Incidence of Acute Kidney Injury among Patients Treated with Piperacillin-Tazobactam or Meropenem in Combination with Vancomycin

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were included. AKI was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. Inverse probability of treatment weighting was utilized to control for differences between groups. In total, 10,236 patients met inclusion criteria, with 9,898 receiving TZP+VAN and 338 receiving MEM+VAN. AKI occurred in 15.4% of MEM+VAN patients and in 27.4% of TZP+VAN patients (P \u3c 0.001). TZP+VAN was associated with increased AKI compared to the level with MEM+VAN (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.82 to 3.52), after controlling for confounders. Use of MEM+VAN should be considered an appropriate alternative therapy to TZP+VAN if nephrotoxicity is a major concern. The results of this study demonstrate that judicial use of TZP+VAN for empirical coverage of infection is needed

Nephrotoxicity in Patients With or Without Cystic Fibrosis Treated With Polymyxin B Compared to Colistin

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%, P = 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%, P = 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%, P \u3c 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture

Nephrotoxicity During Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (P \u3c 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%, P \u3c 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy

Influence of \u3cem\u3eβ\u3c/em\u3e-Lactam Infusion Strategy on Acute Kidney Injury

Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: β-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged β-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI

Fixed Points of Higher Derivative Gravity

We recalculate the beta functions of higher derivative gravity in four dimensions using the one--loop approximation to an Exact Renormalization Group Equation. We reproduce the beta functions of the dimensionless couplings that were known in the literature but we find new terms for the beta functions of Newton's constant and of the cosmological constant. As a result, the theory appears to be asymptotically safe at a non--Gaussian Fixed Point, rather than perturbatively renormalizable and asymptotically free.Comment: Introduction expanded, some references adde

Uplifting and Inflation with D3 Branes

Back-reaction effects can modify the dynamics of mobile D3 branes moving within type IIB vacua, in a way which has recently become calculable. We identify some of the ways these effects can alter inflationary scenarios, with the following three results: (1) By examining how the forces on the brane due to moduli-stabilizing interactions modify the angular motion of D3 branes moving in Klebanov-Strassler type throats, we show how previous slow-roll analyses can remain unchanged for some brane trajectories, while being modified for other trajectories. These forces cause the D3 brane to sink to the bottom of the throat except in a narrow region close to the D7 brane, and do not ameliorate the \eta-problem of slow roll inflation in these throats; (2) We argue that a recently-proposed back-reaction on the dilaton field can be used to provide an alternative way of uplifting these compactifications to Minkowski or De Sitter vacua, without the need for a supersymmetry-breaking anti-D3 brane; and (3) by including also the D-term forces which arise when supersymmetry-breaking fluxes are included on D7 branes we identify the 4D supergravity interactions which capture the dynamics of D3 motion in D3/D7 inflationary scenarios. The form of these potentials sheds some light on recent discussions of how symmetries constrain D term interactions in the low-energy theory.Comment: JHEP.cls, 35 pages, 3 .eps figure

Inflating in a Better Racetrack

We present a new version of our racetrack inflation scenario which, unlike our original proposal, is based on an explicit compactification of type IIB string theory: the Calabi-Yau manifold P^4_[1,1,1,6,9]. The axion-dilaton and all complex structure moduli are stabilized by fluxes. The remaining 2 Kahler moduli are stabilized by a nonperturbative superpotential, which has been explicitly computed. For this model we identify situations for which a linear combination of the axionic parts of the two Kahler moduli acts as an inflaton. As in our previous scenario, inflation begins at a saddle point of the scalar potential and proceeds as an eternal topological inflation. For a certain range of inflationary parameters, we obtain the COBE-normalized spectrum of metric perturbations and an inflationary scale of M = 3 x 10^{14} GeV. We discuss possible changes of parameters of our model and argue that anthropic considerations favor those parameters that lead to a nearly flat spectrum of inflationary perturbations, which in our case is characterized by the spectral index n_s = 0.95.Comment: 20 pages, 7 figures. Brief discussion on the non-gaussianity of this model, one more figure of the field trajectories added as well as other minor changes to the tex

Loop-Generated Bounds on Changes to the Graviton Dispersion Relation

We identify the effective theory appropriate to the propagation of massless bulk fields in brane-world scenarios, to show that the dominant low-energy effect of asymmetric warping in the bulk is to modify the dispersion relation of the effective 4-dimensional modes. We show how such changes to the graviton dispersion relation may be bounded through the effects they imply, through loops, for the propagation of standard model particles. We compute these bounds and show that they provide, in some cases, the strongest constraints on nonstandard gravitational dispersions. The bounds obtained in this way are the strongest for the fewest extra dimensions and when the extra-dimensional Planck mass is the smallest. Although the best bounds come for warped 5-D scenarios, for which the 5D Planck Mass is O(TeV), even in 4 dimensions the graviton loop can lead to a bound on the graviton speed which is comparable with other constraints.Comment: 18 pages, LaTeX, 4 figures, uses revte

Brane-Antibrane Inflation in Orbifold and Orientifold Models

We analyse the cosmological implications of brane-antibrane systems in string-theoretic orbifold and orientifold models. In a class of realistic models, consistency conditions require branes and antibranes to be stuck at different fixed points, and so their mutual attraction generates a potential for one of the radii of the underlying torus or the 4D string dilaton. Assuming that all other moduli have been fixed by string effects, we find that this potential leads naturally to a period of cosmic inflation with the radion or dilaton field as the inflaton. The slow-roll conditions are satisfied more generically than if the branes were free to move within the space. The appearance of tachyon fields at certain points in moduli space indicates the onset of phase transitions to different non-BPS brane systems, providing ways of ending inflation and reheating the corresponding observable brane universe. In each case we find relations between the inflationary parameters and the string scale to get the correct spectrum of density perturbations. In some examples the small numbers required as inputs are no smaller than 0.01, and are the same small quantities which are required to explain the gauge hierarchy.Comment: 30 pages, 2 figures. Substantial changes on version 1. New cosmological scenarios proposed including the dilaton as the inflaton. Main conclusions unchange

A green strategy for shark attack mitigation off Recife, Brazil

Shark attacks on humans have prompted the implementation of shark control programs aiming at reducing local populations of potentially aggressive species using mostly gillnets. However, shark meshing produces ecological disturbances by inflicting severe mortality not only to sharks but also to several harmless, frequently endangered taxa, including cetaceans, sirenians and chelonids. A different methodological approach to mitigate shark peril off Recife combines bottom longlining and drumlines with comparably better results. This region has been experiencing an abnormally high shark attack rate since 1992, but the protective fishing strategy was developed in 2004 only. Unlike traditional shark control programs, the Shark Monitoring Program of Recife (SMPR) aims at removing dangerous sharks not from their populations but from the hazardous area instead, which is achieved by capturing, transporting and releasing sharks offshore. During 8 years, the SMPR caught fish and turtles only and showed high selectivity for sharks compared with shark meshing. Target species comprised carcharhinids and sphyrnids and accounted for 7% of total catch. The fishing mortality of abundant taxa was generally low except for Carcharhinus acronotus and Gymnothorax spp., and protected species had similar to 100% survival. The shark attack rate diminished about 97% while fishing operations were being conducted (W = 1108.5, P < 0.001), whereas no-fishing periods and the period prior to the implementation of the SMPR had similar shark attack rates. Overall, the SMPR seems to be less detrimental than shark meshing strategies while clearly contributing for enhancing bather safety; thus, it may provide an effective, ecologically balanced tool for assisting in shark attack mitigation.State Government of Pernambuco; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/37065/2007]info:eu-repo/semantics/publishedVersio