Antimicrobial stewardship in solid organ transplant-Opportunities in the National Health Service.

BACKGROUND: Antimicrobial stewardship (AMS) is an intervention, which ensures the appropriateness of antimicrobial use to avoid in part the rising problem of antimicrobial resistance and negative effects of inappropriate antimicrobial use. In the solid organ transplant (SOT) population, which is prone to a particularly high risk of infection resulting from immunosuppression and anatomical issues with each type of SOT, the need for good stewardship has never been more important. This article looks at current AMS practice in SOT units in the United Kingdom and how things could be improved in the future. METHODS: The current practice of AMS alongside national antimicrobial resistance rates were reviewed using national mandatory reporting data. The background to the current practice and policies in place in the National Health Service (NHS) were also reviewed and possibilities for future approaches explored. RESULTS: AMS is a requirement within all NHS hospitals in the United Kingdom as per government policy. Mandatory reporting of specific bloodstream infections (BSIs) and antimicrobial consumption alongside financial incentives has been the approach nationwide. Gram-negative resistance rates in BSIs have been increasing prior to the COVID-19 pandemic. Little SOT-specific data on antimicrobial resistance exists, and the general approach to AMS in SOT units has generally modeled the national approach. CONCLUSION: Although there is a good, standardized approach to AMS in the NHS, there is a need for SOT-specific AMS approaches to be developed in the United Kingdom. More data is required on antimicrobial resistance rates, and studies are needed to investigate optimal antimicrobial prophylaxis regimens for each solid organ group. Tools to aid AMS efforts and novel treatment options for complex multiresistant infection must also be explored amongst transplant centers.

First publication of endemic channels as part of a pediatric Antimicrobial Stewardship Program: when to turn on the alarms? Recommendations of a pediatric ASP program.

BACKGROUND: Pediatric Antimicrobial Stewardship Programs (ASP) consider DOT a fundamental measure to quantify the impact of ASP. Novel strategies have been described, but no endemic channels (EC) have been reported to compare antibiotic use within historical patterns. This report describes the process of constructing an EC and analyzing its interpretation. METHODS: This was a descriptive study of the construction, implementation, and analysis of EC. The median and quartile method, as well as the geometric mean (GM) and confidence interval (CI) methods using DOT for the last 4 years were used. ECs have also been elaborated on in critical services (PICU). RESULTS: GM and CI method seem to be more sensitive in identifying changes in antimicrobial use. Ceftriaxone increased its use starting in December 2021, reaching the warning zone in March 2022 in relation to increased cases of bacterial and complicated pneumonia. Piperacillin-tazobactam showed an important increase in PICU during the first 8 months of 2021, reaching the alert zone until August 2021; thereafter, its use decreased, and this variation was related to a modification in the presentation of complicated appendicitis during the COVID 19 pandemic restrictions. The use of ampicillin-sulbactam has increased since January 2022 because of a change in local guidelines regarding its use in appendicitis and peritonitis. The changes identified in each EC allowed ASP to take different conducts. CONCLUSION: EC allowed us to construct a new tool to measure ASP impact, internal comparison of antibiotic use facilitated taking timely interventions. EC could be useful for all pediatric and adult ASP.

Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care.

In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Investigating pharmacy students' therapeutic decision-making with respect to antimicrobial stewardship cases.

