Support Antimicrobial Stewardship Research Articles

Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot.

Mannheimia haemolytica is a major contributor to bovine respiratory disease (BRD), which causes substantial economic losses to the beef industry, and there is an urgent need for rapid and accurate diagnostic tests to provide evidence for treatment decisions and support antimicrobial stewardship. Diagnostic sequencing can provide information about antimicrobial resistance genes in M. haemolytica more rapidly than conventional diagnostics. Realizing the full potential of diagnostic sequencing requires a comprehensive understanding of the genetic markers of antimicrobial resistance. We identified genetic markers of resistance in M. haemolytica to macrolide class antibiotics commonly used for control of BRD. Genome sequences were determined for 99 M. haemolytica isolates with six different susceptibility phenotypes collected over 2 years from a feedlot in Saskatchewan, Canada. Known macrolide resistance genes estT, msr(E), and mph(E) were identified in most resistant isolates within predicted integrative and conjugative elements (ICEs). ICE sequences lacking antibiotic resistance genes were detected in 10 of 47 susceptible isolates. No resistance-associated polymorphisms were detected in ribosomal RNA genes, although previously unreported mutations in the L22 and L23 ribosomal proteins were identified in 12 and 27 resistant isolates, respectively. Pangenome analysis led to the identification of 79 genes associated with resistance to gamithromycin, of which 95% (75 of 79) had no functional annotation. Most of the observed phenotypic resistance was explained by previously identified antibiotic resistance genes, although resistance to the macrolides gamithromycin and tulathromycin was not explained in 39 of 47 isolates, demonstrating the need for continued surveillance for novel determinants of macrolide resistance.IMPORTANCEBovine respiratory disease is the costliest disease of beef cattle in North America and the most common reason for injectable antibiotic use in beef cattle. Metagenomic sequencing offers the potential to make economically significant reductions in turnaround time for diagnostic information for evidence-based selection of antibiotics for use in the feedlot. The success of diagnostic sequencing depends on a comprehensive catalog of antimicrobial resistance genes and other genome features associated with reduced susceptibility. We analyzed the genome sequences of isolates of Mannheimia haemolytica, a major bovine respiratory disease pathogen, and identified both previously known and novel genes associated with reduced susceptibility to macrolide class antimicrobials. These findings reinforce the need for ongoing surveillance for markers of antimicrobial resistance to support improved diagnostics and antimicrobial stewardship.

Bacterial enrichment prior to third-generation metagenomic sequencing improves detection of BRD pathogens and genetic determinants of antimicrobial resistance in feedlot cattle.

Bovine respiratory disease (BRD) is one of the most important animal health problems in the beef industry. While bacterial culture and antimicrobial susceptibility testing have been used for diagnostic testing, the common practice of examining one isolate per species does not fully reflect the bacterial population in the sample. In contrast, a recent study with metagenomic sequencing of nasal swabs from feedlot cattle is promising in terms of bacterial pathogen identification and detection of antimicrobial resistance genes (ARGs). However, the sensitivity of metagenomic sequencing was impeded by the high proportion of host biomass in the nasal swab samples. This pilot study employed a non-selective bacterial enrichment step before nucleic acid extraction to increase the relative proportion of bacterial DNA for sequencing. Non-selective bacterial enrichment increased the proportion of bacteria relative to host sequence data, allowing increased detection of BRD pathogens compared with unenriched samples. This process also allowed for enhanced detection of ARGs with species-level resolution, including detection of ARGs for bacterial species of interest that were not targeted for culture and susceptibility testing. The long-read sequencing approach enabled ARG detection on individual bacterial reads without the need for assembly. Metagenomics following non-selective bacterial enrichment resulted in substantial agreement for four of six comparisons with culture for respiratory bacteria and substantial or better correlation with qPCR. Comparison between isolate susceptibility results and detection of ARGs was best for macrolide ARGs in Mannheimia haemolytica reads but was also substantial for sulfonamide ARGs within M. haemolytica and Pasteurella multocida reads and tetracycline ARGs in Histophilus somni reads. By increasing the proportion of bacterial DNA relative to host DNA through non-selective enrichment, we demonstrated a corresponding increase in the proportion of sequencing data identifying BRD-associated pathogens and ARGs in deep nasopharyngeal swabs from feedlot cattle using long-read metagenomic sequencing. This method shows promise as a detection strategy for BRD pathogens and ARGs and strikes a balance between processing time, input costs, and generation of on-target data. This approach could serve as a valuable tool to inform antimicrobial management for BRD and support antimicrobial stewardship.

Variation in Pen-Level Prevalence of BRD Bacterial Pathogens and Antimicrobial Resistance Following Feedlot Arrival in Beef Calves.

Antimicrobials are crucial for treating bovine respiratory disease (BRD) in beef feedlots. Evidence is needed to support antimicrobial use (AMU) decisions, particularly in the early part of the feeding period when BRD risk is highest. The study objective was to describe changes in prevalence and antimicrobial susceptibility of BRD bacterial pathogens at feedlot processing (1 day on feed (1DOF)), 12 days later (13DOF), and for a subset at 36DOF following metaphylactic antimicrobial treatment. Mixed-origin steer calves (n = 1599) from Western Canada were managed as 16 pens of 100 calves, receiving either tulathromycin (n = 1199) or oxytetracycline (n = 400) at arrival. Deep nasopharyngeal swabs collected at all time points underwent culture and antimicrobial susceptibility testing (AST). Variability in the pen-level prevalence of bacteria and antimicrobial susceptibility profiles were observed over time, between years, and metaphylaxis options. Susceptibility to most antimicrobials was high, but resistance increased from 1DOF to 13DOF, especially for tetracyclines and macrolides. Simulation results suggested that sampling 20 to 30 calves per pen of 200 reflected the relative pen-level prevalence of the culture and AST outcomes of interest. Pen-level assessment of antimicrobial resistance early in the feeding period can inform the evaluation of AMU protocols and surveillance efforts and support antimicrobial stewardship in animal agriculture.

P07 Antimicrobial stewardship in Ireland 2009–22: a scoping review

Abstract Objectives The aim of this scoping review is to examine the current literature to evaluate progress related to the implementation of the Strategy for the Control of Antimicrobial Resistance in Ireland (SARI) Hospital Antimicrobial Stewardship (AMS) Working Group guidance (2009) on antimicrobial stewardship in hospitals in Ireland. Methods Systematic searches were carried out on four electronic databases (PubMed, CINAHL, Embase, Web of Science) and five targeted websites for grey literature sources. Titles and abstracts were screened independently by two reviewers. The remaining full-text publications were reviewed by all authors. Studies were mapped into at least one of four categories defined by recommendation headings from the SARI Hospital Antimicrobial Stewardship Working Group guidance: (A) structure and organization of AMS; (B) roles and responsibilities for prescribers; (C) antimicrobial stewardship interventions; (D) recommendations for non-acute residential healthcare institutions. Results The search yielded 545 peer reviewed papers for screening of which 35 were included and 327 grey reports of which 26 were included. Most articles were mapped to (C) antimicrobial stewardship interventions, with the least number mapped to (A) structure and organization of AMS. The most consistent findings in (C) were numerous implementation challenges requiring commitment by hospital leadership to provide human and financial resources, need for improved diagnostic capacity, and educational pathways for prescribers, pharmacists, nurses and patients. The findings in (A) included inadequate staffing across hospitals to implement stewardship programmes (regardless of hospital acuity) and investment required for information and communication technology resources to further support AMS and infection prevention and control. Conclusions There has been progress on AMS over the last 20 years and implementation remains a significant challenge. Clear identification of AMS programme management, use of data, education and communication need to be considered for the success of future implementation in all healthcare settings.

