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1.
Arch Microbiol ; 204(6): 303, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524073

RESUMO

Biocompatible and non-toxic properties of chitosan make it a candidate with excellent application prospects in developing wound dressing conjugate compounds. Six different chitosan-based nanohybrid membranes were evaluated against multidrug-resistant bacterial isolates. Different combinations of chitosan, ciprofloxacin (CIP), biofunctionalized montmorillonite (MMT), and montmorillonite with sulfate chains (SMMT) were provided, and their antibacterial activity was assessed using the colony count method. Totally, 27 drug-resistant isolates, including 6x methicillin-resistant Staphylococcus aureus, 7 vancomycin-resistant Enterococcus faecalis, 4 Acinetobacter baumannii, and 10 Pseudomonas aeruginosa isolates were identified from burn wound infections. Chitosan and montmorillonite did not show significant antibacterial effect (p > 0.05), but chitosan/SMMT/CIP was the most effective nanocomposite (p < 0.01). Chitosan-based nanocomposites with ciprofloxacin could effectively reduce the susceptibility of drug-resistant bacterial isolates. Bacterial targeting using nanosystems provides an opportunity for effective antibiotic treatment by improving antibacterial efficacy.


Assuntos
Queimaduras , Quitosana , Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Antibacterianos/farmacologia , Bentonita/farmacologia , Queimaduras/complicações , Queimaduras/microbiologia , Quitosana/farmacologia , Ciprofloxacina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
2.
Mymensingh Med J ; 31(2): 431-436, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35383763

RESUMO

Burn injury is still a life-threatening event, associated with high mortality and morbidity inspite of recent advances and infection control practices. This cross sectional study was conducted at Microbiology department of Rajshahi Medical College (RMC), Bangladesh with the objective to provide an insight into the current trend of aerobic bacteria with their antibiogram in burn wound infected patients admitted in Burn and Plastic Surgery Unit of RMCH from 1st January 2016 to 31st December 2016. A total of 212 wound swabs were collected and processed as per standard protocol. The isolates were identified by standard microbiological techniques and antimicrobial susceptibility was performed by Modified Kirby-Bauer disk diffusion method. Burn injurywas highest (44.81%) in age group 21-30 years in fire related burn patients (41.98%) and female were predominant (59.91%). Among 212 samples 89.62% yielded growth and 196 bacterial species were isolated in which P. aeruginosa were the predominant organism (34.18%) followed by Proteus spp. (23.47%), Klebsiella spp. (14.80%), E. coli (11.73%), S. aureus (10.71%), Acinetobacter spp. & CoNS (2.04%) and Enterobacter spp. (1.03%). In this study meropenem, amikacin and vancomycin were highly sensitive drugs but 3rd generation cephalosporin and ciprofloxacin showed resistance. Therefore continuous microbiological surveillance and careful in vitro testing prior to antibiotic treatment is required to reduce the emergence of multidrug resistant pathogens.


Assuntos
Queimaduras , Infecção dos Ferimentos , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Aeróbias , Bangladesh/epidemiologia , Queimaduras/complicações , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Estudos Transversais , Escherichia coli , Feminino , Humanos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Centros de Atenção Terciária , Infecção dos Ferimentos/tratamento farmacológico , Adulto Jovem
3.
Sci Rep ; 12(1): 6414, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440743

