Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.512
Filtrar
1.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 904-909, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506151

RESUMO

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Vancomicina/uso terapêutico , Antibacterianos , Criança , Pré-Escolar , Humanos , Lactente , Meticilina , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Resultado do Tratamento
2.
BMC Infect Dis ; 19(1): 596, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288757

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality and has resultant important economic and societal costs underscoring the need for accurate surveillance. In recent years, prevalence rates reported in East Africa have been inconsistent, sparking controversy and raising concern. METHODS: We described antimicrobial susceptibility patterns of Staphylococcus aureus isolates cultured from patients within the Internal Medicine department of the largest public healthcare facility in East and Central Africa- the Kenyatta National Hospital (KNH) in Nairobi, Kenya. Routine antimicrobial susceptibility data from non-duplicate Staphylococcus aureus isolates cultured between the years 2014-2016 from the medical wards in KNH were reviewed. RESULTS: Antimicrobial susceptibility data from a total of 187 Staphylococcus aureus isolates revealed an overall MRSA prevalence of 53.4%. Isolates remained highly susceptible to linezolid, tigecycline, teicoplanin and vancomycin. CONCLUSIONS: The prevalence of MRSA was found to be much higher than that reported in private tertiary facilities in the same region. Careful interrogation of antimicrobial susceptibility results is important to uproot any red herrings and reserve genuine cause for alarm, as this has a critical bearing on health and economic outcomes for a population.


Assuntos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Adulto , África Oriental/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefoxitina/farmacologia , Cefoxitina/uso terapêutico , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
3.
J Sci Food Agric ; 99(13): 5870-5880, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206687

RESUMO

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds. RESULTS: Treatment with BCP-DHA, at a dose of 200 µL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-α and IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Peritonite/tratamento farmacológico , Sepse/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Interleucina-12/genética , Interleucina-12/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Peritonite/genética , Peritonite/imunologia , Peritonite/microbiologia , Sepse/genética , Sepse/imunologia , Sepse/microbiologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
4.
Nat Commun ; 10(1): 2730, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227691

RESUMO

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.


Assuntos
Antibacterianos/farmacologia , Imunidade Inata/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tiazolidinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Peptídeos/imunologia , Peptídeos Cíclicos/uso terapêutico , Cultura Primária de Células , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Tiazolidinas/uso terapêutico
5.
Pan Afr Med J ; 32: 103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223393

RESUMO

Introduction: Staphylococcus aureus is an important pathogen responsible for hospital and community acquired infection(s). Emerging resistance to methicillin in this organism has left physicians with few therapeutic alternatives to treat infections caused by it. This study was aimed at determining the antibiotic susceptibility patterns of Staphylococcus aureus strains isolated at the Yaounde Central Hospital, Cameroon. Methods: from January 2014 to November 2016, a total of 250 non repeated strains were isolated from various clinical specimens. Isolates and antibiotic susceptibility profiles were identified through standard microbiological techniques. Results: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) accounted respectively for 80% (201/205) and 20% (49/205) of the total strains isolated. MRSA strains displayed high resistance to cefoxitin (100%), cotrimoxazole (89%), vancomycin (79.7%), lincomycin (70.3%), tobramycin (72.5%), doxycycline (68.0%), kanamycin (69.7%) and erythromycin (55.7%). In contrast, a high susceptibility was observed with rifampicin (82.6%). KTG (42.3%) and constitutive MLSB (17.4%) were the most frequent phenotypes recorded. Conclusion: our results show that the carriage of acquired MRSA infections predominates in this population. Despite the noticeable multiresistance of MRSA strains to antibiotics, rifampicin remains the drugs of choice for the therapy of acquired MRSA infections in this setting. In order to slow down antimicrobial resistance, surveillance studies for antimicrobial susceptibility remains essential to identify resistance and inform policy on resistance.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Camarões/epidemiologia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
6.
Vet Res ; 50(1): 49, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221210

