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1.
Klin Mikrobiol Infekc Lek ; 27(1): 4-12, 2021 Mar.
Artigo em Tcheco | MEDLINE | ID: mdl-34648644

RESUMO

AIM: The study aimed to characterize enterococcal infections at the University Hospital Olomouc and to define antibiotic treatment options. MATERIAL AND METHODS: The data was obtained from the ENVIS LIMS laboratory information system. Between 1 January 2015 and 31 December 2019, clinically relevant enterococci in the hospital and their resistance to antibiotics were retrospectively evaluated. Until mid-2016, criteria defined by Facklam and Collins and biochemical properties determined with the Encoccus test were used for identification. Subsequently, all enterococci were identified using the MALDI-TOF MS system. The susceptibility to antibiotics was determined using a standard microdilution method according to the EUCAST criteria. RESULTS: A total of 8 239 clinically relevant enterococci were isolated over the 5-year period. The most frequently isolated species were Enterococcus faecalis and Enterococcus faecium, which accounted for more than 90% in the period 2017-2019. Enterococci were most frequently isolated from urine (35 %), surgical wounds (17 %) and urethral/vaginal swabs (17 %). Clinically relevant enterococci were most commonly isolated from patients with oncological diagnoses (22%), those with urinary and genital diseases (15%) and respiratory diseases (9%). Enterococcus faecalis strains showed very low resistance to the antibiotics tested. Enterococcus faecium was shown to have 24 % proportion of vancomycin-resistant strains (VRE). CONCLUSION: Primary antibiotics suitable for treating infections with the etiological role of Enterococcus faecalis include aminopenicillins, in case of severe infections in combination with aminoglycosides, in particular gentamicin. For Enterococcus faecium strains, glycopeptides must be chosen. To treat VRE, linezolid or tigecycline are indicated.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Vancomicina
2.
Rev Chilena Infectol ; 38(3): 317-323, 2021 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-34479286

RESUMO

BACKGROUND: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics. AIM: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges. METHODS: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined. RESULTS: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity. CONCLUSION: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.


Assuntos
Pediatria , Vancomicina , Amicacina , Antibacterianos/uso terapêutico , Criança , Monitoramento de Medicamentos , Humanos , Recém-Nascido , Estudos Retrospectivos
4.
J Biomed Nanotechnol ; 17(8): 1668-1678, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544543

RESUMO

As infection induced by the implant will lead to operation failure, the implant material must be endowed with certain antibacterial properties. Hydroxyapatite (HA) mesoporous microspheres have been widely used in bone repair due to their advantages, including simple synthesis, good osteogenic properties and drug loading capacity. In this study, vancomycin hydrochloride-loaded mesoporous hydroxyapatite microspheres with micro/nanosurface structures were synthesized to increase osteogenic differentiation and antibacterial ability. Phytic acid (IP6) was used as a template to prepare mesoporous hydroxyapatite microspheres composed of fibres, flakes and smooth surfaces by the hydrothermal homogeneous precipitation method, and the corresponding specific surface areas were 65.20 m²/g, 75.13 m²/g and 71.27 m²/g, respectively. Vancomycin hydrochloride (Van) was used as the drug model to study the drug loading and release characteristics of the microspheres, as well as the in vitro antibacterial properties after treatment. In addition, during cocultivation with MC3T3-E1 preosteoblasts, HA microspheres assembled via flakes exhibited better cell compatibility, which promoted cell proliferation, alkaline phosphatase (ALP) activity, and the formation of calcium nodules and increased the expression of osteogenic differentiation-related proteins such as Runx-2, osteopontin (OPN) and collagen I (COL I). These results indicated that the HA microspheres prepared in this experiment have broad application prospects in drug delivery systems and bone repair.


Assuntos
Durapatita , Osteogênese , Antibacterianos/farmacologia , Diferenciação Celular , Durapatita/farmacologia , Microesferas , Vancomicina/farmacologia
5.
Clin Drug Investig ; 41(10): 885-894, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34480725

RESUMO

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality, and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. METHODS: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. RESULTS: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. CONCLUSION: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB.


