Severe hypercalcemia as a result of disseminated Candida krusei infection.

Candida krusei disseminated infection is a rare complication of protracted neutropenia. Herein, we report a case of a 31-year-old male with relapsed acute myeloid leukemia who developed Candida krusei fungemia with cutaneous, ocular, splenic, renal, bone marrow and osseous involvement leading to severe hypercalcemia, treated with parenteral antifungals followed by oral ibrexafungerp.

A retrospective review of empiric acyclovir prescribing practices for suspected viral central nervous system infections: A single-centre study.

Background: Acyclovir has an important role in the treatment of viral central nervous system (CNS) infection, especially herpes simplex virus (HSV)-1 encephalitis. It is therefore used broadly as empiric therapy for many patients who present to the hospital with symptoms of a possible neurologic infection. We sought to review our practices in acyclovir prescribing, deprescribing, and associated investigations for the clinical syndromes it treats. Methods: Through a retrospective chart review, we identified patients prescribed acyclovir for a possible CNS infection upon admission to Vancouver General Hospital between January 1, 2019, and December 31, 2019. Patient demographics, signs, symptoms, and comorbidities were taken from admission consultation notes or discharge summaries; their investigations, including laboratory tests and imaging, were also recorded. The primary purpose was to describe the appropriateness of empiric acyclovir use in suspected meningoencephalitis cases. Results: Among the 108 patients treated with acyclovir, 94 patients had an indication for starting empiric treatment for encephalitis or meningitis. There was suspicion and workup for encephalitis alone in 76 patients. Among discharge diagnoses, the most common was delirium of a different identified source (18 cases), followed by unknown/other (15 cases). There were seven patients whose CSF viral PCR test was positive for HSV or varicella-zoster virus (VZV); three of them had HSV-1 encephalitis. There were two total adverse events recorded attributed to acyclovir; both cases were of mild acute kidney injury. Conclusion: We found that in many patients, acyclovir was not necessary or could have been stopped earlier, avoiding toxicity and drug costs.

Historique: L'acyclovir joue un rôle important dans le traitement des infections virales du système nerveux central (SNC), notamment l'encéphalite herpétique. Il est donc largement utilisé comme traitement empirique auprès de nombreux patients qui consultent à l'hôpital à cause de symptômes d'éventuelle infection neurologique. Les chercheurs ont révisé leurs pratiques en matière de prescription et de déprescription d'acyclovir ainsi que les examens connexes de syndromes cliniques que traite ce médicament. Méthodologie: Les chercheurs ont procédé à une analyse rétrospective des dossiers pour en extraire les patients à qui on avait prescrit de l'acyclovir à cause d'une éventuelle infection du SNC à leur admission au Vancouver General Hospital entre le 1er janvier et le 31 décembre 2019. Ils ont obtenu la démographie, les signes, les symptômes et les autres maladies des patients dans les notes de consultation à l'admission ou dans les résumés au congé. Ils ont également consigné les examens auxquels les patients ont été soumis, y compris les tests de laboratoire et d'imagerie. L'objectif primaire consistait à décrire le bien-fondé de l'utilisation empirique d'acyclovir en cas de soupçon de méningoencéphalite. Résultats: Chez les 108 patients ayant reçu un traitement à l'acyclovir, 94 présentaient une indication de traitement empirique contre l'encéphalite ou la méningite. Les soupçons et le bilan d'encéphalite seule étaient observés chez 76 patients. Parmi les diagnostics au congé, les plus courants étaient un délire provenant d'une autre source (18 cas), suivi d'un diagnostic inconnu ou autre (15 cas). Chez sept patients, le test PCR du liquide céphalorachidien pour analyser le virus a donné un résultat positif au virus herpès simplex (VHS) ou au virus varicelle-zona, y compris trois cas d'encéphalite à VHS-1. Au total, deux événements indésirables attribués à l'acyclovir ont été consignés, tous deux de lésion rénale aiguë légère. Conclusion: Les chercheurs ont établi que l'aciclovir était inutile ou aurait pu être interrompu plus tôt chez de nombreux patients, ce qui aurait évité la toxicité et réduit les coûts de médicaments.

