Assessing the quality of antimicrobial prescribing in solid organ transplant recipients: a new frontier in antimicrobial stewardship.

Background: Post-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTRs) and local standardized antimicrobial treatment guidelines may contribute to improved clinical outcomes. Our study assessed the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes. Methods: Consecutive adult SOTRs admitted to the transplant floor from January-September 2020 and were treated for an infectious syndrome were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records. Guideline compliance was characterized as either appropriate, effective but unnecessary, undertreatment, or inappropriate. Results: Nine hundred and thirty-six SOTR were admitted to the transplant ward, of which 328 patients (35%) received treatment for infectious syndromes. Guidelines were applicable to 252 patients, constituting 275 syndromes: 86 pneumonias; 82 urinary tract infections; 40 intra-abdominal infections; 38 bloodstream infections; and 29 C. difficile infections. 200/246 (81%) of infectious syndromes received appropriate or effective but unnecessary empiric treatment. In addition, appropriate tailoring of antimicrobials resulted in a significant difference in 30-day all-cause mortality (adjusted OR of 0.07, 95% CI 0.01-0.38; P = .002). Lastly, we found that guideline-compliant empiric therapy was found to prevent the development of multi-drug resistance in a time-dependent analysis (adjusted HR of 0.21, 95% CI 0.08-0.52; P = .001). Conclusion: Our data show that adherence to locally developed guidelines was associated with reduced mortality and resistant-organism development in our cohort of SOTR.

Implementation of Virtual Interactive Cases for Pharmacy Education: A Single-Center Experience.

Patient case simulation software are described in pharmacy education literature as useful tools to improve skills in patient assessment (including medication history-taking and physical assessment), clinical reasoning and communication, and are typically well-received by students and instructors. The virtual interactive case (VIC) system is a web-based software developed to deliver deliberate practice opportunities in simulated patient encounters across a spectrum of clinical topics. This article describes the implementation and utilization of VIC in the undergraduate curriculum at one Canadian pharmacy school. Methods: At our facility, the use of VIC was integrated across the training spectrum in the curriculum, including core and elective didactic courses and practice labs, experiential learning, interprofessional education, and continuing education. Its use was evaluated through student and instructor surveys and qualitative student interviews). VIC is easy to navigate and created a positive and realistic learning environment. Students identified that it enhanced their ability to identify relevant patient information, accurately simulated hospital pharmacy practice and thereby helped them to prepare for their upcoming experiential courses. The use of VIC has expanded beyond its original intended purpose for individual student practice to become a valuable addition to pharmacy undergraduate education. Future plans include ongoing development of cases and exploration of further uses of VIC within the didactic curriculum, for remediation in experiential courses, and for pharmacist continuing education.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

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.

Bring it on again: antimicrobial stewardship in transplant infectious diseases: updates and new challenges.

Advancement in solid organ transplantation and hematopoietic stem cell transplant continues to improve the health outcomes of patients and widens the number of eligible patients who can benefit from the medical progress. Preserving the effectiveness of antimicrobials remains crucial, as otherwise transplant surgeries would be unsafe due to surgical site infections, and the risk of sepsis with neutropenia would preclude stem cell transplant. In this review, we provide updates on three previously discussed stewardship challenges: febrile neutropenia, Clostridioides difficile infection, and asymptomatic bacteriuria. We also offer insight into four new stewardship challenges: the applicability of the "shorter is better" paradigm shift to antimicrobial duration; antibiotic allergy delabeling and desensitization; colonization with multidrug-resistant gram-negative organisms; and management of cytomegalovirus infections. Specifically, data are accumulating for "shorter is better" and antibiotic allergy delabeling in transplant patients, following successes in the general population. Unique to transplant patients are the impact of multidrug-resistant organism colonization on clinical decision-making of antibiotic prophylaxis in transplant procedure and the need for antiviral stewardship in cytomegalovirus. We highlighted the expansion of antimicrobial stewardship interventions as potential solutions for these challenges, as well as gaps in knowledge and opportunities for further research.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals.

