Advances in computational frameworks in the fight against TB: The way forward.

Around 1.6 million people lost their life to Tuberculosis in 2021 according to WHO estimates. Although an intensive treatment plan exists against the causal agent, Mycobacterium Tuberculosis, evolution of multi-drug resistant strains of the pathogen puts a large number of global populations at risk. Vaccine which can induce long-term protection is still in the making with many candidates currently in different phases of clinical trials. The COVID-19 pandemic has further aggravated the adversities by affecting early TB diagnosis and treatment. Yet, WHO remains adamant on its "End TB" strategy and aims to substantially reduce TB incidence and deaths by the year 2035. Such an ambitious goal would require a multi-sectoral approach which would greatly benefit from the latest computational advancements. To highlight the progress of these tools against TB, through this review, we summarize recent studies which have used advanced computational tools and algorithms for-early TB diagnosis, anti-mycobacterium drug discovery and in the designing of the next-generation of TB vaccines. At the end, we give an insight on other computational tools and Machine Learning approaches which have successfully been applied in biomedical research and discuss their prospects and applications against TB.

A parallel and silent emerging pandemic: Antimicrobial resistance (AMR) amid COVID-19 pandemic.

World is in the middle of the pandemic (COVID-19), caused by SARS-COV-2 virus, which is a significant global health crisis after Spanish influenza in the beginning of 20th century. Progressive drastic steps have been enforced to minimize the transmission of the disease. Likewise, in the current years, antimicrobial resistance (AMR) has been referred as one of the potential perils to the global economy and health; however, it is now veiled under the present pandemic. During the current pandemic, AMR to available frontline antibiotics may prove fatal and life threatening to bacterial and fungal infections during routine procedures like elective surgery, C-sections, etc. Currently, a swift elevation in multidrug-resistant organisms (MDROs), like carbapenem-resistant New Delhi metallo-ß-lactamase (NDM)-producing Acinetobacter baumannii, Enterobacterales, extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), multi-triazole-resistant Aspergillus fumigatus and pan-echinocandin-resistant Candida glabrata has been seen. Thereupon, the global outbreak of COVID-19 also offers some important ramification for developing antimicrobial drug resistance. This article aims to highlights episodes and aspects of AMR prevalence, impact of management and mismanagement of COVID-19 crisis, hospital settings, community, environment, and travel on the AMR during the current pandemic.

Evidence of Antimicrobial Resistance in Bats and Its Planetary Health Impact for Surveillance of Zoonotic Spillover Events: A Scoping Review.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine.

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new ß-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance.

Impact Of Different Antimicrobial Stewardship Strategies For Reducing Antimicrobial Resistance And Antimicrobial Uses - A Systematic Literature Review

Antimicrobial resistance (AMR) is a serious global warning to social wellbeing. Antimicrobial stewardship Intervention is evident to provide a good effect on AMR. Antimicrobial Stewardship Programs (ASPs) have been established to minimize the usage of antibiotics, antibiotic resistance, and healthcare expenditure. Prospective audits with feedback, formulary restriction/preauthorization along with many other supportive elements are found effective techniques of antimicrobial stewardship programme. However, the proportional effect of different techniques is unclear. This ASP strategies utilization is compared in hospital setting and adult hospital units implementing ASP have provided much evidence demonstrating their value. This study includes the effectiveness of various explicit AMS strategies, measuring the outcome in various clinical setups such as reducing antibiotic resistance and antibiotic use.The death toll from COVID-19 is the highest of any other respiratory virus outbreak but Multiple Drug Resistant (MDR) and deadly resistant pathogens outbreaks could be at any point of time.Even in this present antibiotic era required primarily require combat it andstrong vigilance is also desired. The primary objective of this study is to enhance patient care and to lower medical expenses, but the ultimate objective is to safeguard already available and newly developed antibiotics against the threat of AMR. It has been noted that Prospective Audit and Feedback (PAF) intervention is one of the most often employed strategies among all other interventions of AMS. Although this is time-taking, it is accepted by physicians for more than formulary restrictions and pre-authorization procedures. There have been several digital initiatives to support antimicrobial stewardship (AMS), while they have been concentrated on individual interventions.Pre-authorization or recommended formulary limitation was found in 31% of all trials. 20% of these studies implemented this intervention independently, and many trials were also undertaken in conjunction with other interventions mostly in addition to training and education. Using the available pool information, we observed in various strategies a significant reduction in antimicrobial resistance and a reduced Days of Therapy (DOT)/Length of Treatment (LOT) ratio. Formulary restriction limited the use of broad-spectrum antibiotics without any major causality. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Paving the way for precise diagnostics of antimicrobial resistant bacteria.

