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1.
Chin Med ; 18(1): 84, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37454125

RESUMEN

BACKGROUND: As a supplement for promoting hair health, Shi-Bi-Man (SBM) is a prescription comprising various traditional Chinese medicines. Though SBM has been reported to promote hair regeneration, its molecular mechanism remains unclear. Cynomolgus monkeys (Macaca fascicularis) are non-human primates with a gene expression profile similar to that of humans. The purpose of this research is to evaluate the effect of SBM on promoting hair regeneration in cynomolgus monkeys and to reveal the underlying mechanism. METHODS: The effect of SBM on hair regeneration was observed by skin administration on 6 cynomolgus monkeys with artificial back shaving. The molecular mechanism of SBM was studied using single-cell RNA sequencing (scRNA-seq) in combination with quantitative polymerase chain reaction (qPCR) detection for gene transcription level, and immunofluorescence staining verification for protein level. RESULTS: SBM significantly induced hair regeneration in cynomolgus monkeys, increased hair follicle number and facilitated hair follicle development. ScRNA-seq revealed an increase in the number of hair follicle stem cells (HFSCs) with a higher activation state, as evidenced by the higher expression of activation marker LDHA related to metabolism and the proliferation marker MKI67. Immunofluorescence analysis at the protein level and qPCR at the mRNA level confirmed the sequencing data. Cellchat analysis revealed an enrichment of ligand-receptor pairs involved in intercellular communication in Laminin-related pathways. CONCLUSION: SBM significantly promotes hair regeneration in cynomolgus monkeys. Mechanically, SBM can up-regulate LDHA-mediated lactic acid metabolism and drive HFSC activation, which in turn promotes the proliferation and differentiation of HFSCs.

3.
Microbiol Spectr ; 11(4): e0033423, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37272820

RESUMEN

Klebsiella pneumoniae, a pathogen of critical clinical concern, urgently demands effective therapeutic options owing to its drug resistance. Polymyxins are increasingly regarded as a last-line therapeutic option for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, polymyxin resistance in K. pneumoniae is an emerging issue. Here, we report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates. To further confirm this, we investigated the efficacy of combined GaNt and colistin in vitro using spot dilution and rapid time-kill assays and growth curve inhibition tests and in vivo using a murine lung infection model. The results showed that GaNt significantly increased the antimicrobial activity of colistin, especially in the iron-limiting media. Mechanistic studies demonstrated that bacterial antioxidant activity was repressed by GaNt, as revealed by RNA sequencing (RNA-seq), leading to intracellular accumulation of reactive oxygen species (ROS) in K. pneumoniae, which was enhanced in the presence of colistin. Therefore, oxidative stress induced by GaNt and colistin augments the colistin-mediated killing of wild-type cells, which can be abolished by dimethyl sulfoxide (DMSO), an effective ROS scavenger. Collectively, our study indicates that GaNt has a notable impact on the antimicrobial activity of colistin against K. pneumoniae, revealing the potential of GaNt as a novel colistin adjuvant to improve the treatment outcomes of bacterial infections. IMPORTANCE This study aimed to determine the antimicrobial activity of GaNt combined with colistin against Klebsiella pneumoniae in vitro and in vivo. Our results suggest that by combining GaNt with colistin, antioxidant activity was suppressed and reactive oxygen species accumulation was induced in bacterial cells, enhancing antimicrobial activity against K. pneumoniae. We found that GaNt functioned as an antibiotic adjuvant when combined with colistin by inhibiting the growth of multidrug-resistant K. pneumoniae. Our study provides insight into the use of an adjuvant to boost the antibiotic potential of colistin for treating infections caused by multidrug-resistant K. pneumoniae.


Asunto(s)
Antiinfecciosos , Infecciones por Klebsiella , Ratones , Animales , Colistina/farmacología , Klebsiella pneumoniae/genética , Especies Reactivas de Oxígeno , Antioxidantes/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Polimixinas/farmacología , Polimixinas/uso terapéutico , Pruebas de Sensibilidad Microbiana , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Farmacorresistencia Bacteriana Múltiple
4.
Fitoterapia ; 163: 105347, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36336137

RESUMEN

Two novel series of 1,2-didehydro-7-hydroxy-3-ox-14-deoxyandrographolide and 1,2-didehydro-8,17-epoxy-3-ox-14-deoxyandrographolide derivatives were designed, synthesized and evaluated for their cytotoxic activity in vitro against two human cancer cell lines HCT-116 (human colon cancer) and MCF-7 (human breast cancer). Most tested compounds, especially those of the first series, displayed better inhibitory activity on both HCT-116 and MCF-7 cells than andrographolide. HCT-116 cells were found to be more sensitive to tested compounds than MCF-7, and compound 13b exhibited the most potent activity against HCT-116, with an IC50 value of 7.32 µM. Further anti-cancer mechanistic investigation demonstrated that compound 13b effectively suppressed the growth of HCT-116 cells by triggering early and late cellular apoptosis in a concentration-dependent manner and arresting cell cycle in S phase.


Asunto(s)
Antineoplásicos , Oxígeno , Humanos , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a Droga , Antineoplásicos/farmacología , Apoptosis , Proliferación Celular , Línea Celular Tumoral , Diseño de Fármacos
5.
Arch Microbiol ; 204(7): 443, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35776209

RESUMEN

Rumex gmelinii Turcz. (RGT) is a medicinal plant of the genus Rumex, family Polygonaceae. Our research group isolated an endophytic fungus, Plectosphaerella cucumerina (Strain J-G) from RGT, which could significantly promote host growth when co-cultured with host seedlings. In this study, we used transcriptome analysis and verification experiments to explore the molecular mechanisms underlying this growth-promoting effect. We found that, during co-culture with Strain J-G, the expression of genes encoding key enzymes in amino acid metabolism and carbohydrate synthesis and metabolism were up-regulated in RGT tissue culture seedlings, providing additional substrate and energy for plant growth. In addition, the expression of genes encoding the responser of RGT seedlings to hormones, including auxin and cytokinin, were significantly enhanced, promoting plant growth and development. Furthermore, RGT seedling defense systems were mobilized by Strain J-G; therefore, more secondary metabolites and substances involved in stress resistance were produced, ensuring normal plant growth and metabolism. The research showed Strain J-G significantly promote the accumulation of biomass and effective components of RGT, which provide basis for its application. This research also provides a reference method for the study of growth-promoting mechanism of endophytic fungi.


Asunto(s)
Rumex , Hongos , Perfilación de la Expresión Génica , Desarrollo de la Planta , Rumex/genética , Plantones , Transcriptoma
6.
Bioorg Med Chem Lett ; 41: 128001, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33811991

RESUMEN

Penicillin-binding protein 2a (PBP2a) is an essential protein involved in the resistance to ß-lactam antibiotics acquired by methicillin-resistant Staphylococcus aureus (MRSA) and is a potential antibacterial target. In the current study, we employed a strategy that combined virtual screening with biological evaluation to discover novel inhibitors of PBP2a. In this investigation, a hybrid virtual screening method, consisting of drug-likeness evaluation (Lipinski's Rule of Five and ADMET) and rigid (LibDock) and semi-flexible (CDOCKER) docking-based virtual screenings, was used for retrieving novel PBP2a inhibitors from commercially available chemical databases. 11 compounds were selected from the final hits and subsequently shifted to experimental studies. Among them, Hit 2, Hit 3, and Hit 10 exhibited excellent anti-MRSA ATCC 33591 activity and weak toxicity in vitro. The affinity of the three compounds to bind to PBP2a was further confirmed by surface plasmon resonance (SPR) experiments and molecular dynamics (MD) simulation. An inter-complex interaction study showed that all hit compounds adapted well to the allosteric site of the PBP2a protein. In addition, Hit 2 (with best binding affinity to PBP2a, KD = 1.29 × 10-7 M) significantly inhibits proliferation of MRSA clinical isolates. Together, the 3 hit compounds, especially Hit 2, may be potential non-ß-lactam antibiotics against MRSA and the work will provide clues for the future development of specific compounds that block the interaction of PBP2a with their targets.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Descubrimiento de Drogas , Proteínas de Unión a las Penicilinas/antagonistas & inhibidores , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Proteínas Bacterianas/metabolismo , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Pruebas de Sensibilidad Microbiana , Simulación de Dinámica Molecular , Estructura Molecular , Proteínas de Unión a las Penicilinas/metabolismo , Staphylococcus aureus/metabolismo , Relación Estructura-Actividad
7.
mSystems ; 5(6)2020 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-33144310