RESUMO

Antimicrobials used to treat burn wound infections have become multidrug-resistant, thus delaying wound healing. When combined with silver nanoparticles, antibiotics create a multifaceted antibacterial mechanism of action to which bacteria are incapable of developing resistance. Similarly, the amniotic membrane has been found to lower the bacterial number. The purpose of the current study was to observe the antibacterial activity of combined topical colistin with silver nanoparticles and decellularized human amniotic membrane as a dressing in burn wounds infected with bacteria with the goal of promoting faster healing. Bacteria commonly isolated from burn wounds and the most sensitive topical antibiotic were identified. Colistin, silver nanoparticles and combined colistin with silver nanoparticles were impregnated into decellularized human amniotic membranes. These wound dressings were evaluated in third-degree multidrug-resistant bacterial infected thermal burns induced in rats. Out of a total of 708 pus samples from burn wounds, Pseudomonas aeruginosa was the most prevalent pathogen 308 (43.5%), followed by Klebsiella pneumoniae 300 (42.4%). Topical colistin was 100% sensitive for both bacteria. Overall, maximum wound contraction (p < 0.05), and increased collagen deposition (+++) with no isolation of bacteria from wound swabs were noted on day 21 for the combined colistin with silver nanoparticle-loaded human amniotic membrane dressing group. Our study concluded that the increased antimicrobial activity of the novel combination of colistin and silver nanoparticle-loaded decellularized human amniotic membrane manifested its potential as an effective burn wound dressing.


Assuntos
Anti-Infecciosos , Queimaduras , Nanopartículas Metálicas , Infecção dos Ferimentos , Âmnio , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Queimaduras/complicações , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Colistina/farmacologia , Humanos , Ratos , Prata/farmacologia , Infecção dos Ferimentos/microbiologia
4.
Photodiagnosis Photodyn Ther ; 38: 102831, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35341978

RESUMO

Burns are among the most debilitating and devastating forms of trauma. Such injuries are influenced by infections, causing increased morbidity, mortality, and healthcare costs. Due to the emergence of multidrug-resistant infectious agents, efficient treatment of infections in burns is a challenging issue. Antimicrobial photodynamic therapy (aPDT) is a promising approach to inactivate infectious agents, including multidrug-resistant. In this review, studies on PubMed were gathered, aiming to summarize the achievements regarding the applications of antimicrobial photodynamic therapy for the treatment of infected burns. A literature search was carried out for aPDT published reports assessment on bacterial, fungal, and viral infections in burns. The collected data suggest that aPDT could be a promising new approach against multidrug-resistant infectious agents. However, despite important results being obtained against bacteria, experimental and clinical studies are necessary yet on the effectiveness of aPDT against fungal and viral infections in burns, which could reduce morbidity and mortality of burned patients, mainly those infected by multidrug-resistant strains.


Assuntos
Anti-Infecciosos , Queimaduras , Fotoquimioterapia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
5.
J Burn Care Res ; 43(2): 336-342, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-34523679

RESUMO

Burn wound infections are often the source of bacteria responsible for systemic infections, including bloodstream infections and pneumonia that ultimately can result in multisystem organ failure and death. Any rapid change in the burn wound appearance or the clinical condition of the burn patient may herald burn wound infection or sepsis. The revival of phage therapy, either in single mode or in combination with conventional antibiotics may represent a valuable alternative, to treat specific bacterial infections such as burn wound infections, including those caused by multidrug-resistant organisms. This systematic review addresses the: 1) general characteristics of bacteriophages; 2) activity of bacteriophages vs conventional antibiotics; 3) activity of bacteriophages against biofilms; 4) bacteriophage administration; and 5) use of bacteriophages in burn wound infections. Although several scientific organizations/societies recognized that phage therapy could be of key value in modern wound care, specific aspects are critical for a burn surgeon and might represent pitfalls discouraging phage therapy adoption in burn wound management; in particular, the unavailability of consensual therapeutic guidelines/regulatory policies and the lack of laboratorial support that might be predictive of its efficacy. The availability of a product/formulation convenient to use, with adequate stability and shelf half-life is also a key condition.


Assuntos
Bacteriófagos , Queimaduras , Terapia por Fagos , Infecção dos Ferimentos , Antibacterianos/uso terapêutico , Queimaduras/complicações , Queimaduras/microbiologia , Queimaduras/terapia , Humanos , Infecção dos Ferimentos/tratamento farmacológico
6.
J Burn Care Res ; 43(2): 423-431, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-34236077

RESUMO

Burn infection continues to be a major issue of concern globally and causes more harm to developing countries. This study aimed to identify the aerobic bacteriological profiles and antimicrobial resistance patterns of burn infections in three hospitals in Abadan, southwest Iran. The cultures of various clinical samples obtained from 325 burn patients were investigated from January to December 2019. All bacterial isolates were identified based on the standard microbiological procedures. Antibiotic susceptibility tests were performed according to the CLSI. A total of 287 bacterial species were isolated from burn patients. Pseudomonas aeruginosa was the most frequent bacterial isolate in Gram-negative bacteria and S. epidermidis was the most frequent species isolated in Gram-positive bacteria. The maximum resistance was found to ampicillin, gentamicin, ciprofloxacin, while in Gram-negative bacteria, the maximum resistance was found to imipenem, gentamicin, ciprofloxacin, ceftazidime, and amikacin. The occurrence of multidrug resistance phenotype was as follows: P. aeruginosa (30.3%), Enterobacter spp (11.1%), Escherichia coli (10.5%), Citrobacter spp (2.1%), S. epidermidis (2.8%), S. aureus, and S. saprophyticus (0.7%). Owing to the diverse range of bacteria that cause burn wound infection, regular investigation, and diagnosis of common bacteria and their resistance patterns is recommended to determine the proper antibiotic regimen for appropriate therapy.


Assuntos
Antibacterianos , Queimaduras , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Ciprofloxacina , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Gentamicinas , Bactérias Gram-Negativas , Humanos , Irã (Geográfico)/epidemiologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Staphylococcus aureus
7.
Bioengineered ; 13(2): 4122-4136, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34898366

RESUMO

Infections of burn wounds, especially those caused by Pseudomonas aeruginosa, could trigger sepsis or septic shock, which is the main cause of death after burn injury. Compared with traditional saline-wet-to-dry dressings, negative pressure wound therapy (NPWT) is more effective for the prevention and treatment of wound infections. However, the mechanism by which NPWT controls infection and accelerates wound healing remains unclear. Accordingly, in this study, the molecular mechanisms underlying the effects of NPWT were explored using a murine model of P. aeruginosa-infected burn wounds. NPWT significantly reduced P. aeruginosa levels in wounds, enhanced blood flow, and promoted wound healing. Additionally, NPWT markedly alleviated wound inflammation and increased the expression of wound healing-related molecules. Recent evidence points to a role of circular RNAs (circRNAs) in wound healing; hence, whole-transcriptome sequencing of wound tissues from NPWT and control groups was performed to evaluate circRNA expression profiles. In total, 12 up-regulated and 25 down-regulated circRNAs were identified between groups. Among these, five significant differentially expressed circRNAs acting as microRNA sponges were identified, and their predicted targets were verified by reverse transcription-quantitative polymerase chain reaction. These results further support the roles of circRNAs in wound healing by NPWT and the prevention of P. aeruginosa infection, providing key molecular targets for further functional analyses.


Assuntos
Queimaduras/genética , Queimaduras/terapia , Tratamento de Ferimentos com Pressão Negativa , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/terapia , RNA Circular/genética , Animais , Queimaduras/metabolismo , Queimaduras/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , RNA Circular/metabolismo , Cicatrização
8.
FEMS Microbiol Lett ; 368(20)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34849758

RESUMO

The prevalence of multidrug-resistant (MDR) strains has caused serious problems in the treatment of burn infections. MDR Enterobactercloacae and Enterobacterhormaechei have been defined as the causative agents of nosocomial infections in burn patients. In this situation, examination of phages side effects on human cell lines before any investigation on human or animal that can provide beneficial information about the safety of isolated phages. The aim of this study was to isolate and identify the specific bacteriophages on MDR E. cloacae and E. hormaechei isolated from burn wounds and to analyze the efficacy, cell viability and cell cytotoxicity of phages on A-375 and HFSF-PI cell lines by MTT (3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide) colorimetric assay and lactate dehydrogenase (LDH) release assay. Phages were isolated from urban sewage Isfahan, Iran. Enterobactercloacae strain Iau-EC100 (GenBank accession number: MZ314381) and E. hormaechei strain Iau-EHO100 (GenBank accession number: MZ348826) were sensitive to the isolated phages. Transmission electron microscopy (TEM) results revealed that PɸEn-CL and PɸEn-HO that were described had the morphologies of Myovirus and Inovirus, respectively. Overall, MTT and LDH assays showed moderate to excellent correlation in the evaluation of cytotoxicity of isolated phages. The results of MTT and LDH assays showed that, phages PɸEn-CL and PɸEn-HO had no significant toxicity effect on A375 and HFSF-PI 3 cells. Phage PɸEn-HO had a better efficacy on the two tested cell lines than other phage. Our results indicated that, there were significant differences between the two cytotoxicity assays in phage treatment compared to control.


Assuntos
Bacteriófagos , Queimaduras , Enterobacter cloacae , Enterobacter , Infecção dos Ferimentos , Bacteriófagos/fisiologia , Queimaduras/complicações , Queimaduras/microbiologia , Linhagem Celular , Enterobacter/virologia , Enterobacter cloacae/virologia , Humanos , Pele/microbiologia , Pele/virologia , Infecção dos Ferimentos/etiologia , Infecção dos Ferimentos/microbiologia
9.
Comput Math Methods Med ; 2021: 8212518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887942

RESUMO

Bleeding and infection can cause significant increases in mortalities. Hydrogel sealants have attracted extensive attention for their ability to control bleeding. In this study, the adjuvant treatment with antibacterial adhesive hydrogel dressings was applied to patients with deep second-degree burns/scalds. The traditional medical dressing was regarded as control adjuvant treatment. The results indicated that the total positive rate of bacteria in wound secretions and the pain during dressing change in patients who used antibacterial adhesive hydrogel dressings were significantly reduced. The number of fibroblasts and new capillaries in the granulation tissue of the wound increased, and the patient's wound healing is accelerated. The overall clinical effectiveness has been significantly improved. It is proven that the antibacterial adhesive hydrogel dressing has a significant effect on wound healing.


Assuntos
Antibacterianos/administração & dosagem , Bandagens , Cicatrização/efeitos dos fármacos , Adesivos/administração & dosagem , Adolescente , Adulto , Idoso , Queimaduras/microbiologia , Queimaduras/patologia , Queimaduras/terapia , Capilares/patologia , Biologia Computacional , Feminino , Fibroblastos/patologia , Tecido de Granulação/irrigação sanguínea , Tecido de Granulação/patologia , Humanos , Hidrogéis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Resultado do Tratamento , Cicatrização/fisiologia , Adulto Jovem
10.
Cell Mol Biol (Noisy-le-grand) ; 67(3): 52-60, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34933733

RESUMO

Pseudomonas aeruginosa is a ubiquitous microorganism that is difficult to treat due to the increasing prevalence of multidrug resistance patterns. A total of 227 samples were taken from different clinical samples during the study period from January 2018 to December 2018. The isolates were identified with antibiotic sensitivity testing with ESBL by the Vitek-2 automated method. MDR, XDR, and PDR were determined. 40 (17.6%) isolates were positive for P. aeruginosa, maximum of ESBL and MBL. Positive isolates were detected in the burn, coexisting ESBL + MBL enzymes in 21 (52.5%) of our isolates. Imipenem followed by Meropenem were found to be effective against ESBL and MBL producers. Resistance was reached between 72-100% to 5 antibiotics. The frequency of PDR, MDR, and XDR were 5%, 50%, and 45%, respectively. The frequency of co-production between MDR, XDR, and PDR with MBL, ESBL, and Biofilm was 35%, 12.5% and 5%, respectively. Among the ESBLs, the frequency of distribution of bla VEB-1gene and blaGES-5 gene was 50% and 40 %, respectively. Bacterial isolates simultaneously carrying blaVEB-1 gene with multiple ß-lactamases of different classes of biofilm, MDR, PDR, and XDR as same as a coexisting blaGES-5 gene. One isolate was detected as new isolates registered in global gene bank as locally P. aeruginosa isolates in Erbil city (LOCUS MN900953). The phylogenetic trees of the blaVEB gene isolates were demonstrated a genotype closely related to others, deposited in GenBank similar to the P. aeruginosa gene; gene sequencing revealed a 99% similarity with other isolates deposited in GenBank.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Biofilmes/crescimento & desenvolvimento , Queimaduras/microbiologia , Genótipo , Humanos , Imipenem/farmacologia , Meropeném/farmacologia , Testes de Sensibilidade Microbiana/métodos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , Homologia de Sequência de Aminoácidos , beta-Lactamases/metabolismo
11.
Int J Syst Evol Microbiol ; 71(11)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34762579

RESUMO

Strain TUM18999T was isolated from the skin of a patient with burn wounds in Japan. The strain was successfully cultured at 20-42 °C (optimum, 30-35 °C) in 1.0-4.0% NaCl (w/v) and at pH 5.5-9.5, optimum pH 5.5-8.5. The phylogenetic tree reconstructed using 16S rRNA, gyrB, rpoB and rpoD gene sequences indicated that strain TUM18999T is closely related to Pseudomonas otitidis MCC10330T. Although the partial 16S rRNA gene sequence (1412 bp) of TUM18999T exhibits high similarity to those of Pseudomonas alcaligenes NBRC 14159T (99.08 %) and Pseudomonas otitidis MCC10330T (98.51 %), multi-locus sequence analysis using 16S rRNA, gyrB, rpoB and rpoD genes reveals a clear distinction between TUM18999T and other Pseudomonas species. In addition, an average nucleotide identity >90 % was not observed in the P. aeruginosa group. Moreover, TUM18999T and P. otitidis can be distinguished based on the minimum inhibitory concentration for carbapenem. Meanwhile, the cellular fatty acids are enriched with C18 : 1 ω7c/C18 : 1 ω6c (34.35 %), C16 : 1 ω7c/C16 : 1 ω6c (24.22 %), C16 : 0 (19.79 %) and C12 : 0 (8.25 %). Based on this evidence, strain TUM18999T can be defined as representing a novel Pseudomonas species, with the proposed name Pseudomonas tohonis sp. nov. The type strain is TUM18999T (GTC 22698T=NCTC 14580T).


Assuntos
Queimaduras , Filogenia , Pseudomonas/classificação , Pele/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Queimaduras/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/química , Genes Bacterianos , Humanos , Japão , Pseudomonas/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
12.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 142-147, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817325

RESUMO

Organic solvent-resistant proteases are used to synthesize valuable pharmaceutical and industrial compounds. Using an available and inexpensive source can be very effective in producing this enzyme. For this purpose, Staphylococcus aureus KP091274 was isolated from burn infection and a medium optimization procedure in the presence of organic solvents was considered for four factors of incubation time, the concentration of Mg2+, glycerol and sorbitol using the response surface methodology. The results of this statistical method showed that incubation time has the most effect and glycerol concentration has the least positive effect on enzyme secretion. As a result of applying the optimized conditions in the bacterial culture medium (3mM of Mg2+, 1.5% W/V of glycerol, 0.4% W/V of sorbitol and 72 hours of incubation), the enzyme secretion reaches its maximum.


Assuntos
Proteínas de Bactérias/metabolismo , Peptídeo Hidrolases/metabolismo , Solventes/química , Staphylococcus aureus/enzimologia , Proteínas de Bactérias/isolamento & purificação , Queimaduras/microbiologia , Meios de Cultura/química , Meios de Cultura/metabolismo , Estabilidade Enzimática , Glicerol/metabolismo , Concentração de Íons de Hidrogênio , Magnésio/metabolismo , Peptídeo Hidrolases/isolamento & purificação , Filogenia , RNA Ribossômico 16S/genética , Sorbitol/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/fisiologia , Especificidade por Substrato , Temperatura
13.
NPJ Biofilms Microbiomes ; 7(1): 73, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504100

RESUMO

Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.


Assuntos
Bactérias/classificação , Biofilmes , Queimaduras/microbiologia , Animais , Antibacterianos , Queimaduras/tratamento farmacológico , Coinfecção , Modelos Animais de Doenças , Humanos , Camundongos , Mariposas , Pele , Suínos , Cicatrização , Infecção dos Ferimentos
14.
Infect Immun ; 89(11): e0033621, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34424744

RESUMO

Cutaneous thermal injuries from burns/explosives are a major cause of morbidity and mortality and represent a monumental burden on our current health care system. Injury severity is predominantly due to potentially lethal sepsis caused by multidrug-resistant (MDR) bacteria such as Pseudomonas aeruginosa (MDR-PA). Thus, there is a critical need to develop novel and effective antimicrobials for the (i) prevention, (ii) treatment, and (iii) healing of such wounds that are complicated by MDR-P. aeruginosa and other bacterial infections. AB569 is a novel bactericidal tandem consisting of acidified NaNO2 (A-NO2-) and Na2-EDTA. Here, we first show that AB569 acts synergistically to kill all human burn wound strains of P. aeruginosa in vitro. This was found to be due, in part, to the generation of A-NO2--mediated nitric oxide (NO) formation coupled with the metal chelating properties of Na2-EDTA. Using a murine scald burn wound model of P. aeruginosa infection, an AB569-Solosite gel formulation eradicated all bacteria. Futher, we also demonstrate enhanced AB569-mediated wound healing by not only accelerating wound contraction, but also by reducing levels of the proinflammatory cytokines interleukin-6 (IL-6) and IL-1ß while increasing the levels of anti-inflammatory cytokine, IL-10, and granulocyte-colony-stimulating factor (G-CSF). We also observed better epidermal restoration in AB569-treated wounds. Taken together, we conclude that this study provides solid foundational evidence that AB569 can be used topically to treat highly problematic dermal insults, including wound, burn, blast, and likely, diabetic infections in civilian and military populations, and help relieve the economical burden that MDR organisms have on the global health care system.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Ácido Edético/farmacologia , Nitritos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Queimaduras/complicações , Queimaduras/microbiologia , Colágeno/genética , Modelos Animais de Doenças , Ácido Edético/uso terapêutico , Géis , Óxido Nítrico/biossíntese , Nitritos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico
15.
Int J Biol Macromol ; 189: 597-606, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34418421

RESUMO

Millions of people are burned worldwide every year and 265,000 of the cases are fatal. The development of burn treatment cannot consist only of the administration of a single drug. Due to the infection risk, antibiotics are used in conjunction with gels and damp bandages. In this work, an inexpensive curative based on silver sulfadiazine (SS) and natural rubber latex (NRL) was developed to treat burn wounds. It was produced by the casting method. The infrared spectrum presented no interaction between drug and biopolymer. At the same time, electronic micrographs showed that the SS crystals are inserted on the polymeric dressing surface. Mechanical properties after the drug incorporation were considered suitable for dermal application. About 32.4% of loaded SS was released in 192 h by the dressings that also inhibited the growth of Candida albicans and Candida parapsilosis at 75.0 and 37.5 µg·mL-1, respectively. The curative proved to be biocompatible when applied to fibroblast cells, in addition to enhancing cellular proliferation and, in the hemocompatibility test, no hemolytic effects were observed. The good results in mechanical, antifungal and biological assays, combined with the average bandage cost of $0.10, represent an exciting alternative for treating burn wounds.