BACKGROUND: Antimicrobial stewardship programs (ASPs) play a big role in minimizing antimicrobial resistance. Pharmacists are essential members of the health care team and in order for them to fulfill roles on ASP teams and become antimicrobial stewards, they must be prepared adequately by pharmacy schools prior to entry into actual practice. Although programming has been implemented into entry-to-practice programs worldwide, little is known about how students interpret antimicrobial stewardship (AMS) data and arrive at clinical decisions. We aimed to explore students' cognitive processes and determine how they formulate therapeutic decisions when presented with AMS cases. METHODS: This was a qualitative study conducted using a case study approach, in which a sample (n=20) of pharmacy students was recruited to interpret AMS cases. Semi-structured 1-on-1 interviews were arranged with each participant. A think-aloud procedure with verbal protocol analysis was adopted to determine students' decision-making processes. Thematic analysis was used to interpret themes from the interview data. RESULTS: Two themes were interpreted from the data: students' focus and students' approach to case interpretation. Students' focus relates to external factors students consider when interpreting AMS case data and use to make and justify therapeutic decisions including patient-centered factors, drug-related factors, AMS interventions, and pharmacist's role. Students' clinical reasoning describes the approach that students use to interpret the data and the decision-making processes they employ to arrive at a clinical decision including a systematic approach versus non-systematic approach. CONCLUSIONS: Students vary in their focus and the cognitive strategies used to interpret AMS cases. Findings support the notion that clinical reasoning and decision-making should be explicitly taught in pharmacy curricula, in order to help students become aware of their own cognitive processes and decision-making abilities.

A multimodal intervention to optimise antimicrobial use in residential aged care facilities (ENGAGEMENT): protocol for a stepped-wedge cluster randomised trial.

BACKGROUND: Inappropriate antibiotic use can cause harm and promote antimicrobial resistance, which has been declared a major health challenge by the World Health Organization. In Australian residential aged care facilities (RACFs), the most common indications for antibiotic prescribing are for infections of the urinary tract, respiratory tract and skin and soft tissue. Studies indicate that a high proportion of these prescriptions are non-compliant with best prescribing guidelines. To date, a variety of interventions have been reported to address inappropriate prescribing and overuse of antibiotics but with mixed outcomes. This study aims to identify the impact of a set of sustainable, multimodal interventions in residential aged care targeting three common infection types. METHODS: This protocol details a 20-month stepped-wedge cluster-randomised trial conducted across 18 RACFs (as 18 clusters). A multimodal multi-disciplinary set of interventions, the 'AMS ENGAGEMENT bundle', will be tailored to meet the identified needs of participating RACFs. The key elements of the intervention bundle include education for nurses and general practitioners, telehealth support and formation of an antimicrobial stewardship team in each facility. Prior to the randomised sequential introduction of the intervention, each site will act as its own control in relation to usual care processes for antibiotic use and stewardship. The primary outcome for this study will be antibiotic consumption measured using defined daily doses (DDDs). Cluster-level rates will be calculated using total occupied bed numbers within each RACF during the observation period as the denominator. Results will be expressed as rates per 1000 occupied bed days. An economic analysis will be conducted to compare the costs associated with the intervention to that of usual care. A comprehensive process evaluation will be conducted using the REAIM Framework, to enable learnings from the trial to inform sustainable improvements in this field. DISCUSSION: A structured AMS model of care, incorporating targeted interventions to optimise antimicrobial use in the RACF setting, is urgently needed and will be delivered by our trial. The trial will aim to empower clinicians, residents and families by providing a robust AMS programme to improve antibiotic-related health outcomes. TRIAL REGISTRATION: US National Library of Medicine Clinical Trials.gov ( NCT04705259 ). Prospectively registered in 12th of January 2021.

Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19: A protocol for a pragmatic clinical trial.

BACKGROUND: The use of broad-spectrum antibiotics is widespread in patients with COVID-19 despite a low prevalence of bacterial co-infection, raising concerns for the accelerated development of antimicrobial resistance. Antimicrobial stewardship (AMS) is vital but there are limited randomized clinical trial data supporting AMS interventions such as prospective audit and feedback (PAF). High quality data to demonstrate safety and efficacy of AMS PAF in hospitalized COVID-19 patients are needed. METHODS AND DESIGN: This is a prospective, multi-center, non-inferiority, pragmatic randomized clinical trial evaluating AMS PAF intervention plus standard of care (SOC) versus SOC alone. We include patients with microbiologically confirmed SARS-CoV-2 infection requiring hospital admission for severe COVID-19 pneumonia. Eligible ward beds and critical care unit beds will be randomized prior to study commencement at each participating site by computer-generated allocation sequence stratified by intensive care unit versus conventional ward in a 1:1 fashion. PAF intervention consists of real time review of antibacterial prescriptions and immediate written and verbal feedback to attending teams, performed by site-based AMS teams comprised of an AMS pharmacist and physician. The primary outcome is clinical status at post-admission day 15 measured using a 7-point ordinal scale. Patients will be followed for secondary outcomes out to 30 days. A total of 530 patients are needed to show a statistically significant non-inferiority, with 80% power and 2.5% one-sided alpha assuming standard deviation of 2 and the non-inferiority margin of 0.5. DISCUSSION: This study protocol presents a pragmatic clinical trial design with small unit cluster randomization for AMS intervention in hospitalized COVID-19 that will provide high-level evidence and may be adopted in other clinical situations. TRIAL REGISTRATION: This study is being performed at the University of Alberta and is registered at ClinicalTrials.gov (NCT04896866) on May 17, 2021.

Protocol for a three-phase prospective study to develop educational resource of antimicrobial resistance and stewardship for medical programme.

INTRODUCTION: Antimicrobial resistance (AMR) is one of the critical medical issues of the 21st century. Medical professionals are the primary prescribers of antimicrobials; their undergraduate education of antimicrobial stewardship (AMS) is considered one of the fundamental approaches in combating the issue of AMR. This education level provides a platform to bridge any gaps in their knowledge and competency in AMS. This study aims to develop an educational resource on microbes, hygiene and prudent antimicrobial use for the undergraduate medical programme. The guideline produced will then be assimilated into the existing curriculum which will help to improve the quality of education which in turn will improve rationale as the use of antimicrobials in the future. METHODS AND ANALYSIS: A three-step approach consensus approach will be adopted for this study for the development of a validated medical curriculum guideline on AMR. A preliminary curriculum for the programme will be drafted from reviews of published literature including syllabi as well as national and international guidelines. A total of 26 potential sources were found to be relevant, and selected for this study. Subsequently, the drafted curriculum will be subjected for validation via online surveys by various infectious disease experts. Finally, a Delphi technique will be employed to obtain consensus on heterogeneous findings to the revised curriculum. The quantitative and qualitative responses will be analysed and discussed among the panel of researchers. ETHICS AND DISSEMINATION: This study protocol has been approved by the Institute of Health Sciences Research Ethics Committee of Universiti Brunei Darussalam (Reference: UBD/PAPRSBIHSREC/2020/124). Informed consent declaration will be collected prior to data collections as indication of agreement of participation in the study. Results will be made available to medical educators and also researchers on AMR and stewardship. The results also will be disseminated at feedback sessions to officers at Ministry of Health and Ministry of Education, Brunei Darussalam.

BSAC Vanguard Series: The future of healthcare workers and antimicrobial stewardship-educate, innovate, or pay the price.

In delivering global healthcare, and in the context of antimicrobial resistance (AMR) and antimicrobial stewardship (AMS) where information and knowledge is rapidly evolving, it is universally accepted that education and training of the healthcare workforce underpins the implementation of AMS and the effective use of existing and new health care technologies, therapies and informatics. Despite this, resourcing healthcare workforce education and training is often seen as a low priority, particularly in the resource-limited settings where the burden of AMR is greatest and healthcare resources are the most stretched. Therefore, it is disappointing to observe that, when funding the multi-dimensional AMR and AMS response, specific funding earmarked to support the development and implementation of both traditional and, increasingly, innovative education (particularly in the form of digital learning) is insufficient or lacking. In this article, I propose several novel strategies for addressing this deficit and to steer us to learn from the significant developments and support for education during the COVID-19 pandemic. If we do not invest in both traditional and innovative forms of education, our ability to create a well-trained healthcare workforce to deliver high-quality care and treatment, with better patient outcomes against AMR, will evaporate-and we will likely pay a far higher price as a consequence.

Understanding the social drivers of antibiotic use during COVID-19 in Bangladesh: Implications for reduction of antimicrobial resistance.

