Swallowability of Minitablets among Children Aged 6–23 Months: An Exploratory, Randomized Crossover Study

Minitablets have garnered interest as a new paediatric formulation that is easier to swallow than liquid formulations. In Japan, besides the latter, fine granules are frequently used for children. We examined the swallowability of multiple drug-free minitablets and compared it with that of fine granules and liquid formulations in 40 children of two age groups (n = 20 each, aged 6–11 and 12–23 months). We compared the percentage of children who could swallow minitablets without chewing with that of children who could swallow fine granules or liquid formulations without leftover. The children who visited the paediatric department of Showa University Hospital were enrolled. Their caregivers were allowed to choose the administration method. In total, 37 out of 40 caregivers dispersed the fine granules in water. Significantly more children (80%, 95% CI: 56–94%) aged 6–11 months could swallow the minitablets than those who could swallow all the dispersed fine granules and liquid formulations (22%, 95% CI: 6–47% and 35%, 95% CI: 15–59%, respectively). No significant differences were observed in children aged 12–23 months. Hence, minitablets may be easier to swallow than dispersed fine granules and liquid formulations in children aged 6–11 months.

Tuberculosis Situation in Volga Federal District in 2016-2020

The objective of the study: to assess changes in the incidence and prevalence of multiple drug resistant tuberculosis (MDR TB) and TB/HIV coinfection (TB/HIV) in Volga Federal District (VFD) and its regions during 2016-2020.Subjects and Methods. Data from FGSN Forms No. 8, 33, and 61, and analytical reviews of main statistical TB rates in the Russian Federation have been studied. The number of those died is presented as per the Rosstat data.Results. An increase in the incidence and prevalence of MDR TB and TB/HIV coinfection has been detected in certain region of Volga Federal District. Perm Region, the Republic of Bashkortostan, the Republic of Udmurtia, and Orenburg and Samara Regions have the highest prevalence of MDR TB and TB/HIV coinfection. In 2020, the Republic of Bashkortostan was the only region where the incidence and prevalence of MDR TB were growing (164.7% and 47.3%, respectively). The highest incidence and prevalence of TB/HIV coinfection was reported in the Republic of Bashkortostan, Perm Kray, Orenburg Region, the Chuvash and Udmurt Republics. Over the last 5 years, the maximum increase in TB/HIV incidence and prevalence was observed in the Republic of Bashkortostan (38.8% and 41.3%, respectively).

Multiplatform Analysis of Primary and Metastatic Breast Tumors from the AURORA US Network identifies microenvironment and epigenetics drivers of metastasis

Patients with metastatic breast cancer (MBC) typically have short survival times and their successful treatment represents one of most challenging aspects of patient care. This poor prognostic behavior is in part due to molecular features including increased tumor cell clonal heterogeneity, multiple drug resistance mechanisms, and alterations of the tumor microenvironment. The AURORA US Metastasis Project was established with the goal to identify molecular features specifically associated with metastasis. We therefore collected and molecularly characterized specimens from 55 metastatic breast cancer (BC) patients representing 51 primary cancers and 102 metastases. The 153 unique tumors were assayed using RNAseq, tumor/germline DNA exomes and low pass whole genome sequencing, and global DNA methylation microarrays. We found intrinsic molecular subtype differences between primary tumors and their matched metastases to be rare in triple negative breast cancer (TNBC)/Basal-like subtype tumors. Conversely, tumor subtype changes were relatively frequent in estrogen receptor positive (ER+) cancers where ~30% of Luminal A cases switched to Luminal B or HER2-enriched (HER2E) subtypes. Clonal evolution studies identified changes in expression subtype coincident with DNA clonality shifts, especially involving HER2 amplification and/or the HER2E expression subtype. We further found evidence for ER-mediated downregulation of genes involved in cell-cell adhesion in metastases. Microenvironment differences varied according to tumor subtype where ER+/Luminal metastases had lower fibroblast and endothelial cell content, while TNBC/Basal-like metastases showed a dramatic decrease in B cells and T cells. In 17% of metastatic tumors, we identified DNA hypermethylation and/or focal DNA deletions near HLA-A that were associated with its’ significantly reduced expression, and with lower immune cell infiltrates. We also identified low immune cell features in brain and liver metastases when compared to other metastatic sites, even within the same patient. These findings have direct implications for the treatment of metastatic breast cancer patients with immune- and HER2-targeting therapies and suggest potential novel therapeutic avenues for the improvement of outcomes for some patients with MBC.

Characterization of virulent Escherichia coli strains isolated from patients with urological infection