Complex Hospital-Based Electronic Prescribing-Based Intervention to Support Antimicrobial Stewardship: Qualitative Study.

Antimicrobial resistance (AMR) represents a growing concern for public health. We sought to explore the challenges associated with development and implementation of a complex intervention designed to improve AMS in hospitals. We conducted a qualitative evaluation of a complex AMS intervention with educational, behavioral, and technological components in 5 wards of an English hospital. At 2 weeks and 7 weeks after initiating the intervention, we interviewed 25 users of the intervention, including senior and junior prescribers, a senior nurse, a pharmacist, and a microbiologist. Topics discussed included perceived impacts of different elements of the intervention and facilitators and barriers to effective use. Interviews were supplemented by 2 observations of ward rounds to gain insights into AMS practices. Data were audio-recorded, transcribed, and inductively and deductively analyzed thematically using NVivo12. Tracing the adoption and impact of the various components of the intervention was difficult, as it had been introduced into a setting with competing pressures. These particularly affected behavioral and educational components (eg, training, awareness-building activities), which were often delivered ad hoc. We found that the participatory intervention design had addressed typical use cases but had not catered for edge cases that only became visible when the intervention was delivered in real-world settings (eg, variations in prescribing workflows across different specialties and conditions). Effective user-focused design of complex interventions to promote AMS can support acceptance and use. However, not all requirements and potential barriers to use can be fully anticipated or tested in advance of full implementation in real-world settings.

Impact of the COVID-19 pandemic on antimicrobial stewardship support for general practices in England: a qualitative interview study.

In England, Clinical Commissioning Group (CCG) (now replaced by Integrated Care Systems (ICS)) and Primary Care Network (PCN) professionals support primary care prescribers to optimise antimicrobial stewardship (AMS). To explore views and experiences of CCG/PCN staff in supporting AMS, and the impact of COVID-19 on this support. Qualitative interview study in primary care in England. Semi-structured interviews-with staff from CCG/PCNs responsible for AMS-at two time-points, via telephone interviews. These were audio-recorded, transcribed, and analysed thematically. Twenty-seven interviews were conducted with 14 participants (nine CCG, five PCN) in Dec 2020/Jan 2021 and Feb/Mar 2021.We found that AMS support was 1) deprioritised- to keep general practice operational and deliver COVID-19 vaccines; 2) disrupted-as social distancing made it harder to build relationships, conduct routine AMS activities, and challenge prescribing decisions; and 3) adapted-with opportunities identified for greater use of technology and from changed patient/public perceptions of viruses and self-care. We also found that resources to support AMS were valued if they were both novel, to counter AMS 'fatigue', and sufficiently familiar to fit with existing/future AMS. AMS needs to be reprioritised in general practice in the post-pandemic era and within the new ICS in England. This should include interventions/strategies that combine novel elements with already familiar strategies to refresh prescribers' motivation and opportunity for AMS. Behaviour change interventions should be aimed at improving the culture and processes for how PCN pharmacists voice concerns about AMS to prescribers in general practice and take advantage of the changed patient/public perceptions of viruses and self-care.

Tackling antimicrobial resistance: developing and implementing antimicrobial stewardship interventions in four African commonwealth countries through a health partnership model.