Novel six-month all oral treatment of pre-extensively drug-resistant tuberculosis in Canada: New treatment options present new implementation challenges.

Drug-resistant tuberculosis (TB) is a major global health challenge in part because there are fewer effective treatments and these treatments have been prolonged and more toxic. The evidence base for more effective, shorter, standardized treatments is evolving rapidly. Herein, we report the first case of pre-extensively drug-resistant pulmonary TB treated with a novel six-month all oral bedaquiline, pretomanid and linezolid (BPaL) regimen in Canada. Recent clinical trial data supporting BPaL therapy is presented in the context of current and evolving clinical guidelines. In this article, we highlight significant implementation challenges and make recommendations for what needs to be addressed to ensure safe programmatic use of BPaL in Canada. Key recommendations include the development of infrastructure for timely access to novel TB drug susceptibility testing, streamlining access to novel TB drugs, and cautious use of such drugs in collaboration with care teams with expertise in drug-resistant TB management.

A Canadian perspective on the revised 2020 ASHP-IDSA-PIDS-SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections.

Background: A revised consensus guideline on therapeutic drug monitoring (TDM) of vancomycin for serious methicillin-resistant Staphylococcus aureus (MRSA) infections was recently published with endorsement of numerous American pharmacy and medical societies. Changing practice from trough TDM to area-under-the-curve-(AUC)-guided dosing was suggested. Methods: Recent literature was critically appraised to determine whether AUC TDM is appropriate for Canadian hospital practice. Results: Previous 2009 vancomycin consensus guidelines recommended trough levels of 15-20 mg/L for serious MRSA infections, based on relatively poor evidence for efficacy or safety. In the past decade, aggressive trough targets have led to unnecessary toxicity. Adoption of a TDM strategy using an alternative parameter (AUC) has been suggested, although the evidence for any outcome benefits is low quality. In addition, implementation would require greater resources at health care institutions in the forms of more frequent serum levels or acquisition of costly Bayesian software programs. Most studies on this subject have been observational and retrospective; therefore, relationships between TDM parameters and outcomes have not been convincingly and consistently demonstrated to be causal in nature. Despite claims to the contrary, based on few in silico experiments, available clinical data suggest correlation of trough levels and AUC is high. TDM with lower target trough levels is a simpler solution to reduce risk of toxicity. Conclusions: There are serious concerns with adoption of AUC TDM of vancomycin into routine practice in Canada. Trough-based monitoring with modest reduction in target levels remains the most evidence-informed practice at this time.

Historique: De nombreuses sociétés pharmaceutiques et médicales américaines ont récemment publié et avalisé des lignes directrices consensuelles révisées sur le suivi thérapeutique pharmacologique (STP) de la vancomycine en cas de graves infections par le Staphylococcus aureus résistant à la méthicilline (SARM). Ces lignes directrices préconisent de passer de la STP des creux à une posologie déterminée par l'aire sous la courbe (ASC). Méthodologie: Les chercheurs ont procédé à une évaluation critique des publications récentes pour déterminer si la STP selon l'ASC est adaptée à la pratique hospitalière au Canada. Résultats: Les lignes directrices consensuelles de 2009 sur la vancomycine recommandaient un creux de 15 mg/L à 20 mg/L en cas d'infection grave par le SARM, en fonction de données probantes d'efficacité et d'innocuité relativement faibles. Depuis dix ans, des creux cibles trop ambitieux ont été responsables de toxicités inutiles. Il est proposé de revoir la stratégie du STP d'après un autre paramètre (l'ASC), même si les données probantes en démontrant les bienfaits sont de faible qualité. De plus, sa mise en œuvre exigerait des ressources plus importantes dans les établissements de santé, soit le dosage plus fréquent des concentrations plasmatiques ou l'acquisition de logiciels bayésiens coûteux. La plupart des articles sur le sujet sont des études d'observation et des études rétrospectives. Par conséquent, la nature causale des relations entre les paramètres et les résultats du STP n'a pas été démontrée de manière convaincante ni systématique. Malgré les prétentions contraires, selon quelques expériences in silico, les données cliniques disponibles font foi d'une corrélation élevée entre les concentrations minimales et l'ASC. Il serait plus simple d'assurer le STP par des concentrations minimales cibles plus basses pour réduire le taux de toxicité. Conclusions: L'adoption du STP de la vancomycine selon l'ASC dans la pratique quotidienne soulève de vives préoccupations au Canada. Pour l'instant, la surveillance des creux assortie à de modestes réductions des concentrations cibles demeure la pratique la plus respectueuse des données probantes.

