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Medicinas Complementares
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1.
J Chemother ; 32(2): 103-106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31992156

RESUMO

Acinetobacter baumannii has evolved as a major pathogen of outbreaks in the healthcare setting with increased morbidity and mortality. In neonates, treatment can be quite challenging due to the resistance profile of A. baumannii as well as limited data on pharmakokinetics and pharmakodynamics of antibiotics in this age group. We present an outbreak of eight cases of extensively-drug resistant (XDR) A. baumannii bacteremias successfully managed with the combination of colistin with high dose ampicillin/sulbactam.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Acinetobacter baumannii , Ampicilina/administração & dosagem , Ampicilina/uso terapêutico , Antibacterianos/administração & dosagem , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Sulbactam/administração & dosagem , Sulbactam/uso terapêutico
2.
Phytomedicine ; 58: 152863, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30836215

RESUMO

BACKGROUND: The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota. PURPOSE: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects. METHODS: Male C57BL/6 J mice were induced with hyperlipidaemia by consuming a high-fat diet (HFD) for 4 weeks. Then, the mice were orally administered PTF, antibiotics (ampicillin+ norfloxacin), PTF+antibiotics or vehicle for another 6 weeks. Body weights and 24-h food intake were assessed weekly. At the end of the experiment, fresh stools were collected for 16S RNA pyrosequencing, and blood and liver and fat tissue were collected for pharmacological analysis. RESULTS: PTF was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia and significantly changed the structure of the gut microbiota. However, the anti-hyperlipidaemic effect of PTF was not influenced by the co-treatment with antibiotics (ampicillin+norfloxacin). A microbiological analysis of the gut microbiotas revealed that PTF selectively enhanced the relative abundance of Lactobacillus and decreased the relative abundance of Bacteroides and Alistipes. A correlation analysis between biochemical indexes and individual taxon showed that Lactobacillus was negatively associated with serum lipids and glucose while Bacteroides and Alistipes were positively associated with serum lipids and glucose. The modulatory effect of PTF on Lactobacillus, Bacteroides and Alistipes was not disturbed by the administration of antibiotics. CONCLUSION: These results demonstrated that the polyphenol-rich PTF as a unique gut microbiota modulating agent and highlighted the richness of Lactobacillus and the decreased abundance of Bacteroides and Alistipes as an effective indicator of the therapeutic effect of medicinal foods on hyperlipidaemia.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Pandanaceae/química , Extratos Vegetais/administração & dosagem , Ampicilina/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/crescimento & desenvolvimento , Glicemia/efeitos dos fármacos , Peso Corporal , Fezes/microbiologia , Frutas/química , Microbioma Gastrointestinal/genética , Humanos , Hiperlipidemias/induzido quimicamente , Lactobacillus/efeitos dos fármacos , Lactobacillus/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Norfloxacino/administração & dosagem , Plantas Medicinais , Polifenóis/farmacologia
3.
Genes Cells ; 23(12): 1043-1055, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30353943

