An innovative tool to prioritize the assessment of investigational COVID-19 therapeutics: A pilot project.

Background: As the COVID-19 pandemic unfolded, hundreds of investigational COVID-19 therapeutics emerged. Maintaining situational awareness of this extensive and rapidly evolving therapeutic landscape represented an unprecedented challenge for the Public Health Agency of Canada, as it worked to promote and protect the health of Canadians. A tool to triage and prioritize the assessment of these therapeutics was needed. Methods: The objective was to develop and conduct an initial validation of a tool to identify investigational COVID-19 therapeutics for further review based on an efficient preliminary assessment, using a systematic and reliable process that would be practical to validate, implement and update. Phase 1 of this pilot project consisted of a literature search to identify existing COVID-19 therapeutic assessment prioritization tools, development of the Rapid Scoring Tool (RST) and initial validation of the tool. Results: No tools designed to rank investigational COVID-19 therapeutics for the purpose of prioritizing their assessment were identified. However, a few publications provided criteria to consider and therapeutic ranking methods, which helped shape the development of the RST. The RST included eight criteria and several descriptors ("characteristics"). A universal characteristic scoring scale from -10 to 10 was developed. The sum of all the characteristic scores yielded an overall benefit score for each therapeutic. The RST appropriately ranked therapeutics using a systematic, reliable and practical approach. Conclusion: Phase 1 was successfully completed. The RST presents several distinct aspects compared with other tools, including its scoring scale and method, and capacity to factor in incomplete or pending information. It is anticipated that the framework used for the RST will lend itself to use in other dynamic situations involving many interventions.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Evaluating Antimicrobial Use and Spectrum of Activity in Ontario Hospitals: Feasibility of a Multicentered Point Prevalence Study.

BACKGROUND: Antimicrobial stewardship, a key component of an overall strategy to address antimicrobial resistance, has been recognized as a global priority. The ability to track and benchmark antimicrobial use (AMU) is critical to advancing stewardship from an organizational and provincial perspective. As there are few comprehensive systems in Canada that allow for benchmarking, Public Health Ontario conducted a pilot in 2016/2017 to assess the feasibility of using a point prevalence methodology as the basis of a province-wide AMU surveillance program. METHODS: Three acute care hospitals of differing sizes in Ontario, Canada, participated. Adults admitted to inpatient acute care beds on the survey date were eligible for inclusion; a sample size of 170 per hospital was targeted, and data were collected for the 24-hour period before and including the survey date. Debrief sessions at each site were used to gather feedback about the process. Prevalence of AMU and the Antimicrobial Spectrum Index (ASI) was reported for each hospital and by indication per patient case. RESULTS: Participants identified required improvements for scalability including streamlining ethics, data sharing processes, and enhancing the ability to compare with peer organizations at a provincial level. Of 457 patients, 172 (38%) were receiving at least 1 antimicrobial agent. Beta-lactam/beta-lactamase inhibitors were the most common (18%). The overall mean ASI per patient was 6.59; most cases were for treatment of infection (84%). CONCLUSIONS: This pilot identified factors and features required for a scalable provincial AMU surveillance program; future efforts should harmonize administrative processes and enable interfacility benchmarking.

Addressing Concerns about Changing the Route of Antimicrobial Administration from Intravenous to Oral in Adult Inpatients.

BACKGROUND: Many health care institutions are in the process of establishing antimicrobial stewardship programs. Changing the route of administration of antimicrobial agents from intravenous to oral (IV to PO) is a simple, well-recognized intervention that is often part of an antimicrobial stewardship program. However, the attending health care team may have concerns about making this switch. OBJECTIVES: To provide insights into common concerns related to IV to PO conversion, with the aim of helping antimicrobial stewardship teams to address them. DATA SOURCES: Published clinical trials and reviews were identified from a literature search of Ovid MEDLINE with the keywords (step down or switch or conversion or transition or sequential) and (antibiotics or antibacterial agents or antimicrobial or anti-infective agents). DATA SYNTHESIS: The following issues are addressed in this review: benefits of the oral route, serum concentrations yielded by the oral formulation, source of pharmacokinetic data, clinical outcomes, provision of care in the intensive care unit, fear of therapeutic failure, and administration of antimicrobials via feeding tube. CONCLUSIONS: When considering a change to oral therapy, it is important to have a thorough understanding of key aspects of the antimicrobial agent, the patient, and the disease being treated. The antimicrobial stewardship team has an important role in facilitating IV to PO conversion, educating prescribers, and addressing any concerns or reservations that may interfere with timely transition from IV to PO administration.

CONTEXTE: Bon nombre d'établissements de santé sont en voie de mettre en place de programmes de gestion responsable des antimicrobiens. Changer de voie d'administration des agents antimicrobiens en passant d'une administration intraveineuse à une administration orale est une intervention simple et reconnue qui fait souvent partie de ces programmes. Cependant, opérer un tel changement pourrait soulever des préoccupations chez les membres de l'équipe de soins de santé traitante. OBJECTIFS: Dégager une meilleure compréhension des préoccupations courantes entourant le passage de la voie d'administration intraveineuse à la voie d'administration orale dans le but d'aider les équipes de gestion responsable des antimicrobiens à y répondre. SOURCES DES DONNÉES: Des analyses documentaires ainsi que des essais cliniques publiés ont été recensés grâce à une recherche dans Ovid MEDLINE à l'aide des mots clés (step down [passage] ou switch [échange] ou conversion [conversion] ou transition [transition] ou sequential [successif]) et (antibiotics [antibiotiques]) ou antibacterial agents [agents antibactériens] ou antimicrobial [antimicrobien] ou anti-infective agents [agents anti-infectieux]). SYNTHÈSE DES DONNÉES: Les préoccupations suivantes sont abordées dans la présente analyse : les avantages de la voie orale, les concentrations sériques obtenues grâce aux préparations orales, la source des données pharmacocinétiques, les résultats cliniques, la prestation des soins à l'unité des soins intensifs, la peur de l'échec thérapeutique et l'administration des antimicrobiens par sonde gastrique. CONCLUSIONS: Lorsque l'on envisage de passer à un traitement par voie orale, il est important de posséder une connaissance approfondie des principaux aspects de l'agent antimicrobien, de l'état du patient et de la maladie traitée. L'équipe de gestion responsable des antimicrobiens détient un rôle important pour ce qui est de simplifier le passage d'une administration intraveineuse à une administration orale, d'éduquer les prescripteurs et de répondre aux préoccupations et doutes qui pourraient faire obstacle à un tel passage en temps voulu.

Extrapyramidal symptoms with ritonavir/indinavir plus risperidone.

OBJECTIVE: To report a case of suspected extrapyramidal symptoms (EPS) in a patient initiated on ritonavir and indinavir while taking risperidone for a tic disorder. CASE SUMMARY: A 35-year-old white man with AIDS received risperidone 2 mg twice daily for treatment of a Tourette's-like tic disorder. Ritonavir and indinavir were initiated, and 1 week later, he experienced significantly impaired swallowing, speaking, and breathing, and worsening of his existing tremors. Ritonavir and indinavir were discontinued. On the same day, the patient increased the risperidone dosage to 3 mg twice daily. Symptoms continued to worsen over the next 3 days. All investigations and laboratory parameters were unremarkable, and vital signs were stable. Risperidone was discontinued and clonazepam initiated. Three days later, the patient's symptoms were significantly improved. DISCUSSION: The symptoms described herein are consistent with neuroleptic-induced acute dystonia and potentially neuroleptic-induced parkinsonism. We believe this adverse effect occurred as a result of a drug interaction between ritonavir/indinavir and risperidone. Based on the pharmacokinetics of these medications, we hypothesize that inhibition of CYP2D6 and CYP3A4 by ritonavir and indinavir may have resulted in an accumulation of the active moiety of risperidone, which may explain the occurrence of EPS in this patient. CONCLUSIONS: This is the second published case report describing a suspected drug interaction with ritonavir, indinavir, and risperidone. Caution is warranted when risperidone is prescribed with ritonavir/indinavir, and possibly with other antiretrovirals that inhibit the same pathways.

Evaluation of HIV drug interaction web sites.

BACKGROUND: Clinicians frequently consult HIV drug interaction Web sites of unknown quality. OBJECTIVE: To systematically review and identify HIV drug interaction Web sites of high quality and usefulness for healthcare professionals. METHODS: Relevant Web sites were identified through a structured search on commonly used search engines. An assessment tool containing 4 domains (content, reliability, access restrictions, ease of navigation) was developed. English and French Web sites were selected for review if they included HIV drug interaction information directed to healthcare professionals. Web sites were excluded if antiretroviral interaction data were not available or were out of date. Commercial online databases and sites that required payment were not included. Seventeen HIV pharmacists from across Canada participated in the review. The Web sites were ranked with total mean scores. Mean scores for each domain were then analyzed. Interrater agreement and ANOVA using the rater as a covariate were determined. RESULTS: Nine Web sites met the criteria for review. Web sites from Toronto General Hospital (Canada), HIVinSite (beta version) (US), and the University of Liverpool (UK) ranked highest for total mean scores and for content. Other Web sites were found to be reliable, accessible, and easy to navigate; however, they did not consistently include unpublished data or data on herbal preparations, recreational drugs, or multiple interactions. CONCLUSIONS: Three HIV interaction Web sites of high quality were identified that can be valuable tools for HIV and non-HIV health-care professionals. Regular reviews are necessary in order to keep pace with the growing body of HIV interaction data and the constant evolution of Web sites.