Background: Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems. Objectives: To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals. Methods: An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations. The survey gathered data about hospital characteristics, TDM methods, inclusion criteria for patient selection, pharmacokinetic and pharmacodynamic targets, vancomycin susceptibility testing and reporting, and perceived barriers and challenges. Results: In total, 120 pharmacists from 10 of the 13 provincial and territorial jurisdictions in Canada, representing 12.5% of Canadian acute care hospitals (n = 962), completed at least 90% of survey questions. The predominant TDM method was trough-based (107/119, 89.9%); another 10.1% of respondents (12/119) reported performing AUC-based TDM (with or without trough-based TDM), and 17.9% (19/106) of those not already using AUC-based TDM were considering implementing it within 1 to 2 years. Among hospitals performing trough-based TDM, 60.5% (66/109) targeted trough levels between 15 and 20 mg/L for serious infections with methicillin-resistant Staphylococcus aureus. One-quarter of the respondents using this method (27/109, 24.8%) agreed that trough-based TDM was of uncertain benefit, and about one-third (33/109, 30.3%) were neutral on this question. Multiple challenges were identified for trough-based TDM, including sub- or supra-therapeutic concentrations and collection of specimens at inappropriate times. Overall, 40.5% (47/116) of respondents agreed that AUC-based TDM was likely safer than trough-based TDM, whereas 23.3% (27/116) agreed that AUC-based TDM was likely more effective. Conclusions: This survey represents a first step in developing evidence-based, standardized best practices for vancomycin TDM that are uniquely suited to the Canadian health care system.

Contexte: On connaît peu de choses sur le paysage actuel du suivi thérapeutique pharmacologique (STP) de la vancomycine dans les hôpitaux canadiens, dont les activités s'inscrivent dans le cadre des systèmes de soins de santé financés par les deniers publics. Objectifs: Déterminer les pratiques actuelles de STP de la vancomycine et les défis associés et recueillir les perceptions concernant le STP sur la base de l'aire sous la courbe de la concentration en fonction du temps (ASC) dans les hôpitaux canadiens. Méthodes: Un sondage a été distribué électroniquement aux pharmaciens d'hôpitaux au printemps 2021 par plusieurs organismes nationaux et provinciaux de gestion de l'utilisation des antimicrobiens, de santé publique et de pharmacie. Le sondage a permis de rassembler des données concernant les caractéristiques des hôpitaux, les méthodes de STP, les critères d'inclusion pour la sélection des patients, les objectifs pharmacocinétiques et pharmacodynamiques, les tests de sensibilité à la vancomycine et les rapports des résultats, ainsi que les obstacles et les défis perçus. Résultats: Au total, 120 pharmaciens de 10 des 13 provinces et territoires du Canada, représentant 12,5 % des hôpitaux canadiens de soins actifs (n = 962), ont répondu à au moins 90 % des questions du sondage. La méthode de STP prédominante utilisée était celle de la concentration minimale (107/119, 89,9 %); un autre 10,1 % des répondants (12/119) ont déclaré effectuer un STP basé sur l'ASC (avec ou sans STP basé sur la concentration minimale), et 17,9 % (19/106) de ceux qui n'effectuaient pas déjà le STP basé sur l'ASC envisageaient de le mettre en œuvre d'ici 1 à 2 ans. Parmi les hôpitaux pratiquant le STP basé sur la concentration minimale, 60,5 % (66/109) ciblaient des concentrations minimales entre 15 et 20 mg/L pour les infections graves à Staphylococcus aureus résistant à la méthicilline. Un quart des répondants qui utilisaient cette méthode (27/109, 24,8 %) convenaient que les avantages du STP basé sur la concentration minimale étaient incertains, et environ un tiers (33/109, 30,3 %) étaient neutres. De multiples défis ont été identifiés pour le STP basé sur la concentration minimale, notamment des concentrations sous-ou supra-thérapeutiques et la collecte d'échantillons à des moments inappropriés. Dans l'ensemble, 40,5 % (47/116) des répondants convenaient que le STP basé sur l'ASC était probablement plus sûr que le STP basé sur la concentration minimale, tandis que 23,3 % (27/116) convenaient que le STP basé sur l'ASC était probablement plus efficace. Conclusions: Ce sondage représente une première étape dans l'élaboration de pratiques exemplaires normalisées et fondées sur des données probantes pour le STP de la vancomycine qui sont particulièrement adaptées au système de santé canadien.

Machine Learning on Medicare Claims Poorly Predicts the Individual Risk of 30-Day Unplanned Readmission After Total Joint Arthroplasty, Yet Uncovers Interesting Population-level Associations With Annual Procedure Volumes.