Objective. Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually.Purpose: Characteristics of non-hospital strains of UPEC isolated from patients with UTI in Yaroslavl in 2016– 2017.Materials and methods. Susceptibility of UPEC strains (n = 20) to antibacterials was measured by the serial dilution method; the antibiotic resistance and virulence genes, phylogroups, O-serogroups and sequence types were identified by PCR and whole genome sequencing. The virulence of the strains was studied using the model of Galleria mellonella larvae.Results. UPEC strains were classified as resistant (n = 11) and multi-drug resistant (n = 9) pathogens. Betalactamase genes blaTEM (n = 10), blaCTX-M (n = 6), class 1 integrons (n = 8), and gene cassettes dfrA17-aadA5 (n = 2), dfrA1 (n = 1) and aacA4-cmlA1 (n = 1) were identified. UPEC-virulence genetic determinants coding adhesins fimH, papG, sfaS, focG, afa/draBC, csgA, siderophores iroN, fyuA, iutA, counteracting factors of host immunity ompT, traT, toxins hlyA, cnf1, usp, capsule transporter kpsMTII, colicin cvaC, and pathogenicity islands I536, II536, III536, IV536, IIJ96 и IICFT073 were detected. Highly virulent and slightly virulent for G. mellonella larvae UPEC strains were obtained with LD50 104–105 and 106–107 CFU, respectively. The phylogroups A, B1, B2, E and F, serogroups О2, О4, О6, O9, O11, О15, О18, О25, О75 and O89, known sequence types ST14, ST58, ST69, ST73, ST93, ST127, ST131, ST-141, ST165, ST297, ST457, ST537, ST744, ST1434 and novel ST9239 and ST10102 were revealed.Conclusions. The identified genetic diversity of non-hospital UPEC strains is consistent with the observed global trend in the spread of human pathogens, which are characterized with both high virulence and multiple drug resistance. This makes possible to assess prospectively the current epidemiological situation, give a forecast for its development in the future, as well as determine the optimal therapeutic options.

Impact of host factors on susceptibility to antifungal agents

An obstacle to drug development, particularly in this era of multiple drug resistance, is the under-appreciation for the role the host environment plays in microbial response to drugs. With the rise in fungal infection and drug resistance, particularly in individuals with co-morbidities, the influence serum and its components have on antimicrobial susceptibility requires assessment. This study examined the impact of physiologically relevant glucose and insulin levels in the presence and absence of 50 % human plasma on MICs for clinical isolates of Candida lusitaniae, Candida parapsilosis, Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The addition of insulin or glucose at physiologic levels in RPMI medium alone altered the MIC in either a positive or negative fashion, depending on the organisms and drug tested, with C. glabrata most significantly altered with a 40, >32- and 46-fold increase in MIC for amphotericin B, itraconazole and miconazole, respectively. The addition of candida-antibody negative plasma also affected MIC, with the addition of glucose and insulin having a tandem effect on MIC. These findings indicate that phenotypic resistance of Candida and Cryptococcus can vary depending on the presence of insulin with glucose and plasma. This modulation of resistance may help explain treatment failures in the diabetic population and facilitate the development of stable drug-resistant strains. Furthermore, these findings indicate the need for a precision approach in the choice of drug treatment and drug development.

First Case of COVID-19 Treated with Monoclonal Anti-Spike Antibodies in a Patient with Cystic Fibrosis in Romania

Patients with chronic lung conditions, including cystic fibrosis, may be prone to severe COVID-19. Therefore, therapeutic intervention should be prompt and tailored to all associated comorbidities. We report the case of a 17-year-old male adolescent with cystic fibrosis and multiple chronic conditions (bronchiectasis, exocrine pancreatic insufficiency, chronic multidrug resistant Pseudomonas aeruginosa colonization, nasal polyposis, chronic sinusitis, ventricular extrasystoles and multiple drug allergies), who presented with an acute episode of productive cough, and was confirmed with moderate COVID-19 based on positive RT-PCR for SARS-CoV-2 and lung imaging showing isolated foci of interstitial pneumonia. Intravenous treatment with the monoclonal antibody cocktail casirivimab and imdevimab was administered. The evolution was favorable, with rapid remission of the inflammatory syndrome and gradual decrease of cough, without progression to severe or critical COVID-19, but with complications such as repeated hemoptysis, which was due to the patient’s underlying conditions, and which required close monitoring for timely adjustment of the patient’s chronic treatment.

Drug Utilization Evaluation of Colistin: A Retrospective Study

Background: Colistin, is used as the last treatment line for infections concluded from multiple drug-resistant gram-negative microorganisms. Increased consumption of colistin leads to resistance to this antibiotic in many countries. This study investigated the usage pattern of colistin administration in a selected hospital in Iran. Methods: This study was conducted in a selected hospital in Ahvaz. Inclusion criteria were all patients who received colistin during this time according to the health information system. Patients who were received less than three doses of colistin were excluded from the study. Prescription of colistin in all patients was evaluated according to the protocol extracted from the last version of Lexicomp written by Wolters Kluwer. The descriptive and analytical statistics were carried out by the R software. Results: Among 27 patients who received colistin, pneumonia (30%) was the main diagnoses. Colistin administration was based on the microbiological culture data in 70% of cases. Considering the involved microorganism, most cases were Acinetobacter spp., followed by Klebsiella spp. Loading dose was prescribed for seven (26%) patients. In only five (19%) cases, colistin dosing, including loading dose, maintenance dose, and the interval of colistin administration, was appropriate during the study time. Increasing in serum creatinine was seen in two (7.4%) patients. In 29.4% of patients, the combination of colistin and carbapenems was observed. Conclusion: Given the lack of appropriate dose adjustment of colistin that may lead to incidence of resistance and adverse effect, applying of the specialist clinical pharmacist will be suggested.

A Drug-free Strategy to Combat Bacterial Infections with Magnetic Nanoparticles Biosynthesized in the Bacterial Pathogens

The extensive and indiscriminate use of antibiotics in the ongoing COVID-19 pandemic might significantly contribute to the growing number of multiple drug resistant (MDR) bacteria. With the dwindling pipeline of...