The changing antibiotic susceptibility of bloodstream infections in the first month of life: informing antibiotic policies for early- and late-onset neonatal sepsis.

This study describes the association between antibiotic resistance of bacteria causing neonatal bloodstream infection (BSI) and neonatal age to inform empirical antibiotic treatment guidelines. Antibiotic resistance data were analysed for 14 078 laboratory reports of bacteraemia in neonates aged 0-28 days, received by the Health Protection Agency's (now Public Health England) voluntary surveillance scheme for England and Wales between January 2005 and December 2010. Linear and restricted cubic splines were used in logistic regression models to estimate the nonlinear relationship between age and resistance; the significance of confounding variables was assessed using likelihood ratio tests. An increase in resistance in bacteria causing BSI in neonates aged <4 days was observed, which was greatest between days 2-3 and identified an age (4-8 days, depending on the antibiotic) at which antibiotic resistance plateaus to almost unchanging levels. Our results indicate important age-associated changes in antibiotic resistance and support current empirical treatment guidelines.

Vancomycin MIC as a predictor of outcome in MRSA bacteraemia in the UK context.

UNLABELLED: Received 29 November 2012; returned 20 February 2013; revised 16 May 2013; accepted 18 May 2013 OBJECTIVES: Raised vancomycin MICs have been associated with poor outcomes for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in the USA and mainland Europe. We investigated if this also applies in the UK, where EMRSA-15 (clonal complex 22) dominates. METHODS: Isolates from UK patients receiving vancomycin therapy for MRSA bacteraemia in 2008-10 were collected, along with clinical details. Outcomes (i.e. patient survival or bacteraemia resolution) were reported 28 days after vancomycin therapy ended. The relationship between clinical outcome and MIC--as determined by CLSI and BSAC agar dilution methods--was assessed. RESULTS: Among 228 MRSA bacteraemias, 82% were caused by EMRSA-15; 65% of the patients were male and the median age was 70.5 years. MICs correlated between methods, but CLSI agar dilution testing gave a mode at 1 mg/L with only 12% of results either side, whereas the BSAC method gave a mode straddling 0.7-1 mg/L with <4% outliers. Twenty-three percent of patients died, with MRSA contributory in half; another 17% had unresolved bacteraemia at 28 days. Neither death nor unresolved bacteraemia was significantly associated with higher vancomycin MICs by either method. Rifampicin co-therapy had no quantifiable effect on outcome. The patient's age was the only significant correlate of patient outcome (P < 0.01); the underlying medical condition of the patient was important for the resolution of bacteraemia (P < 0.01), though not for overall mortality. CONCLUSIONS: Subtle vancomycin MIC differences did not correlate with worse outcomes for vancomycin monotherapy or for vancomycin/rifampicin co-therapy in MRSA bacteraemia. Regardless of the exact MIC-outcome relationship, detecting such small MIC differences seems unlikely to be reliable in routine laboratories.

A review of host major-gene resistance to potato viruses X, Y, A and V in potato: genes, genetics and mapped locations.

In view of modern developments in the technologies available for breeding potatoes for resistance to virus diseases, it is timely to review the host major genes that confer resistance, in Solanum species, to potato viruses X, Y, A and V (the viruses for which the resistance genes have been most extensively studied). Over the course of 60 years, many such genes in Solanum species have been characterized: a comprehensive list is presented. Inheritance studies are reviewed, including linkage studies and molecular mapping, and the positions of resistance genes mapped so far are listed. It is apparent from recent research that disease resistance genes are often clustered in particular regions of the chromosomes; the significance of these resistance gene clusters is discussed. The information presented will be useful for potato breeding, and for genetic and mapping studies and gene cloning.

Breeding virus resistant potatoes (Solanum tuberosum): a review of traditional and molecular approaches.

Tetraploid cultivated potato (Solanum tuberosum) is the World's fourth most important crop and has been subjected to much breeding effort, including the incorporation of resistance to viruses. Several new approaches, ideas and technologies have emerged recently that could affect the future direction of virus resistance breeding. Thus, there are new opportunities to harness molecular techniques in the form of linked molecular markers to speed up and simplify selection of host resistance genes. The practical application of pathogen-derived transgenic resistance has arrived with the first release of GM potatoes engineered for virus resistance in the USA. Recently, a cloned host virus resistance gene from potato has been shown to be effective when inserted into a potato cultivar lacking the gene. These and other developments offer great opportunities for improving virus resistance, and it is timely to consider these advances and consider the future direction of resistance breeding in potato. We review the sources of available resistance, conventional breeding methods, marker-assisted selection, somaclonal variation, pathogen-derived and other transgenic resistance, and transformation with cloned host genes. The relative merits of the different methods are discussed, and the likely direction of future developments is considered.

Resistance to potato leaf roll virus multiplication in potato is under major gene control.

The concentration of potato leaf roll virus (PLRV), as measured by a quantitative enzyme-linked immunosorbent assay, in the foliage of potato plants (Solanum tuberosum) of cv 'Maris Piper' with secondary infection was 2900 ng/g leaf, whereas in clones G7445(1) and G7032(5) it was 180 ng/g leaf and 120 ng/g leaf, respectively. To examine the genetic control of resistance to PLRV multiplication, reciprocal crosses were made between the susceptible cultivar 'Maris Piper' and the two resistant clones, and the three parents were selfed. Seedling progenies of these families were grown to generate tubers of individual genotypes (clones). Clonally propagated plants were graft-inoculated, and their daughter tubers were collected and used to grow plants with secondary infection in which PLRV concentration was estimated. The expression of resistance to PLRV multiplication had a bimodal distribution in progenies from crosses between 'Maris Piper' and either resistant clone, and also in progeny from selfing the resistant parents, with genotypes segregating into high and low virus titre groups. Only the progeny obtained from selfing 'Maris Piper' did not segregate, all genotypes being susceptible to PLRV multiplication. The pattern of segregation obtained from these progenies fits more closely with the genetical hypothesis that resistance to PLRV multiplication is controlled by two unlinked dominant complementary genes, both of which are required for resistance, than with the simpler hypothesis that resistance is conferred by a single dominant gene, as published previously.