Daptomycin is the first available agent from a new class of antibiotics, the cyclic lipopeptides, that has activity against a broad range of gram-positive pathogens, including organisms that are ...resistant to methicillin, vancomycin, and other currently available agents. Daptomycin (4 mg/kg intravenously iv every 24 h for 7–14 days) was compared with conventional antibiotics (penicillinase-resistant penicillins 4–12 g iv per day or vancomycin 1 g iv every 12 h) in 2 randomized, international trials involving 1092 patients with complicated skin and skin-structure infections. Among 902 clinically evaluable patients, clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively (95% confidence interval, -4.0 to 5.6). Among patients successfully treated with iv daptomycin, 63% required only 4–7 days of therapy, compared with 33% of comparator-treated patients (P < .0001). The frequency and distribution of adverse events were similar among both treatment groups. Overall, the safety and efficacy of daptomycin were comparable with conventional therapy.
The tunneling conductance between two parallel 2D electron systems has been measured in a regime of strong interlayer Coulomb correlations. At total Landau level filling nuT=1 the tunnel spectrum ...changes qualitatively when the boundary separating the compressible phase from the ferromagnetic quantized Hall state is crossed. A huge resonant enhancement replaces the strongly suppressed equilibrium tunneling characteristic of weakly coupled layers. The possible relationship of this enhancement to the Goldstone mode of the broken symmetry ground state is discussed.
The antibiotic pipeline is thin and lacks diversity, particularly for agents targeting Gram‐negative pathogens. The reasons for our anemic global development pipeline are often summarized as (i) ...discovery of new antibiotics is difficult, (ii) clinical development of new antibiotics is difficult, and (iii) the economics for new antibiotics are unfavorable for the developer. Here, we review recent efforts directed at the second of these challenges.
Clinical Pharmacology & Therapeutics (2014); 96 2, 166–168. doi:10.1038/clpt.2014.107
Complicated skin and soft-tissue infections (cSSTIs) are a significant clinical problem, partially owing to increasing resistance of infecting bacteria to current antibiotic therapies. Two case ...studies that illustrate complications that can arise when treating cSSTIs are outlined, and methods that can be used to address the problem and the final treatment outcome are detailed. Although these are specific examples, intolerance of and bacterial resistance to current antibacterial therapies are problems that are often seen in the clinical setting and must be addressed appropriately. The use of new antibiotic agents is one potential solution to these problems, and some of these agents are highlighted. Selecting the most appropriate therapy for an infection is often crucial for patient welfare. This article presents some potential approaches to the treatment of cSSTIs.
Using data collected with the CLEO detector operating at the CESR e+e- collider at sqrts=3.97-4.26 GeV, we investigate 15 charmonium decay modes of the psi(4040), psi(4160), and Y(4260) resonances. ...We confirm, at 11 sigma significance, the BABAR Y(4260)-->pi+pi- J/psi discovery, make the first observation of Y(4260)--> pi(0)pi(0) J/psi (5.1 sigma), and find the first evidence for Y(4260)-->K+K- J/psi(3.7 sigma). We measure e+e- cross sections at sqrts=4.26 GeV as sigma(pi+pi- J/psi)=58(+12)(-10)+/-4 pb, sigma(pi(0)pi(0) J/psi)=23(+12)(-8)+/-1 pb, and sigma(K+K- J/psi)=9(+9)(-5)+/-1 pb, in which the uncertainties are statistical and systematic, respectively. Upper limits are placed on other decay rates from all three resonances.
The frictional drag between parallel two-dimensional electron systems has been measured in a regime of strong interlayer correlations. When the bilayer system enters the excitonic quantized Hall ...state at total Landau level filling factor nu(T) = 1, the longitudinal component of the drag vanishes but a strong Hall component develops. The Hall drag resistance is observed to be accurately quantized at h/e(2).
Double-layer two-dimensional electron systems can exhibit a fascinating collective phase believed to display both quantum ferromagnetism and excitonic superfluidity. This unusual phase has recently ...been found to exhibit tunneling phenomena reminiscent of the Josephson effect. A key element of the theoretical understanding of this bizarre quantum fluid is the existence of linearly dispersing Goldstone collective modes. Using the method of tunneling spectroscopy, we have demonstrated the existence of these modes. We find the measured velocity to be in reasonable agreement with theoretical estimates.
We have measured the branching fraction and photon energy spectrum for the radiative penguin process b-->s gamma. We find Beta(b-->s gamma) = (3.21+/-0.43+/-0.27(+0.18)(-0.10))x10(-4), where the ...errors are statistical, systematic, and from theory corrections. We obtain first and second moments of the photon energy spectrum above 2.0 GeV, <E( gamma)> = 2.346+/-0.032+/-0.011 GeV, and <E(2)(gamma)>-<E(gamma)>(2) = 0.0226+/-0.0066+/-0.0020 GeV(2), where the errors are statistical and systematic. From the first moment, we obtain (in the modified minimal subtraction renormalization scheme, to order 1/M(3)(B) and beta(0)alpha(2)(s)) the heavy quark effective theory parameter Lambda = 0.35+/-0.08+/-0.10 GeV.
Daptomycin has been approved and successfully launched for the treatment of complicated skin and skin-structure infections caused by gram-positive pathogens 1 and bacteremia and right-sided ...endocarditis due to Staphylococcus aureus, including strains that are resistant to methicillin or other antibiotics 2. The development of the drug, however, was not straightforward; it involved a cast of characters, including scientists at Eli Lilly and at Cubist Pharmaceuticals. Of most importance, the development of daptomycin involved the tenacious leadership of Dr. Francis Tally. As a tribute to Dr. Tally, we attempt to reconstruct the path of daptomycin from the mountain to the clinic.
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