Combat Antimicrobial Resistance Research Articles

Use of Antibiotics in Tertiary Care Hospitals of Meteropolitan City Islamabad

Background: The global threat of antimicrobial resistance (AMR) necessitates a deeper understanding of antibiotic use patterns within healthcare settings. Previous studies have indicated variable prevalence rates of antibiotic use across different regions, underscoring the need for localized data to inform antimicrobial stewardship initiatives. Objective: This study aimed to determine the prevalence and patterns of antibiotic use in two tertiary care hospitals in Islamabad, Pakistan, to identify opportunities for improving antibiotic prescribing practices and inform the development of targeted antimicrobial stewardship programs. Methods: A descriptive cross-sectional study was conducted through a point prevalence survey in two tertiary care hospitals over three months, from January to March 2022. Data on antibiotic use were collected from patient files, employing a two-stage random sampling method for both hospital and ward selection. The survey assessed the prevalence of antibiotic use, categorized according to the WHO Aware classification (Access, Watch, Reserve, Not Recommended), and analyzed the indications, dosages, routes of administration, and compliance with prescribing guidelines. Statistical analysis was performed using SPSS version 25. Results: The prevalence of antibiotic use among the surveyed population (n=255) was 78%, with a higher prevalence observed in neonatal (100%) and pediatric (100%) departments compared to the adult department (74.66%). Ceftriaxone (27.06%), meropenem (10.98%), and moxifloxacin (9.41%) were the most frequently used antibiotics. The majority of antibiotics prescribed belonged to the 'Watch' group (70%), with 17.6% in the 'Access' group, and 11.6% in the 'Reserve' group. Prophylactic use accounted for 62.9% of all antibiotics prescribed. The study also noted a lack of compliance with prescribing guidelines and a scarcity of culture sensitivity testing. Conclusion: The study reveals a high prevalence of antibiotic use in tertiary care hospitals in Islamabad, with a significant reliance on 'Watch' and 'Reserve' group antibiotics. These findings highlight the critical need for the implementation of antimicrobial stewardship programs and national action plans to promote rational antibiotic use and combat AMR. Background: Antimicrobial resistance is one of the biggest global healthcare concerns as per the World Health Organization. It has impacted high, mid, and low-income countries with mid and low-income countries taking higher tools. Lack of data on the pattern of antibiotic use will lead to difficulty in the implementation of antimicrobial stewardship programs at the facility level. The purpose of this study is to determine the point prevalence of antibiotic use among hospitals in Islamabad and to determine the pattern of the WHO-aware group antibiotics in paediatrics. Methodology: The point prevalence survey methodology was used to collect random sample of 255 in two tertiary care hospitals in Islamabad in three months. All the inpatients admitted on the day of PPS were included in the survey. Data was collected through questionnaires from patients' files and analysed in SPSS Results: Total of two tertiary care hospitals with 375 beds were assessed in this study. Out of these, 255 patients 78.03% patients were receiving at least one antibiotic. Out of 255 antibiotics were used in which 32.1% were prescribed for medical prophylaxis, while 29.8% of the antibiotics prescribed were for surgical prophylaxis. Ceftriaxone and Maropenm accounted for 27% & 10.98% of total antibiotic prescribed respectively. The result also indicates high use of watch group antibiotics in children under 5 years of age. The majority of antibiotics were used as Empirical therapy.  There was no specific institutional guideline for the use of antibiotics, while in 95% of cases there was no reason notes available for the use of antibiotics. Conclusion: We concluded that use of antibiotics in the two hospitals is very high. It has been also seen that there was no proper guideline for the use of antibiotics in hospitals with poor quality documentation. It is an immediate need for the implementation of a national action plan on the antimicrobials resistance and the development of an antibiotics stewardship program at each facility level to protect the resistance to the antibiotic.

Unraveling the epidemiology of urinary tract infections in neonates: Perspective from a Brazilian NICU

BackgroundUrinary tract infections (UTIs) can lead to neonatal complications like sepsis, worsened by empirical treatment, contributing to antimicrobial resistance (AMR). This study examined the incidence, etiology, risk factors, and antimicrobial susceptibility of uropathogens in a Neonatal Intensive Care Unit (NICU) in Brazil. MethodsMedical records of neonates hospitalized in the NICU from January 2015 to June 2022 were retrospectively analyzed through the National Healthcare Safety Network system. ResultsAmong 1,474 neonates, 3.9% developed UTI, with an alarming 24-fold increase in incidence from 2015 to 2021. Genitourinary complications (odds ratio = 4.8) were a major risk factor. Of the 71 uropathogens, 74.6% were Gram-negative bacteria (GNB), 21.2% Gram-positive bacteria (GPB), and 4.2% Candida albicans. AMR was notable, with 13.3% of GPB and 20.7% of GNB exhibiting multidrug-resistant (MDR), while 6.6% of GPB and 1.9% of GNB showed extensive drug-resistant (XDR). UTI was associated with prolonged hospitalization (16-59 days). In 57 neonates with UTI, 40.3% had bloodstream infections, elevating the risk of death (odds ratio = 1.8). ConclusionsThe study underscores the urgency of implementing infection prevention and control measures in the NICU to curb rising UTI incidences, combat AMR, and mitigate severe complications in critically ill neonates.

