Antifungal stewardship in solid-organ transplantation: What is needed?

BACKGROUND: Antifungal stewardship (AFS) lags behind antimicrobial stewardship (AMS) in terms of implementation, evidence base, and workforce experience. Solid-organ transplantation (SOT) carries a significant risk of invasive fungal infection, with high associated mortality, and is therefore associated with significant opportunities to optimize antifungal use. METHODS: A literature search for the terms "antifungal stewardship" and "solid-organ transplant" revealed a small evidence base to support AFS programs in this patient group. RESULTS: There is significant overlap in the methodology used in AMS and AFS programs, with notable differences in diagnostics, which are discussed in detail. The primary AFS interventions tested in SOT recipients are implementation of clinical guidelines and care bundles, digital enablers of AFS, and post-prescription review/audit and feedback. CONCLUSION: There is an urgent need for further research to support effective AFS strategies in this highly susceptible population.

Effectiveness of an antifungal stewardship programme at a London teaching hospital 2010-16.

Background: The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes. Patients and methods: From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases. Results: A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention. Conclusions: Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure.

Stability of Meropenem After Reconstitution for Administration by Prolonged Infusion.

Objective: Meropenem is a parenteral carbapenem antibiotic which has a broad spectrum of activity against aerobes and anaerobes. Meropenem's bactericidal activity is determined by the time during which meropenem concentration remains above the minimal inhibition concentration (MIC) during the dosing interval. Thus, prolonged infusion is the optimal way to maximize the time-dependant activity. However, studies to date have shown that carbapenems and in particular, meropenem, are relatively unstable in solution. The aims of this study were therefore (1) to establish the effects of temperature on the concentration of a generic brand reconstituted meropenem solution and (2) to determine whether 24-hour continuous infusion is possible without concentrations dropping below the recommended 90%. Method: Preliminary examination was carried out by the means of nuclear magnetic resonance (NMR) spectroscopy. Meropenem was subsequently assayed using high-performance liquid chromatography (HPLC). The method was developed and validated in compliance with International Council for Harmonisation (ICH) guidelines. Meropenem's stability was examined at two temperatures 22°C and 33°C to mimic average and high temperature in hospital wards. Solutions were prepared aseptically at the clinically relevant concentration. Results: NMR results obtained showed an increase in open ring methyl groups peak intensity, indicating that meropenem begins to degrade upon dissolution (d=1.05 and 1.25). Results obtained from quantitative HPLC confirm that meropenem concentrations dropped to 90% of initial concentration at 7.4 hours and 5.7 hours at 22°C and 33°C, respectively. Conclusion: Although results obtained indicate that meropenem should not be continuously infused over 24 hours, it is possible that meropenem could be continuously infused for at least 7 hours if temperature does not exceed 22°C and for 5 hours if temperature does not exceed 33°C.

Pressure Injury Knowledge in Critical Care Nurses.

PURPOSE: The purpose of this study was to identify pressure injury knowledge in critical care nurses related to prevention and staging following multimodal education initiatives. DESIGN: Postintervention descriptive study. SETTING AND SAMPLE: The sample comprised 32 RNs employed in medical intensive care/coronary intensive care or surgical intensive care units. The study setting was a 237-bed Veterans Affairs acute care hospital in the Midwestern United States. METHODS: Critical care RNs were asked to participate in this project over a 3-week period following a multimodal 2-year education initiative. Nurses completed the paper version of the 72-item Pieper-Zulkowski Pressure Ulcer Knowledge Test (PZ-PUKT) to determine pressure injury knowledge level. Calculated mean cumulative scores and subscores for items related to prevention and staging, respectively. Pearson correlations were used to examine associations between nursing staff characteristics and the PZ-PUKT prevention and staging scores. RESULTS: The cumulative score on the PZ-PUKT was 51.66 (72%); nurses with 5 to 10 years' experience had a higher mean score than nurses with experiences of 20 years or more (mean ± SD = 54.25 ± 4.37 vs 49.5 ± 7.12), but the difference was not statistically significant. Nurses scored higher on the staging system-related items as compared to the prevention-related items (81% vs 70%). Nurses achieved higher staging subscale scores if they were younger (r =-0.41, P < .05), had less experience (r =-0.43, P < .05), and if they worked in the medical intensive care unit (r = 0.37, P < .05). CONCLUSIONS: Study findings indicate gaps in knowledge related to pressure injury practice; participants had greater knowledge of staging rather than prevention. Cumulative and subscale findings can be used to direct educational efforts needed to improve and maintain an effective pressure injury prevention program.

