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1.
BMC Infect Dis ; 21(1): 1037, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615472

RESUMO

BACKGROUND: Timely and accurate identification of uropathogens and determination of their antimicrobial susceptibility is paramount to the management of urinary tract infections (UTIs). The main objective of this study was to develop an assay using LAMP (Loop mediated isothermal amplification) technology for simple, rapid and sensitive detection of the most common bacteria responsible for UTIs, as well as for the detection of the most prevalent genes (encoding cefotaximases from CTX-M group 1) responsible for resistance to 3rd generation of cephalosporins. METHOD: We designed primers targeting Proteus mirabilis, while those targeting Escherichia coli, Klebsiella pneumoniae and Enterococcus faecalis and the CTX-M group 1 resistance gene were benchmarked from previous studies. The amplification reaction was carried out in a warm water bath for 60 min at 63 ± 0.5 °C. The amplicons were revealed by staining with Sybr Green I. Specificity and sensitivity were determined using reference DNA extracts spiked in sterile urine samples. The analytical performance of the assays was evaluated directly on pellets of urine samples from patients suspected of UTI and compared with culture. RESULTS: We found a high specificity (100%) for LAMP assays targeting the selected bacteria (P. mirabilis, E. coli, K. pneumoniae, E. faecalis) and the CTX-M group 1 when using DNA extracts spiked in urine samples. The sensitivities of the assays were around 1.5 103 Colony Forming Units (CFU) /mL corresponding to the cut-off value used to define bacteriuria or UTIs in patients with symptoms. Out of 161 urine samples tested, using culture as gold standard, we found a sensitivity of the LAMP techniques ranging from 96 to 100% and specificity from 95 to 100%. CONCLUSION: We showed that the LAMP assays were simple and fast. The tests showed high sensitivity and specificity using a simple procedure for DNA extraction. In addition, the assays could be performed without the need of an expensive device such as a thermal cycler. These LAMP assays could be useful as an alternative or a complementary tool to culture reducing the time to diagnosis and guiding for more effective treatment of UTIs but also as a powerful diagnostic tool in resource-limited countries where culture is not available in primary health care structures.


Assuntos
Cefalosporinas , Escherichia coli , Escherichia coli/genética , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico
2.
Nursing ; 51(10): 18-29, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34580258
3.
J Pharm Biomed Anal ; 206: 114378, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592571

RESUMO

Ceftiofur (CEF) residues in animal-derived foods are of great concern to farmers, regulatory agencies and consumers. In this study, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) method was established to quickly monitor CEF residues in edible animal tissues using an easy sample preparation procedure. A monoclonal antibody, 4D5, against CEF has been produced at first, which had IC50 values for CEF, ceftriaxone, cefquinome, cefotaxime and desfuroylceftiofur of 0.78 µg/L, 0.73 µg/L, 13.6 µg/L, 8.99 µg/L and 8.89 µg/L, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) in artificially contaminated animal-derived foods were 0.12-0.19 µg/L and 0.20-0.30 µg/L. The recovery rates were in the range of 89.7-109.0%. The CVs were less than 6.7%. A good correlation (R= 0.9994) between the ic-ELISA and UPLC-MS/MS showed the reliability of the developed ic-ELISA. The ic-ELISA produces a sensitive, accurate and low-cost tool for the screening of residues of CEF in animal-derived foods.


Assuntos
Anticorpos Monoclonais , Espectrometria de Massas em Tandem , Animais , Cefalosporinas , Cromatografia Líquida , Ensaio de Imunoadsorção Enzimática , Reprodutibilidade dos Testes
4.
J Pharm Biomed Anal ; 206: 114358, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34534866

RESUMO

The chromatographic and lipophilicity characters of seven cephalosporins of different four classes (cephradine, cefaclor, cefprozil, cefixime, cefotaxime, ceftazidime and cefepime) were examined by salting out thin-layer chromatography (SOTLC). SOTLC using ammonium sulfate salt was employed to predict the lipophilicity of the proposed drugs via their retention behavior. The calculated RM0 values showed liner relationship with the molar concentration of ammonium sulfate in mobile phase in the range of 0.5-2.5 mol/L. Additionally, quantitative structure retention relationship (QSRR) was generated to figure out the relationship between the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins. Good correlations were found between the chromatographically obtained retention parameters (RM0 and C0) and some molecular descriptors of the examined drugs. Furthermore, an efficient QSAR model was carried out using the calculated chromatographic parameters (RM0 and C0) and log P of the studied cephalosporins to predict minimum inhibitory concentration (MIC) and blood brain barrier (BBB) penetration of the examined drugs. The study was extended to separate and quantify the selected antibiotics in their pure forms and pharmaceutical formulations. Normal phase thin layer chromatographic (NP-TLC) method using a usable developing system of acetone: methanol: water: ammonium hydroxide: glacial acetic acid (90: 10: 18: 3: 2, by volume) was successfully applied to resolve the studied cephalosporins. Linearity was achieved in the range of 0.2-3 µg/mL for most of the studied antibiotics. The developed SOTLC method can be considered as a good start alternative to reversed phase thin layer chromatography (RP-TLC) for prediction of the lipophilic properties of examined cephalosporins. Moreover, the proposed NP-TLC densitometric method can be easily applied for quality control analysis of the chosen drugs and other structurally related components.


Assuntos
Cefalosporinas , Cromatografia de Fase Reversa , Cefepima , Cromatografia em Camada Delgada , Testes de Sensibilidade Microbiana
5.
Microb Pathog ; 160: 105201, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547409

RESUMO

The emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains of animal origin that are resistant to several antibiotics is of great concern. Cefquinome is a fourth-generation cephalosporin developed specifically for veterinary use. The mechanism of MRSA resistance to cefquinome is still not established. Therefore, we designed this study to evaluate the effect of cefquinome on the transcriptome of MRSA1679a, a strain that was isolated from a chicken. The transcriptome analysis indicated that multiple efflux pumps (QacA, NorB, Bcr, and ABCb) were upregulated in MRSA1679a as a resistance mechanism to expel cefquinome. Additionally, penicillin-binding protein 1A was overexpressed, which conferred resistance to cefquinome, a ß-lactam antibiotic. Adhesion and the biofilm-forming capacity of the MRSA strain was also enhanced in addition to overexpression of many stress-related genes. Genes related to carbohydrate metabolism, secretion systems, and transport activity were also significantly upregulated in MRSA1679a. In conclusion, global transcription was triggered to overcome the stress induced by cefquinome, and the MRSA1679a showed a great genetic potential to survive in this challenging environment. This study provides a profound understanding of MRSA1679a as a potentially important pathogen and identifies key resistance characteristics of MRSA against cefquinome. Studies should be aimed to demonstrate multidrug resistance mechanisms of virulent strains by exposing to different antibiotic combinations.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , RNA-Seq
6.
Can Vet J ; 62(9): 975-981, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34475583

RESUMO

This study investigated the pharmacokinetics of ceftiofur after intravenous regional limb perfusion (IVRLP). Six horses were involved in 3 IVRLP sessions. For each session, operators with varying clinical experience placed the tourniquet. A wide-rubber tourniquet was applied in the antebrachium as 2 g of ceftiofur in a total volume of 100 mL was injected into the cephalic vein. Plasma and metacarpophalangeal synovial fluid samples were obtained to evaluate perfusate leakage and synovial fluid concentrations of ceftiofur over 24 h. Overall, mean plasma concentrations were not significantly different before and after tourniquet removal. Mean synovial fluid ceftiofur concentrations were significantly higher 5 min and 8 h after tourniquet removal versus 24 h, after which values above the minimum inhibitory concentration (MIC) (1 µg/mL) were not detected. Concentrations above the MIC were detected in 72% and 50% of the horses at 5 min and 8 h, respectively. Overall, higher synovial fluid concentrations were obtained for the operator with the most recent clinical experience performing IVRLP.


Assuntos
Amicacina , Membro Anterior , Animais , Antibacterianos , Cefalosporinas , Cavalos , Articulação Metacarpofalângica , Perfusão/veterinária , Líquido Sinovial
7.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361749

