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1.
Mikrobiyol Bul ; 55(2): 125-145, 2021 Apr.
Artigo em Turco | MEDLINE | ID: mdl-33882647

RESUMO

Biofilms are often responsible for the difficulties in the treatment of infectious diseases due to their properties that facilitate escape from antibiotic effect and their antiphagocytic effects. At least 65% of all infectious diseases are associated with biofilm-forming bacteria. As Staphylococcus aureus and Staphylococcus epidermidis are among the most common agents of hospital infections and the infections are mostly biofilm-related, they pose an important problem. In infectious isolates, the minimum biofilm eradication concentration (MBEK) values of biofilm forms are much higher than the minimum inhibition concentration (MIC) values of planktonic forms. This situation requires the use of much higher doses of antibiotics in the treatment of infections and causes an increase in antibiotic resistance. The N-acetylcysteine (NAC) molecule is known to be effective against biofilm by disrupting mature biofilms and reducing the adhesion of bacteria to surfaces. In this study, it was aimed to demonstrate i) the biofilm-forming abilities ii) the change in ampicillin and vancomycin MIC values in the presence of NAC molecules, iii) the change in the MBEK values of these antibiotics in the presence of NAC molecule and iv) the change in the expression levels of genes thought to be related to biofilm formation in the presence of the NAC molecule among S.aureus (n= 38) and S.epidermidis (n= 12) isolates isolated from various clinical specimens in Trakya University Health Research and Application Center. In this study, microplate crystal violet method was used to demonstrate the biofilm formation in staphylococci. Broth microdilution and checkerboard method were used to demonstrate the change in the presence of NAC molecule of the MIC and MBEC values of ampicillin and vancomycin. The effect of NAC on the expression of intercellular binding proteins A and D (icaA, icaD) and Staphylococcus regulatory protein A (sarA) genes, which are the genes involved in biofilm formation in staphylococci, was determined by quantitative real-time Polymerase Chain Reaction (qRt-PCR) method. The Student-t test was used to compare the control and experimental groups (concentrations detected with synergy and additive effect); p˂ 0.05 was accepted as the limit value of significance. In this study, when the NAC molecule was used together with ampicillin and vancomycin, it was determined that this combination lowers the MIC values of staphylococcus isolates and staphylococcal biofilm MBEK values; and also the expression levels of icaA, icaD and sarA which were effective in biofilm formation in staphylococci have not changed and decreased. As a result, in this study, it has been determined that the NAC molecule can be a new alternative for combined drug therapy and is promising in terms of bringing a new approach to treatment. In addition, it is thought that it is possible to use the NAC molecule together with different microorganisms and antimicrobial agents, and the results obtained in this study are considered to be guiding for further studies on this subject.


Assuntos
Antibacterianos , Infecções Estafilocócicas , Antibacterianos/farmacologia , Biofilmes , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/genética , Vancomicina/farmacologia
2.
Lett Appl Microbiol ; 72(5): 604-609, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33539564

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) with reduced sensitivity to vancomycin (VAN) has caused many clinical cases of VAN treatment failure, but the molecular mechanism underlying the reduced sensitivity to VAN is still unclear. We isolated a heterogeneous VAN-intermediate Staphylococcus aureus (hVISA), which was also a MRSA strain with reduced sensitivity to VAN. To investigate the molecular mechanism underlying the reduced sensitivity to VAN exhibited by the hVISA strain, we compared the hVISA strain with a VAN-sensitive MRSA strain, known as the N315 strain. The images captured by transmission electron microscopy showed that the cell wall of the hVISA strain was significantly thicker than that of the N315 strain (36·72 ± 1·04 nm vs 28·15 ± 1·25 nm, P < 0·05), and the results of real-time quantitative PCR analysis suggested that the expression levels of the cell wall thickness related genes (glmS, vraR/S, sgtB, murZ and PBP4) of the hVISA strain were significantly higher than those of the N315 strain (P < 0·05). In conclusion, this study indicated that the upregulation of the expression of the genes related to cell wall synthesis might be the molecular mechanism underlying the cell wall thickening of the hVISA strain and might be related to its resistance to VAN.


