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1.
BMC Infect Dis ; 21(1): 183, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596848

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients' treatment outcome individually and minimize resistance amplification. METHODS: TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36-44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24-32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36-44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total). DISCUSSION: Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It's foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs. TRAIL REGISTRATION: ClinicalTrial.gov, NCT03867136 . Registered on March 7, 2019.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Antituberculosos/efeitos adversos , Protocolos Clínicos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Sequenciamento Completo do Genoma , Adulto Jovem
2.
J Environ Sci (China) ; 102: 170-184, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33637242

RESUMO

Seven popular fluoroquinolone antibiotics (FQs) in synthetic marine aquaculture water were subject to sodium hypochlorite (NaClO) disinfection scenario to investigate their reaction kinetics and transformation during chlorination. Reactivity of each FQ to NaClO was following the order of ofloxacin (OFL) > enrofloxacin (ENR) > lomefloxacin (LOM) > ciprofloxacin (CIP) ~ norfloxacin (NOR) >> pipemedic acid (PIP), while flumequine did not exhibit reactivity. The coexisting chlorine ions and sulfate ions in the water slightly facilitated the oxidation of FQs by NaClO, while humic acid was inhibitable to their degradation. The bromide ions promoted degradation of CIP and LOM, but restrained oxidation of OFL and ENR. By analysis of liquid chromatography with tandem mass spectrometry (LC-MS/MS), eight kinds of emerging brominated disinfection byproducts (Br-DBPs) caused by FQS were primarily identified in the chlorinated synthetic marine culture water. Through density functional theory calculation, the highest-occupied molecular orbital (HOMO) and the lowest-unoccupied molecular orbital (LUMO) characteristic as well as the charge distribution of the FQs were obtained to clarify transformation mechanisms. Their formation involved decarboxylation, ring-opening/closure, dealkylation and halogenation. Chlorine substitution occurred on the ortho-position of FQs's N4 and bromine substitution occurred on C8 position. The piperazine ring containing tertiary amine was comparatively stable, while this moiety with a secondary amine structure would break down during chlorination. Additionally, logKow and logBAF of transformation products were calculated by EPI-SuiteTM to analyze their bioaccumulation. The values indicated that Br-DBPs are easier to accumulate in the aquatic organism relative to their chloro-analogues and parent compounds.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Antibacterianos , Brometos , Cromatografia Líquida , Desinfecção , Fluoroquinolonas , Halogenação , Cinética , Hipoclorito de Sódio , Espectrometria de Massas em Tandem , Água , Poluentes Químicos da Água/análise
3.
Toxicol Lett ; 342: 73-84, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609687

RESUMO

Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress.


Assuntos
Autofagia/efeitos dos fármacos , Fluoroquinolonas/toxicidade , Hepatócitos/efeitos dos fármacos , Naftiridinas/toxicidade , Fator de Necrose Tumoral alfa/farmacologia , Antimaláricos/toxicidade , Sobrevivência Celular , Cloroquina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Levofloxacino/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Piperazinas/toxicidade , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Inibidores da Recaptação de Serotonina e Norepinefrina/toxicidade , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Triazóis/toxicidade
4.
BMC Infect Dis ; 21(1): 159, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557769

RESUMO

BACKGROUND: Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes. METHODS: We conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs. RESULTS: Among 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI. CONCLUSIONS: TR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carbapenêmicos/uso terapêutico , Doença Crônica , Combinação de Medicamentos , Fluoroquinolonas/uso terapêutico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sulfadoxina/uso terapêutico , Trimetoprima/uso terapêutico , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/patologia
5.
Sci Total Environ ; 771: 144787, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548726

