier dysfunction via mediating the mRNA expressions of endothelial barrier-related proteins (Claudin 5, Occludin, and ZO-1) and inflammation-related proteins (TLR4, p38 and NF-κB). However, all of those consequences could be partly reversed by Bifidobacterium bifidum treatment, which was closely related to the elevated acetate production, indicating the protective effects of probiotic against antibiotic-induced intestinal dysbiosis. Therefore, the present study demonstrated that oral administration with cephalosporins not only disrupted intestinal microecological homeostasis, but also increased the risk of Spn infection, resulting in severer respiratory inflammation and higher bacterial loads in mice.


Assuntos
Cefalosporinas , Disbiose , Animais , Antibacterianos/farmacologia , Cefaclor/efeitos adversos , Cefdinir , Cefixima/efeitos adversos , Disbiose/microbiologia , Inflamação/microbiologia , Camundongos , Streptococcus pneumoniae
12.
Int J Mol Sci ; 23(18)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36142410

RESUMO

The paper presents various issues related to the increasing drug resistance of Neisseria gonorrhoeae and the occurrence and spread of multidrug-resistant clones. One of the most important is the incidence and evolution of resistance mechanisms of N. gonorrhoeae to beta-lactam antibiotics. Chromosomal resistance to penicillins and oxyimino-cephalosporins and plasmid resistance to penicillins are discussed. Chromosomal resistance is associated with the presence of mutations in the PBP2 protein, containing mosaic variants and nonmosaic amino acid substitutions in the transpeptidase domain, and their correlation with mutations in the mtrR gene and its promoter regions (the MtrCDE membrane pump repressor) and in several other genes, which together determine reduced sensitivity or resistance to ceftriaxone and cefixime. Plasmid resistance to penicillins results from the production of beta-lactamases. There are different types of beta-lactamases as well as penicillinase plasmids. In addition to resistance to beta-lactam antibiotics, the paper covers the mechanisms and occurrence of resistance to macrolides (azithromycin), fluoroquinolones and some other antibiotics. Moreover, the most important epidemiological types of multidrug-resistant N. gonorrhoeae, prevalent in specific years and regions, are discussed. Epidemiological types are defined as sequence types, clonal complexes and genogroups obtained by various typing systems such as NG-STAR, NG-MAST and MLST. New perspectives on the treatment of N. gonorrhoeae infections are also presented, including new drugs active against multidrug-resistant strains.


Assuntos
Neisseria gonorrhoeae , Peptidil Transferases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina , Cefixima , Ceftriaxona , Resistência a Medicamentos , Farmacorresistência Bacteriana/genética , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/genética , Penicilinase , Penicilinas , beta-Lactamases
13.
Drug Des Devel Ther ; 16: 2995-3013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110398

RESUMO

Purpose: The development of effective treatments for coronavirus infectious disease 19 (COVID-19) caused by SARS-Coronavirus-2 was hindered by the little data available about this virus at the start of the pandemic. Drug repurposing provides a good strategy to explore approved drugs' possible SARS-CoV-2 antiviral activity. Moreover, drug synergism is essential in antiviral treatment due to improved efficacy and reduced toxicity. In this work, we studied the effect of approved and investigational drugs on one of SARS-CoV-2 essential proteins, the main protease (Mpro), in search of antiviral treatments and/or drug combinations. Methods: Different possible druggable sites of Mpro were identified and screened against an in-house library of more than 4000 chemical compounds. Molecular dynamics simulations were carried out to explore conformational changes induced by different ligands' binding. Subsequently, the inhibitory effect of the identified compounds and the suggested drug combinations on the Mpro were established using a 3CL protease (SARS-CoV-2) assay kit. Results: Three potential inhibitors in three different binding sites were identified; favipiravir, cefixime, and carvedilol. Molecular dynamics simulations predicted the synergistic effect of two drug combinations: favipiravir/cefixime, and favipiravir/carvedilol. The in vitro inhibitory effect of the predicted drug combinations was established on this enzyme. Conclusion: In this work, we could study one of the promising SARS-CoV-2 viral protein targets in searching for treatments for COVID-19. The inhibitory effect of several drugs on Mpro was established in silico and in vitro assays. Molecular dynamics simulations showed promising results in predicting the synergistic effect of drug combinations.