RESUMEN

ABSRTACTKlebsiella pneumoniae is a common cause of human-pneumonia-derived sepsis with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis. The mechanisms by which the gut microbiota affects the host defenses in the respiratory system systematically, however, remain poorly understood. Here, we show that gut microbiota depletion increases susceptibility to extracellular K. pneumoniae infections in terms of increased bacterial burdens in lung and decreased survival rates. Oral supplementation with gut microbiota-derived short-chain fatty acids (SCFAs), subsequently activating G protein-coupled receptor 43 (GPCR43), enhances a macrophage's capacity to phagocytose invading K. pneumoniae Furthermore, SCFAs and GPR43 increase macrophage bacterial clearance by upregulating LAMTOR2, which is further identified as an antibacterial effector and elucidated to facilitate phagosome-lysosome fusion and extracellular signal-regulated kinase (ERK) phosphorylation. Lastly, conditional ablation of Lamtor2 in macrophages decreases their antimicrobial activity, even though mice were pretreated with exogenous SCFA supplementation.IMPORTANCE These observations highlight that SCFAs promote macrophage elimination of K. pneumoniae via a LAMTOR2-dependent signal pathway and suggest that it is possible to intervene in K. pneumoniae pneumonia by targeting the gut microbiota.

8.
ACS Appl Mater Interfaces ; 12(45): 50260-50274, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33108154

RESUMEN

Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanopartículas/química , Temperatura , Staphylococcus aureus Resistente a Vancomicina/efectos de los fármacos , Vancomicina/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Rayos Infrarrojos , Liposomas/química , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Procesos Fotoquímicos , Puntos Cuánticos/química , Sulfuros/química , Propiedades de Superficie , Compuestos de Tungsteno/química , Vancomicina/química
9.
Microb Drug Resist ; 26(9): 1108-1119, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32349617

RESUMEN

With the stagnancy of antibiotics development, polymyxins have become the last defense for treatment of multidrug-resistant (MDR) Gram-negative bacteria, whereas the effect of polymyxin monotherapy is limited by resistance. The objective of this study was to evaluate the effects of polymyxin B (PMNB)-vorinostat (SAHA) combination therapy against Gram-negative pathogens in vitro and in vivo. The antibacterial activities of PMNB and SAHA were evaluated by susceptibility testing. The synergistic effect was assessed by checkerboard tests and time-killing kinetics experiments. Cellular morphology studies and reactive oxygen species (ROS) assay were conducted to explore potential mechanisms. Also, Galleria mellonella models were made to evaluate the antibacterial effects in vivo. PMNB-SAHA had the synergistic effect against all tested isolates, reducing >2 log10 colony-forming units (CFU)/mL at 40 minutes, and showed more powerful antibacterial effects than PMNB alone in the 24-hour window. Cellular morphology study showed the change of membrane and disruption of integrity. ROS assay showed more oxidative stress in combination than PMNB or SAHA monotherapy. In animal models, PMNB-SAHA showed a higher survival rate than that of monotherapy. This study is the first to report the synergistic antibacterial effect of PMNB-SAHA therapy against MDR Gram-negative bacteria. Further clinical research is needed to confirm the results.


Asunto(s)
Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Polimixina B/farmacología , Vorinostat/farmacología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/crecimiento & desarrollo , Animales , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Combinación de Medicamentos , Sinergismo Farmacológico , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/crecimiento & desarrollo , Escherichia coli K12/efectos de los fármacos , Escherichia coli K12/crecimiento & desarrollo , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/crecimiento & desarrollo , Larva/efectos de los fármacos , Larva/microbiología , Longevidad/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo
10.
J Microbiol Immunol Infect ; 53(5): 731-738, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30638785

RESUMEN

BACKGROUND/PURPOSES: Treatment of Staphylococcus aureus infections is challenging owing to widespread multidrug resistance. There is now considerable interest in the potential of combination therapies. Although linezolid/fosfomycin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of S. aureus infections. METHODS: The antimicrobial activity of linezolid and fosfomycin alone and in combination was assessed versus four S. aureus. Synergy studies were performed using the microtitre plate chequerboard assay and time-kill methodology. The in vivo activity of linezolid/fosfomycin combination was assessed using a G. mellonella larvae model. RESULTS: The combination of linezolid and fosfomycin was synergistic and bacteriostatic against four tested strains. Treatment of G. mellonella larvae infected with lethal doses of S. aureus resulted in significantly enhanced survival rates when low-dose of combination has no significant differences with high-dose combination (P > 0.05), G. mellonella hemolymph burden of S. aureus suggest that combination therapy with rapid and sustained bacteriostatic activity compared monotherapy. CONCLUSION: This work indicated that linezolid combination with fosfomycin has synergistic effect against S. aureus in vitro and in an experimental G. mellonella model, and it suggests that high-dose of linezolid and fosfomycin may not necessary.