RESUMO

Cefquinome and ceftiofur are ß-lactam antibiotics used for the treatment of bacterial infections in swine. Although these antimicrobials are administered intramuscularly, the exposure of the gut microbiota to these cephalosporins is not well described. This exposure can contribute to the emergence and spread of antimicrobials in the environment and to the possible spread of antimicrobial resistance genes. To assess the impact of drug administration on the intestinal excretion of these antimicrobials it is essential to measure the amounts of native compound and metabolites in feces. Two (ultra)-high-performance liquid chromatography-tandem mass spectrometry ((U)HPLC-MS/MS) methods were developed and validated, one for the determination of cefquinome and ceftiofur and the other for the determination of ceftiofur residues, measured as desfuroylceftiofuracetamide, in porcine feces. The matrix-based calibration curve was linear from 5 ng g-1 to 1000 ng g-1 for cefquinome (correlation coefficient (r) = 0.9990 ± 0.0007; goodness of fit (gof) = 3.70 ± 1.43) and ceftiofur (r = 0.9979 ± 0.0009; gof = 5.51 ± 1.14) and quadratic from 30 ng g-1 to 2000 ng g-1 for desfuroylceftiofuracetamide (r = 0.9960 ± 0.0020; gof = 7.31 ± 1.76). The within-day and between-day precision and accuracy fell within the specified ranges. Since ß-lactam antibiotics are known to be unstable in feces, additional experiments were conducted to adjust the sampling protocol in order to minimize the impact of the matrix constituents on the stability of the analytes. Immediately after sampling, 500 µL of an 8 µg mL-1 tazobactam solution in water was added to 0.5 g feces, to reduce the degradation in matrix.


Assuntos
Acetamidas/isolamento & purificação , Antibacterianos/isolamento & purificação , Cefalosporinas/isolamento & purificação , Cromatografia Líquida de Alta Pressão/normas , Furanos/isolamento & purificação , Espectrometria de Massas em Tandem/normas , Acetamidas/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Calibragem , Cefalosporinas/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Fezes/química , Feminino , Furanos/administração & dosagem , Injeções Intramusculares , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Suínos , Espectrometria de Massas em Tandem/métodos , Tazobactam/química
9.
Crit Care ; 25(1): 290, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380538

RESUMO

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding. METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The primary endpoint was 28-day ACM. The key secondary endpoint was clinical response at test-of-cure. Participants with vHABP were a prospectively defined subgroup, but subgroup analyses were not powered for noninferiority testing. We compared baseline and treatment factors, efficacy, and safety between ceftolozane/tazobactam and meropenem in participants with vHABP. We also conducted a retrospective multivariable logistic regression analysis in this subgroup to determine the impact of treatment arm on mortality when adjusted for significant prognostic factors. RESULTS: Overall, 99 participants in the ceftolozane/tazobactam and 108 in the meropenem arm had vHABP. 28-day ACM was 24.2% and 37.0%, respectively, in the intention-to-treat population (95% confidence interval [CI] for difference: 0.2, 24.8) and 18.2% and 36.6%, respectively, in the microbiologic intention-to-treat population (95% CI 2.5, 32.5). Clinical cure rates in the intention-to-treat population were 50.5% and 44.4%, respectively (95% CI - 7.4, 19.3). Baseline clinical, baseline microbiologic, and treatment factors were comparable between treatment arms. Multivariable regression identified concomitant vasopressor use and baseline bacteremia as significantly impacting ACM in ASPECT-NP; adjusting for these two factors, the odds of dying by day 28 were 2.3-fold greater when participants received meropenem instead of ceftolozane/tazobactam. CONCLUSIONS: There were no underlying differences between treatment arms expected to have biased the observed survival advantage with ceftolozane/tazobactam in the vHABP subgroup. After adjusting for clinically relevant factors found to impact ACM significantly in this trial, the mortality risk in participants with vHABP was over twice as high when treated with meropenem compared with ceftolozane/tazobactam. TRIAL REGISTRATION: clinicaltrials.gov, NCT02070757. Registered 25 February, 2014, clinicaltrials.gov/ct2/show/NCT02070757.


Assuntos
Cefalosporinas/normas , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Meropeném/normas , Tazobactam/normas , Idoso , Antibacterianos/farmacologia , Antibacterianos/normas , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Modelos Logísticos , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Estudos Retrospectivos , Tazobactam/farmacologia , Tazobactam/uso terapêutico
10.
Ecotoxicol Environ Saf ; 222: 112503, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34273851

RESUMO

Cephalosporins are one of the most widely used antibiotics. When cephalosporins are discharged into the environment, they not only induce the production of antibiotic resistant genes (ARGs) and antibiotic resistant bacteria (ARBs) but also cause toxic effects on animals and plants. Due to their complicated environmental behavior and lack of relevant data, the environmental behavior remains unclear. In this study, the adsorption-desorption and degradation characteristics of the third-generation cephalosporin drug ceftiofur (CEF) were investigated in three agricultural soils (sandy loam, loam and clay). According to the relevant parameters of the Freundlich adsorption isotherm (the Kf range was 57.63-122.44 µg1-1/n L1/n kg-1), CEF was adsorbed moderately in the soils and had the potential to migrate into groundwater. CEF exhibited low persistence in the soils and faster degradation than other antibiotics, such as tetracyclines and fluoroquinolones. The degradation half-lives (DT50) of CEF in soils ranged from 0.76 days to 4.31 days. Adding feces, increasing the water content, providing light and increasing the temperature significantly accelerated the degradation of CEF in soils. The DT50 values of CEF in soils were significantly prolonged when the soils were sterilized, indicating that both physical degradation and biodegradation played important roles in the degradation of CEF in soils. The DT50 values of CEF in soils were significantly prolonged at high concentrations, indicating that the degradability of CEF in soils was affected by the initial concentration. No significant differences were observed in the DT50 values for the different soil types (p > 0.05). This study provides useful information about the environmental behavior of CEF and improves the environmental risk assessment of CEF.


Assuntos
Poluentes do Solo , Solo , Adsorção , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Animais , Cefalosporinas , Cinética , Poluentes do Solo/análise
11.
Antimicrob Agents Chemother ; 65(9): e0032621, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228542

RESUMO

Vibrio vulnificus is a pathogen that accounts for one of the highest mortality rates and is responsible for most reported seafood-related illnesses and deaths worldwide. Owing to the threats of pathogens with ß-lactamase activity, it is important to identify and characterize ß-lactamases with clinical significance. In this study, the protein sequence of the metallo-ß-lactamase (MBL) fold metallohydrolase from V. vulnificus (designated Vmh) was analyzed, and its oligomeric state, ß-lactamase activity, and metal binding ability were determined. BLASTp analysis indicated that the V. vulnificus Vmh protein showed no significant sequence identity with any experimentally identified Ambler class B MBLs or enzymes containing the MBL protein fold; it was also predicted to have a signal peptide of 19 amino acids at its N terminus and an MBL protein fold from amino acid residues 23 to 216. Recombinant V. vulnificus Vmh protein was overexpressed and purified. Analytical ultracentrifugation and electrospray ionization-mass spectrometry (MS) data demonstrated its monomeric state in an aqueous solution. Recombinant V. vulnificus Vmh protein showed broad degrading activities against ß-lactam antibiotics, such as penicillins, cephalosporins, and imipenems, with kcat/Km values ranging from 6.23 × 102 to 1.02 × 104 M-1 s-1. The kinetic reactions of this enzyme exhibited sigmoidal behavior, suggesting the possibility of cooperativity. Zinc ions were required for the enzyme activity, which was abolished by adding the metal chelator EDTA. Inductively coupled plasma-MS indicated that this enzyme might bind two zinc ions per molecule as a cofactor.


Assuntos
Vibrio vulnificus , beta-Lactamases , Antibacterianos/farmacologia , Cefalosporinas , Monobactamas , Vibrio vulnificus/genética , Inibidores de beta-Lactamases , beta-Lactamases/genética
12.
BMJ Open ; 11(7): e045406, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285004

RESUMO

OBJECTIVES: Transparent reporting of trials is necessary to assess their internal and external validity. Currently, little is known about the quality of reporting in antibiotics trials. Our study investigates the reporting of adverse events, conflicts of interest and funding information in trials of penicillins, cephalosporins and macrolides. DESIGN: A secondary analysis of trials included in a convenience sample of three systematic reviews. METHODS: All randomised controlled trials included in the systematic reviews were included, although duplicates were removed. Eligible trials compared the specified antibiotics to placebo, for any indication. Author pairs independently extracted the data on reporting of adverse events from parent reviews, and data on funding and conflict of interest information from the trial reports. We calculated the overall proportion of trials reporting adverse events, conflict of interest information and funding information, and their proportion before and after the publication of the Consolidated Standards of Reporting Trials (CONSORT) 2001 Statement. RESULTS: We included 432 trials. Overall, 62% of trials reported adverse events of any kind, although reporting of deaths or antibiotic resistance was less frequent (20% and 37%, respectively). Conflict-of-interest information was provided in 26% of the trials, and funding information was provided in 66% of the trials. There was no significant difference in reporting of adverse events before and after the publication of CONSORT 2001 Statement (62% vs 62%, p=0.92). Conflict of interest statements were provided more frequently (2% vs 55%, p<0.001) and conflict was present more often (0% vs 14%, p<0.001). There was no difference in the provision of the information about trial funding before (62%) and after (70%) CONSORT 2001 publication. CONCLUSIONS: Information about adverse events, conflict of interest and funding, remains under-reported in trials of antibiotics.


Assuntos
Antibacterianos , Conflito de Interesses , Ensaios Clínicos Controlados Aleatórios como Assunto , Antibacterianos/efeitos adversos , Cefalosporinas , Humanos , Macrolídeos , Penicilinas
13.
BMC Infect Dis ; 21(1): 679, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256734

RESUMO

BACKGROUND: Oral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory concentration (MIC) testing. Currently, Clinical and Laboratory Standards Institute provides comments to use penicillin MIC ≤0.06 to predict oral cephalosporin susceptibility. However, no guidance is provided when cefotaxime MIC is known, leading to uncertainty with interpretation. The purpose of this study was to evaluate cefotaxime and penicillin MICs and their respective correlation to oral beta-lactam categorical susceptibility patterns. METHODS: 249 S. pneumoniae isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF) and then tested by broth microdilution method to penicillin, cefotaxime, amoxicillin, cefdinir, cefpodoxime, and cefuroxime. RESULTS: Using Clinical and Laboratory Standards Institute (CLSI) non-meningitis breakpoints for cefotaxime, 240/249 isolates were classified as susceptible. Of the cefotaxime susceptible isolates, 23% of the isolates are misrepresented as cefdinir susceptible. Amoxicillin correlated well with penicillin MIC breakpoints with only 1 discordant isolate out of 249. CONCLUSION: The correlation between amoxicillin and penicillin creates a very reliable predictor to determine categorical susceptibility. However oral cephalosporins were not well predicted by either penicillin or cefotaxime leading to the possible risk of treatment failures. Caution should be used when transitioning to oral cephalosporins in cefotaxime susceptible isolates, especially with higher cefotaxime MICs.


Assuntos
Amoxicilina/farmacologia , Cefotaxima/farmacologia , Testes de Sensibilidade Microbiana/métodos , Penicilinas/farmacologia , Pneumonia Pneumocócica , Streptococcus pneumoniae , Administração Oral , Antibacterianos/farmacologia , Cefalosporinas/classificação , Cefalosporinas/farmacologia , Humanos , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , beta-Lactamas/farmacologia
14.
J Med Microbiol ; 70(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34319224

RESUMO

Introduction. The emergence and spread of non-typhoidal Salmonella enterica (NTS) serovars resistant to fluoroquinolones and third- and higher-generation cephalosporins is a matter of great concern. Antimicrobial-resistant NTS is increasingly being discovered in humans, animals, food animals, food products, and agricultural environments. Pigs are considered a major reservoir of antimicrobial-resistant Salmonella spp.Hypothesis/Gap Statement. Fluoroquinolone-resistant Salmonella spp. warrant further surveillance and characterization for a better understanding of the bacteria isolated from animals.Aim. NTS isolated from pork from slaughterhouses across Thailand were characterized in terms of their serovars; resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems; and antimicrobial resistance genes.Methodology. A total of 387 NTS isolates, collected from slaughtered pigs in ten provinces across Thailand between 2014 and 2015, were characterized based on their serovars, antimicrobial resistance genes, and susceptibility to fluoroquinolones, third-generation cephalosporins, and carbapenems.Results. Among all NTS isolates, S. enterica serovar Rissen was predominant. Antimicrobial resistance was exhibited in 93/387 isolates (24 %). Although 24 (6.2 %) isolates were susceptible to all the tested antimicrobials, they were found to possess ß-lactamase genes, such as bla TEM, bla SHV, or bla CTX-M. Mobilized colistin-resistant genes (mcr) and resistance to colistin were not observed in any tested isolate. Carbapenem resistance was detected in ten isolates (10.7 %); however, bla KPC, bla NDM, bla OXA-48-like, and bla IMP were not present. Among the 93 antimicrobial-resistant isolates, 87.1 % showed fluoroquinolone resistance with the quinolone resistance gene (qnrS) combined with topoisomerase genes parC (T57S) or gyrA (S83E/Y and D124E/G) substitutions, or topoisomerase gene substitutions alone.Conclusion. We found high fluoroquinolone resistance rates among the NTS isolates from pigs from slaughterhouses. The fluoroquinolone resistance mechanism in NTS was associated with the combination of qnrS and substitutions in gyrA, parC, or both. To prevent the transmission of antimicrobial-resistant NTS between animals and humans, continuous monitoring, surveillance, and regulation of Salmonella in the pork supply chain are pivotal.


Assuntos
Farmacorresistência Bacteriana/genética , Salmonelose Animal/microbiologia , Salmonella enterica , Suínos/microbiologia , Animais , Cefalosporinas/farmacologia , Fluoroquinolonas/farmacologia , Salmonella enterica/genética , Salmonella enterica/isolamento & purificação , Sorogrupo , Tailândia/epidemiologia
15.
J Antimicrob Chemother ; 76(12 Suppl 2): ii22-ii29, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312658

RESUMO

OBJECTIVES: Data on cephalosporin consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of cephalosporins. METHODS: For the period 1997-2017, data on consumption of cephalosporins (i.e. first-, second-, third- and fourth-generation cephalosporins; ATC subgroups J01DB, J01DC, J01DD and J01DE, respectively) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Cephalosporin consumption was analysed based on ATC-4 subgroup, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, cephalosporin consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 285 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Cephalosporin consumption did not change significantly between the first quarter of 1997 and the last quarter of 2017. Seasonal variation decreased significantly over time. Proportional consumption of second- and third-generation cephalosporins significantly increased over time compared with that of first-generation cephalosporins, and proportional consumption of fourth-generation cephalosporins significantly decreased compared with that of second- and third-generation cephalosporins. CONCLUSIONS: Despite considerable variation between countries in the composition of cephalosporin consumption and trends over time, a significant shift towards consumption of more broad-spectrum cephalosporins in the community was observed across the EU/EEA during 1997-2017.


Assuntos
Infecções Bacterianas , Cefalosporinas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Uso de Medicamentos , União Europeia , Humanos , Pacientes Ambulatoriais
16.
J Nanosci Nanotechnol ; 21(12): 6024-6034, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229800

RESUMO

Carbon dots have good biocompatibility, low toxicity, excellent photoluminescence properties, and good light stability, endowing them good application prospects in drug detection, chemical analysis, drug delivery, and other fields. In this study, p-phenylenediamine was used as the carbon source, and carbon dots were synthesized in hydrochloric acid medium using microwave method. When the excitation wavelength is about 300 nm, a strong emission peak of 689 nm is detected for the synthesized carbon dots. Carbon dots' size is about 4.0±0.2 nm, and the carbon dots with spherical shape are uniformly distributed. The quantum yield of carbon dots is 8.07%. In addition, cephalosporins. were detected and analyzed using synthetic carbon dots. The results show that the presence of cephalosporins reduced the fluorescence intensity of carbon dots, and the reduced fluorescence intensity of the synthesized carbon dots showed a linear correlation with the cephalosporins' concentration. Cephalosporins' detection scope is 0.2 µmol/L to 80 µ mol/L, and the detection limit is 0.084 µ mol/L. A mechanism study shows that the effect of cephalosporins on carbon dot's fluorescence intensity can be attributed to the inner filter effect of cephalosporins. On this basis, a sensitive and 0selective cephalosporins detection method was established. Furthermore, this established method for cephalosporins detection was applied to real samples, resulting in a low relative standard deviation (RSD) and good recoveries.


Assuntos
Carbono , Pontos Quânticos , Cefalosporinas , Corantes Fluorescentes
17.
Antimicrob Agents Chemother ; 65(10): e0087721, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34252309

RESUMO

Cefiderocol (FDC) is a recently developed siderophore cephalosporin showing excellent antibacterial activity against Gram-negative bacteria, including Acinetobacter baumannii. By investigating a series of A. baumannii clinical isolates with elevated MICs of FDC, we showed that PER-like ß-lactamases and, to a lesser extent, NDM-like ß-lactamases, significantly contributed to reduced susceptibility to that antibiotic. Interestingly, we showed that combination of FDC with avibactam exhibited excellent activity against all multidrug-resistant isolates coproducing OXA-23 and PER-type ß-lactamases.


Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/farmacologia
18.
Antimicrob Agents Chemother ; 65(10): e0067921, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34280013

RESUMO

Ceftaroline fosamil, a fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is currently approved for the treatment of pneumonia and complicated skin and soft tissue infections. However, pharmacokinetics data on free lung tissue concentrations in critical patient populations are lacking. The aim of this study was to evaluate the pharmacokinetics of the high-dose regimen of ceftaroline in plasma and lung tissue in cardiac surgery patients during intermittent and continuous administration. Nine patients undergoing elective cardiac surgery on cardiopulmonary bypass were included in this study and randomly assigned to intermittent or continuous administration. Eighteen hundred milligrams of ceftaroline fosamil was administered intravenously as either 600 mg over 2 h every 8 h (q8h) (intermittent group) or 600 mg over 2 h (loading dose) plus 1,200 mg over 22 h (continuous group). Interstitial lung tissue concentrations were measured by in vivo microdialysis. Relevant pharmacokinetics parameters were calculated for each group. Plasma exposure levels during intermittent and continuous administration were comparable to those of previously published studies and did not differ significantly between the two groups. In vivo microdialysis demonstrated reliable and adequate penetration of ceftaroline into lung tissue during intermittent and continuous administration. The steady-state area under the concentration-time curve from 0 to 8 h (AUCss 0-8) and the ratio of AUCSS 0-8 in lung tissue and AUC in plasma (AUClung/plasma) were descriptively higher in the continuous group. Continuous administration of ceftaroline fosamil achieved a significantly higher proportion of time for which the free drug concentration remained above 4 times the minimal inhibitory concentration (MIC) during the dosing interval (% fT>4xMIC) than intermittent administration for pathogens with a MIC of 1 mg/liter. Ceftaroline showed adequate penetration into interstitial lung tissue of critically ill patients undergoing major cardiothoracic surgery, supporting its use for pneumonia caused by susceptible pathogens.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Staphylococcus aureus Resistente à Meticilina , Preparações Farmacêuticas , Antibacterianos/uso terapêutico , Ponte Cardiopulmonar , Cefalosporinas , Humanos , Pulmão/cirurgia , Microdiálise
19.
Antimicrob Agents Chemother ; 65(10): e0127421, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34310206

RESUMO

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of ß-lactamase variants.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Cefalosporinas/farmacologia , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Fenótipo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , beta-Lactamases/genética
20.
J Vet Med Sci ; 83(9): 1345-1355, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34275958

RESUMO

Dissemination of extended-spectrum cephalosporin (ESC)-resistant Salmonella is a public health concern in the egg production industry. ESC-resistant Salmonella often acquires the bla gene via insertion sequences (ISs). Therefore, this study aimed to assess antimicrobial resistance in Salmonella from Japanese layer breeding chains and egg processing chains, and determine the genetic profiles of IS-like elements in ESC-resistant Salmonella. Antimicrobial susceptibility testing was performed on 224 isolates from 49 facilities involving layer breeder farms, hatcheries, pullet-rearing farms, and layer farms in breeding chains along with egg processing chains. ESC-resistant Salmonella strains were whole-genome sequenced. Among them, 40 (17.9%) were resistant to at least streptomycin, tetracycline, ampicillin, chloramphenicol, cefpodoxime, nalidixic acid, ciprofloxacin, and/or kanamycin despite lacking resistance to azithromycin and meropenem. Moreover, 15 were ESC-resistant Salmonella harboring blaCMY-2 (Salmonella enterica serovar Ohio, n=12; S. Braenderup, n=1; untypeable with O7:b:-, n=1) and blaCTX-M-14 (S. Cerro, n=1). IncA/C2 plasmids containing ISEcp1, IS26, and multiple antimicrobial resistance genes (including blaCMY-2) were identified in S. Ohio isolates from pullet-rearing and layer farms belonging to the same company. Chromosomal integration of partial or whole IncA/C2 plasmids was seen with two S. Ohio isolates via ISEcp1 or IS26, respectively. Antimicrobial resistance genes such as blaCMY-2 might be transmitted among the upper and the lower levels of layer breeding chains via the replicon type IncA/C2 plasmids containing ISEcp1 and IS26.


Assuntos
Cefalosporinas , Salmonella enterica , Animais , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Galinhas , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Japão , Plasmídeos/genética , Salmonella/genética , Salmonella enterica/genética , beta-Lactamases/genética
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