RESUMO

Ciprofloxacin (CIP), a widely used fluoroquinolone antibiotic, is frequently detected in aqueous environments, and could be assimilated by vegetable plants to possess potential threats to human and animal health through food chains. However, plant uptake of CIP in different chemical speciation has still far from clear now. Thus, the toxicity and uptake of CIP by rice plants were investigated under different solution pH, owing to its contribution to different chemical speciation of CIP. Results display that high pH-driven changes of CIP from cation (CIP+) to anion (CIP-) decreased its adsorption and uptake by excised roots and intact plants, respectively. However, CIP concentrations in roots, stems and leaves all exhibited no significant differences with increasing solution pH. Moreover, six intermediates of CIP were detected and two possible transformation pathways were proposed in rice plants, including firstly oxidation and following consecutive cleavage of piperazine ring. After accumulated in plant tissues, CIP significantly inhibited the plant growth, decreased the photosynthetic pigments contents and enhanced the antioxidant enzyme activities in a concentration-dependent manner. Besides, high pH exacerbated the growth inhibition and changed the oxidative damage responses of rice plants to CIP. These findings indicate that the uptake and toxicity of CIP in rice plants were influenced by solution pH-driven changes of its chemical speciation.


Assuntos
Ciprofloxacino , Oryza , Adsorção , Ciprofloxacino/toxicidade , Fluoroquinolonas , Humanos , Água
6.
Ann Intern Med ; 174(2): JC22, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524287

RESUMO

SOURCE CITATION: Dong YH, Chang CH, Wang JL, et al. Association of infections and use of fluoroquinolones with the risk of aortic aneurysm or aortic dissection. JAMA Intern Med. 2020;180:1587-95. 32897358.


Assuntos
Aneurisma Dissecante , Aneurisma Aórtico , Amoxicilina , Ampicilina , Aneurisma Dissecante/induzido quimicamente , Aneurisma Aórtico/induzido quimicamente , Ácido Clavulânico , Dissecação , Fluoroquinolonas/efeitos adversos , Humanos , Sulbactam
7.
Chemosphere ; 271: 129529, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33434822

RESUMO

Norfloxacin, a fluoroquinolone antibiotic, is widely used to treat microbial infections. However, untreated norfloxacin-containing wastewater poses serious threats to the ecosystem and human health. The treatment of waste expanded polystyrene (EPS) by landfilling or incineration could cause environmental problems. In this research, the feasibility of converting EPS into a valuable adsorbent for norfloxacin was evaluated. Results showed that EPS treated with H2SO4 (EPSH2SO4) effectively adsorbed norfloxacin. The optimal sulfonation conditions were 95% H2SO4 and 100 °C. Addition of 0.001 M of persulfate during sulfonation obviously shortened the sulfonation time to 7.5 min, and the adsorption ability of modified EPS increased with increasing persulfate dose. Under the experimental conditions of 25 mg L-1 norfloxacin, pH0 6.2, and 0.4 g L-1 EPSH2SO4+persulfate (dry weight), 97.2% of norfloxacin could be removed after 30 min of adsorption. The adsorption ability of EPSH2SO4+persulfate decreased with increasing solution pH0, and the optimal pH0 was 6.2. The Langmuir isotherm best described the adsorption behavior of EPSH2SO4+persulfate (qmax = 140.9 mg L-1, b = 1.97 L mg-1, R2 = 0.9992). 1 M HCl effectively regenerated the exhausted EPSH2SO4+persulfate at the optimal solid/solution ratio of 8 g L-1. EPSH2SO4+persulfate maintained excellent adsorption capacity (>80.9%) after eight adsorption-regeneration cycles.


Assuntos
Poliestirenos , Poluentes Químicos da Água , Adsorção , Antibacterianos , Ecossistema , Fluoroquinolonas , Humanos , Concentração de Íons de Hidrogênio , Cinética , Águas Residuárias , Poluentes Químicos da Água/análise
8.
Int J Food Microbiol ; 340: 109054, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33465549

RESUMO

Foodborne exposure to antimicrobial-resistant bacteria is a growing global health concern. Escherichia coli (E. coli) is well recognised as an indicator of food contamination with faecal materials. In the present study, we investigated the occurrence of E. coli in table eggs sold at retail supermarkets in Western Australia (WA). A total of 2172 visually clean and intact retail eggs were purchased between October 2017 and June 2018. A single carton containing a dozen eggs was considered as a single sample resulting a total of 181 samples. The shells and contents of each sample were separately pooled and tested using standard culture-based methods. Overall, generic E. coli was detected in 36 (19.8%; 95% confidence interval: 14.3; 26.4) of the 181 tested retail egg samples. We characterised 100 of the recovered E. coli isolates for their phenotypic antimicrobial resistance using minimum inhibitory concentration (MIC). A subset of E. coli isolates (n = 14) were selected on the basis of their MIC patterns, and were further characterised using whole genome sequencing (WGS). Fifty-seven (57%) of the recovered generic E. coli isolates (n = 100) were resistant to at least one of the 14 antimicrobials included in the MIC testing panel, of which 22 isolates (22%) showed multi-class resistance. The highest frequencies of non-susceptibility of E. coli isolated from WA retailed eggs were against tetracycline (49%) and ampicillin (36%). WGS revealed that tet(A) and blaTEM-1B genes were present in most of the isolates exhibiting phenotypic resistance to tetracycline and ampicillin, respectively. The majority (98%) of the characterised E. coli isolates were susceptible to ciprofloxacin and azithromycin, and none were resistant to the cephalosporin antimicrobials included in the MIC panel. Two isolates demonstrated reduced susceptibility to ciprofloxacin, with MICs of 0.125 and 0.25 mg/L, and WGS revealed the presence of plasmid mediated qnrs1 gene in both isolates. This is the first report on detection of non-wild-type resistance to fluoroquinolones in supermarket eggs in Australia; one of the two isolates was from a cage-laid eggs sample while the other was from a barn-laid retail eggs sample. Fluoroquinolones have never been permitted for use in poultry farms in Australia. Thus, the detection of low-level ciprofloxacin-resistant E. coli in the absence of local antimicrobial selection pressure at the Australian layer farms warrants further research on the potential role of the environment or human-related factors in the transmission of antimicrobial resistance. The results of this study add to the local and global understanding of antimicrobial resistance spread in foods of animal origin.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Ovos/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Genoma Bacteriano , Animais , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Fluoroquinolonas/farmacologia , Microbiologia de Alimentos , Humanos , Testes de Sensibilidade Microbiana , Resistência a Tetraciclina , Austrália Ocidental
9.
ACS Appl Mater Interfaces ; 13(4): 5357-5367, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471500

RESUMO

Herein, the hydrophobic carboxyl-functionalized ionic liquid (IL-COOH) was encapsulated into the prepared Fe3O4@Zr-MOFs, and the novel water-stable IL-COOH/Fe3O4@Zr-MOF nanocomposites were first synthesized. The polydopamine-functionalized Fe3O4 was introduced to construct the core-shell structure via layer-by-layer modification, and the controlled growth of Zr-MOFs was achieved, which realized the adjustment of charged properties of nanocomposites and simplified the adsorption or extraction process. The IL-COOH/Fe3O4@Zr-MOFs were fully studied by IR, HNMR, XRD, N2 adsorption-desorption isotherms, TEM, EDS mapping, VSM, and so on. Then, they were employed for the selective adsorption and detection of fluoroquinolone antibiotics (FQs). The adsorption isotherms and kinetics demonstrated that the adsorption process followed a pseudo-second-order kinetic model and the Langmuir isotherm model. Among them, IL-COOH/Fe3O4@UiO-67-bpydc showed the best adsorption performance, and the maximum adsorption capacity of ofloxacin was 438.5 mg g-1. Coupled magnetic solid-phase extraction with HPLC-DAD, a convenient, sensitive, and efficient method for extraction and detection of FQs in environmental water, was developed based on IL-COOH/Fe3O4@UiO-67-bpydc. The recoveries of environmental water were ranging from 90.0 to 110.0%, and the detection limits were lower than 0.02 µg L-1. The novel functionalized composites served as solid-phase adsorbents and liquid-phase extractants. This study also provided a promising strategy for designing and preparing multi-functionalized nanocomposites for the removal or detection of pollutants in environmental samples.