RESUMO

An ethanolic extract from Rhodomyrtus tomentosa leaves (RTL) was studied as a natural alternative to control Staphylococcus aureus, which is an important pathogen responsible for bovine mastitis. The minimal inhibitory concentrations (MICs) of the RTL extract and of rhodomyrtone, a pure compound isolated from the plant, were determined by a microdilution method. Rhodomyrtone and the RTL extract exhibited antibacterial activity against S. aureus, including its persistent phenotype (SCV: small-colony variant) and a biofilm hyperproducer strain, with MICs of 0.25-0.5 and 8-16 µg/mL, respectively. Time-kill kinetics showed a strong bactericidal activity for both the RTL extract- and rhodomyrtone-treated bacteria at 2 × MIC as early as 4 h post-exposure. An additive effect of the extract at 0.5 × MIC was observed in a combination with oxytetracycline or pirlimycin against S. aureus by showing a 64- to 128-fold reduction in antibiotic MICs. Moreover, the RTL extract significantly decreased the number of intracellular SCVs inside bovine mammary epithelial cells. However, the extract or its combination with pirlimycin only slightly improved the activity of pirlimycin against the bacterial colonization of mouse mammary glands. In vitro MICs determined in the presence of casein indicated that the limited activity of the RTL extract in the murine model of mastitis could be linked to neutralization of active components by milk proteins. While the RTL extract showed interesting antibacterial properties in vitro, to be considered as an alternative to antibiotics in dairy farms, formulation studies are needed to cope with the observed reduction of activity in vivo.


Assuntos
Antibacterianos/farmacologia , Mastite Bovina/tratamento farmacológico , Myrtaceae/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Animais , Bovinos , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Mastite Bovina/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Xantonas/farmacologia
7.
Dtsch Med Wochenschr ; 144(11): 729-733, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163470

RESUMO

In 2018, the PEG-recommendations for calculated initial parenteral treatment of bacterial diseases in adults were updated to a consensus-based S2k-guideline.This summary of guidelines deals with the classification of new antibiotic substances such as cephalosporin/betalactamase inhibitor combinations and MRSA-effective cephalosporines and with a need for further therapeutic drug monitoring.Due to their influence as major disease entities in intensive care, we also outline core issues regarding respiratory infections and sepsis. With this update, latest recommendations on a high scientific level are available for intensive care units and - if applied consistently - might improve the chances of critically ill patients.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Cuidados Críticos , Adulto , Idoso , Cefalosporinas/uso terapêutico , Estado Terminal , Humanos , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Guias de Prática Clínica como Assunto , Sepse/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico
8.
Pol J Microbiol ; 68(1): 59-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050254

RESUMO

The widespread of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), has necessitated the search for alternative therapies; introduction of new agents being a suggestion. This study compares the in vitro and in vivo activities of zabofloxacin, a novel fluoroquinolone, with moxifloxacin, levofloxacin and ciprofloxacin against clinical isolates of MRSA from patients hospitalized in the Alexandria Main University hospital; a tertiary hospital in Alexandria, Egypt, where zabofloxacin has not been yet introduced. The strains tested showed the highest percentage of susceptibility to zabofloxacin (61.2%) among the tested fluoroquinolones with the most effective MIC50 and MIC90 (0.25 and 2 µg/ml, respectively). Time-kill curve analysis revealed a rapid bactericidal activity of zabofloxacin after 6 h of incubation with a quinolone-resistant isolate and complete killing when tested against a quinolone-sensitive isolate with inhibition of regrowth in both cases. PCR amplification and sequencing of QRDRs in selected strains revealed the following amino acid substitutions: Ser-84→Leu in GyrA, Ser-80→Phe in GrlA and Pro-451→Ser in GrlB. The in vivo studies demonstrated that zabofloxacin possessed the most potent protective effect against systemic infection in mice (ED50: 29.05 mg/kg) with lowest count in the dissected lungs (3.66 log10 CFU/ml). The histopathological examination of lung specimens of mice treated with zabofloxacin displayed least congestion, inflammation, oedema and necrosis with clear alveolar spaces and normal vessels. In conclusion, zabofloxacin was proved to possess high in vitro and in vivo efficacy encompassing its comparators and could be considered as a possible candidate for the treatment of infections caused by MRSA. To our knowledge, this is the first study evaluating the in vitro and in vivo activity of zabofloxacin against Egyptian MRSA clinical isolates.The widespread of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), has necessitated the search for alternative therapies; introduction of new agents being a suggestion. This study compares the in vitro and in vivo activities of zabofloxacin, a novel fluoroquinolone, with moxifloxacin, levofloxacin and ciprofloxacin against clinical isolates of MRSA from patients hospitalized in the Alexandria Main University hospital; a tertiary hospital in Alexandria, Egypt, where zabofloxacin has not been yet introduced. The strains tested showed the highest percentage of susceptibility to zabofloxacin (61.2%) among the tested fluoroquinolones with the most effective MIC50 and MIC90 (0.25 and 2 µg/ml, respectively). Time-kill curve analysis revealed a rapid bactericidal activity of zabofloxacin after 6 h of incubation with a quinolone-resistant isolate and complete killing when tested against a quinolone-sensitive isolate with inhibition of regrowth in both cases. PCR amplification and sequencing of QRDRs in selected strains revealed the following amino acid substitutions: Ser-84→Leu in GyrA, Ser-80→Phe in GrlA and Pro-451→Ser in GrlB. The in vivo studies demonstrated that zabofloxacin possessed the most potent protective effect against systemic infection in mice (ED50: 29.05 mg/kg) with lowest count in the dissected lungs (3.66 log10 CFU/ml). The histopathological examination of lung specimens of mice treated with zabofloxacin displayed least congestion, inflammation, oedema and necrosis with clear alveolar spaces and normal vessels. In conclusion, zabofloxacin was proved to possess high in vitro and in vivo efficacy encompassing its comparators and could be considered as a possible candidate for the treatment of infections caused by MRSA. To our knowledge, this is the first study evaluating the in vitro and in vivo activity of zabofloxacin against Egyptian MRSA clinical isolates.