Antimicrobial resistance (AMR) is a global public health crisis that is now impacted by the COVID-19 pandemic. Little is known how COVID-19 risks influence people to consume antibiotics, particularly in contexts like Bangladesh where these pharmaceuticals can be purchased without a prescription. This paper identifies the social drivers of antibiotics use among home-based patients who have tested positive with SARS-CoV-2 or have COVID-19-like symptoms. Using qualitative telephone interviews, the research was conducted in two Bangladesh cities with 40 participants who reported that they had tested positive for coronavirus (n = 20) or had COVID-19-like symptoms (n = 20). Our analysis identified five themes in antibiotic use narratives: antibiotics as 'big' medicine; managing anxiety; dealing with social repercussions of COVID-19 infection; lack of access to COVID-19 testing and healthcare services; and informal sources of treatment advice. Antibiotics were seen to solve physical and social aspects of COVID-19 infection, with urgent ramifications for AMR in Bangladesh and more general implications for global efforts to mitigate AMR.

Antibiotic stewardship: Early discontinuation of antibiotics based on procalcitonin level in COVID-19 pneumonia.

WHAT IS KNOWN AND OBJECTIVE: Procalcitonin (PCT) levels rise in systemic inflammation, especially if bacterial in origin. COVID-19, caused by the novel coronavirus SARS-CoV-2, presents with acute respiratory distress syndrome. Elevated procalcitonin in COVID-19 is considered as a marker for severity of disease. There is no study available that indicates whether elevated PCT in COVID-19 is associated with inflammation or superimposed bacterial infection. The objective of this study is to evaluate the association between PCT levels and superadded bacterial infection, and the effect of discontinuation of antibiotic in the low PCT (<0.25 ng/ml) group on patients' outcomes. METHODS: A retrospective chart review of patients admitted with COVID-19 pneumonia at a single tertiary care centre. We collected information on demographics, co-morbidities, PCT level, antibiotic use, culture results for bacterial infection, hospital length of stay (LOS) and mortality. STATISTICAL ANALYSIS: Continuous variables were summarized with the sample median, interquartile range, mean and range. Categorical variables were summarized with number and percentage of patients. RESULTS AND DISCUSSION: We studied a total of 147 patients with COVID-19 pneumonia. 101 (69%) patients had a low PCT level (< 0.25 ng/ml). Bacterial culture results were negative for all patients, except 1 who had a markedly elevated PCT level (141.ng/ml). In patients with low PCT, 42% received no antibiotics, 59% received antibiotics initially, 32 (57%) patients antibiotic discontinued early (within 24 hours) and their culture remained negative for bacterial infections during hospitalizations. LOS was shorter (6 days in low PCT group compared to 9 days) in high PCT group. LOS was 1 day shorter (5 days vs 6 days) in no antibiotic group compared to antibiotic group. Our study examines the association between PCT level and superadded bacterial infection in COVID-19 pneumonia. Our results demonstrate that most patients admitted with COVID-19 have a low PCT (<0.25 ng/ml), which suggests no superadded bacterial infection and supports the previously published literature regarding low PCT in viral pneumonia. WHAT IS NEW AND CONCLUSION: Procalcitonin level remains low in the absence of bacterial infection. Early de-escalation/discontinuation of antibiotics is safe without adverse outcomes in COVID-19 pneumonia. Early de-escalation/discontinuation of antibiotics is associated with lower LOS.

Antimicrobial stewardship in the ICU in COVID-19 times: the known unknowns.