Assuntos
Antibacterianos/análise , Fluoroquinolonas/análise , Líquidos Iônicos/química , Estruturas Metalorgânicas/química , Nanocompostos/química , Poluentes Químicos da Água/análise , Adsorção , Antibacterianos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Fluoroquinolonas/isolamento & purificação , Limite de Detecção , Nanopartículas de Magnetita/química , Extração em Fase Sólida/métodos , Água/análise , Poluentes Químicos da Água/isolamento & purificação
11.
Ecotoxicol Environ Saf ; 212: 111973, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33516099

RESUMO

This study developed a comprehensive characterization method for the combined degradation effect of modified fluoroquinolones (FQs) photodegradation and microbial degradation. A combination of revised 3D-QSAR model, molecular docking, path simulation inference, pharmacokinetics, molecular dynamics (MD) simulation and toxicokinetics simulation was used to construct a systematic environment-friendly drug screening system. Five derivatives were screened with significantly improved combined degradation effect (over 20%) and functional characteristics and human health parameters through combined model verification, functional and human health risk assessment. The simulation path of photo- and microbial-degradation of gatifloxacin and new gatifloxacin molecules was derived, and the reaction energy barrier was also calculated. The ratio of the total rate-determining steps change rate of the decreased energy barrier (14.10%:26.30%) was consistent with the ratio of the increased degradation performance predicted by the model (22.87%:19.77%), demonstrating the reliability of revised 3D-QSAR model and it could be applied in molecular modification. MD and toxicokinetics simulation were used to predict the binding energy and aquatic toxicity between photo- and microbial-degradation products and the degradation enzymes, which further to screen the degradation pathways with low potential environmental risks. The findings will be helpful to screen environment-friendly drug and develop appropriate strategies for its risk management.


Assuntos
Biodegradação Ambiental , Fluoroquinolonas/metabolismo , Relação Quantitativa Estrutura-Atividade , Fluoroquinolonas/química , Fluoroquinolonas/toxicidade , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fotólise , Reprodutibilidade dos Testes
12.
Chemosphere ; 270: 129481, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33423001

RESUMO

Fluoroquinolone antibiotics are frequently detected in the environment causing potential hazards to ecological and human health. Inadequate removal efficiencies were reported for fluoroquinolones during conventional wastewater treatment processes whereas the application of photo-Fenton reactions has attracted much attention due to their high reaction rate. This article summarizes the recent proceedings on homogeneous and heterogeneous photo-Fenton degradation of fluoroquinolones. Degradation efficiencies of fluoroquinolones were discussed as well as rate constants for a distinct comparison. The influences of initial fluoroquinolone concentration, H2O2, Fe2+, pH and temperature were also investigated on homogeneous photo-Fenton degradation of fluoroquinolones. The currently applied heterogenous catalysts were considered including iron oxides catalysts, iron-based composite catalysts and iron-based semiconductor. In addition, the degradation pathways for typical fluoroquinolones were proposed with the products identified in the literature. The results indicated the better performance with the aid of heterogeneous catalysts due to the generation of more active species. Intermediate products at smaller molecular weight were obtained through various types of pathways under heterogeneous photo-Fenton degradation of fluoroquinolones, implying a practical application with biological treatment processes for fully mineralization.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Catálise , Fluoroquinolonas , Humanos , Peróxido de Hidrogênio , Ferro , Oxirredução , Poluentes Químicos da Água/análise
13.
J Environ Sci (China) ; 99: 110-118, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33183688

