Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use

Structural role of the tyrosine residues of cytochrome c

The tertiary structures of horse, tuna, Neurospora crassa, horse [Hse65,Leu67]- and horse [Hse65,Leu74]-cytochromes c were studied with high-resolution 1H n.m.r. spectroscopy. The amino acid sequences of these proteins differ at position 46, which is occupied by phenylalanine in the horse proteins but by tyrosine in the remaining two, and at positions 67, 74 and 97, which are all occupied by tyrosine residues in horse and tuna cytochrome c but in the other proteins are substituted by phenylalanine or leucine, though there is only one such substitution per protein. The various aromatic-amino-acid substitutions do not seriously affect the protein structure

Safety and immunogenicity of TetractHib (a vaccine combining DTP vaccine and Haemophilus influenza type b conjugate vaccine) administered to infants at 6, 10 and 14 weeks of age

The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 weeks of age. Serological responses to all component antigens were measured before the first dose and at 18 weeks of age. In addition, anti-PRP antibodies were measured at 9 and 18 months of age to determine long-term immunogenicity. The vaccine was well tolerated by infants and no significant side-effects were reported. Responses to Hib at 18 weeks of age were good in that most infants achieved a level of anti-PRP antibodies <". 0.15 μg/ml, indicative of short-term protection, and 70% achieved a level<". 1 μg/ml, indicative of long-term protection. The proportions of children with protective levels<". 0.15 μg/ml and<". 1 μg/ml were similar at 9 and 18 months of age, i.e. approximately 75% and 45%, respectively. Responses to tetanus and diphtheria toxoids were excellent and all infants achieved protective serological levels. Responses to pertussis were moderate in that approximately 65% achieved 'protective' serum levels of pertussis agglutinins, i.e. titres <". 320. In conclusion, this study has shown that the DTP /PRP-T vaccine is safe, immunogenic and well tolerated in infants immunised at 6, 10 and 14 weeks of age. TETRActHIB is therefore suitable for inclusion in the World Health Organisation Expanded Programme on Immunisation (WHO EPI) schedule

Modeling saltwater intrusion scenarios for a coastal aquifer at the German North Sea

A 3d regional density-driven flow model of a heterogeneous aquifer system at the German North Sea Coast is set up within the joint project NAWAK (“Development of sustainable adaption strategies for the water supply and distribution infrastructure on condition of climatic and demographic change”). The development of the freshwater-saltwater interface is simulated for three climate and demographic scenarios. Groundwater flow simulations are performed with the finite volume code d3f++ (distributed density driven flow) that has been developed with a view to the modelling of large, complex, strongly density-influenced aquifer systems over long time periods

Outcomes of the South African National Antiretroviral Treatment Programme for children: The IeDEA Southern Africa collaboration

Objectives. To assess paediatric antiretroviral treatment (ART)outcomes and their associations from a collaborative cohortrepresenting 20% of the South African national treatment programme.Design and setting. Multi-cohort study of 7 public sectorpaediatric ART programmes in Gauteng, Western Cape andKwaZulu-Natal provinces. Subjects. ART-naive children (.16 years) who commenced treatment with .3 antiretroviral drugs before March 2008.Outcome measures. Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART.Results. The median (interquartile range) age of 6 078 childrenwith 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% bein

Fluctuation-Facilitated Charge Migration along DNA

We propose a model Hamiltonian for charge transfer along the DNA double helix with temperature driven fluctuations in the base pair positions acting as the rate limiting factor for charge transfer between neighboring base pairs. We compare the predictions of the model with the recent work of J.K. Barton and A.H. Zewail (Proc.Natl.Acad.Sci.USA, {\bf 96}, 6014 (1999)) on the unusual two-stage charge transfer of DNA.Comment: 4 pages, 2 figure

Monitoring the South African National Antiretroviral Treatment Programme, 2003 - 2007: The IeDEA Southern Africa collaboration

Objectives. To introduce the combined South African cohortsof the International epidemiologic Databases to EvaluateAIDS Southern Africa (IeDEA-SA) collaboration as reflectingthe South African national antiretroviral treatment (ART)programme; to characterise patients accessing these services;and to describe changes in services and patients from 2003 to2007.Design and setting. Multi-cohort study of 11 ART programmesin Gauteng, Western Cape, Free State and KwaZulu-Natal.Subjects. Adults and children

The association between body dysmorphic symptoms and suicidality among adolescents and young adults: A genetically informative study

BACKGROUND: Previous research indicates that body dysmorphic disorder (BDD) is associated with risk of suicidality. However, studies have relied on small and/or specialist samples and largely focussed on adults, despite these difficulties commonly emerging in youth. Furthermore, the aetiology of the relationship remains unknown. METHODS: Two independent twin samples were identified through the Child and Adolescent Twin Study in Sweden, at ages 18 (N = 6027) and 24 (N = 3454). Participants completed a self-report measure of BDD symptom severity. Young people and parents completed items assessing suicidal ideation/behaviours. Logistic regression models tested the association of suicidality outcomes with: (a) probable BDD, classified using an empirically derived cut-off; and (b) continuous scores of BDD symptoms. Bivariate genetic models examined the aetiology of the association between BDD symptoms and suicidality at both ages. RESULTS: Suicidal ideation and behaviours were common among those with probable BDD at both ages. BDD symptoms, measured continuously, were linked with all aspects of suicidality, and associations generally remained significant after adjusting for depressive and anxiety symptoms. Genetic factors accounted for most of the covariance between BDD symptoms and suicidality (72.9 and 77.7% at ages 18 and 24, respectively), but with significant non-shared environmental influences (27.1 and 22.3% at ages 18 and 24, respectively). CONCLUSIONS: BDD symptoms are associated with a substantial risk of suicidal ideation and behaviours in late adolescence and early adulthood. This relationship is largely explained by common genetic liability, but non-shared environmental effects are also significant and could provide opportunities for prevention among those at high-risk

Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients

Previous studies suggest that the activation (autophosphorylation) of dsRNA-dependent protein kinase (PKR) can stimulate protein degradation, and depress protein synthesis in skeletal muscle through phosphorylation of the translation initiation factor 2 (eIF2) on the α-subunit. To understand whether these mediators are important in muscle wasting in cancer patients, levels of the phospho forms of PKR and eIF2α have been determined in rectus abdominus muscle of weight losing patients with oesophago-gastric cancer, in comparison with healthy controls. Levels of both phospho PKR and phospho eIF2α were significantly enhanced in muscle of cancer patients with weight loss irrespective of the amount and there was a linear relationship between phosphorylation of PKR and phosphorylation of eIF2α (correlation coefficient 0.76, P=0.005). This suggests that phosphorylation of PKR led to phosphorylation of eIF2α. Myosin levels decreased as the weight loss increased, and there was a linear relationship between myosin expression and the extent of phosphorylation of eIF2α (correlation coefficient 0.77, P=0.004). These results suggest that phosphorylation of PKR may be an important initiator of muscle wasting in cancer patients

How Can I Drink Safely?; Perception Versus the Reality of Alcohol Consumption

This article investigates differences between perception and actual consumption of alcohol in young adults within the UK, suggesting that inaccurate information in the public domain may hamper those seeking to drink safely plus the development of moderate drinking cultures. Results confirm that inaccurate information may be preventing the development of safe drinking behaviours among certain groups. In addition, they indicate that some groups choose to ignore safe consumption limits in particular circumstances. Results indicate that many government strategies aimed at reducing unsafe drinking behaviour are inaccurately targeted; changing male public consumption behaviour may trigger changes in female behaviour