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1.
Nat Commun ; 15(1): 107, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167880

RESUMO

Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.


Assuntos
Bacteriemia , Infecções Bacterianas , Trombose , Animais , Coelhos , Heparina/farmacologia , Cateteres/microbiologia , Antibacterianos/farmacologia , Trombose/tratamento farmacológico , Trombose/prevenção & controle
2.
ACS Appl Mater Interfaces ; 15(40): 47810-47821, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37782773

RESUMO

Developing coating materials with low cytotoxicity and high antimicrobial activity has been recognized as an effective way to prevent medical device-associated infections. In this study, a maleic anhydride terpolymer (PPTM) is synthesized and covalently attached to silicone rubber (SR) surface. The formed coating can be further cross-linked (SPM) through the self-condensation of pendent siloxane groups of terpolymer. No crack or delamination of SPM was observed after 500 cycles of bending and 7 day immersion in deionized water. The sliding friction force of a catheter was reduced by 50% after coating with SPM. The SPM coating without adding any extra antibacterial reagents can kill 99.99% of Staphylococcus aureus and Escherichia coli and also significantly reduce bacterial coverage, while the coating displayed no antimicrobial activity when maleic anhydride groups of SPM were aminated or hydrolyzed. The results of the repeated disinfection tests showed that the SR coated with SPM could maintain 87.3% bactericidal activity within 5 cycles. Furthermore, the SPM coating only imparted slight toxic effect (>85% viability) on L929 cells after 36 h of coculture, which is superior to the coating of aminated SPM conjugated with the antimicrobial peptide E6. The terpolymer containing maleic anhydride units have great potential as a flexible and durable coating against implant infections.


Assuntos
Anti-Infecciosos , Anidridos Maleicos , Biofilmes , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Cateteres/microbiologia , Elastômeros de Silicone/química , Escherichia coli , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
3.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675063

RESUMO

Coagulase-negative staphylococci (CoNS) and especially Staphylococcus epidermidis are responsible for health care infections, notably in the presence of foreign material (e.g., venous or central-line catheters). Catheter-related bacteremia (CRB) increases health care costs and mortality. The aim of our study was to evaluate the impact of 15 days of antibiotic exposure (ceftobiprole, daptomycin, linezolid and vancomycin) at sub-inhibitory concentration on the resistance, fitness and genome evolution of 36 clinical strains of S. epidermidis responsible for CRB. Resistance was evaluated by antibiogram, the ability to adapt metabolism by the Biofilm Ring test® and the in vivo nematode virulence model. The impact of antibiotic exposure was determined by whole-genome sequencing (WGS) and biofilm formation experiments. We observed that S. epidermidis strains presented a wide variety of virulence potential and biofilm formation. After antibiotic exposure, S. epidermidis strains adapted their fitness with an increase in biofilm formation. Antibiotic exposure also affected genes involved in resistance and was responsible for cross-resistance between vancomycin, daptomycin and ceftobiprole. Our data confirmed that antibiotic exposure modified bacterial pathogenicity and the emergence of resistant bacteria.


Assuntos
Bacteriemia , Daptomicina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Vancomicina/farmacologia , Daptomicina/farmacologia , Staphylococcus epidermidis , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cateteres/microbiologia , Testes de Sensibilidade Microbiana , Biofilmes
4.
Adv Healthc Mater ; 12(4): e2202096, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36285359

RESUMO

Constructing multifunctional surfaces is one of the practical approaches to address catheter-related multiple complications but is generally time-consuming and substrate-dependent. Herein, a novel anti-adhesion, antibacterial, low friction, and robustness coating on medical catheters are developed via a universal and readily scalable method based on a regulable polyelectrolyte surfactant complex. The complex is rapidly assembled in one step by electrostatic and hydrophobic interactions between organosilicon quaternary ammonium surfactant (N+ Si ) and adjustable polyelectrolyte with cross-linkable, anti-adhesive, and anionic groups. The alcohol-soluble feature of the complex is conducive to the rapid formation of coatings on any medical device with arbitrary shapes via dip coating. Different from the conventional polyelectrolyte-surfactant complex coating, the regulated complex coating with nonleaching mode could be stable in harsh conditions (high concentration salt solution, organic reagents, etc.) because of the cross-linked structure while improving the biocompatibility and reducing the adhesion of various bacteria, proteins, and blood cells. The coated catheter exhibits good antibacterial infection in vitro and in vivo, owing to the synergistic effect of N+ Si and zwitterionic groups. Therefore, the rationally designed complex supplies a facile coating approach for the potential development in combating multiple complications of the medical catheter.


Assuntos
Cateteres , Tensoativos , Polieletrólitos , Tensoativos/farmacologia , Cateteres/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Compostos de Amônio Quaternário , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
5.
JPEN J Parenter Enteral Nutr ; 47(1): 159-164, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129005

RESUMO

BACKGROUND: A fungal-related catheter-related bloodstream infection (CRBSI) is less frequent than those induced by bacteria. In the past, a single episode of fungal CRBSI has been used as a marker of home parenteral nutrition (HPN) failure and thus a possible indication for intestinal transplantation. METHODS: Survival outcomes were assessed from a prospectively maintained database of patients initiated on HPN for underlying chronic intestinal failure between 1993 and 2018, with a censoring date of December 31, 2020. Cox regression was performed to assess predictors of mortality with univariable and multivariable analysis. RESULTS: A total of 1008 patients were included in the study, with a total of 1 364 595 catheter days. There were 513 CRBSI events recorded in 262 patients, equating to a CRBSI rate of 0.38/1000 catheter days. A total of 38/262 (14.5%) patients had at least one episode of fungal CRBSI, whereas 216/262 (82.4%) had at least one bacterial but no fungal CRBSI. The median time between HPN initiation and the first CRBSI episode was 20.6 months (95% confidence interval, 16.5-24.1). Episodes of fungal or bacterial CRBSI and the number of CRBSI episodes were not associated with increased mortality. Overall, 15 CRBSI-related deaths were observed in the observation period (0.01 CRBSI deaths/1000 catheter days), two of these were fungal in origin. CONCLUSION: The occurrence of a fungal CRBSI does not increase the risk of death compared with patients who have bacterial CRBSI or those without a CRBSI event.


Assuntos
Bacteriemia , Infecções Relacionadas a Cateter , Cateteres Venosos Centrais , Insuficiência Intestinal , Nutrição Parenteral no Domicílio , Sepse , Humanos , Infecções Relacionadas a Cateter/etiologia , Estudos Retrospectivos , Cateteres/microbiologia , Nutrição Parenteral no Domicílio/efeitos adversos , Sepse/etiologia , Bacteriemia/epidemiologia , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia
6.
Arq. ciências saúde UNIPAR ; 26(3): 1325-1342, set-dez. 2022.
Artigo em Português | LILACS | ID: biblio-1402281

RESUMO

A infecção do trato urinário (ITU) nada mais é do que o acometimento das vias urinárias por microrganismo. Entre as infecções hospitalares de maior incidência está a infecção do trato urinário, acometendo mais mulheres do que homens. Uma das possíveis causas dessa infecção, em pacientes na unidade de terapia intensiva (UTI), é o uso de cateter vesical. Seu tratamento inadequado pode ocasionar uma pielonefrite, podendo adentrar à circulação sanguínea, gerando uma infecção sistêmica e levar o paciente a óbito. A resistência antimicrobiana é uma das principais dificuldades encontrada em UTI sendo considerado um problema de saúde pública. O objetivo deste trabalho foi realizar um breve relato, baseado na literatura, sobre a resistência antimicrobiana na infecção urinária em unidade de terapia intensiva adulta. Em ambientes hospitalares o principal microrganismo causador de ITU é Escherichia coli, sendo 55,5% das culturas positivas estão associadas a procedimentos invasivos, como as sondas vesicais de demora, como consequência este é o microrganismo que mais apresenta resistência aos antimicrobianos utilizados como a ampicilina, trimetoprima e ciprofloxacino. O uso indiscriminado de antibióticos deixa em evidência a necessidade de análise criteriosa da real necessidade de qual antimicrobianos usar, tempo de uso e forma correta de administração. Portanto é necessária a ação dos profissionais de saúde frente a atenção ao paciente, desde a higiene das mãos, uso do cateter, quando necessário observar a real necessidade do uso do antimicrobianos e que esse seja feito após cultura e antibiograma.