RESUMO

Antibiotics sometimes exert adverse effects on the pathogenesis of colitis due to the dysbiosis resulting from the disruption of gut homeostasis. However, the precise mechanisms underlying colitogenic effects of antibiotic-induced colitis are largely unknown. Here, we show a novel murine fecal occult bleeding model induced by the combinatorial treatment of ampicillin and vancomycin, which is accompanied by an enlarged cecum, upregulation of pro-inflammatory cytokines IL-6 and IL-12, a reduction in Ki-67-positive epithelial cell number and an increase in the apoptotic cell number in the colon. Moreover, gas chromatography-tandem mass analysis showed that various kinds of metabolites, including glutamic acid and butyric acid, were significantly decreased in the cecal contents. In addition, abundance of butyric acid producer Clostridiales was dramatically reduced in the enlarged cecum. Interestingly, supplementation of monosodium glutamate or its precursor glutamine suppressed colonic IL-6 and IL-12, protected from cell apoptosis and prevented fecal occult blood indicating that the reduced level of glutamic acid is a possible mechanism of antibiotic-induced fecal occult bleeding. Our data showed a novel mechanism of antibiotic-induced fecal occult bleeding providing a new insight into the clinical application of glutamic acid for the treatment of antibiotic-induced colitis.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Colo/patologia , Células Epiteliais/patologia , Doenças Metabólicas/complicações , Sangue Oculto , Administração Oral , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Ácido Butírico/farmacologia , Metabolismo dos Carboidratos/efeitos dos fármacos , Ceco/microbiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Citocinas/metabolismo , Glutamina/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metaboloma/efeitos dos fármacos , Metagenômica , Camundongos , Microbiota/efeitos dos fármacos , Microbiota/genética , Células RAW 264.7 , Regeneração/efeitos dos fármacos , Glutamato de Sódio/administração & dosagem , Especificidade da Espécie , Vancomicina/administração & dosagem , Vancomicina/farmacologia
4.
J Clin Pharm Ther ; 43(2): 220-223, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29030859

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump. METHODS: We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017. RESULTS AND DISCUSSION: Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported. WHAT IS NEW AND CONCLUSIONS: Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 µg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.


Assuntos
Antibacterianos/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Endocardite/tratamento farmacológico , Enterococcus faecalis/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ampicilina/administração & dosagem , Ceftriaxona/administração & dosagem , Estudos de Coortes , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Gentamicinas/administração & dosagem , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pacientes Ambulatoriais
5.
J Antimicrob Chemother ; 72(12): 3390-3397, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28962012

RESUMO

OBJECTIVES: We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic Salmonella infections. METHODS: We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing ΔaroC Salmonella strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin. RESULTS: Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment. CONCLUSIONS: In Salmonella infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.


Assuntos
Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Carga Bacteriana , Ciprofloxacina/administração & dosagem , Infecções por Salmonella/microbiologia , Salmonella/isolamento & purificação , Sepse/microbiologia , Estruturas Animais/microbiologia , Animais , Sangue/microbiologia , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos C57BL , Salmonella/efeitos dos fármacos , Infecções por Salmonella/tratamento farmacológico , Sepse/tratamento farmacológico , Análise Espaço-Temporal
6.
Int J Nanomedicine ; 12: 3009-3021, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28442909

RESUMO

Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47-57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7-3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood-brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis.


Assuntos
Peptídeos Penetradores de Células/química , Lipossomos/farmacologia , Meningites Bacterianas/tratamento farmacológico , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Peptídeos Penetradores de Células/farmacocinética , Escherichia coli/efeitos dos fármacos , Humanos , Lipossomos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Streptococcus pneumoniae/efeitos dos fármacos , Vancomicina/administração & dosagem , Vancomicina/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
7.
J Vet Med Sci ; 79(3): 474-478, 2017 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-28190817

RESUMO

We assessed ampicillin (ABPC) concentrations of liver, kidney and skin at a 2-day withdrawal period in ten male and ten female White Leghorn chickens fed the diet containing ABPC (ABPC medicated feed 40 mg/kg body weight/day) for a week. The ABPC residues were measured with liquid chromatography-tandem mass spectrometry and the mean recoveries and quantitation limits ranged from 93.0% to 102.7% and from 0.1 to 1.4 ng/g, respectively. The residual ABPC concentrations were ≤7.82 ng/g for the skin and ≤0.64 ng/g for the kidney, suggesting below the Japanese provisional maximum residue limits. These results revealed that the analytical method is developed for residue ABPC and that the withdrawal period is appropriate.