Assuntos
Daptomicina , Staphylococcus aureus Resistente à Meticilina , Oxazolidinonas , Sepse , Infecções Estafilocócicas , Acetamidas/efeitos adversos , Antibacterianos/efeitos adversos , Análise Custo-Benefício , Humanos , Linezolida , Sepse/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/efeitos adversos
8.
Nat Commun ; 12(1): 5304, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489412

RESUMO

Phenotypic plasticity represents a capacity by which the organism changes its phenotypes in response to environmental stimuli. Despite its pivotal role in adaptive evolution, how phenotypic plasticity is genetically controlled remains elusive. Here, we develop a unified framework for coalescing all single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) into a quantitative graph. This framework integrates functional genetic mapping, evolutionary game theory, and predator-prey theory to decompose the net genetic effect of each SNP into its independent and dependent components. The independent effect arises from the intrinsic capacity of a SNP, only expressed when it is in isolation, whereas the dependent effect results from the extrinsic influence of other SNPs. The dependent effect is conceptually beyond the traditional definition of epistasis by not only characterizing the strength of epistasis but also capturing the bi-causality of epistasis and the sign of the causality. We implement functional clustering and variable selection to infer multilayer, sparse, and multiplex interactome networks from any dimension of genetic data. We design and conduct two GWAS experiments using Staphylococcus aureus, aimed to test the genetic mechanisms underlying the phenotypic plasticity of this species to vancomycin exposure and Escherichia coli coexistence. We reconstruct the two most comprehensive genetic networks for abiotic and biotic phenotypic plasticity. Pathway analysis shows that SNP-SNP epistasis for phenotypic plasticity can be annotated to protein-protein interactions through coding genes. Our model can unveil the regulatory mechanisms of significant loci and excavate missing heritability from some insignificant loci. Our multilayer genetic networks provide a systems tool for dissecting environment-induced evolution.


Assuntos
Adaptação Fisiológica , Epistasia Genética , Escherichia coli/genética , Redes Reguladoras de Genes , Genoma Bacteriano , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Evolução Biológica , Mapeamento Cromossômico , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Teoria do Jogo , Estudo de Associação Genômica Ampla , Genótipo , Fenótipo , Polimorfismo de Nucleotídeo Único , Mapeamento de Interação de Proteínas , Locos de Características Quantitativas , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Vancomicina/farmacologia
9.
ACS Infect Dis ; 7(8): 2565-2582, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34346692

RESUMO

Biofilms, structured communities of bacterial cells embedded in a self-produced extracellular matrix (ECM) which consists of proteins, polysaccharide intercellular adhesins (PIAs), and extracellular DNA (eDNA), play a key role in clinical infections and are associated with an increased morbidity and mortality by protecting the embedded bacteria against drug and immune response. The high levels of antibiotic tolerance render classical antibiotic therapies impractical for biofilm-related infections. Thus, novel drugs and strategies are required to reduce biofilm tolerance and eliminate biofilm-protected bacteria. Here, we showed that gallium, an iron mimetic metal, can lead to nutritional iron starvation and act as dispersal agent triggering the reconstruction and dispersion of mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms in an eDNA-dependent manner. The extracellular matrix, along with the integral bacteria themselves, establishes the integrated three-dimensional structure of the mature biofilm. The structures and compositions of gallium-treated mature biofilms differed from those of natural or antibiotic-survived mature biofilms but were similar to those of immature biofilms. Similar to immature biofilms, gallium-treated biofilms had lower levels of antibiotic tolerance, and our in vitro tests showed that treatment with gallium agents reduced the antibiotic tolerance of mature MRSA biofilms. Thus, the sequential administration of gallium agents (gallium porphyrin and gallium nitrate) and relatively low concentrations of vancomycin (16 mg/L) effectively eliminated mature MRSA biofilms and eradicated biofilm-enclosed bacteria within 1 week. Our results suggested that gallium agents may represent a potential treatment for refractory biofilm-related infections, such as prosthetic joint infections (PJI) and osteomyelitis, and provide a novel basis for future biofilm treatments based on the disruption of normal biofilm-development processes.


Assuntos
Gálio , Staphylococcus aureus Resistente à Meticilina , Porfirinas , Biofilmes , DNA , Gálio/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Vancomicina/farmacologia
10.
BMJ Case Rep ; 14(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389597

RESUMO

Vancomycin is a widely used antibiotic and rarely can cause drug-induced thrombocytopenia. A patient with hospital-acquired meningitis after neurosurgery was treated with systemic and intrathecal vancomycin. On 9th day of antibiotic treatment, the patient's platelets dropped to 0.68×109/L. Multiple platelet transfusions had minimal influence on platelet count. After cessation of vancomycin therapy, platelets returned to normal values without any additional interventions. Diagnosis of vancomycin-induced thrombocytopenia was confirmed by detection of drug-dependent antiplatelet IgG antibodies.


