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1.
Wiad Lek ; 77(1): 171-177, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38431823

RESUMEN

We reported the case of tonsillitis treatment in a 17-years-old boy with use of chemical non-antibiotic preparations, plant derived products and antibiotic benzathine phenoxymethylpenicillin. The antimicrobial agents for treatment were selected on the basis of their activity against a disease agent, the group A ß-hemolytic strain Streptococcus pyogenes BS1 isolated from a patient. The bacterium was susceptible in vitro to ß-lactams, with largest zones conditioned by penicillin G and benzathine phenoxymethylpenicillin discs, to fluoroquinolones and to cephems, with exception of cefazolin. Lincosamide clindamycin, macrolide spiramycin, aminoglycoside gentamicin, erythromycin, tetracycline and combination of sulfamethoxazole and trimethoprim were inactive against this bacterium. The Streptococcus pyogenes BS1 demonstrated intermediate susceptibility to the cephalosporin cephalexin, fluoroquinolone lomefloxacin and glycopeptide vancomycin. Non-antibiotic preparations were evaluated against Streptococcus pyogenes BS1 also. Among them "Stomatidin", "Chlorophyllipt", and phages of "Pyofag" were more effective than "Decatylen", "Decasan" and "Furadonin" in vitro. The antimicrobial applications of "Stomatidin", "Chlorophyllipt" and phages of "Pyofag" in the patient were less effective compared to the result of antibiotic benzathine phenoxymethylpenicillin treatment. Complete recovery of the patient was achieved with use of this antibiotic and Calendula flower extract as an local anti-inflammatory agent.


Asunto(s)
Antiinfecciosos , Etilenodiaminas , Tonsilitis , Adolescente , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Penicilina V/farmacología , Streptococcus pyogenes , Tonsilitis/tratamiento farmacológico
2.
Enzyme Microb Technol ; 149: 109819, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34311875

RESUMEN

The recognition and interaction of FEZ-1 from Legionella (FEZ-1) with penicillin V(PV) and cefoxitin(CFX) were investigated using fluorescence spectra in combination with molecular dynamics simulation (MD). The results revealed that the CFX bind with FEZ-1 in stronger interaction and induced larger conformational change than PV, despite all being forced by the electrostatic interaction and along with the changing in an environment of amino acid residues as well as the polypeptide skeleton inside the FEZ-1. Moreover, only the loop1, loop2, and N-terminal were observed locating near the binding pocket of FEZ-1, consisting of a flexible "gate-like" zone with better adaptability that controlled the entrance of antibiotic into the pocket by allowing the newly introduced antibiotic to match the pocket better through the conformational changes of these three substructures in the binding procedure. The current study may provide some valuable information on the antibiotic hydrolytic process by metallo-beta-lactamase and thus the references for the development of new antibiotics for super bacteria.


Asunto(s)
Cefoxitina , Legionella , Penicilina V , beta-Lactamasas , Cefoxitina/farmacología , Legionella/metabolismo , Simulación de Dinámica Molecular , Penicilina V/farmacología , beta-Lactamasas/metabolismo
3.
J Glob Antimicrob Resist ; 20: 290-297, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31415828

RESUMEN

OBJECTIVES: Antibiotic overuse has led to the global emergence of antimicrobial-resistant bacteria, and children are among the most frequent users of antibiotics. Most studies with broad-spectrum antibiotics show a severe impact on resistome development in patients. Although narrow-spectrum antibiotics are believed to have fewer side effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (penicillin V) on the microbiome and resistome of a child treated for acute otitis media. METHODS: Oral and faecal samples were collected from a 1-year-old child before (Day 0) and after (Days 5 and 30) receiving penicillin V for otitis media. Metagenomic sequencing data were analysed to determine taxonomic profiling using Kraken and Bracken software, and resistance profiling using KMA in combination with the ResFinder database. RESULTS: In the oral samples, antimicrobial resistance genes (ARGs) belonging to four classes were identified at baseline. At Day 5, the abundance of some ARGs was increased, whereas some remained unchanged and others could no longer be detected. At Day 30, most ARGs had returned to baseline levels or lower. In the faecal samples, seven ARGs were observed at baseline and five at Day 5. At Day 30, the number of ARGs had increased to 21. CONCLUSIONS: Following penicillin V, we observed a remarkable enrichment of the aecal resistome, indicating that even narrow-spectrum antibiotics may have important consequences in selecting for a more resistant microbiome.


Asunto(s)
Antibacterianos/uso terapéutico , Bacterias/clasificación , Farmacorresistencia Bacteriana , Metagenómica/métodos , Otitis Media/microbiología , Penicilina V/uso terapéutico , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Proteínas Bacterianas/genética , Heces/microbiología , Femenino , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Boca/microbiología , Otitis Media/tratamiento farmacológico , Penicilina V/farmacología , Filogenia , Análisis de Secuencia de ADN
4.
Clin Pharmacol Ther ; 107(3): 607-616, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31563140

RESUMEN

The antibiotics dicloxacillin and flucloxacillin induce cytochrome P450-dependent metabolism of warfarin. We explored the influence of these drug-drug interactions on the clinical effectiveness of warfarin therapy due to atrial fibrillation or heart valve replacement. Using the population-based Danish registers, we performed a propensity-score matched cohort study including around 50,000 episodes of dicloxacillin/flucloxacillin matched to phenoxymethylpenicillin and to no antibiotic, respectively. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) by comparing 21-day (days 7-28) risks of ischemic stroke/systemic embolism (SE) following initiation of each exposure. When compared with phenoxymethylpenicillin, dicloxacillin/flucloxacillin was associated with an HR of ischemic stroke/SE of 2.09 (95% CI 1.51-2.90; strongest for dicloxacillin (HR 2.17; 95% CI 1.56-3.02)). Use of an untreated comparator strengthened the association (HR 2.84; 95% CI 1.97-4.09). Dicloxacillin should be used with caution in patients receiving warfarin. This may also apply to flucloxacillin; however, more data on the risks associated with flucloxacillin exposure during warfarin therapy are needed.


Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Dicloxacilina/farmacología , Floxacilina/farmacología , Implantación de Prótesis de Válvulas Cardíacas/métodos , Warfarina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Anticoagulantes/farmacología , Fibrilación Atrial/complicaciones , Isquemia Encefálica/epidemiología , Isquemia Encefálica/etiología , Isquemia Encefálica/prevención & control , Estudios de Cohortes , Interacciones Farmacológicas , Embolia/epidemiología , Embolia/etiología , Embolia/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Penicilina V/farmacología , Sistema de Registros , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Warfarina/farmacocinética , Warfarina/farmacología , Adulto Joven
5.
Sci Total Environ ; 651(Pt 1): 1605-1612, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-30360286

RESUMEN

߭Lactam antibiotics are among the most widely used antibiotics in human medicine and their effects on the aquatic environment - concerning bacterial resistance - are controversially discussed. This study focused on the photolysis of the four ߭lactam antibiotics - amoxicillin, ampicillin, penicillin V and piperacillin - under simulated environmental conditions. It was observed that all investigated ߭lactam antibiotics are photolytically degradable by simulated sunlight (1 kW/m2) with half-lives between 3.2 and 7.0 h. Structure elucidation of transformation products performed with liquid chromatography coupled to high resolution mass spectrometry showed that the hydrolysis of the ߭lactam ring is the primary transformation reaction, followed by the elimination of carboxylic and dimethyl thiazolidine carboxylic acid. Growth inhibition tests on Bacillus subtilis showed the loss of bactericide activity of irradiated solutions of amoxicillin, ampicillin and piperacillin, suggesting the transformation of the ߭lactam ring is responsible for the antibiotic effect. In contrast, the solutions of penicillin V did not show any decline of the antibacterial activity after photolytic degradation, probably due to the formation of still active epimers.


Asunto(s)
Antibacterianos/química , Fotólisis , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/química , beta-Lactamas/química , Amoxicilina/química , Amoxicilina/farmacología , Ampicilina/química , Ampicilina/farmacología , Antibacterianos/farmacología , Biodegradación Ambiental , Penicilina V/química , Penicilina V/farmacología , Piperacilina/química , Piperacilina/farmacología , Luz Solar , beta-Lactamas/farmacología
6.
PLoS One ; 12(7): e0180925, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28749949

RESUMEN

There is an urgent need to develop new drug treatment strategies to control the global spread of drug-sensitive and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). The ß-lactam class of antibiotics is among the safest and most widely prescribed antibiotics, but they are not effective against M. tuberculosis due to intrinsic resistance. This study shows that 2-aminoimidazole (2-AI)-based small molecules potentiate ß-lactam antibiotics against M. tuberculosis. Active 2-AI compounds significantly reduced the minimal inhibitory and bactericidal concentrations of ß-lactams by increasing M. tuberculosis cell envelope permeability and decreasing protein secretion including ß-lactamase. Metabolic labeling and transcriptional profiling experiments revealed that 2-AI compounds impair mycolic acid biosynthesis, export and linkage to the mycobacterial envelope, counteracting an important defense mechanism reducing permeability to external agents. Additionally, other important constituents of the M. tuberculosis outer membrane including sulfolipid-1 and polyacyltrehalose were also less abundant in 2-AI treated bacilli. As a consequence of 2-AI treatment, M. tuberculosis displayed increased sensitivity to SDS, increased permeability to nucleic acid staining dyes, and rapid binding of cell wall targeting antibiotics. Transcriptional profiling analysis further confirmed that 2-AI induces transcriptional regulators associated with cell envelope stress. 2-AI based small molecules potentiate the antimicrobial activity of ß-lactams by a mechanism that is distinct from specific inhibitors of ß-lactamase activity and therefore may have value as an adjunctive anti-TB treatment.


Asunto(s)
Antiinfecciosos/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Imidazoles/farmacología , Mycobacterium tuberculosis/citología , Mycobacterium tuberculosis/enzimología , beta-Lactamasas/metabolismo , beta-Lactamas/farmacología , Carbenicilina/farmacología , Colorantes/química , Lípidos/análisis , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Ácidos Nucleicos/metabolismo , Penicilina V/farmacología , Dodecil Sulfato de Sodio/farmacología , Coloración y Etiquetado , Transcripción Genética/efectos de los fármacos , Vancomicina/farmacología
7.
Br J Clin Pharmacol ; 83(8): 1643-1653, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28185274

RESUMEN

AIMS: In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs. METHODS: This study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively. RESULTS: Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. CONCLUSION: Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.


Asunto(s)
Antibacterianos/farmacología , ADN/química , Estrés Oxidativo/efectos de los fármacos , ARN/química , Especies Reactivas de Oxígeno/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Biomarcadores/orina , Claritromicina/farmacología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Guanosina/análogos & derivados , Guanosina/orina , Voluntarios Sanos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/sangre , Oxidación-Reducción , Penicilina V/farmacología , Placebos , Trimetoprim/farmacología , Adulto Joven
8.
Infect Dis (Lond) ; 48(3): 241-5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26523346

RESUMEN

The purpose of the study was to evaluate how use of antibiotics precedes the presence of ESBL-producing E.coli in general practice. The authors performed a triple-case-control study where three case groups were individually compared to a single control group of uninfected individuals. Urine samples were prospectively collected and retrospective statistical analyses were done. This study included 98 cases with urinary tract infection (UTI) caused by ESBL-producing E. coli, 174 with antibiotic-resistant (non-ESBL) E. coli, 177 with susceptible E. coli and 200 with culture negative urine samples. Case groups had significantly higher use of antibiotics than the control group within 30 days before infection (p < 0.0001). The ESBL group had significantly more hospital admissions than the other case groups (p < 0.05). Hospital admission was an independent risk factor for community onset UTI by ESBL-producing E. coli. Exposure to antibiotics was a risk factor for UTI with E. coli, while prior antibiotic usage was not an indisputable predictor for infection with ESBL-producing E.coli in general practice.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/epidemiología , Escherichia coli/enzimología , Infecciones Urinarias/epidemiología , Resistencia betalactámica , beta-Lactamasas/biosíntesis , Adulto , Amdinocilina Pivoxil/farmacología , Amdinocilina Pivoxil/uso terapéutico , Antibacterianos/farmacología , Estudios de Casos y Controles , Dinamarca/epidemiología , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Medicina General , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Penicilina V/farmacología , Penicilina V/uso terapéutico , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , beta-Lactamasas/genética
9.
Toxicol Appl Pharmacol ; 262(3): 283-92, 2012 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-22609641

RESUMEN

Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1ß, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines.


Asunto(s)
Antibacterianos/farmacología , Células Dendríticas/efectos de los fármacos , Células de Langerhans/efectos de los fármacos , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Ampicilina/efectos adversos , Ampicilina/farmacología , Antibacterianos/efectos adversos , Hidrolasas de Éster Carboxílico/análisis , Carcinoma de Células Renales/química , Carcinoma de Células Renales/metabolismo , Proteínas Portadoras/análisis , Línea Celular , Línea Celular Tumoral , Proteínas de Unión al ADN/análisis , Células Dendríticas/química , Dioxigenasas , Glutamato-Cisteína Ligasa/análisis , Humanos , Técnicas In Vitro , Interleucina-1beta/análisis , Interleucina-8/análisis , Células de Langerhans/química , Macrófagos/química , Monocitos/química , NAD(P)H Deshidrogenasa (Quinona)/análisis , Proteínas Nucleares/análisis , Penicilina G/efectos adversos , Penicilina G/farmacología , Penicilina V/efectos adversos , Penicilina V/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Sulfametoxazol/efectos adversos , Sulfametoxazol/farmacología , Factores de Transcripción/análisis , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas
10.
Bioorg Med Chem ; 19(24): 7534-40, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-22075235

RESUMEN

Two well-known antibiotic heterocycles, the 'quinolone' nalidixic acid and the ß-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether-ester junction to the p-tert-butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dis-symmetrical podand incorporating one penicillin and one nalidixic ester moieties.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Ácido Nalidíxico/química , Ácido Nalidíxico/farmacología , Penicilina V/análogos & derivados , Penicilina V/farmacología , Antibacterianos/síntesis química , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Calixarenos/síntesis química , Calixarenos/química , Calixarenos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Nalidíxico/síntesis química , Penicilina V/síntesis química , Staphylococcus aureus/efectos de los fármacos
11.
J Mol Model ; 16(7): 1291-306, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20112037

RESUMEN

Inhibitive and adsorption properties of Penicillin G, Amoxicillin and Penicillin V potassium were studied using gravimetric, gasometric and quantum chemical methods. The results obtained indicate that these compounds are good adsorption inhibitors for the corrosion of mild steel in HCl solution. The adsorption of the inhibitors on mild steel surface is spontaneous, exothermic and supports the mechanism of physical adsorption. From DFT results, the sites for nucleophilic attacks in the inhibitors are the carboxylic acid functional group while the sites for electrophilic attacks are in the phenyl ring. There was a strong correlation between theoretical and experimental inhibition efficiencies.


Asunto(s)
Ácido Clorhídrico/química , Modelos Químicos , Penicilinas/química , Acero/química , Algoritmos , Amoxicilina/química , Amoxicilina/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Corrosión , Ácido Clorhídrico/farmacología , Modelos Moleculares , Estructura Molecular , Penicilina G/química , Penicilina G/farmacología , Penicilina V/química , Penicilina V/farmacología , Penicilinas/farmacología , Propiedades de Superficie/efectos de los fármacos
12.
Biomacromolecules ; 10(3): 623-9, 2009 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-19173575

RESUMEN

Surface reactions were performed on polypropylene (PP) surfaces to retard the simultaneous growth of Staphylococcus aureus (S. aureus) and Pseudomonas putida (P. putida) bacteria. Microwave plasma reactions in the presence of maleic anhydride (MA) resulted in the formation of acid groups on the surface of PP. Such surfaces were further modified by conducting two parallel reactions: (1) poly(ethylene glycol) (PEG) was attached to COOH groups of the PP surface, followed by penicillin V (PEN) reactions to target S. aureus destruction and (2) diglycidyl PEG was attached, followed by gentamicin (GEN) reactions, to create antimicrobial surfaces targeted at P. putida . Simultaneous gram "+" and gram "-" resistance was obtained by varying the PEN/GEN ratios on such modified PP surfaces, thus providing the controllable degree of gram "+" and gram "-" antimicrobial strength. While spectroscopic analyses revealed chemical attachments of PEN and GEN, the effectiveness against proliferation of S. aureus (Gram +) and P. putida (Gram -) bacteria was determined using liquid culture tests. These studies show for the first time the formation of tunable antimicrobial polypropylene surfaces with controllable strength.


Asunto(s)
Antibacterianos/farmacología , Gentamicinas/farmacología , Penicilina V/farmacología , Polipropilenos/farmacología , Pseudomonas putida/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Gentamicinas/química , Sustancias Macromoleculares/química , Sustancias Macromoleculares/farmacología , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Penicilina V/química , Polietilenglicoles/química , Polipropilenos/química , Pseudomonas putida/crecimiento & desarrollo , Staphylococcus aureus/crecimiento & desarrollo , Propiedades de Superficie
13.
Clin Infect Dis ; 43(11): 1398-406, 2006 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-17083011

RESUMEN

BACKGROUND: Group A streptococci (Streptococcus pyogenes; GAS) invades human epithelial cell lines. Failure of penicillin to eradicate GAS from the throats of patients, especially those who are GAS "carriers," has been increasingly reported. However, there has been no comprehensive evaluation of how effectively antibiotics that are used to treat GAS enter upper respiratory tract epithelial cells and kill internalized GAS. We examined the viability of ingested, intracellular GAS after epithelial cell exposure to antibiotics commonly recommended for therapy of GAS infections. METHODS: A human laryngeal epithelial cell line (HEp-2) was used. Three techniques were used to study antibiotic (penicillin V, erythromycin, azithromycin, cephalothin, and clindamycin) killing of ingested GAS: examination by electron microscopy of ultrathin sections of ingested GAS, qualitative determination of intra-epithelial cell antibiotic, and special stain evaluation of intracellular GAS viability after epithelial cell exposure to antibiotics. RESULTS: GAS survived intracellularly despite exposure of the GAS-containing epithelial cells to penicillin. In contrast, there was killing of ingested GAS after exposure of epithelial cells to either erythromycin or azithromycin. Electron microscopy confirmed a lack of intracellular GAS fragmentation (cell death) after exposure of epithelial cells to penicillin in contrast to obvious GAS fragmentation after epithelial cell exposure to erythromycin or azithromycin. Cephalothin, a cephalosporin, and clindamycin were more effective in killing ingested GAS than was penicillin, but they were less effective than erythromycin or azithromycin. CONCLUSIONS: These observations strongly suggest that if the GAS upper respiratory tract carrier state results from intra-epithelial cell GAS survival, the failure of penicillin to kill ingested GAS may be related to a lack of effective penicillin entry into epithelial cells. These unique observations may have clinical implications for understanding GAS respiratory tract carriers and managing GAS infections.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Células Epiteliales/microbiología , Penicilina V/farmacología , Streptococcus pyogenes/efectos de los fármacos , Azitromicina/farmacología , Línea Celular , Cefalotina/farmacología , Clindamicina/farmacología , Relación Dosis-Respuesta a Droga , Células Epiteliales/ultraestructura , Eritromicina/farmacología , Humanos , Pruebas de Sensibilidad Microbiana
14.
Clin Microbiol Infect ; 10(7): 615-23, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15214873

RESUMEN

A pooled analysis of two double-blind, multicentre, Phase III studies compared oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus; GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS tonsillopharyngitis were randomised to receive telithromycin (n = 430), penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S. pyogenes (n = 590) obtained from throat swab samples on study entry were tested for their in-vitro susceptibility to telithromycin, clarithromycin and azithromycin. Telithromycin demonstrated in-vitro activity against the clinical isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively), including erythromycin-resistant strains. At the post-therapy/test of cure (TOC) visit (days 16-23), satisfactory bacteriological outcome was demonstrated for 88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated patients, respectively (per-protocol population). Overall, GABHS eradication rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6% (248/265) and 90.9% (220/242) for telithromycin and pooled comparators, respectively. Telithromycin was generally well-tolerated. Most adverse events considered to be possibly related to study medication were gastrointestinal and of mild intensity. Discontinuations as a result of adverse events were few in both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days was as effective as penicillin V or clarithromycin for 10 days in the treatment of GABHS tonsillopharyngitis.


Asunto(s)
Antibacterianos/uso terapéutico , Cetólidos , Macrólidos/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes/efectos de los fármacos , Tonsilitis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Niño , Preescolar , Claritromicina/administración & dosificación , Claritromicina/farmacología , Claritromicina/uso terapéutico , Femenino , Humanos , Lactante , Macrólidos/administración & dosificación , Macrólidos/farmacología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Penicilina V/administración & dosificación , Penicilina V/farmacología , Penicilina V/uso terapéutico , Faringitis/microbiología , Infecciones Estreptocócicas/microbiología , Tonsilitis/microbiología , Resultado del Tratamiento
15.
Int J Antimicrob Agents ; 23(1): 67-71, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14732316

RESUMEN

The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue.


Asunto(s)
Antibacterianos/farmacología , Claritromicina/farmacología , Penicilina V/farmacología , Faringitis/microbiología , Streptococcus pyogenes/efectos de los fármacos , Antibacterianos/uso terapéutico , Niño , Claritromicina/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Penicilina V/uso terapéutico , Faringitis/tratamiento farmacológico , Estudios Prospectivos , Seguridad , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Resultado del Tratamiento
16.
J Biomater Sci Polym Ed ; 14(10): 1043-56, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14661878

RESUMEN

Starburst PAMAM dendrimers are potential carriers for drug delivery due to their unique structure. Drug-delivery scaffolds were designed and built up based on the polyethylene glycolpolyamidoamine (PEG-PAMAM) star polymer. Penicillin V was used as a model carboxylic group containing drug to conjugate with full- and half-generation PAMAM dendrimers. G2.5 PAMAM (with 32 carboxylic groups on the surface) dendrimers and G3.0 (with 32 primary amine groups on the surface) were typically chosen. There are two strategies given in the paper where a drug carrying a carboxylic group (e.g. penicillin V) was coupled to star polymer via amide and ester bonds, respectively. FT-IR, UV-Vis and 1H-NMR were used to characterize the intermediates and drug-star polymer conjugates. A single-strain bacterium, Staphylococcus aureus, was grown up for penicillin-conjugated PEG-PAMAM (G3.0) star polymer activity test. The result verified the bioavailability of modified penicillin after the ester bond was cleaved.


Asunto(s)
Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos/métodos , Penicilina V/química , Poliaminas/química , Polietilenglicoles/química , Antibacterianos/química , Antibacterianos/farmacología , Materiales Biocompatibles/síntesis química , Dendrímeros , Espectroscopía de Resonancia Magnética , Penicilina V/farmacología , Poliaminas/síntesis química , Polietilenglicoles/síntesis química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética
17.
Curr Med Res Opin ; 19(5): 421-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-13678479

RESUMEN

OBJECTIVE: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes. RESEARCH DESIGN AND METHODS: A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture. MAIN OUTCOME MEASURES: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8-12; visit 4: study days 13-20; and visit 5: study days 40-50). RESULTS: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (-8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (-10.0, 4.4)). Clinical cure was achieved in > or = 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< or = 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea. CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.


Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Penicilina V/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Tonsilitis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Análisis de Varianza , Antibacterianos/farmacología , Niño , Claritromicina/farmacología , Preparaciones de Acción Retardada , Método Doble Ciego , Farmacorresistencia Bacteriana , Humanos , Persona de Mediana Edad , Cooperación del Paciente , Penicilina V/farmacología , Faringitis/microbiología , Streptococcus pyogenes/efectos de los fármacos , Tonsilitis/microbiología , Resultado del Tratamiento
18.
J Endod ; 29(1): 44-7, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12540219

RESUMEN

Antibiotics to treat endodontic infections are routinely prescribed based on previously published susceptibility tests. There is increased concern that bacteria have increased resistance to the currently recommended antibiotics. The purpose of this investigation was to perform antibiotic susceptibility tests on a panel of bacteria recently isolated from endodontic infections. The bacteria in this study were aseptically aspirated with a needle from endodontic abscesses, cultivated, and identified at the species level. Each of the 98 species of bacteria was tested for antibiotic susceptibility to a panel of six antibiotics using the Etest. The antibiotics were penicillin V, amoxicillin, amoxicillin + clavulanic acid, clindamycin, metronidazole, and clarithromycin. The percentages of susceptibility for the 98 species were penicillin V: 83/98 (85%), amoxicillin: 89/98 (91%), amoxicillin + clavulanic acid: 98/98 (100%), clindamycin: 94/98 (96%), and metronidazole: 44/98 (45%). Metronidazole had the greatest amount of bacterial resistance; however, if it is used in combination with penicillin V or amoxicillin, susceptibility of the combination with penicillin V or amoxicillin increased to 93% and 99%, respectively. Clarithromycin seems to have efficacy, but it is still considered an antibiotic under investigation because the minimum inhibitory concentration has not been established.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Absceso Periapical/microbiología , Amoxicilina/farmacología , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Antibacterianos/uso terapéutico , Bacterias Anaerobias/efectos de los fármacos , Clindamicina/farmacología , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Penicilina V/farmacología , Absceso Periapical/tratamiento farmacológico
19.
Artículo en Inglés | MEDLINE | ID: mdl-12464902

RESUMEN

OBJECTIVE: The purpose of the study was to identify the bacterial composition of the microbiota from acute endodontic abscesses/cellulitis and their antimicrobial susceptibilities. STUDY DESIGN: Purulence from 17 patients with acute endodontic abscesses/cellulitis was obtained by needle aspiration and processed under anaerobic conditions. Bacteria were isolated and identified by biochemical or molecular methods. The antimicrobial susceptibility of isolated bacteria was determined by using the Etest. RESULTS: All 17 aspirates contained a mix of microorganisms. A total of 127 strains of bacteria were isolated. Of 127 strains, 80 strains were anaerobes and 47 strains were aerobes. The mean number of strains per sample was 7.5 (range, 3 to 13). The average number of viable bacteria was 6.37 x 10(7) (range, 10(4) to 10(8)) colony-forming units/mL. Strict anaerobes and microaerophiles were the dominant bacteria in 82% (14 of 17) of the cases. The genera of bacteria most frequently encountered were Prevotella and Streptococcus. Prevotella and Peptostreptococcus were frequently found to dominate the mixture. The combination of Prevotella and Streptococcus was found in 53% (9 of 17). The previously reported uncultured Prevotella clone PUS9.180 was frequently identified. The percentage of bacteria susceptible/intermediate for each antibiotic in this study was penicillin V, 81% (95 of 118); metronidazole, 88% (51 of 58); amoxicillin, 85% (100 of 118); amoxicillin + clavulanic acid, 100% (118 of 118); and clindamycin, 89% (105 of 118). CONCLUSIONS: The present results confirm the existence of mixed infection with the predominance of anaerobic bacteria in acute endodontic abscesses/cellulitis. The frequency of uncultured Prevotella clone PUS9.180 suggests the possible key role of this Prevotella species in acute endodontic infections. Penicillin V still possesses antimicrobial activity against the majority of bacteria isolated from acute endodontic infections. However, if penicillin V therapy has failed to be effective, the combination of penicillin V with metronidazole or amoxicillin with clavulanic acid is recommended. Switching to clindamycin is another good alternative.


Asunto(s)
Bacterias Anaerobias/patogenicidad , Enfermedades de la Pulpa Dental/microbiología , Absceso/microbiología , Adolescente , Adulto , Amoxicilina/farmacología , Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Bacterias Anaerobias/aislamiento & purificación , Niño , Ácido Clavulánico/farmacología , Clindamicina/farmacología , Recuento de Colonia Microbiana , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Metronidazol/farmacología , Persona de Mediana Edad , Penicilina V/farmacología , Peptostreptococcus/efectos de los fármacos , Peptostreptococcus/aislamiento & purificación , Peptostreptococcus/patogenicidad , Prevotella/efectos de los fármacos , Prevotella/aislamiento & purificación , Prevotella/patogenicidad , Streptococcus/efectos de los fármacos , Streptococcus/aislamiento & purificación , Streptococcus/patogenicidad
20.
Pediatr Infect Dis J ; 21(4): 304-8, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12075761

RESUMEN

OBJECTIVE: To compare a 3-day azithromycin vs. a 10-day penicillin V regimen for treatment of acute group A streptococcal (GAS) pharyngitis in children and to determine whether viral infection and/or pharyngeal GAS carriage in patients and adult contacts affect clinical and bacteriologic efficacy. METHODS: This multicenter, randomized, comparative, open label study compared 3-day, once daily 10 mg/kg azithromycin oral suspension with a 10-day regimen of 100,000 IU/kg/day penicillin V oral suspension in three divided doses in children with acute GAS pharyngitis. Clinical and bacteriologic efficacy and tolerability of the antibiotics were evaluated. Recurrence of symptoms and infection was monitored for 6 months. RESULTS: In total, 292 children (age range, 2 to 12 years) received at least one dose of study medication. Clinical success (cure/improvement) with either antibiotic was similar at the end of therapy (Day 14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin, 94%; penicillin V, 95%). Bacteriologic eradication was significantly less with azithromycin than with penicillin V at Day 14 (azithromycin, 38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin, 31%; penicillin V, 68%; P < 0.001). There was no associated increase in GAS-related sequelae. The lower incidence of bacteriologic eradication with azithromycin was not the result of possible concomitant viral infections in the patients, GAS carriage in one parent/guardian or any reduced susceptibility in pretreatment GAS isolates. Both antibiotics were equally well-tolerated. CONCLUSIONS: Treatment with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis is associated with similar high levels of clinical efficacy, but lower levels of bacteriologic eradication, than with 10-day 100,000 IU/kg/day penicillin V.


Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Azitromicina/administración & dosificación , Azitromicina/farmacología , Penicilina V/administración & dosificación , Penicilina V/farmacología , Penicilinas/administración & dosificación , Penicilinas/farmacología , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes/patogenicidad , Administración Oral , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Niño , Preescolar , Esquema de Medicación , Femenino , Humanos , Lactante , Masculino , Faringitis/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/aislamiento & purificación , Resultado del Tratamiento
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