Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

Kasuistik des traditionellen Gesetzes über das Schächten, Visitieren und Beschauen der von Moses in der h. Schrift für rein erklärten vierfüßigen Thiere und Vögel : für israelitische Schächter

hrsg. von I. Levisoh

Regulation of Extracellular Protease Production in <i>Bacillus cereus</i>

Both sporulation and protease production can be inhibited by growing Bacillus cereus T in a medium containing a high concentration of a mixture of amino acids. Mutants selected for the ability to sporulate in this inhibitory medium were found to produce high levels of protease in the normal and inhibitory media. Comparison of the mutant and wild-type enzymes by gel electrophoresis and heat inactivation suggested that they were identical. One of the mutants proved to be a purine-requiring auxotroph. Reversion to prototrophy resulted in the loss of the capacity to sporulate in the inhibitory medium and loss of the ability to produce large amounts of protease. Mutants capable of producing high levels of protease and of sporulating in the inhibitory medium were also found when selecting for a purine, pyrimidine, or lysine requirement or for the capacity to sporulate in the presence of a high concentration of glucose. Protease production could be considerably delayed in the purine auxotrophs or completely inhibited in the pyrimidine auxotrophs by growing the cells in a medium containing the inhibitory mixture of amino acids plus hypoxanthine for the former or a pyrimidine for the latter. The fact that a variety of metabolic alterations could lead to excessive protease production suggested that a common catabolic or biosynthetic intermediate was involved in the control of the production of this enzyme(s). </jats:p

Rapid Detection of a Point Mutation in the parC Gene Associated with Decreased Susceptibility to Fluoroquinolones in Mycoplasma bovis

Comparison of the quinolone resistance-determining regions (QRDRs) in 42 Mycoplasma bovis clinical isolates revealed amino acid substitutions at both GyrA (position 83) and ParC (position 84) in 10/11 enrofloxacin-resistant strains. The mutation present in the parC QRDR was discriminative for enrofloxacin resistance by parC PCR-restriction fragment length polymorphism. Comparison of molecular profiles by insertion sequence typing suggests that the currently prevalent enrofloxacin-resistant M. bovis strain evolved by selection under field conditions from one of the susceptible strains

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

ABSTRACT The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to &gt;16 μg/ml. The estimated MIC 50 and MIC 90 values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of ≥2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested. </jats:p