RESUMO

Over the recent past, fluoroquinolone antibiotics (FQs) have raised extensive attention due to their potential to induce the formation of resistance genes and "superbugs", thus various advanced oxidation techniques have been developed to eliminate their release into the environment. In the present study, the prototype tetraamido macrocyclic ligand (FeIII-TAML)/hydrogen peroxide (H2O2) system is employed to degrade FQs (i.e., norfloxacin and ciprofloxacin) over a wide pH range (i.e., pH 6-10), and the reaction rate increases with the increase in pH level. The effect of dosage of FeIII-TAML and H2O2 on the degradation of FQs is evaluated, and the reaction rate is linearly correlated with the added amount of chemicals. Moreover, the impact of natural organic matters (NOM) on the removal of FQs is investigated, and the degradation kinetics show that both NOM type and experimental concentration exhibit negligible influence on the oxidative degradation of selected antibiotics. Based on the results of liquid chromatography-high resolution mass spectrometry and theoretical calculations, the reaction sites and pathways of FQs by FeIII-TAML/H2O2 system are further predicted and elucidated.


Assuntos
Peróxido de Hidrogênio , Poluentes Químicos da Água , Antibacterianos , Compostos Férricos , Fluoroquinolonas , Oxirredução
14.
Ecotoxicol Environ Saf ; 207: 111305, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32942101

RESUMO

Poultry litter is one of the main sources of fluoroquinolones (FQs) in agricultural soils. In this study, our main goal was to investigate FQ-contaminated poultry litter effects on Eisenia andrei earthworms. To achieve this, acute and chronic tests covered several endpoints, such as avoidance, biomass, lethality, reproduction and changes to immune cells. FQs (enrofloxacin and ciprofloxacin) were determined in a poultry litter sample through high performance liquid chromatography with a fluorescence detector. The avoidance test indicates that poultry litter strongly repels earthworms, even at the lowest concentration (50 g kg-1). In the acute test, the lethal concentration of poultry litter to 50% of the earthworms (LC50), was estimated at 28.5 g kg-1 and a significant biomass loss (p < 0.05) occurred at 40 g kg-1. In the chronic test, a significant reproduction effect was observed at 20 g kg-1. Cell typing, density and feasibility indicated significant effects ranging from 5 to 20 g kg-1. A high risk quotient was estimated based on recommended poultry litter applications in field studies. Although FQ contamination in poultry litter and soils has been widely reported in previous studies, this is, to the best of our knowledge, the first toxicological assessment concerning earthworms exposed to FQ-contaminated poultry litter.


Assuntos
Fluoroquinolonas/toxicidade , Oligoquetos/efeitos dos fármacos , Aves Domésticas , Poluentes do Solo/toxicidade , Solo/química , Resíduos Sólidos/análise , Agricultura , Animais , Biomassa , Fluoroquinolonas/análise , Dose Letal Mediana , Oligoquetos/crescimento & desenvolvimento , Reprodução/efeitos da radiação , Poluentes do Solo/análise , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
15.
Food Chem ; 339: 128079, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152872

RESUMO

In this work, an efficient method for the determination of ß-agonists and fluoroquinolones was established, based on a mixed-mode sorbent of magnetic sulfonated covalent organic framework composites. By coupling with HPLC-MS/MS, the main factors that affect the extraction procedure were optimized. Under the optimal conditions, the proposed HPLC-MS/MS method was successfully utilized for the extraction of ß-agonists and fluoroquinolones in milk and pork meat samples. The method showed good linearities (R2 ≥ 0.9916), and low LOQs of 0.1-0.2 ng g-1 for ß-agonists and fluoroquinolones. The adsorption mechanism was investigated with the assistance of quantum chemistry calculation method, and it is worth noting that the sorbent relied mainly on the multiple adsorption mechanisms, including π-π stacking, hydrophobic, electrostatic attraction and hydrogen-bonding interactions. This work not only provides a simple method for the preparation of a mixed-mode sorbent, but also a routine analysis strategy for monitoring the illegal use of ß-agonists and fluoroquinolones.