Assuntos
Proteases 3C de Coronavírus , Amidas , Antivirais/química , Antivirais/farmacologia , Carvedilol , Cefixima , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Drogas em Investigação , Humanos , Ligantes , Simulação de Dinâmica Molecular , Pirazinas , SARS-CoV-2 , Proteínas Virais
14.
BMJ Case Rep ; 15(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36113957

RESUMO

We present a case of gonococcal septic arthritis of the right hip diagnosed via synovial fluid cultures. Antimicrobial susceptibility testing of the synovial fluid demonstrated susceptibility to tetracycline, ciprofloxacin, cefixime and ceftriaxone. Our patient was initially treated with ceftriaxone and was successfully de-escalated to oral levofloxacin to complete the treatment. This case is interesting given the rarity of disseminated gonococcal infections in the 21st century and that most clinical isolates of Neisseria gonorrhoeae are increasingly resistant to fluoroquinolones.


Assuntos
Artrite Infecciosa , Gonorreia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Cefixima/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Fluoroquinolonas/uso terapêutico , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Levofloxacino/uso terapêutico , Tetraciclina/uso terapêutico
15.
Chemosphere ; 308(Pt 2): 136297, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36064026

RESUMO

The continuous rise in the amount of industrial and pharmaceutical waste in water sources is an alarming concern. Effective strategies should be developed for the treatment of pharmaceutical industrial waste. Hence the alternative renewable source of energy, such as solar energy, should be utilized for a sustainable future. Herein, a series of Au plasmonic nanoparticle decorated ternary photocatalysts comprising graphitic carbon nitride and Ti3C2 MXene has been designed to degrade colourless pharmaceutical pollutants, cefixime under visible light irradiation. These photocatalysts were synthesized by varying the amount of Ti3C2 MXene, and their catalytic potential was explored. The optimized photocatalyst having 3 wt% Ti3C2 MXene achieved 64.69% removal of the pharmaceutical pollutant, cefixime within 105 min of exposure to visible light. The presence of the Au nanoparticles and MXene in the nanocomposite facilitates the excellent charge carrier separation and increased the number of active sites due to the formation of interfacial contact with graphitic carbon nitride nanosheets. Besides, the plasmonic effect of the Au nanoparticles improves the absorption of light causing enhanced photocatalytic performance of the nanocomposite. Based on the obtained results, a plausible mechanism has been formulated to understand the contribution of different components in photocatalytic activity. In addition, the optimized photocatalyst shows excellent activity and can be reused for up to three cycles without any significant loss in its photocatalytic performance. Overall, the current work provides deeper physical insight into the future development of MXene graphitic carbon nitride-based plasmonic ternary photocatalysts.


Assuntos
Poluentes Ambientais , Nanopartículas Metálicas , Cefixima , Ouro , Grafite , Resíduos Industriais , Nanopartículas Metálicas/química , Compostos de Nitrogênio , Preparações Farmacêuticas , Água
16.
Virus Res ; 321: 198915, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36084746

RESUMO

The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (RBD) and found that peptide 391-465 aa is the major hACE2-interacting sites in SARS-CoV-2 spike RBD. We then identified essential amino acid residues (403R, 449Y, 454R) of peptide 391-465 aa that were critical for the interaction between the RBD and hACE2. Additionally, a pseudotyped virus containing SARS-CoV-2 spike with individual mutation (R454G, Y449F, R403G, N439I, or N440I) was determined to have very low infectivity compared with the pseudotyped virus containing the wildtype (WT) spike from reference strain Wuhan 1, respectively. Furthermore, we showed the key amino acids had the potential to drug screening. For example, molecular docking (Docking) and infection assay showed that Cephalosporin derivatives can bind with the key amino acids to efficiently block infection of the pseudoviruses with wild type spike or new variants. Moreover, Cefixime inhibited live SARS-CoV-2 infection. These results also provide a novel model for drug screening and support further clinical evaluation and development of Cephalosporin derivatives as novel, safe, and cost-effective drugs for prevention/treatment of SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2 , Aminoácidos/metabolismo , Aminoácidos Essenciais/metabolismo , Antivirais/química , Antivirais/farmacologia , Sítios de Ligação , Cefixima , Humanos , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química
17.
Microbiol Spectr ; 10(5): e0233522, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36000906

