Thailand's national strategic plan on antimicrobial resistance: progress and challenges.

Antimicrobial resistance is a serious threat that affects all countries. The Global Action Plan on antimicrobial resistance and the United Nations Political Declaration on antimicrobial resistance set standards for countries to resolve antimicrobial resistance challenges under the One Health approach. We assess progress and challenges in implementing Thailand's national strategic plan on antimicrobial resistance 2017-2022, discuss interim outcomes and share lessons learnt. Major progress includes: establishing a national governance mechanism that leads high-impact policy on antimicrobial resistance and consolidates actions and multisectoral collaboration; creating a monitoring system and platform to track implementation of the strategic plan; and converting strategies of the strategic plan into actions such as controlling the distribution and use of antimicrobials in humans and animals. Interim results indicate that antimicrobial consumption in animals has nearly halved (exceeding the national goal of a 30% reduction) whereas other goals have not yet reached their targets. We have learnt that elevating antimicrobial resistance to high-level visibility and establishing a national governance mechanism is an important first step, and a monitoring and evaluation system should be developed in parallel with implementation. Securing funds is crucial. Policy coherence is needed to avoid duplication of actions. Highly ambitious goals, although yet to be achieved, can advance actions beyond expectations. Political commitment and collaboration across different sectors will continue to play important roles but might not be sustained without a well-designed governance structure to support long-term actions to address antimicrobial resistance.

La résistance aux antimicrobiens fait peser une sérieuse menace sur la planète tout entière. Le Plan d'action mondial pour combattre la résistance aux antimicrobiens ainsi que la Déclaration politique des Nations Unies sur la résistance aux agents antimicrobiens ont défini des normes pour les pays, afin qu'ils puissent faire face aux enjeux liés à la résistance aux antimicrobiens selon l'approche «One Health¼. Nous avons évalué les progrès et défis de la mise en œuvre du plan stratégique national de la Thaïlande en la matière pour 2017­2022, mais aussi discuté des résultats provisoires et partagé les enseignements tirés. Parmi les principaux progrès accomplis figurent l'établissement d'un mécanisme de gouvernance national pour mener une politique à impact élevé sur la résistance aux antimicrobiens, renforcer les actions et favoriser la collaboration intersectorielle; la création d'un système de surveillance et d'une plateforme pour suivre la mise en œuvre du plan stratégique; et enfin, la conversion des stratégies du plan en actions telles que le contrôle de la distribution et de l'usage des antimicrobiens chez les humains et les animaux. Les résultats provisoires indiquent que la consommation d'antimicrobiens chez les animaux a diminué de moitié (ce qui est supérieur à l'objectif national d'une réduction de 30%), tandis que les autres objectifs n'ont pas encore été atteints. Nous avons constaté qu'accroître la visibilité de la résistance aux antimicrobiens et instaurer un mécanisme de gouvernance national constituaient des étapes cruciales, et qu'un système de surveillance et d'évaluation devait être développé parallèlement à la mise en œuvre. L'obtention de financements est elle aussi essentielle. Une politique cohérente est nécessaire pour éviter de multiplier les actions similaires. Fixer des objectifs très ambitieux, même s'ils ne sont pas encore atteints, permet en outre de faire progresser les actions au-delà des attentes. Enfin, l'engagement politique et la collaboration entre différents secteurs continueront à jouer un rôle prépondérant, mais ne pourront peut-être pas se poursuivre sans une structure de gouvernance bien conçue, capable de soutenir des actions à long terme visant à remédier à la résistance aux antimicrobiens.

