AbstractBackgroundAntimicrobial Resistance Research Articles

Estimating tuberculosis drug resistance amplification rates in high-burden settings

BackgroundAntimicrobial resistance develops following the accrual of mutations in the bacterial genome, and may variably impact organism fitness and hence, transmission risk. Classical representation of tuberculosis (TB) dynamics using a single or two strain (DS/MDR-TB) model typically does not capture elements of this important aspect of TB epidemiology. To understand and estimate the likelihood of resistance spreading in high drug-resistant TB incidence settings, we used epidemiological data to develop a mathematical model of Mycobacterium tuberculosis (Mtb) transmission.MethodsA four-strain (drug-susceptible (DS), isoniazid mono-resistant (INH-R), rifampicin mono-resistant (RIF-R) and multidrug-resistant (MDR)) compartmental deterministic Mtb transmission model was developed to explore the progression from DS- to MDR-TB in The Philippines and Viet Nam. The models were calibrated using data from national tuberculosis prevalence (NTP) surveys and drug resistance surveys (DRS). An adaptive Metropolis algorithm was used to estimate the risks of drug resistance amplification among unsuccessfully treated individuals.ResultsThe estimated proportion of INH-R amplification among failing treatments was 0.84 (95% CI 0.79–0.89) for The Philippines and 0.77 (95% CI 0.71–0.84) for Viet Nam. The proportion of RIF-R amplification among failing treatments was 0.05 (95% CI 0.04–0.07) for The Philippines and 0.011 (95% CI 0.010–0.012) for Viet Nam.ConclusionThe risk of resistance amplification due to treatment failure for INH was dramatically higher than RIF. We observed RIF-R strains were more likely to be transmitted than acquired through amplification, while both mechanisms of acquisition were important contributors in the case of INH-R. These findings highlight the complexity of drug resistance dynamics in high-incidence settings, and emphasize the importance of prioritizing testing algorithms which allow for early detection of INH-R.

116. Impact of an Antimicrobial Stewardship Program in the First Year of Pandemic 2020 in a Large,Academic, Public Network Hospitals in Bogotá,Colombia

BackgroundAntimicrobial resistance is a major public health threat internationally but, particularly in Colombia. High and increasing rates of carbapenemases are challenging. Implementing antimicrobial stewardship programs (AMSs) in a large, academic, public network hospitals in Bogotá, Colombia.will help curb inappropriate antibiotic use. Adherence to AMS Program 2020. Subred Integrada de Servicios de Salud Sur Occidente E.S.E Bogotá, Colombia. Impact of an Antimicrobial Use Optimization Program in the First Year of Pandemic 2020 in a Large, Academic, Public Network Hospitals in Bogota ColombiaMethodsAMS was established in April 2020 consisting of an administrative champion, Infectious Diseases staff, nurse, General Physician, microbiologist, and pharmacists. Antimicrobial stewardship program interventions included postprescriptive audit and establishment of institutional guidelines. The AMS tracked appropriate drug selection including loading dose, maintenance dose, frequency, route, duration of therapy, de-escalation, and compliance with AMS recommendations. Defined daily dose (DDD) of drugs and health economics evaluations of antimicrobials (April-December 2020). Recommendations are placed in the electronic medical record as a progress note.ResultsFrom April to December 2020, 1013 patients were evaluated by means of a prospective methodology. Unnecessary 689 days of hospitalization and 4420 days of antibiotic therapy were avoided. Among the top antibiotics discontinued were piperacillin tazobactam for the months of July, August, November and December, while for September and October was meropenem. The intensive care unit was the most frequently intervened service (52%), followed by hospitalization (43%) and the emergency department (5%).Over the course of the year, there was significant adherence to the program, with 100% in July, followed by 93.3% in April, 87% in December, 86.6% in May and June, 83% in November, 80% in September, 73.3% in August and 57% in October. The AMS program was able to save &47.409US in antibiotics and &55.529US in hospitalization, and 11% decrease in nephrotoxicity events (14 renal failures were avoided), which also saved additionally & 23.503 US for a total of an estimated cost saving for the network public hospitals of & 126.441 US by 2020.ConclusionImplementation of a multidisciplinary antibiotic stewardship program in this academic, large, academic, public network hospitals in Bogotá, Colombia demonstrated feasibility and economic benefits even in a Covid19 pandemic situation.Disclosures All Authors: No reported disclosures