BACKGROUND: Unplanned hospital readmissions after total joint arthroplasty (TJA) represent potentially serious adverse events and remain a critical measure of hospital quality. Predicting the risk of readmission after TJA may provide patients and clinicians with valuable information for preoperative decision-making. QUESTIONS/PURPOSES: (1) Can nonlinear machine-learning models integrating preoperatively available patient, surgeon, hospital, and county-level information predict 30-day unplanned hospital readmissions in a large cohort of nationwide Medicare beneficiaries undergoing TJA? (2) Which predictors are the most important in predicting 30-day unplanned hospital readmissions? (3) What specific information regarding population-level associations can we obtain from interpreting partial dependency plots (plots describing, given our modeling choice, the potentially nonlinear shape of associations between predictors and readmissions) of the most important predictors of 30-day readmission? METHODS: National Medicare claims data (chosen because this database represents a large proportion of patients undergoing TJA annually) were analyzed for patients undergoing inpatient TJA between October 2016 and September 2018. A total of 679,041 TJAs (239,391 THAs [61.3% women, 91.9% White, 52.6% between 70 and 79 years old] and 439,650 TKAs [63.3% women, 90% White, 55.2% between 70 and 79 years old]) were included. Model features included demographics, county-level social determinants of health, prior-year (365-day) hospital and surgeon TJA procedure volumes, and clinical classification software-refined diagnosis and procedure categories summarizing each patient's Medicare claims 365 days before TJA. Machine-learning models, namely generalized additive models with pairwise interactions (prediction models consisting of both univariate predictions and pairwise interaction terms that allow for nonlinear effects), were trained and evaluated for predictive performance using area under the receiver operating characteristic (AUROC; 1.0 = perfect discrimination, 0.5 = no better than random chance) and precision-recall curves (AUPRC; equivalent to the average positive predictive value, which does not give credit for guessing "no readmission" when this is true most of the time, interpretable relative to the base rate of readmissions) on two holdout samples. All admissions (except the last 2 months' worth) were collected and split randomly 80%/20%. The training cohort was formed with the random 80% sample, which was downsampled (so it included all readmissions and a random, equal number of nonreadmissions). The random 20% sample served as the first test cohort ("random holdout"). The last 2 months of admissions (originally held aside) served as the second test cohort ("2-month holdout"). Finally, feature importances (the degree to which each variable contributed to the predictions) and partial dependency plots were investigated to answer the second and third research questions. RESULTS: For the random holdout sample, model performance values in terms of AUROC and AUPRC were 0.65 and 0.087, respectively, for THA and 0.66 and 0.077, respectively, for TKA. For the 2-month holdout sample, these numbers were 0.66 and 0.087 and 0.65 and 0.075. Thus, our nonlinear models incorporating a wide variety of preoperative features from Medicare claims data could not well-predict the individual likelihood of readmissions (that is, the models performed poorly and are not appropriate for clinical use). The most predictive features (in terms of mean absolute scores) and their partial dependency graphs still confer information about population-level associations with increased risk of readmission, namely with older patient age, low prior 365-day surgeon and hospital TJA procedure volumes, being a man, patient history of cardiac diagnoses and lack of oncologic diagnoses, and higher county-level rates of hospitalizations for ambulatory-care sensitive conditions. Further inspection of partial dependency plots revealed nonlinear population-level associations specifically for surgeon and hospital procedure volumes. The readmission risk for THA and TKA decreased as surgeons performed more procedures in the prior 365 days, up to approximately 75 TJAs (odds ratio [OR] = 1.2 for TKA and 1.3 for THA), but no further risk reduction was observed for higher annual surgeon procedure volumes. For THA, the readmission risk decreased as hospitals performed more procedures, up to approximately 600 TJAs (OR = 1.2), but no further risk reduction was observed for higher annual hospital procedure volumes. CONCLUSION: A large dataset of Medicare claims and machine learning were inadequate to provide a clinically useful individual prediction model for 30-day unplanned readmissions after TKA or THA, suggesting that other factors that are not routinely collected in claims databases are needed for predicting readmissions. Nonlinear population-level associations between low surgeon and hospital procedure volumes and increased readmission risk were identified, including specific volume thresholds above which the readmission risk no longer decreases, which may still be indirectly clinically useful in guiding policy as well as patient decision-making when selecting a hospital or surgeon for treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

A national survey of antimicrobial stewardship content in Canadian entry-to-practice pharmacy programs.

Objective: To describe the current landscape of antimicrobial stewardship (AMS) instruction in Canadian entry-to-practice pharmacy programs and the perceived barriers and facilitators to optimizing teaching and learning. Design: Electronic survey. Participants: Faculty representatives from the 10 Canadian entry-to-practice pharmacy programs, including content experts and faculty leadership. Methods: A review of international literature pertaining to AMS in pharmacy curricula informed a 24-item survey, which was open for completion from March to May of 2021. Curriculum content questions were developed using AMS topics recommended by pharmacy educators in the United States, and professional roles described by the Association of Faculties of Pharmacy of Canada. Results: All 10 Canadian faculties returned a completed survey. All programs reported teaching AMS principles in their core curricula. Content coverage varied, with programs teaching, on average, 68% of the recommended AMS topics from the United States. Potential gaps were identified within the professional roles of "communicator" and "collaborator." Didactic methods of content delivery and student assessment, such as lectures and multiple-choice questions, were most frequently used. Three programs offered additional AMS content in their elective curricula. Experiential rotations in AMS were commonly offered, though teaching AMS in formalized interprofessional settings was rare. Curricular time constraints were identified by all programs as a barrier to enhancing AMS instruction. A course to teach AMS, a curriculum framework, and prioritization by the faculty's curriculum committee were perceived as facilitators. Conclusions: Our findings highlight potential gaps and areas of opportunity within Canadian pharmacy AMS instruction.

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. RESULTS: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Going local: Evaluating guideline adherence and appropriateness of antibiotic prescribing in patients with febrile neutropenia at an academic teaching hospital.

Background: Febrile neutropenia (FN) is a medical emergency with significant morbidity and mortality for oncology patients, requiring comprehensive workup and timely antibiotic administration. We evaluated concordance with locally developed FN guidelines and outcomes of cancer patients admitted to general internal medicine at an academic teaching hospital. Methods: We conducted a retrospective observational cohort study of patients admitted between July 1, 2016, and June 30, 2017, for FN. Patients were classified as having low-risk or high-risk FN according to their malignancy and chemotherapy. Primary outcome was the proportion of patients receiving guideline-concordant antibiotics within 48 hours of admission to general internal medicine. Secondary outcomes were the proportion of patients in whom empirical antibiotics were active against pathogens isolated, rate of antibiotic-associated adverse events, and in-hospital mortality. We used logistic regression to model relationship between FN risk and guideline-concordant antibiotics. Results: Among 100 patients included, 34 (34%) were low-risk FN and 66 (66%) were high-risk. Proportion of guideline-concordant empirical antibiotics was significantly lower among low-risk FN patients than high-risk patients: 12 (35%) of 34 versus 47 (71%) of 66 (P = .001). Empirical antibiotics were active against 17 (94%) of 18 isolated pathogens. The mortality rate was 3%, and 16% of patients experienced antibiotic-associated adverse events. Hematological malignancy and infectious diseases-trained physician involvement were associated with guideline-concordant prescribing, with adjusted odds ratios of 3.76 (95% CI, 1.46-9.70; P = .006) and 3.71 (95% CI, 1.49-9.23; P = .005), respectively. Conclusions: Guideline concordance was low compared to published reports. Factors influencing appropriate antimicrobial prescribing in patients with FN warrant further exploration.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them.

Antimicrobial therapies are essential tools for transplant recipients who are at high risk for infectious complications. However, judicious use of antimicrobials is critical to preventing the development of antimicrobial resistance. Treatment of multidrug-resistant organisms is challenging and potentially leads to therapies with higher toxicities, intravenous access, and intensive drug monitoring for interactions. Antimicrobial stewardship programs are crucial in the prevention of antimicrobial resistance, though balancing these strategies with the need for early and frequent antibiotic therapy in these immunocompromised patients can be challenging. In this review, we summarize 5 frequently encountered transplant infectious disease stewardship challenges, and we suggest strategies to improve practices for each clinical syndrome. These 5 challenging areas are: asymptomatic bacteriuria in kidney transplant recipients, febrile neutropenia in hematopoietic stem cell transplantation, antifungal prophylaxis in liver and lung transplantation, treatment of left-ventricular assist device infections, and Clostridioides difficile infection in solid-organ and hematopoietic stem-cell transplant recipients. Common themes contributing to these challenges include limited data specific to transplant patients, shortcomings in diagnostic testing, and uncertainties in pharmacotherapy.

Antibiotic prescribing patterns among patients admitted to an academic teaching hospital for COVID-19 during the first wave of the pandemic in Toronto: A retrospective, controlled study.

