Preparation and characterization of lapatinib-loaded PVP nanofiber amorphous solid dispersion by electrospinning

Lapatinib-loaded polyvinylpyrrolidone-based nanofibrous solid dispersions were prepared by electrospinning in order to enhance the aqueous solubility and dissolution rate of the anticancer drug. The prepared nanofibers were characterized by smooth-surfaced, homogenous filaments with average diameters of 462±160 nm determined by scanning electron microscopy. The crystalline to amorphous transition of the active ingredient was confirmed by differential scanning calorimetry, while Raman spectroscopy showed that amorphous lapatinib was uniformly distributed in the fibrous structures. Gas chromatographic analyses revealed that residual solvents in the nanofiber mats were below the ICH Guideline Q3C recommended limits, namely ethanol 10.9±2.3 ppm (recommended limit 5000 ppm) and dimethyl formamide 780±56 ppm (recommended limit 880 ppm). Determination of drug content and in vitro dissolution studies were performed in order to observe the influence of electrospinning on the drug release characteristics of the product obtained. The lapatinib content in the nanofibers were measured to be 16.76±0.11 w/w%, whereas the dissolution study at pH 6.8 indicated a rapid disintegration of the nanofibrous mats, releasing ~70% of the drug loading under 5 minutes compared to the ~0.05% dissolution of the neat lapatinib ditosylate. The results confirm the applicability of electrospinning for the improvement of physicochemical characteristics of the poorly bioavailable anticancer agent

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (similar to 5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted. (C) 2022 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease.

Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization. A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April-June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon β-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon β-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised

Factors affecting mortality in COVID-19-associated pulmonary aspergillosis: An international ID-IRI study

Background This study aimed to identify factors that influence the mortality rate of patients with coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA). Methods In this cross-sectional study, data from 23 centers across 15 countries, spanning the period of March 2020 to December 2021, were retrospectively collected. The study population comprised patients who developed invasive pulmonary aspergillosis while being treated for COVID-19 in the intensive care unit. Cox regression and decision tree analyses were used to identify factors associated with mortality in patients with CAPA. Results A total of 162 patients (males, 65.4 %; median age: 64 [25th–75th: 54.0–73.8] years) were included in the study, of whom 113 died during the 90-day follow-up period. The median duration from CAPA diagnosis to death was 12 (25th–75th: 7–19) days. In the multivariable Cox regression model, an age of ≥65 years (hazard ratio [HR]: 2.05, 95 % confidence interval [CI]: 1.37–3.07), requiring vasopressor therapy at the time of CAPA diagnosis (HR: 1.80, 95 % CI: 1.17–2.76), and receiving renal replacement therapy at the time of CAPA diagnosis (HR: 2.27, 95 % CI: 1.35–3.82) were identified as predictors of mortality. Decision tree analysis revealed that patients with CAPA aged ≥65 years who received corticosteroid treatment for COVID-19 displayed higher mortality rates (estimated rate: 1.6, observed in 46 % of patients). Conclusion This study concluded that elderly patients with CAPA who receive corticosteroids are at a significantly higher risk of mortality, particularly if they experience multiorgan failure

Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia

Background: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection.Objectives: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection.Patients/Methods: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021.Results: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020).Conclusions: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study

Objectives: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management.Methods: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). Results: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120- 3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. Conclusions: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.&amp; COPY; 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved