Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection.

INTRODUCTION: : Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. While the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance, evidence of the effect on outcome following severe infection is lacking. METHODS: : In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following Gram-negative bacteraemia in the 2-year period around implementation. RESULTS: : Introduction of restrictive antibiotic guidelines was associated with a reduction in utilization of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. Approximately 1593 episodes of bacteremia were included in the study. The mortality over 1-year following Gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. CONCLUSION: : Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following Gram-negative bacteraemia. There was a small reduction in one year mortality.

Assessment of the use of a diffuser in propagation-based x-ray phase contrast imaging.

A rotating random-phase-screen diffuser is sometimes employed on synchrotron x-ray imaging beamlines to ameliorate field-of-view inhomogeneities due to electron-beam instabilities and beamline optics phase artifacts. The ideal result is a broader, more uniformly illuminated beam intensity for cleaner coherent x-ray images. The spinning diffuser may be modeled as an ensemble of transversely random thin phase screens, with the resulting set of intensity maps over the detector plane being incoherently averaged over the ensemble. Whilst the coherence width associated with the source is unaffected by the diffuser, the magnitude of the complex degree of second-order coherence may be significantly reduced [K. S. Morgan, S. C. Irvine, Y. Suzuki, K. Uesugi, A. Takeuchi, D. M. Paganin, and K. K. W. Siu, Opt. Commun. 283, 216 (2010)]. Through use of a computational model and experimental data obtained on x-ray beamline BL20XU at SPring-8, Japan, we investigate the effects of such a diffuser on the quality of Fresnel diffraction fringes in propagation-based x-ray phase contrast imaging. We show that careful choice of diffuser characteristics such as thickness and fiber size, together with appropriate placement of the diffuser, can result in the ideal scenario of negligible reduction in fringe contrast whilst the desired diffusing properties are retained.

Technical knockout, a Drosophila model of mitochondrial deafness.

Mutations in mtDNA-encoded components of the mitochondrial translational apparatus are associated with diverse pathological states in humans, notably sensorineural deafness. To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko). The prototypic mutant tko(25t) exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound. On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein. The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA. A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions. We infer that the tko(25t) mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.