In recent years, health partnerships have shared infection prevention and control innovations between United Kingdom hospitals and Low-Middle-Income Countries. However, none had focused on antimicrobial stewardship (AMS), a core component of tackling antimicrobial resistance (AMR). This paper documents an effective approach to developing a program to increase AMS capacity in four African countries: Ghana, Tanzania, Uganda, and Zambia as part of the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) program. A systematic approach was applied to assess gaps in AMS interventions and inform the development of the CwPAMS program through deskbased assessments, including National Action Plans on AMR, online focus group meetings, and expert advisory group reviews. Twelve partnerships were selected for the CwPAMS program. AMS support tools were developed based on recommendations from the scoping, including an AMS checklist tool, a healthcare worker knowledge and attitudes questionnaire, and an antimicrobial prescribing app to support clinical decision-making. Training workshops on AMS were developed and delivered to volunteers in Africa and the UK using a train-the-trainer model. The tools and workshops facilitated capacity building for AMS through the generation and strengthening of knowledge, skills, commitment, structures, systems, and leadership among stakeholders in the UK and Africa. The overall average rating assigned to the program following independent evaluation using the Organisation for Economic Cooperation and Development Assistance Committee Evaluation Criteria was very good. The evaluation also highlighted that the majority of the HPs (75%) focused on AMS and/or improved prescribing practice; all HPs have developed and implemented AMS strategies, guidelines, and tools within their hospitals; and NHS staff were able to translate the knowledge and skills they had received early on in the program into clinical practice in response to COVID-19 challenges.

The Use of the TARGET Antibiotic Checklist to Support Antimicrobial Stewardship in England's Community Pharmacies.

Antimicrobial Stewardship (AMS) requires effective teamwork between healthcare professionals, with patients receiving consistent messages from all healthcare professionals on the appropriate antimicrobial use. Patient education may reduce patients' expectations to receive antibiotics for self-limiting conditions and reduce the pressure on primary care clinicians to prescribe antibiotics. The TARGET Antibiotic Checklist is part of the national AMS resources for primary care and aims to support interaction between community pharmacy teams and patients prescribed antibiotics. The Checklist, completed by the pharmacy staff with patients, invites patients to report on their infection, risk factors, allergies, and knowledge of antibiotics. The TARGET antibiotic checklist was part of the AMS criteria of England's Pharmacy Quality Scheme for patients presenting with an antibiotic prescription from September 2021 to May 2022. A total of 9950 community pharmacies claimed for the AMS criteria and 8374 of these collectively submitted data from 213,105 TARGET Antibiotic Checklists. In total, 69,861 patient information leaflets were provided to patients to aid in the knowledge about their condition and treatment. 62,544 (30%) checklists were completed for patients with an RTI; 43,093 (21%) for UTI; and 30,764 (15%) for tooth/dental infections. An additional 16,625 (8%) influenza vaccinations were delivered by community pharmacies prompted by discussions whilst using the antibiotic checklist. Community pharmacy teams promoted AMS using the TARGET Antibiotic Checklist, providing indication-specific education and positively impacting the uptake of influenza vaccinations.

O02 Improving antimicrobial use in HSE older persons residential care facilities

Abstract Background Antimicrobial use in Irish older persons residential care facilities (OP RCFs) is higher than in other European countries. In 2020/21, for the first time, an antimicrobial pharmacist (AMP) was appointed to each community healthcare organization (CHO) to monitor, develop and promote antimicrobial stewardship in community settings. Objectives To establish baseline antibiotic use, develop antimicrobial stewardship tools for OP RCFs, promote best practice in relation to antimicrobial stewardship (AMS) and monitor trends in antimicrobial use in HSE (state-run) OP RCFs. Methods A baseline point prevalence survey (PPS) of antimicrobial use was conducted across all HSE OP RCFs between October 2020 and August 2021. Following the survey, key national recommendations and AMS resources were developed in collaboration with the national Antimicrobial Resistance and Infection Control Programme. Feedback was provided to participating facilities by CHO AMPs with antimicrobial stewardship support and education for nursing and medical staff. In September 2021, monthly monitoring of antibiotic use was established in HSE OP RCFs in collaboration with local managers, to capture the proportion of antibiotics used for prophylaxis or treatment each month. Results A baseline PPS of antimicrobial use in 2020/21 showed that 11.9% (528/4446) of residents were on a systemic antibiotic, with 6.3% on antibiotic prophylaxis. Urinary tract infection accounted for 51% of antibiotic prescriptions. Following the baseline PPS, CHO AMPs developed an AMS toolkit for OP RCFs, engaged with nursing and medical staff to communicate PPS results, AMS resources and support implementation of AMS recommendations. Subsequently, monthly self-reporting of antimicrobial use in HSE OP RCFs was commenced in September 2021 and showed a sustained decrease in antimicrobial use with 7.9% residents on an antibiotic in Quarter 2 2022, with 2.7% on antibiotic prophylaxis. Conclusions Newly appointed CHO AMPs have successfully promoted AMS across HSE OP RCFs. Following audit, feedback, education, development and promotion of antimicrobial stewardship resources, there was a sustained decrease in the proportion of residents on antibiotics used for treatment and prophylaxis of infection.

A Host-Directed Approach to the Detection of Infection in Hard-to-Heal Wounds.

Wound infection is traditionally defined primarily by visual clinical signs, and secondarily by microbiological analysis of wound samples. However, these approaches have serious limitations in determining wound infection status, particularly in early phases or complex, chronic, hard-to-heal wounds. Early or predictive patient-derived biomarkers of wound infection would enable more timely and appropriate intervention. The observation that immune activation is one of the earliest responses to pathogen activity suggests that immune markers may indicate wound infection earlier and more reliably than by investigating potential pathogens themselves. One of the earliest immune responses is that of the innate immune cells (neutrophils) that are recruited to sites of infection by signals associated with cell damage. During acute infection, the neutrophils produce oxygen radicals and enzymes that either directly or indirectly destroy invading pathogens. These granular enzymes vary with cell type but include elastase, myeloperoxidase, lysozyme, and cathepsin G. Various clinical studies have demonstrated that collectively, these enzymes, are sensitive and reliable markers of both early-onset phases and established infections. The detection of innate immune cell enzymes in hard-to-heal wounds at point of care offers a new, simple, and effective approach to determining wound infection status and may offer significant advantages over uncertainties associated with clinical judgement, and the questionable value of wound microbiology. Additionally, by facilitating the detection of early wound infection, prompt, local wound hygiene interventions will likely enhance infection resolution and wound healing, reduce the requirement for systemic antibiotic therapy, and support antimicrobial stewardship initiatives in wound care.

Ceftolozane-tazobactam activity against clinical isolates of Pseudomonas aeruginosa from ICU patients with pneumonia: United States, 2015–2018

To report on the activity of ceftolozane-tazobactam and comparators against Pseudomonas aeruginosa isolates collected from hospitalized patients with pneumonia in US intensive care units (ICUs) between 2015 and 2018. Activity against all P. aeruginosa and common resistant phenotypes are described to better inform decision-making and support antimicrobial stewardship efforts. In total, 781 P. aeruginosa isolates were collected from 28 US hospitals. These isolates were tested for susceptibility to ceftolozane-tazobactam and comparators by Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodology using CLSI (2020) breakpoints. Phenotypes analysed included piperacillin-tazobactam-non-susceptible (NS), cefepime-NS, ceftazidime-NS, meropenem-NS and difficult-to-treat resistance (DTR). Ceftolozane-tazobactam was the most potent agent tested (minimum inhibitory concentration to inhibit 50% and 90% of isolates of 0.5 and 2 mg/L, respectively, inhibiting 97.2% at the susceptible breakpoint of ≤4 mg/L). Traditional first-line antipseudomonal β-lactam antibiotics (piperacillin-tazobactam, cefepime and ceftazidime) demonstrated <33% susceptibility when P. aeruginosa was NS to one or more agent. Although escalation of therapy to meropenem is commonly employed clinically, meropenem susceptibility ranged from 33.6% to 44.9% if P. aeruginosa was NS to any traditional first-line antipseudomonal β-lactam agent. Conversely, ceftolozane-tazobactam remained active against isolates that were NS to other agents, inhibiting 88.4% of isolates NS to piperacillin-tazobactam, 85.0% of isolates NS to cefepime and ceftazidime, and 90.3% of isolates NS to meropenem. Ceftolozane-tazobactam also maintained activity against 73.0% of DTR isolates. Ceftolozane-tazobactam maintained high activity against P. aeruginosa isolated from hospitalized patients with pneumonia in US ICUs, and had the greatest activity against isolates NS to one or more antipseudomonal β-lactams and DTR isolates.

