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The objective was to evaluate the incidence of nephrotoxicity related to vancomycin and other anti-MRSA antibiotics (linezolid and daptomycin). Patients receiving any of these drugs between July 2014 and December 2020 at a tertiary hospital were included. Renal failure was evaluated using the acute renal injury (AKIN) system. Univariate analysis was conducted on the 5806 patients who were included. Among them, 1023 patients (17.62%) developed renal failure. The renal damage incidence was 14.74% (496/3365) for vancomycin, 19.13% (367/1918) for linezolid, and 30.59% (160/523) for daptomycin. Patients with lower basal glomerular filtration had a higher risk of AKIN. In the vancomycin group, the risk factors were high creatinine and urea serum basal values, duration of treatment (DOT), body mass index (BMI), ICU stay, age, and low CKDEPI and albumin levels. In the linezolid group, AKIN was linked to high creatinine and urea levels, BMI, age, and ICU stay and to low CKDEPI levels; for daptomycin, AKIN was associated with low CKDEPI and albumin levels and a long DOT. Patients with AKIN showed higher mortality rates. Vancomycin-associated nephrotoxicity remains a great concern. However, linezolid and daptomycin could also cause nephrotoxicity. Bearing in mind risk factors that may prompt nephrotoxicity in hospitalized patients taking anti-staphylococcal antibiotics will result in better pharmacotherapeutic management.

In this work, we seek to design a model that contributes to the study and resolution of a multi-objective rescheduling problem in dynamic permutation flow shop contexts. In this type of problem, where the objectives can be valued in heterogeneous units, the difficulty of achieving an optimal solution leads to finding a set of non-dominated efficient solutions (also called Pareto front). On the other hand, we will also consider the potential appearance of disruptions in planned scheduling (such as machine breakdowns or arrival of new priority jobs) that require a rapid re-planning of the aforementioned scheduling. In this paper, a hybrid dynamic non-dominated sorting genetic II metaheuristic (HDNSGA-II) is proposed to find the optimal Pareto front. The algorithm is applied to a benchmark already tested in previous studies, defined by three conflicting objective functions (makespan, total weighted tardiness, and stability) and three different types of disruption (machine breakdowns, incorporation of new jobs, and modifications in process times). According to the statistical comparison performed, the HDNSGA-II algorithm performs better in the designed environment, especially in larger problems.

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing K. pneumoniae with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing K. pneumoniae were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of ompK35 and ompK36 were performed in silico. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing K. pneumoniae isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in ompK35 were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing K. pneumoniae. OXA-48-producing K. pneumoniae with porin disruptions are a cause of concern; ceftazidime/avibactam showed good in vitro activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates.

The aim of this paper is to analyse, model, and solve the rescheduling problem in dynamic permutation flow shop environments while considering several criteria to optimize. Searching optimal solutions in multiobjective optimization problems may be difficult as these objectives are expressing different concepts and are not directly comparable. Thus, it is not possible to reduce the problem to a single-objective optimization, and a set of efficient (nondominated) solutions, a so-called Pareto front, must be found. Moreover, in manufacturing environments, disruptive changes usually emerge in scheduling problems, such as machine breakdowns or the arrival of new jobs, causing a need for fast schedule adaptation. In this paper, a mathematical model for this type of problem is proposed and a restarted iterated Pareto greedy (RIPG) metaheuristic is used to find the optimal Pareto front. To demonstrate the appropriateness of this approach, the algorithm is applied to a benchmark specifically designed in this study, considering three objective functions (makespan, total weighted tardiness, and steadiness) and three classes of disruptions (appearance of new jobs, machine faults, and changes in operational times). Experimental studies indicate the proposed approach can effectively solve rescheduling tasks in a multiobjective environment.

Four colistin susceptibility testing methods were compared with the standard broth microdilution (BMD) in a collection of 75 colistin-susceptible and 75 mcr-positive E. coli, including ST131 isolates. Taking BMD as reference, all methods showed similar categorical agreement rates (CA) of circa 90%, and a low number of very major errors (VME) (0% for the MicroScan system and Etest®, 0.7% for UMIC®), except for the disc diffusion assay (breakpoint ≤ 11 mm), which yielded false-susceptible results for 8% of isolates. Of note is the number of mcr-positive isolates (17.3%) categorized as susceptible (≤2 mg/L) by the BMD method, but as resistant by the MicroScan system. ST131 mcr-positive E. coli were identified as colistin-resistant by all MIC-based methods. Our results show that applying the current clinical cut-off (>2 mg/L), many mcr-positive E. coli remain undetected, while applying a threshold of >1 mg/L the sensitivity of detection increases significantly without loss of specificity. We propose two possible workflows, both starting with the MicroScan system, since it is automated and, importantly, it categorized all mcr-positive isolates as colistin-resistant. MicroScan should be followed by either BMD or MIC-based commercial methods for colistin resistance detection; or, alternatively, MicroScan, followed by PCR for the mcr screening.

This paper introduces a method for the distribution of any and all population-based metaheuristics. It improves on the naive approach, independent multiple runs, while adding negligible overhead. Existing methods that coordinate instances across a cluster typically require some compromise of more complex design, higher communication loads, and solution propagation rate, requiring more work to develop and more resources to run. The aim of the new method is not to achieve state-of-the-art results, but rather to provide a better baseline method than multiple independent runs. The main concept of the method is that one of the instances receives updates with the current best solution of all other instances. This work describes the general approach and its particularization to both genetic algorithms and ant colony optimization for solving Traveling Salesman Problems (TSPs). It also includes extensive tests on the TSPLIB benchmark problems of resulting quality of the solutions and anytime performance (solution quality versus time to reach it). These tests show that the new method yields better solutions for about two thirds of the problems and equivalent solutions in the remaining third, and consistently exhibits better anytime performance.