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1.
Ugeskr Laeger ; 186(16)2024 Apr 15.
Artigo em Dinamarquês | MEDLINE | ID: mdl-38704724

RESUMO

Pyomyositis is a bacterial infection of striated muscle, usually located to muscles in the extremities or pelvis. We present a microbiologically unique case report of pyomyositis in the sternocleidomastoid muscle (the first of its kind in Denmark) caused by Staphylococcus epidermidis, S. capitis and possibly Streptococcus pneumoniae. Pyomyositis is very rare but can lead to critical complications such as endocarditis and sepsis. It is therefore important to know the condition when evaluating an infected patient with muscle pain. Treatment consists of antibiotics and - if relevant - surgical abscess drainage.


Assuntos
Antibacterianos , Músculos do Pescoço , Piomiosite , Infecções Estafilocócicas , Humanos , Piomiosite/microbiologia , Piomiosite/diagnóstico , Piomiosite/tratamento farmacológico , Feminino , Adulto , Músculos do Pescoço/patologia , Músculos do Pescoço/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/uso terapêutico , Staphylococcus epidermidis/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação
2.
Pathog Dis ; 822024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38730561

RESUMO

Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.


Assuntos
Antibacterianos , Biofilmes , Gases em Plasma , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Gases em Plasma/farmacologia , Animais , Humanos , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Modelos Animais de Doenças , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico
3.
ACS Biomater Sci Eng ; 10(5): 3401-3411, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38624061

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) causes great health hazards to society because most antibiotics are ineffective. Photodynamic treatment (PDT) has been proposed to combat MRSA due to the advantage of imaging-guided no-drug resistance therapy. However, the traditional photosensitizers for PDT are limited by aggregation-caused quenching for imaging and low photodynamic antibacterial efficiency. In this work, we synthesize a new aggregation-induced emission (AIE) photosensitizer (APNO), which can ultrafast distinguish between Gram-positive and Gram-negative bacteria within 3 s by AIE-active photosensitizer imaging. Meanwhile, APNO can generate antibacterial reactive oxygen species under light irradiation, which holds potential for antibacterial PDT. Then, APNO is loaded by PHEAA hydrogel to obtain a highly efficient photodynamic hydrogel (APNO@gel). In vitro results show complete inhibition of MRSA by APNO@gel under lower-power light irradiation. Transcriptome analysis is performed to investigate antibacterial mechanism of APNO@gel. Most importantly, APNO@gel also exhibits significant inhibition and killing ability of MRSA in the MRSA wound infection model, which will further promote rapid wound healing. Therefore, the photodynamic hydrogel provides a promising strategy toward MRSA ultrafast imaging and killing.


Assuntos
Antibacterianos , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Fármacos Fotossensibilizantes , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico por imagem , Camundongos , Testes de Sensibilidade Microbiana , Humanos
4.
ACS Infect Dis ; 10(5): 1576-1589, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38581387

RESUMO

Exploring novel antimicrobial drugs and strategies has become essential to the fight MRSA-associated infections. Herein, we found that membrane-disrupted repurposed antibiotic salifungin had excellent bactericidal activity against MRSA, with limited development of drug resistance. Furthermore, adding salifungin effectively decreased the minimum inhibitory concentrations of clinical antibiotics against Staphylococcus aureus. Evaluations of the mechanism demonstrated that salifungin disrupted the level of H+ and K+ ions using hydrophilic and lipophilic groups to interact with bacterial membranes, causing the disruption of bacterial proton motive force followed by impacting on bacterial the function of the respiratory chain and adenosine 5'-triphosphate, thereby inhibiting phosphatidic acid biosynthesis. Moreover, salifungin also significantly inhibited the formation of bacterial biofilms and eliminated established bacterial biofilms by interfering with bacterial membrane potential and inhibiting biofilm-associated gene expression, which was even better than clinical antibiotics. Finally, salifungin exhibited efficacy comparable to or even better than that of vancomycin in the MRSA-infected animal models. In conclusion, these results indicate that salifungin can be a potential drug for treating MRSA-associated infections.


Assuntos
Antibacterianos , Biofilmes , Reposicionamento de Medicamentos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Animais , Camundongos , Farmacorresistência Bacteriana/efeitos dos fármacos
5.
Cell Rep ; 43(4): 114082, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38583155

RESUMO

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S. aureus isolates. The regulatory 3' UTR of the vigR mRNA contributes to vancomycin tolerance and upregulates the autolysin IsaA. Using MS2-affinity purification coupled with RNA sequencing, we find that the vigR 3' UTR also regulates dapE, a succinyl-diaminopimelate desuccinylase required for lysine and peptidoglycan synthesis, suggesting a broader role in controlling cell wall metabolism and vancomycin tolerance. Deletion of the 3' UTR increased virulence, while the isaA mutant is completely attenuated in a wax moth larvae model. Sequence and structural analyses of vigR indicated that the 3' UTR has expanded through the acquisition of Staphylococcus aureus repeat insertions that contribute sequence for the isaA interaction seed and may functionalize the 3' UTR.


Assuntos
Regiões 3' não Traduzidas , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Regiões 3' não Traduzidas/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Regulação Bacteriana da Expressão Gênica , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mariposas/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Virulência/genética
6.
Int J Nanomedicine ; 19: 3697-3714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681091

RESUMO

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections. Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied. Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy. Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.


Assuntos
Alginatos , Antibacterianos , Biofilmes , Ouro , Nanotubos , Polietilenos , Compostos de Amônio Quaternário , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Alginatos/química , Alginatos/farmacologia , Nanotubos/química , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Antibacterianos/farmacologia , Antibacterianos/química , Polietilenos/química , Polietilenos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Linhagem Celular , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química
7.
Biomater Sci ; 12(10): 2730-2742, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38639196

RESUMO

Polypropylene (PP) mesh is widely used in hernioplasty, but it is prone to contamination by pathogenic bacteria. Here, we present an infection microenvironment-responsive metal-phenolic network (MPN) coating, which is made up of Cu2+ and tannic acid (TA) (referred to as CT coating), and is fabricated on PP meshes by layer-by-layer (LbL) assembly. The CT coating provided a robust protection for the PP mesh from pathogenic bacterial infection in a pH-responsive manner due to the pH-responsive disassembly kinetics of MPN complexes. Moreover, the PP meshes with ten CT coating cycles (PP-CT(10)) exhibited excellent stability in a physiological environment, with the killing ratio against "superbug" methicillin-resistant Staphylococcus aureus (MRSA) at pH 5.5 exceeding 99% even after 28 days of PBS (pH 7.4) immersion. In addition, the PP-CT(10) exhibited excellent in vivo anti-infective ability in a rodent subcutaneous implant MRSA infection model, and the results of histological and immunohistochemical analyses demonstrated that the reduced bacterial number alleviated the inflammatory response at implant sites. This study revealed that MPN coating is a promising strategy, which could provide a self-defensive ability for various implants to combat post-surgical infections in a pH-responsive manner.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Polipropilenos , Telas Cirúrgicas , Taninos , Concentração de Íons de Hidrogênio , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Polipropilenos/química , Taninos/química , Taninos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Herniorrafia , Cobre/química , Cobre/farmacologia , Camundongos
8.
Eur J Med Chem ; 271: 116401, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38640870

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.


Assuntos
Antibacterianos , Flavonoides , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Enterococos Resistentes à Vancomicina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Animais , Camundongos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Infecções Estafilocócicas/tratamento farmacológico , Humanos
9.
J Colloid Interface Sci ; 666: 434-446, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608638

RESUMO

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.


Assuntos
Antibacterianos , Cobre , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Nanoestruturas , Terapia Fototérmica , Cobre/química , Cobre/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Nanoestruturas/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Propriedades de Superfície , Tamanho da Partícula , Selênio/química , Selênio/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico
10.
Medicine (Baltimore) ; 103(16): e37860, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640320

RESUMO

Staphylococcus aureus is an important human pathogen that has a major impact on public health. The objective of the present work was to determine the prevalence and the pattern of antibiotic susceptibility in S aureus (MRSA) isolates from the King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The isolates were collected from different body sites of infection and the antibiotic susceptibility was confirmed on the Vitek 2 system. A total of 371 MRSA isolates from clinical samples were received over a 12-month period from January 2021 to December 2021. The results showed that infection was predominant among males (55.8%) and most of the isolates occurred in the older age groups, with a mean age of 43.7 years and an age span from <1 to 89 years old. The majority (34.5%) recovered from wound infection followed by (14.6%) from blood. We have observed peaks of MRSA infections during the autumn, especially in September and November. All MRSA isolates were resistant to Amoxicillin + clavulanic acid, Ampicillin, Imipenem, Oxacillin, Cloxacillin, and Penicillin while all isolates were sensitive to Daptomycin and Nitrofurantoin. Furthermore, Vancomycin was resistant in (0.3%) of MRSA isolates, and (2.9%) was resistant to Linezolid. The current study concluded that MRSA strains had developed resistance toward 24 tested antibiotics, including the previous effective drugs vancomycin and linezolid. Therefore, there is an urgent need for continuous review of infection control practices to prevent any further spread of resistant strains.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Masculino , Humanos , Idoso , Adulto , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Vancomicina/farmacologia , Linezolida/farmacologia , Arábia Saudita/epidemiologia , Centros de Atenção Terciária , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia
11.
Ital J Pediatr ; 50(1): 78, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641615

RESUMO

BACKGROUND: Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU). CASE PRESENTATION: Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution. CONCLUSIONS: Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.