Assuntos
Agonistas Adrenérgicos beta/análise , Fluoroquinolonas/análise , Análise de Alimentos/métodos , Imãs/química , Estruturas Metalorgânicas/síntese química , Extração em Fase Sólida/métodos , Ácidos Sulfônicos/química , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Adsorção , Animais , Técnicas de Química Sintética , Fluoroquinolonas/química , Fluoroquinolonas/isolamento & purificação , Contaminação de Alimentos/análise , Carne/análise , Estruturas Metalorgânicas/química , Leite/química , Suínos , Fatores de Tempo
16.
Sci Total Environ ; 758: 143954, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33333305

RESUMO

Protein carbonylation is an irreversible oxidative modification that has been associated with a decrease in the quality and nutritional value of products of animal origin. Generally, the carbonylation is attributed to processes of slaughter, processing, and cold storage of products. However, in vitro studies have shown that fluoroquinolone and organophosphate pesticides residues at their maximum residue limits (MRL) can promote carbonylation of animal proteins. Though, this effect on in vivo conditions has not yet been evaluated. Thus, Eisenia fetida was chosen as a model to assay their oxidant effect. For this, adult earthworms were exposed to artificial soil contaminated with ciprofloxacin, danofloxacin, fenthion, and diazinon at three concentrations (0.5, 1.0, and 1.5 MRL) for 28 days. Then, these were purged and sacrificed to obtain the muscle region between the anus and preclitellum. The muscle samples were cold macerated to obtain muscle proteins, which were used for protein quantification, determination of carbonyl levels, and carbonyl protein profiles employing Bradford, Dot-blot, and Western blot assays, respectively. The results showed that at each concentration assayed, all pollutants induced significant carbonylation respect to control (p < 0.05). Additionally, mass spectrometry-based analysis (MALDI-TOF/TOF) identified actin as the protein most susceptible to carbonylation promoted by these substances. Therefore, these findings show for the first time the oxidant power of fluoroquinolones and organophosphates pesticides at MRLs concentrations on muscle proteins under in vivo conditions. Fact causes concern due to the homology of muscle proteins in eukaryotes, which allow to hypothesize that this effect could also be experienced by proteins from food-producing animals in the same way that observed in in vitro studies.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Antibacterianos/toxicidade , Fluoroquinolonas , Proteínas Musculares , Solo , Poluentes do Solo/toxicidade
17.
Viruses ; 13(1)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374514

RESUMO

Repurposing FDA-approved drugs that treat respiratory infections caused by coronaviruses, such as SARS-CoV-2 and MERS-CoV, could quickly provide much needed antiviral therapies. In the current study, the potency and cellular toxicity of four fluoroquinolones (enoxacin, ciprofloxacin, levofloxacin, and moxifloxacin) were assessed in Vero cells and A549 cells engineered to overexpress ACE2, the SARS-CoV-2 entry receptor. All four fluoroquinolones suppressed SARS-CoV-2 replication at high micromolar concentrations in both cell types, with enoxacin demonstrating the lowest effective concentration 50 value (EC50) of 126.4 µM in Vero cells. Enoxacin also suppressed the replication of MERS-CoV-2 in Vero cells at high micromolar concentrations. Cellular toxicity of levofloxacin was not found in either cell type. In Vero cells, minimal toxicity was observed following treatment with ≥37.5 µM enoxacin and 600 µM ciprofloxacin. Toxicity in both cell types was detected after moxifloxacin treatment of ≥300 µM. In summary, these results suggest that the ability of fluoroquinolones to suppress SARS-CoV-2 and MERS-CoV replication in cultured cells is limited.


