Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

Identification of a host cell target for the thiazolide class of broad-spectrum anti-parasitic drugs

The thiazolide nitazoxanide (NTZ) and some derivatives exhibit considerable in vitro activities against a broad range of parasites, including the apicomplexans Neospora caninum and Toxoplasma gondii tachyzoites. In order to identify potential molecular targets for this compound in both parasites, RM4847 was coupled to epoxy-agarose and affinity chromatography was performed. A protein of approximately 35 kDa was eluted upon RM4847-affinity-chromatography from extracts of N. caninum-infected human foreskin fibroblasts (HFF) and non-infected HFF, but no protein was eluted when affinity chromatography was performed with T. gondii or N. caninum tachyzoite extracts. Mass spectrometry analysis identified the 35 kDa protein as human quinone reductase NQO1 (P15559; QR). Within 8h after infection of HFF with N. caninum tachyzoites, QR transcript expression levels were notably increased, but no such increase was observed upon infection with T. gondii tachyzoites. Treatment of non-infected HFF with RM4847 did also lead to an increase of QR transcript levels. The enzymatic activity of 6-histidine-tagged recombinant QR (recQR) was assayed using menadione as a substrate. The thiazolides NTZ, tizoxanide and RM4847 inhibited recQR activity on menadione in a concentration-dependent manner. Moreover, a small residual reducing activity was observed when these thiazolides were offered as substrates.

Fecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in swine and cattle at slaughter in Switzerland

During the past decade, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have become a matter of great concern in human medicine. ESBL-producing strains are found in the community, not just in hospital-associated patients, which raises a question about possible reservoirs. Recent studies describe the occurrence of ESBL-producing Enterobacteriaceae in meat, fish, and raw milk; therefore, the impact of food animals as reservoirs for and disseminators of such strains into the food production chain must be assessed. In this pilot study, fecal samples of 59 pigs and 64 cattle were investigated to determine the occurrence of ESBL-producing Enterobacteriaceae in farm animals at slaughter in Switzerland. Presumptive-positive colonies on Brilliance ESBL agar were subjected to identification and antibiotic susceptibility testing including the disc diffusion method and E-test ESBL strips. As many as 15.2% of the porcine and 17.1% of the bovine samples, predominantly from calves, yielded ESBL producers. Of the 21 isolated strains, 20 were Escherichia coli, and one was Citrobacter youngae. PCR analysis revealed that 18 strains including C. youngae produced CTX-M group 1 ESBLs, and three strains carried genes encoding for CTX-M group 9 enzymes. In addition, eight isolates were PCR positive for TEM beta-lactamase, but no bla(SHV) genes were detected. Pulsed-field gel electrophoresis showed a high genetic diversity within the strains. The relatively high rates of occurrence of ESBLproducing strains in food animals and the high genetic diversity among these strains indicate that there is an established reservoir of these organisms in farm animals. Further studies are necessary to assess future trends.

Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach

Purpose of review: We aimed to review literature on the efficacy and tolerability of psychosocial and psychopharmacological interventions in youth with early-onset schizophrenia spectrum disorders (EOS). A rationale for pragmatic psychopharmacology in EOS, including dosing, switching and adverse effect monitoring and management, is provided. Recent findings: Three randomized controlled trials (RCTs) over the last 8 years demonstrated benefits of psychosocial interventions (i.e. psychoeducation, cognitive remediation, cognitive behavioural therapy) for EOS without clear advantages of one psychosocial treatment over another. Six large, placebo-controlled, short-term RCTs over the last 4 years demonstrated that aripiprazole, olanzapine, paliperidone, quetiapine and risperidone, but not ziprasidone, were superior to placebo. Except for clozapine's superiority in treatment-refractory EOS, efficacy appeared similar across studied first-generation and second-generation antipsychotics, but tolerability varied greatly across individual agents. Summary: Antipsychotics are efficacious in the treatment of EOS. Given the lack of efficacy differences between antipsychotics (except for clozapine for treatment-refractory EOS), we propose that tolerability considerations need to guide choice of antipsychotics. Further and longer-term efficacy and effectiveness studies are urgently needed that should also explore pharmacologic and nonpharmacologic augmentation strategies.

Comparing the prodrome of schizophrenia-spectrum psychoses and affective disorders with and without psychotic features

Following encouraging results in the early detection of psychotic disorders, interest in the early detection of affective, especially bipolar disorders, has recently been renewed. However, the differentiation between affective disorders with and without psychotic features is often missing, although it has been suggested that affective disorders with psychotic features may be distinct from those without psychotic features and closely linked to non-affective psychoses.

