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Objective: The objective of this study is to evaluate the awareness of cross-infection control measures followed by DHCPs during the 5th wave of Covid-19 pandemic, Omicron variant in a government sector university of Karachi, Pakistan. Method(s): A Cross-sectional study was conducted from June till September 2022 at Sindh Institute of Oral Health Science during the 5th wave of Covid 19 pandemic, Omicron variant. Data was collected from 153 DHCPs from government sector university using a self-administered questionnaire, comprising of 20 closed ended question to assess the awareness and practice of cross infection protocols by DHCPs. Result(s): 98.7% of the participants were vaccinated against Covid 19. 96% of the participants used surgical gowns, face shields, and face masks as part of PPE during examining patients and while performing procedure. After treatment 99.3% of participants washed hands with hand wash, soap or used antiseptic solution. 77.1% of participants asked for Covid 19 test report and 68.6% of participants asked for proof of vaccination against covid 19 before treating patients. 96.1% of participants recommended disinfection of dental unit after every patient. 98% of participants changed glove after every patient. 88.2% of the participants said they would carry all elective and emergency procedures. Conclusion(s): The results of this study show that DHCPs practicing at government sector university have adequate knowledge regarding prevention of cross infection protocols and their importance to limit spread of infections. But their practice of prevention of cross infection during Covid 19 pandemic is not ideal as percentage of DHCPs requiring proof of vaccination or negative reports for Covid 19 were rather low and the percentage of DHCPs willing to carry elective procedures along with emergency ones was rather high.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.
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The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
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Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.
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In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.
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Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors? Introduction: Interleukin-6 (IL-6) inhibitors have been shown to reduce mortality in hospitalised COVID-19 patients. There is, however, concern that induced immunosuppression may increase the risk of secondary nosocomial infection. Objective(s): Our primary aim was to determine if there was increased incidence of bacteraemia in COVID-19 patients requiring critical care admission who had received IL-6 inhibitors compared to those who had not. Method(s): A retrospective review of all COVID-19 admissions to two critical care units in Liverpool from 4th March 2020 to 31st October 2021. Patients were divided into those who received an IL-6 inhibitor (sarilumab or tociluzimab) and those who did not. Hospital antimicrobial policy was to administer a five day prophylactic course of co-amoxiclav and clarithromycin for patients with severe COVID-19 during the study period. Blood culture results from 14 days before admission to critical care and 90 days after admission were included. The blood culture results comprised cultures taken in both critical care and on the wards. Data were linked and analysed using Stata V15.1 (StataCorp, Stata Statistical Software: Release 15, College Station, Texas, USA). Result(s): 894 patients were included in the study. 134 patients had at least one positive blood culture result. The most commonly identified pathogens were Coliforms (23/134, 17.2%), Enterobacter (22/134, 16.4%) and Escherichia coli (16/134, 11.9%). Of patients administered an IL-6 antagonist, 16.8% (114/565) developed a positive blood culture compared to 11.6% (20/172) who did not, p=0.096. We did not observe an increased frequency of antimicrobial resistant culture in the IL-6 administered group 22.8% (26/114) vs. 20.0% (4/20) in this cohort, p=0.781. Data have not been adjusted for demographic and clinical factors in this preliminary analysis. Conclusion(s): We observed a trend toward increased frequency of blood culture positivity in patients administered an IL-6 antagonist within this COVID-19 positive cohort but this was not statistically significant. Further analysis is required to adjust for relevant demographic and clinical factors.
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Objective: To determine the frequency of antibiotic use and to know which clinical and socio-demographic variables were related to the probability of suffering infections associated with COVID-19. Method(s): Adults hospitalized for COVID-19 who received one or more antibiotics during hospitalization were evaluated. We performed a descriptive analysis of variables in the general population' bivariate analysis in two groups (documented vs. suspected infection) and multivariate logistic regression of factors associated with mortality. Result(s): It was determined that 60.4% of adults hospitalized for COVID-19 received antibiotics. Coinfection was documented in 6.2% and superinfection in 23.3%. Gram-negative germs were reported in 75.8% of cultures, fungi in 17.8% and gram-positive in 14.2%. Variables such as age, comorbidities, ICU, anemia, steroids, mechanical ventilation, hemofiltration were statistically significantly related to documented infection. High-flow cannula was associated as a protective factor. Overall mortality was 43.9%, 57.8% in the first group and 38.1% in the second (p=0.002). Conclusion(s): There is a considerable frequency of antibiotic use in subjects hospitalized for COVID-19, particularly related to relevant findings of bacterial superinfection, in those with comorbidities, such as diabetes mellitus, immunosuppression, anemia and fragility, in whom the behavior of the disease is more severe and lethal.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.