Urinary tract infection (UTI) is nothing more than the involvement of the urinary tract by a microorganism. Among the hospital infections with the highest incidence is urinary tract infections, affecting more women than men. One of the possible causes of this infection in patients in the intensive care unit (ICU) is the use of a bladder catheter. Its inadequate treatment can cause pyelonephritis, which can enter the bloodstream, generating a systemic infection and leading the patient to death. Antimicrobial resistance is one of the main difficulties encountered in ICUs and is considered a public health problem. The objective of this study was to present a brief report, based on the literature, on antimicrobial resistance in urinary tract infections in an adult intensive care unit. In hospital environments, the main microorganism that causes UTI is Escherichia coli, and 55.5% of positive cultures are associated with invasive procedures, such as indwelling urinary catheters, as a consequence, this is the microorganism that is most resistant to antimicrobials used, such as ampicillin, trimethoprim and ciprofloxacin. The indiscriminate use of antibiotics highlights the need for a careful analysis of the real need for which antimicrobials to use, time of use, and correct form of administration. Therefore, it is necessary for the action of health professionals in the care of the patient, from the hygiene of the professional to, the use of the catheter, when necessary to observe the real need for the use of antimicrobials and that this is done after culture and antibiogram.


La infección del tracto urinario (ITU) no es más que la afectación de las vías urinarias por un microorganismo. Entre las infecciones hospitalarias con mayor incidencia se encuentra la infección del tracto urinario, que afecta más a mujeres que a hombres. Una de las posibles causas de esta infección en pacientes en la unidad de cuidados intensivos (UCI) es el uso de una sonda vesical. Su tratamiento inadecuado puede causar pielonefritis, la cual puede ingresar al torrente sanguíneo, generando una infección sistémica y llevando al paciente a la muerte. La resistencia a los antimicrobianos es una de las principales dificultades encontradas en las UCI y se considera un problema de salud pública. El objetivo de este estudio fue presentar un breve informe, basado en la literatura, sobre la resistencia antimicrobiana en infecciones del tracto urinario en una unidad de cuidados intensivos de adultos. En ambientes hospitalarios, el principal microorganismo causante de ITU es Escherichia coli, y el 55,5% de los cultivos positivos están asociados a procedimientos invasivos, como sondas vesicales permanentes, por lo que este es el microorganismo más resistente a los antimicrobianos utilizados, como la ampicilina. ., trimetoprima y ciprofloxacino. El uso indiscriminado de antibióticos pone de relieve la necesidad de un análisis cuidadoso de la necesidad real de qué antimicrobianos utilizar, el momento de uso y la forma correcta de administración. Por lo tanto, es necesaria la actuación de los profesionales de la salud en el cuidado del paciente, desde la higiene del profesional, uso del catéter, cuando sea necesario observar la necesidad real del uso de antimicrobianos y que este se realice previo cultivo y antibiograma.


Assuntos
Humanos , Feminino , Infecções Urinárias/complicações , Infecções Urinárias/mortalidade , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Sistema Urinário , Mulheres , Ciprofloxacina/uso terapêutico , Infecção Hospitalar/complicações , Infecção Hospitalar/transmissão , Escherichia coli/patogenicidade , Cateteres/microbiologia , Higiene das Mãos , Ampicilina/uso terapêutico , Unidades de Terapia Intensiva , Anti-Infecciosos/uso terapêutico , Antibacterianos/uso terapêutico
7.
Sci Rep ; 12(1): 13992, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978046