RESUMO

Treatment regimens for gonorrhea have limited efficacy worldwide due to the rapid spread of antimicrobial resistance. Cefixime (CFM) is currently not recommended as a first-line treatment for gonorrhea due to the increasing number of resistant strains worldwide. Nonetheless, Neisseria gonorrhoeae strains can be eradicated by CFM at a 400 mg/day dose, provided that the strains are CFM responsive (MIC ≤ 0.064 mg/L). To develop a nonculture test for predicting the CFM responsiveness of N. gonorrhoeae strains, we developed an assay to detect N. gonorrhoeae nonmosaic penA using loop-mediated isothermal amplification (LAMP). To avoid false-positive reactions with commensal Neisseria spp. penA, we amplified specific regions of the N. gonorrhoeae penA (NG-penA-LAMP1) and also the nonmosaic N. gonorrhoeae penA (NG-penA-LAMP3). This assay was validated using isolated N. gonorrhoeae (n = 204) and Neisseria spp. (n = 95) strains. Clinical specimens (n = 95) with confirmed positivity in both culture and real-time PCR were evaluated to validate the system. The combination of the previously described NG-penA-LAMP1 and our new NG-penA-LAMP3 assays had high sensitivity (100%) and specificity (100%) for identifying N. gonorrhoeae carrying the nonmosaic type. To determine whether CFM could be applicable for gonorrhea treatment without culture testing, we developed a LAMP assay that targets penA allele-specific nonmosaic types for use as one of the tools for point-of-care testing of antimicrobial resistance. IMPORTANCE Neisseria gonorrhoeae is among the hot topics of "resistance guided therapy," one of the top 5 urgent antimicrobial threats according to the Centers for Disease Control and Prevention (CDC). There is a need either to develop new agents or to make effective use of existing agents, with the current limited number of therapeutic agents available. Knowing the drug susceptibility information of the target microorganism prior to treating patients is very useful in selecting an effective antibiotic, especially in gonococcal infections where drug resistance is prominent, and is also important in preventing treatment failure. In this study, we developed a new method for obtaining drug susceptibility profiles of Neisseria gonorrhoeae using the loop-mediated isothermal amplification (LAMP) method. The LAMP assay does not require expensive devices. Therefore, this method is expected to be a tool for point-of-care testing of antimicrobial resistance for individualized treatment in the future.


Assuntos
Anti-Infecciosos , Gonorreia , Humanos , Neisseria gonorrhoeae/genética , Cefixima/farmacologia , Cefixima/uso terapêutico , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana , Ceftriaxona/uso terapêutico
18.
Front Cell Infect Microbiol ; 12: 924764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967879

RESUMO

The emergence of Neisseria gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESCs) is a worldwide concern because this class of antibiotics represents the last empirical treatment option for gonorrhea. The abusive use of antimicrobials may be an essential factor for the emergence of ESC resistance in N. gonorrhoeae. Cephalosporin resistance mechanisms have not been fully clarified. In this study, we mapped mutations in the genome of N. gonorrhoeae isolates after resistance induction with cefixime and explored related metabolic pathways. Six clinical isolates with different antimicrobial susceptibility profiles and genotypes and two gonococcal reference strains (WHO F and WHO Y) were induced with increasing concentrations of cefixime. Antimicrobial susceptibility testing was performed against six antimicrobial agents before and after induction. Clinical isolates were whole-genome sequenced before and after induction, whereas reference strains were sequenced after induction only. Cefixime resistance induction was completed after 138 subcultures. Several metabolic pathways were affected by resistance induction. Five isolates showed SNPs in PBP2. The isolates M111 and M128 (ST1407 with mosaic penA-34.001) acquired one and four novel missense mutations in PBP2, respectively. These isolates exhibited the highest minimum inhibitory concentration (MIC) for cefixime among all clinical isolates. Mutations in genes contributing to ESC resistance and in other genes were also observed. Interestingly, M107 and M110 (ST338) showed no mutations in key determinants of ESC resistance despite having a 127-fold increase in the MIC of cefixime. These findings point to the existence of different mechanisms of acquisition of ESC resistance induced by cefixime exposure. Furthermore, the results reinforce the importance of the gonococcal antimicrobial resistance surveillance program in Brazil, given the changes in treatment protocols made in 2017 and the nationwide prevalence of sequence types that can develop resistance to ESC.