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Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment). Objective(s): systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action. Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data. Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail. Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.Copyright © 2023 Modern Medical Technology. All rights reserved.
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It is now well-recognised that antimicrobial resistance (AMR), or the ability of organisms to resist currently available antibiotics and other antimicrobial drugs, represents one of the greatest dangers to human health in the 21st Century. As of 2022, AMR is a top-10 global public health threat. Various national and transnational initiatives have been implemented to address accelerating AMR, and the pressure to find local and global solutions is increasing. Despite this urgency, surprisingly limited progress is being made in rolling back or even slowing resistance. A multitude of perspectives exist regarding why this is the case. Key concerns include an enduring dependency on market-driven drug development, the lacklustre governance and habitual over-prescribing of remaining antimicrobial resources, and rampant short-termism across societies. While rarely presented in such terms, these disparate issues all speak to the social production of vulnerability. Yet vulnerability is rarely discussed in the AMR literature, except in terms of 'disproportionate effects' of AMR. In this paper, we offer a reconceptualisation of vulnerability as manifest in the AMR scene, showing that vulnerability is both a predictable consequence of AMR and, critically, productive of AMR to begin with. We underline why comprehending vulnerability as embodied, assembled, multivalent and reproduced through surveillance matters for international efforts to combat resistance.Copyright © 2022 Informa UK Limited, trading as Taylor & Francis Group.
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Background: Although over 100 million pregnant women worldwide are at risk of infection with SARS-CoV-2, little data exists on the impact of COVID-19 and related treatments on maternal/neonatal health. Objective(s): (1) To quantify the prevalence of medication use in pregnancy to treat COVID-19, and (2) To quantify and compare the risk of adverse pregnancy/neonatal outcomes in those with and without COVID-19. Method(s): In the Canadian Mother-Child population-based cohort (CAMCCO), two sub-cohorts were identified using prospective data collection of medical services, prescription drugs, hospitalization archives data, and COVID-19 surveillance testing program (02/28/2020- 2021). The first cohort included all pregnant women during the study period regardless of pregnancy status (delivery, induced/planned or spontaneous abortion);this cohort was further stratified on COVID-19 status. The second cohort included all nonpregnant women (aged 15-45) with a positive COVID-19 test. COVID-19 in pregnant or nonpregnant women was assessed using COVID-19 test results or ICD-10CM code U07.1 from hospital data. COVID-19 severity was categorized based on hospital admission. Women were considered exposed to COVID-19 medications if they filled at least one prescription for a medicine included in the WHO list in the 30 days pre- or 30 days post-COVID-19 positive test/diagnosis. Considering potential confounders, association between COVID-19 during pregnancy, treated vs not, and perinatal outcomes were quantified using log-binomial regression models. Result(s): 150,345 pregnant women (3,464 (2.3%) had COVID-19), and 112,073 nonpregnant women with COVID-19 diagnoses were included. Pregnant women with COVID-19 were more likely to have severe infections compared to nonpregnant women with COVID-19 (11.4% vs 1.6%, p<0.001). The most frequent medications used in pregnancy to treat COVID-19 were antibacterials (13.96%), psychoanaleptics (7.35%), and medicines for obstructive airway disease (3.20%). In pregnancy COVID-19 was associated with spontaneous abortions (adjRR 1.76, 95%CI 1.37, 2.25), gestational diabetes (adjRR 1.52, 95%CI 1.18, 1.97), prematurity (adjRR 1.30, 95%CI 1.01, 1.67), NICU admissions (adjRR 1.32, 95%CI 1.10, 1.59);COVID-19 severity was increasing these risks but exposures to COVID-19 medications reduced all risks. Conclusion(s): COVID-19 severity was higher in pregnancy. Antibacterials, psychoanaleptics, and medicines for obstructive airway disease were the most used overall. COVID-19 was associated with adverse outcomes for mothers and newborns.
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Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.
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Secondary bacterial infection is one of the important risk factors for the development of severe course and death in COVID-19. The rational choice of antibacterial therapy is based on the data of microbiological monitoring of pathogens of healthcare-associated infections. The aim of the study is to determine the main options for antibiotic therapy of Acinetobacter baumannii bloodstream infection in COVID-19 patients. Material and methods. A retrospective, single-centre, uncontrolled study of the incidence of A. baumannii bacteremia in COVID-19 patients treated at the City Clinical Hospital No. 52 in Moscow from October 2020 to September 2021 was performed. For each strain of A. baumannii sensitivity to the main antibacterial agents was determined. Genetic determinants of antibiotic resistance were studied by real-time multiplex polymerase chain reaction. The main therapeutic options for A. baumannii bloodstream infection were analyzed. Results and discussion. Bloodstream infections were diagnosed in 4.7% of hospitalized patients with COVID-19 (758/16 047). Gram-negative bacteria were the causative agents of bloodstream infections in 76% of cases. A. baumannii were isolated from the blood of 143 patients (0.89%). Detection of the pathogen in the blood of COVID-19 patients was associated with severe and extremely severe course of the disease. Most of the strains (93%) were isolated in the intensive care unit. The A. baumannii strains studied were carbapenem-resistant (CRAb) and phenotypically belonged to the XDR class. According to a PCR study, A. baumannii strains were producers of oxacillinases OXA-23, OXA-40, and OXA-51. Conclusion. The circulation of A. baumannii CRAb in intensive care units makes empiric therapy based on carbapenems irrational and ineffective. For the etiotropic therapy of A. baumannii bloodstream infection it is recommended to use combined antibiotic therapy regimens with the inclusion of polymyxin B and sulbactam.Copyright © Eco-Vector, 2022.
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The removal and defense mechanisms of the respiratory system of patients with pneumoconiosis are impaired. Once patients with pneumoconiosis and other underlying lung diseases are infected with novel coronavirus, they are likely to progress to severe cases with COVID-19, a tough condition with a high mortality and poor prognosis. Herein we presented a case of pneumoconiosis and tuberculosis complicated with severe COVID-19. Active administration of anti-viral, anti-infection, phlegm-removing, anti-asthmatic, and high-flow oxygen therapies did not alleviate the patient's acute respiratory distress syndrome symptoms. Then tracheal intubation, ventilator assisted breathing, and lung protective ventilation were given but did not effectively treat the patient's respiratory failure. Finally, the patient died clinically despite use of extracorporeal membrane oxygenation (ECMO).Copyright © 2021, Shanghai Municipal Center for Disease Control and Prevention. All rights reserved.
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Intro: This study aimed at evaluating healthcare-related sepses caused by three multi-drug resistant Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa) in a tertiary hospital in 2018-2020, particularly concerning therapy, antibiotic-resistance and outcomes, by also comparing the pre-COVID (2018-2019) and COVID (2020) periods. Method(s): An observational, retrospective-cohort analysis was based on data related to patients admitted to the "SS. Antonio e Biagio e Cesare Arrigo" Hospital in Alessandria (Italy) between 2018 and 2020, with septic episodes from bacteria of the examined species, whose antibiogram proved resistance to >= 2 antimicrobial classes indicated by the European Centre for Disease Prevention and Control. Data were retrieved from patients' medical records and the hospital's computer-based application. Statistics involved Fisher-test comparisons and cumulative incidence analyses. Finding(s): Inclusion criteria led to enrolment of 174 patients. Comparison between 2020 and 2018-2019 showed a relative increase in A. baumannii cases, at the expense of the other species (p<0.0001), and an increasing resistance trend for K. pneumoniae, with a higher proportion of cases resistant to 3-4 classes of antimicrobials (p<0.0001). Overall, most patients were treated with carbapenems (72.4%), although the COVID period saw a significant rise in the use of polymyxins, particularly colistin (62.5% vs 36%, p=0.0005). In both periods, more than half patients recovered (53-57%) and around one third died (27-34%), but with different outcomes according to the infecting bacterium, generally better for P. aeruginosa (70% recovered at 60 days) and worse for A. baumannii (55% recovered). Discussion(s): The study confirmed the importance of the burden connected to healthcare-related sepses. Moreover, since the COVID outbreak, a trend could be spotted towards higher relative incidence of complex cases, caused by antimicrobial-resistant bacteria and thus requiring second-line therapy. Conclusion(s): These findings underline the importance of appropriate antimicrobial stewardship and infection control in view of the evolving healthcare needs.Copyright © 2023
