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1.
J Med Microbiol ; 68(11): 1585-1590, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31647400

RESUMO

Purpose. Acute bacterial meningitis continues to be a potentially life threatening condition. Hospital-acquired meningitis is rapidly increasing and adding an immense burden to the health system due to the emergence of multidrug resistance isolates. The purpose of this study is to find the antibiotic susceptibility pattern of the bacteria detected from hospital- and community-acquired meningitis.Methodology. A total of 400 Cerebrospinal fluid (CSF) samples from the suspected meningitis cases were collected and processed for cell count, biochemical examination, Gram staining, latex agglutination and culture. Bacteria grown on blood, chocolate and Mac-conkey agar were identified by matrix-assisted laser desorption/ionization-time of flight. Antibiotic susceptibility tests were performed as per Clinical and Laboratory Standard Institute guidelines.Results. Of the isolates, most prevalent Gram negative organisms in hospital-acquired bacterial meningitis were Escherichia coli 13 (27.08 %), Acinetobacter baumannii 12 (25 %), Klebsiella pneumoniae 5 (10.42 %), Pseudomonas aeruginosa 4 (8.33 %) and Gram positive organisms were Staphylococcus aureus 4 (8.33 %), Enterococcus faecium 3 (6.25 %) and CONS 2 (4.16 %). Streptococcus pneumoniae 3 (6.25 %) was the predominant organism in community-acquired bacterial meningitis. All the Gram negative isolates were multidrug resistance. Only colistin and imipenem were effective antibiotics against them. Likewise Gram positive organisms were susceptible to most of the antibiotics tested. However, E. faecium was only susceptible to Vanco+Teicoplanin.Conclusion. In hospital-acquired bacterial meningitis, multidrug resistance Gram negative bacteria are a huge challenge for the treatment of patients. Hence, antimicrobial stewardship should be followed to counteract with the emerging multidrug resistance isolates.


Assuntos
Bactérias/efeitos dos fármacos , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Meningites Bacterianas/microbiologia , Antibacterianos/farmacologia , Gestão de Antimicrobianos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Colistina/farmacologia , Humanos , Imipenem/farmacologia , Índia , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária/estatística & dados numéricos , Vancomicina/farmacologia
2.
Int J Nanomedicine ; 14: 5943-5955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447553

RESUMO

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


Assuntos
Antibacterianos/uso terapêutico , Lisostafina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Vancomicina/uso terapêutico , Idoso , Animais , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Contagem de Colônia Microbiana , Quimioterapia Combinada , Humanos , Lipossomos , Lisostafina/farmacologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Infecções Cutâneas Estafilocócicas/patologia , Vancomicina/farmacologia
3.
APMIS ; 127(11): 717-726, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407405

RESUMO

This study aims to determine the prevalence of Staphylococcus aureus colonizing patients and ICU environment of a teaching hospital, the virulence and antimicrobial susceptibility profile of the isolates, and to evaluate the genetic relationship among them. A total of 536 swabs (134 of patients and 402 of ICU environment) were collected and analyzed to detect S. aureus. The antimicrobial susceptibility of the isolates was determined by disk diffusion test, and the detection of the mecA and virulence factors genes was performed by PCR, in addition to SCCmec typing. The genetic similarity of the isolates was determined by PFGE. Staphylococcus aureus was isolated in 12.7% of the swabs. The prevalence of colonization was 13.4% in patients and 12.4% in the environmental samples. The multidrug resistance was determined in 82.4% of the isolates. The prevalence of methicillin-resistant S. aureus was 20.6%, with 50.0% classified as SCCmec IV. The intermediate resistance to vancomycin was detected in 5.9% and 4.4% of the isolates obtained from patients and environment, respectively. Identical isolates obtained from different patients and sources were grouped into several clusters. The results showed dissemination of multidrug-resistant strains between patients and fomites and the persistence of MRSA and VISA isolates in the ICU environment.