Depressive symptoms in first episode schizophrenia spectrum disorder

Depressive symptoms in 'non-affective' first episode schizophrenia spectrum disorders (FES) are common, but poorly understood, resulting in a range of conceptual and clinical management issues. This study had three aims: (i) to determine the prevalence of moderate to severe depressive symptoms (defined as a Clinical Global Impressions Scale-Bipolar Disorder (CGI-BP depression) score >3) in a large representative sample of FES patients; (ii) to compare the clinical and functional characteristics of FES patients with and without these depressive symptoms at service entry; and (iii) to compare the characteristics of FES patients with and without persistent depressive symptoms.

INCREASING PARTICIPATION IN THE CLASSROOM FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS

Active participation is as essential a skill to children with autism as it is for children without autism, as children are expected to engage in these skills both in and outside the classroom. Without participation skills, children are at a disadvantage when it comes to school and other settings, such as extracurricular activities and the workforce. Recent research has shown that there are interventions available that aim to improve the social skills of children in the home and in the school. These interventions can be delivered in varying forms with the primary caregiver as the interventionist, the specialist as the interventionist, and naturalistic interventions. The purpose of this study was to investigate one of the naturalistic interventions, the Competent Learner Model, and determine its effects on the participation and social skills of students with autism. Three middle school male students diagnosed with autism from a rural northeast middle school participated in the study. They were assessed using the Competent Learner Repertoire Assessments of the Competent Learner Model and the adaptive measures of the Vineland-II and ABAS-II. The results showed improvement for one of the three students and little to no improvement for the other two students.

Examining The Genetic, Social-Cognitive, And Neural Correlates Of Autism Spectrum Disorder Behaviors In Typically Developing Chi

Autism spectrum disorders (ASD) are pervasive developmental disorders that affect approximately 1 in 50 children (Blumberg et al., 2013). Due to the social nature of the deficits that characterize the disorders, many have classified them as disorders of social cognition, which is the process that individuals use in order to successfully interact with members of their own species (Frith & Frith, 2007). Previous research has typically neglected the spectrum nature of ASD in favor of a more categorical approach of ¿autistic¿ versus ¿non-autistic,¿ but the spectrum requires a more continuous approach. Thus, the present study sought to examine the genetic, social-cognitive, and neural correlates of ASD-like traits as well as the relationship between these dimensions in typically developing children. Parents and children completed several quantitative measures examining several areas of social-cognitive functioning, including theory of mind and social functioning, restricted/repetitive behaviors and interests, and adaptive/maladaptive functioning. Children were also asked to undergo an EEG and both parents and children contributed a saliva sample that was used to sequence four single nucleotide polymorphisms (SNPs) of the OXTR gene, rs1042778, rs53576, rs2254298, and rs237897. We successfully demonstrated a significant relationship between behavioral measures of social-cognition and differences in face perception via the N170. However, the directionality of these relationships varied based on the behavioral measure and particular N170 difference scores. We also found support for the associations between the G_G allelic combination of rs1042778 and the A_A and A_G allelic combinations of rs2254298 and increased ASD-like behavior with decreased social-cognitive functioning. In contrast, our results contradict previous findings with rs237897 and imply that individuals with the A_A and A_G genotypes are less similar to those with ASD and have higher social cognitive functioning than those with the G_G genotype. In conclusion, we have demonstrated the existence of ASD-like traits in typically developing children and have shown a link between behavioral, genetic, and neural correlates of social-cognition. These findings demonstrate the importance of considering autism as a spectrum disorder and provide support for the move to a more continuous approach to neurodevelopmental disorders.

Transmission dynamics of extended-spectrum β-lactamase-producing Enterobacteriaceae in the tertiary care hospital and the household setting

Studies about transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in hospitals and households are scarce.

Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations

Pontocerebellar hypoplasia with spinal muscular atrophy, also known as PCH1, is a group of autosomal recessive disorders characterized by generalized muscle weakness and global developmental delay commonly resulting in early death. Gene defects had been discovered only in single patients until the recent identification of EXOSC3 mutations in several families with relatively mild course of PCH1. We aim to genetically stratify subjects in a large and well-defined cohort to define the clinical spectrum and genotype-phenotype correlation.

[Invasive meningococcal infections: two cases that demonstrate the broad spectrum in clinical manifestation and outcome]

Invasive meningococcal infections show a broad clinical picture including sepsis and meningitis. Here we report on a case of sepsis and a case of meningitis, two clinical manifestations of meningococcal infections with striking differences in the clinical presentation and outcome. Meningococcal sepsis is characterized by a systemic release of endotoxins, that triggers an intense cytokine response of the host that can lead to shock and multi organ failure and death within hours. Meningococcal meningitis occurs when bacteria breach into the subarachnoidal and ventricular space during bacteremia and mortality is much lower that in sepsis. Thus meningitis may be seen as a consequence of lower pathogenicity and/or more efficient host control of the meningococci compared to sepsis.