Assuntos
Ampicilina/farmacocinética , Antibacterianos/farmacocinética , Cromatografia Líquida/veterinária , Resíduos de Drogas/farmacocinética , Espectrometria de Massas em Tandem/veterinária , Ampicilina/administração & dosagem , Ração Animal , Animais , Antibacterianos/administração & dosagem , Galinhas , Suplementos Nutricionais , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Pele/metabolismo
8.
BMC Microbiol ; 16(1): 205, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27599570

RESUMO

BACKGROUND: This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. RESULTS: In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level. CONCLUSION: No fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in relation to optimal treatment strategies. The modeling approach used in the study is generic, and could be used for prediction of the effect of treatment with other drugs and other administration routes for effect on resistance development in the intestine of pigs.


Assuntos
Ampicilina/farmacologia , Ampicilina/farmacocinética , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Intestinos/microbiologia , Ampicilina/administração & dosagem , Ampicilina/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Carga Bacteriana , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Injeções Intramusculares/métodos , Testes de Sensibilidade Microbiana/métodos , Modelos Teóricos , Suínos , Fatores de Tempo
9.
Eur J Pharm Biopharm ; 94: 411-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26117185

RESUMO

To date the effectiveness of antibiotics is undermined by microbial resistance, threatening public health worldwide. Enhancing the efficacy of the current antibiotic arsenal is an alternative strategy. The administration of antimicrobials encapsulated in nanocarriers, such as liposomes, is considered a viable option, though with some drawbacks related to limited affinity between conventional liposomes and bacterial membranes. Here we propose a novel "top-down" procedure to prepare unconventional liposomes from the membranes of prokaryotes (PD-liposomes). These vectors, being obtained from bacteria with limited growth requirements, also represent low-cost systems for scalable biotechnology production. In depth physico-chemical characterization, carried out with dynamic light scattering (DLS) and Small Angle X-ray Scattering (SAXS), indicated that PD-liposomes can be suitable for the employment as antibiotic vectors. Specifically, DLS showed that the mean diameter of loaded liposomes was ∼200-300nm, while SAXS showed that the structure was similar to conventional liposomes, thus allowing a direct comparison with more standard liposomal formulations. Compared to free penicillin G, PD-liposomes loaded with penicillin G showed minimal inhibitory concentrations against E. coli that were up to 16-times lower. Noteworthy, the extent of the bacterial growth inhibition was found to depend on the microorganisms from which liposomes were derived.


Assuntos
Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Portadores de Fármacos/química , Penicilina G/administração & dosagem , Fosfolipídeos/química , Tecnologia Farmacêutica/métodos , Ampicilina/farmacologia , Antibacterianos/farmacologia , Cyanothece/química , Portadores de Fármacos/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Lipossomos , Testes de Sensibilidade Microbiana , Penicilina G/farmacologia , Fosfolipídeos/isolamento & purificação , Rodopseudomonas/química
10.
Infect Dis (Lond) ; 47(6): 370-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25746600

RESUMO

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex has become an important cause of nosocomial pneumonia. Sulbactam is a ß-lactamase inhibitor with antimicrobial activity against MDR Acb complex. METHODS: To investigate outcomes of pneumonia involving MDR Acb complex treated with sulbactam or ampicillin/sulbactam for at least 7 days, we conducted a retrospective study of 173 adult patients over a 34 month period. RESULTS: Of 173 patients, 138 (79.8%) received combination therapy, mainly with carbapenems (119/138, 86.2%). The clinical response rate was 67.6% and the 30 day mortality rate was 31.2%. The independent predictors of clinical failure were malignancy, bilateral pneumonia and shorter duration of treatment. In patients with sulbactam-susceptible strains, there was no difference in clinical and microbiological outcome between combination therapy and monotherapy. Compared to the sulbactam-susceptible group, the sulbactam-resistant group had a lower rate of airway eradication, a longer duration of treatment and a higher rate of combination therapy with predominantly carbapenems (p < 0.05). There was no significant difference between the two groups in clinical resolution and 30 day mortality rates. CONCLUSIONS: Sulbactam could be a treatment option for pneumonia involving MDR Acb complex, and combination therapy with carbapenems could be considered for sulbactam-resistant cases.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter calcoaceticus/efeitos dos fármacos , Antibacterianos/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Sulbactam/uso terapêutico , Infecções por Acinetobacter , Acinetobacter baumannii/isolamento & purificação , Acinetobacter calcoaceticus/isolamento & purificação , Adulto , Idoso , Ampicilina/administração & dosagem , Ampicilina/uso terapêutico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Estudos Retrospectivos , Sulbactam/administração & dosagem , Taiwan , Fatores de Tempo
11.
Nanoscale ; 7(8): 3511-9, 2015 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-25628231