Asunto(s)
Antibacterianos/uso terapéutico , Fosfomicina/uso terapéutico , Linezolid/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Pruebas de Sensibilidad Microbiana , Mariposas Nocturnas
11.
Nanoscale Res Lett ; 14(1): 177, 2019 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-31139948

RESUMEN

Non-volatile memory (NVM) will play a very important role in the next-generation digital technologies, including the Internet of things. The metal-oxide memristors, especially based on HfO2, have been favored by lots of researchers because of its simple structure, high integration, fast operation speed, low power consumption, and high compatibility with advanced (complementary metal oxide silicon) CMOS technologies. In this paper, a 20-level stable resistance states Al-doped HfO2-based memristor is presented. Its cycles endurance, data retention time, and resistance ratio are larger than 103, > 104 s, and > 10, respectively.

12.
J Microbiol Immunol Infect ; 51(1): 70-75, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26906264

RESUMEN

BACKGROUND/PURPOSE: To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further. METHODS: The antimicrobial activity of colistin alone and in combination with imipenem was assessed versus an imipenem-susceptible isolate, E. cloacae GN1059, or an imipenem-resistant strain, E. cloacae GN0791, isolated in Anhui, China. The potential synergy of imipenem-colistin was evaluated using a checkerboard assay, as well as static time-kill experiments at 1× and 2× minimum inhibitory concentration (MIC). A simple invertebrate model (Galleria mellonella) was developed to assess the in vivo efficacy of imipenem-colistin in treating E. cloacae infection. RESULTS: In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of ≤ 0.5) was observed between imipenem and colistin for both isolates tested. In time-kill assays, the combination of imipenem-colistin at 1× or 2× MIC resulted in complete killing of both strains. In the G. mellonella larvae model infected with lethal doses of E. cloacae, the combination therapy led to significantly increased survival of the larvae as compared with imipenem or colistin monotherapy alone (p < 0.05). CONCLUSION: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.


Asunto(s)
Antibacterianos/farmacología , Colistina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Imipenem/farmacología , Lepidópteros/efectos de los fármacos , Animales , China , Sinergismo Farmacológico , Quimioterapia Combinada , Enterobacter cloacae/efectos de los fármacos , Enterobacter cloacae/aislamiento & purificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Humanos , Larva/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Modelos Animales , Factores de Tiempo
13.
Zhongguo Zhong Yao Za Zhi ; 42(7): 1277-1280, 2017 Apr.
Artículo en Chino | MEDLINE | ID: mdl-29052386

RESUMEN

In order to develop and utilize the macrofungi in Heilongjiang province, numerous literatures have been investigated to make a comprehensive analysis of the number of known species of fungi in Heilongjiang province. There exists a total of 546 species of macrofungus in Heilongjiang province belonging to 53 families and 13 orders of 6 classes and 2 subdivisions. And its application value is classified, summarized and reviewed. Three hundred and twenty kinds of edible fungi, 214 species of fungi with medicinal value, medicinal value in the anti-cancer effects of 167 species of fungi, 141 wood rot fungi, 141 species of ectomycorrhizal fungi, 88 poisonous species, 67 macrofungus which are not clarified whether could be edible or toxic. It shows a broad prospects for development and utilization of macrofungus resources in Heilongjiang province.


Asunto(s)
Hongos , Materia Medica/farmacología , Medicina Tradicional China , Micorrizas
14.
Environ Technol ; 37(9): 1045-53, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26508265

RESUMEN

Anaerobic/anoxic biodegradation of hydrocarbons offers an attractive approach to the removal of these compounds from polluted environments such as aquifers, aquatic sediments, submerged soils and subsurface soils. The application of nitrate was investigated to accelerate the degradation of gasoline components such as mono-aromatic hydrocarbons and total petroleum hydrocarbons (TPH) in soil by indigenous microorganisms under anoxic condition. The addition of nitrate had little effect on the degradation of mono-aromatic hydrocarbons m- & p-xylene, o-xylene, sec-butylbenzene and 1,2,4-trimethylbenzene, but facilitated the degradation of TPH (C6-C12) and mono-aromatic hydrocarbons toluene and ethylbenzene markedly. Furthermore, the more nitrate added, the higher the percentage of toluene, ethylbenzene and TPH (C6-C12) degraded after 180 days of anoxic incubation. Microorganisms capable of degrading toluene, ethylbenzene and TPH (C6-C12) with nitrate as the electron acceptor under anaerobic/anoxic condition are composed predominantly of Alpha-, Beta-, Gamma- or Delta-proteobacteria. Beta- and Gamma-proteobacteria were the main components of indigenous microorganisms, and accounted for 83-100% of the total amount of indigenous microorganisms in soil used in this study. Furthermore, the total amount of indigenous microorganisms increased with nitrate added. The addition of nitrate stimulated the growth of indigenous microorganisms, and therefore facilitated the degradation of toluene, ethylbenzene and TPH (C6-C12).


Asunto(s)
Gasolina/análisis , Hidrocarburos Aromáticos/análisis , Nitratos/metabolismo , Proteobacteria/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/análisis , Suelo/química , Anaerobiosis , Derivados del Benceno/análisis , Derivados del Benceno/aislamiento & purificación , Derivados del Benceno/metabolismo , Biodegradación Ambiental , Hidrocarburos Aromáticos/aislamiento & purificación , Hidrocarburos Aromáticos/metabolismo , Petróleo/análisis , Petróleo/metabolismo , Contaminantes del Suelo/aislamiento & purificación , Contaminantes del Suelo/metabolismo , Tolueno/análisis , Tolueno/aislamiento & purificación , Tolueno/metabolismo
15.
Chin Med J (Engl) ; 128(14): 1969-76, 2015 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-26168840

RESUMEN

OBJECTIVE: To review the origin, diagnosis, treatment and public health concern of New Delhi metallo-ß-lactamase (NDM)-producing bacteria. DATA SOURCES: We searched database for studies published in English. The database of PubMed from 2007 to 2015 was used to conduct a search using the keyword term "NDM and Acinetobacter or Enterobacteriaceae or Pseudomonas aeruginosa." STUDY SELECTION: We collected data including the relevant articles on international transmission, testing methods and treatment strategies of NDM-positive bacteria. Worldwide NDM cases were reviewed based on 22 case reports. RESULTS: The first documented case of infection caused by bacteria producing NDM-1 occurred in India, in 2008. Since then, 13 blaNDM variants have been reported. The rise of NDM is not only due to its high rate of genetic transfer among unrelated bacterial species, but also to human factors such as travel, sanitation and food production and preparation. With limited treatment options, scientists try to improve available therapies and create new ones. CONCLUSIONS: In order to slow down the spread of these NDM-positive bacteria, a series of measures must be implemented. The creation and transmission of blaNDM are potentially global health issues, which are not issues for one country or one medical community, but for global priorities in general and for individual wound care practitioners specifically.


Asunto(s)
Salud Pública , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple , Enterobacteriaceae/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos
16.
J Antimicrob Chemother ; 67(11): 2700-6, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22809703

RESUMEN

OBJECTIVES: To test the mutant selection window (MSW) hypothesis with Staphylococcus aureus exposed to vancomycin in an animal model and to compare in vivo and in vitro exposures that restrict the enrichment of resistant mutants. METHODS: Local infection with S. aureus was established in rabbits, and the infected animals were treated with various doses of twice-daily vancomycin (half-life 6 h) for 3 consecutive days to provide antibiotic concentrations below the MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC. Changes in susceptibility and the numbers of surviving organisms were monitored daily on agar plates containing 2× and 4× MIC of vancomycin. RESULTS: S. aureus lost vancomycin susceptibility when drug concentrations at the site of infection fluctuated between the lower and upper boundaries of the MSW, defined in vitro as the MIC(99) and the MPC, respectively. Both boundaries were determined in vitro, before starting animal studies. The value at which resistant mutants are not enriched in vivo was estimated as an AUC(24)/MPC value of ∼15 h, where AUC(24) is the area under the drug concentration time curve in a 24 h interval. The estimated anti-mutant AUC/MIC ratio in vivo was ≥200 h. CONCLUSIONS: These findings support the MSW hypothesis and the anti-mutant AUC/MIC ratio estimated in vivo is consistent with that reported in in vitro studies. Keeping vancomycin concentrations above the MPC or AUC(24)/MPC >15 h is a straightforward way to restrict the acquisition of resistance.


Asunto(s)
Antibacterianos/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Resistencia a la Vancomicina , Vancomicina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Femenino , Pruebas de Sensibilidad Microbiana , Conejos , Factores de Tiempo
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