963. Antibiotic Talk on TikTok: An Opportunity for Patient Education?

BackgroundAntimicrobial resistance is increasing at an alarming rate. Patient education is a critical component of stewardship and many patients access resources online. TikTok is a video-sharing social media platform with 700 million monthly users and contains videos that discuss health information. The objective of this study was to evaluate antibiotic-themed TikTok videos for their validity and reliability. MethodsIn March 2021, a search on TikTok using the term “antibiotics” was performed and the top 300 consecutive videos were identified. Data collected included: number of likes, associated disease state, medications, educational aim, mention of COVID-19, and if performed by a healthcare professional (HCP). Non-English videos were excluded. The DISCERN score was used to evaluate all videos for reliability. ResultsThe first 300 consecutive videos were assessed using the DISCERN score. Of the 300 videos, most (n=224) were not created by HCPs (non-HCPs). The number of “likes” per video ranged from 1 like to 2 million likes with a mean of 34,949 ± 143,482. Videos produced by HCPs were significantly more valid and reliable (mean DISCERN score of 1.65 vs 1.17, p < .00001) than non-HCPs. They were found to be more relevant (p< .00001), have clearer aims (p< .00001), and were more balanced/unbiased (p=.00188). Videos created by HCPs were more likely to have an educational focus (p< .0001). There was no difference between groups in clarity of sources utilized or risk/benefits discussed of each treatment. Across all videos, the most common disease states mentioned were urinary tract infection, skin and soft tissue infection, and upper respiratory tract infection. Natural products, penicillins, and sulfa antibiotics were the most commonly discussed medications.ConclusionVideos created by HCPs were significantly more valid and reliable than those created by non-HCPs. The videos created by HCPs were also more likely to have clear aims and be more relevant. However, the majority of the videos evaluated were created by non-HCPs. It may be beneficial for HCPs to provide TikTok videos that are valid and reliable for patient education.Disclosures All Authors: No reported disclosures

1270. Molecular Characterization of Carbapenemase Producing Enterobacterales, Acinetobacter spp. and Pseudomonas spp. in Nosocomial and Community-acquired Clinical Isolates in Bogota, Colombia

BackgroundAntimicrobial resistance (AMR) in low-income and middle-income countries (LMICs) is a public health problem. AMR is a concerning problem in Gram-negative bacteria such are Enterobacterales, which are frequently carbapenem-resistant pathogens (CRP), and few therapeutic options are available. However, scarce data is known regarding the clinical, molecular characteristics, and clinical outcomes of patients infected with carbapenem-resistant pathogens in LMICs. Thus, this study will attempt to bring novel data in these regards.MethodsThis is a retrospective cohort study conducted in two reference hospitals in Colombia, South America. All consecutive patients infected with CRPs between 2017 and 2021 were included. Clinical data were gathered by retrospective chart review. Bacterial pathogens and antibiotic susceptibility were prospectively identified and stored by each hospital. Molecular characterization was performed by PCR in isolated bacteria.ResultsA total of 220 patients were included. The mean (SD) age was 60.6 (18.4) years, and 32% (71/220) were female. The most frequently identified CRPs were Pseudomonas aeruginosa (85/220, 39%) and Klebsiella pneumoniae (81/220, 37%). CRPs were most frequently identified in urine, blood, and respiratory samples (Figure 1). Community-acquired infections were frequently diagnosed in patients infected with CRPs in our study (73% [161/220]), and most of the patients were admitted to the ICU (163/220, 74%). The in-hospital mortality rate was 28% (62/220) and 38% (62/163) in ICU admitted patients. PCR was carried out in 105 CRP; KPC (69%, 73/105) and VIM (37%, 39/105) were the most frequently identified mechanisms. Of the K. pneumoniae isolates with PCR assessment, 94% (33/35) had KPC and 3% (1/35) had VIM. In contrast, in P. aeruginosa isolates with PCR assessment, 53% (29/54) had KPC and 59% (32/54) had VIM. Seven (13%) patients infected with P. aeruginosa had both KPC and VIM genes identified. ConclusionThe most frequently identified carbapenem-resistant pathogens in these two Colombian reference hospitals were P. aeruginosa and K. pneumoniae, with high mortality rates. KPC was the most commonly identified mechanism of carbapenem resistance in our cohort.Disclosures All Authors: No reported disclosures