Assuntos
Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Carga Bacteriana/efeitos dos fármacos , Ciprofloxacino/farmacologia , DNA Girase/efeitos dos fármacos , DNA Girase/genética , DNA Topoisomerase IV/efeitos dos fármacos , DNA Topoisomerase IV/genética , Egito , Hospitais Universitários , Humanos , Levofloxacino/farmacologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Camundongos , Testes de Sensibilidade Microbiana , Moxifloxacina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
9.
An Acad Bras Cienc ; 91(2): e20180117, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31090789

RESUMO

One manner in which plant-derived compounds exert their antibiotic potential is the synergism, a positive interaction between two compounds. Studies indicate that the use of plant extracts combined with antimicrobials may promote a significant reduction of the minimum inhibitory concentrations of antibiotics for bacterial strains. This study aimed to evaluate the activity of plant extracts and antibiotics as well as their combination on Staphylococcus aureus. The activity of 15 plant extracts was evaluated using diffusion assay. The minimum inhibitory concentrations (MICs) and the interactions between the extracts and antibiotics as well as compound emodin were evaluated with the checkerboard method. The active extracts were a hexane extract of the leaves of Baccharis dracunculifolia and the ethanol extracts of the leaves of Plectranthus ornatus, Inga edulis, Salvia officinalis and Senna macranthera. The Plectranthus ornatus extract displayed synergism with ampicillin (a ß-lactam), kanamycin and gentamicin (aminoglycosides), with 8-fold reductions in the MIC. The same reduction was observed for the extracts of Salvia officinalis and Senna macranthera, which displayed the lowest MIC. Using these combinations resulted in a reduction in the minimum dose required for effective antimicrobial effects, which is interesting because it may decrease both the risk of side effects and the costs of treatment.


Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/classificação , Bovinos , Sinergismo Farmacológico , Feminino , Mastite Bovina/tratamento farmacológico , Extratos Vegetais/classificação , Folhas de Planta/química , Infecções Estafilocócicas/tratamento farmacológico
10.
mSphere ; 4(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043516

RESUMO

Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and P. aeruginosa PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of -1.0 V, -1.5 V, or -1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for P. aeruginosa, was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at -1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a >6-log reduction in MRSA and no detectable planktonic P. aeruginosa All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at -1.0 V and -1.5 V against MRSA. Remarkably, there were no detectable P. aeruginosa CFU following prevention CVCES at -1.0 V or -1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI.IMPORTANCE Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Titânio/química , Aderência Bacteriana/efeitos dos fármacos , Estimulação Elétrica , Eletrodos , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/prevenção & controle , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controle , Células-Tronco , Titânio/uso terapêutico
11.
J Med Microbiol ; 68(6): 957-960, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31050633

RESUMO

The qacA/B gene is one of the major determinants of resistance to antiseptics in methicillin-resistant Staphylococcus aureus (MRSA). Here, we compared the fast-acting bactericidal activity of skin antiseptics, including olanexidine gluconate (OLG), a new biguanide antiseptic agent introduced in Japan, against clinical qacA/B-positive MRSA strains by determination of minimum bactericidal concentration and time-kill assay. Our findings provide, for the first time, data indicating that the fast-acting bactericidal activity of OLG against qacA/B-positive MRSA is higher than that of chlorhexidine gluconate, even though both are biguanide antiseptics.