RESUMO

Proteus mirabilis (P. mirabilis) is a frequent cause of catheter-associated urinary tract infections. This study aims to investigate the anti-infective effect of Alhagi maurorum extract (AME), the traditional medicinal plant in the middle east, on the biofilm-forming P. mirabilis isolates. Hydroalcoholic extract and oil of A. maurorum were characterized by HPLC and GC-MS. The antiproliferative, anti-biofilm, and bactericidal activity of AME at various concentrations were assessed by turbidity, crystal violet binding, and agar well diffusion assays, respectively. The AME's effect on adhesion and quorum sensing (QS) were investigated by in vitro adhesion assay on cell culture and agar overlay assay using Janthinobacterium lividum (ATCC 12472) as a biosensor strain. In addition, the expression level of selected genes involved in QS and biofilm regulation were determined by quantitative Real-Time PCR. Furthermore, the bladder phantom model was created to evaluate the assays and investigate the catheter's calcium deposition. The most effective chemical compounds found in AME were tamarixetin, quercetin, and trans-anethole. Although AME did not inhibit swarming motility, it reduced biofilm production and exerted a concentration-dependent anti-adhesive and anti-QS activity against P. mirabilis. AME also downregulated the expression level of selected genes involved in biofilm formation and QS. This study showed that AME as a natural compound reduced biofilm formation of P. mirabilis by targeting virulence factor genes, quorum sensing, and other strategies that include preventing the adhesion of P. mirabilis to the cells. The results suggest that A. maurorum extract might have the potential to be considered for preventing UTIs caused by P. mirabilis.


Assuntos
Biofilmes , Fabaceae , Extratos Vegetais , Plantas Medicinais , Proteus mirabilis , Percepção de Quorum , Ágar , Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cateteres/efeitos adversos , Cateteres/microbiologia , Fabaceae/química , Humanos , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/genética , Proteus mirabilis/patogenicidade , Proteus mirabilis/fisiologia , Percepção de Quorum/efeitos dos fármacos , Percepção de Quorum/genética , Infecções Urinárias/microbiologia , Virulência/efeitos dos fármacos , Virulência/genética
8.
Biomater Adv ; 134: 112563, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35525746

RESUMO

Controlling bacterial biofilm formation on silicone-based bloodstream catheters is of great concern to prevent related-infections. In this study, rhamnolipids (RLs), glycolipid biosurfactants, specifically a RLs mixture and the purified di-RL (RhaRhaC10:0C10:0) were covalently bonded to silicone with the intention of reaching long-lasting antibiofilm surfaces. RLs mixture and di-RL were identified by an UHPLC-MS method that also allowed the confirmation of compound isolation by automated flash chromatography. Silicone surfaces underwent air-plasma treatment, inducing reactive oxygen radicals able to promote the RLs grafting that was confirmed by contact angle, FTIR-ATR and AFM measurements. The antibiofilm activity towards different Gram positive strains was evaluated by colony forming units (CFU) count and confocal laser microscopy. In addition, protein adsorption and biocompatibility were also investigated. RLs were successfully grafted onto silicone and RLs mixture and RhaRhaC10C10:0 functionalized specimens reduced the biofilm formation over 2.3 log units against methicillin sensitive Staphylococcus aureus. Additionally, a decrease of 1 log unit was observed against methicillin resistant S. aureus and S. epidermidis. Functionalized samples showed cytocompatibility towards human dermal fibroblasts, hemocompatibility and no vascular irritation potential. The results mentioned above revealed a synergy between the antimicrobial and the anti-adhesive properties of RLs, making these compounds good candidates for the improvement of the medical devices antibiofilm properties.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Biofilmes , Cateteres/microbiologia , Dimetilpolisiloxanos , Glicolipídeos/farmacologia , Humanos , Staphylococcus epidermidis
9.
BMJ Case Rep ; 15(3)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35332006

RESUMO

A 34-year-old man on active chemotherapy was hospitalised with fever, chills and rigours after power-washing a pig pen on a farm. His blood cultures grew Leclercia adecarboxylata, a gram-negative rod in the Enterobacteriaceae family, which has been isolated from a variety of environments including soil, surface water, as well as in the gastrointestinal flora of farm animals. The likely source of infection was his tunnelled central venous catheter exposed to water contaminated by faeces when he was washing the pig pen. While there have been several cases reported of catheter-related L. adecarboxylata bacteraemia, to our knowledge there are very few reports of infection spread in this manner.