32. Impact of a Four-Year Antimicrobial Stewardship Program on Antimicrobial Resistance

Abstract Background Antimicrobial resistance (AMR) is an increasing threat to public health and antimicrobial consumption is a primary driver of resistance. Many studies have shown that the implementation of an antibiotic stewardship program (ASP) improves prescribing of antibiotics and can reduce AMR. Purpose of the study was to assess the impact of a successful ASP, implemented for four years, on AMR in our 427-bed tertiary general hospital. Methods We monitored pharmacy data for the years 2015 (pre-intervention) and 2016-2019 (post-intervention) for antibiotic consumption (DDD/100 bed-days) and resistance rates. AMR data were obtained from the clinical microbiology laboratory’s electronic database. To achieve the goals of ASP we used a range of interventions as pre-authorization strategy for the protected antibiotics (tigecycline, carbapenems, quinolones, glycopeptides, daptomycin, colistin, linezolid), prospective audit and feedback with direct intervention, de-escalation or switch from iv to oral administration and appropriate selection and duration of chemoprophylaxis in surgery. Results Significant reductions were observed for: total antibiotics, colistin, carbapenems, quinolones and tigecycline consumption during study period. Significantly lower resistance rates were documented in 2019 compared to 2015 for Pseudomonas aeruginosa and for Klebsiella pneumoniae. As for Acinetobacter baumannii isolates, which in our hospital are highly-resistant exhibiting &amp;gt;90% resistance to carbapenems, no significant changes were noted during the study period. Infections caused by Gram-positive pathogens are less prevalent in our hospital. Lower rates of vancomycin-resistant enterococci were noted after the implementation of our ASP (30.4% in 2019 vs. 50.0% in 2015 for E. faecium and 0.6% vs. 6% for E. faecalis, respectively), whereas methicillin-resistant S. aureus isolates increased (40% in 2019 vs. 31.1% in 2015), possibly because most of these infections were not hospital-acquired. Resistance rates of Pseudomonas and Klebsiella Conclusion Our ASP was successful in reducing antibiotic consumption and AMR for important pathogens. Disclosures All Authors: No reported disclosures

Developing a theory-based behavior change intervention to improve the prescription of surgical prophylaxis

Background Antimicrobial resistance (AMR) is increasingly pervasive due to multiple, complex prescribing and consuming behaviours. Accordingly, behaviour change is an important component of response to AMR. Little is known about the best approaches to change antibiotic use practices and behaviours. Aim This project aims to develop a context-specific behaviour change strategy focusing on promoting appropriate prescription practices following the World Health Organization recommendations for surgical prophylaxis in an orthopaedic surgery unit in Egypt. Method The project included a formative qualitative research study with 31 in-depth interviews with orthopaedic surgeons that was based on the Theoretical Domains Framework (TDF) and an intervention that was developed to following the Behaviour Change Wheel (BCW) in a knowledge co-production workshop with ten public health experts that ensured that the theory based intervention was a culturally acceptable, practical and implementable intervention. Results The prescription of surgical prophylaxis was influenced by eight TDF domains from which workshop participants selected five to be included in the behaviour change intervention including, knowledge, belief in consequences (mistrust towards infection prevention and control measures), environmental factors (lack of prescription guidelines), professional role and reinforcement (a lack of appropriate follow up actions influenced prescription of surgical prophylaxis). The appropriate set of behaviour change functions of BCW and related activities to improve the current practices included education, enablement, persuasion, environmental restructuring and restriction. Conclusion The study showed that a theory based, and context specific intervention can be created by using the TDF and BCW together with knowledge-co creation to improve the prescription of surgical prophylaxis in and Egyptian orthopaedic unit. The intervention needs to piloted and scaled up.

Dispensing antibiotics without prescription at pharmacies: barriers and strategies for improvement

Abstract Background Antimicrobial resistance (AMR) is a worldwide public health challenge, and non-prudent use of antibiotics is one of key drivers of AMR. In some countries antibiotics are often sold without a prescription at pharmacies. In Armenia this problem is also observed despite national regulation. The objective of this work was to identify perception of pharmacy staff on main barriers for dispensing antibiotics with a prescription at community pharmacies and perceived strategies for improving the situation in Armenia. Methods Survey was conducted at community pharmacies in different regions of Armenia. Pharmacists and pharmacy technicians were asked to complete pretested questionnaire. Data were analysed with SPSS statistical software. Results Despite most of professionals reported that they are aware about regulation, 78.4% of 241 participants indicated that patients can buy antibiotics at their pharmacy without a prescription from doctor. Most of participants reported that the percentage of patients whom antibiotics were sold without a prescription is high. More than a half of responders indicated the following barriers for dispensing antibiotics with a prescription at community pharmacies: lack of patients' awareness about effectiveness and safety of antibiotics (61.0%), difficulties for doctors to prescribe using approved forms (60.6%), poor prescribing practice (56.4%). More than a half of professionals consider that it is necessary to introduce the following strategies: organizing public awareness campaigns (68.0%), organizing special training courses for physicians and pharmacists (63.9%), introducing Medicines and therapeutic committees at health facilities (54.8%). Conclusions Patients can buy antibiotics without a prescription at community pharmacies in Armenia. There are certain barriers for dispensing antibiotics with a prescription at community pharmacies. Educational and organizational strategies can be helpful for improving the situation. Key messages Lack of patients’ awareness about antibiotics is a very important barrier for dispensing antibiotics with a prescription at community pharmacies. Most of pharmacy professionals are interested in improving the situation and indicate necessity of appropriate measures.

Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students

BackgroundAntimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of ‘stool and stories’ that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR.MethodsA longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis.ResultsThe incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling.ConclusionThe microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the ‘stool and stories’ approach is important for a transdisciplinary basis of AMR stewardship.

Occurrence of potentially zoonotic and cephalosporin resistant enteric bacteria among shelter dogs in the Central and South-Central Appalachia

BackgroundAntimicrobial resistance and presence of zoonotic enteropathogens in shelter dogs pose a public health risk to shelter workers and potential adopters alike. In this study we investigated the prevalence of zoonotic bacterial pathogens and cephalosporin resistant (CefR) enteric bacteria in the feces of apparently healthy shelter dogs in the Cumberland Gap Region (CGR) in the US states of Kentucky, Tennessee and Virginia.ResultsFecal samples of 59 dogs from 10 shelters in the CGR of Central and South-Central Appalachia were screened for the presence of Campylobacter jejuni, Clostridium perfringens, Salmonella and CefR enteric bacteria. C. jejuni, C. perfringens were detected by PCR based assays. Culture and PCR were used for Salmonella detection. Of 59 dogs, fecal samples from 14 (23.7%) and 8 (13.6%) dogs tested positive for cpa and hipO genes of C. perfringens and C. jejuni, respectively. Salmonella was not detected in any of the tested samples by PCR or culture. CefR enteric bacteria were isolated on MacConkey agar supplemented with ceftiofur followed by identification using MALDI-TOF. Fecal samples from 16 dogs (27.1%) yielded a total of 18 CefR enteric bacteria. Majority of CefR isolates (14/18, 77.8%) were E. coli followed by, one isolate each of Enterococcus hirae, Acinetobacter baumannii, Acinetobacter pittii, and Pseudomonas aeruginosa. CefR enteric bacteria were tested for resistance against 19- or 24-antibiotic panels using broth microdilution method. Seventeen (94.4%) CefR bacteria were resistant to more than one antimicrobial agent, and 14 (77.8%) displayed multidrug resistance (MDR).ConclusionsThis study shows that shelter dogs within the CGR not only carry zoonotic bacterial pathogens, but also shed multidrug resistant enteric bacteria in their feces that may pose public health risks.

A protocol for a systematic literature review of economic evaluation studies of interventions to address antimicrobial resistance

BackgroundAntimicrobial resistance (AMR) is accelerated by the widespread and often indiscriminate use of antimicrobials in humans, animals, and the environment. In 2015, the World Health Organization recognised AMR as one of the top ten global health threats, due to its potential to neutralise humanity’s advancements in western medicine by enabling the emergence of new strains of existing pathogens, many of which have no available treatments. Over the past decade, several countries, including those in low- and middle-income contexts, have started implementing interventions to tackle AMR. However, economic evidence regarding the cost-effectiveness of these interventions remains weak. To address this evidence gap, we will conduct a systematic literature review to provide a comprehensive summary on the value for money of different AMR interventions.MethodsWe aim to conduct a systematic literature review of all available economic evaluations on interventions addressing AMR and will provide a narrative synthesis of our findings. Systematic searches for relevant studies will be performed across all suitable databases as well as in grey literature sources such as unpublished studies, reports, and other relevant documents. All economic evaluation studies will be included as long as they report an economic outcome and have stated that the analysed intervention will reduce antimicrobial resistance or antimicrobial use in the abstract. Those studies reporting clinical endpoints alone will be excluded. Selection for final inclusion and data extraction will be performed by two independent reviewers.DiscussionThe review will be one of the first of its kind, and the most recent, to systematically review literature on the cost-effectiveness of AMR interventions, an important evidence gap in the economics of AMR. The findings will enable policy and decision-makers, particularly in resource-constrained settings, to better use available resources when selecting interventions to address AMR burdens,Systematic review registrationPROSPERO CRD42020190310