Assuntos
Antibacterianos/farmacologia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Feminino , Variação Genética , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Filogenia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologia , Virulência , Fatores de Virulência/genética
4.
Eur J Pharm Biopharm ; 142: 322-333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295503

RESUMO

The purpose of this work was the development of antibacterial delivery systems for vancomycin, with potential application in the prevention or treatment of orthopedic implant infections. Previous studies have shown tandem thermal gelling and Michael addition cross-linking of hydrogels based on methacrylate, acrylate or vinylsulfone triblock copolymers of PEG-p(HPMAm-lac1-2) and thiolated hyaluronic acid. In this work we exploited these α-ß unsaturated derivatives of PEG-p(HPMAm-lac1-2) triblock copolymers and used them in combination with thiolated hyaluronic acid as controlled delivery systems for vancomycin. It was found that the antibiotic was sustainably released from the hydrogel networks for at least 5 days with release kinetics depending on diffusion and dissociation of the positively charged vancomycin from the negatively charged hyaluronic acid. The release of vancomycin could be tailored mainly by HA-SH solid content and degree of thiolation. The developed hydrogels were demonstrate efficacious in preserving the structural and functional integrity of the encapsulated drug by physical immobilization within the gel network and ionic interaction with hyaluronic acid, thereby preventing vancomycin deamidation processes. Furthermore, the antimicrobial activity of vancomycin loaded hydrogels was assessed, demonstrating retention of inhibitory activity towards Staphylococcus aureus during formulation and release, with slightly increased activity of vancomycin encapsulated in hydrogels of higher HA-SH content as compared to controls.


Assuntos
Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Hidrogéis/química , Infecções Relacionadas à Prótese/tratamento farmacológico , Vancomicina/química , Vancomicina/farmacologia , Acrilatos/química , Antibacterianos/química , Antibacterianos/farmacologia , Ácido Hialurônico/química , Metacrilatos/química , Ortopedia/métodos , Polietilenoglicóis/química , Polímeros/química , Próteses e Implantes/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
5.
Bone Joint J ; 101-B(7): 848-851, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256673

RESUMO

AIMS: The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an in vitro medium environment against methicillin-sensitive Staphylococcus aureus (MSSA). MATERIALS AND METHODS: Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon's test. RESULTS: MSSA was inhibited for 12 days by the tantalum cylinders and for nine days by the cement cylinders. At day one, the mean zone of inhibition was 28.6 mm for the tantalum and 19.8 mm for the cement group (p < 0.001). At day ten, the mean zone of inhibition was 3.8 mm for the tantalum and 0 mm for the cement group (p < 0.001). The porous tantalum cylinders soaked only with phosphate buffered solution showed no zone of inhibition. CONCLUSION: Compared with cement, tantalum could release antibiotics for longer. Further studies should assess the advantages of using antibiotic-loaded porous tantalum implants at revision arthroplasty. Cite this article: Bone Joint J 2019;101-B:848-851.


Assuntos
Antibacterianos/administração & dosagem , Cimentos para Ossos , Sistemas de Liberação de Medicamentos , Staphylococcus aureus/efeitos dos fármacos , Tantálio , Vancomicina/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artroplastia de Substituição/instrumentação , Humanos , Prótese Articular , Testes de Sensibilidade Microbiana , Variações Dependentes do Observador , Infecções Relacionadas à Prótese/prevenção & controle , Fatores de Tempo , Vancomicina/farmacologia , Vancomicina/uso terapêutico
6.
Paediatr Drugs ; 21(4): 303-312, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218605

RESUMO

BACKGROUND: Vancomycin is one of the commonly used anti-microbial drugs in intensive care units (ICUs). Guidelines recommend maintaining therapeutic trough levels of vancomycin (10-20 mg/L). The success of achieving the recommended therapeutic concentration of vancomycin is influenced by several factors, and this is even more complex in children, particularly those admitted in the ICU. Hence, we carried out the present study in children admitted in the ICU who were administered vancomycin. METHODS: We carried out a chart review of children admitted in the paediatric ICU unit of a tertiary care hospital over a period of 3 years. Information on their demographic factors, diagnoses, duration of hospital stay, vancomycin treatment (dose, frequency and time of administration) and concomitant drugs, and vancomycin trough levels were retrieved. Descriptive statistics were used for representing the demographic factors, and multivariable logistic regression analyses were carried out to assess the determining factors. RESULTS: One-hundred and two children were identified, of whom 13 had renal dysfunction. Two-hundred and fifty-two vancomycin trough levels were available, of which only 25% were observed in the recommended range (10-20 mg/L) amongst patients without any renal dysfunction and 22% amongst patients with renal dysfunction. Vancomycin was administered intravenously at an average [standard deviation (SD)] dose (mg/dose) of 13 (3.9) mostly either thrice or four times daily. Even in patients receiving vancomycin as a definitive therapy, only 40.9% achieved the recommended trough levels. Lower trough levels were associated with an increased risk of mortality. Nearly 4% of the levels were above 20 mg/L (toxic range). Seven children were suspected to have acute kidney injury (AKI) during the course of therapy where the cumulative vancomycin dose and mortality rate was higher. Only one serum vancomycin level during augmented renal clearance was observed in the recommended range. All the patients received at least one concomitant drug that either had nephrotoxic potential or predominant renal elimination, and use of a greater number of such drugs was associated with an increased risk of AKI. CONCLUSION: The current vancomycin dosing strategy is ineffective in achieving therapeutic trough levels in children admitted to the ICU. Sub-therapeutic vancomycin trough levels significantly increase the risk of mortality.


Assuntos
Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva Pediátrica/tendências , Centros de Atenção Terciária/tendências , Vancomicina/uso terapêutico , Antibacterianos/farmacologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vancomicina/farmacologia
7.
Phytother Res ; 33(8): 2056-2063, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209949

RESUMO

Vancomycin is a glycopeptide antibiotic widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse side effect, and the development of effective nephroprotective agents remains a priority in antimicrobial chemotherapy. In this study, we investigated the cell protective effects of the flavonol glycoside rutin against vancomycin-induced toxicity. Vancomycin added to porcine renal tubular LLC-PK1 cells caused an increase of production of intracellular reactive oxygen species and subsequent apoptotic cell death. Pretreatment of LLC-PK1 cells with rutin at 5, 10, and 20 µM for 2 hr prior to 2-mM vancomycin exposure for 24 hr significantly decreased intracellular reactive oxygen species and increased superoxide dismutase and catalase activities. Rutin pretreatment also protected cells from vancomycin-induced caspase activation, mitochondrial membrane depolarization, and subsequent apoptosis. This study demonstrates a protective effect of rutin and suggests that rutin coadministration is an alternative therapy for treatment of vancomycin-induced nephrotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Rutina/uso terapêutico , Vancomicina/efeitos adversos , Animais , Rutina/farmacologia , Suínos , Vancomicina/farmacologia
8.
Future Microbiol ; 14: 581-586, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31172805

RESUMO

Aim: To assess the effect of colistin-glycopeptide combination against a multidrug-resistant strain of Acinetobacter baumannii. Materials & methods: We used in vitro procedures (Etest method, checkerboard test and kill-time assays) and a mouse model of a carbapenem-resistant A. baumannii pneumonia. Results: The colistin-teicoplanin combination allowed a 74% increase of the survival in the mouse model within the 4 days following bacterial inoculation as compared with saline or colistin alone (p = 0.06). Concurrently, the colistin-vancomycin combination presented a similar efficacy as compared with saline or colistin alone in the mouse model. Conclusion: According to those preliminary results, using the colistin-teicoplanin combination in therapeutic deadlocks encountered in certain multiresistant A. baumannii pneumonia could be envisaged if the results are confirmed.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Glicopeptídeos/farmacologia , Pneumonia/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos C3H , Testes de Sensibilidade Microbiana , Taxa de Sobrevida , Teicoplanina/farmacologia , Vancomicina/farmacologia
9.
J Med Microbiol ; 68(6): 848-859, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31136294