Assuntos
Bacteriemia , Infecções por Enterobacteriaceae , Animais , Bacteriemia/diagnóstico , Bacteriemia/etiologia , Cateteres/efeitos adversos , Cateteres/microbiologia , Enterobacteriaceae , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/etiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Suínos
10.
J Appl Microbiol ; 132(5): 3915-3924, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35157342

RESUMO

AIMS: Since management of catheter-associated infections, which are generally biofilm-based, is attempted in certain patients such as older and frail patients by using a catheter lock solution (CLS), we examined the combination of N-acetyl cysteine (NAC), an antibiofilm agent, and levofloxacin, a broad-spectrum antimicrobial agent, for this purpose. METHODS AND RESULTS: Intravascular catheters were colonized with methicillin-resistant Staphylococcus epidermidis, levofloxacin-sensitive/methicillin-resistant Staph. aureus, levofloxacin-resistant/methicillin-resistant Staph. aureus, vancomycin-resistant Enterococcus, Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa and treated with a CLS containing normal saline, NAC, levofloxacin or NAC plus levofloxacin (NACLEV) and then cultured to assess their antimicrobial activities. We also examined antibiofilm and antimicrobial activities of each CLS by scanning electron microscopy (SEM) and the mechanical integrity of catheters exposed to CLS. Treatment of colonized catheters with NACLEV-CLS significantly reduced colonization (p < 0.005) against all pathogens. SEM images also indicate reduction in colonization with NACLEV-CLS with considerable reduction in both visible bacteria and the associated biofilm. Mean tensile strength of catheters exposed to CLS was not significantly different compared to controls (p > 0.05). CONCLUSIONS: These in vitro results suggest that NACLEV-CLS can significantly reduce all bacterial colonization and potentially help salvage infected catheters without affecting the catheter's mechanical integrity. SIGNIFICANCE AND IMPACT OF STUDY: This study presents a novel CLS with a broad spectrum of antimicrobial activity against catheter-associated infections, particularly in long-term catheters.


Assuntos
Anti-Infecciosos , Infecções Relacionadas a Cateter , Staphylococcus aureus Resistente à Meticilina , Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres/microbiologia , Escherichia coli , Humanos , Levofloxacino/farmacologia , Staphylococcus aureus
11.
Carbohydr Polym ; 275: 118683, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742413

RESUMO

Microbial colonization of catheter surfaces is responsible for most healthcare-associated infections. Quaternized chitin and chitosan have excellent antimicrobial and biocompatible properties and can be used to provide safe and prolonged protection for biomedical catheters. Herein, we prepared quaternized ß-chitin derivative (QC)- and quaternized chitosan derivative (QCS)-based antimicrobial surfaces. The quaternized polysaccharides modified TPU surfaces exhibited hydrophilicity, good biocompatibility. Among these, QCS2-modified TPU exhibited excellent antibacterial properties against Gram-positive and Gram-negative bacteria, and prevented the adherence of bacteria compared with pristine TPU. The antibacterial activity of QCS2-modified surfaces maintained for 8 weeks under the condition of immersion in serum. An in vivo subcutaneous implantation experiment revealed 99.87% reduction of bacteria and reduced expression of inflammation-related factors in the surrounding tissue five days after implantation with QCS2-modified TPU. Therefore, quaternized polysaccharide-modified surfaces have promising potential in preventing medical catheter-associated infections.


Assuntos
Antibacterianos/farmacologia , Infecções Relacionadas a Cateter/prevenção & controle , Quitina/química , Quitina/farmacologia , Animais , Aderência Bacteriana/efeitos dos fármacos , Materiais Biocompatíveis/química , Cateteres/microbiologia , Quitina/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Feminino , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Testes de Sensibilidade Microbiana/métodos , Poliuretanos/química , Staphylococcus aureus/efeitos dos fármacos
12.
Sci Rep ; 11(1): 21676, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737361

RESUMO

Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.


Assuntos
Colistina/uso terapêutico , Ácido Edético/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Cateteres/microbiologia , Colistina/metabolismo , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Virulência
13.
Microbiol Spectr ; 9(2): e0055721, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34704827

RESUMO

Central line-associated bloodstream infection (CLABSI) contributes to mortality and cost. While aseptic dressings and antibiotic-impregnated catheters prevent some extraluminal infections, intraluminal infections remain a source of CLABSIs. In this proof-of-concept study, an electrochemical intravascular catheter (e-catheter) prototype capable of electrochemically generating hypochlorous acid intraluminally using platinum electrodes polarized at a constant potential of 1.5 electrode potential relative to saturated silver/silver chloride reference electrode measured in volts (VAg/AgCl) was developed. After 24 h of prepolarization at 1.5 VAg/AgCl, their activity was tested against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and Escherichia coli derived from catheter-related infections. e-catheters generated a mean HOCl concentration of 15.86 ± 4.03 µM and had a mean pH of 6.14 ± 0.79. E-catheters prevented infections of all four species, with an average reduction of 8.41 ± 0.61 log10 CFU/ml at 48 h compared to controls. Polarized e-catheters which generate low amounts of HOCl continuously should be further developed to prevent intraluminal infection. IMPORTANCE Catheter-related infections constitute an economic and mortality burden in health care. Several options are available to reduce the risk of infection, but only a few focus on preventing intraluminal infection, which occurs in long-term catheters, most often used for dialysis, prolonged treatment, or chemotherapy. A prototype of a catheter called an "e-catheter" composed of three electrodes, capable of producing hypochlorous acid (HOCl) electrochemically in its lumen, was developed. When polarized at 1.5 V, chloride ions in the solution are oxidized to continuously produce low amounts of HOCl, which exhibits antibacterial activity in the lumen of the catheter. Here, this prototype was shown to be able to generate HOCl as well as prevent infection in a preliminary in vitro catheter model. This approach is a potential strategy for catheter infection prevention.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateteres , Ácido Hipocloroso/farmacologia , Antibacterianos/farmacologia , Infecções Relacionadas a Cateter/microbiologia , Cateteres/microbiologia , Técnicas Eletroquímicas , Escherichia coli , Feminino , Humanos , Masculino , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle
14.
ACS Appl Mater Interfaces ; 13(31): 36784-36799, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34328312

RESUMO

Bacterial adhesion and the succeeding biofilm formation onto surfaces are responsible for implant- and device-associated infections. Bifunctional coatings integrating both nonfouling components and antimicrobial peptides (AMPs) are a promising approach to develop potent antibiofilm coatings. However, the current approaches and chemistry for such coatings are time-consuming and dependent on substrates and involve a multistep process. Also, the information is limited on the influence of the coating structure or its components on the antibiofilm activity of such AMP-based coatings. Here, we report a new strategy to rapidly assemble a stable, potent, and substrate-independent AMP-based antibiofilm coating in a nonfouling background. The coating structure allowed for the screening of AMPs in a relevant nonfouling background to identify optimal peptide combinations that work in cooperation to generate potent antibiofilm activity. The structure of the coating was changed by altering the organization of the hydrophilic polymer chains within the coatings. The coatings were thoroughly characterized using various surface analytical techniques and correlated with the efficiency to prevent biofilm formation against diverse bacteria. The coating method that allowed the conjugation of AMPs without altering the steric protection ability of hydrophilic polymer structure results in a bifunctional surface coating with excellent antibiofilm activity. In contrast, the conjugation of AMPs directly to the hydrophilic polymer chains resulted in a surface with poor antibiofilm activity and increased adhesion of bacteria. Using this coating approach, we further established a new screening method and identified a set of potent surface-tethered AMPs with high activity. The success of this new peptide screening and coating method is demonstrated using a clinically relevant mouse infection model to prevent catheter-associated urinary tract infection (CAUTI).


