How can lessons from the COVID-19 pandemic enhance antimicrobial resistance surveillance and stewardship?

COVID-19 demanded urgent and immediate global attention, during which other public health crises such as antimicrobial resistance (AMR) increased silently, undermining patient safety and the life-saving ability of several antimicrobials. In 2019, WHO declared AMR a top ten global public health threat facing humanity, with misuse and overuse of antimicrobials as the main drivers in the development of antimicrobial-resistant pathogens. AMR is steadily on the rise, especially in low-income and middle-income countries across south Asia, South America, and Africa. Extraordinary circumstances often demand an extraordinary response as did the COVID-19 pandemic, underscoring the fragility of health systems across the world and forcing governments and global agencies to think creatively. The key strategies that helped to contain the increasing SARS-CoV-2 infections included a focus on centralised governance with localised implementation, evidence-based risk communication and community engagement, use of technological methods for tracking and accountability, extensive expansion of access to diagnostics, and a global adult vaccination programme. The extensive and indiscriminate use of antimicrobials to treat patients, particularly in the early phase of the pandemic, have adversely affected AMR stewardship practices. However, there were important lessons learnt during the pandemic, which can be leveraged to strengthen surveillance and stewardship, and revitalise efforts to address the AMR crisis.

Indian microbiology EQAS registered laboratory's capacity building and infection control practices during the COVID-19 pandemic in India: Lessons learnt and gaps identified.

PURPOSE: The COVID-19 pandemic was unique in the history of outbreaks because of the massive scaling up of resources related to diagnostics, treatment modalities, and vaccines. To understand the impact of the pandemic among laboratory professionals, we aimed to conduct a survey to assess the improvement in the lab capacity post-covid in terms of infrastructure and accreditation status across various levels of hospitals and to determine the changes in the practice of infection control precautions during the pandemic. METHODS: This was an anonymous, online-based survey (using 58 item questionnaire) conducted between July 09, 2021, and August 07, 2021. The survey targeted all EQAS registered diagnostic laboratories located in India. RESULTS: The survey reached out to 1182 participants, out of which 721 (61%) laboratories completed the questionnaire. During pre-COVID times, only 39% (282/721) of the laboratories had an RT-PCR facility. Among these 721 labs, 514 used open system RT-PCR assay, 217 labs used Truenat assay, 188 labs used GeneXpert assay, 31 used Abbott ID Now and 350 labs performed rapid antigen tests. During the pandemic, 55.3% got NABL accreditation and 7.4% were in the process of applying for COVID-19 molecular testing. In this, 80.7% of the laboratories participated in the ICMR - COVID quality control assessment. It was estimated that 41.4% of the laboratory professionals were re-using N95 masks. Overall, the infection prevention and control practices varied across each laboratory and hospital. CONCLUSION: These survey findings helped us to understand the strength and efficiency of laboratories in India in setting up new assays during a crisis time. Based on our findings, we propose to connect this network in a sustained manner to efficiently utilize the existing platforms to adapt to future pandemics.

Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement.

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.

Stenotrophomonas isolates in a tertiary care centre in South India.

PURPOSE: Stenotrophomonas maltophilia is an emerging multi-drug resistant pathogen increasingly isolated in India. This study aimed to identify patients from whom Stenotrophomonas maltophilia had been isolated and assess predictors of mortality in this population. METHODS: This was a retrospective cohort study of hospitalized patients with a positive culture for S. maltophilia over a 3-year period. Clinical details and laboratory results were assessed from hospital records. Bivariate and multivariate analysis was used to identify risk factors for mortality. RESULTS: One hundred and nineteen patients (mean age 48.6 years) were included in the study. Of these, 111 patients were hospitalized for at least 48 â€‹hours prior to culture and 98 were admitted in the intensive care unit. Bivariate analysis revealed multiple associations with mortality, including a background of renal, cardiac, autoimmune disease, recent carbapenam use and COVID-19 infection and increasing ventilatory requirement, lower PaO2/FiO2 (P/F) ratio, vasopressor use, thrombocytopenia, and hypoalbuminemia at the time of positive isolate. Multivariate analysis showed that autoimmune disease [OR 27.38; 95% CI (1.39-540)], a P/F ratio of less than 300 [OR 7.58; 95% CI (1.52-37.9)], vasopressor requirement [OR 39.50; 95% CI (5.49-284)] and thrombocytopenia [OR 11.5; 95% CI (2.04-65.0)] were statistically significantly associated with increased mortality, while recent surgery and receipt of antibiotics [OR 0.16; 95% CI (0.03-0.8)] targeted against S. maltophilia were associated with decreased mortality. CONCLUSION: Stenotrophomonas maltophilia is primarily isolated in patients in the intensive care unit. In our study the need for vasopressors, autoimmune disease, lower P/F ratios and thrombocytopenia were associated with higher mortality. The association of targeted antibiotics with reduced mortality suggests that the pathogenic role of S. maltophilia should not be underestimated. This finding needs to be confirmed with larger, prospective studies.

Relevance of immune response and vaccination strategies of SARS-CoV-2 in the phase of viral red queen dynamics.

BACKGROUND: Following a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines. OBJECTIVES: The purpose of this article is to provide an additional explanation in the context of the evolutionary trajectory of SARS-CoV-2 variants in India, the vaccine-induced immune response to the variants of concern (VOC), and various vaccine deployment strategies to rapidly increase population immunity. CONTENT: Phylogenetic analysis of SARS-CoV-2 isolates circulating in India suggests the emergence and spread of B.1.617 variant. The immunogenicity of currently approved vaccines indicates that the majority of vaccines elicit an antibody response and some level of protection. According to current data, vaccines in the pre-fusion configuration (2p substitution) have an advantage in terms of nAb titer, but the duration of vaccine-induced immunity, as well as the role of T cells and memory B cells in protection, remain unknown. Since vaccine efficacy on virus variants is one of the major factors to be considered for achieving herd immunity, existing vaccines need to be improved or effective next-generation vaccines should be developed to cover the new variants of the virus.

Evolutionary Tracking of SARS-CoV-2 Genetic Variants Highlights an Intricate Balance of Stabilizing and Destabilizing Mutations.

The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage-defining mutations were analyzed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X), and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore leading to well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount in the coming months, the task of mapping viral mutations and recording their impact on key viral proteins should be crucial to preemptively catch any escape mechanism for which SARS-CoV-2 may evolve. IMPORTANCE Since its initial isolation in Wuhan, China, large numbers of SARS-CoV-2 genome sequences have been shared in publicly accessible repositories, thus enabling scientists to do detailed evolutionary analysis. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed the phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast-expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage-defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines that have recently been approved or are in development. In this vein, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.

Secondary Infections in Hospitalized COVID-19 Patients: Indian Experience.

PURPOSE: Critically ill coronavirus disease 2019 (COVID-19) patients need hospitalization which increases their risk of acquiring secondary bacterial and fungal infections. The practice of empiric antimicrobial prescription, due to limited diagnostic capabilities of many hospitals, has the potential to escalate an already worrisome antimicrobial resistance (AMR) situation in India. This study reports the prevalence and profiles of secondary infections (SIs) and clinical outcomes in hospitalized COVID-19 patients in India. PATIENTS AND METHODS: A retrospective study of secondary infections in patients admitted in intensive care units (ICUs) and wards of ten hospitals of the Indian Council of Medical Research (ICMR) AMR surveillance network, between June and August 2020, was undertaken. The demographic data, time of infection after admission, microbiological and antimicrobial resistance data of secondary infections, and clinical outcome data of the admitted COVID-19 patients were collated. RESULTS: Out of 17,534 admitted patients, 3.6% of patients developed secondary bacterial or fungal infections. The mortality among patients who developed secondary infections was 56.7% against an overall mortality of 10.6% in total admitted COVID-19 patients. Gram-negative bacteria were isolated from 78% of patients. Klebsiella pneumoniae (29%) was the predominant pathogen, followed by Acinetobacter baumannii (21%). Thirty-five percent of patients reported polymicrobial infections, including fungal infections. High levels of carbapenem resistance was seen in A. baumannii (92.6%) followed by K. pneumoniae (72.8%). CONCLUSION: Predominance of Gram-negative pathogens in COVID-19 patients coupled with high rates of resistance to higher generation antimicrobials is an alarming finding. A high rate of mortality in patients with secondary infections warrants extra caution to improve the infection control practices and practice of antimicrobial stewardship interventions not only to save patient lives but also prevent selection of drug-resistant infections, to which the current situation is very conducive.

Novel cyclohexanone compound as a potential ligand against SARS-CoV-2 main-protease.

No commercially available drug candidate has yet been devised which is unique to and not repurposed against SARS-CoV-2 and has high efficacy or safe toxicity profile or both. Taking curcumin as a reference compound, we identified a new commercially available cyclohexanone compound, ZINC07333416 with binding energy (-8.72 kcal/mol) better than that of popularly devised anti-Covid-19 drugs like viral protease inhibitor Lopinavir, nucleoside analogue Remdesivir and the repurposed drug hydroxychloroquine when targeted to the active-site of SARS-CoV-2 Main protease (Mpro) through docking studies. The ligand ZINC07333416 exhibits crucial interactions with major active site residues of SARS-CoV-2 Mpro viz. Cys145 and His41 involving in the protease activity; as well as GLU-166 and ASN-142 which plays the pivotal role in the protein-dimerization. The protein-ligand stable interaction was further confirmed with molecular dynamics simulation (MDS) studies. Based on virtual assessment, ZINC07333416 also have significant values in terms of medicinal chemistry, pharmacokinetics, synthetic accessibility and anti-viral activity that encourage its experimental applications against COVID-19.

Genomic evolution of severe acute respiratory syndrome Coronavirus 2 in India and vaccine impact.

Recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent containment procedures have impacted the world as never seen before. Therefore, there is considerable curiosity about the genome evolution related to the origin, transmission and vaccine impact of this virus. We have analysed genome sequences of SARS-CoV-2 isolated from Indian patients to gain an in-depth understanding of genomic evolution and transmission in India. Phylogenetic analysis and mutation profiling revealed major lineages being evolved by characteristic mutations. As the mutation frequency in spike protein is comparatively lesser, the candidate vaccines expected to have wide coverage worldwide including India.