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1.
J Chemother ; 32(1): 7-14, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31631801

RESUMEN

Escherichia coli is a common pathogen of bacterial biofilm infections. Sub-minimum inhibitory concentration ceftazidime (sub-MIC CAZ) could inhibit the biofilm formation of E. coli. Deletion of the ibpAB genes could increase the extracellular indole concentration of E. coli and then inhibit biofilm formation. Therefore, we speculated that sub-MIC CAZ might inhibit biofilm formation via ibpAB. In this study, the results showed that sub-MIC CAZ could significantly inhibit biofilm formation, swimming motility and the expression of the ibpA gene, while it could increase the expression of tnaA gene and extracellular indole concentration. Knockout of the ibpA gene resulted in a decrease in biofilm formation and swimming motility and an increase in the indole concentration. When treated with sub-MIC CAZ, the tnaA gene expression, indole concentration, biofilm formation and swimming motility of MG1655 ΔibpA were similar to those of the control group. The results indicated that sub-MIC CAZ might inhibit the biofilm formation of E. coli by increasing the extracellular indole concentration and downregulating the ibpA gene.

2.
Int Immunopharmacol ; 78: 106078, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31830620

RESUMEN

BACKGROUND: Data on therapeutic drug monitoring of voriconazole in elderly patients are limited. Impaired liver function and an inflammatory state in elderly individuals are hypothesized to impact the voriconazole serum level. METHODS: A total of 166 adult patients (317 trough concentrations) who underwent voriconazole therapeutic drug monitoring were enrolled. The voriconazole trough concentration, its associated covariates, and its correlation with adverse effects in 73 elderly (≥60 years) patients (116 trough concentrations) were analyzed and compared to those in 93 adult (<60 years) patients. RESULTS: The voriconazole trough concentration was 4.31 ± 3.03 µg/mL (range, 0.4-15.5 µg/mL) in the elderly patients, which was significantly higher than the 3.11 ± 2.13 µg/mL (range, 0.4-14.3 µg/mL) in the adult patients (P = 0.001). The proportion of voriconazole trough concentrations higher than 5 µg/mL was 35.3% in the elderly patients, which was also significantly higher than the 15.4% in the adult patients (P < 0.001). A stepwise multivariable linear regression model showed that procalcitonin and gamma-glutamyl transpeptidase were independently associated factors in the elderly patients (OR = 2.590, 95% confidence interval [CI] = 1.506-3.673, P = 0.001; OR = -0.016, 95% CI = -0.027 to -0.006, P = 0.005). Receiver operating characteristic (ROC) curve analysis indicated that procalcitonin concentrations of ≥1.31 ng/mL increased the incidence of a voriconazole trough concentration higher than 5 µg/mL (95% CI = 0.53-0.87 µg/mL) (P = 0.03). The incidence of decreased albumin concentrations was higher in the elderly cohort than that in the adult cohort independent of the voriconazole trough concentration (P < 0.05). CONCLUSIONS: The voriconazole trough concentrations in the elderly patients were significantly higher than those in the adult patients who received voriconazole therapy and were significantly affected by severe inflammation as evaluated by the procalcitonin concentration. Frequent monitoring of the voriconazole serum concentration and procalcitonin concentration during and after severe inflammation is critical to maintain the voriconazole serum concentration within the therapeutic range.

3.
Pharmacogenomics J ; 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31636355

RESUMEN

Clinical data on the relationships of cytochrome P450 (CYP2) B6 516G>T polymorphisms with efavirenz-induced central nervous system (CNS) side effects and virological response in HIV-infected adults are controversial. We sought to analyze the associations by meta-analysis. To identify eligible studies, we systematically searched PubMed, Embase, ScienceDirect, and Web of Science. The strength of the associations was measured by odds ratio (OR) and effect size (ES) with 95% confidence interval (CI). Seventeen studies comprising a total of 3598 HIV-infected adults were included. The results showed that the CYP2B6-516 GG genotype was significantly associated with a decreased risk of efavirenz-induced CNS side effects compared with the GT and TT genotypes (GG + GT vs. TT: OR = 0.60, 95% CI = 0.41-0.87, P = 0.006; GG vs. GT + TT: OR = 0.68, 95% CI = 0.51-0.91, P = 0.008; GG vs. GT: OR = 0.70, 95% CI = 0.51-0.94, P = 0.018), and there was no significant association between the genetic variants GT and TT (GT vs. TT: OR = 0.82, 95% CI = 0.54-1.26, P = 0.372). However, there was no significant association between CYP2B6-516 GG and GT + TT genotypes in virological response (GT + TT vs. GG: ES = 1.06, 95% CI = 0.95-1.18, P = 0.321; OR = 1.01, 95% CI = 0.65-1.58, P = 0.963). Taken together, our results demonstrated that compared with the normal efavirenz clearance genotype CYP2B6-516 GG, the slow and very slow efavirenz clearance genotypes GT and TT were significantly associated with an increased risk of efavirenz-induced CNS side effects but not an increased virological response. To promote the tolerance of efavirenz, it is better to adjust the dosage of efavirenz according to the polymorphisms of CYP2B6-516 in HIV-infected adults.

4.
Artículo en Inglés | MEDLINE | ID: mdl-31628088

RESUMEN

PURPOSE: The aim of this study was to investigate the changes over a ten-year period in the resistance and epidemiological characteristics of Pseudomonas aeruginosa strains isolated from the Department of Respiratory in Southwest Hospital. METHODS: Antimicrobial resistance was detected using the plate double dilution method. PCR amplification and sequencing were performed to evaluate the carbapenemase genes and the oprD gene. Bacterial genotypes were analyzed by multilocus sequence typing (MLST). Quantitative real-time PCR experiments were performed to assess the expression of efflux pump (mexA and mexX) and ampC gene. RESULTS: We collected 233 P. aeruginosa isolates in 2006-2007 and 128 isolates in 2016-2017. The resistance rate of P. aeruginosa strains to the tested antibiotics was significantly lower in 2016-2017 than in 2006-2007. The MLST results showed 27 genotypes in 2006-2007 and 18 genotypes in 2016-2017. ST235 was the most prevalent sequence type, and there was no significant change in the genotypes over the ten-year period. Both VIM-2 and IMP-4 genes were found in 2006-2007, whereas only IMP-4 was found in 2016-2017. The oprD mutational inactivation was the main factor responsible for carbapenem resistance, and the overexpression of mexX had a good correlation with aminoglycoside resistance. CONCLUSION: These results indicated that the antibiotic resistance of P. aeruginosa in our respiratory department decreased. The loss of oprD gene was the main mechanism of carbapenem resistance, and mexX overexpression was the major contributing factor to aminoglycoside resistance.

5.
J Nanobiotechnology ; 17(1): 103, 2019 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-31581948

RESUMEN

BACKGROUND: Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs). RESULTS: MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs. CONCLUSIONS: Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

6.
Medicine (Baltimore) ; 98(37): e17157, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31517862

RESUMEN

Antimicrobial resistance, a major threat to human health, is mainly driven by the overuse of antimicrobials. The purpose of this study was to further investigate the relationship between antimicrobial use and resistance with a 15-year record in Southwest hospital, one of the largest hospitals in Southwest China and a university affiliated hospital, thus to further predict the antimicrobial resistance in an autoregressive integrated moving average (ARIMA) manner. Kirby-Bauer tests were carried out to figure out the drug sensitivity of Gram-negative bacterial. Antimicrobials (ß-lactamase inhibitor complex, aminoglycosides, quinolones, third and fourth-generation cephalosporins, carbapenems, cephamycins, oxacephems, and sulfonamides) consumption were calculated according to World Health Organization (WHO) anatomical therapeutic chemical classification index and expressed as annual defined daily dose (DDD) or DDD per 1000 out patients. Resistance rates of levofloxacin-resistant Escherichia coli, ceftazidime-resistant Klebsiella pneumoniae, amikacin-resistant Bacterium levans, imipenem-resistant Pseudomonas aeruginosa is positively correlated with the usage of aminoglycosides and quinolones; resistance rates of imipenem-resistant Acinetobacter baumanii is positively correlated with the usage of carbapenemes (P-value between the drug resistance of levofloxacin-resistant E. coli, ceftazidime-resistant K. pneumoniae and the usage of aminoglycosides is under .05, the other P-value are under .01); resistance rates of the drug resistance of levofloxacin-resistant E. coli is positively correlated with the usage of oxacephems (P < .01); resistance rates of imipenem-resistant P. aeruginosa is positively correlated with the usage of oxacephems and sulfonamides (P < .01).The present study presents one of the largest and longest retrospective analyses in China between antimicrobial consumption and antimicrobial resistance. Change of the usage of several antibacterial drugs has great influence on the drug resistance of Gram-negative bacterial. Of particular, ARIMA forecasting revealed that carbapenem related bacterial resistance should be closely watched.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Utilización de Medicamentos , Bacterias Gramnegativas/efectos de los fármacos , Aceptación de la Atención de Salud , Monitoreo Epidemiológico , Hospitales Universitarios , Humanos , Estudios Retrospectivos
7.
Infect Drug Resist ; 11: 1447-1460, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30254476