BACKGROUND: Empirical antibiotics are not recommended for coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, patients admitted to Toronto General Hospital's general internal medicine from the emergency department for COVID-19 between March 1 and August 31, 2020 were compared with those admitted for community-acquired pneumonia (CAP) in 2020 and 2019 in the same months. The primary outcome was antibiotics use pattern: prevalence and concordance with COVID-19 or CAP guidelines. The secondary outcome was antibiotic consumption in days of therapy (DOT)/100 patient-days. We extracted data from electronic medical records. We used logistic regression to model the association between disease and receipt of antibiotics, linear regression to compare DOT. RESULTS: The COVID-19, CAP 2020, and CAP 2019 groups had 67, 73, and 120 patients, respectively. Median age was 71 years; 58.5% were male. Prevalence of antibiotic use was 70.2%, 97.3%, and 90.8% for COVID-19, CAP 2020, and CAP 2019, respectively. Compared with CAP 2019, the adjusted odds ratio (aOR) for receiving antibiotics was 0.23 (95% CI 0.10 to 0.53, p = 0.001) and 3.42 (95% CI 0.73 to 15.95, p = 0.117) for COVID-19 and CAP 2020, respectively. Among patients receiving antibiotics within 48 hours of admission, compared with CAP 2019, the aOR for guideline-concordant combination regimens was 2.28 (95% CI 1.08 to 4.83, p = 0.031) for COVID-19, and 1.06 (95% CI 0.55 to 2.05, p = 0.856) for CAP 2020. Difference in mean DOT/100 patient-days was -24.29 (p = 0.009) comparing COVID-19 with CAP 2019, and +28.56 (p = 0.003) comparing CAP 2020 with CAP 2019. CONCLUSIONS: There are opportunities for antimicrobial stewardship to address unnecessary antibiotic use.

HISTORIQUE: L'antibiothérapie empirique n'est pas recommandée pour le traitement de la maladie à coronavirus 2019 (COVID-19). MÉTHODOLOGIE: Dans cette étude rétrospective, les chercheurs ont comparé les patients atteints de COVID-19 hospitalisés au département de médecine interne générale du Toronto General Hospital entre le 1er mars et le 31 août 2020 après être passés par l'urgence à ceux hospitalisés à cause d'une pneumonie d'origine communautaire (POC) au cours des mêmes mois en 2020 et 2019 (POC-20 et POC-19). Le résultat primaire était le schéma d'utilisation des antibiotiques, c'est-à-dire la prévalence et le respect des lignes directrices sur la COVID-19 ou la POC. Le résultat secondaire correspondait à la consommation d'antibiotiques pendant les jours de traitement (JdT)/100 jours-patients. Les chercheurs ont puisé les données dans les dossiers médicaux électroniques. Ils se sont servi de la régression logistique pour modéliser l'association entre la maladie et la réception des antibiotiques, et de la régression linéaire pour comparer les JdT. RÉSULTATS: Le groupe COVID-19, le groupe POC-20 et le groupe POC-19 étaient composés de 67, 73 et 120 patients, respectivement. Ils avaient un âge médian de 71 ans, et 58,5 % étaient de sexe masculin. La prévalence d'utilisation d'antibiotiques s'élevait à 70,2 %, 97,3 % et 90,8 % dans les groupes COVID-19, POC-20 et POC-19, respectivement. Par rapport au groupe POC-19, le rapport de cotes rajusté (RCr) relatif à la réception d'antibiotiques s'élevait à 0,23 (IC à 95 %, 0,10 à 0,53, p = 0,001) et 3,42 (IC à 95 %, 0,73 à 15,95, p = 0,117) dans les groupes COVID-19 et POC-20, respectivement. Chez les patients qui avaient reçu des antibiotiques dans les 48 heures suivant leur hospitalisation par rapport au POC-19, le RCr relatif à la posologie d'association conforme aux lignes directrices était de 2,28 (IC à 95 %, 1,08 à 4,83, p = 0,031) et de 1,06 (IC à 95 %, 0,55 à 2,05, p = 0,856) dans le groupe POC-20. La différence quant au nombre moyen de JdT/100 jours-patients correspondait à ­24,29 (p = 0,009) lorsqu'on comparait le groupe COVID-19 au groupe POC-19, et à +28,56 (p = 0,003) lorsqu'on comparait le groupe POC-20 au groupe POC-19. CONCLUSIONS: L'utilisation inutile d'antibiotiques pourrait très bien être prise en charge par la gérance des antimicrobiens.

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.