Assuntos
Resistência às Cefalosporinas , Gonorreia , Neisseria gonorrhoeae , Cefixima/farmacologia , Cefixima/uso terapêutico , Resistência às Cefalosporinas/genética , Gonorreia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/genética
19.
J Biomed Nanotechnol ; 18(4): 1215-1226, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35854445

RESUMO

Cefixime; widely employed cephalosporin antibiotic is unfortunately coupled to poor water solubility with resultant low oral bioavailability issues. To solve this problem micro-emulsion technique was used to fabricate binary SLNs using blend of solid and liquid lipids, surfactant as well as co-surfactant. The optimized nano suspension was characterized followed by modification to solidified dosage form. During characterization, optimized nano-suspension (CFX-4) produced particle size 189±2.1 nm with PDI 0.310±0.02 as well as -33.9±2 mV zeta potential. Scanning electron microscopy (SEM) presented nearly identical and spherical shaped particles. Differential scanning calorimetry and X-ray powder diffraction analysis ascertained decrease in drug's crystallinity. In-vitro release of drug pursued zero-order characteristics and demonstrated non-fickian pattern of diffusion. The freeze dried nano suspension (CFX-4) was transformed to capsule dosage form to perform comparison based In-Vivo studies. In-Vivo evaluation corresponded to 2.20-fold and 2.11-fold enhancement in relative bioavailability of CFX nano-formulation (CFX-4) as well as the prepared capsules respectively in contrast to the commercialized product (Cefiget®). In general; the obtained results substantiated superior oral bioavailability along with sustained pattern of drug release for CFX loaded binary nano particles. Thus, binary SLNs could be employed as a resourceful drug carrier for oral CFX delivery.


Assuntos
Lipídeos , Nanopartículas , Administração Oral , Animais , Disponibilidade Biológica , Cefixima , Portadores de Fármacos/química , Lipídeos/química , Lipossomos , Nanopartículas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Solubilidade , Tensoativos/química
20.
BMC Infect Dis ; 22(1): 607, 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810277

RESUMO

OBJECTIVES: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the commonest bacterial causes of sexually transmitted infections in humans with high incidence of co-infection. Treatment with high doses of ceftriaxone (CRO) and cefixime (CFM) is strongly recommended due to the reduced drug susceptibility of NG. However, their safety and efficacy have not been confirmed. We compared the safety and efficacy of a single 1 g intravenous (IV) dose of ceftriaxone (CRO) plus doxycycline (DOX) versus a single 800 mg oral dose of cefixime (CFM) plus DOX for the treatment of NG-CT co-infection. METHODS: An open-label randomized controlled trial was conducted on 125 individuals aged > 18 years with untreated gonorrhea and chlamydia to compare a single 1 g intravenous dose of CRO + DOX and a single 800 mg oral dose of CFM + DOX. The primary outcome was the clearance of NG from all the initially infected sites. Secondary outcomes included symptom resolution, changes in the serum clearance levels, glomerular filtration rate, and antibiotic minimum inhibitory concentrations. RESULTS: Both regimens were highly effective in treating gonorrhea with success rates of 96.7% (95% confidence interval [CI] 88.8-99.1%) for CRO and 95.3% (95% CI 87.1-98.4%) for CFM. However, CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection (odds ratio 4.41, 95% CI 1.11-25.7). The safety profiles of the two regimens were similar. CONCLUSIONS: CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection. CFM + DOX may be indicated in patients with CRO allergy and in settings where CRO is unavailable. Trial registration ClinicalTrials.gov (NCT05216744) on 31/01/22.


Assuntos
Infecções por Chlamydia , Coinfecção , Gonorreia , Antibacterianos/farmacologia , Cefixima/farmacologia , Cefixima/uso terapêutico , Ceftriaxona/farmacologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Coinfecção/tratamento farmacológico , Doxiciclina/uso terapêutico , Gonorreia/epidemiologia , Humanos , Neisseria gonorrhoeae
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