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Incrustação Biológica/prevenção & controle , Materiais Revestidos Biocompatíveis/farmacologia , Proteínas Imobilizadas/farmacologia , Acrilamidas/química , Animais , Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Cateteres/microbiologia , Materiais Revestidos Biocompatíveis/síntese química , Humanos , Proteínas Imobilizadas/síntese química , Indóis/química , Masculino , Camundongos Endogâmicos BALB C , Polímeros/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus saprophyticus/efeitos dos fármacos , Staphylococcus saprophyticus/fisiologia , Infecções Urinárias/prevenção & controle
15.
Infect Immun ; 89(10): e0017721, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34280035

RESUMO

Proteus mirabilis is a leading uropathogen of catheter-associated urinary tract infections (CAUTIs), which are among the most common health care-associated infections worldwide. A key factor that contributes to P. mirabilis pathogenesis and persistence during CAUTI is the formation of catheter biofilms, which provide increased resistance to antibiotic treatment and host defense mechanisms. Another factor that is important for bacterial persistence during CAUTI is the ability to resist reactive oxygen species (ROS), such as through the action of the catalase enzyme. Potent catalase activity is one of the defining biochemical characteristics of P. mirabilis, and the single catalase (katA) gene in strain HI4320 was recently identified as a candidate fitness factor for UTI, CAUTI, and bacteremia. Here, we show that disruption of katA results in increased ROS levels, increased sensitivity to peroxide, and decreased biofilm biomass. The biomass defect was due to a decrease in the production of extracellular polymeric substances (EPS) by the ΔkatA mutant and specifically due to reduced carbohydrate content. Importantly, the biofilm defect resulted in decreased antibiotic resistance in vitro and a colonization defect during experimental CAUTI. The ΔkatA mutant also exhibited decreased fitness in a bacteremia model, supporting a dual role for catalase in P. mirabilis biofilm development and immune evasion.


Assuntos
Biofilmes/crescimento & desenvolvimento , Catalase/metabolismo , Infecções Relacionadas a Cateter/microbiologia , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Infecções por Proteus/microbiologia , Proteus mirabilis/enzimologia , Infecções Urinárias/microbiologia , Animais , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Biofilmes/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Cateteres/microbiologia , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos CBA , Infecções por Proteus/tratamento farmacológico , Proteus mirabilis/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico
16.
J Mater Chem B ; 9(23): 4746-4762, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34095937

RESUMO

The surfaces of indwelling catheters offer sites for the adherence of bacteria to form biofilms, leading to various infections. Therefore, the development of antibacterial materials for catheters is imperative. In this study, combining the strong antibacterial effect of a quaternary ammonium salt (QAS) and the high biocompatibility of tannic acid (TA), we prepared a quaternary tannic acid (QTA) by grafting a synthesized quaternary ammonium salt, dimethyl dodecyl 6-bromohexyl ammonium bromide, onto TA. To prepare antibacterial catheters, QTA was blended with thermoplastic polyurethane (TPU) via melt extrusion, which is a convenient and easy-to-control process. Characterization of the TPU blends showed that compared with those of the QAS, dissolution rate and biocompatibility of QTA were significantly improved. On the premise that the introduction of QTA had only a slight effect on the original mechanical properties of pristine TPU, the prepared TPU/QTA maintained satisfactory antibacterial activities in vitro, under a flow state, as well as in vivo. The results verified that the TPU/QTA blend with a QTA content of 4% is effective, durable, stable, and non-toxic, and exhibits significant potential as a raw material for catheters.


Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis , Cateteres/microbiologia , Plásticos/química , Poliuretanos/química , Taninos/farmacologia , Testes de Sensibilidade Microbiana , Propriedades de Superfície
18.
Virulence ; 12(1): 835-851, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33682623

RESUMO

Biofilm-associated polymicrobial infections tend to be challenging to treat. Candida albicans and Staphylococcus aureus are leading pathogens due to their ability to form biofilms on medical devices. However, the therapeutic implications of their interactions in a host is largely unexplored. In this study, we used a mouse subcutaneous catheter model for in vivo-grown polymicrobial biofilms to validate our in vitro findings on C. albicans-mediated enhanced S. aureus tolerance to vancomycin in vivo. Comparative assessment of S. aureus recovery from catheters with single- or mixed-species infection demonstrated failure of vancomycin against S. aureus in mice with co-infected catheters. To provide some mechanistic insights, RNA-seq analysis was performed on catheter biofilms to delineate transcriptional modulations during polymicrobial infections. C. albicans induced the activation of the S. aureus biofilm formation network via down-regulation of the lrg operon, repressor of autolysis, and up-regulation of the ica operon and production of polysaccharide intercellular adhesin (PIA), indicating an increase in eDNA production, and extracellular polysaccharide matrix, respectively. Interestingly, virulence factors important for disseminated infections, and superantigen-like proteins were down-regulated during mixed-species infection, whereas capsular polysaccharide genes were up-regulated, signifying a strategy favoring survival, persistence and host immune evasion. In vitro follow-up experiments using DNA enzymatic digestion, lrg operon mutant strains, and confocal scanning microscopy confirmed the role of C. albicans-mediated enhanced eDNA production in mixed-biofilms on S. aureus tolerance to vancomycin. Combined, these findings provide mechanistic insights into the therapeutic implications of interspecies interactions, underscoring the need for novel strategies to overcome limitations of current therapies.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Infecções Relacionadas a Cateter/tratamento farmacológico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Candida albicans/genética , Infecções Relacionadas a Cateter/microbiologia , Cateteres/microbiologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Staphylococcus aureus/genética , Fatores de Virulência
19.
Folia Med (Plovdiv) ; 63(1): 148-152, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33650409

RESUMO

The use of central venous catheters for hemodialysis continues to grow worldwide, despite the efforts of many specialists. Patients with end-stage renal disease have impaired immunity, which is why infections are the most common complication seen in them. It worsens their quality of life and is a major cause of high morbidity and mortality, especially in hemodialysis patients.We report two cases of catheter-related bloodstream infection in hemodialysis patients caused by Ochrobactrum anthropi, which are the first reported cases in Bulgaria and present a brief literature review of the known facts.


Assuntos
Bacteriemia/etiologia , Infecções Relacionadas a Cateter/microbiologia , Cateteres/efeitos adversos , Infecções por Bactérias Gram-Negativas/etiologia , Falência Renal Crônica/terapia , Ochrobactrum anthropi/isolamento & purificação , Diálise Renal/efeitos adversos , Idoso , Bacteriemia/microbiologia , Bulgária , Infecções Relacionadas a Cateter/etiologia , Cateteres/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Biomater Appl ; 36(3): 385-405, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33530824

RESUMO

Nosocominal infections associated with biofilm formation on urinary catheters cause serious complications. The aim of this study was to investigate the feasibility of the polyurethane (PU) catheter modified with tetracycline hydrochloride (TCH) attached Ag nanoparticles embedded PolyRicinoleic acid-Polystyrene Nanoparticles (PU-TCH-AgNPs-PRici-PS NPs) and the influence on antimicrobial and antibiofilm activity of urinary catheters infected by Escherichia coli and Staphylococcus aureus. For this purpose, AgNPs embedded PRici graft PS graft copolymers (AgNPs-PRici-g-PS) were synthesized via free radical polymerization and characterized by FTIR, HNMR and DSC. AgNPs-PRici-PS NPs were prepared and optimized by the different parameters and the optimized size of nanoparticle was found as about 150 ± 1 nm. The characterization of the nanoparticles and the morphological evaluation were carried out by FTIR and SEM. Short term stability of nanoparticles was realised at 4°C for 30 days. In vitro release profiles of TCH and Ag NPs were also investigated. The formation of biofilm on PU modified TCH-Ag NPs-PRici-PS NPs, was evaluated and the biocompatibility test of the nanoparticles was realized via the mouse fibroblast (L929) and mouse urinary bladder cells (G/G An1). This is the first time that TCH-AgNPs-PRici-PS NPs used in the modification of PU catheter demonstrated high antimicrobial and antibiofilm activities against the urinary tract infection.


Assuntos
Antibacterianos/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Poliestirenos/química , Ácidos Ricinoleicos/química , Prata/administração & dosagem , Infecções Urinárias/prevenção & controle , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cateteres/efeitos adversos , Cateteres/microbiologia , Linhagem Celular , Portadores de Fármacos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Camundongos , Nanopartículas/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
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