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1.
Biomed Res Int ; 2022: 7228259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187170

RESUMO

In addition to the physical barrier, the epidermis acts as a natural barrier against microbial proliferation. It is prone to bacterial infections on the skin and in the nose, such as Staphylococcus aureus, as well as a variety of other skin illnesses. Green nanomaterial production, which eliminates the use of harmful chemicals while simultaneously reducing time, is gaining popularity in the nanotechnology area. Using the leaf extract of the pharmacologically valuable plant Moringa oleifera, we described a green synthesis of ZnO NPs (zinc oxide nanoparticles). ZnO NPs had a particle size of 201.6 nm and a zeta potential of -56.80 mV, respectively. A novel aminoketone antibacterial medication was synthesized and tested for antibacterial activity using ZnO NPs as a phytocatalyst in this work. This method produces high yields while maintaining efficient and gentle reaction conditions. Moringa oleifera extract can reduce ZnO to ZnO NPs in a straightforward manner. FT-IR, 1H-NMR, 13C-NMR, mass spectra, elemental analysis, and morphological analysis were used to synthesize and describe the antibacterial medicines (1a-1g) and (2a-2g). In addition, antibacterial activity was evaluated against bacteria such as Enterococcus faecalis and Staphylococcus aureus, and compound 1c (63 µg/mL, E. faecalis) and compound 2e (0.12 µg/mL, S. aureus) were found to be very active when compared to other medications. mupirocin is used as a reference. In addition, studies of in silico molecular docking for the bacterial DsbA protein were conducted. The strong molecules 1c (-4.3 kcal/mol) and 2e (-5.1 kcal/mol) exhibit a high binding affinity through hydrogen bonding, according to docking tests.


Assuntos
Antibacterianos/síntese química , Moringa oleifera/química , Nanopartículas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Química Verde , Simulação de Acoplamento Molecular , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos
2.
J Mater Chem B ; 10(3): 456-467, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34982090

RESUMO

Bacterial infections and antibiotic resistance have become a global healthcare crisis. Herein, we designed and synthesized a series of cationic amphiphilic dendrons with cationic dendrons and hydrophobic alkyl chains for potential antibacterial applications. Our results showed that the antimicrobial activities of the cationic amphiphilic dendrons were highly dependent upon the length of the hydrophobic alkyl chain, whereas the number of cationic charges was less important. Among these cationic amphiphilic dendrons, a prime candidate was identified, which possessed excellent antimicrobial activity against various pathogens (minimum inhibitory concentrations of 9, 3, and 3 µg mL-1 for Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, respectively). Scanning electron microscopy and fluorescence microscopy analyses showed that it could disrupt the integrity of a pathogen's membrane, leading to cell lysis and death. In addition, in vitro bacteria-killing kinetics showed that it had rapid bactericidal efficiency. It also had excellent antimicrobial activities against MRSA in vivo and promoted wound healing. In general, the synthesized cationic amphiphilic dendrons, which exhibited rapid and broad-spectrum bactericidal activity, may have great potential in antimicrobial applications.


Assuntos
Antibacterianos/uso terapêutico , Dendrímeros/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Tensoativos/uso terapêutico , Animais , Antibacterianos/síntese química , Membrana Celular/efeitos dos fármacos , Dendrímeros/síntese química , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ratos , Infecções Cutâneas Estafilocócicas/patologia , Tensoativos/síntese química , Cicatrização/efeitos dos fármacos
3.
ACS Appl Mater Interfaces ; 13(41): 48403-48413, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34610742

RESUMO

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Incrustação Biológica/prevenção & controle , Materiais Revestidos Biocompatíveis/uso terapêutico , Cobre/uso terapêutico , Taninos/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/efeitos da radiação , Materiais Revestidos Biocompatíveis/toxicidade , Cobre/química , Cobre/efeitos da radiação , Cobre/toxicidade , Escherichia coli/efeitos dos fármacos , Raios Infravermelhos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Terapia Fototérmica , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Ratos Sprague-Dawley , Pele/patologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Taninos/química , Taninos/efeitos da radiação , Taninos/toxicidade
4.
ACS Appl Mater Interfaces ; 13(39): 47155-47162, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34565147