Assuntos
Antibacterianos/farmacologia , Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Fluoroquinolonas/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , /efeitos dos fármacos , Células A549 , Animais , Linhagem Celular , Chlorocebus aethiops , Ciprofloxacino/farmacologia , Enoxacino/farmacologia , Humanos , Levofloxacino/farmacologia , Moxifloxacina/farmacologia , Células Vero
18.
BMC Infect Dis ; 20(1): 950, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308173

RESUMO

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/uso terapêutico , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/genética , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , China/epidemiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/isolamento & purificação , Prevalência , RNA Ribossômico 23S/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia
19.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352719

RESUMO

Phototoxicity of fluoroquinolones is connected with oxidative stress induction. Lomefloxacin (8-halogenated derivative) is considered the most phototoxic fluoroquinolone and moxifloxacin (8-methoxy derivative) the least. Melanin pigment may protect cells from oxidative damage. On the other hand, fluoroquinolone-melanin binding may lead to accumulation of drugs and increase their toxicity to skin. The study aimed to examine the antioxidant defense system status in normal melanocytes treated with lomefloxacin and moxifloxacin and exposed to UV-A radiation. The obtained results demonstrated that UV-A radiation enhanced only the lomefloxacin-induced cytotoxic effect in tested cells. It was found that fluoroquinolones alone and with UV-A radiation decreased superoxide dismutase (SOD) activity and SOD1 expression. UV-A radiation enhanced the impact of moxifloxacin on hydrogen peroxide-scavenging enzymes. In turn, lomefloxacin alone increased the activity and the expression of catalase (CAT) and glutathione peroxidase (GPx), whereas UV-A radiation significantly modified the effects of drugs on these enzymes. Taken together, both analyzed fluoroquinolones induced oxidative stress in melanocytes, however, the molecular and biochemical studies indicated the miscellaneous mechanisms for the tested drugs. The variability in phototoxic potential between lomefloxacin and moxifloxacin may result from different effects on the antioxidant enzymes.


Assuntos
Antioxidantes/metabolismo , Fluoroquinolonas/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Melanócitos/patologia , Moxifloxacina/farmacologia , Pele/patologia , Raios Ultravioleta/efeitos adversos , Antibacterianos/farmacologia , Antioxidantes/efeitos da radiação , Catalase/metabolismo , Catalase/efeitos da radiação , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/efeitos da radiação , Humanos , Melaninas/metabolismo , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Estresse Oxidativo , Pele/efeitos dos fármacos , Pele/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/efeitos da radiação
20.
BMC Infect Dis ; 20(1): 866, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213390

RESUMO

BACKGROUND: Mycolicibacterium fortuitum is a species of the rapidly growing mycobacteria that can cause pulmonary infection. It is susceptible to multiple antibiotics both in vitro and in clinical practice, so that any combination of susceptible drugs is effective. However, we encountered a case of infection due to fluoroquinolone-resistant M. fortuitum. In this study, we report the case and describe the mechanism of resistance. CASE PRESENTATION: A 65-year-old man with a history of total gastrectomy and immunosuppressant treatment for rheumatoid arthritis developed a recurrence of pulmonary infection caused by M. fortuitum. He was treated with clarithromycin and levofloxacin as a first-line treatment, based on the favorable susceptibility at that time. After recurrence, a high minimum inhibitory concentration to fluoroquinolones was detected. DNA sequencing of the pathogen showed the substitution of serine for tryptophan at residue 83 in the gyrA gene. He was successfully treated with a combination of other antibiotics. CONCLUSION: This is the first report on the treatment of fluoroquinolone-resistant M. fortuitum and investigation of the mechanism of resistance. We suggest that the susceptibility test remains effective for determining the next line of treatment after a pathogen has acquired resistance, and resistance to fluoroquinolones in M. fortuitum can be attributed to a single change of amino acid.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Pneumopatias/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium fortuitum/efeitos dos fármacos , Idoso , Substituição de Aminoácidos , DNA Girase/química , DNA Girase/genética , DNA Girase/metabolismo , Humanos , Pneumopatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium fortuitum/genética , Mycobacterium fortuitum/isolamento & purificação , Recidiva , Análise de Sequência de DNA
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