Application of Pharmacokinetics/Pharmacodynamics (PK/PD) in Designing Effective Antibiotic Treatment Regimens

Designing antibiotic dosing regimens is often not optimal and the dose-response relationship for most antibiotics is not well-known1. Both Pharmacokinetics (PK) and Pharmacodynamics (PD) are characteristics of antimicrobial agents that should be considered in the development of effective antibiotic therapy. By linking the concentration time profile at the site of action to the drug effect (PK/PD), the effect of varying dosage regimens against pathogens could be simulated enabling the identification of effective dosage strategies. It is known that inadequate antibiotic dosing could not only lead to a therapeutic failure, but also to the development of bacterial resistance. Importantly, the evolution of resistance in pathogenic bacteria combined with the decreasing interest from the pharmaceutical industry in developing new antibiotics has created a major public health problem3. Therefore, the activities to maintain the effects of existing antibiotics and prolong their useful life span have a high priority.https://digitalcommons.chapman.edu/pharmacy_books/1007/thumbnail.jp

Bacteriophage ZCSE2 is a Potent Antimicrobial against Salmonella enterica Serovars: Ultrastructure, genomics and efficacy

© 2020 by the authors. Developing novel antimicrobials capable of controlling multidrug-resistant bacterial pathogens is essential to restrict the use of antibiotics. Bacteriophages (phages) constitute a major resource that can be harnessed as an alternative to traditional antimicrobial therapies. Phage ZCSE2 was isolated among several others from raw sewage but was distinguished by broad-spectrum activity against Salmonella serovars considered pathogenic to humans and animals. Lytic profiles of ZCSE2 against a panel of Salmonella were determined together with low temperature activity and pH stability. The morphological features of the phage and host infection processes were characterized using a combination of transmission electron and atomic force microscopies. Whole genome sequencing of ZCSE2 produced a complete DNA sequence of 53,965 bp. No known virulence genes were identified in the sequence data, making ZCSE2 a good candidate for phage-mediated biological control purposes. ZCSE2 was further tested against S. Enteritidis in liquid culture and was observed to reduce the target bacterium to below the limits of detection from initial concentrations of 107–108 Colony Forming Units (CFU)/mL. With a broad host-range against pathogenic Salmonella serovars, phage ZCSE2 constitutes a potential tool against a major cause of human and animal disease

New analysis of VSC-based modular multilevel DC-DC converter with low interfacing inductor for hybrid LCC/VSC HVDC network interconnections

The integration of multiterminal hybrid HVDC grids connecting LCC- and VSC-based networks faces several technical challenges such as DC fault isolation, ensuring multi-vendor interoperability, managing high DC voltage levels, and facilitating high-speed power reversal without interruptions. The two-stage DC-DC converter emerges as a key solution to address these challenges. By implementing the modular multilevel converter (MMC) structure, the converter's basic topology includes half-bridge sub-modules on the VSC side and full-bridge sub-modules on the LCC side. However, while this topology has been discussed in the literature, its connection to an LCC-based network with controlled current magnitude lacks detailed analysis regarding operational challenges, control strategies under various scenarios, and design considerations. This paper fills this gap by providing comprehensive mathematical analysis, design insights, and control strategies for the modular DC-DC converter to regulate DC voltage on the LCC-HVDC side. Additionally, the proposed control scheme minimizes the interfacing inductor between the two bridges, ensuring uninterrupted power flow during reversal and effective handling of DC faults. Validation through Control-Hardware-in-the-Loop testing across diverse operational and fault scenarios, along with a comparative analysis of different converters, further strengthens the findings

Safety of Transcatheter Aortic Valve Replacement in Patients with Aortic Aneurysm: A Propensity-Matched Analysis

Introduction There is a paucity of data regarding the outcomes of transcatheter aortic valve replacement (TAVR) among patients with thoracic or abdominal aortic aneurysms (AA). Using the Nationwide Inpatient Sample (NIS) database, we explored the safety of TAVR among patients with a diagnosis of AA. Methods We queried the National Inpatient Sample database (2012–2017) for hospitalized patients undergoing TAVR, using ICD-9 and ICD-10 codes for endovascular TAVR. Reports show that \u3e 95% of endovascular TAVR in the US is via transfemoral access, so our population are mostly patients undergoing transfemoral TAVR. Using propensity score matching, we compared the trends and outcomes of TAVR procedures among patients with versus without AA. Results From a total sample of 29,517 individuals who had TAVR procedures between January 2012 and December 2017, 910 had a diagnosis of AA. In 774 matched-pair analysis, all-cause in-hospital mortality was similar in patients with and without AA OR 0.63 [(95% CI 0.28–1.43), p = 0.20]. The median length of stay was higher in patients with AA: 4 days (IQR 2.0–7.0) versus 3 days (IQR 2.0–6.0) p = 0.01. Risk of AKI [OR 1.01 (0.73–1.39), p = 0.87], heart block requiring pacemaker placement [OR 1.17 (0.81–1.69), p = 0.40], aortic dissection [OR 2.38 (0.41–13.75), p = 0.25], acute limb ischemia [OR 0.46 (0.18–1.16), p = 0.09], vascular complications [OR 0.80 (0.34–1.89), p = 0.53], post-op bleeding [OR 1.12 (0.81–1.57), p = 0.42], blood transfusion [OR 1.20 (0.84–1.70), p = 0.26], and stroke [OR 0.58 (0.24–1.39), p = 0.25] were similar in those with and without AA. Conclusions Data from a large nationwide database demonstrated that patients with AA undergoing TAVR are associated with similar in-hospital outcomes compared with patients without AA. Key Summary Points Patients with a diagnosis aortic aneurysm (thoracic or abdominal) undergoing transcatheter aortic valve replacement (TAVR) have same risk of periprocedural complications as those without a diagnosis of aortic aneurysms (AA). Patients with a diagnosis of aortic aneurysm had a longer length of hospital stay. Further studies are needed to determine how specific features of aortic aneurysm such as size, shape, thrombus burden, or calcifications affect the safety of TAVR