La resistencia a los antimicrobianos es una grave amenaza que afecta a todos los países. El Plan de Acción Mundial sobre la resistencia a los antimicrobianos y la Declaración Política de las Naciones Unidas sobre la resistencia a los antimicrobianos establecen normas para que los países resuelvan los problemas de resistencia a los antimicrobianos en el marco del enfoque «Una única salud¼. Evaluamos los avances y los desafíos en la aplicación del plan estratégico nacional de Tailandia sobre la resistencia a los antimicrobianos 2017-2022, analizamos los resultados provisionales y compartimos las lecciones aprendidas. Entre los principales avances se encuentran: el establecimiento de un mecanismo de gobernanza nacional que lidera la política de alto impacto sobre la resistencia a los antimicrobianos y consolida las acciones y la colaboración multisectorial; la creación de un sistema de seguimiento y una plataforma para seguir la aplicación del plan estratégico; y la conversión de las estrategias del plan estratégico en acciones como el control de la distribución y el uso de antimicrobianos en humanos y animales. Los resultados provisionales indican que el consumo de antimicrobianos en animales se ha reducido casi a la mitad (superando el objetivo nacional de una reducción del 30 %), mientras que otros objetivos aún no han alcanzado sus metas. Hemos aprendido que elevar la resistencia a los antimicrobianos a una visibilidad de alto nivel y establecer un mecanismo de gobernanza nacional es un primer paso importante, y que debe desarrollarse un sistema de seguimiento y evaluación en paralelo a la implementación. Asegurar los fondos es crucial. La coherencia política es necesaria para evitar la duplicación de acciones. Unos objetivos muy ambiciosos, aunque todavía no se hayan alcanzado, pueden hacer avanzar las acciones más allá de las expectativas. El compromiso político y la colaboración entre los distintos sectores seguirán desempeñando un papel importante, pero podrían no mantenerse sin una estructura de gobernanza bien diseñada que apoye las acciones a largo plazo para hacer frente a la resistencia a los antimicrobianos.

Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning.

OBJECTIVES: Fluoroquinolones are routinely overprescribed for uncomplicated urinary tract infection (uUTI), acute sinusitis, and acute bronchitis. In 2016, the United States (US) Food and Drug Administration (FDA) updated the boxed warning on fluoroquinolones, recommending against their use as first-line agents for the routine pharmacologic management of uUTI, acute sinusitis, and acute bronchitis in patients who have other treatment options. The primary objective of this study was to determine if the 2016 expanded boxed warning was associated with decreased fluoroquinolone prescription rates for these three diagnoses. METHODS: We retrospectively reviewed antibiotics prescribed at a single, large, academic outpatient center for these three diagnoses between January 2013 and May 2018. Interrupted time series analysis was used to compare the rate of fluoroquinolone prescriptions before and after the May 2016 FDA boxed warning. RESULTS: A total of 10 087 antibiotic prescriptions for these three diagnoses were examined. There was no significant change in fluoroquinolone prescription rates after the FDA boxed warning. The majority of inappropriate fluoroquinolone prescriptions were given for the management of uUTI. CONCLUSION: The 2016 US FDA boxed warning against fluoroquinolone use for uUTI, acute sinusitis, and acute bronchitis was not associated with a statistically significant reduction in the rate of fluoroquinolone prescriptions for these diagnoses. Additional research is needed to define how US FDA boxed warnings may be incorporated into broader antibiotic stewardship programs to decrease overuse of fluoroquinolones and avoid adverse effects of the drug class, including Clostridioides difficile infections and emergence of resistant organisms.

A whole-health-economy approach to antimicrobial stewardship: Analysis of current models and future direction.

In a Policy Forum, Alison Holmes and colleagues discuss coordinated approaches to antimicrobial stewardship.

Long-term outcomes of an educational intervention to reduce antibiotic prescribing for childhood upper respiratory tract infections in rural China: Follow-up of a cluster-randomised controlled trial.

BACKGROUND: Inappropriate antibiotic prescribing causes widespread serious health problems. To reduce prescribing of antibiotics in Chinese primary care to children with upper respiratory tract infections (URTIs), we developed an intervention comprising clinical guidelines, monthly prescribing review meetings, doctor-patient communication skills training, and education materials for caregivers. We previously evaluated our intervention using an unblinded cluster-randomised controlled trial (cRCT) in 25 primary care facilities across two rural counties. When our trial ended at the 6-month follow-up period, we found that the intervention had reduced antibiotic prescribing for childhood URTIs by 29 percentage points (pp) (95% CI -42 to -16). METHODS AND FINDINGS: In this long-term follow-up study, we collected our trial outcomes from the one county (14 facilities and 1:1 cluster randomisation ratio) that had electronic records available 12 months after the trial ended, at the 18-month follow-up period. Our primary outcome was the antibiotic prescription rate (APR)-the percentage of outpatient prescriptions containing any antibiotic(s) for children aged 2 to 14 years who had a primary diagnosis of a URTI and had no other illness requiring antibiotics. We also conducted 15 in-depth interviews to understand how interventions were sustained. In intervention facilities, the APR was 84% (1,171 out of 1,400) at baseline, 37% (515 out of 1,380) at 6 months, and 54% (2,748 out of 5,084) at 18 months, and in control facilities, it was 76% (1,063 out of 1,400), 77% (1,084 out of 1,400), and 75% (2,772 out of 3,685), respectively. After adjusting for patient and prescribing doctor covariates, compared to the baseline intervention-control difference, the difference at 6 months represented a 6-month intervention-arm reduction in the APR of -49 pp (95% CI -63 to -35; P < 0.0001), and compared to the baseline difference, the difference at 18 months represented an 18-month intervention-arm reduction in the APR of -36 pp (95% CI -55 to -17; P < 0.0001). Compared to the 6-month intervention-control difference, the difference at 18 months represented no change in the APR: 13 pp (95% CI -7 to 33; P = 0.21). Factors reported to sustain reductions in antibiotic prescribing included doctors' improved knowledge and communication skills and focused prescription review meetings, whereas lack of supervision and monitoring may be associated with relapse. Key limitations were not including all clusters from the trial and not collecting returned visits or sepsis cases. CONCLUSIONS: Our intervention was associated with sustained and substantial reductions in antibiotic prescribing at the end of the intervention period and 12 months later. Our intervention may be adapted to similar resource-poor settings. TRIAL REGISTRATION: ISRCTN registry ISRCTN14340536.

Improved Antibiotic Prescribing within a Veterans Affairs Primary Care System through a Multifaceted Intervention Centered on Peer Comparison of Overall Antibiotic Prescribing Rates.

Reducing inappropriate outpatient antibiotic use is an important national goal. Limited data exist on targeted education and peer comparison of overall antibiotic prescribing rates as an antimicrobial stewardship strategy. Primary care professionals (PCPs) from all seven clinics within our health care system were offered an education session, followed by monthly e-mails with their antibiotic prescribing rate, peer prescribing rates, and a system target. A pre-post analysis was conducted to compare prescribing rates during the intervention period (January to June 2017) to a seasonal baseline (January to June 2016) using a regression model. A random sample of prescriptions was reviewed for adherence to consensus guidelines. Educational sessions were attended by 68.5% (50/73) of PCPs. From the baseline to the intervention period, the mean rate of monthly antibiotic prescriptions declined from 76.9 to 49.5 per 1,000 office visits (35.6% reduction [P < 0.001]). Among reviewed cases, unnecessary antibiotic prescribing declined (58.8% [80/136] versus 38.9% [70/180]; 33.9% reduction [P = 0.0006]), and the rate of optimally prescribed antibiotics increased (19.9% [27/136] versus 30% [54/180]; 50.8% increase [P = 0.05]). If an antibiotic was indicated, there were no significant differences in prescribing of guideline-discordant agents (21.4% [12/56] versus 19.1% [21/110] [P = 0.8]) or guideline-concordant agents for a guideline-discordant duration (38.6% [17/44] versus 39.3% [35/89] [P = 1]). There were significant reductions in azithromycin and fluoroquinolone prescriptions (50.9% and 59.4% [P values of <0.001], respectively), but most prescriptions for these agents in the intervention period remained inappropriate. Initial education followed by monthly peer comparison of overall antibiotic prescribing rates reduced total and unnecessary antibiotic prescribing in primary care clinics.

Trend of antibiotics usage for acute pyelonephritis in Korea based on national health insurance data 2010-2014.

BACKGROUND: The objective of this study is to describe the changes in prescribing practices of antibiotics to treat acute pyelonephritis (APN) in Korea. METHODS: The claim data base of the Health Insurance Review and Assessment Service in Korea was used to select patients with ICD-10 codes N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, not specified as acute nor chronic) as the primary discharge diagnosis during 2010-2014. Consumption of each class of antibiotics was converted to Defined Daily Dose (DDD)/event. RESULTS: Throughout the five-year period, the average antibiotic consumption were 11.3 DDD per inpatient event and 6.0 DDD per outpatient event. The annual average antibiotic consumption increased for inpatients (P = 0.002), but remained stable for outpatients (P = 0.066). The use of parenteral antibiotics increased for inpatients (P < 0.001), but decreased for outpatients (P = 0.017). As for the the antibiotic classes, 3rd generation cephalosporins (3rd CEPs) was the most commonly prescribed (41.4%) for inpatients, followed by fluoroquinolones (FQs) (28.5%); for outpatient, FQs (54.8%) was the most commonly prescribed, followed by 3rd CEPs (13.1%). The use of 3rd CEPs (P < 0.001), beta-lactam/beta-lactamase inhibitors (P = 0.007), and carbapenems (P < 0.001) increased substantially for the treatment of hospitalized APN patients. In particular, carbapenems use increased 3.1-fold over the 5 years. CONCLUSIONS: Prescription of broad-spectrum antibiotics increased much for the treatment of APN in Korea during 2010-2014.

Antimicrobial use trends, Israel, 2012 to 2017.

BackgroundIn 2012, Israel's National Center for Infection Control initiated a national stewardship programme that included mandatory annual reporting of antimicrobial use. Here we present nationwide Israeli data for the period 2012 to 2017.AimThe goal of this study was to detect trends in antimicrobial use in Israel following the introduction of the stewardship programme, as part of an assessment of the programme's impact.MethodsIn this retrospective observational study, data were collected from Israel's health maintenance organisations (HMOs), acute care hospitals and post-acute care hospitals (PACHs). Acute care hospital data were collected for general medical and surgical wards, and medical/surgical intensive care units (ICUs). Data were converted into defined daily doses (DDD), with use rates presented as DDD per 1,000 insured/day in the community and DDD per 100 patient-days in hospitals and PACHs. Trends were analysed using linear regression.ResultsAntimicrobial use decreased across sectors between 2012 and 2017. In the community, the decrease was modest, from 22.8 to 21.8 DDD per 1,000 insured per day (4.4%, p = 0.004). In acute care hospitals, antibiotic DDDs per 100 patient-days decreased from 100.0 to 84.0 (16.0%, p = 0.002) in medical wards, from 112.8 to 94.2 (16.5%, p = 0.004) in surgical wards and from 154.4 to 137.2 (11.1%, p = 0.04) in ICUs. Antimicrobial use decreased most markedly in PACHs, from 29.1 to 18.1 DDD per 100 patient-days (37.8%, p = 0.005).ConclusionBetween 2012 and 2017, antimicrobial use decreased significantly in all types of healthcare institutions in Israel, following the introduction of the nationwide antimicrobial stewardship programme.

Decreasing and stabilising trends of antimicrobial consumption and resistance in Escherichia coli and Klebsiella pneumoniae in segmented regression analysis, European Union/European Economic Area, 2001 to 2018.

Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.

Towards a global definition of responsible antibiotic use: results of an international multidisciplinary consensus procedure.

Background: Conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project, this study aimed to identify key elements for a global definition of responsible antibiotic use based on diverse stakeholder input. Methods: A three-step RAND-modified Delphi method was applied. First, a systematic review of antibiotic stewardship literature and relevant organization web sites identified definitions and synonyms of responsible use. Identified elements of definitions were presented by questionnaire to a multidisciplinary international stakeholder panel for appraisal of their relevance. Finally, questionnaire results were discussed in a consensus meeting. Results: The systematic review and the web site search identified 17 synonyms (e.g. appropriate, correct) and 22 potential elements to include in a definition of responsible use. Elements were grouped into patient-level (e.g. Indication, Documentation) or societal-level elements (e.g. Education, Future Effectiveness). Forty-eight stakeholders with diverse backgrounds [medical community, public health, patients, antibiotic research and development (R&D), regulators, governments] from 18 countries across all continents participated in the questionnaire. Based on relevance scores, 21 elements were retained, 9 were rephrased and 1 was added. Together, the 22 elements and associated best-practice descriptions comprise an exhaustive list of elements to be considered when defining responsible use. Conclusions: Combination of concepts from the literature and stakeholder opinion led to an international multidisciplinary consensus on a global definition of responsible antibiotic use. The widely diverging perspectives of stakeholders providing input should ensure the comprehensiveness and relevance of the definition for both individual patients and society. An aspirational goal would be to address all elements.

[Obstacles and perspectives of new antimicrobial concepts within research and development]. / Hürden und Aussichten neuer antimikrobieller Konzepte in Forschung und Entwicklung.

Antimicrobial resistance (AMR) has developed into a serious problem for the healthcare sector worldwide. Research on fundamentally novel antibiotics has been insufficient for decades and only a few new compounds have reached the market. Thus, the pressure to implement novel and effective concepts for the reduction of infections through problematic pathogens has dramatically increased. This demand has been recognized by politicians and comprehensive national and international funding programs have been launched. A major role of many funding lines is the investigation and development of therapeutics exerting a novel mechanism of action and/or minimizing the frequency of resistance. In addition to the actual clinical pipeline, this article lists selected examples from research and early development with a special focus on antibiotics. Moreover, alternative approaches like antivirulence and phage therapy as well as immunomodulation are summarized. AMR is no longer solely a healthcare policy, but is of societal significance as a whole. A consolidation of infrastructures and public-private partnerships, a reduction of regulatory obstacles and a continuous pursuit of innovations for antimicrobial therapy are urgently needed.

Irrational antibiotic prescribing practice among children in critical care of tertiary hospitals.

This study assessed the prescribing pattern of irrational use of antibiotic among children under age of 12 years in public and private sector hospitals in Pakistan. The prospective clinical evaluation of drug utilization pattern of antimicrobials from Patient Bedside File (PBF) of in-patients and Culture Sensitivity Test (CST) reports were evaluated to determine the antibiotic resistance. Two indicators recorded to assess antibiotic prescribing were; dose of prescribed antibiotic (low-dose, rational and high -dose) and Indication (valid or invalid). Antibiotics resistance for 25 selected antibiotics was determined by culture sensitivity test. This study showed that in Private Sector Hospital 77.7% neonates, 13.3% infants and 9% children admitted in ICU were receiving antibiotics, among them only 57.3% neonates, 62% infants and 59.9% children were found valid that is prescribed antibiotics for right indication. 27% neonates, 19% infants and 22.1% children were prescribed under dose of antibiotics, which may lead to antimicrobial resistance and increased cost of hospital stay. Only 29.1% neonates, 30% infants and 36.8% children were receiving rational dosing. In Public Sector Hospital, 65.6% neonates, 19.4% infants and 15% children were receiving antibiotics. Among them valid indication was found in 35.3% neonates, 35.6% infants and 39.8% in children. 33.3% neonates, 26.6% infants and 28.2% children were receiving under dose that may lead to resistance not only among those who were prescribed under dose but also such bacteria become resistant and spread to other population to increase antimicrobial resistance. The irrational prescribing of antibiotics was found very high (above 50%) in Public sector hospital (Hospital-B) for every age group whereas in Private sector hospital (Hospital-A) this practice was found near to 50%. In this study the prescribing frequency of Amikacin, Cefixime, Cefotaxime, Meropenem, Amoxicillin, Vancomycin, Azithromycin, Levofloxacin and Clarithromycin was found above 80% in both hospitals (A and B). Among these, Amoxicillin, Penicillin, Erythromycin and Cephalexin showed higher resistance i.e. 49.2%.

Knowledge, perceptions and practices on antibiotic use among Sri Lankan doctors.

INTRODUCTION: Prescribers have a major role in preventing antimicrobial resistance (AMR) through appropriate prescribing. However, in countries like Sri Lanka, where continuous professional development is not mandatory for license renewal and antimicrobial stewardship is not implemented, prescribing practices go largely unchecked. OBJECTIVES: To identify the knowledge on antibiotic use and practices related to antibiotic prescribing among Sri Lankan doctors. METHODS: This cross-sectional study was conducted in 2020. We used a validated, pretested Google-form based questionnaire with multiple choices, single best answer questions, polar questions (Yes/No) and five-point Likert scale questions. The Google-sheet generated was used for data analysis. Knowledge and practice scores were calculated. RESULTS: Of the 262 respondents, 40.1% were males. Majority (61.8%) were aged 25-35-years and in medical practice for 0-5 years (48.9%) while 46.2% had or were engaged in post graduate studies. Knowledge scores ranged from 98.31% to 46.55% [mean:71.27% (SD±10.83); median:71.18% (IQR 64.4-79.7)]. Most (98.09%) obtained ≥50 marks while 45.8% scored more than the mean. The practice scores ranged from 100% to 0% [mean:65.33% (SD±18.16), median:66.67% (IQR53.3-80)]. The majority (81.3%) scored ≥50 in the practice score while 52.3% achieved more than the mean practice score. The knowledge score and the practice score differed significantly (p<0.001, related sample Wilcoxon Signed Rank Test) but the knowledge and practice scores were significantly correlated [Spearman correlation, p<0.001, r = 0.343 (Bias corrected 95% CI 0.237-0.448)]. Knowledge scores and the practice scores were significantly higher in those with or undergoing postgraduate training. CONCLUSIONS: While the knowledge and practice scores were high, and knowledge and practice scores were correlated, the practices score was lower than that of knowledge indicating the need to encourage correct practices through means other than solely promoting knowledge.

Perceptions of surgeons on surgical antibiotic prophylaxis use at an urban tertiary hospital in Tanzania.

BACKGROUND: Surgical Site Infections are a major cause of morbidity and mortality among operated patients. In spite of the accessibility of universal and national guidelines for surgical prophylaxis, recent studies surveying the present routine of prophylaxis have demonstrated overutilization of a wide range antibacterial medication for a single patient. Few studies have shown qualitatively factors influencing this and perceptions of surgeons on surgical antibiotic prophylaxis use. Unfortunately, none of these studies have been done in Tanzania. OBJECTIVE: To describe the perceptions of surgeons on surgical antibiotic prophylaxis use at an urban tertiary hospital. METHODS: A qualitative study involving in-depth interviews with surgeons was conducted in English by the primary investigator. The interviews were audio-recorded and transcribed verbatim. Systematic text condensation by Malterud was used for data analysis. FINDINGS: Fourteen surgeons and obstetrics and gynaecologists participated. Their perceptions were summarized into three main categories: Inadequate data to support practice; one who sees the patient decides the antibiotic prophylaxis; prolonged antibiotic use for fear of unknown. The participants perceived that choice of antibiotic should be based on local hospital data for bacterial resistance pattern, however the hospital guidelines and data for surgical site infection rates are unknown. Fear of getting infection and anticipating complications led to prolonged antibiotics use. CONCLUSION: The study provides an understanding of surgical antibiotic prophylaxis use and its implementation challenges. This was partly expressed by unavailability of local data and guidelines to enhance practice. To improve this, there is a need of guidelines that incorporates local resistance surveillance data and enhanced antibiotic stewardship programmes. A strong consideration should be placed into ways to combat the fears of surgeons for complications, as these significantly affect the current practise with use of surgical antibiotic prophylaxis.