Case Report: Ivermectin and Albendazole Plasma Concentrations in a Patient with Disseminated Strongyloidiasis on Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.

Disseminated strongyloidiasis is often fatal, despite treatment with oral albendazole and parenteral ivermectin (IVM). Here, we report elevated plasma IVM and albendazole sulfoxide concentrations in the context of extracorporeal membrane oxygenation and continuous renal replacement therapy in a patient with disseminated strongyloidiasis treated with subcutaneous IVM and nasogastric albenzadole. Despite elevated drug plasma concentrations, live filariform larvae were detected in endotracheal aspirates after 2 weeks of treatment.

Survey of sterile admixture practices in canadian hospital pharmacies: part 1. Methods and results.

BACKGROUND: The 1996 Guidelines for Preparation of Sterile Products in Pharmacies of the Canadian Society of Hospital Pharmacists (CSHP) represent the current standard of practice for sterile compounding in Canada. However, these guidelines are practice recommendations, not enforceable standards. Previous surveys of sterile compounding practices have shown that actual practice deviates markedly from voluntary practice recommendations. In 2004, the United States Pharmacopeia (USP) published its "General Chapter <797> Pharmaceutical Compounding-Sterile Preparations", which set a more rigorous and enforceable standard for sterile compounding in the United States. OBJECTIVES: To assess sterile compounding practices in Canadian hospital pharmacies and to compare them with current CSHP recommendations and USP chapter <797> standards. METHODS: An online survey, based on previous studies of sterile compounding practices, the CSHP guidelines, and the chapter <797> standards, was created and distributed to 193 Canadian hospital pharmacies. RESULTS: A total of 133 pharmacies completed at least part of the survey, for a response rate of 68.9%. All respondents reported the preparation of sterile products. Various degrees of deviation from the practice recommendations were noted for virtually all areas of the CSHP guidelines and the USP standards. Low levels of compliance were most notable in the areas of facilities and equipment, process validation, and product testing. Availability in the central pharmacy of a clean room facility meeting or exceeding the criteria of International Organization for Standardization (ISO) class 8 is a requirement of the chapter <797> standards, but more than 40% of responding pharmacies reported that they did not have such a facility. Higher levels of compliance were noted for policies and procedures, garbing requirements, aseptic technique, and handling of hazardous products. Part 1 of this series reports the survey methods and results relating to policies, personnel, raw materials, storage and handling, facilities and equipment, and garments. Part 2 will report results relating to preparation of aseptic products, expiry dating, labelling, process validation, product testing and release, documentation, records, and disposal of hazardous pharmaceuticals. It will also highlight some of the key areas where there is considerable opportunity for improvement. CONCLUSION: This survey identified numerous deficiences in sterile compounding practices in Canadian hospital pharmacies. Awareness of these deficiencies may create an impetus for critical assessment and improvements in practice.

Survey of sterile admixture practices in canadian hospital pharmacies: part 2. More results and discussion.