Since the start of the COVID-19 pandemic, there has been concern about the concomitant rise of antimicrobial resistance. While bacterial co-infections seem rare in COVID-19 patients admitted to hospital wards and intensive care units (ICUs), an increase in empirical antibiotic use has been described. In the ICU setting, where antibiotics are already abundantly-and often inappropriately-prescribed, the need for an ICU-specific antimicrobial stewardship programme is widely advocated. Apart from essentially warning against the use of antibacterial drugs for the treatment of a viral infection, other aspects of ICU antimicrobial stewardship need to be considered in view of the clinical course and characteristics of COVID-19. First, the distinction between infectious and non-infectious (inflammatory) causes of respiratory deterioration during an ICU stay is difficult, and the much-debated relevance of fungal and viral co-infections adds to the complexity of empirical antimicrobial prescribing. Biomarkers such as procalcitonin for the decision to start antibacterial therapy for ICU nosocomial infections seem to be more promising in COVID-19 than non-COVID-19 patients. In COVID-19 patients, cytomegalovirus reactivation is an important factor to consider when assessing patients infected with SARS-CoV-2 as it may have a role in modulating the patient immune response. The diagnosis of COVID-19-associated invasive aspergillosis is challenging because of the lack of sensitivity and specificity of the available tests. Furthermore, altered pharmacokinetic/pharmacodynamic properties need to be taken into account when prescribing antimicrobial therapy. Future research should now further explore the 'known unknowns', ideally with robust prospective study designs.

Suboptimal antimicrobial stewardship in the COVID-19 era: is humanity staring at a postantibiotic future?

In the absence of potent antimicrobial agents, it is estimated that bacterial infections could cause millions of deaths. The emergence of COVID-19, its complex pathophysiology and the high propensity of patients to coinfections has resulted in therapeutic regimes that use a cocktail of antibiotics for disease management. Suboptimal antimicrobial stewardship in this era and the slow pace of drug discovery could result in large-scale drug resistance, narrowing future antimicrobial therapeutics. Thus, judicious use of current antimicrobials is imperative to keep up with existing and emerging infectious pathogens. Here, we provide insights into the potential implications of suboptimal antimicrobial stewardship, resulting from the emergence of COVID-19, on the spread of antimicrobial resistance.

Tackling Antimicrobial Resistance in the Shadow of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a challenge for ongoing efforts to combat antimicrobial-resistant (AMR) bacterial infections. As we learn more about COVID-19 disease and drug stewardship evolves, there is likely to be a lasting impact of increased use of antimicrobial agents and antibiotics, as well as a lack of consistent access to health care across many populations. Sexually transmitted infections have been underreported during the pandemic and are often caused by some of the most drug-resistant pathogens. In their recent article in mBio, Parzych et al. (E. M. Parzych, S. Gulati, B. Zheng, M. A. Bah, et al., mBio 12:e00242-21, 2021, https://doi.org/10.1128/mBio.00242-21) focus on protection against Neisseria gonorrhoeae infection via in vivo delivery of an antigonococcal DNA-encoded antibody that has been modified for increased complement activation. Nucleic acid approaches are highly adaptable and could be tremendously beneficial for personalized strategies to combat AMR pathogens.

Procalcitonin as a biomarker for ventilator associated pneumonia in COVID-19 patients: Is it an useful stewardship tool?

Ventilator associated pneumonia(VAP) is a severe complication that can lead to high mortality when not early identified or when therapy is delayed. The aim of this study was to evaluate procalcitonin(PCT) as a biomarker for VAP development. In total, 73 hospitalized patients with COVID-19 were analyzed. PCT levels greater than 0.975ng/mL were more related to VAP. No association was found for C-reactive protein (CRP). The results show that procalcitonin may be a pertinent biomarker for VAP diagnosis and can be a helpful tool for antibiotic withdrawal.

Coronavirus Disease 2019 and Antibiotic Stewardship-Antibiotic Usage in Adult Patients: Is It Necessary? When Should It be Concerned?

Antibiotic consumption rates were quite high in number, although the bacterial coinfection rates were low in coronavirus disease 2019 pneumonia. Generally, empirical antibiotic treatment is not recommended for uncomplicated coronavirus disease 2019 mild to moderate pneumonia cases. On the other hand, antibiotic treatment and de-escalation are recommended for intubated intensive care unit patients or critical patients with sepsis, septic shock, or acute respiratory distress syndrome. The presentation of patients with severe coronavirus disease 2019 pneumonia can direct the clinicians to use antibiotics. We believe that wait and watch strategy can be preferred in such cases without sepsis, secondary bacterial infection findings, or procalcitonin < 0.5 ng/ mL. We think that a new wave of resistance will occur inevitably if we cannot perform the antibiotic stewardship properly.

Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study.

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.