Assuntos
Anti-Infecciosos Locais/farmacologia , Proteínas de Bactérias/genética , Biguanidas/farmacologia , Glucuronatos/farmacologia , Proteínas de Membrana Transportadoras/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/enzimologia , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico
12.
Chem Pharm Bull (Tokyo) ; 67(5): 481-486, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061374

RESUMO

Quinolone 006 is under development as an anti-methicillin-resistant Staphylococcus aureus quinolone antibiotic. A linear synthetic route was utilized to prepare the compound on a multi-kilogram scale with an overall yield of 71%. The process was optimized by controlling the temperature and the vacuum pressure. Examples of parameters examined in an effort to control the polymorphism of the 006 active pharmaceutical ingredient are described.


Assuntos
Antibacterianos/síntese química , Quinolonas/síntese química , Antibacterianos/química , Técnicas de Química Sintética/economia , Técnicas de Química Sintética/métodos , Cristalização , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Quinolonas/química , Infecções Estafilocócicas/tratamento farmacológico
13.
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
14.
Emerg Microbes Infect ; 8(1): 707-716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119985

RESUMO

Staphylococcus aureus (S. aureus) is one of the most serious human pathogens. α-Hemolysin (Hla) secreted by S. aureus is a key toxin for various infections. We herein report that Honokiol, a natural plant polyphenol, inhibits the secretion and hemolytic activity of staphylococcal Hla with concomitant growth inhibition of S. aureus and protection of S. aureus-mediated cell injury within subinhibitory concentrations. In parallel, Honokiol attenuates the staphylococcal Hla-induced inflammatory response by inhibiting NLRP3 inflammasome activation in vitro and in vivo. Consequently, the biologically active forms of the inflammatory cytokines IL-1ß and IL-18 are reduced significantly in response to Honokiol in mice infected with S. aureus. Experimentally, we confirm that Honokiol binds to monomeric Hla with a modest affinity without impairing its oligomerization. Based on molecular docking analyses in silico, we make a theoretical discovery that Honokiol is located outside of the triangular region of monomeric Hla. The binding model restricts the function of the residues related to membrane channel formation, which leads to the functional disruption of the assembled membrane channel. This research creates a new paradigm for developing therapeutic agents against staphylococcal Hla-mediated infections.


Assuntos
Toxinas Bacterianas/metabolismo , Compostos de Bifenilo/administração & dosagem , Proteínas Hemolisinas/metabolismo , Inflamassomos/antagonistas & inibidores , Lignanas/administração & dosagem , Receptores de Superfície Celular/antagonistas & inibidores , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Células A549 , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Toxinas Bacterianas/toxicidade , Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas Hemolisinas/toxicidade , Histocitoquímica , Humanos , Lignanas/metabolismo , Lignanas/farmacologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Ligação Proteica , Infecções Estafilocócicas/patologia , Staphylococcus aureus/metabolismo , Resultado do Tratamento
15.
BMC Infect Dis ; 19(1): 472, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138139

RESUMO

BACKGROUND: Bicycle-spoke injuries rarely cause late complications of infection, including sepsis and sepsis-associated encephalopathy, with appropriate treatments. CASE PRESENTATION: We experienced a 2-year-old girl who developed the signs of encephalopathy with fever 6 months after a spoke-injury. On admission, the injured skin was inflamed with cellulitis. The blood culture was positive for methicillin-sensitive Staphylococcus aureus. Electroencephalogram showed diffuse slow-wave activity. Diffusion-weighted magnetic resonance imaging detected a high-intensity lesion with decreased diffusivity at the right frontal cortex. She received immunoglobulin and combined antibiotics treatments in the intensive care unit, and successfully overcame the sepsis-associated encephalopathy without neurological impairments. CONCLUSION: This is the first report demonstrating that sepsis and its associated encephalopathy occurs in a remote period after the bicycle-spoke injury.