Assuntos
Meningite , Trombocitopenia , Antibacterianos/efeitos adversos , Humanos , Meningite/tratamento farmacológico , Contagem de Plaquetas , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Vancomicina/efeitos adversos
11.
J Infect Chemother ; 27(11): 1614-1620, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34366231

RESUMO

INTRODUCTION: Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development. METHODS: The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis. RESULTS: In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20-5.44 and OR 3.22, 95 % CI 1.31-7.89, respectively). CONCLUSION: Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.


Assuntos
Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Quimioterapia Combinada , Humanos , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Vancomicina/efeitos adversos
12.
BMC Pediatr ; 21(1): 343, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388991

RESUMO

BACKGROUND: Vancomycin is commonly used as part of empiric antibiotic therapy in the preterm infants who develop signs and symptoms of infection. Although skin necrosis has been noted to occur following injection of vancomycin into a peripheral vein in an adult patient, this complication has not been previously described in a preterm infant. CASE PRESENTATION: We report the case of a very low birthweight male infant born at 30 weeks gestational age who developed skin necrosis, most likely as a complication of vancomycin administration via a peripheral venous catheter. The immature skin and endothelial cells of this preterm infant may have increased the risk of drugs related venous and skin toxicity. In this case, assumption of a cumulative toxicity with other drugs administered concomitantly via the same catheter can't be excluded. CONCLUSIONS: To prevent the risk of skin damage, we advocate that in newborn infants, the administration of vancomycin should be limited to a concentration of < 2.5 mg/mL via a peripheral intravenous catheter if a central venous catheter is not available.


Assuntos
Estado Terminal , Vancomicina , Adulto , Células Endoteliais , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Necrose/induzido quimicamente , Vancomicina/efeitos adversos
13.
Talanta ; 234: 122695, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364491

RESUMO

In this study, we aim to develop an antibiotic-based biosensor platform 'Antibiotsensor' for the specific detection of gram-positive bacteria using vancomycin modified Screen Printed Gold Electrodes (SPGEs). Through this pathway, vancomycin molecules were first functionalized with thiol groups and characterized with quadrupole time of flight (q-TOF) mass spectroscopy analysis. Immobilization of thiolated vancomycin molecules (HS-Van) onto SPGEs was carried out based on self-assembled monolayer (SAM) phenomenon. Electrochemical impedance spectroscopy (EIS) was employed to test the detection and showed a considerable change in impedance value upon the binding of HS-Van molecules onto the electrode surface. Atomic Force Microscopy analysis indicated that SPGE was successfully modified upon the treatment with HS-Van molecules based on the shift in surface roughness from 173 ± 2 nm to 301 ± 3 nm. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy proved the EIS and AFM results as well by showing characteristic peaks of immobilized HS-Van molecule. As a proof-of-concept, EIS-based susceptibility testing was performed using Escherichia coli, Staphylococcus aureus and Mycobacterium smegmatis bacteria to prove the specificity of obtained SPGE-Van. EIS data showed that the charge transfer resistance (Rct) values changed from 1.08, 1.18 to 26.5, respectively, indicating that vancomycin susceptible S. aureus was successfully attached onto SPGE-Van surface strongly, while vancomycin resistance E. coli and M. smegmatis did not show any significant attachment properties. In addition, different concentration (108-10 CFU/mL) of S. aureus was performed to investigate sensitivity of proposed sensor platform. Limit of detection and limit of quantitation was calculated as 101.58 and 104.81 CFU/mL, respectively. Scanning electron microscopy (SEM) analysis also confirmed that only S. aureus bacteria was attached to the surface in a dense monolayer distribution. We believe that the proposed approach is selective and sensitive towards the whole-cell detection of vancomycin-susceptible bacteria and can be modified for different purposes in the future.