RESUMO

PURPOSE: The purpose of the present study was to determine the relatedness of Staphylococcus aureus strains successively isolated over a 7-day period from a single bacteraemic patient undergoing antibiotic treatment with vancomycin. METHODS: The S. aureus strains had been isolated and sequenced previously. Antibiotic susceptibility testing, population analysis profiling, and lysostaphin sensitivity and phagocytic killing assays were used to characterize these clonal isolates. RESULTS: The seven isolates (MEH1-MEH7) were determined to belong to a common multilocus sequence type (MLST) and spa type. Within the third and fifth day of vancomycin treatment, mutations were observed in the vraS and rpsU genes, respectively. Population analysis profiles revealed that the initial isolate (MEH1) was vancomycin-susceptible S. aureus (VSSA), while those isolated on day 7 were mostly heteroresistant vancomycin-intermediate S. aureus (hVISA). Supporting these findings, MEH7 was also observed to be slower in growth, to have an increase in cell wall width and to have reduced sensitivity to lysostaphin, all characteristics of VISA and hVISA strains. In addition, MEH7, although phagocytosed at numbers comparable to the initial isolate, MEH1, survived in higher numbers in RAW 264.7 macrophages. Macrophages infected with MEH7 also released more TNF-α and IFN-1ß. CONCLUSION: We report an increasing resistance to vancomycin coupled with daptomycin that occurred within approximately 3 days of receiving vancomycin and steadily increased until the infection was cleared with an alternative antibiotic therapy. This study reiterates the need for rapid, efficient and accurate detection of hVISA and VISA infections, especially in high-bacterial load, metastatic infections like bacteraemia.


Assuntos
Antibacterianos/farmacologia , Macrófagos/fisiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Idoso , Bacteriemia/microbiologia , Parede Celular/efeitos dos fármacos , Daptomicina/farmacologia , Humanos , Lisostafina/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Mutação , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/virologia
10.
Microb Drug Resist ; 25(5): 668-676, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31099708

RESUMO

Characteristics of Staphylococcus aureus infections include biofilm formation, leading to the spread of bacteria to the bloodstream causing sepsis and metastatic infections. In particular, in methicillin-resistant S. aureus (MRSA) infections, biofilm formation critically hampers treatment and causes poor prognosis. We explored the biofilm formation of MRSA in the presence or absence of plasma and compared morphological characteristics, accumulation of antibiotics, and resistance to bactericidal activity, using continuous optimizing confocal reflection microscopy. Addition of plasma significantly increased biofilm formation, which is characterized by an uneven surface and aggregation of bacteria (hereafter plasma biofilm). The flow-cell system, which enabled a continuous supply of plasma, accelerated biofilm formation in both the tested strains of MRSA (BAA1556 and N315). Accumulation of green fluorescence-labeled vancomycin was observed within 5 minutes in the plasma-free biofilm, but not in the plasma biofilm. Delay of accumulation was also observed for daptomycin in plasma biofilm. Plasma biofilm bacteria were more resistant to anti-MRSA antibiotics than plasma-free biofilm bacteria. These data demonstrate that the plasma biofilm of S. aureus is substantially different from the plasma-free biofilm. Plasma biofilm, especially in the flow-cell system, could be a clinically relevant model to analyze MRSA infections and treatment.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Daptomicina/farmacologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Vancomicina/farmacologia , Biofilmes/crescimento & desenvolvimento , Meios de Cultura Livres de Soro/química , Meios de Cultura Livres de Soro/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Reologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
11.
Clin Nephrol ; 92(1): 44-51, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31131821