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The COVID-19 epidemic has once again highlighted the challenges to achieve equitable access to critical antimicrobials and vaccines. The problem is particularly acute for antimicrobials. Despite recent investments improving the pipeline for new treatments, most new treatments are not available to populations most in need, especially in low- and middle-income countries. Once a drug is approved a range of factors may hinder access, from lack incentives to register and commercialize products due to unattractive market potential to unfunded national action plans that can help improve the uptake and appropriate use of new tools to combat antibiotic resistance. Previous studies have shown that the majority of the 18 new antibacterials approved and launched between 2010-2020 were accessible in only 3 out of 14 high-income countries (Sweden, UK, and US). In low- and middle-income countries, the problem is even worse, with only 10 of the 25 new antibiotics that entered the market between 1999 and 2014 registered in more than ten countries. While lack of equitable access to life-saving medicines, diagnostics, and vaccines is not a new problem for infectious diseases, emerging opportunities and innovative approaches can help improve access globally. This talk will review promising recent developments in governance and collaborations, policies, economic models and initiatives that may help correct deadly inequities. For example, the objectives of the Access to COVID-19 Tools Accelerator may serve as model that convenes diverse actors to mount a coordinated access response which may be applied to access to other antimicrobials and vaccines. In addition, novel licensing agreements for access and stewardship to cefiderocol, an antimicrobial that is on the WHO Essential Medicines List can help serve as a pathfinder to accelerate equitable access to novel antimicrobials. The talk will also surface critiques of ongoing initiatives and raise questions for further study and discussion.Copyright © 2023
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Intro: The Out-Patient Parenteral Antimicrobial Therapy (OPAT) is a form of Antimicrobial Stewardship that is now widely-practise throughout the world. However, in Malaysia, this has just only begun to take root and the OPAT in Universiti Malaya (UM) has only just begin operating on 2 August, 2018. The OPAT in Universiti Malaya has been operating for 4 years and is a collaboration between the General Medical Unit and the Infectious Control Unit. Method(s): This was a longitudinal study of all the patients that has been admitted to the OPAT since the start of the service. For each patient the starting and ending date in OPAT, anitbiotic used, the diagnosis, the referring unit, and any problems were recorded. Finding(s): The total patient-days of antibiotics served in the OPAT was 4978, with a mean duration of 66.37 days per patient and a median of 31 days. The majority of cases was referred from the medical department with 41 cases (54.67%) followed by Surgery with 22 cases (29.33%). Ertapenem was the most common antimicrobial served with 39 patients on it (52%) and ceftriaxone was second with 8 patients served (10.67%). All antibiotics have been agreed upon by the Infectious Disease Unit. In our study, 2 patients in OPAT has died but the rest none of them were admitted for hospital associated infection. Discussion(s): We found that OPAT on average save at least ten beds per day in the hospital. The patients are happy because they do not need to be warded in hospital to receive their antimicrobials. However, we faced limitations in recruitment of patients to the OPAT during the COVID-19 pandemic, staff shortages, the lack of infusion pumps for serving multidose antimicrobials, and bureacratic red-tape. Conclusion(s): OPAT was useful in reducing bed occupancy rate and hospital associated infection. Patients also are happy with the service.Copyright © 2023
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Preventive vaccination against SARS-CoV-2 infection is currently receiving close attention in the Russian Federation. Improving public confidence in immunisation with new vaccines largely depends on a guarantee of the absence of side effects caused by contamination. A high risk of contamination is inherent to biological products, including coronavirus prevention vaccines, due to their properties and the nature of raw materials used. This risk adds to the need for using effective contaminant detection approaches. The aim of the study was to evaluate the possibility to improve sterility testing of preventive vaccines against SARS-CoV-2 infection. This article presents an analysis of the procedures proposed by pharmaceutical developers for sterility testing of ten Russian vaccines approved in the country for COVID-19 prevention. The authors considered specific characteristics of these vaccines, including their physical and chemical properties, the presence of antimicrobial components, and other critical factors affecting the correctness of the experimental setup. The results suggest that it is possible to improve sterility testing. According to the authors, the main directions for its improvement are the proposal to develop an alternative procedure based on compendial method 2 (OFS.1.2.4.0003.15, Ph. Rus. XIV), as well as the use of a universal culture medium. If used for refining the established procedures and developing new ones, the authors' recommendations will improve the reliability and applicability of sterility testing during both manufacturing and pre-approval regulatory assessment of updated coronavirus vaccines for subsequent release to the market. The proposed approaches can be applied to testing other medicinal products for sterility.Copyright © 2023 National Electronic-Information Consortium (NEICON). All rights reserved.