Avascular bone necrosis of the femoral head after renal transplantation: Is it avoidable?

Background: Avascular osteonecrosis (AVN) is a seriousosseous complication after renal transplantation (RT). Itsprevalence clearly decreased from 20% to 4% possiblydue to the use of calcinurin inhibitors (CNI), reduction ofsteroid doses and use of steroid free regimens. The aimof our study was to evaluate the frequency of AVNamong our kidney transplant recipients and to determinethe risk factors for its occurrence.Patients and methods: Among 1785 kidney transplantrecipients who received renal allografts between March1976 and December 2005, 40 patients (2.24%) developedAVN with a mean age of 31.3 10.2 years. Eightykidney transplant recipients without AVN were selectedto be a matched control group. The localization of AVNwas the femoral head in all cases.Results: AVN was diagnosed at a mean of 20.4 monthsafter transplantation. The following risk factors werestatistically significant; sirolimus-based regimen,hypercholesterolemia, overweight with body mass index(BMI)>26 and those with HLA A9, HLA B35 and DRB15.Conclusions: We concluded that the proper managementof hypercholesterolemia, maintenance of ideal bodyweight as well as avoidance of sirolimus-basedimmunosuppressive regimen in genetically predisposedpatients may be an effective preventive strategy to avoidAVN

A new hybrid multilevel thyristor-based DC-DC converter

The rapid growth in HVDC grids is becoming inevitable for long-distance power transmission. Therefore, the idea of interconnection between the point-to-point links becomes essential. However, these point-to-point connections face several challenges such as the requirement of DC fault blocking capability, interfacing of different grounding schemes, offering multi-vendor interoperability, and difficulty to achieve high DC voltage stepping. DC-DC converters are considered the optimum solution to tackle these challenges in DC grids interconnection. In this paper, a new hybrid modular DC-DC converter is proposed that achieves a low number of semiconductors, low losses, and cost in comparison to other DC-DC converters due to the utilization of thyristors. The new DC-DC converter consists of two hybrid MMC bridges connected through an isolating transformer. Each MMC bridge is comprised of half bridge submodules and bidirectional thyristors. Detailed mathematical analysis, design, and control are illustrated. A comparison is carried out between different topologies in terms of semiconductor count, power loss, and cost. Also, both simulation model and experimental test rig are built to validate the proposed hybrid modular DC-DC converter under different scenarios. Finally, another variant of the hybrid-thyristor based converter (version two) is proposed for multiport DC-Hub application to achieve DC fault blocking without turning off all connected bridges

Trends in the assessment of multidrug efficiency against identified bacterial strains isolated from wounds at El-Demerdash Hospital, Egypt

Multidrug-resistant (MDR) bacteria is a severe problem for universal public health which increases morbidity and mortality rate. These resistant bacteria lead to ineffective treatment of drugs resulting in the spreading and persistence of infections. So, the major target of this study is to estimate the competence of multidrug antibacterial agents against bacterial strains isolated from wound samples and then identify the most potent Multidrug-resistant (MDR) bacteria. Fifty wound swab specimens were gathered from various wounds and several patients from the Central Microbiology Laboratory of El-Demerdash Hospital, Cairo, Egypt. Eighty- nine bacterial isolates were isolated from fifty wound samples then cultured on different media and tested for their susceptibility to different thirty antibiotic discs using the agar disc diffusion method. After recording the results of the susceptibility test, the post potent resistant bacterial isolates recorded 3 bacterial isolates which resistant to 30 different antibiotic types. These resistant bacterial isolates were identified using morphological, biochemical, and molecular techniques. The results recorded that the post potent resistant bacterial isolates identified as Klebsiella oxytoca, Pseudomonas aeruginosa, and Escherichia coli. This study concluded that with the increase in the random use of antibiotic drugs resulted in the presence of multi-antibacterial resistant strains. There are bacterial strains that were isolated from wounds in patients at El-Demerdash Hospital, Egypt, and identified. They can resist about thirty different antibiotic discs. Abbreviation: Multiple antibiotic resistance (MAR)