Assuntos
Técnicas Biossensoriais , Vancomicina , Bactérias , Eletrodos , Escherichia coli , Ouro , Staphylococcus aureus , Vancomicina/farmacologia
14.
Korean J Intern Med ; 36(5): 1204-1210, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34399571

RESUMO

BACKGROUND/AIMS: Multi-drug resistant pathogens are increasing among healthcare-associated infections. It is well known that copper and copper alloys have antimicrobial activity. We evaluated the activity of copper against bacteria in a hospital setting in Korea. METHODS: This study was conducted in a laboratory and medical intensive care unit (ICU). Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecium (VRE) were inoculated onto copper, copper alloy and stainless steel plates. After 24 hours of incubation, colony-forming units (CFU) were counted in the laboratory. Two similar rooms were chosen in the ICU; one room had copper-containing surface, and the other room contained items with a stainless steel surfaces. Items were sampled weekly for 8 weeks when the rooms were not crowded and when the rooms were busier with healthcare workers or visitors. RESULTS: In vitro time-kill curves showed copper or, a copper alloy yielded a significant reduction in MRSA and VRE CFUs over 15 minutes. Upon exposure to stainless steel plates, CFUs were slowly reduced for 24 hours. In vivo, MRSA CFUs were lower in rooms with copper-containing surfaces compared with controls, both after cleaning and after patients had received visitors (p < 0.05). Analysis of VRE revealed similar results, but VRE CFUs from copper-containing surfaces of drug carts in the ICU did not decrease significantly. CONCLUSION: Copper has antimicrobial activity and appears to reduce the number of multi-drug resistant microorganisms in a hospital environment. This finding suggests the potential of the use of copper fittings, instruments and surfaces in hospital.


Assuntos
Infecção Hospitalar , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Ligas , Cobre , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Vancomicina
15.
ACS Infect Dis ; 7(9): 2746-2754, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34387988

RESUMO

Vancomycin functions by binding to lipid II, the penultimate bacterial cell wall building block used by both Gram-positive and Gram-negative species. However, vancomycin is generally only able to exert its antimicrobial effect against Gram-positive strains as it cannot pass the outer membrane (OM) of Gram-negative bacteria. To address this challenge, we here describe efforts to conjugate vancomycin to the OM disrupting polymyxin E nonapeptide (PMEN) to yield the hybrid "vancomyxins". In designing these hybrid antibiotics, different spacers and conjugation sites were explored for connecting vancomycin and PMEN. The vancomyxins show improved activity against Gram-negative strains compared with the activity of vancomycin or vancomycin supplemented with PMEN separately. In addition, the vancomyxins maintain the antimicrobial effect of vancomycin against Gram-positive strains and, in some cases, show enhanced activity against vancomycin-resistant strains. The hybrid antibiotics described here have reduced nephrotoxicity when compared with clinically used polymyxin antibiotics. This study demonstrates that covalent conjugation to an OM disruptor contributes to sensitizing Gram-negative strains to vancomycin while retaining anti-Gram-positive activity.


Assuntos
Polimixinas , Vancomicina , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Vancomicina/farmacologia
16.
Int J Pharm ; 607: 120960, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34333022

RESUMO

In this study, ascorbyl tocopherol succinate (ATS) was designed, synthesized and characterized via FT-IR, HR-MS, H1 NMR and C13 NMR, to simultaneously confer biomimetic and dual responsive properties of an antibiotic nanosystem to enhance their antibacterial efficacy and reduce antimicrobial resistance. Therefore, an in silico-aided design (to mimic the natural substrate of bacterial lipase) was employed to demonstrate the binding potential of ATS to lipase (-32.93 kcal/mol binding free energy (ΔGbind) and bacterial efflux pumps blocking potential (NorA ΔGbind: -37.10 kcal/mol, NorB ΔGbind: -34.46 kcal/mol). ATS bound stronger to lipase than the natural substrate (35 times lower Kd value). The vancomycin loaded solid lipid nanoparticles (VM-ATS-SLN) had a hydrodynamic diameter, zeta potential, polydispersity index and entrapment efficiency of 106.9 ± 1.4 nm, -16.5 ± 0.93 mV, 0.11 ± 0.012 and 61.9 ± 1.31%, respectively. In vitro biocompatibility studies revealed VM-ATS-SLN biosafety and non-haemolytic activity. Significant enhancement in VM release was achieved in response to acidified pH and lipase enzyme, compared to controls. VM-ATS-SLN showed enhanced sustained in vitro antibacterial activity for 5 days, 2-fold greater MRSA biofilm growth inhibition and 3.44-fold reduction in bacterial burden in skin infected mice model compared to bare VM. Therefore, ATS shows potential as a novel multifunctional adjuvant for effective and targeted delivery of antibiotics.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Animais , Antibacterianos , Biomimética , Concentração de Íons de Hidrogênio , Lipase , Lipídeos , Camundongos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Vancomicina , Vitaminas
18.
Int J Pharm ; 607: 120990, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34389419

