Antibiotic administration in the critically ill - in need of intensive care!

A better understanding of antibiotic dosing in the critically ill will go a long way to enhancing the longevity of what is becoming an increasingly scarce resource. There are no new antibiotic classes nearing clinical production. We believe that correct antibiotic dosing will limit the increasing burden of antimicrobial resistance, minimise therapeutic failures and, most importantly, improve patient outcomes.

RedisGraph GraphBLAS Enabled Graph Database

RedisGraph is a Redis module developed by Redis Labs to add graph database functionality to the Redis database. RedisGraph represents connected data as adjacency matrices. By representing the data as sparse matrices and employing the power of GraphBLAS (a highly optimized library for sparse matrix operations), RedisGraph delivers a fast and efficient way to store, manage and process graphs. Initial benchmarks indicate that RedisGraph is significantly faster than comparable graph databases.Comment: Accepted to IEEE IPDPS 2019 GrAPL worksho

The effect of pathophysiology on pharmacokinetics in the critically ill patient — Concepts appraised by the example of antimicrobial agents

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The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis

INTRODUCTION: High-risk surgical patients are at increased risk of fungal infections and candidaemia. Evidence from observational and small randomised controlled studies suggests that prophylactic fluconazole may be effective in reducing fungal infection and mortality. We evaluated the effects of prophylactic fluconazole on the incidence of candidaemia and hospital mortality in immunocompetent high-risk surgical patients. METHODS: Randomised controlled studies involving the use of fluconazole in immunocompetent high-risk surgical patients from the Cochrane Controlled Trial Register (2005, issue 1) and from the EMBASE and MEDLINE databases (1966–30 April 2005), without any language restriction, were included. Two reviewers reviewed the quality of the studies and performed data extraction independently. RESULTS: Seven randomised controlled studies with a total of 814 immunocompetent high-risk surgical patients were considered. The use of prophylactic fluconazole was associated with a reduction in the proportion of patients with candidaemia (relative risk [RR] = 0.21, 95% confidence interval [CI] = 0.06–0.72, P = 0.01; I(2 )= 0%) and fungal infections other than lower urinary tract infection (RR = 0.39, 95% CI = 0.24–0.65, P = 0.0003; I(2 )= 0%), but was associated with only a trend towards a reduction in hospital mortality (RR = 0.82, 95% CI = 0.62–1.08, P = 0.15; I(2 )= 7%). The proportion of patients requiring systemic amphotericin B as a rescue therapy for systemic fungal infection was lower after prophylactic use of fluconazole (RR = 0.35, 95% CI = 0.17–0.72, P = 0.004; I(2 )= 0%). The proportion of patients colonised with or infected with fluconazole-resistant fungi was not significantly different between the fluconazole group and the placebo group (RR = 0.66, 95% CI = 0.22–1.96, P = 0.46; I(2 )= 0%). CONCLUSION: The use of prophylactic fluconazole in immunocompetent high-risk surgical patients is associated with a reduced incidence of candidaemia but with only a trend towards a reduction in hospital mortality

Mattia Damiani (1705–1776), poet and scientist in eighteenth century Tuscany

Mattia Damiani da Volterra (1705–1776), “renowned Doctor,” was the author in 1754 of a collection of scientifi c poems, Le Muse Fisiche (The Physical Muses) on two subjects: Newtonian physics and the plurality of the worlds. Damiani’s interest in science was precocious, but even at that, it was superimposed on his studies in jurisprudence completed in Pisa in 1726. In 2003, Damiani’s lost text, De Hygrometris et eorum defectibus disputatio (Disputation about hygrometers and their defects), which was printed in 1726 in Pisa, was brought to light. It characterizes him as a young scientist who refl ected upon the properties and limits of laboratory instruments and on nascent aspects of climatology. In this Disputation, a delightful amalgamation of scientifi c and humanistic literature is pursued. A discussion of the properties and limits of contemporary hygrometers and a comparison of the Cartesian and Newtonian hypotheses about cloud formations are interspersed with quotations of verses on natural phenomena, mostly from poems of the classic age—a prelude to the author’s future involvement in writing scientifi c verses. The poetry of Damiani, which often shows a musicality comparable to that of the poet Giacomo Leopardi (1798–1837), deserves to be recognized and saved from oblivion. Especially remarkable is the implicit “multimedia” project of a union among science, poetry, theater, and music. The rediscovered Disputation about hygrometers opens a new window on the personages involved and on the evolution of meteorological concepts in Europe in the context of the then-new Galilean and Newtonian physics

Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>= 25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (C-max)/MIC ratio of >= 8 and a minimal concentration o

Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients

Infections in critically ill patients continue to result in unacceptably high morbidity and mortality. Although few data exist for correlating antibiotic exposure with outcome, antibiotic dosing is likely to be highly important for maximizing resolution of infection in many patients. The practical and financial difficulties of performing pharmacokinetic (PK) studies in critically ill patients mean that analyses to maximize data such as Monte Carlo simulation (MCS) are highly valuable. MCS uses computer software to perform virtual clinical trials. The building blocks for MCS are: firstly, a robust population PK model from the patient population of interest; secondly, descriptors of the effect of covariates that influence the PK parameters; thirdly, description of the susceptibility of bacteria to the antibiotic and finally a PK/pharmacodynamic (PD) target associated with antibiotic efficacy. Probability of target attainment (PTA) outputs can then be generated that describe the proportion of patients that will achieve a pre-specified PD target for an MIC distribution. Such analyses can then inform dosing requirements, which can be used to have a high likelihood of achieving PK/PD targets for organisms with different MICs. In this issue of JAC, Zelenitsky et al. provide a very useful example of MCS for interpreting the optimal methods for dosing meropenem, piperacillin/tazobactam, cefepime and ceftobiprole in critically ill patients