RESUMO

BACKGROUND: Peritoneal dialysis-associated peritonitis (PDAP) is one of the major causes of peritoneal dialysis (PD) failure and death. Therefore, it is important to determine how to effectively treat patients with PDAP. MATERIALS AND METHODS: We analyzed the pathogen spectrum and bacterial resistance in 203 PDAP cases that were enrolled in this study from January 1, 2015 to December 31, 2017. All patients were infected with peritonitis and had been treated with antibiotics while at our center. Bacterial culture results of PD fluid and pathogen drug resistance were collected and analyzed. A total of 159 cases (78.3%) had a positive bacterial culture of PD fluid. RESULTS: A total of 47 pathogens were identified, including 19 (40.4%) Gram-positive cocci strains (the most common was Staphylococcus spp.), 15 (31.9%) Gram-negative bacilli strains (the most common was Escherichia coli, 4 fungal strains, and 9 other strains. The drug sensitivity test showed that Gram-positive cocci were sensitive to vancomycin (94.9%), but had a high resistance to cefazolin (67.7%). Gram-negative bacilli were sensitive to imipenem (96.2%), but had a high resistance to ceftriaxone (60.0%). Voriconazole and itraconazole were sensitive in fungal infections. A total of 162 cases were cured, 37 cases were unresponsive to antibiotic treatment and converted to hemodialysis after Tenckhoff catheter removal, and 4 cases resulted in death. CONCLUSION: Gram-positive cocci are still the primary pathogen of PDAP cases in our center, but demonstrate a high resistance to first-generation cephalosporin, which is the suggested treatment per International Society for Peritoneal Dialysis 2016 Peritonitis Recommendations. Therefore, an individualized treatment based on the distribution of pathogens and drug resistance in different centers is more conducive to improve the cure rate of PDAP.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Cocos Gram-Positivos/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Peritonite/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antifúngicos/uso terapêutico , Infecções Bacterianas , Cefazolina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Imipenem/uso terapêutico , Itraconazol/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Peritonite/etiologia , Vancomicina/farmacologia , Voriconazol/uso terapêutico , Adulto Jovem
12.
Eur J Pharm Biopharm ; 140: 50-59, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055065

RESUMO

The aim of this study was to develop a biodegradable nanostructured electrospun layer based on collagen (COL), hydroxyapatite nanoparticles (HA), vancomycin hydrochloride (V), gentamicin sulphate (G) and their combination (VG) for the treatment of prosthetic joint infections and the prevention of infection during the joint replacement procedure. COL/HA layers containing different amounts of HA (0, 5 and 15 wt%) were tested for the in vitro release kinetics of antibiotics, antimicrobial activity against MRSA, gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis isolates and cytocompatibility using SAOS-2 bone-like cells. The results revealed that the COL/HA layers released high concentrations of vancomycin and gentamicin for 21 days and performed effectively against the tested clinically-relevant bacterial isolates. The presence of HA in the collagen layers was found not to affect the release kinetics of the vancomycin from the layers loaded only with vancomycin or its combination with gentamicin. Conversely, the presence of HA slowed down the release of gentamicin from the COL/HA layers loaded with gentamicin and its combination with vancomycin. The combination of both antibiotics exerted a positive effect on the prolongation of the conversion of vancomycin into its degradation products. All the layers tested with different antibiotics exhibited potential antibacterial activity with respect to both the tested staphylococci isolates and enterococci. The complemental effect of vancomycin was determined against both gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis in contrast to the application of gentamicin as a single agent. This combination was also found to be more effective against MRSA than is vancomycin as a single agent. Importantly, this combination of vancomycin and gentamicin in the COL/HA layers exhibited sufficient cytocompatibility to SAOS-2, which was independent of the HA content. Conversely, only gentamicin caused the death of SAOS-2 independently of HA content and only vancomycin stimulated SAOS-2 behaviour with an increased concentration of HA in the COL/HA layers. In conclusion, COL/HA layers with 15 wt% of HA impregnated with vancomycin or with a combination of vancomycin and gentamicin offer a promising treatment approach and the potential to prevent infection during the joint replacement procedures.


Assuntos
Antibacterianos/farmacologia , Colágeno/química , Durapatita/química , Gentamicinas/farmacologia , Vancomicina/farmacologia , Antibacterianos/química , Cimentos para Ossos/química , Linhagem Celular , Sinergismo Farmacológico , Enterococcus faecalis/efeitos dos fármacos , Gentamicinas/química , Humanos , Cinética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Staphylococcus epidermidis/efeitos dos fármacos , Vancomicina/química
13.
Molecules ; 24(10)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121813

RESUMO

An expedient synthesis of hitherto unexplored novel hybrid heterocycles comprising dispiropyrrolidine, N-styrylpiperidone and indeno[1,2-b]quinoxaline units has been developed via domino multicomponent 1,3-dipolar cycloaddition strategy employing a new class of azomethine ylide in ionic liquid, 1-butyl-3-methylimidazolium bromide. This domino protocol involves, 1,3-dipolar cycloaddition and concomitant enamine reaction affording the dispiropyrrolidine tethered N-styrylpiperidone hybrid heterocycles in moderate to good yield in a single step. These compounds were evaluated for their antimicrobial activity against bacterial and fungal pathogens, therein compounds 8f, 8h, and 8l displayed significant activity against tested microbial pathogens. The synergistic effect revealed that the combination of compound 8h with streptomycin and vancomycin exhibited potent synergistic activity against E. coli ATCC 25922. In addition, molecular docking simulation has also been studied for the most active compound.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Antibacterianos/química , Reação de Cicloadição , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Imidazóis/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinoxalinas/química , Estreptomicina/farmacologia , Relação Estrutura-Atividade , Vancomicina/farmacologia
14.
BMC Res Notes ; 12(1): 292, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133071

RESUMO

OBJECTIVES: Enterococcus faecalis as part of the normal floras of human gastrointestinal and genitourinary tracts are an important cause of nosocomial infections. The present study aimed to investigate the prevalence of genes encoding antimicrobial resistance and genetic relatedness of clinical isolates of E. faecalis among Iranian hospitalized patients. RESULTS: Antibiotic susceptibility testing results indicated that 53 (22.8%) out of 232 E. faecalis isolates were vancomycin resistant (MIC ≥ 256 µg/ml). All of the 53 vancomycin-resistant E. faecalis isolates carried the vanA and ermB genes; whereas aac (6')-Ie aph (2″), msrA, and ermA gene were found in 96.2%, 30.2% and 3.8% of vancomycin-resistant isolates, respectively. ERIC-PCR typing revealed that 53 vancomycin-resistant isolates were classified into 14 ERIC types. In our results, the high level of resistance to gentamicin, erythromycin and vancomycin in enterococci isolates were mainly related to the presence of aac (6')-Ie aph (2″), ermB and vanA genes, respectively. Meanwhile, ERIC-PCR analysis demonstrated that most of the evaluated isolates have a close genetic relatedness.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Enterococcus faecalis/efeitos dos fármacos , Eritromicina/farmacologia , Genes Bacterianos , Gentamicinas/farmacologia , Vancomicina/farmacologia , Técnicas de Tipagem Bacteriana , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Estudos Transversais , Enterococcus faecalis/genética , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecalis/metabolismo , Feminino , Genótipo , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Irã (Geográfico) , Masculino , Testes de Sensibilidade Microbiana , Fenótipo
15.
Cornea ; 38(8): 1017-1022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31090593

