Synergistic Activity of Fosfomycin, Ciprofloxacin, and Gentamicin Against Escherichia coli and Pseudomonas aeruginosa Biofilms

Gram-negative (GN) rods cause about 10% periprosthetic joint infection (PJI) and represent an increasing challenge due to emergence of antimicrobial resistance. Escherichia coli and Pseudomonas aeruginosa are among the most common cause of GN-PJI and ciprofloxacin is the first-line antibiotic. Due to emergence of fluoroquinolone resistance, we evaluated in vitro the activity of fosfomycin, ciprofloxacin, and gentamicin, alone and in combinations, against E. coli and P. aeruginosa biofilms. Conventional microbiological tests and isothermal microcalorimetry were applied to investigate the anti-biofilm activity of the selected antibiotics against standard laboratory strains as well as clinical strains isolated from patients with prosthetic joint associated infections. The biofilm susceptibility to each antibiotic varied widely among strains, while fosfomycin presented a poor anti-biofilm activity against P. aeruginosa. Synergism of two-pair antibiotic combinations was observed against different clinical strains from both species. Highest synergism was found for the fosfomycin/gentamicin combination against the biofilm of E. coli strains (75%), including a gentamicin-resistant but fosfomycin-susceptible strain, whereas the gentamicin/ciprofloxacin combination presented synergism with higher frequency against the biofilm of P. aeruginosa strains (71.4%). A hypothetical bacteriolysis effect of gentamicin could explain why combinations with this antibiotic seem to be particularly effective. Still, the underlying mechanism of the synergistic effect on biofilms is unknown. In conclusion, combinatorial antibiotic application has shown to be more effective against biofilms compared to monotherapy. Further in vivo and clinical studies are essential to define the potential treatment regimen based on our results

Antibacterial Efficacy of Two Commercially Available Bacteriophage Formulations, Staphylococcal Bacteriophage and PYO Bacteriophage, Against Methicillin-Resistant Staphylococcus aureus: Prevention and Eradication of Biofilm Formation and Control of a Systemic Infection of Galleria mellonella Larvae

Sessile bacteria growing on surfaces are more resistant to standard antibiotics than their planktonic counterpart. Due to their antimicrobial properties, bacteriophages have re-emerged as a promising approach to treat bacterial biofilm-associated infections. Here, we evaluated the ability of two commercially available phage formulations, Staphylococcal bacteriophage (containing the monophage Sb-1) and PYO bacteriophage (a polyphage), in preventing and eradicating an in vitro biofilm of methicillin-resistant Staphylococcus aureus (MRSA) by isothermal microcalorimetry and high-resolution confocal laser scanning microscopy (CLSM). Moreover, to assess the potential in vivo efficacy of both phage preparations, a Galleria mellonella model of MRSA systemic infection was used. Microcalorimetry measurement showed that 107 PFU/ml (the highest tested titer) of both phage formulations were able to inhibit planktonic growth in a concentration-dependent manner. However, MRSA biofilm was eradicated only by co-incubation of 5-7 days with the highest phage titers, respectively. In the experiments of biofilm prevention, isothermal microcalorimetry revealed that the heat production was completely abolished in the presence of sub-inhibitory titers (104 PFU/ml) of phages. These data were also confirmed by confocal laser scanning microscopy. Both phage formulations increased the survival of G. mellonella larvae preventing or treating MRSA infection compared to untreated control. In conclusion, tested phage formulations are promising for preventing device colonization and killing biofilm bacteria attached on a surface. Novel strategies for direct coating and release of phages from material should be investigated

Emergent behavior of soil fungal dynamics:influence of soil architecture and water distribution

Macroscopic measurements and observations in two-dimensional soil-thin sections indicate that fungal hyphae invade preferentially the larger, air-filled pores in soils. This suggests that the architecture of soils and the microscale distribution of water are likely to influence significantly the dynamics of fungal growth. Unfortunately, techniques are lacking at present to verify this hypothesis experimentally, and as a result, factors that control fungal growth in soils remain poorly understood. Nevertheless, to design appropriate experiments later on, it is useful to indirectly obtain estimates of the effects involved. Such estimates can be obtained via simulation, based on detailed micron-scale X-ray computed tomography information about the soil pore geometry. In this context, this article reports on a series of simulations resulting from the combination of an individual-based fungal growth model, describing in detail the physiological processes involved in fungal growth, and of a Lattice Boltzmann model used to predict the distribution of air-liquid interfaces in soils. Three soil samples with contrasting properties were used as test cases. Several quantitative parameters, including Minkowski functionals, were used to characterize the geometry of pores, air-water interfaces, and fungal hyphae. Simulation results show that the water distribution in the soils is affected more by the pore size distribution than by the porosity of the soils. The presence of water decreased the colonization efficiency of the fungi, as evinced by a decline in the magnitude of all fungal biomass functional measures, in all three samples. The architecture of the soils and water distribution had an effect on the general morphology of the hyphal network, with a "looped" configuration in one soil, due to growing around water droplets. These morphologic differences are satisfactorily discriminated by the Minkowski functionals, applied to the fungal biomass

Connected and disconnected quark contributions to hadron spin

By introducing an external spin operator to the fermion action, the quark spin fractions of hadrons are determined from the linear response of the hadron energies using the Feynman-Hellmann (FH) theorem. At our SU(3)-flavour symmetric point, we find that the connected quark spin fractions are universally in the range 55-70\% for vector mesons and octet and decuplet baryons. There is an indication that the amount of spin suppression is quite sensitive to the strength of SU(3) breaking. We also present first preliminary results applying the FH technique to calculations of quark-line disconnected contributions to hadronic matrix elements of axial and tensor operators. At the SU(3)-flavour symmetric point we find a small negative contribution to the nucleon spin from disconnected quark diagrams, while the corresponding tensor matrix elements are consistent with zero.Comment: 7 pages, 5 figures, 32nd International Symposium on Lattice Field Theor

Heat metering: socio-technical challenges in district-heated social housing

Individual heat metering and charging (IMC) are seen as promising methods to reduce domestic heating and hot water use through the provision of financial incentives. The heat consumption measured by meters is influenced by both the dwelling characteristics and the behaviour of the occupant, but heating charges would ideally relate to occupant behaviour only. This dilemma can be especially relevant under two circumstances: if the thermal performance of the dwelling is poor and/or if heating costs represent a substantial part of the occupants’ income, i.e. in social housing. The case of a district-heated council block in London is presented where the installation of individual heat meters was planned in 2010 but had to be suspended due to concerns about implications for occupant heating costs in light of the thermal performance of the building. It illustrates a technically and socially complex environment where fairness in allocating heating costs is an important concern. The case also shows how lack of funding or other issues on the infrastructure side can hinder behaviour-orientated measures such as IMC. A holistic energy conservation strategy addressing both physical building properties and occupant behaviour is therefore essential and should be supported by policy

A Probabilistic Analysis of Kademlia Networks

Kademlia is currently the most widely used searching algorithm in P2P (peer-to-peer) networks. This work studies an essential question about Kademlia from a mathematical perspective: how long does it take to locate a node in the network? To answer it, we introduce a random graph K and study how many steps are needed to locate a given vertex in K using Kademlia's algorithm, which we call the routing time. Two slightly different versions of K are studied. In the first one, vertices of K are labelled with fixed IDs. In the second one, vertices are assumed to have randomly selected IDs. In both cases, we show that the routing time is about c*log(n), where n is the number of nodes in the network and c is an explicitly described constant.Comment: ISAAC 201