Assuntos
Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Recém-Nascido , Humanos , Feminino , Controle de Infecções/métodos , Celulite (Flegmão) , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecção Hospitalar/prevenção & controle , Unidades de Terapia Intensiva Neonatal
12.
Eur J Med Res ; 29(1): 246, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649897

RESUMO

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia. METHODS: Biofilm and slime production of 68 methicillin-susceptible S. aureus (MSSA) and 54 methicillin-resistant (MRSA) isolates were determined using a a plate-based crystal violet assay and Congo Red agar method, respectively. The minimum inhibitory concentration values against 14 antibiotics were determined using VITEK® AST-GP67 cards and interpreted according to CLSI-M100 guidelines. Genetic profiling of 11 S. aureus biofilm-associated genes and agr/sar quorum sensing genes was performed using single or multiplex polymerase chain reaction (PCR) assays. RESULTS: In this study, 75.9% (n = 41) of MRSA and 83.8% (n = 57) of MSSA isolates showed strong biofilm-forming capabilities. Intermediate slime production was detected in approximately 70% of the isolates. Compared to MSSA, significantly higher resistance of clindamycin, erythromycin, and fluoroquinolones was noted among the MRSA isolates. The presence of intracellular adhesion A (icaA) gene was detected in all S. aureus isolates. All MSSA isolates harbored the laminin-binding protein (eno) gene, while all MRSA isolates harbored intracellular adhesion D (icaD), clumping factors A and B (clfA and clfB) genes. The presence of agrI and elastin-binding protein (ebpS) genes was significantly associated with biofilm production in MSSA and MRSA isolates, respectively. In addition, agrI gene was also significantly correlated with oxacillin, cefoxitin, and fluoroquinolone resistance. CONCLUSIONS: The high prevalence of biofilm and slime production among MSSA and MRSA isolates correlates well with the detection of a high prevalence of biofilm-associated genes and agr quorum sensing system. A significant association of agrI gene was found with cefoxitin, oxacillin, and fluoroquinolone resistance. A more focused approach targeting biofilm-associated and quorum sensing genes is important in developing new surveillance and treatment strategies against S. aureus biofilm infection.


Assuntos
Antibacterianos , Biofilmes , Hospitais de Ensino , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Percepção de Quorum , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Percepção de Quorum/genética , Percepção de Quorum/efeitos dos fármacos , Malásia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Antibacterianos/farmacologia , Staphylococcus aureus/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Proteínas de Bactérias/genética
13.
Carbohydr Polym ; 336: 122102, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670773

RESUMO

Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds.


Assuntos
Antibacterianos , Escherichia coli , Glucanos , Hidrogéis , Nanopartículas , Polilisina , Staphylococcus aureus , Cicatrização , Xilanos , Glucanos/química , Glucanos/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Xilanos/química , Xilanos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Polilisina/química , Polilisina/farmacologia , Camundongos , Nanopartículas/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Reagentes de Ligações Cruzadas/química , Infecção dos Ferimentos/tratamento farmacológico , Masculino
14.
Diagn Microbiol Infect Dis ; 109(2): 116295, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579431

RESUMO

BACKGROUND: Patients colonized with Staphylococcus aureus in their nasal passages have a higher risk of acquiring infection, especially if they are immunocompromised or have comorbidities such as chronic renal failure undergoing hemodialysis (HD). OBJECTIVE: This study aimed to report the prevalence of nasal carriage of S. aureus among HD patients utilizing a seven-week sampling protocol and to assess the susceptibility of these isolates to various antimicrobial agents. METHODS: Over seven consecutive weeks, nasal swab samples were collected from 47 HD patients, resulting in a total of 329 samples. The microorganisms were identified using biochemical methods and subjected to antimicrobial susceptibility testing via disk diffusion and microdilution techniques. RESULTS: Out of all the patients analyzed, 25 individuals (53.19%) were found to be colonized by S. aureus, with 21 of them displaying intermittent colonization. Additionally, 38% showed positive results for S. aureus in only the 6th or 7th week of sampling. Within the 58 isolates, 17.2% (n=10) exhibited methicillin (oxacillin)-resistance and 25.86% (n=15) displayed elevated vancomycin MIC values (2 µg/ml). Based on the results, daptomycin and gentamicin were found to be effective treatment options. However, 31% of the isolates (n=18) exhibited a MIC of 1 µg/ml for daptomycin. CONCLUSION: Over half of the patients were colonized by S. aureus, but mostly on an intermittent basis. The identification of oxacillin resistance and high vancomycin and daptomycin MICs serve as warnings for possible future complications in managing bacteremia caused by S. aureus in these patients.


Assuntos
Antibacterianos , Portador Sadio , Testes de Sensibilidade Microbiana , Diálise Renal , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Diálise Renal/efeitos adversos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Portador Sadio/microbiologia , Portador Sadio/epidemiologia , Idoso , Adulto , Prevalência , Idoso de 80 Anos ou mais
15.
Int J Pharm ; 656: 124095, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38588757

RESUMO

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.


Assuntos
Antibacterianos , Antioxidantes , Catequina , Catequina/análogos & derivados , Escherichia coli , Ferrocianetos , Nanopartículas , Polímeros , Espécies Reativas de Oxigênio , Staphylococcus aureus , Catequina/química , Catequina/farmacologia , Catequina/administração & dosagem , Ferrocianetos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos , Polímeros/química , Nanopartículas/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/química , Masculino , Ratos Sprague-Dawley , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Camundongos , Terapia Fototérmica/métodos , Estresse Oxidativo/efeitos dos fármacos
16.
Sci Rep ; 14(1): 8272, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594253

RESUMO

Human hemoglobin (Hb) is the preferred iron source of Staphylococcus aureus. This pathogenic bacterium exploits a sophisticated protein machinery called Iron-regulated surface determinant (Isd) system to bind Hb, extract and internalize heme, and finally degrade it to complete iron acquisition. IsdB, the surface exposed Hb receptor, is a proven virulence factor of S. aureus and the inhibition of its interaction with Hb can be pursued as a strategy to develop new classes of antimicrobials. To identify small molecules able to disrupt IsdB:Hb protein-protein interactions (PPIs), we carried out a structure-based virtual screening campaign and developed an ad hoc immunoassay to screen the retrieved set of commercially available compounds. Saturation-transfer difference (STD) NMR was applied to verify specific interactions of a sub-set of molecules, chosen based on their efficacy in reducing the amount of Hb bound to IsdB. Among molecules for which direct binding was verified, the best hit was submitted to ITC analysis to measure the binding affinity to Hb, which was found to be in the low micromolar range. The results demonstrate the viability of the proposed in silico/in vitro experimental pipeline to discover and test IsdB:Hb PPI inhibitors. The identified lead compound will be the starting point for future SAR and molecule optimization campaigns.


Assuntos
Proteínas de Transporte de Cátions , Infecções Estafilocócicas , Humanos , Staphylococcus aureus/metabolismo , Hemoglobinas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Heme/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Ferro/metabolismo
17.
BMJ Case Rep ; 17(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569736

RESUMO

A healthy man in his late 20s was admitted to the emergency department due to a flare-up in his severe chronic stomatitis, along with flu-like symptoms. CXR showed multiple bilateral consolidations and subsequent CT revealed thrombosis of the left facial and internal jugular vein, together with septic embolism in both lungs. Blood cultures showed penicillin-susceptible Staphylococcus aureus The patient was diagnosed with Lemierre's syndrome, despite atypical bacteria and clinical presentation. During hospitalisation, he developed pulmonary empyema as a complication and was admitted for 4 weeks. During hospitalisation and after discharge, the patient was examined for multiple rheumatic, immunological and dermatological diseases, but no underlying cause for Lemierre's syndrome has been found. We present this case due to the rarity of its nature, with atypical clinical presentation and pathogen for Lemierre's syndrome, but with classic radiological findings.


