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Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions. Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Objectives To investigate the appropriateness of antibiotic prescribing among GPs in the private primary healthcare sector in South Africa. Methods An anonymized national database of claims for antibiotic prescriptions was obtained from a large medical insurer. Antibiotic prescriptions were categorized based on International Classification of Diseases (ICD-10) codes as ‘appropriate’, ‘potentially appropriate’ and ‘inappropriate’ using a classification scheme developed by Chua et al. (BMJ 2019; 364: k5092). Further assessments of antibiotic choice, dosage and duration of treatment were carried out to determine the appropriateness of ‘appropriate’ and ‘potentially appropriate’ prescriptions in comparison with treatment guidelines. Results In February 2018, 188 141 antibiotics were prescribed for 174 889 patients who consulted GPs in the private sector. Penicillins were the most frequently prescribed antibiotic class, making up 40.7% of all antibiotics prescribed. Amoxicillin/clavulanic acid was the most frequently prescribed antibiotic, making up 28.6% of all antibiotics prescribed. Diseases of the respiratory system generated the highest number of prescriptions, making up 46.1% of all diagnoses. Of all prescriptions, 8.8% were appropriate, 32.0% were potentially appropriate, 45.4% were inappropriate and 13.8% could not be assessed. Of the appropriately and potentially appropriately prescribed antibiotics, 30.8% were correct antibiotic selections. Of the correctly selected antibiotics for adults, 57.7% had correct doses. Of the antibiotics prescribed with correct doses for adults, 76.7% had correct dosage frequencies and durations of treatment. Conclusions The study revealed that antibiotics were frequently prescribed inappropriately by GPs in the private primary healthcare sector. There is thus a need to develop stewardship interventions in the sector.

Assessing the effectiveness of antibiotics and communicating the problem of resistance are essential when devising antimicrobial stewardship programs (ASPs) in hospital settings. The Drug Resistance Index (DRI) is a useful tool that combines antibiotic consumption and bacterial resistance into a single measure. In this study, we used the DRI to assess the impact of introducing a new antibiotic restriction form on antibiotic effectiveness for the treatment of Gram-negative infections in the intensive care unit (ICU).This was an observational study to assess and evaluate the antibiotic susceptibility of Gram-negative bacteria and antibiotic prescribing rates for the antibiotics indicated for Gram-negative bacteria following the introduction of a new antibiotic restriction form. The study was conducted from 2015 to 2017 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. Changes in antibiotic effectiveness before and after the introduction of the form were evaluated by calculating the DRI for four of the most common Gram-negative pathogens and eight commonly used antibiotic classes.The overall DRI for the adult ICU was higher (59.45) in comparison to the hospital-wide DRI (47.96). A higher DRI was evident for carbapenems and antipseudomonal penicillins + beta-lactamase inhibitors.The DRI is a useful tool for tracking the effectiveness of antibiotics over time. The results of our study are significant in the way that it highlights the importance of having an effective antibiotic stewardship program in healthcare settings and regular feedback of antibiotic consumption data to the stakeholders to keep the antibiotic prescriptions in check, thereby ensuring their sustained effectiveness.

Conventional culture-based phenotypic and genomic surveillance has drawbacks and may not necessarily reflect the true burden of antibiotic resistance. The integration of metagenomic surveillance with transcriptomics and proteomics will yield a step change in the utility of surveillance data from treatment options to precision medicine.

The resistome, virulome and mobilome of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) isolated from pigs in Cameroon and South Africa were assessed using whole genome sequencing (WGS). Eleven clonally related phenotypic ESBL-Ec isolates were subjected to WGS. The prediction of antibiotic resistance genes, virulence factors (VFs) and plasmids was performed using ResFinder, VirulenceFinder and PlasmidFinder, respectively. Diverse sequence types (STs) were detected with ST2144 and ST88 being predominant and blaCTX-M-15 (55%) being the principal ESBL gene. All except two isolates harboured various aminoglycoside resistance genes, including aph(3″)-Ib (6/11, 55%) and aph(6)-1d (6/11, 55%), while the qnrS1 gene was identified in four of the isolates. The ESBL-Ec isolates showed a 93.6% score of being human pathogens. The fim, ehaB, ibeB/C were the leading virulence factors detected. All isolates harboured at least three extraintestinal pathogenic E. coli (ExPEC) VFs, with one isolate harbouring up to 18 ExPEC VFs. Five isolates (45.45%) harboured the plasmid incompatibility group IncF (FII, FIB, FIC, FIA). The study revealed that there is an urgent need to implement effective strategies to contain the dissemination of resistant and virulent ESBL-Ec through the food chain in Cameroon and South Africa.

Objectives/Purpose The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level.Methods GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level. Results The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies. Conclusion In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats.

Objectives/PurposeThe costs attributable to antimicrobial resistance (AMR) across human, animal, and environmental health remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network aimed to develop a global, One Health AMR Cost Framework, that can be used by countries, regions, and other entities to quantify the economic burden attributable to AMR.MethodsGAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. It operated by means of Delphi rounds, teleconferences (TCs) and face-to-face (F2F) meetings. It assumes a bottom-up cost estimate, at the National level, with a global scope across all One Health Areas.ResultsThe resulting framework consists of the epidemiological data and the direct and indirect cost components, linked by the likelihood of each AMR-related health state that imposes such costs, across all One Health Areas for a large number of relevant pathogens. It represents a first step towards more comprehensive analyses for comparing cost-effectiveness of AMR interventions at the local level as well as more harmonised analyses at the global level.ConclusionThis is the first full AMR costing framework to be developed for bacterial pathogens in human and animal health and the environment. It aims to provide guidance on the data items necessary to calculate AMR costs in a global, One Health perspective to facilitate harmonized, full economic analyses. It is only through building a realistic cost picture that we can make informed decisions about potential strategies and political priorities.

Background: Assessing the effectiveness of antibiotics and communicating the problem of resistance is essential when devising antimicrobial stewardship programs in hospital settings. The drug resistance index (DRI) is a useful tool that combines antibiotic consumption and bacterial resistance into a single measure. In this study, we used the DRI to assess the impact of introducing a new antibiotic restriction form on antibiotic effectiveness for the treatment of gram-negative infections in the intensive care unit (ICU). Methods: We conducted a before-and-after intervention study from 2015 to 2017 at King Abdulaziz Medical City, a tertiary-care facility in Jeddah, Saudi Arabia. The antibiotic susceptibility of gram-negative bacteria and antibiotic prescribing rates for antibiotics indicated for gram-negative bacteria were assessed to evaluate the impact of a new antibiotic restriction form introduced in the ICU in July 2016. Changes in antibiotic effectiveness before and after the intervention were evaluated by calculating the DRI for 4 of the most common gram-negative pathogens and 8 commonly used antibiotic classes. Results: The overall DRI for the adult ICU (59.45) was higher than the hospital-wide DRI (47.96). A higher DRI was evident for carbapenems and antipseudomonal penicillins + β-lactamase inhibitors. A. baumannii had the highest DRI, followed by K. pneumoniae in both the adult ICU and hospital-wide. After implementation of antibiotic restriction in the adult ICU, the DRI for carbapenems was significantly lower in the postintervention phase, from 31.61 to 26.05 (P = 0.031). Conclusions: DRI is a useful tool for tracking the effectiveness of antibiotics over time. The results highlight the importance of having effective antibiotic stewardship program in healthcare settings as well as regular feedback of antibiotic consumption data to the stakeholders to keep the antibiotic prescriptions in check, thereby ensuring their sustained effectiveness.Funding: NoneDisclosures: None

Background The increase in incidence of multidrug-resistant (MDR) organisms, especially gram-negative bacteria, in healthcare facilities is a serious cause of concern worldwide. This study was done at King Abdulaziz Medical City, Jeddah, a tertiary care hospital. The World Health Organization has published a priority pathogens list of antibiotic-resistant bacteria. The priority pathogens have been categorized into three major priorities (i.e., critical, high, and medium). The critical priority pathogens include common gram-negative bacteria (GNB) such as carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli. The current study identified risk factors for the acquisition of these MDR gram-negative critical priority pathogens in King Abdulaziz Medical City, Jeddah, to inform strategies for their containment. Methods A case-control study was carried out from January to April 2015, in which 100 patients with healthcare-associated infections (infections arising 48 hours after admission) caused by MDR GNB were compared with two control groups, i.e., 100 patients with healthcare-associated infections caused by non-MDR GNB (not meeting the criteria of MDR) and 100 patients without infection caused by GNB. MDR bacteria were defined as bacteria that were non-susceptible to at least one antibiotic in three or more classes of antibiotics. Data were analyzed using descriptive statistics (frequency and percentage of categorical variables). Multivariate regression analysis was undertaken to identify significant predictors of MDR GNB. Odds ratios (ORs) with 95% CIs were calculated and the level of significance was determined as p Results A total of 388 organisms were isolated during the study period from 332 patients. 56 (14%) patients were infected with more than one organism. Antibiotic therapy (OR 5.50, 95% CI 2.19–13.84; OR 3.98, 95% CI 1.68–9.44), stay in intensive care unit (OR 11.11, 95% CI 4.58–26.93; OR 8.60, 95% CI 3.28–22.57), and having indwelling medical devices (OR 3.02, 95% CI 1.45–6.33; OR 2.43, 95% CI 1.11–5.33) were the significant risk factors in patients infected with MDR GNB compared with each of the other two control groups, respectively. Conclusion The risk factors identified in our study provide guidance for healthcare workers for the prevention and containment of MDR GNB with special emphasis on effective implementation of an antimicrobial stewardship program and enhancing infection control practices in intensive care units.

The high prevalence of resistance to nalidixic acid and reduced susceptibility to ciprofloxacin of Salmonella spp. obtained from stool samples of neonates presenting with acute diarrhea in 2001 at the King Edward VIII hospital in Durban, South Africa, prompted this study to determine if there were any mutations in the QRDR of these isolates and to search for the qnrA gene. All isolates with nalidixic acid MICs > 48 μg/ml had the single mutation D87N, or D87G in the QRDR of the gyrA gene, and only 2 strains had an additional mutation; S83L and S83F respectively. The mutation S83T was present in only one isolate with the nalidixic acid MIC of 10 μg/ml whilst the 6 other strains with nalidixic acid MICs < 10 μg/ml had no changes in the QRDR of the gyrA gene. The qnrA gene was not found. These findings indicate that there are mutations in the gyrA of Salmonella isolates which could contribute to resistance to nalidixic acid with reduced susceptibility to ciprofloxacin and there is the co-expression of quinolone and extended-spectrum ß-lactam resistance among Salmonella spp.