RESUMEN

Background: Plasmid-mediated multi-drug resistance (MDR) has been widely found in Citro-bacter freundii. C. freundii P10159 was isolated from a human case of postoperative urinary tract infection in a Chinese teaching hospital. Methods: The complete nucleotide sequences of five resistance plasmids pP10159-1, pP10159-2, pP10159-3, pP10159-4 and pP10159-5 from C. freundii P10159 were determined through high-throughput genome sequencing, and then compared with related plasmids sequences. Plasmid transfer, CarbaNP test of carbapenemase activity, and bacterial antimicrobial susceptibility test were performed to characterize resistance phenotypes mediated by these plasmids. Results: pP10159-1 carrying blaNDM-1and pP10159-2 harboring blaIMP-4 plus qnrS1 were almost identical to IncX3 plasmid pNDM-HN380 and IncN1 plasmid pP378-IMP, respectively. The blaKPC-2-carrying plasmids pP10159-3, pHS062105-3 and pECN49-KPC were highly similar to each other, and constituted a novel group of plasmids belonging to an unknown incomparability group. The MDR plasmids pP10159-4 and pP10159-5 had the backbones highly similar to IncHI4 plasmid pNDM-CIT and type 2 IncC plasmid pR55, respectively, but their accessory resistance regions differed from pNDM-CIT and pR55, respectively. The five plasmids from the P10159 isolate contained a total of 24 different genes or gene loci, which contributed to resistance to 13 distinct antibiotic molecules or toxic compounds. Conclusion: This is the first report of co-occurrence of five different resistance plasmids, with determination of their complete sequences. Data presented here provide a deeper insight into co-selection and maintenance of multiple plasmids and an extremely large number of resistance genes in a single bacterial isolate.

8.
J Chemother ; 30(3): 145-149, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29304717

RESUMEN

The objective of this study was to analyse the distribution and antimicrobial resistance of bacterial uropathogens isolated from outpatients at Henan Provincial People's Hospital. A total of 1419 samples from 823 newly diagnosed and 596 recurrent UTI outpatients culture positive. Escherichia coli was the most common uropathogen. Compared with the recurrent group, the newly diagnosed group had a higher isolation rate of E. coli and Enterobacter cloacae but a lower isolation rate of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Except for P. aeruginosa, the resistance of Gram-negative bacteria to most antibiotics was less than 30%. All Enterococcus and Staphylococcus spp. were sensitive to linezolid, vancomycin and teicoplanin. Both Gram-negative and -positive bacteria exhibited high susceptibility to fosfomycin. Uropathogens isolated from recurrent outpatients had higher resistance rates than did those isolated from newly diagnosed outpatients. Our study indicated that fosfomycin might be an excellent treatment option for outpatients with UTIs.


Asunto(s)
Antibacterianos/farmacología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Bacterianas/complicaciones , Farmacorresistencia Bacteriana , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/efectos de los fármacos , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pacientes Ambulatorios/estadística & datos numéricos , Prevalencia , Estudios Prospectivos , Centros de Atención Terciaria , Infecciones Urinarias/microbiología , Adulto Joven
9.
J Trop Pediatr ; 64(3): 231-236, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28985401

RESUMEN

Background: The improvement of medical condition requires prolonged hospital stays, which increase the risk of nosocomial bloodstream infections (BSIs). Methods: All nosocomial BSI newborns in two hospitals were included, and the demographic and clinical characteristics of bacteremia patients were obtained from the information systems. Isolates were identified by biochemical assays. Antimicrobial susceptibility was determined using disk diffusion method. Results: Except for three same risk factors, intubation with mechanical ventilation was a risk factor in Chongqing, while low birth weight was a risk factor in Henan. Klebsiella pneumoniae was the predominant strain in Chongqing, and Escherichia coli was the most prevalent strain in Henan. The resistance rate of gram-negative bacteria in Henan was higher than that of strains in Chongqing. Conclusions: The risk factors and resistance rate of pathogens were different in different areas. Therefore, treatment protocols should be established based on the trends of drug resistance and bacterial spectrum.


Asunto(s)
Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infección Hospitalaria/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/epidemiología , China/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana , Escherichia coli/aislamiento & purificación , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Recién Nacido , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Pruebas de Sensibilidad Microbiana
10.
Chemotherapy ; 63(1): 20-28, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29145175

RESUMEN

Backgroud: Antibiotic treatment for infections caused by vancomycin-intermediate Staphylococcus aureus (VISA) strains is challenging, and only a few effective and curative methods have been developed to combat these strains. This study aimed to investigate the antimicrobial activity of galangin against S. aureus and its effects on the murein hydrolases of VISA strain Mu50. This is the first report on these effects of galangin, and it may help to improve the treatment for VISA infections by demonstrating the effective use of galangin. METHODS: Firstly, the minimum inhibitory concentration (MIC) and growth curve were used to investigate the antimicrobial activity of galangin against S. aureus. Secondly, transmission electron microscopy (TEM) was used to observe morphological changes of VISA strain Mu50. Thirdly, Triton X-100-induced autolysis and cell wall hydrolysis assays were performed to determine the activities of the murein hydrolases of Mu50. Finally, fluorescence real-time quantitative PCR was used to investigate the expression of the murein hydrolase-related Mu50 genes. RESULTS: The results indicated that the MIC of galangin was 32 µg/mL against ATCC25293, N315, and Mu50, and galangin could significantly suppress the bacterial growth (p < 0.05) with concentrations of 4, 8 and 16 µg/mL, compared with control group (0 µg/mL). To explore the possible reasons of bacteriostatic effects of galangin, we observed morphological changes using TEM which showed that the division of Mu50 daughter cells treated with galangin was obviously inhibited. Considering the vital role of murein hydrolases in cellular division, assays were performed, and galangin markedly decreased Triton X-100-induced autolysis and cell wall hydrolysis. Galangin also significantly inhibited the expression of the murein hydrolase genes (atl, lytM, and lytN) and their regulatory genes (cidR, cidA, and cidB). CONCLUSIONS: Our findings indicated that galangin can effectively inhibit murein hydrolase activity as well as the growth of VISA strain Mu50.


Asunto(s)
Antiinfecciosos/metabolismo , Proteínas Bacterianas/metabolismo , Flavonoides/farmacología , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/química , Antiinfecciosos/farmacología , Proteínas Bacterianas/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Flavonoides/química , Flavonoides/metabolismo , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , N-Acetil Muramoil-L-Alanina Amidasa/genética , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Vancomicina/farmacología
11.
Oncotarget ; 8(34): 55958-55966, 2017 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-28915566

RESUMEN

The treatment of drug-resistant infections is complicated and the alarming rise in infectious diseases poses a unique challenge for development of effective therapeutic strategies. Antibiotic-induced liberation of the bacterial endotoxin lipopolysaccharide (LPS) may have immediate adverse effects promoting septic shock in patients. In the present study, we first confirmed our previous finding that looped antimicrobial peptide CLP-19 exerts non-specific direct antibacterial activity with no toxic to mammalian cells and second revealed that CLP-19 has synergistic effect to enhance the antibacterial activities of other conventional bactericidal (ampicillin and ceftazidime) and bacteriostatic (erythromycin and levofloxacin) agents. Third, the underlying mechanism of antibiotic effect was likely associated with stimulation of hydroxyl radical generation. Lastly, CLP-19 was shown to effectively reduce the antibiotic-induced liberation of LPS, through direct neutralization of the LPS. Thus, CLP-19 is a potential therapeutic agent for combinatorial antibiotic therapy.

12.
Exp Ther Med ; 14(2): 1647-1652, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28810631

RESUMEN

Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen in hospital-acquired infection and is readily able to form biofilms. Due to its high antibiotic resistance, traditional antibacterial treatments exert a limited effect on P. aeruginosa biofilm infections. It has been indicated that hyperoside inhibits P. aeruginosa PAO1 (PAO1) biofilm formation without affecting growth. Therefore, the current study examined the biofilm formation and quorum sensing (QS) system of PAO1 in the presence of hyperoside. Confocal laser scanning microscopy analysis demonstrated that hyperoside significantly inhibited biofilm formation. It was also observed that hyperoside inhibited twitching motility in addition to adhesion. Data from reverse transcription-quantitative polymerase chain reaction indicated that hyperoside inhibited the expression of lasR, lasI, rhlR and rhlI genes. These results suggest that the QS-inhibiting effect of hyperoside may lead to a reduction in biofilm formation. However, the precise mechanism of hyperoside on P. aeruginosa pathogenicity remains unclear and requires elucidation in additional studies.

13.
Future Microbiol ; 12: 573-584, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28660784

RESUMEN

AIM: This study aims to characterize a multidrug-resistant (MDR) plasmid p12969-2 coexistent with the previously reported one p12969-DIM in clinical Pseudomonas putida. MATERIALS & METHODS: The complete sequence of p12969-2 was determined using next-generation sequencing technology. RESULTS: p12969-2 contains a 29.2 kb MDR region, which carries In127 harboring three resistance genes aadA2, qacED1 and sul1. The MDR region is derived from the connection of Tn5041D and Tn5045, which is facilitated by two copies of miniature inverted-repeat transposable element. Conclusion & future perspective: p12969-2 represents a novel lineage with the highest but limited nucleotide sequence similarity with the plasmid pGRT1 that does not carry any of the resistance genes. This is the first report of coexistence of two MDR plasmids in P. putida.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Plásmidos/genética , Pseudomonas putida/genética , Antibacterianos/farmacología , Elementos Transponibles de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Infecciones por Pseudomonas/microbiología , Pseudomonas putida/efectos de los fármacos , Análisis de Secuencia de ADN , beta-Lactamasas/genética
14.
J Glob Antimicrob Resist ; 8: 142-147, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28216097

RESUMEN

OBJECTIVES: Pseudomonas aeruginosa is one of the most common pathogens causing nosocomial pneumonia. The aim of this study was to investigate the epidemiology and resistance of P. aeruginosa isolated from hospitalised patients in the respiratory department of a hospital in China. METHODS: Clinical isolates were collected from the respiratory department of Southwest Hospital (Chongqing, China) from January 2013 to December 2014. Patients' social and demographic information was obtained from the hospital's information system. Antimicrobial susceptibility was assessed using the agar dilution method. Screening for carbapenemase production among carbapenem-resistant P. aeruginosa was performed using the modified Hodge test and MBL Etest, and carbapenemase-encoding genes were amplified by PCR. Amplification and sequencing of the oprD gene were performed for carbapenem-resistant P. aeruginosa. Sequence types were determined by multilocus sequence typing (MLST). RESULTS: A total of 92 P. aeruginosa isolates were collected from patients in the respiratory department, and piperacillin/tazobactam was the most effective antibiotic against these isolates. Multivariate analysis revealed that antibiotic use prior to admission was an independent risk factor for P. aeruginosa infection. The isolates comprised 25 genotypes, the most common of which were ST235 and ST111. The blaIMP-4 gene was present in 4 isolates and blaVIM-2 in 1 isolate among the 24 carbapenem-resistant isolates. Most of the carbapenem-resistant isolates contained mutational inactivation of the oprD gene. CONCLUSIONS: These results suggested that patients and the hospital environment were sources of P. aeruginosa in nosocomial infections. Mutational inactivation of the oprD gene might be the main mechanism of carbapenem resistance.


Asunto(s)
Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana , Neumonía Bacteriana/epidemiología , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Infección Hospitalaria/microbiología , Femenino , Genotipo , Hospitales , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Neumonía Bacteriana/microbiología , Reacción en Cadena de la Polimerasa , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/genética , Adulto Joven
15.
Biochem Biophys Res Commun ; 480(3): 486-491, 2016 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-27780729

RESUMEN

Endotoxin tolerance (ET) is a complex protective mechanism against endotoxin shock. The looped CLP-19 peptide derived from Limulus anti-LPS peptide induced the ET phenomenon but the molecular mechanism has yet to be fully elucidated. Here, we confirmed that CLP-19 attenuated upon LPS stimulated pro-inflammatory factor secretion of TNF-α and IL-6 but increased anti-inflammatory factor production of IL-10 in dose- and time-dependent manners. CLP-19 also inhibited subsequent LPS stimulated expression of TLR4 on the cell membrane. Moreover, the CLP-19 inhibited degradation of the inhibitor of NF-κB (IκBα and IκBß) and reduced LPS induced NF-κB activity, but not of effects on expression of MyD88 and TRAF-6. Finally CLP-19 significantly increased survival of lethal LPS shock mouse models with significantly less pathological injury to lung. These findings collectively suggest that CLP-19 induces ET phenomenon involved inhibition of NF-κB activation. In conclusion, this study has revealed a novel function of CLP-19 that appears to represent a potential therapeutic agent for clinical treatment of septic shock.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/administración & dosificación , Proteínas de Artrópodos/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Lipopolisacáridos/uso terapéutico , FN-kappa B/metabolismo , Animales , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos/fisiología , Endotoxinas/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7
16.
Sci Rep ; 6: 33982, 2016 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-27658354

RESUMEN

We previously reported the complete sequence of the resistance plasmid pP10164-NDM, harboring blaNDM (conferring carbapenem resistance) and bleMBL (conferring bleomycin resistance), which is recovered from a clinical Leclercia adecarboxylata isolate P10164 from China. This follow-up work disclosed that there were still two multidrug-resistant (MDR) plasmids pP10164-2 and pP10164-3 coexisting in this strain. pP10164-2 and pP10164-3 were completely sequenced and shown to carry a wealth of resistance genes, which encoded the resistance to at least 10 classes of antibiotics (ß-lactams. macrolides, quinolones, aminoglycosides, tetracyclines, amphenicols, quaternary ammonium compounds, sulphonamides, trimethoprim, and rifampicin) and 7 kinds of heavy mental (mercury, silver, copper, nickel, chromate, arsenic, and tellurium). All of these antibiotic resistance genes are associated with mobile elements such as transposons, integrons, and insertion sequence-based transposable units, constituting a total of three novel MDR regions, two in pP10164-2 and the other one in pP10164-3. Coexistence of three resistance plasmids pP10164-NDM, pP10164-2 and pP10164-3 makes L. adecarboxylata P10164 tend to become extensively drug-resistant.

17.
Sci Rep ; 6: 33419, 2016 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-27641711

RESUMEN

A total of 26 blaIMP-4-carrying strains of Pseudomonas aeruginosa and Klebsiella pneumoniae were isolated from 2009 to 2013 in a Chinese teaching hospital, and these strains can be assigned into multiple sequence types or allelic profiles as determined by multilocus sequence typing. Of these strains, P. aeruginosa P378 and K. pneumoniae 1220 harbor the IMP-4-encoding plasmids pP378-IMP and p1220-IMP, respectively, whose complete nucleotide sequences are determined to be genetically closely related to the IncN1-type plasmid pIMP-HZ1. pP378-IMP/p1220-IMP-like plasmids are hinted to be present in all the other blaIMP-4-carrying strains, indicating the dissemination of pIMP-HZ1-related plasmids among K. pneumoniae or P. aeruginosa of different genotypes in this hospital. pP378-IMP carries two distinct accessory resistance regions, a blaIMP-4-carrying class 1 integron In823b, and a truncated Tn3-family unit transposon ΔTn6292-3' harboring the quinolone resistance gene qnrS1. Massive fragmentation and rearrangement of these accessory genetic contents occur among p1220-IMP and IMP-HZ1 relative to pP378-IMP. blaIMP-4 is also present in the In823b remnants from p1220-IMP and IMP-HZ1, while qnrS1 is located in a Tn6292-derive fragment from pIMP-HZ1 but not found in p1220-IMP. pP378-IMP represents the first fully sequenced IncN-type plasmid from P. aeruginosa.


Asunto(s)
Hospitales de Enseñanza , Klebsiella pneumoniae/enzimología , Plásmidos/genética , Pseudomonas aeruginosa/enzimología , beta-Lactamasas/genética , Antibacterianos/farmacología , China , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Genes Bacterianos , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Regulón/genética
18.
Microb Pathog ; 97: 221-5, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27289037

RESUMEN

Vibrio parahaemolyticus is a leading cause of seafood-associated diarrhea and gastroenteritis. This bacteria expresses a major virulence determinant called T3SS1. Expression of T3SS1 is tightly regulated by the ExsA-ExsC-ExsD regulatory system. The transcription of exsA and probably exsC is repressed directly by the H-NS protein. In this study, the regulation of exsD by H-NS was investigated using quantitative RT-PCR, primer extension, LacZ fusion, electrophoretic mobility shift, and DNase I footprinting assays. The results showed that His-H-NS protected a single region from 61 bp to 174 bp upstream of exsD against DNase I digestion, and a transcription start site located at 105 bp upstream of exsD was detected and its activity was repressed by H-NS. Therefore, a single H-NS-dependent promoter was transcribed for exsD in V. parahaemolyticus. Thus, all three genes in the ExsA-ExsC-ExsD regulatory system of T3SS1 are directly repressed by H-NS in V. parahaemolyticus.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación Bacteriana de la Expresión Génica , Genes Reguladores , Proteínas de la Membrana/biosíntesis , Transcripción Genética , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Fusión Artificial Génica , Huella de ADN , Ensayo de Cambio de Movilidad Electroforética , Perfilación de la Expresión Génica , Genes Bacterianos , Proteínas de la Membrana/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Sitio de Iniciación de la Transcripción , beta-Galactosidasa/análisis , beta-Galactosidasa/genética
19.
J Sep Sci ; 39(15): 2890-5, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27257129

RESUMEN

A sensitive and specific liquid chromatography with tandem mass spectrometry method was firstly developed for the measurement of isomangiferin in rat plasma. Chloramphenicol was selected as the internal standard. Sample preparation was carried out through a simple one-step protein precipitation procedure with methanol. Negative electrospray ionization was performed using multiple reaction monitoring mode with transitions of m/z 421.1/301.1 for isomangiferin, and 321.1/151.9 for chloramphenicol. The calibration curve was linear over the range of 0.1-600 ng/mL, with a lower limit of quantification at 0.1 ng/mL. The intra- and interday precisions (relative standard deviation) were no more than 8.2% and accuracies (relative error) were within the range of -8.4 to 2.2%. The recovery, matrix effect and stability under different conditions were all proved acceptable. The validated method has been successfully applied to a preclinical pharmacokinetic study of isomangiferin in rats for the first time.


Asunto(s)
Xantonas/sangre , Xantonas/farmacocinética , Animales , Cromatografía Liquida , Masculino , Conformación Molecular , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Xantonas/química
20.
J Chemother ; 28(6): 476-481, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27077932

RESUMEN

The aim of this study was to analyse the resistance and epidemiological data of 117 Acinetobacter baumannii isolates from Southwest Hospital, Chongqing, China. Except for polymyxin B, tigecycline, minocycline, cefoperazone/sulbactam, amikacin and levofloxacin, the resistance rates of other antimicrobial agents were above 90%. All the clinical isolates had the blaOXA-51 gene and 114 isolates had the blaOXA-23 gene. Forty-nine isolates were found to contain the blaIMP-4 gene. PFGE data showed that 117 isolates were divided into 25 groups. Sixty-three (53.85%) were found to carry the class 1 integron, and the sequence analysis of the class 1 integron internal variable regions - five types, one of which had the blaIMP-4 gene. For the blaIMP-4 positive strain without class 1 integron, we found the flanking sequence had the TnpA gene. The result suggested that the resistance gene was widely distributed in our hospital; moreover, the modes of presence and transmission are different and complicated. The results of our study can improve the infection empirical treatment method and infection control programme.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana/genética , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/transmisión , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , China , Infección Hospitalaria/epidemiología , Infección Hospitalaria/transmisión , Humanos , Centros de Atención Terciaria
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