Antibiotic prescribing for acute, non-complicated infections in primary care in Germany: baseline assessment in the cluster randomized trial ARena

BackgroundAntimicrobial resistance is fueled by inappropriate use of antibiotics. Global and national strategies support rational use of antibiotics to retain treatment options and reduce resistance. In Germany, the ARena project (Sustainable reduction of antibiotic-induced antimicrobial resistance) intended to promote rational use of antibiotics for acute non-complicated infections by addressing network-affiliated physicians, primary care teams and patients through multiple interacting interventions. The present study documented patterns of antibiotic prescribing for patients with acute non-complicated infections who consulted a physician in these networks at the start of the ARena project. It explored variation across subgroups of patients and draws comparisons to prescribing patterns of non-targeted physicians.MethodsThis retrospective cross-sectional analysis used mixed logistic regression models to explore factors associated with the primary outcome, which was the percentage of patient cases with acute non-complicated respiratory tract infections consulting primary care practices who were treated with antibiotics. Secondary outcomes concerned the prescribing of different types of antibiotics. Descriptive methods were used to summarize the data referring to targeted physicians in primary care networks, non-targeted physicians (reference group), and patient subgroups.ResultsOverall, antibiotic prescribing rates were 32.0% in primary care networks and 31.7% in the reference group. General practitioners prescribed antibiotics more frequently than other medical specialist groups (otolaryngologists vs. General practitioners OR = 0.465 CI = [0.302; 0.719], p < 0.001, pediatricians vs. General practitioners: OR = 0.369 CI = [0.135; 1.011], p = 0.053). Quinolone prescribing rates were 9.9% in primary care networks and 8.1% in reference group. Patients with comorbidities had a higher likelihood of receiving an antibiotic and quinolone prescription and were less likely to receive a guideline-recommended substance. Younger patients were less likely to receive antibiotics (OR = 0.771 CI = [0.636; 0.933], p = 0.008). Female gender was more likely to receive an antibiotic prescription (OR = 1.293 CI = [1.201, 1.392], p < 0.001).ConclusionThis study provided an overview of observed antibiotic prescribing for acute non-complicated respiratory tract infections in German primary care at the start of the ARena project. Findings indicate potential for improvement and will serve as comparator for the post-interventional outcome evaluation to facilitate describing of potential changes.

Using a public database of Neisseria gonorrhoeae genomes to detect mutations associated with zoliflodacin resistance.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat. Zoliflodacin is a novel antibiotic undergoing clinical trials for the treatment of gonorrhoea. While there are limited data regarding zoliflodacin resistance in N. gonorrhoeae, three amino acid mutations have been associated with increased MICs of zoliflodacin. To determine the prevalence of three amino acid mutations associated with zoliflodacin resistance within a large, public database of nearly 13 000 N. gonorrhoeae genomes. PathogenWatch is an online genomic epidemiology platform with a public database of N. gonorrhoeae genomes. That database was used to extract gyrB sequence data and a Basic Local Alignment Search Tool (BLAST) search was performed to identify any of the three amino acid mutations in GyrB that are associated with increased zoliflodacin MICs: D429N, K450N or K450T. As a control for the search methodology, all GyrA sequences were also extracted and S91F mutations were identified and compared with the PathogenWatch database. In total, 12 493 N. gonorrhoeae genomes from the PathogenWatch database were included. Among those genomes, none was identified that harboured any of the three mutations associated with increased zoliflodacin MICs. One genome was identified to have a mutation at position 429 in GyrB (D429V). The findings suggest that the prevalence of the three mutations associated with zoliflodacin resistance in N. gonorrhoeae is very low. However, further research into the mechanisms of zoliflodacin resistance in N. gonorrhoeae is needed. Genomic epidemiology platforms like PathogenWatch can be used to enhance the global surveillance of AMR.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods\xa0for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies

BackgroundAntimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area.MethodsResearchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study.DiscussionThis is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Antimicrobial use in hospitalized patients: a multicentre point prevalence survey across seven hospitals in Ghana.

BackgroundAntimicrobial resistance (AMR) is a public health crisis of global proportions. Data is required to understand the local drivers of antimicrobial resistance and support decision-making processes including implementation of appropriate antimicrobial stewardship strategies.ObjectivesTo measure antimicrobial usage in hospitals in Ghana.MethodsUsing the Global Point Prevalence instruments and processes, we conducted point prevalence surveys across AMR surveillance sentinel hospitals in Ghana, between September and December 2019. Hospital records of all inpatients on admission at 0800 hours on a specific day were reviewed for antimicrobial use at the time of the survey. Data on antibiotic use, including indication for use and quality of prescribing were recorded.ResultsOverall prevalence of antibiotic use across the sentinel sites was 54.9% (n = 1591/2897), ranging between 48.4% (n = 266/550) and 67.2% (n = 82/122). The highest prevalence of antibiotic use 89.3% (n = 25/28) was observed in adult ICUs. The average number of antibiotics prescribed per patient was 1.7 (n = 1562/2620), with the majority (66%, n = 728/2620) administered via the parenteral route. The five most-commonly used antibiotics were metronidazole (20.6%, n = 541/2620), cefuroxime (12.9%, n = 338/2620), ceftriaxone (11.8%, n = 310/2620), amoxicillin/clavulanic acid (8.8%, n = 231/2620) and ciprofloxacin (7.8%, n = 204/2620). The majority (52.2%; n = 1367/2620) of antibiotics were prescribed to treat an infection, whilst surgical prophylaxis accounted for 26.1% (n = 684/2620).ConclusionsWe observed a high use of antibiotics including metronidazole and cephalosporins at the participating hospitals. Most antibiotics were empirically prescribed, with low use of microbiological cultures. High usage of third-generation cephalosporins especially for community-acquired infections offers an opportunity for antibiotic stewardship interventions.

Confidence interval methods for antimicrobial resistance surveillance data

BackgroundAntimicrobial resistance (AMR) is one of the greatest global health challenges today, but burden assessment is hindered by uncertainty of AMR prevalence estimates. Geographical representation of AMR estimates typically pools data collected from several laboratories; however, these aggregations may introduce bias by not accounting for the heterogeneity of the population that each laboratory represents.MethodsWe used AMR data from up to 381 laboratories in the United States from The Surveillance Network to evaluate methods for estimating uncertainty of AMR prevalence estimates. We constructed confidence intervals for the proportion of resistant isolates using (1) methods that account for the clustered structure of the data, and (2) standard methods that assume data independence. Using samples of the full dataset with increasing facility coverage levels, we examined how likely the estimated confidence intervals were to include the population mean.ResultsMethods constructing 95% confidence intervals while accounting for possible within-cluster correlations (Survey and standard methods adjusted to employ cluster-robust errors), were more likely to include the sample mean than standard methods (Logit, Wilson score and Jeffreys interval) operating under the assumption of independence. While increased geographical coverage improved the probability of encompassing the mean for all methods, large samples still did not compensate for the bias introduced from the violation of the data independence assumption.ConclusionGeneral methods for estimating the confidence intervals of AMR rates that assume data are independent, are likely to produce biased results. When feasible, the clustered structure of the data and any possible intra-cluster variation should be accounted for when calculating confidence intervals around AMR estimates, in order to better capture the uncertainty of prevalence estimates.

Development and randomized controlled trial of an animated film aimed at reducing behaviours for acquiring antibiotics.

BackgroundAntimicrobial resistance (AMR) is a global health crisis but reducing antibiotic use can help. Some antibiotic use is driven by patient demand.ObjectivesTo develop an intervention to discourage antibiotic-seeking behaviour in adults.MethodsLiterature reviewed to identify behaviours for acquiring antibiotics among adults in the community. Behaviour change wheel approach was used to select the target behaviour and behaviour change techniques. An intervention in the form of a short animated film was developed and its potential impact evaluated in a randomized, controlled, online questionnaire study.ResultsAsking a general medical/dental practitioner for antibiotics was identified as the target behaviour. A short stop-motion animated film was chosen to deliver several behaviour-change techniques. Education and persuasion were delivered around information about the normal microbial flora, its importance for health, the negative effect of antibiotics, and about AMR. 417 UK-based individuals completed the questionnaire; median age 34.5 years, 71% female, 91% white ethnicity. 3.8% of participants viewing the test film intended to ask for antibiotics compared with 7.9% viewing the control film. Test film viewers had significantly higher knowledge scores. At 6 week follow up, knowledge scores remained significantly different, while most attitude and intention scores were not different.ConclusionsSome patients continue to ask for antibiotics. The film increased knowledge and reduced intentions to ask for antibiotics. At 6 weeks, knowledge gains remained but intentions not to ask for antibiotics had waned. Evaluation in the clinical environment, probably at the point of care, is needed to see if antibiotic prescribing can be impacted.

