Dose Optimization of Colistin: A Systematic Review

Colistin is considered a last treatment option for multi-drug and extensively resistant Gram-negative infections. We aimed to assess the available data on the dosing strategy of colistin. A systematic review was performed to identify all published studies on the dose optimization of colistin. Grey literature and electronic databases were searched. Data were collected in a specified form and the quality of the included articles was then assessed using the Newcastle-Ottawa scale for cohort studies, the Cochrane bias tool for randomized clinical trials (RCT), and the Joanna Briggs Institute (JBI) critical checklist for case reports. A total of 19 studies were included, of which 16 were cohort studies, one was a RCT, and two were case reports. A total of 18 studies proposed a dosing regimen for adults, while only one study proposed a dosing schedule for pediatric populations. As per the available evidence, a loading dose of 9 million international units (MIU) of colistin followed by a maintenance dose of 4.5 MIU every 12 h was considered the most appropriate dosing strategy to optimize the safety and efficacy of treatment and improve clinical outcomes. This review supports the administration of a loading dose followed by a maintenance dose of colistin in severe and life-threatening multi-drug Gram-negative bacterial infections

Dose optimization of β-lactams antibiotics in pediatrics and adults:A systematic review

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: “vancomycin”, “safety”, “efficacy” and “loading dose” combined with the Boolean operator “AND” or “OR”. Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Recurrence and progression in nonmuscle invasive transitional cell carcinoma of urinary bladder treated with intravesical Bacillus Calmette–Guerin: A single center experience and analysis of prognostic factors

Background: Intravesical Bacillus Calmette–Guerin (BCG) has been the standard of care for the prevention of nonmuscle invasive bladder cancer (NMIBC) recurrence following resection. Attempts to improve on the result by combining it with other agents have largely failed. This study addresses the result of BCG therapy in our patient population and compares the result with our combination BCG and interferon therapy published earlier. Materials and Methods: The medical records of patients diagnosed with NMIBC and treated with transurethral resection and intravesical BCG were reviewed. Univariate analysis was performed on most known prognostic factors. Results were compared to published data on the use of BCG and interferon from the same institution. Results: Thirty-one patients were identified. Median age was 66 (range 33–109), 80.6% were males. Fourteen patients (45%) had ≤ 3 tumors and 18 (58.1%) had T1 lesions. Four patients (12.9%) had Grade 3 tumors and 25 (80.6%) had Grade 2 tumors. One patient (3.2) had concurrent carcinoma in situ and 11 (35.5%) were treated upon initial diagnosis. At 5 years, the relapse-free survival was 61.3% (95% confidence interval (CI) 44.2–78.4%), progression-free survival was 85.6% (95% CI 73.3–97.9%), and overall survival was 93% (95% CI 84.1–100%). Comparison with the BCG and interferon data showed no significant difference. Conclusion: The result of BCG therapy in our patient population is similar to western reported data. Efficacy of BCG alone is equal to BCG and interferon within our institution

Defects oriented hydrothermal synthesis of TiO2 and MnTiO2 nanoparticles as photocatalysts for wastewater treatment and antibacterial applications

Pure and manganese-doped titanium dioxide nanoparticles (MnTiO2-NPs) were synthesized by the defect-oriented hydrothermal approach. The synthesized material was then characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX), and UV–visible spectroscopy (UV–Vis). The agar well diffusion method assessed the antibacterial efficiency of TiO2 and MnTiO2-NPs against E. coli and S. aureus. Zone of inhibition (ZOI) formed by pure TiO2 was observed as 12 mm and 11.5 mm against E. coli and S. aureus, while for MnTiO2-NPs it was observed as 19 mm (E. coli) and 21 mm (S. aureus). The concentration of synthesized nanoparticles (10 mg/ml, and 20 mg/ml) was used for antibacterial studies. The efficacy of the pure and MnTiO2-NPs as an active photocatalyst for the degradation of methylene blue (MB) dye was also assessed using a UV light. It was observed that the photodegradation efficiency of 1 g of MnTiO2-NPs was higher than the same amount of pure TiO2. The results suggest that the photocatalyst concentration directly impacts the photodegradation of MB dye. The pH value was found to influence the photodegradation of MB dye at higher pH values. Based on the obtained results, MnTiO2-NPs were observed as a promising agent for microbial resistance and water remediation