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Introduction: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), is a clinical syndrome characterized by hepatomegaly, right-upper quadrant pain, and ascites that occurs most commonly in the setting of high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT). The diagnosis can be confirmed on biopsy. Cemiplimab is an immune checkpoint inhibitor recently approved for the treatment of cutaneous squamous cell carcinoma. There are currently no known reports of immune checkpoint inhibitor-related VOD/SOS. Case Description/Methods: A 58-year-old female with a history of locally advanced basal cell carcinoma of the left eye treated with six months of Cemipilimab presented with ascites. On admission, labs were notable for a total bilirubin of 1.2, mildly elevated liver function tests, alkaline phosphatase 884, and international normalized ratio 2.1. A diagnostic tap revealed a high SAAG ascites that was negative for infection. A comprehensive serological workup for viral, metabolic and autoimmune causes was unrevealing. A transjugular liver biopsy demonstrated a hepatic venous pressure gradient of 18mmHg, nodular regenerative hyperplasia (NRH), and portal venopathy. The patient was discharged on steroids but returned one month later for recurrent ascites and worsening bilirubin to 12.6 (direct 7.3);COVID PCR was negative. A full rheumatologic and vasculitis workup was unremarkable. Repeat biopsy (Figure 1) demonstrated moderate NRH changes, prominent central vein sclerosis with fibrous obliteration, signs of SOS/ VOD and central venulitis with fibrotic changes with sinusoidal portal hypertension. Discussion(s): VOD occurs most often with hematopoietic stem cell transplantation, and chemotherapeutic agents. Here we present the first case of checkpoint inhibitor-induced VOD/SOS. Despite discontinuation of the offending agent and a trial of steroids, the patient's clinical course continued to deteriorate. She eventually developed refractory ascites and portosystemic encephalopathy. She was deemed not a candidate for liver transplant given her underlying malignancy. She was transitioned to home hospice before further treatment, such as Defibrotide could have been pursued. VOD associated with immune checkpoint inhibition should be considered in the differential of patients who develop new onset liver dysfunction and ascites while receiving these medications (Figure Presented).
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Drug resistance or multidrug resistance is multidimensional and complex. Over the past decade and especially during the covid-19 pandemic, the incidence of drug resistant infections increased despite the implementation of infection control precautions. This was most commonly seen in low- and middle-income countries, due to the higher burden of infectious diseases, lack of proper infrastructure, unregulated antimicrobial prescriptions over the counter, limited surveillance of antimicrobial use and resistance patterns. This was further compounded by the dearth of healthcare personnel trained in appropriate infectious disease management. Strategies in high income countries to prevent and manage drug resistant infections are unfortunately, not implementable in LMICs due to differences in antimicrobial resistance (AMR) burden, access to newer antibiotics, limited infrastructure and human resources with requisite expertise with lack of economic investment by regulatory authorities to tackle AMR. During the covid-19 pandemic, the lack of therapeutic options and the similar clinical picture initially led to rampant antimicrobial use which in turn contributed to rise in multi-drug resistant infections (MDR). Along with inappropriate antimicrobial use, redistribution of staff assigned to enforce infection control practices, shortage of personnel protective equipment, overcrowded healthcare settings, use of prolonged broad-spectrum antimicrobials in patients requiring during intensive care and mechanical ventilation contributed to the rise in hospital transmission of multidrug resistant infections during the pandemic. To mitigate the effects of drug resistance, healthcare systems must ensure effective implementation of surveillance of antimicrobials, AMR patterns especially in MDR HAIs and antimicrobial stewardship interventions to promote optimal antimicrobial use. National level investment to improve diagnostics must be given priority as it can limit drug resistance and promote the role of biomarkers in streamlining antimicrobial use. These need to be planned to facilitate future integration with any future pandemic surveillance.Copyright © 2023
ABSTRACT
In recent days, the increasing number of microbes and their increasing resistance power against conventional drugs have led to enormous worldwide mortalities, hence they pose a great threat to human health. The modern era is already going through the threat of COVID-19, also caused by one of those microbes called the virus. In order to get a clear understanding, all the microbes have been classified in certain types. Nowadays, to develop new alternative antimicrobial medicines, scientists must acquire clarity about the responsible functional groups of different conventional drugs with proper mechanistic elucidation on different types of microbes. This information not only clarifies the functionalities and properties responsible for exhibiting antimicrobial effects, but also facilitates the idea of new drug development through proper functional group incorporation or modification. These modifications increase the efficacy of antimicrobial drugs as well as their activity and water solubility. In this review, my focus will majorly be on the four main types of microbes and their possible mechanistic elucidation of commonly used antibiotics and alternative antimicrobial medicines discovered till now. I thank the Science and Engineering Research Board (SERB), Council of Scientific and Industrial Research (CSIR), and Government of India for my fellowship and research grants during my Ph.D in Indian Institute of Science Education and Research, Kolkata and Postdoctoral journey in the University of Burdwan. I acknowledge Prof. Bimalendu Ray (Chemistry department, The University of Burdwan), Prof. Priyadarsi De, (Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata), Prof. Punyasloke Bhadury (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata), Dr. Anwesha Ghosh (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata) for many helpful discussions and laboratory use.Copyright © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.