The antimicrobial resistance (AMR) crisis from bacterial pathogens is frequently emerging and rapidly disseminated during the sustained antimicrobial exposure in human-dominated communities, posing a compelling threat as one of the biggest challenges in humans. The frequent incidences of some common but untreatable infections unfold the public health catastrophe that antimicrobial-resistant pathogens have outpaced the available countermeasures, now explicitly amplified during the COVID-19 pandemic. Nowadays, biotechnology and machine learning advancements help create more fundamental knowledge of distinct spatiotemporal dynamics in AMR bacterial adaptation and evolutionary processes. Integrated with reliable diagnostic tools and powerful analytic approaches, a collaborative and systematic surveillance platform with high accuracy and predictability should be established and implemented, which is not just for an effective controlling strategy on AMR but also for protecting the longevity of valuable antimicrobials currently and in the future.

Review and Analysis of National Monitoring Systems for Antimicrobial Resistance in Animal Bacterial Pathogens in Europe: A Basis for the Development of the European Antimicrobial Resistance Surveillance Network in Veterinary Medicine (EARS-Vet).

The monitoring of antimicrobial resistance (AMR) in bacterial pathogens of animals is not currently coordinated at European level. To fill this gap, experts of the European Union Joint Action on Antimicrobial Resistance and Healthcare Associated Infections (EU-JAMRAI) recommended building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet). In this study, we (i) identified national monitoring systems for AMR in bacterial pathogens of animals (both companion and food-producing) among 27 countries affiliated to EU-JAMRAI, (ii) described their structures and operations, and (iii) analyzed their respective strengths, weaknesses, opportunities and threats (SWOT). Twelve countries reported having at least one national monitoring system in place, representing an opportunity to launch EARS-Vet, but highlighting important gaps in AMR data generation in Europe. In total, 15 national monitoring systems from 11 countries were described and analyzed. They displayed diverse structures and operations, but most of them shared common weaknesses (e.g., data management and representativeness) and common threats (e.g., economic vulnerability and data access), which could be addressed collectively under EARS-Vet. This work generated useful information to countries planning to build or improve their system, by learning from others' experience. It also enabled to advance on a pragmatic harmonization strategy: EARS-Vet shall follow the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards, collect quantitative data and interpret AMR data using epidemiological cut-off values.

Investigation of Antibiotic Resistome in Hospital Wastewater during the COVID-19 Pandemic: Is the Initial Phase of the Pandemic Contributing to Antimicrobial Resistance?

Since the COVID-19 pandemic started, there has been much speculation about how COVID-19 and antimicrobial resistance may be interconnected. In this study, untreated wastewater was sampled from Hospital A designated to treat COVID-19 patients during the first wave of the COVID-19 pandemic alongside Hospital B that did not receive any COVID-19 patients. Metagenomics was used to determine the relative abundance and mobile potential of antibiotic resistant genes (ARGs), prior to determining the correlation of ARGs with time/incidence of COVID-19. Our findings showed that ARGs resistant to macrolides, sulfonamides, and tetracyclines were positively correlated with time in Hospital A but not in Hospital B. Likewise, minor extended spectrum beta-lactamases (ESBLs) and carbapenemases of classes B and D were positively correlated with time, suggesting the selection of rare and/or carbapenem-resistant genes in Hospital A. Non-carbapenemase blaVEB also positively correlated with both time and intI1 and was copresent with other ARGs including carbapenem-resistant genes in 6 metagenome-assembled genomes (MAGs). This study highlighted concerns related to the dissemination of antimicrobial resistance (AMR) during the COVID-19 pandemic that may arise from antibiotic use and untreated hospital wastewater.

Antibiotic prescription practices amongst veterinarians in Nigeria.

The high rate of antibiotic resistance constitutes a global threat to the continuous use of these drugs, because of increasing treatment failures. The aim of this study was to survey antibiotic prescription practices of veterinarians and the possible contribution to antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) in Nigeria during the COVID era. This was a cross-sectional study that used a 33-question survey questionnaire administered to registered veterinarians in Nigeria. The study was both online survey and hard copy administered during the annual meeting of the veterinarians from July to October 2021. Descriptive statistics, bivariate analysis using Chi-square test were also done to analyze the results, while a two-tailed P-value of <0.05 at 95% confidence level was considered statistically significant. IBM SPSS Version 26 was used to analyze the data. A total of 172 respondents completed the online and hard copy questionnaire. Majority of the respondents engaged majorly in mixed veterinary practice (72.1%). A total of 53.5% were aware of the country's policy concerning antibiotic prescription, while majority (64.5%) do not do culture and sensitivity before antibiotic prescription. Majority (34.3%) felt that the risk of potential adverse drug reaction could affect their decision when choosing to prescribe an antibiotic to the owner. Majority (51.2%) felt that some antibiotics were over prescribed, while 26.7% opined that all antibiotics were appropriately prescribed. To improve antibiotic use and practice amongst veterinarians in Nigeria, dependence on laboratory services for antibiotic prescription, enforcement of national guidelines and monitoring of antibiotic prescription amongst the veterinarians is essential to curb over-prescription and strengthen antimicrobial stewardship.

Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non-tubercular mycobacterial infections.

The COVID-19 pandemic has set back progress made on antimicrobial resistance (AMR). Without urgent re-focus, we risk slowing down drug discovery and providing treatment for drug resistant Mycobacterium tuberculosis. Unique in its immune evasion, dormancy and resuscitation, the causal pathogens of tuberculosis (TB) have demonstrated resistance to antibiotics with efflux pumps and the ability to form biofilms. Repurposing drugs is a prospective avenue for finding new anti-TB drugs. There are many advantages to discovering novel targets of an existing drug, as the pharmacokinetic and pharmacodynamic properties have already been established, they are cost-efficient and can be commercially accelerated for the new development. One such group of drugs are non-steroidal anti-inflammatory drugs (NSAIDs) that are originally known for their ability to supress the host proinflammatory responses. In addition to their anti-inflammatory properties, some NSAIDs have been discovered to have antimicrobial modes of action. Of particular interest is Carprofen, identified to inhibit the efflux mechanism and disrupt biofilm formation in mycobacteria. Due to the complexities of host-pathogens interactions in the lung microbiome, inflammatory responses must carefully be controlled alongside the in vivo actions of the prospective anti-infectives. This critical review explores the potential dual role of a selection of NSAIDs, as an anti-inflammatory and anti-tubercular adjunct to reverse the tide of antimicrobial resistance in existing treatments.

Consumption Trends of Antibiotics in Brazil During the COVID-19 Pandemic.

Background: In 2019, a new type of coronavirus emerged and spread to the rest of the world. Numerous drugs were identified as possible treatments. Among the candidates for possible treatment was azithromycin alone or in combination with other drugs. As a result, many clinicians in Brazil have prescribed azithromycin in an attempt to combat or minimize the effects of COVID19. Aim: This study analyzed the sales data of the main antibiotics prescribed in Brazil to verify the change in consumption trends of these drugs during the COVID-19 pandemic. Methods: This is an interrupted time series that analyzed antimicrobial sales data between January 2014 and July 2021, publicly accessible information obtained from the Brazilian government's website. Monthly means of "defined daily doses of DDDs" (DDDs per 1,000 inhabitants per day) of antibiotics were compared by analysis of variance, followed by the Dunnett Multiple Comparisons Test. Monthly trend changes in antibiotic use were verified using Joinpoint regression. Results: Amoxicillin (31.97%), azithromycin (18.33%), and cefalexin (16.61%) were the most sold antibiotics in Brazil during the evaluation period. Azithromycin consumption rose from 1.40 DDDs in February 2020 to 3.53 DDDs in July 2020. Azithromycin sales showed a significant increase in the pandemic period [Monthly Percent Change (MPC) 5.83%, 95% 1.80; 10.00], whereas there was a fall in amoxicillin sales (MPC -9.00%, 95% CI -14.70; -2.90) and cefalexin [MPC-2.70%, 95% (CI -6.30; -1.10)] in this same period. Conclusion: The COVID-19 pandemic changed the pattern of antibiotic consumption in Brazil, with a decrease in the use of amoxicillin and cefalexin and an increase in the consumption of azithromycin.

Phage therapeutics: from promises to practices and prospectives.

The rise in multi-drug resistant bacteria and the inability to develop novel antibacterial agents limits our arsenal against infectious diseases. Antibiotic resistance is a global issue requiring an immediate solution, including the development of new antibiotic molecules and other alternative modes of therapy. This article highlights the mechanism of bacteriophage treatment that makes it a real solution for multidrug-resistant infectious diseases. Several case reports identified phage therapy as a potential solution to the emerging challenge of multi-drug resistance. Bacteriophages, unlike antibiotics, have special features, such as host specificity and do not impact other commensals. A new outlook has also arisen with recent advancements in the understanding of phage immunobiology, where phages are repurposed against both bacterial and viral infections. Thus, the potential possibility of phages in COVID-19 patients with secondary bacterial infections has been briefly elucidated. However, significant obstacles that need to be addressed are to design better clinical studies that may contribute to the widespread use of bacteriophage therapy against multi-drug resistant pathogens. In conclusion, antibacterial agents can be used with bacteriophages, i.e. bacteriophage-antibiotic combination therapy, or they can be administered alone in cases when antibiotics are ineffective.Key points• AMR, a consequence of antibiotic generated menace globally, has led to the resurgence of phage therapy as an effective and sustainable solution without any side effects and high specificity against refractory MDR bacterial infections.• Bacteriophages have fewer adverse reactions and can thus be used as monotherapy as well as in conjunction with antibiotics.• In the context of the COVID-19 pandemic, phage therapy may be a viable option.

Outcomes and Future Prospect of Japan's National Action Plan on Antimicrobial Resistance (2016-2020).

The threat from antimicrobial resistance (AMR) continues to grow. Japan's National Action Plan on Antimicrobial Resistance, which was formulated in 2016 and targets six areas, has already had a major impact on the countermeasures implemented against AMR. Particular advances have been made in AMR-related surveillance, and we now know the situation regarding antimicrobial use and antimicrobial-resistant bacteria in the country. Educational and awareness-raising activities for medical professionals and the general public have been actively implemented and seem to have contributed to a gradual move toward an appropriate use of antimicrobials. However, there is still insufficient understanding of the issue among the general public. Determining how to use surveillance results and implementing further awareness-raising activities are crucial to address this. Tasks for the future include both raising awareness and the promotion of AMR research and development and international cooperation. The government's next Action Plan, which will detail future countermeasures against AMR based on the outcomes of and tasks identified in the current Action Plan, has been delayed due to the COVID-19 pandemic and is urgently awaited.

Antimicrobial resistance and COVID-19 syndemic: Impact on public health.

The COVID -19 pandemic has had a catastrophic impact on the global economy and the healthcare industry. Unfortunately, the scientific community still hasn't discovered a definite cure for this virus. Also, owing to the unscrupulous use of antibiotics in wake of the current situation, another ongoing pandemic of antimicrobial resistance (AMR) has been entirely eclipsed. However, increased compliance to infection control measures like hand hygiene (both at hospital and community level), and restricted travel might be favorable. It is evident that the AMR strategies will be impacted disproportionately varying with the respective policies followed by the countries and hospitals to deal with the pandemic. The vaccination drive initiated globally has provided a glimmer of hope. In this article, the possible reciprocity between the two contemporaneous pandemics has been addressed. The world needs to be vigilant to punctuate the symphony between these lethal threats to global health. The restraint to combat against AMR will be boosted as our discernment of the problem also changes with the epidemiological interplay becoming more apparent in near future.

Antimicrobial resistance in low- and middle-income countries: current status and future directions.

INTRODUCTION: Rising rates of antimicrobial resistance (AMR) globally continue to pose agrave threat to human health. Low- and middle-income countries (LMICs) are disproportionately affected, partly due to the high burden of communicable diseases. AREAS COVERED: We reviewed current trends in AMR in LMICs and examined the forces driving AMR in those regions. The state of interventions being undertaken to curb AMR across the developing world are discussed, and the impact of the current COVID-19 pandemic on those efforts is explored. EXPERT OPINION: The dynamics that drive AMR in LMICs are inseparable from the political, economic, socio-cultural, and environmental forces that shape these nations. The COVID-19 pandemic has further exacerbated underlying factors that increase AMR. Some progress is being made in implementing surveillance measures in LMICs, but implementation of concrete measures to meaningfully impact AMR rates must address the underlying structural issues that generate and promote AMR. This, in turn, will require large infrastructural investments and significant political will.

Antibiotics or No Antibiotics, That Is the Question: An Update on Efficient and Effective Use of Antibiotics in Dental Practice.

The antimicrobial resistance (AMR) phenomenon is an emerging global problem and is induced by overuse and misuse of antibiotics in medical practice. In total, 10% of antibiotic prescriptions are from dentists, usually to manage oro-dental pains and avoid postsurgical complications. Recent research and clinical evaluations highlight new therapeutical approaches with a reduction in dosages and number of antibiotic prescriptions and recommend focusing on an accurate diagnosis and improvement of oral health before dental treatments and in patients' daily lives. In this article, the most common clinical and operative situations in dental practice, such as endodontics, management of acute alveolar abscesses, extractive oral surgery, parodontology and implantology, are recognized and summarized, suggesting possible guidelines to reduce antibiotic prescription and consumption, maintaining high success rates and low complications rates. Additionally, the categories of patients requiring antibiotic administration for pre-existing conditions are recapitulated. To reduce AMR threat, it is important to establish protocols for treatment with antibiotics, to be used only in specific situations. Recent reviews demonstrate that, in dentistry, it is possible to minimize the use of antibiotics, thoroughly assessing patient's conditions and type of intervention, thus improving their efficacy and reducing the adverse effects and enhancing the modern concept of personalized medicine.