Assuntos
Bacteriemia/etiologia , Ciclismo/lesões , Encefalopatias/etiologia , Infecções Estafilocócicas/etiologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Encefalopatias/diagnóstico por imagem , Pré-Escolar , Eletroencefalografia , Feminino , Febre/tratamento farmacológico , Humanos , Imagem por Ressonância Magnética , Infecções Estafilocócicas/tratamento farmacológico , Ferimentos Penetrantes/etiologia
16.
mSphere ; 4(3)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092603

RESUMO

Intraocular infections are prevalent after traumatic injuries or after common ocular surgeries. Infections cause inflammation that can damage the retina and architecture of the eye, often resulting in poor visual outcomes. Severe cases may result in blindness or require enucleation of the eye. Treatments for intraocular infections include intravitreal antibiotics and corticosteroids or surgical vitrectomy in serious cases. The increase in multidrug-resistant infections calls for novel treatment options. In the present study, a biomimetic erythrocyte-derived nanosponge was tested for the ability to neutralize pore-forming toxins from the most frequent Gram-positive bacterial causes of intraocular infections (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus). Nanosponge pretreatment of supernatants reduced hemolytic activity in vitro. In a murine sterile endophthalmitis model, nanosponge pretreatment of injected supernatants resulted in greater retinal function and less ocular pathology compared to that in eyes injected with untreated supernatants from all pathogens except methicillin-resistant S. aureus In a murine bacterial endophthalmitis model, treatment with gatifloxacin and gatifloxacin-nanosponges reduced intraocular bacterial burdens, except in the case of methicillin-sensitive S. aureus For all pathogens, eyes in both treatment groups showed decreased ocular pathology and inflammation. Overall, reductions in retinal function loss afforded by gatifloxacin-nanosponge treatment were significant for E. faecalis, S. pneumoniae, and methicillin-resistant S. aureus but not for B. cereus and methicillin-sensitive S. aureus These results suggest that clinical improvements in intraocular infections following nanosponge treatment were dependent on the complexity and types of toxins produced. Nanosponges might serve as an adjunctive therapy for the treatment of ocular infections.IMPORTANCE Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.


Assuntos
Toxinas Bacterianas/antagonistas & inibidores , Materiais Biomiméticos , Infecções Oculares Bacterianas/tratamento farmacológico , Nanoestruturas/uso terapêutico , Animais , Eritrócitos/química , Gatifloxacina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Nanoestruturas/química , Nanotecnologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
17.
Expert Opin Drug Saf ; 18(8): 635-650, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31106600

RESUMO

INTRODUCTION: Acute bacterial skin and skin-structure infections (ABSSSI) may develop in both in-patients and out-patients, possibly with a severe clinical presentation. Since most phase 3 randomized clinical trials have shown non-inferiority in efficacy across different agents, considerations regarding their different safety profiles inevitably play a crucial role in the everyday choice about which of them should be employed for the treatment of ABSSSI. AREAS COVERED: In this review, the authors discuss the safety profile of different treatment options for ABSSSI. EXPERT OPINION: The spread of methicillin-resistant Staphylococcus aureus (MRSA) in the last decades has inevitably influenced the therapeutic approach to ABSSSI. Adequate knowledge of the peculiar toxicity profile of each drug active against MRSA is essential for guiding, monitoring and managing adverse events, in turn reducing any unfavorable impact of toxicity on patients' outcomes. In the next five years, potential toxicity will play a critical role in establishing the best available therapy for each specific patient, together with consideration regarding the possibility of avoiding hospitalization or allowing a switch from intravenous to oral therapy and early discharge.


Assuntos
Antibacterianos/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Doença Aguda , Administração Intravenosa , Administração Oral , Antibacterianos/efeitos adversos , Monitoramento de Medicamentos/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Dermatopatias Bacterianas/microbiologia , Infecções Estafilocócicas/microbiologia
18.
Int J Infect Dis ; 84: 44-47, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075509

RESUMO

The case of a patient with left ventricular assist device (LVAD)-associated endocarditis involving multiple clones of Staphylococcus aureus is presented. Different clones with distinct colony morphology were identified from blood cultures collected on the same day and showed diverse antimicrobial resistance patterns. In addition, a difference in antimicrobial susceptibility was observed even within an identical clone recovered 400 days apart due to the loss of SCCmec for methicillin and modification of the 23S rRNA target site for linezolid during a long-term treatment course.