BACKGROUND: The 1996 Guidelines for Preparation of Sterile Products in Pharmacies of the Canadian Society of Hospital Pharmacists (CSHP) represent the current standard of practice for sterile compounding in Canada. However, these guidelines are practice recommendations, not enforceable standards. Previous surveys of sterile compounding practices have shown that actual practice deviates markedly from voluntary practice recommendations. In 2004, the United States Pharmacopeia (USP) published its "General Chapter <797> Pharmaceutical Compounding-Sterile Preparations", which set a more rigorous and enforceable standard for sterile compounding in the United States. OBJECTIVES: To assess sterile compounding practices in Canadian hospital pharmacies and to compare them with current CSHP recommendations and USP chapter <797> standards. METHODS: An online survey, based on previous studies of sterile compounding practices, the CSHP guidelines, and the chapter <797> standards, was created and distributed to 193 Canadian hospital pharmacies. RESULTS: A total of 133 pharmacies completed at least part of the survey, for a response rate of 68.9%. All respondents reported the preparation of sterile products. Various degrees of deviation from the practice recommendations were noted for virtually all areas of the CSHP guidelines and the USP standards. Low levels of compliance were most notable in the areas of facilities and equipment, process validation, and product testing. Availability in the central pharmacy of a clean room facility meeting or exceeding the criteria of International Organization for Standardization (ISO) class 8 is a requirement of the chapter <797> standards, but more than 40% of responding pharmacies reported that they did not have such a facility. Higher levels of compliance were noted for policies and procedures, garbing requirements, aseptic technique, and handling of hazardous products. The survey methods for this study and results relating to policies, personnel, raw materials, storage and handling, facilities and equipment, and garments were reported in Part 1. Part 2 reports results relating to preparation of aseptic products, expiry dating, labelling, process validation, product testing and release, documentation, records, and disposal of hazardous pharmaceuticals. It also highlights some of the key areas where there is considerable opportunity for improvement. CONCLUSION: This survey identified numerous deficiencies in sterile compounding practices in Canadian hospital pharmacies. Awareness of these deficiencies may create an impetus for critical assessment and improvements in practice.

Drug-related problems in patients undergoing elective total joint arthroplasty of the hip or knee.

BACKGROUND: Few studies have evaluated drug-related problems in patients undergoing elective total hip or knee arthroplasty. OBJECTIVE: To quantify, for patients undergoing elective total joint arthroplasty, drug-related problems arising from medication orders written before or immediately after the surgery. The primary outcome was the proportion of patients with at least one drug-related problem. The secondary outcomes were the total number and descriptions of these problems, according to the patient's age and the category, type, and severity of the drug-related problem. METHODS: From among patients who underwent elective total joint arthroplasty in a large Canadian regional health authority in 2005, 150 were randomly selected for this chart audit. Patients were included if they had been taking more than one medication before surgery. The charts were examined for drug-related problems, which were categorized according to whether the problem involved a prescription for a home medication, an order for a postoperative medication, or a potential indication for drug therapy. The problems were further described by type and potential severity. RESULTS: Of the 146 patients whose charts were available, 116 (79.5%) had at least one drug-related problem, with a mean of 1.88 drug-related problems per patient. Of the 146 patients, 88 (60.3%) had at least one drug-related problem involving a home medication, 34 (23.3%) had problems related to postoperative orders, and 37 (25.3%) had problems related to a potential indication. The mean number of drug-related problems per patient was 2.03 for those 65 years of age or older and 1.56 for those younger than 65 years (p = 0.09); however, more of the older patients experienced at least one drug-related problem related to home medications (67% [67/100] versus 46% [21/46], p = 0.02). The most common types of problems were medication omissions, illegible drug orders, inappropriate dose or frequency, and drug-allergy interactions. Of the 275 drug-related problems identified, 147 (53.5%) were deemed potentially harmful, 78 (28.4%) required monitoring, and 50 (18.2%) were considered not harmful. CONCLUSIONS: In this study, patients who underwent total joint arthroplasty experienced many drug-related problems. Pharmacists may have opportunities to optimize patient care by identifying, resolving, and preventing drug-related problems in this patient population.