Functional antagonism and insights into the biosynthetic potential of human gut-derived microbes

The specialised small molecules encoded by commensal microbes mediate distinct functional interactions. However, there is a landscape of antagonistic interactions mediated by specialised strains and their small molecules. Herein, the antagonistic landscape within a collection of 330 human gut-derived commensal microbial strains was elucidated to evaluate antimicrobial interactions as a defensive contributor, and gain new insights into structure-related functions. The potential antagonistic gut-derived strains displayed strain-specific selective inhibition. This is in contrast to common antimicrobial drugs, which typically wipe out a broad range of species and are usually found in environmental microbes. Genome sequencing of representative gut strains revealed the presence of significant biosynthetic gene clusters (BGCs) encoding compound families that contribute to antagonistic activities, and are important in host defence and maintaining gut homeostasis. Subsets of these BGCs were abundant in metagenomic sequencing data from healthy individuals. Furthermore, the cell culture secretome of these strains revealed potential biomarkers linked to hallmark pathways. These microorganisms have biosynthetic novelty and are a source of biologically significant natural products. Such natural products are essential in the development of new antimicrobial agents to reduce the usage of broad-spectrum antibiotics and combat antimicrobial resistance.

One Health Paradigm: An Inclusive Approach to Tackling Global Health Complexities

The One Health paradigm, a holistic approach encompassing human, animal, and environmental health, has gained significant attention in addressing the complexities of contemporary global health challenges. This extensive review explores the foundational principles, historical evolution, and diverse applications of One Health. By promoting interdisciplinary collaboration and recognizing the interdependence of health domains, One Health emerges as a potent strategy to counter emerging diseases, combat antimicrobial resistance, and address multifaceted health threats.

Uncovering doctors' perceived barriers and facilitators of antibiotic prescribing behaviours: a qualitative study using the theoretical domains framework.

Uncovering the barriers and facilitators of antibiotic prescribing is crucial in order to develop effective strategies for promoting responsible and evidence-based antibiotic use, thereby combating antibiotic resistance and enhancing patient care. This qualitative study, informed by the Theoretical Domains Framework (TDF) - specifically designed to understand and analyze the factors that influence human behavior, with a focus on identifying barriers and facilitators to behavior change, was aimed to explore the determinants (barriers and facilitators) of antibiotic prescribing behaviors from the perspective of doctors. Semi-structured interviews were conducted with healthcare professionals, and data analysis followed a theory-driven approach guided by the TDF. The analysis identified eight TDF domains influencing antibiotic prescribing, including memory, attention, and decision processes; knowledge; skills; belief about capabilities; goals; belief about consequences; emotions; and environmental context and resources. These domains were clustered into three overarching themes according to a bottom-up logic: the decision-making prescribing process itself, intrinsic factors related to the physician, and extrinsic factors influencing the decision. This research provides a comprehensive understanding of the complex interactions between these determinants in antibiotic prescribing. The evidence gained from the study valuable information for developing targeted interventions to improve antibiotic prescribing practices and combat antimicrobial resistance considering psychosocial and environmental variables impacting on antibiotic prescription decision making.

Bacterial Profile, Antimicrobial Susceptibility Patterns, and Associated Factors of Puerperal Sepsis in Asella, Central Ethiopia: A Cross-sectional Study

Sepsis, caused by various bacterial pathogens, is a significant contributor to maternal mortality worldwide. In many developing countries, including Ethiopia, empirical or syndromic treatment is commonly employed for puerperal sepsis, which may promote antimicrobial resistance (AMR). We conducted a cross-sectional study to investigate bacterial pathogens, their antimicrobial susceptibility patterns, and associated factors among women with suspected puerperal sepsis attending Asella Referral and Teaching Hospital from September 2020 to August 2021. A total of 174 participants were enrolled, and the sociodemographic and obstetric data were collected using a pretested structured questionnaire and checklist, respectively. Blood samples (approximately 20 ml) were collected from all study participants and incubated in BacT/ALERT® 3D automated blood culture system. In addition, endocervical swabs were collected in Amies transport media. Bacterial isolation and identification were performed following standard bacteriological methods. Antimicrobial susceptibility profiles of bacterial isolates were determined using the disc diffusion method. Data were entered into EpiData version 4.6 and analyzed using SPSS version 25.0. The overall positivity rate of bacterial isolates among puerperal sepsis-suspected women was 48.9%. Among these, 87.1% of the isolates were Gram-negative bacteria. The most common isolates were Escherichia coli (54.1%), followed by Klebsiella spp. (23.5%) and Staphylococci aureus (10.6%). High resistance rates were observed in E. coli to piperacillin (87%), in Klebsiella spp. to aztreonam (65%) and ceftriaxone (65%), and in S. aureus to trimethoprim-sulfamethoxazole (66.6%). Multidrug-resistant bacterial pathogens accounted for 81.2% of the isolates in this study. Multivariate regression analysis did not reveal any statistically significant association between the presence of bacteria and the sociodemographic and obstetrics factors. Our findings emphasize the urgency of strengthening microbiology services to optimize patient management and combat AMR in puerperal sepsis.

Antibiotic consumption and antimicrobial resistance in the SARS-CoV-2 pandemic: A single-center experience.

Introduction: Antimicrobial resistance and the rapid spread of multiresistant bacteria represent one of the main public health problem in limited resources countries. This issue is significantly worsening since the COVID-19 pandemic due to the unreasonably increased antibiotics prescription to patients with confirmed SARS-CoV-2 infection. The aim of this study was to examine whether COVID-19 pandemic (2020, 2021) was associated with increased antibiotic consumption in inpatient and outpatient settings in the middle size urban region (Republic of Srpska/Bosnia and Herzegovina) in comparison to period before the pandemic (2019). Additionally, we aimed to determine antimicrobial resistance and the presence of multiresistant bacteria in the regional hospital ("Saint Apostol Luka" Hospital Doboj) in 2021. Methodology: The consumption of antibiotics in inpatient was calculated as Defined Daily Dose per one hundred of patient-days. The consumption of antibiotics in outpatient was calculated as Defined Daily Dose per thousand inhabitants per day. Resistance of bacteria to antibiotics is expressed as a rates and density for each observed antibiotic. The rate of resistance was calculated as a percentage in relation to the total number of isolates of individual bacteria. The density of resistance of isolated bacteria against a specific antibiotic was expressed as the number of resistant pathogens/1000 patient days. Results: Antibiotic consumption in hospital setting registered during 2019, 2020 and 2021 was as follows: carbapenems (meropenem: 0.28; 1.91; 2.33 DDD/100 patient-days, respectively), glycopeptides (vancomycin: 0.14; 1.09, 1.54 DDD/100 patient-days, respectively), cephalosporins (ceftriaxone: 6.69; 14.7; 14.0 DDD/100 patient-days, respectively) and polymyxins (colistin: 0.04; 0.25; 0.35 DDD/100 bed-days, respectively). Consumption of azithromycin increased drastically in 2020, and dropped significantly in 2021 (0.48; 5.61; 0.93 DDD/100 patient-days). In outpatient setting, an increase in the consumption of oral forms of azithromycin, levofloxacin and cefixime, as well as parenteral forms of amoxicillin-clavulanic acid, ciprofloxacin and ceftriaxone, was recorded. In 2021, antimicrobial resistance to reserve antibiotics in hospital setting was as follows: Acinetobacter baumanii to meropenem 66.0%, Klebsiella spp to cefotaxime 67.14%, Pseudomonas to meropenem 25.7%. Conclusion: Recent COVID-19 pandemic was associated with increased antibiotic consumption in inpatient and outpatient settings, with characteristic change of pattern of azithromycin consumption. Also, high levels of antimicrobial resistance to reserve antibiotics were registered in hospital setting with low prevalence of identified pathogen-directed antimicrobial prescription. Strategies toward combat antimicrobial resistance in the Doboj region are urgently needed.

Advancement of Phage Therapy Approaches in The Battle of Multi-Drug Resistance: A Review

One of the most significant issues faced by humanity today is antibiotic resistance. Drugs are used in such vast amounts for human health, aquatic life, and agricultural animals that harmful bacteria have developed antibiotic resistance to various antibiotics. Further, the usage of antibiotics is increasing because of situations such as increased infections and chronic diseases that need antimicrobial treatment. Since antimicrobial resistance is rising, it is necessary to take action to help reduce and eliminate infectious diseases and ensure animal and human health. Because of this, many attempts are being made to tackle multi-drugresistant bacteria. Among the many advanced techniques that are occurring, the use of phage therapy is one such emerging procedure. The main aim of this prospective review is to identify the various new phage formulations available as a potential therapeutic intervention to combat multidrug resistance among bacteria and the objective is to identify the various reasons associated with the induction of the phenomenon of "multidrug resistance" among different bacteria, focusing on the use of phage therapy, its advantages as well as disadvantages over antibiotics as a possible therapeutic intervention. Various phage formulations, such as phage cocktails with antibiotics, nanoparticles, phage-delivering hydrogels, and many more, are emerging formulations that have successful results in fighting against multi-drug-resistant bacteria. Commercial phage solutions have helped combat antimicrobial resistance in poultry and livestock farms, improving everyone's health worldwide. As a result, this study shall serve as a source of information and understanding of the concerns mentioned above for the entirety of society and every human community. 

Harnessing CRISPR-Cas9 as an anti-mycobacterial system

Rapid emergence of drug resistance has posed new challenges to the treatment of mycobacterial infections. As the pace of development of new drugs is slow, alternate treatment approaches are required. Recently, CRISPR-Cas systems have emerged as potential antimicrobials. These sequence-specific nucleases introduce double strand cuts in the target DNA, which if left unrepaired, prove fatal to the host. For most bacteria, homologous recombination repair (HRR) is the only pathway for repair and survival. Mycobacteria is one of the few bacteria which possesses the non-homologous end joining (NHEJ) system in addition to HRR for double strand break repair. To assess the antimicrobial potential of CRISPR-system, Cas9-induced breaks were introduced in the genome of Mycobacterium smegmatis and the survival was studied. While the single strand breaks were efficiently repaired, the organism was unable to repair the double strand breaks efficiently. In a mixed population of antibiotic-resistant and sensitive mycobacterial cells, selectively targeting a factor that confers hygromycin resistance, turned the entire population sensitive to the drug. Further, we demonstrate that the sequence-specific targeting could also be used for curing plasmids from mycobacterium cells. Considering the growing interest in nucleic acid-based therapy to curtail infections and combat antimicrobial resistance, our data shows that CRISPR-systems hold promise for future use as an antimicrobial against drug-resistant mycobacterial infections.

Community Knowledge and Practices Regarding Antibiotics use Across Five States in Nigeria

The rational use of drugs is mandatory and properly captured by the World Health Organization (WHO). This study was aimed at assessing the knowledge and practices of community members regarding antibiotic use. This was a cross-sectional study conducted across six states in Nigeria. The study included 8,370 respondents drawn from Taraba, Benue State, Enugu State, Nasarawa State, Osun State, and Rivers States. The participants were stratified into such as; community members, in-school and out-of-school youths and patient groups. The study revealed significant gaps in understanding the behaviors related to antibiotics use and antimicrobial resistance. Key findings indicated a lack of awareness about antimicrobials among a substantial proportion of participants, suggesting the need for educational campaigns and awareness. Misconceptions about the uses of antimicrobials were evident, with participants associating them with a range of diseases, sometimes inaccurately. The issue of partial compliance to antibiotic treatment was also note, with participants discontinuing treatments prematurely. Participants indicated some awareness of the concept of antimicrobial resistance, highlighting a potential starting point for education on this topic. The study underscored the role of community pharmacies and patent store owners in antibiotic distribution, often without proper education on safety protocols. This emphasizes the importance of regulatory measures and training for responsible dispensing for proper patient care. To address these issues, recommendations include comprehensive public awareness campaigns, educational initiatives in schools and communities, healthcare provider training, and promoting adherence to treatment guidelines. Multisectoral collaboration, cultural sensitivity, and ongoing research and evaluation are also recommended to address the gaps identified and combat antimicrobial resistance effectively.

Recombinant Helicobacter pylori Vaccine Delivery Vehicle: A Promising Tool to Treat Infections and Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) has become a global public health threat. Experts agree that unless proper actions are taken, the number of deaths due to AMR will increase. Many strategies are being pursued to tackle AMR, one of the most important being the development of efficient vaccines. Similar to other bacterial pathogens, AMR in Helicobacter pylori (Hp) is rising worldwide. Hp infects half of the human population and its prevalence ranges from <10% in developed countries to up to 90% in low-income countries. Currently, there is no vaccine available for Hp. This review provides a brief summary of the use of antibiotic-based treatment for Hp infection and its related AMR problems together with a brief description of the status of vaccine development for Hp. It is mainly dedicated to genetic tools and strategies that can be used to develop an oral recombinant Hp vaccine delivery platform that is (i) completely attenuated, (ii) can survive, synthesize in situ and deliver antigens, DNA vaccines, and adjuvants to antigen-presenting cells at the gastric mucosa, and (iii) possibly activate desired compartments of the gut-associated mucosal immune system. Recombinant Hp vaccine delivery vehicles can be used for therapeutic or prophylactic vaccination for Hp and other microbial pathogens.

Impact of an Antimicrobial Stewardship Intervention on the Appropriateness of Carbapenem Use at a Tertiary Hospital in Malaysia.

Introduction Carbapenems are broad-spectrum antibiotics used to treat infections caused by multidrug-resistant organisms. The inappropriate use of carbapenem results in the development of antimicrobial resistance. The aimof this study was to determine the impact of an antimicrobial stewardship intervention on the appropriateness of carbapenem use. Method The study includes a baseline/pre-intervention audit, an intervention, and a post-intervention study to examine the impact of antimicrobial stewardship activities on carbapenem use. Audit and data collection were carried out by filling up an audit form. The indicator for this study will be the appropriateness of carbapenem use (appropriate, suboptimal, or inappropriate) pre- and post-intervention. Results The overall appropriateness of carbapenem prescription in the medical wards increased from 65% to 83.3% following the implementation of antimicrobial stewardship intervention. The most common indication of carbapenem usage in our study was hospital-acquired pneumonia/ventilator-associated pneumonia. Conclusion Antimicrobial stewardship intervention is effective in improving the appropriateness of carbapenem use. Tailored stewardship programs are required to better control carbapenem use and combat antimicrobial resistance.

Combat antimicrobial resistance emergence and biofilm formation through nanoscale zero-valent iron particles

The emergence of antimicrobial resistance (AMR) and bacterial biofilm formation in water-related systems (e.g., drinking water distribution pipes) have been posing challenges to public health. Compared to conventional disinfection processes, nanomaterial-based approaches hold promise for mitigating AMR emergence and controlling biofilm formation. In this study, we investigated the performance and mechanisms of nanoscale zero-valent iron (nZVI) and its derivates (carboxymethyl cellulose-nZVI, oxidized or “Aged” nZVI, and Fe3O4 nanoparticles) on preventing AMR emergence and biofilm formation. Results show that the long-term exposure to subminimum inhibitory concentrations of nanoparticles except for Fe3O4 are able to prevent AMR emergence and biofilm formation. Except for Fe3O4, other nZVI nanoparticles are also capable of eradicating pre-established biofilms. The capability of these nanoparticles against AMR and biofilm can be attributed to the overproduction of reactive oxygen species, cell membrane damage and repression of efflux pumps. Collectively, our findings suggest that nZVI nanoparticles are promising alternatives to combat bacterial AMR emergence and biofilm formation in water-related systems.

Exploring antibiotic consumption between urban and sub-urban catchments using both parent drugs and related metabolites in wastewater-based epidemiology

Consumption of antibiotics leads to the dissemination of antimicrobial resistance worldwide. Better knowledge of temporal and spatial consumption of antibiotics helps public health authorities to control their usage and combat antimicrobial resistance. However, measuring antibiotic consumption with population surveys, sales data, and production statistics remains challenging due to the complexity of prescription preference, patient compliance, and direct disposal of unused drugs. With the approach of wastewater-based epidemiology (WBE), this study aims to evaluate the consumption of eight commonly-used antibiotics between developed urban and developing sub-urban catchments in China and to characterise the ratios of parent drugs to metabolites in studying the consumption. Seven parent antibiotics were detected in all the wastewater samples (n = 56), whereas some metabolites were detected sporadically. The ratios of parent chemicals to metabolites varied among locations and were often higher than the ratios in pharmacokinetic studies. Estimated consumption of antibiotics ranged from 3.2 ± 2.0 mg/day/1000 inhabitants for trimethoprim to 28,400 ± 7800 mg/day/1000 inhabitants for roxithromycin in the studied catchments. Higher consumption of sulfapyridine, sulfadiazine and roxithromycin was observed in urban than suburban catchments, while consumption of sulfamethoxazole, norfloxacin, and trimethoprim was higher in suburban than in urban catchments. Using the literature data, we found more than 95% reduction of antibiotic use in an urban catchment. Our study revealed the geographical pattern in antibiotic use across different urban and suburban catchments via WBE, and the potential of monitoring parent-to-metabolite ratios for WBE in estimating antibiotic use. These results provide a basis for health authorities to plan different drug-specific control policies between urban and suburban catchments, and for future WBE studies to be aware of other sources, such as animal husbandry and disposals of unused drugs, that can influence the estimated consumption.

Antimicrobial Stewardship and Infection Prevention and Control in Low- and Middle-income Countries: Current Status and Best Practices.

The history of infection prevention and control (IPC) dates back at least 2500 years, with recommendations for large rooms with adequate ventilation to help reduce the spread of infections in hospitals dating back to 500 BCE.1 Scientific study of how to prevent infection in hospitals began in the mid-18th century, predating the discovery of bacteria. Sir John Pringle noted the importance of poor ventilation and overcrowding, whereas Florence Nightingale, after her experience in the Balkans, promoted cleanliness and hospital reform.2 Penicillin, the first antibiotic, was discovered in 1928 by Alexander Fleming and naturally occurring penicillinases in 1940, preceding its introduction for therapy. Sulfonamides, the first broadly effective antimicrobial agents, were introduced in 1937, with resistance reported already in the late 1930s.3 Since then, the rapid rise of antibiotic resistance has outpaced antibiotic development and use.4 Also, most new antibiotics focus on adult populations. Although well documented in high-income settings, resistance data are scanty in more poorly resourced settings. Reasons include poor laboratory capacity, lack of health information systems and insufficient resources for many sick patients.5 Given these issues, it is very possible that antibiotic resistance, especially multi-drug resistance, is even more common in less-resourced countries. Antimicrobial stewardship (AMS), a means for preserving antimicrobial effectiveness through judicious use, first appeared in the medical literature in 1999, with a logarithmic increase in PubMed citations from 2010.6 AMS, by limiting antimicrobial consumption through responsible use, and IPC measures, by preventing the spread of resistant organisms in healthcare settings, are interlinked essential activities in which healthcare providers have some control. While both complementary programs are gaining more attention, especially after the World Health Organization adopted a global action plan to combat antimicrobial resistance in 2015, implementation in resource-limited settings, especially for children, is difficult. Most guidance, although highly relevant, is designed for well-resourced settings. In many less resourced settings, clinicians often face overcrowded wards and clinics, insufficient space and personnel, insufficient laboratory back-up and long turn-around times for results. There are too few dedicated infection control practitioners, often without adequate career tracks for professional advancement. Most importantly, there are many critically ill children requiring intervention. However, the core principles are universal. Background to Supplement In 2017, at its 10th conference in Shenzhen, China, the World Society of Pediatric Infectious Diseases (WSPID) launched its declaration on combatting antimicrobial resistance.7 Key emphases were that children, including neonates, require special consideration for both AMS and IPC programs. The 5 key components are illustrated in Table 1. In December 2019, a WSPID working group met at its 11th World Conference in Manilla, the Philippines, to plan a series of articles on AMS and IPC reflecting their status in less resourced settings and to offer practical guidance. This supplement, the outcome of much work and collaboration, focuses on what we, as doctors, can do in healthcare settings. In addition, we add our voices to advocate for limiting easy antibiotic availability without medical prescriptions in many countries, lack of microbiology diagnostic resources and antimicrobial abuse in agriculture. Table 1. - Key Components of the WSPID Declaration on Combatting Antimicrobial Resistance in Children, 2017 1. Improve awareness and understanding of antimicrobial resistance through effective communication, education and training 2. Strengthen knowledge base through surveillance and research 3. Reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures 4. Optimize the use of antimicrobial medicines in human and animal health 5. Develop the economic case for sustainable investment, considering the needs of all countries and increase investment in new medicines (including vaccines), diagnostic tools and other interventions Content of Supplement Led by Penelope Bryant for AMS and Susan Coffin for IPC, the supplement begins with reporting on a widely circulated questionnaire representing a situational analysis of these programs from 135 respondents in 39 low- and middle-income and 27 high-income settings. The responses highlight resource scarcity and an enormous need for ongoing education which WSPID is committed to tackling through its educational program. This was followed by systematic reviews on the status of AMS and IPC programs in resource-limited healthcare settings and practical case studies by colleagues from Africa, Asia and Latin America. Both systematic reviews highlight the importance of bundled interventions, already shown in many studies from high-resource settings to be effective, but with limited evidence to support these or other practices in resource-limited settings. This is an area with a huge research agenda. The case studies present narratives from the real world that are often not obvious in data-driven research publications but are well recognized by hard-pressed clinicians. The vignettes illustrate almost insurmountable problems, most of which were addressed through teamwork, motivation and innovation. CONCLUSIONS Ongoing education and international collaboration are essential components necessary to minimize antimicrobial resistance and maintain the efficacy of interventions. Many interventions, such as meticulous handwashing and avoiding unnecessary antibiotic use, are relatively simple concepts, but not always that easy either to implement or monitor. We hope that this supplement will complement ongoing activities to promote safe healthcare settings for children to survive and thrive. WSPID’s CALL TO ACTION In developing and reflecting upon the content of this supplement, we propose a modified antimicrobial resistance declaration that is more child focused, with emphasis on what we must do for pediatric populations in hospitals and clinics. While we strongly support broader initiatives such as developing new medications and interventions and improving sanitation in communities, we must focus on our core responsibility: improving childhood outcomes (Table 2). Table 2. - Modified WSPID Declaration for Combatting Antimicrobial Resistance 1. Support and advocate for pediatric antimicrobial stewardship and infection prevention and control programs globally through mentorship, discussion groups, webinars and focused training on appropriate research. 2. Encourage and develop multiple education initiatives to improve the understanding and practice of optimal antibiotic prescribing by all those involved in giving antibiotics to children. 3. Assist with developing appropriate metrics and monitoring methods of deficiencies in care impacting on AMR and IPC outcomes for hospitalized neonates and children globally. 4. Assist with developing appropriate metrics and quality indicators of good prescribing for children in primary healthcare and hospital settings, using the WHO AWaRe system. 5. Assist with developing simple metrics and quality indicators for hospital-acquired infections, including clinical and health economic outcomes. AWaRe – Access, Watch and Reserve (https://adoptaware.org – updated 2019, accessed 27 July 2021). ACKNOWLEDGMENTS AMR working group: Mike Sharland – Chair (UK), Mark Cotton – Co-Chair (South Africa), Ramesh Agarwal (India), Daniela Pavez (Chile), Penelope Bryant (Australia), Susan Coffin (USA), Mohammad Issack (Mauritius), Shamim Qazi (Switzerland), Ilan Youngster (Israel), Mehreen Arshad and Celina Hanson (USA), Devika Dixit (Canada), Tinsae Alemayehu (Ethiopia), Mei Zeng (China) AMR portal development group: Anna Markowich (Italy), Danilo Buonsenso (Italy), Joycelyn Dame (Ghana), Kevin Meesters (Belgium), Olha Shvaratska (Ukraine), Sofia Benou (Greece), Tinsae Alemayehu (Ethiopia) Kenes support: Evelyn Zuberbuhler and Hester Lanting.

Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

Antimicrobial Resistance and Machine Learning: Challenges and Opportunities

Antimicrobial Resistance (AMR) has been identified by the World Health Organisation (WHO) as one of the top ten global health threats. Inappropriate use of antibiotics around the world and in particular in Low-to-Middle-Income Countries (LMICs), where antibiotics use and prescription are poorly managed, is considered one of the main reasons for this problem. It is projected that the COVID-19 pandemic will accelerate the threat of AMR due to the increasing use of antibiotics across the world, and especially in countries with limited resources. In recent years, machine learning-based methods showed promising results and proved capable of providing the necessary tools to inform antimicrobial prescription and combat AMR. This timely paper provides a critical and technical review of existing machine learning-based methods for addressing AMR. First, an overview of the AMR problem as a global threat to public health, and its impact on countries with limited resources (LMICs) are presented. Then, a technical review and evaluation of existing literature that utilises machine learning to tackle AMR are provided with emphasis on methods that use readily available demographic and clinical data as well as microbial culture and sensitivity laboratory data of clinical isolates associated with multi-drug resistant infections. This is followed by a discussion of challenges and limitations that are considered barriers to scaling up the use of machine learning to address AMR. Finally, a framework for accelerating the use of AMR data-driven framework, and building a feasible solution that can be realistically implemented in LMICs is presented with a discussion of future directions and recommendations.

125. Antimicrobial Stewardship Hospital Activities to Promote Antibiotic Awareness Week 2019, Chicago, IL

BackgroundU.S. Antibiotic Awareness Week (USAAW) is an annual campaign to increase knowledge of antimicrobial resistance (AMR) threats and the importance of appropriate antibiotic use. USAAW will be observed November 18-24, 2021 in cadence with World Antimicrobial Awareness Week. MethodsIn October 2019, the Chicago Department of Public Health (CDPH) surveyed 25 Chicago acute care hospital (ACH) antimicrobial stewardship programs (ASPs) via REDCap, an electronic data capture system, to assess their planned activities for USAAW in November 2019. Survey results from 14 (56%) respondent ACHs were collated and disseminated to all 25 ACHs prior to USAAW. ResultsACH ASP survey responses were categorized by ACH size: smaller hospitals (SH) < 350 beds (n=7) and larger hospitals (LH) > 350 beds (n=7) and displayed in the Table. Nine respondents were Infectious Disease (ID) Pharmacists, 3 were ID Physicians, 1 was an Administrator and 1 was an Infection Prevention Nurse. Among SHs, the ASP was funded for an ID Pharmacist salaried position (FTE) < 0.5 at 4 ACHs, 0.5 in 2, and 1 FTE at 1 ACH. LHs reported ID Pharmacist funding ranging from < 0.5 – 2.5 FTE, with the majority with 1 FTE at 3 LHs. All ACHs reported 0.5 FTE or less ID Physician support for their ASPs. Eleven (79%) of respondent ACHs did not report an annual budget for ASP activities. Ten (71%) ACHs disagreed or strongly disagreed that funding was adequate in the outpatient setting compared to inpatient both for adult and pediatric ASP services. Types of planned activities for USAAW included social media posts, provider education, digital displays, and/or go-live with a new antimicrobial policy. Top three barriers to ASP advancements were financial considerations (n=9), competing responsibilities for ASP leads (n=7), and tied for third was personnel shortages (n=6) and other clinical initiatives with higher priority (n=6). ConclusionPublic Health Departments can facilitate assessment of ACH ASPs within their jurisdiction to identify ways to advance the ASP agenda and combat AMR. A variety of strategies were used by Chicago ACHs to promote ASP initiatives during USAAW. Challenges continue with inadequate funding, especially in outpatient settings.Disclosures All Authors: No reported disclosures

New York State dairy veterinarians’ perceptions of antibiotic use and resistance: A qualitative interview study

Antimicrobial resistance (AMR) limits the ability to prevent and treat infection, making AMR one of the foremost threats to human and animal health. Animal agriculture’s large use of antibiotics in food animals is an important factor in AMR. As such, policies to reduce antibiotic use and combat AMR in animal agriculture in the United States (US) have been in place or are developed. One key to the success of these policies in the US is understanding how a major stakeholder - veterinarians treating dairy cattle - perceive the scale of antibiotic use, the threat of AMR and the utility of antibiotic use policies. We interviewed 9 dairy veterinarians in New York State and conducted an iterative thematic analysis of their responses, through which five themes were identified: 1. veterinarians’ views of the frequency and reasons for antibiotic misuse, 2. their ideas on reducing antibiotic use, 3. perceptions of AMR within the dairy industry, 4. view of organic farming and how it relates to animal welfare, and 5. the impact of consumers’ beliefs on the dairy industry. Participants viewed antibiotic overuse as largely due to farmers’ concern for the welfare of their cattle and desire to treat ailments swiftly. Interviewees believed that it was possible to reduce antibiotic use through regulation, such as the Veterinary Feed Directive and improved herd management activities, such as better colostrum management, culture-based mastitis treatment, and improved housing conditions. They did not view the dairy industry as a significant contributor to AMR, particularly when compared to the human medical industry. Interviewees also offered their (unsolicited) opinion on organic dairy farming in the US and expressed frustration with the limited treatment options available in organic dairy farming and how this dynamic may potentially compromise animal welfare. Finally, they commented on the impact of consumers’ beliefs on the dairy industry, expressing frustration with how misinformation about the dairy industry has led to consumer driven changes. As consumer beliefs have an impact on the dairy industry, this influence could be leveraged to further decrease antibiotic use. These findings can help guide future efforts in veterinarian-client communication and the development and implementation of effective policies in New York State. These results also highlight the need for more quantitative research on antibiotic use in the dairy industry, as without this data it will be difficult to ascertain the true impact of policy interventions.

Efforts to Identify and Combat Antimicrobial Resistance in Uganda: A Systematic Review.

The global burden of antimicrobial resistance is on the rise, resulting in higher morbidity and mortality in our communities. The spread of antimicrobial resistance in the environment and development of resistant microbes is a challenge to the control of antimicrobial resistance. Approaches, such as antimicrobial stewardship programmes and enhanced surveillance, have been devised to curb its spread. However, particularly in lower- and middle-income countries, the overall extent of antimicrobial resistance and knowledge on ongoing surveillance, stewardship or investigation efforts, are often poorly understood. This study aimed to look at the efforts that have been undertaken to detect and combat antimicrobial resistance in Uganda as a means of establishing an overview of the situation, to help inform future decisions. We conducted a systematic literature review of the PubMed database to assess these efforts. A search combining keywords associated with antimicrobial resistance were used to find relevant studies between 1995 and 2020 on surveillance of antimicrobial resistance in Uganda, and susceptibility of microbes to different drugs. The search yielded 430 records, 163 of which met the inclusion criteria for analysis. The studies were categorized according to country and region, the type of antimicrobial resistance, context of the study, study design and outcome of the study. We observed that antibacterial resistance and antimalarial resistance had the most published studies while antiviral and antifungal resistance were represented by very few studies each. Most studies were conducted in humans and hospital settings, with few in veterinary and One Health contexts, and only one that included environmental sampling. The majority of studies have focused on surveillance, susceptibility testing or resistance genes; none of our included papers had a policy or stewardship focus. The results from our work can inform public health policy on antimicrobial stewardship as it contributes to understanding the status of antimicrobial resistance surveillance in Uganda, and can also help to guide future research efforts. Notably, a One Health approach needs to be followed with respect to surveillance of antimicrobial resistance to better understand the mechanisms of resistance transfer across the human-animal–environment interface, including additional investigation in antiviral and antifungal resistance.