Assuntos
COVID-19 , Síndrome de Lemierre , Infecções Estafilocócicas , Masculino , Humanos , Staphylococcus aureus , Síndrome de Lemierre/complicações , Síndrome de Lemierre/tratamento farmacológico , Síndrome de Lemierre/diagnóstico , Penicilinas/uso terapêutico , COVID-19/complicações , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico
18.
J Nepal Health Res Counc ; 21(4): 616-622, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38616592

RESUMO

BACKGROUND: Staphylococcus aureus (S.aureus) is an emerging antibiotic resistant bacterium responsible for various infections in human. Resistance to methicillin and vancomycin are of prime concern in S. aureus. The study aims to determine the minimum inhibitory concentration (MIC) of Vancomycin and evaluate the existence of mecA and vanA genes, associated with antibiotic resistance. METHODS: Clinical specimens from three Kathmandu hospitals were processed and S. aureus was identified using conventional microbiological procedures. MRSA was phenotypically identified with cefoxitin (30µg) disc diffusion, while vancomycin susceptibility was assessed using the Ezy MICTM stripes. The mecA and vanA genes were detected by polymerase chain reaction (PCR). RESULTS: Out of 266 S. aureus samples from various clinical specimen subjected for analysis, 77 (28.9%) were found methicillin-resistant (MRSA) and 10 (3.8%) were observed vancomycin-resistant (VRSA). Vancomycin resistant isolates showed a significant correlation between resistance to ampicillin, chloramphenicol, and cefoxitin. The mecA gene was found in 39 of the MRSA isolates, having 50.64% of MRSA cases, while the vanA gene was detected in 4 of the VRSA cases, constituting 40% of VRSA occurrences. CONCLUSIONS: The strains with higher vancomycin minimum inhibitory concentration values (≥ 1.5 µg/ml) displayed increased resistance rates to various antibiotics compared to strains with lower minimum inhibitory concentration values (< 1.5 µg/ml). The presence of vanA genes was strongly associated (100%) with vancomycin resistance, while the 10.3% mecA gene was identified from MRSA having resistance towards vancomycin also.


Assuntos
Infecções Estafilocócicas , Vancomicina , Humanos , Vancomicina/farmacologia , Staphylococcus aureus/genética , Cefoxitina/farmacologia , Nepal , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia
19.
Malays J Pathol ; 46(1): 95-102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38682849

RESUMO

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) are mecA-negative strains with oxacillin minimum inhibitor concentration (MIC) close to the resistance breakpoint of ≥ 4µg/mL. Instead of producing penicillin-binding protein with low affinity to methicillin (oxacillin) mediated by mecA gene as in methicillin-resistant S. aureus (MRSA), BORSA strains are characterised by the hyperproduction of ß-lactamase enzymes, thus able to break down methicillin. Common laboratory methods to detect MRSA such as cefoxitin disk diffusion alone may fail to detect methicillin resistance due to BORSA. We report five cases of BORSA blood-stream infections in a university teaching hospital. All isolates were found to be susceptible to cefoxitin using disk diffusion, resistant to oxacillin using automated MIC method, and did not harbour mecA gene. All patients were suscessfully treated with anti-MRSA antibiotics, and removal of primary sources were done if identified. A more cost-effective method for screening and diagnosis of BORSA is needed in addition to cefoxitin disk diffusion test, in order to monitor the spread, and to enable routine detection and treatment of this pathogen.


Assuntos
Antibacterianos , Oxacilina , Infecções Estafilocócicas , Humanos , Oxacilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Feminino , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Adulto , Idoso , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Cefoxitina/farmacologia , Cefoxitina/uso terapêutico
20.
Int Wound J ; 21(5): e14878, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38682897

RESUMO

The primary objective of this study was to develop a carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCS) hydrogel containing ethylene diamine tetra acetic acid (EDTA) as the materials for wound healing. CMC and CMCS solutions were prepared with a concentration of 4% (w/v). These solutions were made using normal saline serum with a concentration of 0.5% (v/v). Additionally, EDTA with the concentrations of 0.01%, 0.05%, 0.1%, 0.5%, 1%, and 2% (w/v) was included in the prepared polymer solution. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with average in size 88.71 ± 5.93 µm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. The antibacterial experiments showed that the formulated CMC/CMCS/EDTA 0.5% hydrogel inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, the produced hydrogels were haemocompatible and biocompatible. At the last stage, the evaluation of wound healing in the animal model demonstrated that the use of the produced hydrogels significantly improved the process of wound healing. Finally, the findings substantiated the effectiveness of the formulated hydrogels as the materials for promoting wound healing and antibacterial agents.


Assuntos
Biofilmes , Carboximetilcelulose Sódica , Quitosana , Quitosana/análogos & derivados , Ácido Edético , Hidrogéis , Pseudomonas aeruginosa , Staphylococcus aureus , Cicatrização , Animais , Quitosana/farmacologia , Ratos , Ácido Edético/farmacologia , Ácido Edético/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Carboximetilcelulose Sódica/farmacologia , Cicatrização/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Hidrogéis/farmacologia , Modelos Animais de Doenças , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ratos Wistar , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico
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