RESUMO

Transdermal drug delivery is an attractive route of administration relative to other routes as it offers enhanced therapeutic efficacy. However, due to poor skin permeability of certain drugs, their application in transdermal delivery is limited. The ultra-deformable nature of transferosomes makes them suitable vehicles for transdermal delivery of drugs that have high molecular weights and hydrophilicity. However, their low viscosity, which leads to low contact time on the surface of the skin, has restricted their application in transdermal delivery. Therefore, this study aimed to deliver transferosomes loaded with a highly water-soluble and high molecular weight vancomycin hydrochloride (VCM-HCl) via a bigel for systemic delivery and treatment of microbial infections. VCM-HCl-loaded transferosomal formulations (TNFs) were prepared using a reverse-phase evaporation method and then loaded into a bigel. Both the TNFs and TNFs-loaded bigel (TNF-L-B) were characterized by a range of in vitro and ex vivo techniques. TNFs and TNF-L-B were tested for biosafety via the MTT assay and found to be biosafe. Prepared TNFs had sizes, zeta potential and entrapment efficiency of 63.02 ± 5.34 nm, -20.93 ± 6.13 mV and 84.48 ± 1.22% respectively. VCM-HCl release from TNF-L-B showed a prolonged release profile with 39.76 ± 1.6% after 24hrs when compared to bare VCM-HCl loaded in the bigel (74.81 ± 8.84%). Ex-vivo permeation of prepared TNF-L-B showed a higher permeation flux of 0.56 µg/cm2/h compared to the bare VCM-HCl-loaded bigel of 0.23 µg/cm2/h, indicating superior permeation and bioavailability of the drug. Additionally, the prepared TNF-L-B demonstrated improved antimicrobial activity. The TNF-L-B showed minimum inhibitory concentrations (MIC) of 0.97 µg/ml against Staphylococcus aureus (SA) and 1.95 µg/ml against methicillin-resistant SA (MRSA), which were 2-fold lower MIC values than the bare drug. The time-kill assay showed that both TNFs and TNF-L-B systems caused a 5.6-log reduction (100%) in MRSA compared to bare VCM-HCl after 24 hrs of incubation. Furthermore, as opposed to the bare VCM-HCl solution, the degree of biofilm reduction caused by TNFs (55.72%) and TNF-L-B (34.58%) suggests their dominance in eradicating MRSA biofilm. These findings indicate that TNF-L-B is a promising system for transdermal delivery of hydrophilic and high molecular weight drugs.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Humanos , Lipossomos , Vancomicina
19.
Am J Physiol Renal Physiol ; 321(4): F455-F465, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34423680

RESUMO

Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion. Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to ischemia-reperfusion injury.NEW & NOTEWORTHY This study aimed to determine the impact of antibiotic-induced microbiome depletion (AIMD) on renal glucose metabolism in mice. This is the first report confirming that AIMD is associated with decreased levels of pyruvate, a key intermediate in glucose metabolism, which may have been caused by activation of renal gluconeogenesis. We hypothesized that AIMD can increase the susceptibility of the kidney to ischemia-reperfusion injury.


Assuntos
Injúria Renal Aguda/patologia , Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/metabolismo , Rim/metabolismo , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/etiologia , Animais , Glicemia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Levofloxacino/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Ácido Pirúvico/metabolismo , Vancomicina/farmacologia
20.
Orthop Nurs ; 40(4): 248-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34397982

RESUMO

Antibiotic administration in the perioperative period is the foundation of preventing surgical site infections. ß-Lactam antibiotics, notably the first-generation cephalosporin cefazolin, are the drugs of choice for this indication. However, reported antibiotic allergies often result in the use of suboptimal alternative agents that can lead to an increased risk of infection and adverse effects. A comprehensive allergy history and risk stratification should be completed preoperatively to determine whether or not a patient can be rechallenged with a ß-lactam antibiotic and what testing may be necessary prior to administration. Nursing staff can play a critical role in understanding the implications and management of reported antibiotic allergies in surgical patients in order to optimize patient care.


Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade/diagnóstico , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Antibacterianos/administração & dosagem , Aztreonam/administração & dosagem , Aztreonam/efeitos adversos , Cefazolina/administração & dosagem , Cefazolina/efeitos adversos , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Humanos , Estudos Retrospectivos , Vancomicina/administração & dosagem , Vancomicina/efeitos adversos , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos
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