Real-World Budget Impact of Fidaxomicin versus Vancomycin or Metronidazole for In-Hospital Treatment of Clostridioides difficile Infection

Fidaxomicin, a macrocyclic antibiotic, selectively kills Clostridioides difficile and reduces C. difficile infection (CDI) recurrence compared with vancomycin, but some studies and guidelines report fidaxomicin as being less cost-effective. The aim of this study was to compare the cost-effectiveness and budget impact of fidaxomicin versus vancomycin or metronidazole for treating CDI in a real-world UK setting. Data were retrospectively collected from medical records of 86 patients with CDI treated with vancomycin or metronidazole at a single UK hospital between April 2011 and March 2012, and prospectively from 62 patients with CDI treated with fidaxomicin between August 2012 and July 2013. CDI cases were matched by age, financial year, and healthcare resource use to control cases. CDI recurrence rates were lower with fidaxomicin (6.5%) than vancomycin/metronidazole (19.8%). An estimated 12 additional recurrent CDIs were prevented with fidaxomicin treatment. Patients with CDI had significantly higher healthcare costs than those without CDI, with a mean excess spend of GBP 10,748 and GBP 17,451 per patient in the fidaxomicin (p = 0.015) and vancomycin/metronidazole cohorts (p < 0.001), respectively. A second CDI was associated with mean excess costs of GBP 8373 and GBP 20,249 per patient in the fidaxomicin and vancomycin/metronidazole cohorts, respectively. Despite higher fidaxomicin drug costs, overall cost savings were estimated at GBP 140,292 (GBP 2125 per CDI). In this real-world study, first-line CDI treatment with fidaxomicin reduced healthcare costs versus vancomycin/metronidazole, consistent with previous studies.

Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time.

OBJECTIVES: The majority of HA-MRSA infections are caused by endogenous infection and by only a small number of clones. The reasons for the success of some clones over others are unknown. METHODS: We investigated the evolution of an MRSA population from a large, acute-care teaching hospital in London, UK over a 10 year period. MRSA incidence and antibiotic prescribing were correlated with changes in resistance genes and prevalence of clonal groups. RESULTS: Three clones caused the majority of infections, CC30 SCCmecII (EMRSA-16), CC22 SCCmecIV (EMRSA-15) and ST239 SCCmecIII. Clones that were multidrug resistant were selected for, and CC22 became dominant once it acquired a wide range of extra resistance genes. CC22 MRSA was also the fittest clone in an independent growth assay and a competition assay, and had a greater ability to survive desiccation. No individual isolate was fully drug resistant, and there was evidence of substantial horizontal gene transfer (HGT) as well as resistance gene loss within the clonal groups. The exception was fluoroquinolone resistance, which was rarely lost by any of the dominant hospital clones, suggesting that this resistance contributes to selection and survival of HA-MRSA. In support of this, a decrease in hospital-wide ciprofloxacin (a fluoroquinolone) prescribing was strongly associated with an overall decrease in MRSA infection. CONCLUSION: Our data suggest successful HA-MRSA clones such as CC22 SCCmecIV are resistant to fluoroquinolones as well as fitter and able to acquire, but not necessarily accumulate, resistance to a wide range of additional antibiotics.

Violence Exposure, Child Asthma Morbidity, and Maternal Depressive Symptoms: A Longitudinal Analysis of Cumulative Risk.

Low-income mothers of children with uncontrolled asthma are an underserved population at risk for psychological distress. We examined the impact of violence exposure and child asthma morbidity on depressive symptoms in mothers of youths with uncontrolled asthma. Asthma symptoms and health care utilization, socio-demographics, and standardized measures of depressive symptoms and violence exposure were ascertained by self-report. Latent Growth Curve Modeling tested the associations of violence and asthma morbidity with depressive symptoms. Participating mothers (N=276) reported high baseline violence exposure (59.5%) and depressive symptoms (34.4%); nearly a quarter had clinically significant depressive symptoms at 12 months. Violence exposure was consistently associated with maternal depressive symptoms. Individual indicators of asthma morbidity were nonsignificant, but the cumulative effect of asthma morbidity was predictive of higher depressive symptoms. Findings suggest holistic risk assessment and interventions may be needed to ameliorate the chronic distress observed in mothers of youths with uncontrolled asthma.

Advance Care Planning and Communication Skills Improve after an Interprofessional Team Simulation with Standardized Patients.

Background: Improving rates of advance care planning (ACP) and advance directive completion is a recognized goal of health care in the United States. No prior study has examined the efficacy of standardized patient (SP)-based student interprofessional ACP trainings. Objectives: The present study aims to evaluate an interprofessional approach to ACP education using SP encounters. Design: We designed a pre-post evaluation of an innovative interprofessional ACP training curriculum using multimodal adult learning techniques to test the effects of completing ACP discussions with SPs. Three surveys (pre-training T1, post-training T2, and post-clinical encounter T3) evaluated student knowledge, Communication Self-Efficacy (CSES), ACP self-efficacy, and interprofessional teamwork (using SPICE-R2). Setting/Subjects: Students from the schools of medicine, nursing, and social work attended three training modules and two SP encounters focused on ACP. Measurements/Results: During academic year 2018-2019, 36 students participated in the training at University of Maryland. Results demonstrated statistically significant improvements in ACP self-efficacy, M T1 = 2.9 (standard deviation [SD]T1 = 0.61) compared with M T3 = 3.9 (SDT3 = 0.51), p < 0.001, and CSES, M T1 = 4.6 (SDT1 = 1.35) versus M T3 = 7.3 (SDT3 = 0.51), p < 0.001, from T1 to T3. There was a medium-to-large improvement in knowledge from an average score of 4.3 (SD = 1.0) at T1 to an average score of 5.5 (SD = 1.4) at T2, p = 0.005, d = 0.67. Conclusions: Our interprofessional training module and SP encounter was successful in improving medical, social work, and nursing students' self-reported communication skills and knowledge regarding ACP.

Differential antibiotic dosing in critical care: survey on nurses' knowledge, perceptions and experience.

BACKGROUND: With the discovery of new antibiotics diminishing, optimizing the administration of existing antibiotics has become a necessity. Critical care nurses play a crucial role in combating antimicrobial resistance and are involved in preparing and administering antibiotics as well as monitoring their effects on patients. A dosing strategy proposed to reduce the development of ever-evolving antimicrobial resistance involves differential dosing regimens such as prolonged/continuous infusions. OBJECTIVES: To assess critical care nurses' knowledge, perceptions, comfort and experience in relation to prolonged/continuous infusion antibiotics. METHODS: A descriptive cross-sectional study was conducted using an investigator-developed, self-administered survey consisting of open- and closed-ended questions. Obtained data were computed using SPSS. Descriptive and inferential statistics were used to analyse the data. RESULTS: Fifty-two critical care nurses participated in the survey. Data revealed that nurses have adequate levels of knowledge and comfort relating to the use of prolonged/continuous infusion antibiotics along with the ability to communicate effectively on the topic. Results indicate there is a need for further learning, especially in terms of multiplicity of methods for preparing and administering prolonged/continuous infusions and dose calculations. Overall, results are promising as nurses support the wider implementation of prolonged/continuous infusion treatment regimens in critical care. CONCLUSION: Although critical care nurses had a good understanding surrounding the use of prolonged/continuous infusion antibiotics, there is a need for further learning beyond information gained from nursing education courses. Findings from this study indicate that nurses are supportive of prolonged/continuous infusion antibiotics. However, further research is needed to determine the most effective mode of antibiotic administration.

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug-drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. 'Breakthrough' invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3-4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one 'probable' and one 'possible'. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

Assessment and Management of Delirium in Critically Ill Veterans.

BACKGROUND: Delirium is a complex syndrome prevalent in the intensive care unit. It has been associated with significant morbidity including distress, longer hospital stays, prolonged cognitive impairment, and increased mortality. OBJECTIVE: To describe a nurse-led interdisciplinary quality improvement initiative to increase nurses' knowledge of delirium, documentation of delirium assessment, and patient mobility. METHODS: Sixty-seven nurses in medical and surgical intensive care units were required to attend an interactive education program on delirium assessment and management. Scores on tests taken before and after the education program were used to evaluate knowledge. Medical records and bedside rounds were used to validate Confusion Assessment Method for the Intensive Care Unit documentation and interventions. Descriptive statistics were used to describe changes over time. A delirium resource team composed of nurses, physicians, and therapists provided didactic education paired with simulation training and bedside coaching. Mobility screening tests and computer templates guided assessments and interventions. RESULTS: Documentation of the Confusion Assessment Method improved from less than 50% to consistently 99%. Mobilization in the surgical intensive care unit increased from 90% to 98% after intervention. Days of delirium significantly decreased from 51% before intervention to 31% after intervention (χ12=7.01, P = .008). CONCLUSIONS: The success of this quality improvement project to enhance recognition of delirium and increase mobility (critical components of the pain assessment, breathing, sedation choice, delirium, early mobility, and family education bundle) was contingent on nursing leaders hip, interdisciplinary team collaboration, and interactive education.

Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists.

Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK.

Treatment principles for Candida and Cryptococcus.

The yeasts Candida and Cryptococcus spp. are important human opportunistic pathogens. Candida spp. rely on skin or mucosal breach to cause bloodstream infection, whereas Cryptococcus spp. exploit depressed cell-mediated immunity characteristic of advanced HIV infection. The treatment for both organisms relies on the administration of rapidly fungicidal agents. In candidaemia, source control is important, with removal of prosthetic material and drainage of collections, as well as hunting for and tailoring therapy to disseminated sites of infection, particularly the eyes and heart. For cryptococcal meningitis, restoration of immune function through antiretroviral therapy (ART) is key, together with careful management of the complications of raised intracranial pressure and relapsed infection, both pre- and post-ART.