RESUMO

The excellent adhesion of mussels under wet conditions has inspired the development of numerous catechol-based wet adhesives. Nevertheless, the performance of catechol-based wet adhesive suffers from the sensitivity toward temperature, pH, or oxidation stimuli. Therefore, it is of great significance to develop non-catechol-based wet adhesives to fully recapitulate nature's dynamic function. Herein, a novel type of non-catechol-based wet adhesive is reported, which is readily formed by self-assembly of commercially available branched polyethylenimine and phosphotungstic acid in aqueous solution through the combination of electrostatic interaction and hydrogen bonding. This wet adhesive shows reversible, tunable, and strong adhesion on diverse substrates and further exhibits high efficacy in promoting biological wound healing. During the healing of the wound, the as-prepared wet adhesive also possesses inherent antimicrobial properties, thus avoiding inflammations and infections due to microorganism accumulation.


Assuntos
Adesivos/uso terapêutico , Antibacterianos/uso terapêutico , Hemostáticos/uso terapêutico , Ácidos Fosfóricos/uso terapêutico , Polietilenoimina/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Compostos de Tungstênio/uso terapêutico , Adesividade , Adesivos/química , Animais , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Hemostáticos/química , Ligação de Hidrogênio , Camundongos , Ácidos Fosfóricos/química , Polietilenoimina/química , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática , Compostos de Tungstênio/química , Água/química , Cicatrização/efeitos dos fármacos
5.
ACS Appl Mater Interfaces ; 13(37): 44041-44053, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34491724

RESUMO

Treatment of chronic wound infections caused by Gram-positive bacteria such as Staphylococcus aureus is highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid-glycine-glycine conjugate (A6) that self-assembles into a supramolecular viscoelastic hydrogel (A6 gel) suitable for topical applications. The A6 hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded A6 hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the A6 gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears S. aureus-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.


Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Portadores de Fármacos/química , Hidrogéis/química , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Ácidos Cólicos/síntese química , Ácidos Cólicos/química , Ciprofloxacina/química , Dipeptídeos/síntese química , Dipeptídeos/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Hidrogéis/síntese química , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Staphylococcus aureus/efeitos dos fármacos
6.
Mol Pharm ; 18(11): 4099-4110, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34554755

RESUMO

Skin and soft tissue infections require effective and sustained topical administration. Platensimycin (PTM) is a natural drug lead that targets bacterial fatty acid synthases and has a great potential to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the use of PTM against local MRSA infections, we prepared polyacrylamide hydrogels containing polyamidoamine (PAMAM)/PTM nanoparticles (NP-gel(PTM)) for the controlled release of PTM. NP-gel(PTM) can continuously inhibit the growth of MRSA and its biofilm formation in simulated drug flow models in vitro. In situ implantation of NP-gel(PTM) could treat MRSA-infected subcutaneous soft tissues without toxicity. For MRSA-infected skin wounds, NP-gel(PTM) not only showed strong anti-MRSA activity but also accelerated more wound healing than the widely used antibiotic mupirocin. Collectively, PTM is expected to be used in this safe and effective NP-gel delivery platform for the treatment of local infections, which might help to alleviate the current antibiotic resistance crisis.


Assuntos
Adamantano/administração & dosagem , Aminobenzoatos/administração & dosagem , Anilidas/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Adamantano/farmacocinética , Aminobenzoatos/farmacocinética , Anilidas/farmacocinética , Animais , Biofilmes/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Humanos , Hidrogéis/química , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Camundongos , Testes de Sensibilidade Microbiana , Poliaminas/química , Infecções Cutâneas Estafilocócicas/microbiologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia
7.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472332

RESUMO

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.


