Daptomycin at standard doses, and especially at high doses, may be a useful alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis.
CSF TNF-α levels were significantly lower in rabbits treated with daptomycin than in rabbits treated with ceftriaxone. Daptomycin avoided the inflammatory peak after administration observed in ceftriaxone-treated rabbits. The use of daptomycin plus dexamethasone achieved a significantly larger reduction in CSF TNF-α levels.
Introducción. La malformación de Chiari tipo I (MC-I) es una entidad de baja prevalencia, cuya clínica es muy variada dependiendo del cortejo malformativo asociado, y en la que pueden existir síntomas ansiosodepresivos y una pérdida no definida de la calidad de vida de los pacientes. El objetivo principal de este estudio es determinar la repercusión de la MC-I en la calidad de vida, así como la presencia de ansiedad y depresión en estos pacientes. Pacientes y métodos. Estudio prospectivo de una cohorte de 67 pacientes afectos de MC-I en los que se valoraron la calidad de vida, la presencia de ansiedad y síntomas depresivos mediante las escalas Sickness Impact Profile, inventario de ansiedad estado-rasgo e inventario de depresión de Beck, respectivamente. En cada paciente se registró la presencia de siringomielia o hidrocefalia, así como el grado de ectopia de las amígdalas del cerebelo. Resultados. El impacto de la MC-I en la calidad de vida fue nulo en seis pacientes (9%), leve en 36 (53,7%), moderado en 17 (25,4%) y grave en ocho (11,9%). El área de actividad más afectada fue el trabajo. El 86,6% de los pacientes presentó un nivel de ansiedad moderado o elevado. En el 25,4% de los pacientes también se constataron síntomas depresivos moderados o graves. Conclusiones. La gran mayoría de los pacientes con una MC-I considera que su enfermedad implica una pérdida de calidad de vida que, en muchos casos, se asocia a una alta ansiedad y a síntomas depresivos. Palabras clave. Ansiedad. Calidad de vida. Depresión. Ectopia amigdalar. Hidrocefalia. Malformación de Chiari tipo I. Siringomielia.
Meropenem is a carbapenem antibiotic that is highly active against the pathogens causing meningitis. Results with meropenem in the experimental rabbit model of penumococcal meningitis have been controversial, and the possible role of renal dehydropeptidase I in meropenem efficacy has been suggested. The aim of this study was to determine the efficacy of meropenem in two meningitis models and the possible influence of the animal model over results. Two strains of Streptococcus pneumoniae with different susceptibility to beta-lactams have been used in a guinea pig model and the classical rabbit meningitis model. Meropenem was bactericidal at 6 h in the guinea pig model against both strains with a reduction of >4 log ufc/ml. In the rabbit model it was bactericidal at 6 h against the susceptible strain, but against the resistant 3/8 therapeutical failures were recorded at 6 h, being bactericidal at 24 h. In conclusion, meropenem has shown bactericidal activity in both experimental models. This work emphasises the importance of an adequate election of the animal model for the appropriate development of studies of antimicrobial efficacy. We believe that guinea pig should be considered the best choice among laboratory animal species when assessing meropenem efficacy.
Meropenem is a broad-spectrum carbapenem antibiotic that is highly active against the pathogens causing meningitis. The aims of this study was to determine the efficacies of meropenem alone and combined with rifampin against two Streptococcus pneumoniae strains with different susceptibility to beta-lactams using the guinea pig meningitis model and compare them with the standard ceftriaxone plus vancomycin therapy. All treatments except rifampin were bactericidal from 6 h. The addition of rifampin did not improve the activity of meropenem alone. Our results provide good evidence of the efficacy of meropenem in the treatment of penicillin- and cephalosporin-susceptible and -resistant pneumococcal meningitis similar to that of ceftriaxone plus vancomycin, suggesting that meropenem might be a good option in the management of this infection.
To study the in vitro and in vivo activity of LZD, VAN and its combinations with RIF in a rabbit meningitis model, caused by two strains of S. aureus with different susceptibilities to glycopeptides. Methods In vitro MICs (mg/L): Strain A (LZD = 2, VAN = 1, RIF = 0.018) and B (LZD = 4, VAN = 8, RIF = 512). The bactericidal activity and synergy (time-kill curves) were studied over 24 h. Drugs were tested for a range of concentrations according to their MICs and achievable human serum levels (1/4x-4xMIC) against both strains. In vivo New Zealand rabbits (2.5-3 kg) were used, with an inoculum of 8.5-9 Log cfu/mL. PK/PD parameters (blood and CSF) were determined (Cmax [mg/L]; AUC [mg.h/L]; t1/2 [h]; t > MIC [h]; AUC/MIC) after a single dose of each antimicrobial on infected rabbits. In the therapy experiments, animals (n = 6 per schedule) were grouped in untreated (CON), or treated with LZD (20 mg/kg), VAN (25 mg/kg every 4 hours, 4 doses), RIF (15 mg/kg) every 24 hours (1 dose), LZD+RIF or VAN+RIF. CSF variables analyzed at 0, 4, 6 and 24 h of treatment were: bacterial from Infectious diseases of the nervous system: pathogenesis and worldwide impact Paris, France. 10
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