Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature

Objectives: We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time. Methods: PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes. Results: In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an antistaphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + beta-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms. Conclusion: Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases

Invariant Amplitudes for Pion Electroproduction

The invariant amplitudes for pion electroproduction on the nucleon are evaluated by dispersion relations at constant t with MAID as input for the imaginary parts of these amplitudes. In the threshold region these amplitudes are confronted with the predictions of several low-energy theorems derived in the soft-pion limit. In general agreement with Chiral Perturbation Theory, the dispersive approach yields large corrections to these theorems because of the finite pion mass.Comment: 18 pages, 8 figure

Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.

BACKGROUND: Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling. METHODOLOGY AND PRINCIPAL FINDINGS: Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2(-/-), TLR4(-/-) and TLR2/4(-/-) animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/-) animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. CONCLUSIONS AND SIGNIFICANCE: DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies

Precise Neutron Magnetic Form Factors

Precise data on the neutron magnetic form factor G_{mn} have been obtained with measurements of the ratio of cross sections of D(e,e'n) and D(e,e'p) up to momentum transfers of Q^2 = 0.9 (GeV/c)^2. Data with typical uncertainties of 1.5% are presented. These data allow for the first time to extract a precise value of the magnetic radius of the neutron.Comment: 10 pages, 2 figures, submitted to Physics Letters

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

New anomalous trajectory in Regge theory

We show that a new Regge trajectory with \alpha_{f_1} (0) \approx 1 and slope \alpha_{f_1}'(0) \approx 0 explains the features of hadron-hadron scattering and photoproduction of the rho and phi mesons at large energy and momentum transfer. This trajectory with quantum numbers P = C = +1 and odd signature can be considered as a natural partner of the Pomeron which has even signature. The odd signature of the new exchange leads to contributions to the spin-dependent cross sections, which do not vanish at large energy. The links between the anomalous properties of this trajectory, the axial anomaly and the flavor singlet axial vector f_1 (1285) meson are discussed.Comment: 20 pages, REVTeX, 8 figures (9 eps files), version to appear in Phys. Rev.

Measurement of Rlt and Atl in the 4He(e,e'p)3H Reaction at pmiss of 130-300 MeV/c

We have measured the 4He(e,e'p)3H reaction at missing momenta of 130-300 MeV/c using the three-spectrometer facility at the Mainz microtron MAMI. Data were taken in perpendicular kinematics to allow us to determine the response function Rlt and the asymmetry term Atl. The data are compared to both relativistic and non-relativistic calculations.Comment: To be published in the European Physical Journal