Assuntos
Parede Celular/metabolismo , Parede Celular/fisiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Resistência a Vancomicina/genética , /crescimento & desenvolvimento , Antibacterianos/farmacologia , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Regulação para Cima/genética , Vancomicina/farmacologia
3.
BMC Infect Dis ; 21(1): 153, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549035

RESUMO

BACKGROUND: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. METHODS: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 µg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 µg/mL compared to those at 15-20 µg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality. CONCLUSIONS: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.


Assuntos
Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos , Vancomicina/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Adulto , Antibacterianos/farmacologia , Área Sob a Curva , Bacteriemia/tratamento farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Razão de Chances , Segurança , Infecções Estafilocócicas/tratamento farmacológico , Falha de Tratamento , Vancomicina/farmacologia
4.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33448923

RESUMO

Introduction. There is an urgent need for effective therapies against bacterial infections, especially those caused by antibiotic-resistant Gram-negative pathogens.Hypothesis. Synergistic combinations of existing antimicrobials show promise due to their enhanced efficacies and reduced dosages which can mitigate adverse effects, and therefore can be used as potential antibacterial therapy.Aim. In this study, we sought to characterize the in vitro interaction of 5-nitrofurans, vancomycin and sodium deoxycholate (NVD) against pathogenic bacteria.Methodology. The synergy of the NVD combination was investigated in terms of growth inhibition and bacterial killing using checkerboard and time-kill assays, respectively.Results. Using a three-dimensional checkerboard assay, we showed that 5-nitrofurans, sodium deoxycholate and vancomycin interact synergistically in the growth inhibition of 15 out of 20 Gram-negative strains tested, including clinically significant pathogens such as carbapenemase-producing Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, and interact indifferently against the Gram-positive strains tested. The time-kill assay further confirmed that the triple combination was bactericidal in a synergistic manner.Conclusion. This study demonstrates the synergistic effect of 5-nitrofurans, sodium deoxycholate and vancomycin against Gram-negative pathogens and highlights the potential of the combination as a treatment for Gram-negative and Gram-positive infections.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Ácido Desoxicólico/farmacologia , Sinergismo Farmacológico , Nitrofuranos/farmacologia , Vancomicina/farmacologia
5.
Adv Mater ; 33(8): e2005477, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33475193

RESUMO

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.


Assuntos
Antibacterianos/síntese química , Materiais Biomiméticos/síntese química , Óxidos/síntese química , Peroxidase/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Materiais Biomiméticos/farmacologia , Catálise , Humanos , Peróxido de Hidrogênio/metabolismo , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Simulação de Dinâmica Molecular , Molibdênio/farmacologia , Óxidos/farmacologia , Peroxidase/metabolismo , Esterilização , Vancomicina/farmacologia
6.
Lett Appl Microbiol ; 72(5): 535-541, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33421175

RESUMO

Exudative epidermatitis or greasy pig disease (GPD) is a contagious disease of pig and endemic worldwide caused by toxigenic strains under genus Staphylococcus. The present study reported an outbreak of GPD in Champhai district of Mizoram adjoining to the southern border of Myanmar. A total of 60 samples were collected from 22 clinically affected animals and processed for isolation and identification of Staphylococcus spp. All the isolates were subjected to antimicrobial sensitivity assay, biofilm production assay and detection of virulence genes, biofilm genes and mec genes followed by cloning and sequencing for phylogenetic analysis. A total of 44 staphylococci belonged to four species (S. sciuri, S. aureus,S. lentus, and S. hyicus) were isolated. Majority of the isolates were multidrug resistant with maximum resistance against ampicillin, penicillin including vancomycin. None of the S. hyicus isolates was methicillin resistant (MRSH) but 66·67% isolates were MRSA. By PCR, mecA gene was detected in S. aureus (n = 2), S. sciuri (n = 4) and S. lentus (n = 3). Biofilm associated gene icaD was detected in S. aureus (n = 3), S. sciuri (n = 5), S. hyicus (n = 4) and S. lentus (n = 6). The exfoliative toxin genes (ehxB, shetA and tsst1) were detected in S. hyicus (n = 3) and S. aureus (n = 1) isolates. All the isolates were closely related with the isolates from pigs of China, Germany, Japan and USA. The pathogens might be transmitted through illegal migration of pigs from Myanmar to India.


Assuntos
Epidermite Exsudativa do Suíno/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/veterinária , Staphylococcus hyicus/isolamento & purificação , Staphylococcus/isolamento & purificação , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Epidermite Exsudativa do Suíno/microbiologia , Índia/epidemiologia , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética , Penicilinas/farmacologia , Filogenia , Infecções Estafilocócicas/epidemiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética , Staphylococcus hyicus/efeitos dos fármacos , Staphylococcus hyicus/genética , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/microbiologia , Vancomicina/farmacologia , Virulência
7.
Am J Sports Med ; 49(2): 426-434, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33406371

RESUMO

BACKGROUND: The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft. PURPOSE: To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression. RESULTS: Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05). CONCLUSION: Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment. CLINICAL RELEVANCE: Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais/efeitos dos fármacos , Tendões dos Músculos Isquiotibiais/transplante , Vancomicina/farmacologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Apoptose , Humanos , Técnicas de Cultura de Tecidos , Transplante Autólogo
8.
Int J Med Microbiol ; 311(2): 151473, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33445057

RESUMO

With the treatment failure by vancomycin and poor clinical outcomes, the emergence and spread of vancomycin intermediate-resistant Staphylococcus aureus (VISA) has raised more concerns in recent years. While most VISA strains are isolated from methicillin-resistant S. aureus (MRSA), the mechanism underlying the generation of VISA from methicillin-susceptible S. aureus (MSSA) is still largely unknown. Here, we identified a total of 10 mutations in 9 genes through comparative genome analysis from laboratory-derived VISA strain. We verified the role of a novel mutation of WalK (I237T) and our results further indicated that the introduction of WalK (I237T) by allelic replacement can confer vancomycin resistance in MSSA with common VISA characteristics, including thickened cell walls, reduced autolysis, and attenuated virulence. Consistent with these phenotypes, real-time quantitative reverse transcription-PCR revealed the altered expression of several genes associated with cell wall metabolism and virulence control. In addition, electrophoretic mobility shift assay indicated that WalR can directly bind to the promoter regions of oatA, sle1, and mgt, fluorescence-based promoter activity and ß-galactosidase assays revealed WalK (I237T) can alter promoter activities of oatA, mgt, and sle1, thus regulating genes expression. These findings broaden our understanding of the regulatory network by WalKR system and decipher the molecular mechanisms of developmental VISA resistance in MSSA with point mutations.


Assuntos
Genes Bacterianos , Mutação , Staphylococcus aureus/genética , Resistência a Vancomicina/genética , Antibacterianos/farmacologia , Hibridização Genômica Comparativa , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia
9.
Int J Biol Macromol ; 169: 330-341, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310092

RESUMO

Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCM-DMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.


Assuntos
Endoftalmite/tratamento farmacológico , Polietilenoimina/análogos & derivados , Vancomicina/farmacologia , Antibacterianos/farmacologia , Linhagem Celular , Portadores de Fármacos , Liberação Controlada de Fármacos , Olho/efeitos dos fármacos , Humanos , Ácido Hialurônico/metabolismo , Ácido Hialurônico/farmacologia , Nanopartículas , Tamanho da Partícula , Polietilenoimina/química , Polietilenoimina/farmacologia , Vancomicina/química
10.
Methods Mol Biol ; 2223: 281-293, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226601

RESUMO

Allergic disease is on the rise and yet the underlying cause and risk factors are not fully understood. While lifesaving in many circumstances, the use of antibiotics and the subsequent disruption of the microbiome are positively correlated with the development of allergies. Here, we describe the use of the antibiotic vancomycin in combination with the papain-induced mouse model of allergic disease that allows for the assessment of microbiome perturbations and the impact on allergy development.


Assuntos
Antibacterianos/farmacologia , Asma/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Coloração e Rotulagem/métodos , Vancomicina/farmacologia , Animais , Animais Recém-Nascidos , Asma/induzido quimicamente , Asma/genética , Asma/microbiologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Modelos Animais de Doenças , Amarelo de Eosina-(YS)/química , Feminino , Hematoxilina/química , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Papaína/administração & dosagem , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia
11.
Carbohydr Polym ; 254: 117465, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357924

RESUMO

Designing multifunctional surfaces is key to develop advanced materials for orthopedic applications. In this study, we design a double-layer coating, assembled onto the completely regular titania nanotubes (cRTNT) array. Benefiting from the biological and topological characteristics of chitosan nanofibers (CH) and reduced graphene oxide (RGO) through a unique assembly, the designed material features promoted osteoblast cell viability, prolonged antibiotic release profile, as well as inhibited bacterial biofilm formation. The synergistic effect of RGO and CH on the biological performance of the surface is investigatSed. The unique morphology of the nanofibers leads to the partial coverage of RGO-modified nanotubes, providing an opportunity to access the sublayer properties. Another merit of this coating lies in its morphological similarity to the extracellular matrix (ECM) to boost cellular performance. According to the results of this study, this platform holds promising advantages over the bare and bulk biopolymer-modified TNTs.


Assuntos
Quitosana/síntese química , Materiais Revestidos Biocompatíveis/química , Grafite/química , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Titânio/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Cinética , Nanocompostos/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologia
12.
Anal Chem ; 93(3): 1569-1577, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33369400

RESUMO

Herein, an interference-free surface-enhanced Raman scattering (SERS) platform with a "sandwich" structure has been developed for reliable detection and photothermal killing of bacteria with whole blood as the real sample. The multifunctional platform comprised a plasmonic gold film (pAu) functionalized with bacteria-capturing units of 4-mercaptophenylboronic acid and internal reference of 4-mercaptobenzonitrile as the SERS substrate and vancomycin-modified core (gold)-shell (Prussian blue) nanoparticles (Au@PB@Van NPs) as the SERS tag. The detected SERS signals were from the Raman-silent region where no background signals occurred from biological sources, eliminating the interference and improving the detection sensitivity and accuracy. As a proof-of-concept, model bacterial strain, Staphylococcus aureus, was captured and detected in the whole blood samples. Furthermore, high antibacterial efficiency of approximately 100% was reached under the synergistic photothermal effect from pAu and Au@PB@Van NPs. This study provides a new avenue for bacteria detection in real samples and their subsequent in situ elimination.


Assuntos
Antibacterianos/química , Bacillus subtilis/isolamento & purificação , Escherichia coli/isolamento & purificação , Salmonella typhimurium/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Vancomicina/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Ácidos Borônicos/química , Escherichia coli/efeitos dos fármacos , Ouro/química , Humanos , Nitrilos/química , Tamanho da Partícula , Processos Fotoquímicos , Salmonella typhimurium/efeitos dos fármacos , Análise Espectral Raman , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfidrila/química , Propriedades de Superfície , Temperatura , Vancomicina/farmacologia
13.
PLoS Biol ; 18(12): e3000987, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33332354

RESUMO

The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantitative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogen Enterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations of E. faecium. We performed a cohort study in which the daptomycin resistance of E. faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance of E. faecium from the off-target population was on average 50% higher than resistance in the control group (n = 428 clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. In patients where multiple samples over time were available, a wide variability in temporal dynamics were observed, from long-term maintenance of resistance to rapid return to sensitivity after daptomycin treatment stopped. Sequencing of isolates from a subset of patients supports the argument that selection occurs within patients. Our results demonstrate that off-target gastrointestinal populations rapidly respond to intravenous antibiotic exposure. Focusing on the off-target evolutionary dynamics may offer novel avenues to slow the spread of antibiotic resistance.


Assuntos
Daptomicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/fisiologia , Adulto , Antibacterianos/uso terapêutico , Estudos de Coortes , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/metabolismo , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Filogenia , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/metabolismo
14.
Int J Nanomedicine ; 15: 8437-8449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162754

RESUMO

Background: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand. Methods: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages. Results: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls. Conclusion: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.


Assuntos
Antibacterianos/farmacologia , Sistemas de Liberação de Medicamentos , Espaço Intracelular/microbiologia , Macrófagos/microbiologia , Nanopartículas/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Lipídeos/química , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/efeitos dos fármacos , Tamanho da Partícula , Polímeros/química , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia
15.
BMC Infect Dis ; 20(1): 816, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167886

RESUMO

BACKGROUND: The prevalence of Staphylococcus aureus varies depending on the healthcare facility, region and country. To understand its genetic diversity, transmission, dissemination, epidemiology and evolution in a particular geographical location, it is important to understand the similarities and variations in the population being studied. This can be achieved by using various molecular characterisation techniques. This study aimed to provide detailed molecular characterisation of South African mecA-positive S. aureus blood culture isolates by describing the SCCmec types, spa types and to lesser extent, the sequence types obtained from two consecutive national surveillance studies. METHODS: S. aureus blood culture isolates from a national laboratory-based and enhanced surveillance programme were identified and antimicrobial susceptibility testing was performed using automated systems. A real-time PCR assay confirmed the presence of the methicillin-resistance determinant, mecA. Conventional PCR assays were used to identify the SCCmec type and spa type, which was subsequently analysed using the Ridom StaphType™ software. Multilocus sequence typing was performed on selected isolates using conventional methods. MRSA clones were defined by their sequence type (ST), SCCmec type and spa type. RESULTS: A detailed description of findings is reported in this manuscript. SCCmec type III predominated overall followed by type IV. A total of 71 different spa types and 24 novel spa types were observed. Spa type t037 was the most common and predominated throughout followed by t1257. Isolates were multidrug resistant; isolates belonging to all SCCmec types were resistant to most of the antibiotics with the exception of type I; isolates with spa type t045 showed resistance to all antibiotics except vancomycin. The most diverse SCCmec-spa type complex was composed of the SCCmec type IV element and 53 different spa types. CONCLUSION: Although ST data was limited, thereby limiting the number of clones that could be identified, the circulating clones were relatively diverse.


Assuntos
Proteínas de Bactérias/genética , Variação Genética , Sequências Repetitivas Dispersas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/genética , Infecções Estafilocócicas/epidemiologia , Proteína Estafilocócica A/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/sangue , Hemocultura , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Meticilina/farmacologia , Meticilina/uso terapêutico , Resistência a Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Proteínas de Ligação às Penicilinas/sangue , Reação em Cadeia da Polimerase em Tempo Real , África do Sul/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico
16.
Anal Chem ; 92(19): 13396-13404, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32867467

RESUMO

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.


Assuntos
Bactérias/química , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/síntese química , Nanotecnologia/métodos , Antibacterianos/farmacologia , Aptâmeros de Nucleotídeos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/microbiologia , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Microbiologia de Alimentos/métodos , Humanos , Nanopartículas , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/microbiologia , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao Infravermelho , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/química , Vancomicina/farmacologia
17.
Int J Nanomedicine ; 15: 4779-4791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753866

RESUMO

Background: Considering the timeline required for the development of novel antimicrobial drugs, increased attention should be given to repurposing old drugs and improving antimicrobial efficacy, particularly for chronic infections associated with biofilms. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are common causes of biofilm-associated infections but produce different biofilm matrices. MSSA biofilm cells are typically embedded in an extracellular polysaccharide matrix, whereas MRSA biofilms comprise predominantly of surface proteins and extracellular DNA (eDNA). Nanoparticles (NPs) have the potential to enhance the delivery of antimicrobial agents into biofilms. However, the mechanisms which influence the interactions between NPs and the biofilm matrix are not yet fully understood. Methods: To investigate the influence of NPs surface chemistry on vancomycin (VAN) encapsulation and NP entrapment in MRSA and MSSA biofilms, mesoporous silica nanoparticles (MSNs) with different surface functionalization (bare-B, amine-D, carboxyl-C, aromatic-A) were synthesised using an adapted Stöber method. The antibacterial efficacy of VAN-loaded MSNs was assessed against MRSA and MSSA biofilms. Results: The two negatively charged MSNs (MSN-B and MSN-C) showed a higher VAN loading in comparison to the positively charged MSNs (MSN-D and MSN-A). Cellular binding with MSN suspensions (0.25 mg mL-1) correlated with the reduced viability of both MSSA and MRSA biofilm cells. This allowed the administration of low MSNs concentrations while maintaining a high local concentration of the antibiotic surrounding the bacterial cells. Conclusion: Our data suggest that by tailoring the surface functionalization of MSNs, enhanced bacterial cell targeting can be achieved, leading to a novel treatment strategy for biofilm infections.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes , Staphylococcus aureus Resistente à Meticilina/fisiologia , Nanopartículas/química , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Espectroscopia de Prótons por Ressonância Magnética , Dióxido de Silício/química , Vancomicina/farmacologia
18.
Saudi Med J ; 41(7): 753-756, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601645

RESUMO

Elizabethkingia meningoseptica (E. meningoseptica ) are Gram-negative bacteria commonly associated with nosocomial infections in neonates. This is a case study of E. meningoseptica, presented as meningitis and sepsis in a term baby. The female infant was born by vaginal delivery at 37 weeks gestational age. The case was peculiar because the baby was neither premature nor immuno-compromised, which are known risk factors for E. meningoseptica infection. The onset began on the second day of the neonate's life. On day 3, peripheral blood culture and cerebrospinal fluid findings isolated a gram-negative bacteria identified as E. meningoseptica. The first-line antibiotics therapy was changed to ciprofloxacin, vancomycin, and rifampicin, based on the laboratory determination of antimicrobial sensitivity. The patient's clinical condition improved, although post hemorrhagic ventricular dilatation was revealed by imaging studies. Clinicians should possess proper awareness of the antibiotic sensitivity of E. meningoseptica, as it is important in preventing high rates of morbidity and mortality.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacino/administração & dosagem , Infecções por Flavobacteriaceae , Flavobacteriaceae , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Rifampina/administração & dosagem , Sepse/tratamento farmacológico , Sepse/microbiologia , Vancomicina/administração & dosagem , Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Flavobacteriaceae/efeitos dos fármacos , Flavobacteriaceae/isolamento & purificação , Humanos , Recém-Nascido , Rifampina/farmacologia , Arábia Saudita , Resultado do Tratamento , Vancomicina/farmacologia
19.
J Med Microbiol ; 69(8): 1095-1099, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32639226

RESUMO

Introduction. Empirical vancomycin (VAN) treatment failure for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia, with significantly higher mortality, has been reported for MRSA strains with reduced VAN susceptibility.Aim. Our goal was to study the effect of sub-culture on VAN minimum inhibitory concentration (MIC) values compared to direct susceptibility of MRSA-positive blood cultures.Methodology. Using 19 MRSA-positive blood cultures and 19 seeded MRSA-positive blood cultures, we compared the VAN MICs from direct susceptibility testing of MRSA-positive blood cultures and MRSA sub-cultured from positive blood cultures.Results. In comparing direct VAN MICs from MRSA-positive blood cultures and standard agar dilution, nearly half of the MICs from agar dilution were lower, with one sample decreasing from 1.5 to 0.75 µg ml-1. Furthermore, in seeded blood cultures, 80 % or more showed lower values from standard agar dilution compared to direct VAN MICs.Conclusion. Our results reveal a trend towards lower MICs after positive blood culture isolates are sub-cultured. Some clinical failures among MRSA infections treated with VAN may result from this phenomenon.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Hemocultura/métodos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Infecções Estafilocócicas/microbiologia , Vancomicina/farmacologia , Animais , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ovinos
20.
J Urol ; 204(6): 1249-1255, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32602771

RESUMO

PURPOSE: We evaluate the prevalent microorganisms, antibiotic sensitivity patterns and associated outcomes in patients with Fournier's gangrene. MATERIALS AND METHODS: A retrospective chart review of patients with Fournier's gangrene was conducted between October 2011 and April 2018 at our institution. Univariate analysis was performed using the independent t-test or Kruskal-Wallis H test for continuous variables and exact test for categorical variables. RESULTS: Of the 143 patients included in this study, wound culture was available in 131 (92%) patients with a median number of 3 microorganisms per wound. The most commonly grown pathogens were Staphylococcus species (66, 46%), Streptococcus species (53, 37%), Bacteroides species (34, 24%), Candida species (31, 22%), Escherichia coli (28, 20%) and Prevotella species (26, 18%). Most bacteria were sensitive to ampicillin-sulbactam, ceftriaxone, piperacillin-tazobactam, amikacin and cefepime, and resistant to ampicillin, trimethoprim-sulfamethoxazole, levofloxacin and clindamycin. Enterococcus faecalis and Streptococcus anginosus were resistant to vancomycin. The overall Fournier's gangrene mortality count was 14 (10%) patients. No association was noted between the type of infection and Fournier's gangrene severity index, length of hospital stay or mortality. CONCLUSIONS: At our institution Candida is a prevalent pathogen in the wound culture of patients with Fournier's gangrene. The resistance patterns for clindamycin and vancomycin are concerning. Addition of an antifungal agent to the empiric treatment should be considered based on clinical presentation.


Assuntos
Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Candida/isolamento & purificação , Gangrena de Fournier/microbiologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Desbridamento , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Feminino , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/mortalidade , Gangrena de Fournier/terapia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Pessoa de Meia-Idade , Períneo/microbiologia , Períneo/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária/estatística & dados numéricos , Vancomicina/farmacologia , Vancomicina/uso terapêutico
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