Assuntos
Anti-Inflamatórios/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/efeitos da radiação , Anti-Inflamatórios/toxicidade , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Luz , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Doadores de Óxido Nítrico/efeitos da radiação , Doadores de Óxido Nítrico/toxicidade , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Staphylococcus aureus/efeitos dos fármacos
8.
ACS Appl Mater Interfaces ; 13(34): 40302-40314, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34412471

RESUMO

Nanozyme has been regarded as one of the antibacterial agents to kill bacteria via a Fenton-like reaction in the presence of H2O2. However, it still suffers drawbacks such as insufficient catalytic activity in near-neutral conditions and the requirement of high H2O2 levels, which would minimize the side effects to healthy tissues. Herein, a mesoporous ceria hollow sphere/enzyme nanoreactor is constructed by loading glucose oxidase in the mesoporous ceria hollow sphere nanozyme. Due to the mesoporous framework, large internal voids, and high specific surface area, the obtained nanoreactor can effectively convert the nontoxic glucose into highly toxic hydroxyl radicals via a cascade catalytic reaction. Moreover, the generated glucose acid can decrease the localized pH value, further boosting the peroxidase-like catalytic performance of mesoporous ceria. The generated hydroxyl radicals could damage severely the cell structure of the bacteria and prevent biofilm formation. Moreover, the in vivo experiments demonstrate that the nanoreactor can efficiently eliminate 99.9% of bacteria in the wound tissues and prevent persistent inflammation without damage to normal tissues in mice. This work provides a rational design of a nanoreactor with enhanced catalytic activity, which can covert glucose to hydroxyl radicals and exhibits potential applications in antibacterial therapy.


Assuntos
Antibacterianos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Antibacterianos/química , Antibacterianos/farmacologia , Biocatálise , Biofilmes/efeitos dos fármacos , Cério/química , Cério/uso terapêutico , Enzimas Imobilizadas/química , Enzimas Imobilizadas/uso terapêutico , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Glucose/química , Glucose Oxidase/química , Glucose Oxidase/uso terapêutico , Peróxido de Hidrogênio/química , Radical Hidroxila/metabolismo , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Porosidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
9.
ACS Appl Mater Interfaces ; 13(31): 37535-37544, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34324300

RESUMO

Combined therapeutic strategies for bacterial infection have attracted worldwide attention owing to their faster and more effective therapy with fewer side effects compared with monotherapy. In this work, gold-platinum nanodots (AuPtNDs) are simply and quickly synthesized by a one-step method. They not only exhibit powerful peroxidase-like activity but also confer a higher affinity for hydrogen peroxide (H2O2), which is 3.4 times that of horseradish peroxidase. Under 808 nm laser irradiation, AuPtNDs also have excellent photothermal conversion efficiency (50.53%) and strong photothermal stability. Excitingly, they can combat bacterial infection through the combination of chemodynamic and photothermal therapy. In vitro antibacterial results show that the combined antibacterial strategy has a broad-spectrum antibacterial property against both Escherichia coli (Gram negative, 97.1%) and Staphylococcus aureus (Gram positive, 99.3%). Animal experiments further show that nanodots can effectively promote the healing of bacterial infection wounds. In addition, owing to good biocompatibility and low toxicity, they are hardly traceable in the main organs of mice, which indicates that they can be well excreted through metabolism. These results reveal the application potential of AuPtNDs as a simple and magic multifunctional nanoparticle in antibacterial therapy and open up new applications for clinical anti-infective therapy in the near future.


Assuntos
Antibacterianos/uso terapêutico , Pontos Quânticos/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Catálise , Escherichia coli/efeitos dos fármacos , Ouro/química , Ouro/efeitos da radiação , Ouro/uso terapêutico , Ouro/toxicidade , Células HEK293 , Humanos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Terapia Fototérmica , Platina/química , Platina/efeitos da radiação , Platina/uso terapêutico , Platina/toxicidade , Pontos Quânticos/química , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
10.
ACS Appl Mater Interfaces ; 13(29): 33802-33811, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34282616

RESUMO

Antibiotic abuse resulted in the emergence of multidrug-resistant Gram-positive pathogens, which pose a severe threat to public health. It is urgent to develop antibiotic substitutes to kill multidrug-resistant Gram-positive pathogens effectively. Herein, the antibacterial dialdehyde nanocrystalline cellulose (DNC) was prepared and characterized. The antibacterial activity and biosafety of DNC were studied. With the increasing content of aldehyde groups, DNC exhibited high antibacterial activity against Gram-positive pathogens in vitro. DNC3 significantly reduced the amounts of methicillin-resistant Staphylococcus aureus (MRSA) on the skin of infected mice models, which showed low cytotoxicity, excellent skin compatibility, and no acute oral toxicity. DNC exhibited potentials as antibiotic substitutes to fight against multidrug-resistant bacteria, such as ingredients in salves to treat skin infection and other on-skin applications.


Assuntos
Antibacterianos/uso terapêutico , Celulose/análogos & derivados , Nanopartículas/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Linhagem Celular , Celulose/química , Celulose/uso terapêutico , Celulose/toxicidade , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Nanopartículas/química , Nanopartículas/toxicidade , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Infecções Cutâneas Estafilocócicas/patologia
11.
ACS Appl Mater Interfaces ; 13(28): 32716-32728, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34227797

RESUMO

Bacterial cellulose (BC) holds several unique properties such as high water retention capability, flexibility, biocompatibility, and high absorption capacity. All these features make it a potential material for wound healing applications. However, it lacks antibacterial properties, which hampers its applications for infectious wound healings. This study reported BC-based dressings containing ε-polylysine (ε-PL), cross-linked by a biocompatible and mussel-inspired polydopamine (PDA) for promoting infectious wound healing. BC membranes were coated with PDA by a simple self-polymerization process, followed by treating with different contents of ε-PL. The resulted membranes showed strong antibacterial properties against tested bacteria by both in vitro and in vivo evaluations. The membranes also exhibited hemocompatibility and cytocompatibility by in vitro investigations. Moreover, the functionalized membranes promoted infected wound healing using Sprague-Dawley rats as a model animal. A complete wound healing was observed in the group treated with functionalized membranes, while wounds were still open for control and pure BC groups in the same duration. Histological investigations indicated that the thickness of newborn skin was greater and smoother in the groups treated with modified membranes in comparison to neat BC or control groups. These results revealed that the functionalized membranes have great potential as a dressing material for infected wounds in future clinical applications.


Assuntos
Antibacterianos/uso terapêutico , Bandagens , Celulose/química , Polilisina/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Celulose/toxicidade , Escherichia coli/efeitos dos fármacos , Indóis/química , Indóis/uso terapêutico , Indóis/toxicidade , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Polilisina/análogos & derivados , Polilisina/toxicidade , Polímeros/química , Polímeros/uso terapêutico , Polímeros/toxicidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/patologia
12.
Protein Expr Purif ; 188: 105949, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34324967

RESUMO

PURPOSE: The production of alternative novel antimicrobial agents is considered an efficient way to cope with multidrug resistance among pathogenic bacteria. E50-52 and Ib-AMP4 antimicrobial peptides (AMPs) have illustrated great proven antibacterial effects. The aim of this study was recombinant production of these AMPs and investigation of their synergistic effects on methicillin-resistant Staphylococcus aureus (MRSA). METHOD: At first, the codon optimized sequences of the Ib-AMP4 (UniProt: 024006 (PRO_0000020721), and E50-52 (UniProtKB: P85148) were individually ligated into the pET-32α vector and transformed into E. coli. After the optimization of production and purification steps, the MIC (Minimum inhibitory concentration), time kill and growth kinetic tests of recombinant proteins were determined against MRSA. Finally, the in vivo wound healing efficiency was tested. RESULTS AND CONCLUSION: The recorded MIC of recombinant Trx-Ib-AMP4, Trx-E50-52 against MRSA bacterium were 0.375 and 0.0875 mg/mL respectively. The combination application of the produced AMPs by the checkerboard method confirmed their synergic activity. The results of the time-kill showed sharply decrease of the number of viable cells with over five time reductions in log10 CFU/mL by the combination of Trx-E50-52 and Trx-IbAMP4 at 2 × MIC within 240 min. The growth kinetic results confirmed the combination of Trx-E50-52 and Trx-IbAMP4 had much greater success in the reduction of over 50 % of MRSA suspensions' turbidity within the first hour. Wound healing assay and histological analysis of infected mice treated with Trx-Ib-AMP4 or Trx-E50-52 compared with those treated with a combination of Trx-Ib-AMP4 and Trx-E50-52 showed significant synergic effects.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Antibacterianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/genética , Clonagem Molecular , Sinergismo Farmacológico , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Masculino , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Ratos , Ratos Wistar , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Pele/efeitos dos fármacos , Pele/lesões , Pele/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/microbiologia , Ferimentos não Penetrantes/patologia
13.
Int J Biol Macromol ; 183: 447-456, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33932414

RESUMO

The preparation of ointments from natural compounds is essential for accelerating infected wounds. This study investigated the effects of topical uses of gold nanoparticles (Au)/perlite (Au/Perl) nanocomposites (NCs) by the help of Urtica dioica extract and its chitosan-capped derivative (Chit) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing in a mouse model. Furthermore, Au/Perl/Chit nanocomposite was prepared using protonated chitosan solution. The physicochemical properties of the as-synthesized nanocomposites were also investigated. The effects of Au/Perl/Chit NC were assessed by antibacterial, histopathological parameters as well as molecular evaluations. Then, they were compared with synthetic agent of mupirocin. The results revealed that Au/Perl NC was mesoporous and spherical in a range of 13-15 nm. Topical administration of Au/Perl/Chit ointment accelerated wound healing by reducing bacteria colonization and wound rate enhancing collagen biosynthesis and re-epithelialization, the expressions of IL-10, PI3K, AKT, bFGF, and COL1A genes, which is in agreement with the obtained results for mupirocin. In conclusion, the results strongly demonstrated that administration of ointments prepared from Au/Perl and Au/Perl/Chit nanocomposites stimulates MRSA-infected wound healing by decreasing the length of healing time and regulating PI3K/AKT/bFGF signaling pathway and is a promising candidate in stimulating MRSA-infected wound regeneration.


Assuntos
Óxido de Alumínio/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitosana/farmacologia , Compostos de Ouro/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Dióxido de Silício/farmacologia , Pele/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Urtica dioica/metabolismo , Cicatrização/efeitos dos fármacos , Óxido de Alumínio/metabolismo , Animais , Antibacterianos/metabolismo , Antioxidantes/metabolismo , Proliferação de Células/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/microbiologia , Fibroblastos/patologia , Compostos de Ouro/metabolismo , Química Verde , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanopartículas , Nanotecnologia , Transdução de Sinais , Dióxido de Silício/metabolismo , Pele/metabolismo , Pele/microbiologia , Pele/patologia , Infecções Cutâneas Estafilocócicas/metabolismo , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Fatores de Tempo
14.
Eur J Pharm Biopharm ; 160: 65-76, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33508436

RESUMO

Biofilm mediated infection caused by multi-drug resistant bacteria are difficult to treat since it protects the microorganisms by host defense system, making them resistant to antibiotics and other antimicrobial agents. Combating such type of nosocomial infection, especially in immunocompromised patients, is an urgent need and foremost challenge faced by clinicians. Therefore, antimicrobial photodynamic therapy (aPDT) has been intensely pursued as an alternative therapy for bacterial infections. aPDT leads to the generation of reactive oxygen species (ROS) that destroy bacterial cells in the presence of a photosensitizer, visible light and oxygen. Here, we elucidated a possibility of its clinical application by reducing the treatment time and exposing curcumin to 20 J/cm2 of blue laser light, which corresponds to only 52 s to counteract vancomycin resistant Staphylococcus aureus (VRSA) both in vitro and in vivo. To understand the mechanism of action, the generation of total reactive oxygen species (ROS) was quantified by 2'-7'-dichlorofluorescein diacetate (DCFH-DA) and the type of phototoxicity was confirmed by fluorescence spectroscopic analysis. The data showed more production of singlet oxygen, indicating type-II phototoxicity. Different anti-biofilm assays (crystal violet and congo red assays) and microscopic studies were performed at sub-MIC concentration of curcumin followed by treatment with laser light against preformed biofilm of VRSA. The result showed significant reduction in the preformed biofilm formation. Finally, its therapeutic potential was validated in skin abrasion wistar rat model. The result showed significant inhibition of bacterial growth. Furthermore, immunomodulatory analysis with rat serum was performed. A significant reduction in expression of proinflammatory cytokines TNF-α and IL-6 were observed. Hence, we conclude that curcumin mediated aPDT with 20 J/cm2 of blue laser treatment (for 52 s) could be used against multi-drug resistant bacterial infections and preformed biofilm formation as a potential therapeutic approach.


Assuntos
Anti-Infecciosos/administração & dosagem , Curcumina/administração & dosagem , Fotoquimioterapia/métodos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus Resistente à Vancomicina/efeitos dos fármacos , Administração Cutânea , Animais , Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/efeitos da radiação , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Biofilmes/efeitos da radiação , Modelos Animais de Doenças , Farmacorresistência Bacteriana Múltipla , Humanos , Lasers Semicondutores , Masculino , Testes de Sensibilidade Microbiana , Fotoquimioterapia/instrumentação , Ratos , Espécies Reativas de Oxigênio/metabolismo , Pele/microbiologia , Pele/patologia , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus Resistente à Vancomicina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Vancomicina/isolamento & purificação
15.
Pak J Pharm Sci ; 34(6(Supplementary)): 2303-2308, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35039267

RESUMO

In this cross-sectional study, the isolation and identification of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Resistant S. epidermidis (MRSE) was described from skin infections (n=100). Initial isolation was done by conventional procedures followed by amplification/ sequence analysis of 16S rRNA. Methicillin resistance was determined using cefoxitin discs and resistant isolates were screened for mec-A gene followed by Minimum Inhibitory Concentrations (MIC) determination of vancomycin. In second phase, we investigated extract of Azadirachta indica leaves using Fourier Transformed Infrared Spectroscopy (FTIR-Spectroscopy) and investigated in vitro activity. Initially, total of 28 Staphylococci were identified. 16S rRNA gene sequence confirmed S. aureus (22), S. epidermidis (3) and S. saprophyticus (3) isolates. Cefoxitin discs showed (7/22) MRSA, (3/3) (MRSE) and none of the methicillin resistant S. saprophyticus. MRSA and MRSE isolates showed presence of mec-A gene. However, all isolates were sensitive to vancomycin MIC (0.5-2µg/mL) and sensitive to Linezolid. FTIR-Spectroscopy of A. indica indicated the presence of azadirachtin and nimbolinin. The mean zone of inhibition was measured 14.23±1.37 and 13.66±0.70 against MRSA and MRSE isolates, respectively. Altogether, MRSA and MRSE is significant public health concern. However, vancomycin and linezolid were found effective and extract of A. indica showed in vitro effects.


Assuntos
Antibacterianos/farmacologia , Azadirachta , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Azadirachta/química , Estudos Transversais , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus epidermidis/genética , Staphylococcus epidermidis/isolamento & purificação
16.
Recent Pat Antiinfect Drug Discov ; 15(2): 137-156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32814540

RESUMO

AIM: To design controlled release topical delivery of mupirocin for the treatment of skin infection. BACKGROUND: Mupirocin is an antibacterial drug. Mupirocin works to kill the bacteria, which include strains of Staphylococcus aureus and Streptococcus pyogenes. It is also used for the treatment of inflammation of a hair follicle. The half-life of mupirocin is only 20-40 min. It has very slight solubility in water. Patent literature had shown work on ointment, antibiotic composition, nasal and topical composition. Emulgel is a duel control release system for the topical delivery of hydrophobic drugs. OBJECTIVE: The objective was to formulate emulgel with controlled delivery of mupirocin using Sepineo P 600. METHODS: Soya oil, tween 80 and polyethylene glycol 400 (Oil:Surfactant:Cosurfactant) were used for emulsion formulation. Emulgel was optimized by 32 factorial design. Sepineo P 600 and hydroxy propyl methyl cellulose K4M were used as independent variables. Drug excipient compatibility analysis was carried out by FTIR, UV and DSC spectra. Emulgel was evaluated for its physical characterization, in vitro release, ex vivo release, antimicrobial and anti-inflammatory study. RESULTS: DSC, UV and FTIR analysis confirmed drug excipient compatibility. FE SEM showed a size range between 228-255 nm. Zeta potential was found to be -25.1 mV, which showed good stability of the emulsion. Design expert software showed F2 as an optimized batch. Release studies indicated that the controlled release of drugs forms Sepineo P 600 gel due to its higher gelling capacity. Batch F2 showed comparable results with marketed formulation against Staphylococcus aureus. For batch F2, 40 µg/ml was the minimal inhibitory concentration. CONCLUSION: Antimicrobial and anti-inflammatory study proved successful development of stably controlled release mupirocin emulgel.


Assuntos
Antibacterianos/administração & dosagem , Excipientes/química , Mupirocina/administração & dosagem , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Administração Cutânea , Animais , Antibacterianos/farmacocinética , Embrião de Galinha , Galinhas , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Géis , Cabras , Meia-Vida , Humanos , Masculino , Testes de Sensibilidade Microbiana , Mupirocina/farmacocinética , Patentes como Assunto , Pele/efeitos dos fármacos , Pele/microbiologia , Solubilidade , Infecções Cutâneas Estafilocócicas/microbiologia
17.
Rev Col Bras Cir ; 47: e20202471, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32667581

RESUMO

PURPOSE: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. METHODS: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. RESULTS: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. CONCLUSIONS: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.


Assuntos
Antibacterianos/uso terapêutico , Pé Diabético/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Dermatopatias Bacterianas/microbiologia , Idoso , Antibacterianos/farmacologia , Complicações do Diabetes , Diabetes Mellitus , Pé Diabético/tratamento farmacológico , Resistência Microbiana a Medicamentos , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Infecções , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Dermatopatias Bacterianas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia
18.
Biomed Mater Eng ; 31(2): 95-105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32568170

RESUMO

BACKGROUND: Scallop shell powder is called bioshell calcium oxide (BiSCaO), which is known to possess deodorizing properties and broad antimicrobial activity against various pathogenic microbes, including viruses, bacteria, spores, and fungi. OBJECTIVE: This study aims to investigate the applications of BiSCaO suspension cleansing in clinical situations, for instance for the prevention and treatment of infections in chronic wounds in healing-impaired patients, without delaying wound healing. METHODS: The bactericidal activities of 1000 ppm BiSCaO suspension; 500 ppm hypochlorous acid; 1000 ppm povidone iodine; and saline were compared to evaluate in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. RESULTS: Cleansing of the infected wounds with BiSCaO suspension daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts, in comparison to hypochlorous acid, povidone iodine, and saline. Furthermore, histological examinations showed significantly advanced granulation tissue and capillary formation in the wounds cleansed with BiSCaO suspension than in those cleansed with the other solutions. CONCLUSIONS: This study suggested that the possibility of using BiSCaO suspension as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects on wound repair.


Assuntos
Compostos de Cálcio/uso terapêutico , Óxidos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Exoesqueleto/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carga Bacteriana/efeitos dos fármacos , Compostos de Cálcio/isolamento & purificação , Compostos de Cálcio/farmacologia , Modelos Animais de Doenças , Desinfecção/métodos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Óxidos/isolamento & purificação , Óxidos/farmacologia , Povidona-Iodo/farmacologia , Povidona-Iodo/uso terapêutico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Ratos , Ratos Pelados , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Irrigação Terapêutica/métodos , Cicatrização/efeitos dos fármacos
19.
Sci Rep ; 10(1): 5596, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221396

RESUMO

Wound infection is a serious clinical problem, and the most common infection-causing bacteria are Staphylococcus aureus and Pseudomonas aeruginosa. Angelica dahurica and Rheum officinale extract (ARE) was reported to accelerate excisional wound healing in rats. In this study, we investigated the therapeutic effects of ARE on bacterial-infected wounds. Thirty Sprague-Dawley rats were divided into three groups: normal saline (NS), ARE, and biomycin ointment (BO). Full-thickness dorsal excisions in all the rats were infected with 108 colony-forming units of S. aureus; the treatments were applied once daily for 7 days. Results showed that the residual wound area in ARE group was smaller than those in NS and BO groups. TBCs on wound sites gradually decreased in ARE and BO groups. The body temperature and plasma inflammatory cytokines (TNF-α, IL-6) levels increased after bacterial infection at 24 h in all groups. After treatment, BT and inflammatory cytokines levels decreased in ARE group. Histological observations showed ARE group exhibited earlier scab formation, denser dermal granulation tissue, thicker epidermis, and more angiogenesis markers than the other groups. In conclusion, ARE accelerated wound healing in S. aureus-infected wounds. We proposed ARE exhibited potential antimicrobial and anti-inflammatory effects and stimulated angiogenesis, thus improving healing in infected wounds.


Assuntos
Angelica/química , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Extratos Vegetais/uso terapêutico , Rheum/química , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Interleucina-6/sangue , Masculino , Testes de Sensibilidade Microbiana , Ratos , Ratos Sprague-Dawley , Infecções Cutâneas Estafilocócicas/patologia , Fator de Necrose Tumoral alfa/sangue
20.
Rev. Col. Bras. Cir ; 47: e20202471, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1136576

RESUMO

ABSTRACT Purpose: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. Methods: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. Results: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. Conclusions: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.


RESUMO Objetivo: identificar o perfil sociodemográfico, microbiológico e de resistência bacteriana em pacientes com pé diabético infectado. Métodos: tratou-se de estudo observacional, transversal que avaliou os perfis sóciodemográfico e microbiológico de pacientes portadores de pé diabético infectado internados em Pronto Socorro de referência. Os dados sociodemográficos foram coletados por meio de entrevista. Foram colhidos, durante os procedimentos cirúrgicos, fragmentos de tecidos das lesões podais infectadas para realização de cultura/antibiograma. Resultados: a amostra foi composta por 105 pacientes. O perfil sociodemográfico mais prevalente foi o de pacientes do sexo masculino, acima dos 50 anos, casados e com baixa escolaridade. Das 105 amostras de fragmentos de tecidos colhidos para realização de cultura e antibiograma, 95 foram positivas, com crescimento de um único germe em cada um dos exames. Houve predomínio de germes da família Enterobacteriaceae (51,5%). Germes Gram-negativos foram isolados em 60,0% das culturas e os espécimes mais isolados individualmente foram os cocos Gram-positivos, Staphylococcus aureus (20,0%) e Enterococcus faecalis (17,9%). Considerando-se os perfis de resistência bacteriana, verificou-se alta taxa de Staphylococcus aureus resistente à meticilina (63,0%) e à ciprofloxacino (55,5%); verificou-se, também, que 43,5% dos germes Gram-negativos eram resistentes à ciprofloxacino. Conclusões: o perfil sociodemográfico majoritário, foi o de homens, com mais de 50 anos e com baixa escolaridade. Concluímos que os germes mais prevalentes nas lesões podais dos pacientes diabéticos foram os Gram-negativos, resistentes ao ciprofloxacino e que o germe mais isolado individualmente foi o Staphylococcus aureus resistente à meticilina.


Assuntos
Humanos , Masculino , Feminino , Idoso , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Pé Diabético/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/uso terapêutico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , Dermatopatias Bacterianas/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Complicações do Diabetes , Diabetes Mellitus , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Infecções , Pessoa de Meia-Idade , Antibacterianos/farmacologia
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