Neonatal sepsis in a tertiary unit in South Africa

BackgroundAntimicrobial resistance (AMR) has emerged as a global threat to healthcare resulting in an increase in morbidity and mortality. Neonatal sepsis is ranked as the third highest cause of neonatal demise globally, in which AMR accounted for 31.0% of deaths. AMR in neonates has been poorly characterised in Durban, South Africa. Thus, the resultant effect of AMR on empiric regimens for neonatal sepsis is uncertain in this setting. Therefore, this study analysed the aetiology and antimicrobial susceptibility patterns of bloodstream infections within the neonatal intensive care unit at a tertiary hospital in Durban, with the aim of establishing an effective empiric regimen for the unit.MethodsA retrospective data review on positive blood cultures from the neonatal intensive care unit at Inkosi Albert Luthuli Central Hospital was conducted. Three time periods were analysed: 2014, 2016 and 2018. Culture data from neonates aged 0–30 days were included and repeat cultures were de-duplicated. The frequency of common organisms and their antimicrobial susceptibilities were analysed. Fischer’s exact test was used for subgroup analysis. Poisson and logistic regressions were used to assess significant trends in organisms and antimicrobial susceptibilities over time.ResultsLate-onset sepsis (86.8%) predominated over early-onset sepsis (13.2%). A preponderance of gram-positive organisms (68.7%) over gram-negatives (26.8%) and fungi (4.5%) was detected. Common pathogens included coagulase-negative staphylococci (53.5%), Klebsiella pneumoniae (11.6%), enterococci (9.3%), and Acinetobacter baumannii (7.7%). Despite the small contribution of fungi to the microbial profile, fluconazole-resistant Candida parapsilosis predominated within that group. High rates of resistance to first- and second-line antibiotics were also noted among gram-positive and gram-negative organisms. Multidrug resistant organisms included extended-spectrum beta-lactamase (ESBL) K. pneumoniae (7.6%) and extensively-drug resistant A. baumannii (7.0%). However, a statistically significant decrease in ESBL-producing organisms was documented during the entire study period (p = 0.005).ConclusionsIt was determined that first-line antimicrobials, advocated by the World Health Organization for treatment of neonatal sepsis, proved ineffective in this unit due to high levels of AMR. Therefore, this study advises that meropenem with or without vancomycin provides optimal empiric cover. Amphotericin B is advocated for empiric antifungal therapy. Ongoing surveillance is necessary.

Ruminal resistome of dairy cattle is individualized and the resistotypes are associated with milking traits

BackgroundAntimicrobial resistance is one of the most urgent threat to global public health, as it can lead to high morbidity, mortality, and medical costs for humans and livestock animals. In ruminants, the rumen microbiome carries a large number of antimicrobial resistance genes (ARGs), which could disseminate to the environment through saliva, or through the flow of rumen microbial biomass to the hindgut and released through feces. The occurrence and distribution of ARGs in rumen microbes has been reported, revealing the effects of external stimuli (e.g., antimicrobial administrations and diet ingredients) on the antimicrobial resistance in the rumen. However, the host effect on the ruminal resistome and their interactions remain largely unknown. Here, we investigated the ruminal resistome and its relationship with host feed intake and milk protein yield using metagenomic sequencing.ResultsThe ruminal resistome conferred resistance to 26 classes of antimicrobials, with genes encoding resistance to tetracycline being the most predominant. The ARG-containing contigs were assigned to bacterial taxonomy, and the majority of highly abundant bacterial genera were resistant to at least one antimicrobial, while the abundances of ARG-containing bacterial genera showed distinct variations. Although the ruminal resistome is not co-varied with host feed intake, it could be potentially linked to milk protein yield in dairy cows. Results showed that host feed intake did not affect the alpha or beta diversity of the ruminal resistome or the abundances of ARGs, while the Shannon index (R2 = 0.63, P < 0.01) and richness (R2 = 0.67, P < 0.01) of the ruminal resistome were highly correlated with milk protein yield. A total of 128 significantly different ARGs (FDR < 0.05) were identified in the high- and low-milk protein yield dairy cows. We found four ruminal resistotypes that are driven by specific ARGs and associated with milk protein yield. Particularly, cows with low milk protein yield are classified into the same ruminal resistotype and featured by high-abundance ARGs, including mfd and sav1866.ConclusionsThe current study uncovered the prevalence of ARGs in the rumen of a cohort of lactating dairy cows. The ruminal resistome is not co-varied with host feed intake, while it could be potentially linked to milk protein yield in dairy cows. Our results provide fundamental knowledge on the prevalence, mechanisms and impact factors of antimicrobial resistance in dairy cattle and are important for both the dairy industry and other food animal antimicrobial resistance control strategies.

Antimicrobial resistance among uropathogens in the Asia-Pacific region: a systematic review.

BackgroundAntimicrobial resistance (AMR) in urinary tract infections (UTI) is a global public health problem. However, estimates of the prevalence of AMR, required for empirical treatment guidelines, are lacking for many regions.ObjectivesTo perform a systematic review and summarize the available information about AMR prevalence among urinary Escherichia coli and Klebsiella pneumoniae, the two priority uropathogens, in the Asia-Pacific region (APAC).MethodsPubMed, EBSCO and Web of Science databases were searched for articles (2008–20), following PRISMA guidelines. The prevalence of resistance was calculated and reported as point estimate with 95% CI for antimicrobial drugs recommended in WHO treatment guidelines. Data were stratified by country and surveillance approach (laboratory- or population-based surveillance). The quality of included articles was assessed using a modified Newcastle-Ottawa Quality Assessment Scale.ResultsOut of 2400 identified articles, 24 studies, reporting on 11 (26.8%) of the 41 APAC countries, met the inclusion criteria. Prevalence of resistance against trimethoprim/sulfamethoxazole, ciprofloxacin, and ceftriaxone ranged between 33% and 90%, with highest prevalence reported from Bangladesh, India, Sri Lanka and Indonesia. Resistance against nitrofurantoin ranged between 2.7% and 31.4%. Two studies reported data on fosfomycin resistance (1.8% and 1.7%). Quality of reporting was moderate.ConclusionsWe show very high prevalence estimates of AMR against antibiotics commonly used for the empirical treatment of UTI, in the limited number of countries in the APAC for which data are available. Novel feasible and affordable approaches that facilitate population-based AMR surveillance are needed to increase knowledge on AMR prevalence across the region.

30. Antimicrobial Resistance Genes Are Reduced Following Administration of Investigational Microbiota-based Therapeutic RBX7455 to Individuals with Recurrent clostrioides Difficile Infection

BackgroundAntimicrobial resistance (AMR) is a challenge in individuals at risk for recurrent Clostrioides difficile infection (rCDI). Recognizing that AMR bacteria colonize the intestinal microbiota, therapeutic approaches that decolonize the gut of AMR bacteria would be valuable. Herein, we assessed the microbial resistome before and after treatment with RBX7455—a room temperature-stable, orally-administered investigational microbiota-based therapeutic—in a Phase 1 trial for reducing CDI recurrence.MethodsThis investigator-sponsored trial enrolled 30 rCDI patients in 3 open-label treatment groups (n=10 per group): 1) Four RBX7455 capsules BID for 4 days, 2) Four RBX7455 capsules BID for 2 days, 3) Two RBX7455 capsules BID for 2 days. RBX7455 administration began 48 hours after finishing CDI antibiotics. Participants were asked to submit stool samples at baseline, 1, 7, 28 and 56 days after treatment. These were extracted and sequenced using a shallow shotgun method. Relative taxonomic abundances at the class level and the presence of AMR genes were determined for 148 participant samples and 11 product samples using 90% K-mer sequence coverage based on the MEGARes database.ResultsNinety percent of participants met the primary endpoint of no CDI recurrence through 8 weeks after treatment, and participant microbiome compositions became more similar to RBX7455 after treatment. The total AMR counts per participant decreased from before to after treatment (p< .05, mixed effects model), with the pattern of AMRs identified (resistome) becoming more like the RBX7455 resistome (Figure 1). Most notably, AMRs associated with multi-drug, fluoroquinolone, and betalactam resistance decreased from before to after treatment. There was no significant difference among the groups with respect to clinical response or changes in microbiome composition and AMR content.Figure 1 Average total and per-class AMR gene counts in participant samples before and after RBX7455 treatment. ConclusionIn a Phase 1 trial of RBX7455 for rCDI, AMR gene content decreased after treatment. This underscores the potential of microbiota-based therapies for decolonizing AMR bacteria from the gut microbiota. Continued clinical evaluation of RBX7455 is underway.Disclosures Dana Walsh, PhD, Rebiotix Inc. (Employee) Carlos Gonzalez, MS, BioRankings, LLC (Employee) Bill Shannon, PhD MBA, BioRankings, LLC (Employee) Ken Blount, PhD, Rebiotix Inc. (Employee)