RESUMO

The rapidly diminishing number of effective antibiotics that can be used to treat infectious diseases and associated complications in a physician's arsenal is having a drastic impact on human health today. This study explored the development and optimization of a polymersome nanocarrier formed from a biodegradable diblock copolymer to overcome bacterial antibiotic resistance. Here, polymersomes were synthesized containing silver nanoparticles embedded in the hydrophobic compartment, and ampicillin in the hydrophilic compartment. Results showed for the first time that these silver nanoparticle-embedded polymersomes (AgPs) inhibited the growth of Escherichia coli transformed with a gene for ampicillin resistance (bla) in a dose-dependent fashion. Free ampicillin, AgPs without ampicillin, and ampicillin polymersomes without silver nanoparticles had no effect on bacterial growth. The relationship between the silver nanoparticles and ampicillin was determined to be synergistic and produced complete growth inhibition at a silver-to-ampicillin ratio of 1 : 0.64. In this manner, this study introduces a novel nanomaterial that can effectively treat problematic, antibiotic-resistant infections in an improved capacity which should be further examined for a wide range of medical applications.


Assuntos
Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Resistência Microbiana a Medicamentos , Nanopartículas Metálicas/química , Polímeros/química , Prata/química , Ampicilina/administração & dosagem , Portadores de Fármacos , Sinergismo Farmacológico , Escherichia coli/metabolismo , Humanos , Hidrólise , Ácido Láctico/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Nanomedicina/métodos , Tamanho da Partícula , Poliésteres , beta-Lactamases/química
12.
Biomed Res Int ; 2014: 965348, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25101303

RESUMO

The inhibitory activity of a semipure fraction from the plant, Acalypha wilkesiana assigned as 9EA-FC-B, alone and in combination with ampicillin, was studied against methicillin-resistant Staphylococcus aureus (MRSA). In addition, effects of the combination treatment on PBP2a expression were investigated. Microdilution assay was used to determine the minimal inhibitory concentrations (MIC). Synergistic effects of 9EA-FC-B with ampicillin were determined using the fractional inhibitory concentration (FIC) index and kinetic growth curve assay. Western blot experiments were carried out to study the PBP2a expression in treated MRSA cultures. The results showed a synergistic effect between ampicillin and 9EA-FC-B treatment with the lowest FIC index of 0.19 (synergism ≤ 0.5). The presence of 9EA-FC-B reduced the MIC of ampicillin from 50 to 1.56 µg mL(-1). When ampicillin and 9EA-FC-B were combined at subinhibitory level, the kinetic growth curves were suppressed. The antibacterial effect of 9EA-FC-B and ampicillin was shown to be synergistic. The synergism is due the ability of 9EA-FC-B to suppress the activity of PBP2a, thus restoring the susceptibility of MRSA to ampicillin. Corilagin was postulated to be the constituent responsible for the synergistic activity showed by 9EA-FC-B.


Assuntos
Ampicilina/administração & dosagem , Sinergismo Farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Acalypha/química , Resistência a Ampicilina/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/biossíntese , Peptídeo Sintases/biossíntese , Extratos Vegetais/química
13.
J Chemother ; 25(4): 213-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23906074

RESUMO

Appendicitis is a frequent clinical condition in normal children that may be complicated by community-acquired secondary peritonitis (CASP). We evaluated the potential efficacy of different drugs for initial treatment of this condition, as recommended by recent Consensus Conference and Guidelines for paediatric patients. Susceptibility to ampicillin-sulbactam, ertapenem, gentamycin, piperacillin, piperacillin-tazobactam, vancomycin, and teicoplanin was evaluated according to EUCST 2012 recommendations in aerobic bacteria isolated from peritoneal fluid in CASP diagnosed from 2005 to 2011 at 'Istituto Giannina Gaslini', Genoa, Italy. A total of 114 strains were analysed: 83 E. coli, 15 P. aeruginosa, 6 Enterococci, and 10 other Gram-negatives. Resistance to ampicillin-sulbactam was detected in 37% of strains, while ertapenem showed a potential resistance of 13% (all P. aeruginosa strains). However, the combination of these drugs with gentamicin would have been increased the efficacy of the treatment to 99 and 100%, respectively. Resistance to piperacillin-tazobactam was 3%, while no strain was resistant to meropenem. Our data suggest that monotherapy with ampicillin-sulbactam or ertapenem for community-acquired secondary peritonitis would present a non-negligible rate of failure, but the addition of gentamycin to these drugs could reset to zero this risk. On the contrary, monotherapy with piperacillin-tazobactam or meropenem is highly effective.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Farmacorresistência Bacteriana , Peritonite/tratamento farmacológico , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/farmacologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Criança , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Quimioterapia Combinada , Ertapenem , Gentamicinas/administração & dosagem , Gentamicinas/farmacologia , Gentamicinas/uso terapêutico , Hospitais Pediátricos , Humanos , Itália/epidemiologia , Meropeném , Testes de Sensibilidade Microbiana , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Ácido Penicilânico/uso terapêutico , Peritonite/epidemiologia , Peritonite/microbiologia , Piperacilina/administração & dosagem , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Guias de Prática Clínica como Assunto , Sulbactam/administração & dosagem , Sulbactam/farmacologia , Sulbactam/uso terapêutico , Tienamicinas/administração & dosagem , Tienamicinas/farmacologia , Tienamicinas/uso terapêutico , beta-Lactamas/administração & dosagem , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
14.
Intern Med ; 52(10): 1131-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23676604

RESUMO

Aminoglycosides are useful antimicrobial agents for treating infective endocarditis; however, they occasionally cause troublesome side effects, such as nephrotoxicity and ototoxicity. We herein report a case of infective endocarditis caused by Enterococcus faecalis that was treated successfully with continuous infusion of ampicillin without adjunctive aminoglycosides. The serum ampicillin concentrations were higher than the minimal inhibitory concentration for the target strain. Although the use of ampicillin monotherapy is currently avoided because double ß-lactam therapy is reportedly more effective, continuous penicillin administration remains an effective therapeutic choice for treating infective endocarditis.


Assuntos
Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Enterococcus faecalis/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Idoso , Aminoglicosídeos/efeitos adversos , Ampicilina/administração & dosagem , Ampicilina/sangue , Ampicilina/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacologia , Anticoagulantes/uso terapêutico , Artroplastia de Quadril , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Contraindicações , Diagnóstico Diferencial , Endocardite Bacteriana/sangue , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Enterococcus faecalis/efeitos dos fármacos , Fraturas do Colo Femoral/cirurgia , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Valva Mitral/microbiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Guias de Prática Clínica como Assunto , Pielonefrite/diagnóstico , Estreptomicina , Varfarina/uso terapêutico
15.
Salvador; s.n; 2013. 50 p. ilus, tab.
Tese em Português | LILACS | ID: biblio-1000900

RESUMO

A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL)...


Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL...


Assuntos
Animais , Ampicilina/administração & dosagem , Ampicilina/análise , Ampicilina/uso terapêutico , Leptospira/crescimento & desenvolvimento , Leptospirose/diagnóstico , Leptospirose/epidemiologia , Leptospirose/patologia , Leptospirose/prevenção & controle , Leptospirose/transmissão
16.
Arch Pharm Res ; 35(11): 1919-26, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23212633

RESUMO

A new triterpenoid, named alisol Q 23-acetate, as well as fourteen known terpenes, alisol B 23-acetate (2), alisol B (3), alismol (4), 10-O-methyl-alismoxide (5), alismoxide (6), 11-deoxyalisol C (7), 13ß,17ß-epoxyalisol B 23-acetate (8), 4ß,12-dihydroxyguaian-6,10-diene (9), alisol C 23-acetate (10), alisolide (11), 16ß-methoxyalisol B monoacetate (12), alisol A (13), 16ß-hydroxyalisol B 23-acetate (14), alisol A 24-acetate (15) were isolated from the rhizomes of Alisma orientale. The structures of compounds (1-15) were identified based on 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Among these isolates, antibacterial effect of compounds 2, 3, 10, and 15, major constituents of A. orientale was examined. The MIC values of compounds 2, 10, and 15 were 5-10 ßg/mL against eight antibiotic resistant strains, which were lower than those from the positive controls (MICs of chloramphenicol and ampicillin were 5-80 µg/mL). Therefore, compounds 2, 10 and 15 exhibited the potent antibacterial activity.


Assuntos
Alisma/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Triterpenos/farmacologia , Ampicilina/administração & dosagem , Ampicilina/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Cloranfenicol/administração & dosagem , Cloranfenicol/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rizoma , Triterpenos/química , Triterpenos/isolamento & purificação
17.
Ann Pharmacother ; 46(7-8): e17, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22811349

RESUMO

OBJECTIVE: To describe a case of extensively drug-resistant (XDR) Acinetobacter baumannii peritoneal dialysis (PD)-associated peritonitis successfully treated with combination antibiotics, including intraperitoneal polymyxin B, with retention of the catheter. CASE SUMMARY: A 54-year-old woman with end-stage renal disease receiving chronic PD and recent antibiotic and hospital exposure presented with abdominal pain, nausea, and vomiting. She was found to have XDR A. baumannii PD peritonitis. Treatment was initiated with intravenous and intraperitoneal ampicillin-sulbactam, followed by the addition of intraperitoneal polymyxin B based on susceptibilities. The patient recovered without the need for catheter removal or switch to hemodialysis. DISCUSSION: The frequency of XDR A. baumannii as a nosocomial pathogen is increasing, and polymyxins are being used more often as part of combination therapy for infections caused by this organism. Neither XDR A. baumannii PD peritonitis nor the use of intraperitoneal polymyxin B has been well described. In our patient, intraperitoneal dosing of polymyxin B was determined based on limited published pharmacokinetic and pharmacodynamic data. CONCLUSIONS: A case of XDR A. baumannii PD peritonitis was successfully treated with combination antibiotic therapy, including intraperitoneal polymyxin B, without major complications.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/administração & dosagem , Infecção Hospitalar/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Polimixina B/administração & dosagem , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/crescimento & desenvolvimento , Ampicilina/administração & dosagem , Combinação de Medicamentos , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Peritonite , Sulbactam/administração & dosagem
18.
J Med Microbiol ; 61(Pt 8): 1156-1158, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22516132

RESUMO

We report what is believed to be the first case of pulmonary Actinomyces graevenitzii infection presenting as organizing pneumonia. Fever and night sweats developed in a 69-year-old male. The only abnormal laboratory data were an elevated erythrocyte sedimentation rate and C-reactive protein level. On chest images, multiple consolidations with air bronchograms were seen in the bilateral lungs. Histological examination from lung biopsy revealed a pattern of organizing pneumonia with microabscesses, but definitive diagnosis was not obtained because culture from lung specimen was negative. A. graevenitzii was eventually identified in the lung biopsy specimen by detection of an Actinomyces-specific PCR product followed by 16S rRNA gene sequencing. The patient was treated with high-dose ampicillin intravenously for 1 month, followed by oral amoxicillin and clarithromycin for 6 months, and recovered. We suggest that actinomycosis can present as organizing pneumonia, and identification of infection by PCR analysis and rRNA gene sequencing is a useful strategy in cases that are difficult to diagnose.


Assuntos
Actinomyces/isolamento & purificação , Actinomicose/diagnóstico , Actinomicose/patologia , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/patologia , Reação em Cadeia da Polimerase/métodos , Actinomyces/classificação , Actinomyces/genética , Actinomicose/tratamento farmacológico , Actinomicose/microbiologia , Idoso , Amoxicilina/administração & dosagem , Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Técnicas Bacteriológicas/métodos , Biópsia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Claritromicina/administração & dosagem , Pneumonia em Organização Criptogênica/tratamento farmacológico , Pneumonia em Organização Criptogênica/microbiologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Histocitoquímica , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Radiografia Torácica , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
J Oral Maxillofac Surg ; 68(2): 344-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20116706

RESUMO

PURPOSE: The purpose of this study was to evaluate the prophylactic value of single-dose antibiotic prophylaxis on postoperative infection in patients undergoing orthognathic surgery, compared to single-day antibiotics. MATERIALS AND METHODS: One hundred fifty patients were included in the study; 57 males and 93 females were divided into 2 groups with 75 in each group. Group 1 received a single dose of antibiotic prophylaxis and group 2 received a single day of antibiotic prophylaxis. These patients were assessed for rates of infection postoperatively after orthognathic surgery. RESULTS: Seven patients (9.3%) in group 1 developed infection, whereas 2 patients (2.6%) in group 2 developed infection. The difference in rates of infection in both groups was of interest but not statistically significant (P > .05). CONCLUSION: The results from the present study show that there is a clinically significant difference, but no statistically significant difference, between single-dose antibiotic prophylaxis and single-day antibiotic prophylaxis in reducing the rates of infection in orthognathic procedures. We recommend further studies with a larger sample size to determine whether there truly is no statistical difference between both groups.


Assuntos
Ampicilina/administração & dosagem , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Cronofarmacoterapia , Feminino , Humanos , Masculino , Estudos Prospectivos , Infecção da Ferida Cirúrgica/etiologia , Adulto Jovem
20.
Environ Entomol ; 39(4): 1170-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22127168

RESUMO

Folsomia candida Willem (Isotomidae: Collembola) is an edaphic parthenogenetic species commonly used in ecotoxicity studies. We exposed F. candida to a high dose of three antibiotics, tylosin, ampicillin, and oxytetracycline, that target different bacterial groups. Possible toxic effects were assessed through egg production, hatching, and body size. All three antibiotics caused toxic effects. Treatment with oxytetracycline proved the most toxic. This group showed the smallest body size and lowest number of eggs laid, likely the result of a combination of antibiotic toxicity and avoidance of the antibiotic spiked food. Active toxin avoidance by F. candida in toxicological assays may play a role in minimizing their exposure to toxic compounds. Despite the administration of high doses of oxytetracycline, F. candida individuals remained infected with the intracellular bacteria Wolbachia indicating that this strain is resistant to this antibiotic or that the host or its gut flora had detoxified the compound. An increase in percent egg hatch with time was seen in the ampicillin and oxytetracycline treatments, indicating a possible accommodation of the host and/or gut-flora to these antibiotics.


Assuntos
Antibacterianos/toxicidade , Artrópodes/efeitos dos fármacos , Tamanho Corporal/efeitos dos fármacos , Oviparidade/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Ampicilina/administração & dosagem , Ampicilina/toxicidade , Animais , Antibacterianos/administração & dosagem , Artrópodes/microbiologia , Feminino , Oxitetraciclina/administração & dosagem , Oxitetraciclina/toxicidade , Partenogênese , Simbiose , Tilosina/administração & dosagem , Tilosina/toxicidade , Wolbachia
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