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1.
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
2.
BMC Infect Dis ; 20(1): 118, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041554

RESUMO

BACKGROUND: Previous publications indicated an emerging issue with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly skin and soft tissue infections (SSTIs), in Indigenous communities in Canada. The objectives of this analysis were to explore the prevalence of SSTIs due to CA-MRSA and patterns of antimicrobial use in the community setting. METHODS: A retrospective chart review was conducted as part of an environmental scan to assess antibiotic prescriptions in 12 First Nations communities across five provinces in Canada including Alberta, Saskatchewan, Manitoba, Ontario, and Québec. Charts were randomly selected from nursing stations and patients who had accessed care in the previous 12 months and were ≥ 18 years were included in the review. Data was collected from September to December, 2013 on antibiotic prescriptions, including SSTIs, clinical symptoms, diagnostic information including presence of CA-MRSA infection, and treatment. RESULTS: A total of 372 charts were reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec. Among 372 patients, 224 (60.2%) patients had at least one antibiotic prescription in the previous 12 months and 569 prescriptions were written in total. The prevalence of SSTIs was estimated at 36.8% (137 cases of SSTIs in 372 charts reviewed). In 137 cases of SSTIs, 34 (24.8%) were purulent infections, and 55 (40.2%) were due to CA-MRSA. CONCLUSIONS: This study has identified a high prevalence of antibiotic use and SSTIs due to CA-MRSA in remote and isolated Indigenous communities across Canada. This population is currently hard to reach and under-represented in standard surveillance system and randomized retrospective chart reviews can offer complimentary methodology for monitoring disease burden, treatment and prevention.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Canadá/etnologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etnologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Povos Indígenas , Masculino , Pessoa de Meia-Idade , Saúde das Minorias , Prevalência , Estudos Retrospectivos , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/etnologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/etnologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Adulto Jovem
3.
BMJ Case Rep ; 12(12)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801778

RESUMO

We report a case of a catheter-related bloodstream infection due to oxacillin-susceptible Staphylococcus pseudintermedius in a patient receiving haemodialysis who possibly acquired the organism from her pets. Because of persistent bacteremia and the organism's ability to form biofilm, catheter removal and antimicrobial therapy were indicated to attain source control. Both clinical and microbiological cure were confirmed. Catheter care education should include information about pet exposure and the possibility of zoonotic infections.


Assuntos
Infecções Relacionadas a Cateter/transmissão , Infecções Estafilocócicas/transmissão , Infecções Cutâneas Estafilocócicas/transmissão , Zoonoses/transmissão , Adulto , Animais , Animais Domésticos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Infecções Relacionadas a Cateter/tratamento farmacológico , Gatos , Cães , Feminino , Humanos , Falência Renal Crônica/terapia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/transmissão , Diálise Renal/efeitos adversos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus , Resultado do Tratamento , Zoonoses/tratamento farmacológico
5.
Nat Commun ; 10(1): 4792, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636263

RESUMO

The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)-block-poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections.


Assuntos
Biofilmes/efeitos dos fármacos , Glucose/síntese química , Lisina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , beta-Lactamas/síntese química , Células 3T3 , Animais , Farmacorresistência Bacteriana Múltipla , Glucose/farmacologia , Glucose/uso terapêutico , Humanos , Técnicas In Vitro , Lisina/síntese química , Lisina/farmacologia , Lisina/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Polimerização , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
6.
Bull Exp Biol Med ; 167(6): 784-786, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31656000

RESUMO

Antibacterial activity of powdered preparations based on copper and silver nanoparticles was compared with activity of the reference preparation Baneocin on the model of local staphylococcal infection in white rats. The developed preparations exhibited pronounced antibacterial activity against methicillin-resistant S. epidermidis strains in vivo significantly (p<0.001) exceeding that of Baneocin, reduced microbial contamination of the wound on day 5 of study by 2 lg and more in comparison with bacterial load before treatment, and provided effective decontamination of the wound within 7-10 days.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Animais não Endogâmicos , Antibacterianos/administração & dosagem , Antibacterianos/química , Anti-Infecciosos Locais/química , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/química , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Prata/administração & dosagem , Prata/química , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
7.
Eur J Pharm Biopharm ; 144: 154-164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542438

RESUMO

Curcumin, a multi-targeting pharmacologically active compound, is a promising molecule for the treatment of skin inflammation and infection in chronic wounds. However, its hydrophobic nature remains to be a challenge in development of its pharmaceutical products, including dermatopharmaceuticals. Here we propose deformable liposomes (DLs) as a mean to overcome the curcumin limitations in skin treatment. We explored the properties and biological effects of curcumin containing DLs (curcumin-DLs) with varying surface charge by preparing the neutral (NDLs), cationic (CDLs) and anionic (ADLs) nanocarriers. The vesicles of mean diameter 200-300 nm incorporated high curcumin load mirroring the type of employed surfactant. Curcumin-CDLs provided the most sustained ex vivo penetration of curcumin through the full thickness human skin. Although the curcumin-CDLs were the most potent regarding the in vitro anti-inflammatory activity, all curcumin-DLs were superior to curcumin in solution (control). No cytotoxicity in human skin fibroblasts was detected. All DLs significantly inhibited bacterial Staphylococcus aureus and Streptococcus pyogenes growth in vitro. The curcumin-CDLs were found superior to other DLs. The incorporation of curcumin in DLs enabled both its sustained skin penetration and enhancement of its biological properties. Cationic nanocarriers enhanced the activities of curcumin to the greatest extent.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Lipossomos/química , Pele/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Administração Cutânea , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Fibroblastos/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tamanho da Partícula , Pele/microbiologia , Absorção Cutânea/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Tensoativos/química
8.
Int J Nanomedicine ; 14: 5943-5955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447553

RESUMO

Background and aim: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of surgical infection, and its resistance to numerous conventional antibiotics makes treatment difficult. Although vancomycin is often an effective agent for the initial therapy of MRSA, clinical failure sometimes occurs. Therefore, there is an urgent need to develop better therapies. Here, we prepared some vancomycin-loaded nanoliposomes coupled with anti-staphylococcal protein (lysostaphin) and evaluated their in vitro and in vivo efficacy as a topical MRSA therapy. Methods: Vancomycin was encapsulated in liposomes, and the coupling of lysostaphin with the surface of liposomes was carried out through cyanuric functional groups. The bactericidal efficacies and a full characterization were evaluated. To define different nanoliposomal-bacterium interactions and their bactericidal effect, flow cytometry was employed. Finally, in vivo, the topical antibacterial activity of each formulation was measured against surgical wound MRSA infection in a mouse model. Results: High encapsulation and conjugation efficiency were achieved for all formulations. All the formulations showed a significant reduction in bacterial counts (p<0.05). The targeted liposomes more effectively suppress bacterial infection in vitro and in vivo relative to equivalent doses of untargeted vancomycin liposome. The flow cytometry results confirmed liposome-bacterium interactions, which increased during the incubation time. The maximum binding rate and the bactericidal effect were significantly higher in targeted liposomes (p<0.05) compared with control liposomes. Conclusion: Our data suggest a novel nano-vehicle (lysostaphin-conjugated coupled liposomal vancomycin) which could be used as a great topical antimicrobial construct for treatment of MRSA skin infections.


Assuntos
Antibacterianos/uso terapêutico , Lisostafina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Vancomicina/uso terapêutico , Idoso , Animais , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Contagem de Colônia Microbiana , Quimioterapia Combinada , Humanos , Lipossomos , Lisostafina/farmacologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Infecções Cutâneas Estafilocócicas/patologia , Vancomicina/farmacologia
9.
Discov Med ; 28(151): 7-16, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31465721

RESUMO

Staphylococcus aureus can cause persistent infections and is known to develop persister cells in vitro. However, the in vivo significance of in vitro persisters in general is largely unclear. Here, we evaluated S. aureus stationary phase cultures and biofilm bacteria enriched in persister bacteria in comparison with actively growing log phase bacteria in terms of their ability to cause disease in a mouse skin infection model. We found that mice infected with the stationary phase and biofilm bacteria, which were enriched with persisters, produced more pronounced skin lesions that took longer to heal, and had more severe skin pathology and higher bacterial load than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in mice. Analogous findings were observed in a Caenorhabditis elegans model, where stationary phase S. aureus caused greater virulence or mortality than log phase bacteria as early as two days post-infection. Our findings associate in vitro persisters and biofilm bacteria with more persistent and more severe infections and emphasize the importance of quality or metabolic status of the inoculum bacteria (persister bacteria versus growing bacteria) not just the number of bacteria in causing disease. The persistent infection mouse model we developed with persister inocula should have implications for understanding the process of disease establishment and pathogenesis, for developing persistent infection animal models, and for developing more effective treatments for chronic persistent infections in general.


Assuntos
Biofilmes/efeitos dos fármacos , Doxiciclina/farmacologia , Rifampina/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/fisiologia , Animais , Caenorhabditis elegans/microbiologia , Modelos Animais de Doenças , Feminino , Camundongos , Infecções Cutâneas Estafilocócicas/metabolismo , Infecções Cutâneas Estafilocócicas/patologia
11.
Int J Infect Dis ; 87: 60-66, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330321

RESUMO

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) represent a major clinical problem in Colombia. The aim of this study was to evaluate the risk factors associated with MRSA SSTI in Colombia. METHODS: A multicenter cohort study with nested case-control design was performed. Patients with an SSTI with at least 48h of inpatient care were included. Patients with an MRSA SSTI were considered the case group and patients with either a non-MRSA SSTI or with an Methicillin-susceptible S. aureus (MSSA) SSTI were the control groups. A multivariate logistic regression approach was used to evaluate risk factors associated with MRSA SSTI with two different statistical models. RESULTS: A total 1134 patients were included. Cultures were positive for 498 patients, of which 52% (n=259) were Staphylococcus aureus. MRSA was confirmed in 68.3% of the S. aureus cultures. In the first model, independent risk factors for MRSA SSTI were identified as the presence of abscess (P<0.0001), cellulitis (P=0.0007), age 18-44 years (P=0.001), and previous outpatient treatment in the previous index visit (P=0.003); surgical site infection was a protective factor (P=0.008). In the second model, the main risk factor found was previous outpatient treatment in the previous index visit (P=0.013). CONCLUSIONS: Community-acquired SSTIs in Colombia are commonly caused by MRSA. Therefore, clinicians should consider MRSA when designing the initial empirical treatment for purulent SSTI in Colombia, although there seems to be low awareness of this fact.


Assuntos
Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Estudos de Casos e Controles , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Fatores de Risco , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/epidemiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia , Adulto Jovem
12.
Int J Antimicrob Agents ; 54(3): 283-291, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279155

RESUMO

In the light of pandemic spreads of multi-drug-resistant micro-organisms, alternative antimicrobial strategies to the use of antibiotics are the focus of research attention. As a prerequisite for medical application, the aim of this study was to develop a three-dimensional full skin infection model to evaluate the bioactivity and biocompatibility of antiseptics in application-relevant concentrations. A three-dimensional (3D) full skin model consisting of collagen-embedded fibroblasts as dermis and a fully differentiated epidermis built from keratinocytes was infected with Staphylococcus aureus. Infected skin models were treated for 24 h with the antiseptics polihexanide, octenidine dihydrochloride, chlorhexidine digluconate and povidone-iodine. Infection resulted in detrimental effects, a strong immune response with increased secretion of lactate dehydrogenase and pro-inflammatory cytokines, and increased gene expression of pro-inflammatory cytokines and antimicrobial peptides after 24 h. Application of antiseptics protected the skin models from damage due to S. aureus infection while demonstrating good biocompatibility. The best ratio of bioactivity to biocompatibility was observed for polihexanide. Polihexanide also enhanced the innate immune response by increasing the gene expression levels of antimicrobial peptides such as human ß-defensin 2, human ß-defensin 3, psoriasin and ribonuclease 7. The developed model provides an excellent tool to investigate the response of human cells to microbial infections in a complex 3D structure. Furthermore, the infection model is appropriate for evaluation of bioactivity and biocompatibility of antiseptics. As such, the model presented in this study is a promising approach to evaluate the mechanisms and effectiveness of new antimicrobial strategies.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Modelos Teóricos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Humanos , Resultado do Tratamento
13.
Int J Antimicrob Agents ; 54(5): 610-618, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356860

RESUMO

Skin bacterial colonization/infection is a frequent cause of morbidity in patients with chronic wounds and allergic/inflammatory skin diseases. This study aimed to develop a novel approach to eradicate meticillin-resistant Staphylococcus aureus (MRSA) from human skin. To achieve this, the stability and antibacterial activity of the novel LL-37-derived peptide P10 in four ointments was compared. Results indicate that P10 is chemically stable and antibacterial in hypromellose gel and Softisan-containing cream, but not in Cetomacrogol cream (with or without Vaseline), at 4 °C for 16 months. Reduction in MRSA counts on Leiden human epidermal models (LEMs) by P10 in hypromellose gel was greater than that of the peptide in Cetomacrogol cream or phosphate buffered saline. P10 did not show adverse effects on LEMs irrespective of the ointment used, while Cetomacrogol with Vaseline and Softisan cream, but not hypromellose gel or Cetomacrogol cream, destroyed MRSA-colonized LEMs. Taking all this into account, P10 in hypromellose gel dose-dependently reduced MRSA colonizing the stratum corneum of the epidermis as well as biofilms of this bacterial strain on LEMs. Moreover, P10 dose-dependently reduced MRSA counts on ex-vivo human skin, with P10 in hypromellose gel being more effective than P10 in Cetomacrogol and Softisan creams. P10 in hypromellose gel is a strong candidate for eradication of MRSA from human skin.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pomadas/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Administração Tópica , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cetomacrogol/farmacologia , Portadores de Fármacos/farmacologia , Humanos , Derivados da Hipromelose/farmacologia , Lipídeos/farmacologia , Testes de Sensibilidade Microbiana , Vaselina/farmacologia , Pele/microbiologia
14.
Mater Sci Eng C Mater Biol Appl ; 103: 109764, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349470

RESUMO

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO2-CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.


Assuntos
Antibacterianos , Vidro/química , Modelos Biológicos , Nanopartículas/química , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/crescimento & desenvolvimento , Prata , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/crescimento & desenvolvimento , Células 3T3 , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Camundongos , Prata/química , Prata/farmacologia
15.
Mater Sci Eng C Mater Biol Appl ; 103: 109741, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349480

RESUMO

Wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilm represent a high risk in patients with diabetes. Nitric oxide (NO) has shown promise in dispersing biofilm and wound healing. For an effective treatment of MRSA biofilm-infected wounds, however, NO needs to be supplied to the biofilm matrix in a sustainable manner due to a short half-life and limited diffusion distance of NO. In this study, polyethylenimine/diazeniumdiolate (PEI/NONOate)-doped PLGA nanoparticles (PLGA-PEI/NO NPs) with an ability to bind to the biofilm matrix are developed to facilitate the NO delivery to MRSA biofilm-infected wound. In simulated wound fluid, PLGA-PEI/NO NPs show an extended NO release over 4 days. PLGA-PEI/NO NPs firmly bind to the MRSA biofilm matrix, resulting in a greatly enhanced anti-biofilm activity. Moreover, PLGA-PEI/NO NPs accelerate healing of MRSA biofilm-infected wounds in diabetic mice along with complete biofilm dispersal and reduced bacterial burden. These results suggest that the biofilm-binding NO-releasing NPs represent a promising NO delivery system for the treatments of biofilm-infected chronic wounds.


Assuntos
Antibacterianos/farmacologia , Complicações do Diabetes/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanopartículas/química , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Ferimentos e Lesões/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Compostos Azo/química , Biofilmes/efeitos dos fármacos , Complicações do Diabetes/microbiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/microbiologia , Liberação Controlada de Fármacos , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Óxido Nítrico/farmacocinética , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Infecções Cutâneas Estafilocócicas/complicações , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/complicações , Ferimentos e Lesões/microbiologia , Ferimentos e Lesões/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31192163

RESUMO

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo, and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 µg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.


Assuntos
Administração Tópica , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Modelos Animais de Doenças , Feminino , Lipídeos/química , Camundongos , Testes de Sensibilidade Microbiana , Nanocápsulas , Poloxâmero/uso terapêutico , Proteínas Serina-Treonina Quinases/administração & dosagem , Proteínas Serina-Treonina Quinases/farmacologia , Proteínas Serina-Treonina Quinases/uso terapêutico , Testes de Irritação da Pele , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Suínos
17.
Curr Pharm Biotechnol ; 20(9): 707-718, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223082

RESUMO

BACKGROUND: Daptomycin is a popular anti-MRSA antibiotic, especially for surgical wound infections. The side-effects of Daptomycin dosage through intravenous administration have prompted the experimental use of topical Daptomycin. Also, combinatorial drug therapy involving noble metal nanoparticles and conventional antibiotics have proved beneficial in the past. The synergistic oligodynamic effect of Daptomycin with nanoparticles for topical application was attempted for the first time in this work. OBJECTIVES: The present study was focused on topical gel formulation containing Daptomycin combined with mycogenic gold, silver and bimetallic gold and silver nanoparticles and evaluation of their synergistic antibacterial effect against an MRSA strain. METHODS: An efficient approach for fungal growth was discussed wherein the biomass was cultivated under non-limiting conditions, followed by the addition of gold salt, silver salt and bimetallic (Gold and silver) solution. The metal salt reduction efficacy was evaluated using Cyclic Voltammetry. Formation of nanoparticles was observed by visual color changes and confirmed by UV-visible characteristic peaks. The mycosynthesized metallic and bimetallic nanoparticles were characterized by various advanced analytical methods. Further, Daptomycin was combined with nanoparticles in a topical gel formulation. The properties of the topical gels were evaluated and their antimicrobial activity was investigated against an MRSA strain associated with burn infections though disc diffusion method. RESULTS: Formation of nanoparticles was observed by visual color changes and confirmed by UVvisible characteristic peaks. XRD spectra revealed the crystalline nature of nanoparticles whereas TEM confirmed the presence of spherical nanoparticles. The bio fabricated nanoparticles were characterized using ICP-MS, XRD and TEM. The UV-Visible spectrum of the gold, silver, bimetallic nanoparticles showed a characteristic peak at 550 nm, 450 nm, and 480 nm, respectively. ICP-MS of the residual salt concentration depicted more than 75% bioconversion of metal salt to metal nanoparticles. TEM showed the formation of uniform, spherical monometallic nanoparticles. XRD results were in sync with the dynamic light scattering experiments which determined that the gold, silver, bimetallic nanoparticles ranged between 10-20 nm, 5-30 nm, and 20-40 nm respectively and were crystalline in nature with the face centered cubic symmetry. Topical gels combining Daptomycin and nanoparticles were formulated and characterized. The in-vitro drug release studies indicated controlled release of antibiotic from bimetallic nanoparticles and Daptomycin combination in topical gel formulation. The MIC values reduced for the combinatorial drug and the average synergistic antimicrobial effect was 37% and the increase in efficacy of Daptomycin due to the synergistic effect with bimetallic nanoparticles was 43%. CONCLUSION: Topical gels were formulated using the biologically synthesized gold, silver and bimetallic gold-silver nanoparticles and modern-day antibiotic Daptomycin to combat burn infections. The topical gel formulations showed enhanced antimicrobial activity against methicillin-resistant Staphylococcus aureus at lower MIC values as compared to individual nanoparticle or antibiotic. The best results were obtained with bimetallic nanoparticles in topical gel formulation as it assisted in controlled drug release up to 94.6% and improved antimicrobial effect i.e. 43%.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Prata/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Daptomicina/administração & dosagem , Daptomicina/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Géis , Ouro/administração & dosagem , Ouro/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Prata/administração & dosagem , Prata/química , Infecções Cutâneas Estafilocócicas/tratamento farmacológico
18.
Eur J Clin Microbiol Infect Dis ; 38(9): 1781-1785, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222396

RESUMO

The study is aimed at retrospectively estimating the percentage of inpatients with severe acute bacterial skin and skin structure infections (ABSSSI) who met the early discharged (ED) criteria adapted from Nathwani et al. (Int J Antimicrob Agents. 2016 Aug;48(2):127-36) and to calculate the number of hospitalization days that could be potentially saved. A retrospective study was conducted in a tertiary care hospital in Florence, Italy. We included all patients admitted for cellulitis and post-surgical infections from 2014 to 2017. Demographic and clinical data were obtained from electronic medical records. We a priori defined the following as a risk factor for non-adherence (RFNA): active or on methadone intravenous drug users, homeless, migrants without health care assistance, and patients who need a caregiver to take prescribed medications. One hundred sixty-two subjects were enrolled. Of them, 94 (58.0%) were male, and 113 (69.7%) had cellulitis/erysipelas. A microbiological isolate was obtained in 51 patients (31.4%); Staphylococcus aureus was the most frequent (47%). Eighty-four (51.8%) were ED suitable, with 258 (49.0%) patient days potentially saved. Among the 78 not ED suitable patients, the most common reason for prolonged length of stay (LOS) was having at least one RFNA (34.6%). Fourteen (18.0%) had one RFNA. Half of the patients admitted in our hospital met the ED criteria with a sparing close to 50% in terms of hospitalization days. Unstable social and personal factors were the most frequent causes for prolonged LOS. In this selected subset of patients, more recent and easier to administer treatments, including long-acting agents, could be proposed.


Assuntos
Hospitais de Ensino , Alta do Paciente , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos Transversais , Registros Eletrônicos de Saúde , Feminino , Hospitalização , Humanos , Itália , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Pele/patologia , Infecções Cutâneas Estafilocócicas/microbiologia
19.
J Med Microbiol ; 68(6): 898-902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31050628

RESUMO

The incidence and patient outcomes of Staphylococcus aureus isolates by iclaprim MIC was determined among patients from two phase 3 studies for the treatment of acute bacterial skin and skin structure infections (ABSSSI), REVIVE-1 and -2. Iclaprim MIC90 values were 0.12 µg ml-1 for S. aureus (0.12 µg ml-1 against methicillin-sensitive and 0.25 µg ml-1 against methicillin-resistant S. aureus). The incidence of culture confirmed S. aureus isolates among patients with ABSSSI with an iclaprim MIC > 8 µg ml-1 was 2.0  % (16/790). The clinical outcomes varied by MICs for early clinical response (63-100  %), end of therapy response (81-100  %) and the test of cure response (75-100  %). For microbiological outcomes of these infections, the end of therapy response was 80-100  % and the test of cure response was 88-100  %.


Assuntos
Antibacterianos/farmacologia , Pirimidinas/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Doença Aguda , Método Duplo-Cego , Humanos , Incidência , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Vancomicina/farmacologia
20.
Pediatr Dermatol ; 36(4): 482-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31124167

RESUMO

BACKGROUND/OBJECTIVES: Staphylococcus aureus is the most prevalent bacterial pathogen in atopic dermatitis (AD) patients presenting with skin infections. Despite the known association between S aureus and AD, guidance on empiric antibiotics for skin infections in pediatric AD patients is limited. METHODS: We conducted a retrospective study over a five-year period to characterize the S aureus strains recovered from pediatric AD patients with clinically apparent bacterial skin infections treated in an academic medical center. We assessed patient demographics and dilute bleach bath usage to determine whether these factors were correlated with methicillin resistance. Culture results from our AD cohort were also compared to those from pediatric patients presenting to the Saint Louis Children's Hospital emergency department (ED) with S aureus skin abscesses from 2013 to 2015. RESULTS: Methicillin-sensitive S aureus (MSSA) was more prevalent (77.8%) than methicillin-resistant S aureus (MRSA) (22.2%). There was no correlation between MRSA and age, sex, race, or dilute bleach bath use. In comparison with pediatric patients presenting to the ED, AD patients had lower rates of MSSA susceptibility to doxycycline and MRSA susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: First-generation cephalosporins remain appropriate empiric therapy for most pediatric AD patients. In patients with a history of MRSA, empiric doxycycline or TMP-SMX could be considered, given their high MRSA susceptibility rates.


Assuntos
Dermatite Atópica/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Dermatite Atópica/epidemiologia , Dermatite Atópica/microbiologia , Serviço Hospitalar de Emergência , Feminino , Hospitais Pediátricos , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Infecções Cutâneas Estafilocócicas/diagnóstico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
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