Assuntos
Bandagens , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Candida/fisiologia , Borracha/farmacologia , Sulfadiazina de Prata/uso terapêutico , Animais , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Cinética , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Ovinos , Sulfadiazina de Prata/química , Sulfadiazina de Prata/farmacologia , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Microbiol Spectr ; 9(1): e0023321, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346751

RESUMO

Dimethyl sulfoxide (DMSO) and polyethylene glycols (PEGs) are frequently used as potent excipients in pharmaceutical formulations. However, these agents also have an interesting antimicrobial and anti-inflammatory profile that could interfere with the efficacy testing of anti-infective compounds when the latter are solubilized in DMSO or PEGs. Here, we demonstrate the antimicrobial and anti-inflammatory effects of DMSO-PEG400 in a murine Pseudomonas aeruginosa infection model, aiming to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infectives. IMPORTANCE Our study demonstrates the antimicrobial and anti-inflammatory effects of the combination of DMSO and PEG400 against Pseudomonas aeruginosa in vitro and in vivo in a murine infection model of heightened intestinal permeability. The aim of this study is to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infective compounds, to avoid interference with the assay or system tested. This is an extremely important consideration, since potential antimicrobial and anti-inflammatory effects of the solvent vehicle are detrimental to research studies on the efficacy of new anti-infective agents, given that the vehicle effect can mask the effect of the tested compounds. Our results can therefore be of great value to the scientific community, as they can guide researchers in the future to avoid this significant pitfall that can cost substantial amounts of money and valuable time during investigations of the effects of novel, difficult-to-solubilize antimicrobial compounds.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Dimetil Sulfóxido/farmacologia , Polietilenoglicóis/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Queimaduras/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Solventes , Virulência/efeitos dos fármacos
17.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202446

RESUMO

Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells.


Assuntos
Antibacterianos , Queimaduras , Terapia Baseada em Transplante de Células e Tecidos , Dendrímeros , Proteínas Citotóxicas Formadoras de Poros , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/crescimento & desenvolvimento , Percepção de Quorum/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Queimaduras/microbiologia , Queimaduras/patologia , Queimaduras/terapia , Células Cultivadas , Dendrímeros/química , Dendrímeros/farmacologia , Humanos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/mortalidade
18.
Mol Immunol ; 136: 118-127, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34130152

RESUMO

Pseudomonas aeruginosa (PA) is one of the most dominant causes of nosocomial infections in burn patients. Increasing emergence of antibiotic-resistant strains highlights the need for novel antimicrobial agents. Flagellin, the main component protein of flagellum, is determined as the major antigen interacting with anti-P. aeruginosa IgY antibodies. The current study was aimed to evaluate the antibacterial potency of IgY antibodies raised against recombinant type A, and B flagellins. The immunogenicity and specificity of IgY antibodies were confirmed through indirect ELISA and western blot analysis, respectively. Anti-flagellin IgYs reduced the motility, biofilm formation and invasion potency of both strains. The cell surface hydrophobicity (CSH) of bacteria was increased upon IgY treatment, and in vitro opsonophagocytosis assay confirmed the high protective potency of specific antibodies via polymorphonuclear leukocyte (PMN)-augmented bacterial cell killing. The protective efficacy of IgYs was also studied in both acute pneumonia and burn wound murine models. Anti-flagellin B-IgY induced 100 % and 40 % protection against laboratory, and hospital strains in burn wound model, respectively. Protection in acute pneumonia against all strains was 100 %. Anti-flagellin A-IgY failed to protect mice in burn wound model, but provided 100 % protection against all strains in acute pneumonia challenge. In vitro, ex vivo and in vivo experiments confirmed the dose-dependent and non-type specific essence of anti-flagellin IgY antibodies, providing the benefit of covering all strain types in a dose dependent manner. Our findings provide evidence that anti-flagellin IgY antibodies qualify as novel economical therapeutic option against PA infection.


Assuntos
Queimaduras/microbiologia , Flagelina/imunologia , Imunoglobulinas/imunologia , Pneumonia/microbiologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Animais , Biofilmes/crescimento & desenvolvimento , Queimaduras/imunologia , Galinhas , Infecção Hospitalar/microbiologia , Modelos Animais de Doenças , Imunização Passiva , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Pneumonia/imunologia , Infecções por Pseudomonas/imunologia
19.
Drug Deliv Transl Res ; 11(4): 1532-1544, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34125402

RESUMO

There is an urgent need for treatments for hydrofluoric acid (HF) burns and their derivative problems that prevent hydrogen ion dissociation and fluoride ion binding to tissues. This study evaluated the ability of chitosan-based hydrogels combined with a buffer solution containing either boric acid or Tris and calcium gluconate (CHS-BA-CG and CHS-Tris-CG) to repair HF burn wounds and prevent wound infections. We assessed calcium release rates and biocompatability and constructed a mouse HF burn model to assess the tissue repair effects of the hydrogels. Finally, we performed disc diffusion tests from burn tissue and quantified the bacterial counts to assess the anti-infection properties of the hydrogels. Calcium was gradually released in the CHS-BA-CG and CHS-Tris-CG groups (73% and 43%, respectively, after 48 h). The cell viabilities at 48 h after HF burn in these groups were significantly higher than those in the phosphate-buffered saline (PBS) and CG-treated groups. Histopathological evaluation showed a clear boundary between the epidermal and dermal layers in both CHS-BA-CG and CHS-Tris-CG-treated groups, indicating their effectiveness in tissue repair. In the disc diffusion test, CHS-BA-CG and CHS-Tris-CG exhibited larger inhibition zones against Acinetobacter baumannii than those for PBS and CG. The bacterial counts on HF burn wounds were significantly lower in the CHS-BA-CG and CHS-Tris-CG-treated groups than those in the PBS and CG-treated groups. The in vitro studies demonstrated the biocompatibility and antimicrobial effects of the CHS-BA-CG and CHS-Tris-CG hydrogels. Both gels also demonstrated tissue repair and anti-infection effects. Thus, chitosan-based hydrogels may be candidates for HF burn therapy.


Assuntos
Queimaduras Químicas , Queimaduras , Quitosana , Infecção dos Ferimentos , Animais , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Ácido Fluorídrico , Hidrogéis/química , Camundongos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/prevenção & controle
20.
Infect Immun ; 89(10): e0009121, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34152806

RESUMO

Of the 486,000 burn injuries that required medical treatment in the United States in 2016, 40,000 people were hospitalized, with >3,000 fatalities. After burn injury, humans are at increased risk of sepsis and mortality from infections caused by Pseudomonas aeruginosa, an opportunistic pathogen. We hypothesize that systemic events were initiated from the burn that increased the host's susceptibility to P. aeruginosa. A nonlethal 10% total body surface area (TBSA), full-thickness flame burn was performed in CD-1 mice without and with subsequent P. aeruginosa (strain M2) infection. The 50% lethal dose for subcutaneous infection with P. aeruginosa M2 at the burn site immediately after the burn decreased by 6 log, with mortality occurring between 18 and 26 h, compared with P. aeruginosa-infected mice without burn injury. Bacteria in distal organs were detected by 18 h, concurrent with the onset of clinical symptoms. Serum proinflammatory cytokines (interleukin-6 [IL-6], IL-1ß, gamma interferon, and tumor necrosis factor alpha) and the anti-inflammatory cytokine IL-10 were first detected at 12 h postburn with infection and continued to increase until death. Directly after burn alone, serum levels of HMGB1, a danger-associated molecular pattern and TLR4 agonist, transiently increased to 50 ng/ml before returning to 20 ng/ml. Burn with P. aeruginosa infection increased serum HMGB1 concentrations >10-fold (250 ng/ml) at the time of death. This HMGB1-rich serum stimulated TLR4-mediated NF-κB activation in a TLR4 reporter cell line. Treatment of infected burned mice with P5779, a peptide inhibitor of HMGB1, increased the mean survival from 23 to 42 h (P < 0.0001). We conclude that the high level of serum HMGB1, which preceded the increase in proinflammatory cytokines, is associated with postburn mortality.


Assuntos
Queimaduras/imunologia , Queimaduras/microbiologia , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Modelos Animais de Doenças , Feminino , Proteína HMGB1/imunologia , Inflamação/imunologia , Inflamação/microbiologia , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-6/imunologia , Camundongos , NF-kappa B/imunologia , Sepse/imunologia , Sepse/microbiologia , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/imunologia
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