RESUMO

PURPOSE: To determine in-use stability and sterility of fortified cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone eye drops in a simulated inpatient setting with and without a mobile refrigerated container (MR). METHODS: Each drug was prepared and divided into 4 groups: 1) simulated patient use with the MR group: stored at 4°C and kept in the MR during drug administration, 2) simulated patient use without the MR (NoMR) group: stored at 4°C and no MR, 3) refrigerated control group: stored at 4°C, and 4) room temperature control group: stored at room temperature. Stability and sterility data were evaluated at days 0, 4, 7, 14, 21, and 28. Linear mixed-effects model and survival analysis were performed. RESULTS: Median time to 10% loss of concentration for in-use medications (MR/NoMR groups) was >28/27.9, 22.2/22.2, 19.4/19.4, 10.18/<4, and >28/>28 days for cefazolin, ceftazidime, vancomycin, amphotericin B, and methylprednisolone, respectively. There was no significant difference in the predicted concentration loss per day among all groups for vancomycin and methylprednisolone (all P > 0.05). For the other study medications, all room temperature control groups, the cefazolin NoMR group, and the ceftazidime NoMR group had significantly greater predicted concentration loss per day compared with the refrigerated control groups (all P ≤ 0.02). Culture results were negative for all drugs throughout the study. CONCLUSIONS: The NoMR group showed that the drug significantly degraded rapidly for cefazolin, ceftazidime, and amphotericin B. Implementation of MR could decrease the predicted loss of concentration per day for cefazolin and ceftazidime. In vitro antimicrobial activity and sterility were retained for 28 days.


Assuntos
Antibacterianos/análise , Estabilidade de Medicamentos , Glucocorticoides/análise , Preparações Farmacêuticas/análise , Esterilização , Anfotericina B/análise , Anfotericina B/farmacologia , Antibacterianos/farmacologia , Cefazolina/análise , Cefazolina/farmacologia , Ceftazidima/análise , Ceftazidima/farmacologia , Armazenamento de Medicamentos , Glucocorticoides/farmacologia , Metilprednisolona/análise , Metilprednisolona/farmacologia , Soluções Oftálmicas , Conservantes Farmacêuticos , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Vancomicina/análise , Vancomicina/farmacologia
16.
Can J Microbiol ; 65(8): 623-628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31063703

RESUMO

In this study, vancomycin-intermediate Staphylococcus aureus (VISA) cells carrying vraS and (or) graR mutations were shown to be more resistant to oxidative stress. Caenorhabditis elegans infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appear to be physiological adaptations associated with the VISA phenotype in the Mu50 lineage.


Assuntos
Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Vancomicina/farmacologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Caenorhabditis elegans , Humanos , Testes de Sensibilidade Microbiana , Mutação , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Staphylococcus aureus/genética , Resistência a Vancomicina , Virulência/efeitos dos fármacos
17.
J Med Microbiol ; 68(6): 898-902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31050628

RESUMO

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


Assuntos
Antibacterianos/farmacologia , Pirimidinas/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Doença Aguda , Método Duplo-Cego , Humanos , Incidência , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Vancomicina/farmacologia
18.
BMC Infect Dis ; 19(1): 301, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943906

RESUMO

BACKGROUND: Lactococcus garvieae is an unusual cause of infective endocarditis (IE). No current diagnostic and therapeutic guidelines are available to treat IE caused by these organisms. Based on a case report, we provide a review of the literature of IE caused by L. garvieae and highlight diagnostic and treatment challenges of these infections and implications for management. CASE PRESENTATION: A 50-year-old Asian male with mitral prosthetic valve presented to the hospital with intracranial haemorrhage, which was successfully treated. Three weeks later, he complained of generalized malaise. Further work up revealed blood cultures positive for Gram-positive cocci identified as L. garvieae by MALDI-TOF. An echocardiogram confirmed the diagnosis of IE. Susceptibility testing showed resistance only to clindamycin. Vancomycin plus gentamicin were started as empirical therapy and, subsequently, the combination of ceftriaxone plus gentamicin was used after susceptibility studies were available. After two weeks of combination therapy, ceftriaxone was continued as monotherapy for six additional weeks with good outcome. CONCLUSIONS: Twenty-five cases of IE by Lactococcus garvieae have been reported in the literature. Compared to other Gram-positive cocci, L. garvieae affects more frequently patients with prosthetic valves. IE presents in a subacute manner and the case fatality rate can be as high as 16%, comparable to that of streptococcal IE (15.7%). Reliable methods for identification of L. garvieae include MALDI-TOF, 16S RNA PCR, API 32 strep kit and BD Automated Phoenix System. Recommended antimicrobials for L. garvieae IE are ampicillin, amoxicillin, ceftriaxone or vancomycin in monotherapy or in combination with gentamicin.


Assuntos
Endocardite Bacteriana/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Lactococcus/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Quimioterapia Combinada , Ecocardiografia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Próteses Valvulares Cardíacas , Humanos , Lactococcus/química , Lactococcus/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Vancomicina/farmacologia , Vancomicina/uso terapêutico
19.
Braz J Infect Dis ; 23(2): 139-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028723

RESUMO

INTRODUCTION: This study aimed to characterize Staphylococcus aureus isolates from bloodstream infections in patients attending a teaching hospital, between 2011 and 2015. METHODS: The minimum inhibitory concentration for daptomycin, linezolid, oxacillin, teicoplanin, vancomycin, and trimethoprim/sulfamethoxazole was accessed by broth microdilution. SCCmec type and clonal profile were determined by molecular tests. Vancomycin heteroresistance was evaluated using screening tests and by population analysis profile/area under the curve. RESULTS: Among 200 S. aureus isolates, 55 (27.5%) were MRSA, carrying SCCmec II (45.5%) or IV (54.5%). The most frequent MRSA lineages were USA100 (ST5-II) (45.5%) and USA800 (ST5-IV) (30.9%). Six isolates were confirmed as vancomycin heteroresistant, showing area under the curve ratio 1.1, 1.2 or 1.3 (four USA100, one USA800 and one USA1100 isolates). CONCLUSIONS: Daptomycin and vancomycin non-susceptible MRSA clonal lineages were found in bloodstream infections over five years, highlighting the importance of continuous surveillance of multiresistant bacteria in hospitals.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Vancomicina/farmacologia , Brasil , Infecção Hospitalar/microbiologia , Hospitais de Ensino , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia
20.
Appl Microbiol Biotechnol ; 103(13): 5193-5213, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31025073

RESUMO

There is an urgent need to discover new active drugs to combat methicillin-resistant Staphylococcus aureus, which is a serious threat to humans and animals and incompletely eliminated by antibiotics due to its intracellular accumulation in host cells, production of biofilms, and persisters. Fungal defensin-like peptides (DLPs) are emerging as a potential source of new antibacterial drugs due to their potent antibacterial activity. In this study, nine novel fungal DLPs were firstly identified by querying against UniProt databases and expressed in Pichia pastoris, and their antibacterial and anti-biofilm ability were tested against multidrug-resistant (MDR) S. aureus. Results showed that among them, P2, the highest activity and expression level, showed low toxicity, no resistance, and high stability. Minimal inhibitory concentrations (MICs) of P2 against Gram-positive bacteria were < 2 µg/mL. P2 exhibited the potent activity against intracellular MDR S. aureus (bacterial reduction in 80-97%) in RAW264.7 macrophages. P2 bound to/disrupted bacterial DNA, wrinkled outer membranes and permeabilized cytoplasmic membranes, but maintained the integrity of bacterial cells. P2 inhibited/eradicated the biofilm and killed 99% persister bacteria, which were resistant to 100× MIC vancomycin. P2 upregulated the anti-inflammatory cytokine (IL-10) and downregulated pro-inflammatory cytokines (TNF-α/IL-1ß) and chemokine (MCP-1) levels in RAW 264.7 macrophages and in mice, respectively. Five milligram per kilogram P2 enhanced the survival of S. aureus-infected mice (100%), superior to vancomycin (30 mg/kg), inhibited the bacterial translocation, and alleviated multiple-organ injuries (liver, spleen, kidney, and lung). These data suggest that P2 may be a candidate for novel antimicrobial agents against MDR staphylococcal infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Defensinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Defensinas/genética , Descoberta de Drogas , Farmacorresistência Bacteriana Múltipla , Feminino , Interleucina-10/genética , Interleucina-10/imunologia , Camundongos , Testes de Sensibilidade Microbiana , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Pichia/genética , Células RAW 264.7 , Infecções Estafilocócicas , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vancomicina/farmacologia
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