Assuntos
Antibacterianos/farmacologia , Endocardite Bacteriana/etiologia , Ventrículos do Coração , Coração Auxiliar/efeitos adversos , Infecções Estafilocócicas/etiologia , Staphylococcus aureus , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Humanos , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , RNA Ribossômico 23S , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética
19.
Biomed Res Int ; 2019: 1714358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080808

RESUMO

This study reports a facile and ecofriendly approach for the ultrasound assisted synthesis of silver and iron oxide nanoparticles and their enhanced antibacterial and antioxidant activities. The fenugreek seed extract was used as reducing, capping, and stabilizing agent in the synthesis of nanoparticles. The transmission electron microscopy results showed that nanoparticles synthesized by ultrasonication have a smaller size (~20 nm) as compared to the nanoparticles fabricated by magnetic stirring (~40 nm). The color change of the solution from milky white to brown suggested the formation of silver nanoparticles which was confirmed by the presence of an absorbance peak at 396 nm. The results of powder X-ray diffraction and energy dispersive X-ray spectroscopy confirmed the crystallinity and elements present in nanoparticles synthesized using fenugreek seed extract. Fourier transform infrared analysis showed that the fenugreek seed phytochemicals were coated on the nanoparticle surface. Thermal gravimetric analysis showed the thermal degradation and stability of nanoparticles. Magnetization study of iron oxide nanoparticles confirmed the superparamagnetic nature. The silver nanoparticles showed antibacterial activities against both gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria, while no antibacterial activities were observed for iron oxide nanoparticles. The ultrasound assisted nanoparticles showed higher stability and antibacterial and antioxidant activity compared with the nanoparticles fabricated by magnetic stirring.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Compostos Férricos/química , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Sementes/química , Prata/química , Trigonella/química , Antibacterianos/química , Antioxidantes/química , Escherichia coli/efeitos dos fármacos , Química Verde/métodos , Testes de Sensibilidade Microbiana/métodos , Microscopia Eletrônica de Transmissão/métodos , Extratos Vegetais/química , Folhas de Planta/química , Espectrometria por Raios X/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos
20.
Braz J Infect Dis ; 23(2): 86-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31078574

RESUMO

BACKGROUND: Early antibiotic switch and early discharge protocols have not been widely studied in Latin America. Our objective was to describe real-world treatment patterns, resource use, and estimate opportunities for early switch from intravenous to oral antibiotics and early discharge for patients hospitalized with methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections. MATERIALS/METHODS: This retrospective medical chart review recruited 72 physicians from Brazil to collect data from patients hospitalized with documented methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections between May 2013 and May 2015, and discharged alive by June 2015. Data collected included clinical characteristics and outcomes, hospital length of stay, methicillin-resistant Staphylococcus aureus-targeted intravenous and oral antibiotic use, and early switch and early discharge eligibility using literature-based and expert-validated criteria. RESULTS: A total of 199 patient charts were reviewed, of which 196 (98.5%) were prescribed methicillin-resistant Staphylococcus aureus -active therapy. Only four patients were switched from intravenous to oral antibiotics while hospitalized. The mean length of methicillin-resistant Staphylococcus aureus-active treatment was 14.7 (standard deviation, 10.1) days, with 14.6 (standard deviation, 10.1) total days of intravenous therapy. The mean length of hospital stay was 22.2 (standard deviation, 23.0) days. The most frequent initial methicillin-resistant Staphylococcus aureus-active therapies were intravenous vancomycin (58.2%), intravenous clindamycin (19.9%), and intravenous daptomycin (6.6%). Thirty-one patients (15.6%) were discharged with methicillin-resistant Staphylococcus aureus -active antibiotics of which 80.6% received oral antibiotics. Sixty-two patients (31.2%) met early switch criteria and potentially could have discontinued intravenous therapy 6.8 (standard deviation, 7.8) days sooner, and 65 patients (32.7%) met early discharge criteria and potentially could have been discharged 5.3 (standard deviation, 7.0) days sooner. CONCLUSIONS: Only 2% of patients were switched from intravenous to oral antibiotics in our study while almost one-third were early switch eligible. Additionally, one-third of hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections were early discharge eligible indicating opportunity for reducing intravenous therapy and days of hospital stay. These results provide insight into possible benefits of implementation of early switch/early discharge protocols in Brazil.


Assuntos
Antibacterianos/administração & dosagem , Substituição de Medicamentos/estatística & dados numéricos , Staphylococcus aureus Resistente à Meticilina , Alta do Paciente/estatística & dados numéricos , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Administração Intravenosa , Administração Oral , Brasil , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA