Pharmacologic and Bacteriologic Properties of SCH‐27899 (Ziracin), an Investigational Antibiotic from the Everninomicin Family

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90360/1/phco.19.15.1111.30576.pd

Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy

Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets

PRUSSIC I - a JVLA survey of HCN/HCO+/HNC (1-0) emission in z∼\sim3 dusty galaxies: Low dense-gas fractions in high-redshift star-forming galaxies

Dusty star-forming galaxies (DSFGs) at redshift z$\geq$1 are among the most vigorously star-forming galaxies in the Universe. However, their dense ($\geq$10$^5$ cm$^{-3}$ ) gas phase - typically traced by HCN(1-0) - remains almost entirely unexplored: only two DSFGs have been detected in HCN(1-0) to date. We present results of a JVLA survey of the J=1-0 transition of HCN, HCO+, and HNC(1-0) in six strongly lensed DSFGs at z = 2.5 - 3.3, effectively doubling the number of DSFGs with deep observations of these lines. We detect HCN(1-0) emission in one source (J1202+5354, 4.4$\sigma$), with a tentative HCO+ (1-0) detection in another (J1609+6045, 3.3$\sigma$). Spectral stacking yields strict upper limits on the HCN/FIR ($\leq$3.6$\times$10$^{-4}$) and HCN/CO(1-0) ratios ($\leq$0.045). The inferred HCN/FIR ratios (a proxy for the star-formation efficiency) are consistent with those in z$\sim$0 FIR-luminous starbursts. However, the HCN/CO ratios - a proxy for the dense-gas fraction - are a factor of a few lower than suggested by the two previous DSFG detections. Our results imply that most DSFGs have low dense-gas fractions. A comparison with Krumholz & Thompson (2007) models of star-forming galaxies indicates that the bulk of gas in DSFGs is at lower densities ($\approx$10$^2$ cm$^{-3}$ ), similar to "normal" star-forming galaxies, rather than ultraluminous starbursts.Comment: Submitted to A&A 28th April 2022, accepted 19th July 202

At the end of cosmic noon: Short gas depletion times in unobscured quasars at z∼z \sim 1

Unobscured quasars (QSOs) are predicted to be the final stage in the evolutionary sequence from gas-rich mergers to gas-depleted, quenched galaxies. Studies of this population, however, find a high incidence of far-infrared-luminous sources -suggesting significant dust-obscured star formation-but direct observations of the cold molecular gas fuelling this star formation are still necessary. We present a NOEMA study of CO(2-1) emission, tracing the cold molecular gas, in ten lensed z=1-1.5 unobscured QSOs. We detected CO(2-1) in seven of our targets, four of which also show continuum emission (\lambda_rest = 1.3mm). After subtracting the foreground galaxy contribution to the photometry, spectral energy distribution fitting yielded stellar masses of 10^9-11 M_\odot, with star formation rates of 25-160 M_\odot yr^-1 for the host galaxies. These QSOs have lower $L'_\mathrm{CO}$ than star-forming galaxies with the same L_IR, and show depletion times spanning a large range (50-900 Myr), but with a median of just 90 Myr. We find molecular gas masses in the range 2-40 x 10^9(alpha_CO/4) M_\odot, which suggest gas fractions above ~50% for most of the targets. Despite the presence of an unobscured QSO, the host galaxies are able to retain significant amounts of cold gas. However, with a median depletion time of ~90 Myr, the intense burst of star formation taking place in these targets will quickly deplete their molecular gas reservoirs in the absence of gas replenishment, resulting in a quiescent host galaxy. The non-detected QSOs are three of the four radio-loud QSOs in the sample, and their properties indicate that they are likely already transitioning into quiescence. Recent cosmological simulations tend to overestimate the depletion times expected for these z~1 QSO-host galaxies, which is likely linked to their difficulty producing starbursts across the general high-redshift galaxy population.Comment: 20 pages. Accepted for publication in A&

Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime–Avibactam

Background The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime–avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections. Methods Retrospective, multicenter, cohort study of patients with CRE infections treated with ceftazidime–avibactam between 2015 and 2019. The primary outcome was 30-day all-cause mortality. Predictive performance was determined by assessing discrimination, calibration and precision. Results In total, 109 patients were included. Thirty-day mortality occurred in 18 (16.5%) patients. There were no significant differences in discrimination of the three scores [area under the curve (AUC) ICS 0.7039, 95% CI 0.5848–0.8230, PBS 0.6893, 95% CI 0.5709–0.8076, and qPitt 0.6847, 95% CI 0.5671–0.8023; P > 0.05 all pairwise comparisons]. All scores showed adequate calibration and precision. When dichotomized at the optimal cut-points of 11, 3, and 2 for the ICS, PBS, and qPitt, respectively, all scores had NPV > 90% at the expense of low PPV. Patients in the high-risk groups had a relative risk for mortality of 3.184 (95% CI 1.35–8.930), 3.068 (95% CI 1.094–8.606), and 2.850 (95% CI 1.016–7.994) for the dichotomized ICS, PBS, and qPitt, scores respectively. Treatment-related variables (early active antibiotic therapy, combination antibiotics and renal ceftazidime–avibactam dose adjustment) were not associated with mortality after controlling for the risk scores. Conclusions In patients treated with ceftazidime–avibactam for CRE infections, mortality risk scores demonstrated variable performance. Modifications to scoring systems to more accurately predict outcomes in the era of novel antibiotics are warranted

Waves and Magnetism in the Solar Atmosphere (WAMIS)

Comprehensive measurements of magnetic fields in the solar corona have a long history as an important scientific goal. Besides being crucial to understanding coronal structures and the Sun's generation of space weather, direct measurements of their strength and direction are also crucial steps in understanding observed wave motions. In this regard, the remote sensing instrumentation used to make coronal magnetic field measurements is well suited to measuring the Doppler signature of waves in the solar structures. In this paper, we describe the design and scientific values of the Waves and Magnetism in the Solar Atmosphere (WAMIS) investigation. WAMIS, taking advantage of greatly improved infrared filters and detectors, forward models, advanced diagnostic tools and inversion codes, is a long-duration high-altitude balloon payload designed to obtain a breakthrough in the measurement of coronal magnetic fields and in advancing the understanding of the interaction of these fields with space plasmas. It consists of a 20 cm aperture coronagraph with a visible-IR spectro-polarimeter focal plane assembly. The balloon altitude would provide minimum sky background and atmospheric scattering at the wavelengths in which these observations are made. It would also enable continuous measurements of the strength and direction of coronal magnetic fields without interruptions from the day–night cycle and weather. These measurements will be made over a large field-of-view allowing one to distinguish the magnetic signatures of different coronal structures, and at the spatial and temporal resolutions required to address outstanding problems in coronal physics. Additionally, WAMIS could obtain near simultaneous observations of the electron scattered K-corona for context and to obtain the electron density. These comprehensive observations are not provided by any current single ground-based or space observatory. The fundamental advancements achieved by the near-space observations of WAMIS on coronal field would point the way for future ground based and orbital instrumentation