Management of infectious disease syndromes in thoracic organ transplants and mechanical circulatory device recipients: a Delphi panel.

PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.

Auditing tools for antimicrobial prescribing in solid organ transplant recipients: The why, the how, and an assessment of current options.

BACKGROUND: Antimicrobial stewardship (AMS) aims to optimize antimicrobial use. Auditing and reporting of antimicrobial prescribing are essential. Auditing tools for solid organ transplant (SOT) patients should tailor to their needs. METHODS: We reviewed published data describing auditing tools in the general and SOT population. RESULTS: We focused on three internationally or nationally available auditing tools. The National Antimicrobial Prescribing Survey (NAPS) is web-based tool to report antimicrobial consumption and assess appropriateness using standardized definitions based on consensus guidelines. In the absence of guidelines, adjudication is based on AMS principles. An automated dashboard, analyses by indication or antimicrobial, and benchmarking reports are available. The National Healthcare Safety Network Antimicrobial Use/Resistance module was developed by the Centers for Disease Control and Prevention for hospitals to upload monthly data, which are standardized for benchmarking. It does not assess appropriateness or address SOT wards. The Global-Point Prevalence Survey from bioMérieux collects data on antimicrobial regimen, indication and microbial resistance. Variables unique to SOT include comorbidities and devices. Assessment of appropriateness is limited to guideline adherence, and benchmarking may require prearrangement with bioMérieux. Benchmarking requires prearrangement. Advances in electronic health record systems and clinical decision support tools can improve the efficiency of the auditing process. CONCLUSION: Each AMS auditing tool has unique features for SOT patients. Capturing immunosuppression, source control, organ dysfunction, donor-derived infection, serology, and colonization status will enhance their applicability.

Knowledge, perspectives and health outcome expectations of antibiotic therapy in hospitalized patients.

Background: The World Health Organization (WHO) has recognized antimicrobial resistance (AMR) as a top threat to global health. However, the public has an incomplete understanding of AMR and its consequences. Aim: The aim of this study was to explore patients' understanding, perspective and health outcome expectations for antibiotic therapy within an inpatient internal medicine population. Methods: A mixed methods study, combining a cross-sectional survey with qualitative methods. Fourteen questions (10 paper survey and four open ended interview questions) were used, and were completed by the participant in one sitting. Participants were recruited from General Internal Medicine units at two academic hospitals in Canada (convenience sample). Findings: Thirty participants were included. Out of a scale of 1-100%, participants indicated moderate concern (mean of 40%) about getting an infection that could not be cured by antibiotics. The majority agreed that they trusted their healthcare team to decide on appropriate antibiotic therapy (mean of 81%). The participants strongly agreed (mean of 90%) that it was important to understand the rationale for their antibiotic therapy. Three themes emerged from the qualitative analysis: 1) varying levels of knowledge; 2) viewing antibiotics as beneficial while emphasizing effectiveness; and 3) trusting the healthcare team with expectations for inclusion in decision making. Conclusion: The study results showed varying levels of patients' antibiotic knowledge and large gaps in awareness related to AMR. Exploring the role and workflow of interdisciplinary healthcare professionals may be a potential strategy to minimize patients' knowledge gap related to antimicrobial therapy and AMR.

The feasibility and generalizability of assessing the appropriateness of antimicrobial prescribing in hospitals: a review of the Australian National Antimicrobial Prescribing Survey.

The National Antimicrobial Prescribing Survey (NAPS) is a web-based qualitative auditing platform that provides a standardized and validated tool to assist hospitals in assessing the appropriateness of antimicrobial prescribing practices. Since its release in 2013, the NAPS has been adopted by all hospital types within Australia, including public and private facilities, and supports them in meeting the national standards for accreditation. Hospitals can generate real-time reports to assist with local antimicrobial stewardship (AMS) activities and interventions. De-identified aggregate data from the NAPS are also submitted to the Antimicrobial Use and Resistance in Australia surveillance system, for national reporting purposes, and to strengthen national AMS strategies. With the successful implementation of the programme within Australia, the NAPS has now been adopted by countries with both well-resourced and resource-limited healthcare systems. We provide here a narrative review describing the experience of users utilizing the NAPS programme in Canada, Malaysia and Bhutan. We highlight the key barriers and facilitators to implementation and demonstrate that the NAPS methodology is feasible, generalizable and translatable to various settings and able to assist in initiatives to optimize the use of antimicrobials.

A pragmatic randomized trial of a primary care antimicrobial stewardship intervention in Ontario, Canada.

BACKGROUND: More than 90% of antibiotics are prescribed in primary care, but 50% may be unnecessary. Reducing unnecessary antibiotic overuse is needed to limit antimicrobial resistance. We conducted a pragmatic trial of a primary care provider-focused antimicrobial stewardship intervention to reduce antibiotic prescriptions in primary care. METHODS: Primary care practitioners from six primary care clinics in Toronto, Ontario were assigned to intervention or control groups to evaluate the effectiveness of a multi-faceted intervention for reducing antibiotic prescriptions to adults with respiratory and urinary tract infections. The intervention included provider education, clinical decision aids, and audit and feedback of antibiotic prescribing. The primary outcome was total antibiotic prescriptions for these infections. Secondary outcomes were delayed prescriptions, prescriptions longer than 7 days, recommended antibiotic use, and outcomes for individual infections. Generalized estimating equations were used to estimate treatment effects, adjusting for clustering by clinic and baseline differences. RESULTS: There were 1682 encounters involving 54 primary care providers from January until May 31, 2019. In intervention clinics, the odds of any antibiotic prescription was reduced 22% (adjusted Odds Ratio (OR) = 0.78; 95% Confidence Interval (CI) = 0.64.0.96). The odds that a delay in filling a prescription was recommended was increased (adjusted OR=2.29; 95% CI=1.37, 3.83), while prescription durations greater than 7 days were reduced (adjusted OR=0.24; 95% CI=0.13, 0.43). Recommended antibiotic use was similar in control (85.4%) and intervention clinics (91.8%, p=0.37). CONCLUSIONS: A community-based, primary care provider-focused antimicrobial stewardship intervention was associated with a reduced likelihood of antibiotic prescriptions for respiratory and urinary infections, an increase in delayed prescriptions, and reduced prescription durations. TRIAL REGISTRATION: clinicaltrials.gov ( NCT03517215 ).

Development and evaluation of a primary care antimicrobial stewardship program (PC-ASP) in Toronto, Ontario, Canada.

Background: Effective community-based antimicrobial stewardship programs (ASPs) are needed because 90% of antimicrobials are prescribed in the community. A primary care ASP (PC-ASP) was evaluated for its effectiveness in lowering antibiotic prescriptions for six common infections. Methods: A multi-faceted educational program was assessed using a before-and-after design in four primary care clinics from 2015 through 2017. The primary outcome was the difference between control and intervention clinics in total antibiotic prescriptions for six common infections before and after the intervention. Secondary outcomes included changes in condition-specific antibiotic use, delayed antibiotic prescriptions, prescriptions exceeding 7 days duration, use of recommended antibiotics, and emergency department visits or hospitalizations within 30 days. Multi-method models adjusting for demographics, case mix, and clustering by physician were used to estimate treatment effects. Results: Total antibiotic prescriptions in control and intervention clinics did not differ (difference in differences = 1.7%; 95% CI -12.5% to 15.9%), nor did use of delayed prescriptions (-5.2%; 95% CI -24.2% to 13.8%). Prescriptions for longer than 7 days were significantly reduced (-21.3%; 95% CI -42.5% to -0.1%). However, only 781 of 1,777 encounters (44.0%) involved providers who completed the ASP education. Where providers completed the education, delayed prescriptions increased 17.7% (p = 0.06), and prescriptions exceeding 7 days duration declined (-27%; 95% CI -48.3% to -5.6%). Subsequent emergency department visits and hospitalizations did not increase. Conclusions: PC-ASP effectiveness on antibiotic use was variable. Shorter prescription durations and increased use of delayed prescriptions were adopted by engaged primary care providers.

Historique: Des programmes de gestion antimicrobienne (PGA) communautaires efficaces doivent exister, parce que 90 % des antimicrobiens sont prescrits dans la communauté. Des chercheurs ont évalué un PGA en première ligne (PGA-PL) afin d'en déterminer l'efficacité à réduire les prescriptions d'antibiotiques pour six infections courantes. Méthodologie: Les chercheurs ont évalué un programme de formation polyvalent au moyen d'une méthodologie avant-après dans quatre cliniques de soins de première ligne entre 2015 et 2017. Le résultat clinique primaire était la différence entre les cliniques de contrôle et d'intervention pour ce qui est du total de prescriptions antibiotiques contre six infections courantes avant et après l'intervention. Les résultats cliniques secondaires incluaient des modifications à l'utilisation des antibiotiques propres au trouble de santé, le report des prescriptions d'antibiotiques, des prescriptions de plus de sept jours, l'utilisation des antibiotiques recommandés et les visites à l'urgence ou les hospitalisations dans les 30 jours. Les chercheurs ont utilisé des méthodes multimodèles tenant compte de la démographie, du mélange de cas et du regroupement par médecin pour évaluer l'effet des traitements. Résultats: Les prescriptions totales d'antibiotiques dans les cliniques de contrôle et d'intervention ne différaient pas (différences des différences = 1,7 %; IC à 95 %, ­12,5 % à 15,9 %), ni l'utilisation de prescriptions reportées (­5,2 %; IC à 95 %, ­24,2 % à 13,8 %). Les prescriptions de plus de sept jours étaient très peu courantes (­21,3 %; IC à 95 %, ­42,5 % à ­0,1 %). Cependant, seulement 781 des 1 777 rencontres (44,0 %) avaient eu lieu avec des dispensateurs qui avaient suivi la formation sur le PGA. Lorsque les dispensateurs avaient suivi la formation, les reports de prescriptions augmentaient de 17,7 % (p = 0,06) et les prescriptions de plus de sept jours diminuaient (­27 %; IC à 95 %, ­48,3 % à ­5,6 %). Les visites subséquentes à l'urgence et les hospitalisations n'ont pas augmenté. Conclusions: L'efficacité du PGA-PL pour l'utilisation d'antibiotiques était variable. Les dispensateurs de soins de première ligne qui y avaient participé préparaient des prescriptions de moins longue durée et reportaient davantage leurs prescriptions.

Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel prognostic test in acute liver failure in children.

BACKGROUND: Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS). OBJECTIVE: Because we had previously shown that glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices. METHODS: Twenty-four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA) and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high-pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M. RESULTS: The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria. CONCLUSION: Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.