Building the European Antimicrobial Resistance Surveillance network in veterinary medicine (EARS-Vet).

Antimicrobial resistance (AMR) should be tackled through a One Health approach, as stated in the World Health Organization Global Action Plan on AMR. We describe the landscape of AMR surveillance in the European Union/European Economic Area (EU/EEA) and underline a gap regarding veterinary medicine. Current AMR surveillance efforts are of limited help to veterinary practitioners and policymakers seeking to improve antimicrobial stewardship in animal health. We propose to establish the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) to report on the AMR situation, follow AMR trends and detect emerging AMR in selected bacterial pathogens of animals. This information could be useful to advise policymakers, explore efficacy of interventions, support antimicrobial stewardship initiatives, (re-)evaluate marketing authorisations of antimicrobials, generate epidemiological cut-off values, assess risk of zoonotic AMR transmission and evaluate the burden of AMR in animal health. EARS-Vet could be integrated with other AMR monitoring systems in the animal and medical sectors to ensure a One Health approach. Herein, we present a strategy to establish EARS-Vet as a network of national surveillance systems and highlight challenges of data harmonisation and bias. Strong political commitment at national and EU/EEA levels is required for the success of EARS-Vet.

Safety and efficacy of de-labelling penicillin allergy in adults using direct oral challenge: a systematic review.

BackgroundApproximately 10% of people have an unverified penicillin allergy, with multiple personal and public health consequences.ObjectivesTo assess the efficacy and safety of direct oral challenge, without prior skin testing, in this population.MethodsMEDLINE, EMBASE, CINAHL, the Cochrane Library and Google Scholar were searched from inception to 28 June 2020 (updated November 2020) to find published and unpublished studies that reported direct oral challenge for the purpose of removal of penicillin allergy labels. Population weighted mean was used to calculate the proportion of patients who developed an immediate or delayed reaction to direct oral challenge across the studies.ResultsThirteen studies were included in the review, with a sample size of 1202 (range 7–328). Studies included inpatient and outpatient cohorts assessed as low risk for true allergy. In pooled analysis of all 13 studies there were 41/1202 (3.41%) mild immediate or delayed reactions to direct oral challenge. The population-weighted mean incidence of immediate or delayed reaction to an oral challenge across studies was also 3.41% (95% CI: 2.38%–4.43%). There were no reports of serious adverse reactions, 96.5% of patients could be de-labelled and many were subsequently successfully treated with penicillin.ConclusionsDirect oral challenge is safe and effective for de-labelling patients assessed as low risk for true allergy. Non-specialist clinicians competent in using an assessment algorithm can offer evaluation of penicillin allergy labels using direct oral challenge in appropriate patients. These measures will facilitate optimal infection treatment for patients, support antimicrobial stewardship, and minimize antimicrobial resistance.

Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship

Antibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of “wisdom of crowds”, which states that a group’s collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance.

Supporting antimicrobial stewardship in Ghana: evaluation of the impact of training on knowledge and attitudes of healthcare professionals in two hospitals.

BackgroundA Commonwealth Partnership for Antimicrobial Stewardship was created between the Scottish Antimicrobial Prescribing Group (SAPG), Ghana Police Hospital and Keta Municipal Hospital. During a scoping visit, requirements for implementing antimicrobial stewardship (AMS), areas for improvement and training needs were identified.MethodsA multidisciplinary team from SAPG and health psychologists from The Change Exchange developed and delivered multi-professional evidence-based teaching incorporating behavioural science, supported by partner pharmacists in each hospital. Four sessions were delivered over 2 days to 60 participants across both sites. Before and after the sessions, participants were asked to complete a knowledge quiz and a behaviours survey. Results were analysed using t-tests.ResultsComparison of the participants’ pre- and post-test quiz scores (Keta Municipal Hospital 9.4 and 10.9, Ghana Police Hospital 9.2 and 11.1, respectively) demonstrated statistically significant improvement in knowledge of antimicrobial resistance and appropriate use of antibiotics. Comparison of survey responses before and after the education sessions indicated that the education had a positive impact on participants’ attitudes towards the issue of antimicrobial resistance, their role in AMS and confidence in using the Ghana Standard Treatment Guidelines. Participants were also more likely to question colleagues about compliance with guidelines. Forty-eight participants (80%) completed a training evaluation and all responded positively.ConclusionsThe education sessions appeared to be successful in improving knowledge and behaviours of hospital staff. Cascade of an abbreviated version of the training by partner pharmacists and AMS teams in Ghana will ensure that all staff have the opportunity to develop skills and knowledge to support AMS.

Multicenter Evaluation of the BioFire FilmArray Pneumonia/Pneumonia Plus Panel for Detection and Quantification of Agents of Lower Respiratory Tract Infection.

The ability to provide timely identification of the causative agents of lower respiratory tract infections can promote better patient outcomes and support antimicrobial stewardship efforts. Current diagnostic testing options include culture, molecular testing, and antigen detection. These methods may require collection of various specimens, involve extensive sample treatment, and can suffer from low sensitivity and long turnaround times. This study assessed the performance of the BioFire FilmArray Pneumonia Panel (PN panel) and Pneumonia Plus Panel (PNplus panel), an FDA-cleared sample-to-answer assay that enables the detection of viruses, atypical bacteria, bacteria, and antimicrobial resistance marker genes from lower respiratory tract specimens (sputum and bronchoalveolar lavage [BAL] fluid). Semiquantitative results are also provided for the bacterial targets. This paper describes selected analytical and clinical studies that were conducted to evaluate performance of the panel for regulatory clearance. Prospectively collected respiratory specimens (846 BAL and 836 sputum specimens) evaluated with the PN panel were also tested by quantitative reference culture and molecular methods for comparison. The PN panel showed a sensitivity of 100% for 15/22 etiologic targets using BAL specimens and for 10/24 using sputum specimens. All other targets had sensitivities of ≥75% or were unable to be calculated due to low prevalence in the study population. Specificity for all targets was ≥87.2%, with many false-positive results compared to culture that were confirmed by alternative molecular methods. Appropriate adoption of this test could provide actionable diagnostic information that is anticipated to impact patient care and antimicrobial stewardship decisions.

A Feasible Laboratory-Strengthening Intervention Yielding a Sustainable Clinical Bacteriology Sector to Support Antimicrobial Stewardship in a Large Referral Hospital in Ethiopia.

Background: Access to clinical bacteriology in low resource settings (LRS) is a key bottleneck preventing individual patient management of treatable severe infections, detection of antimicrobial resistance (AMR), and implementation of effective stewardship interventions. We sought to demonstrate the feasibility of a practical bundle of interventions aimed at implementing sustainable clinical bacteriology services at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on cost and intensity of supervision.Methods: Starting in Dec 2015, an intervention based on the CLSI QMS01-A guideline was established, consisting of (i) an initial needs assessment, (ii) development of key standard operating procedures, (iii) adaptation of processes for LRS, (iv) training and supervision of laboratory staff via consultant visits and existing online resources, and (v) implementation of a practical quality systems approach. A guiding principle of the bundle was sustainability of all interventions post implementation.Outcomes and challenges: An initial investment of ~US$ 26,200 for laboratory reagents, and a total of 50 visit-days per year from three Canadian and Norwegian microbiologists were committed. Twelve SOPs, including antimicrobial susceptibility testing, were adapted, and an automated blood culture platform was donated (bioMerieux). In the first 18 months of implementation of the intervention, the average volume of specimens analyzed in the lab went from 15/day to 75/day. The number of blood cultures tested increased from an average of 2/day to over 45/day. Antimicrobial susceptibility testing was introduced and cumulative antibiograms were generated for the institution. Quality control was implemented for all procedures and quality assurance tools implemented included external quality assurance and proficiency testing of six technologists with longitudinal follow-up. The laboratory is on the path toward SLIPTA accreditation by the African Society for Laboratory Medicine. Reagent costs, staff training and retention, and engagement of clinical personnel with the lab proved to be manageable challenges. Key external challenges include in-country supply-chain management issues, lack of competition among distributors, and foreign-currency exchange distortions.Conclusions: Using a relatively low-intensity intervention based on existing training tools and accreditation schemes, we demonstrate that establishment of reasonable-quality clinical bacteriology is not only within reach but also a critical step toward assessing the burden of AMR in settings like this one and implementing effective stewardship strategies.

Evaluation of a Pharmacist-Driven Procalcitonin Protocol for Lower Respiratory Tract Infections Using a Clinical Decision Support System.

Purpose: Procalcitonin (PCT) may be an effective biomarker in the management of lower respiratory tract infections (LRTI) when combined with antimicrobial stewardship support. We assessed the impact of a PCT protocol with clinical pharmacy support for LRTI using a clinical decision support system (CDSS) for monitoring. Methods: This was a single-center retrospective cohort study conducted at a large, nonteaching hospital in Nashville, TN. All patients who met eligibility requirements and were initiated on the PCT protocol for a suspected LRTI between February and March 2018 were included and matched to historical control patients from 2016 to 2017 on a 1:1 basis based on antibiotics, indication, and time of year. Results: During this 2-month period, a total of 126 patients met eligibility requirements for inclusion in the PCT group and were matched to historical control patients. Patients in the PCT group received decreased median antibiotic days of therapy (DOT) compared to controls (11 vs 14, P = .004). There was no change in median length of stay (LOS) between groups. The acceptance rate for patient-specific antibiotic de-escalation recommendations from the clinical pharmacist was 62.5%. Conclusion: PCT protocols that utilize clinical pharmacist interpretation and a CDSS may be an effective intervention of the antimicrobial stewardship program (ASP) for decreasing antibiotic DOT for LRTI.

What Resources Do NHS Commissioning Organisations Use to Support Antimicrobial Stewardship in Primary Care in England?

Professional education and public engagement are fundamental components of any antimicrobial stewardship (AMS) strategy. The National Institute for Health and Care Excellence (NICE), Public Health England (PHE), Health Education England (HEE) and other professional organisations, develop and publish resources to support AMS activity in primary care settings. The aim of this study was to explore the adoption and use of education/training and supporting AMS resources within NHS primary care in England. Questionnaires were sent to the medicines management teams of all 209 Clinical Commissioning Groups (CCGs) in England, in 2017. Primary care practitioners in 168/175 (96%) CCGs received AMS education in the last two years. Respondents in 184/186 (99%) CCGs reported actively promoting the TARGET Toolkit to their primary care practitioners; although 137/176 (78%) did not know what percentage of primary care practitioners used the TARGET toolkit. All respondents were aware of Antibiotic Guardian and 132/167 (79%) reported promoting the campaign. Promotion of AMS resources to general practices is currently excellent, but as evaluation of uptake or effect is poor, this should be encouraged by resource providers and through quality improvement programmes. Trainers should be encouraged to promote and highlight the importance of action planning within their AMS training. AMS resources, such as leaflets and education, should be promoted across the whole health economy, including Out of Hours and care homes. Primary care practitioners should continue to be encouraged to display a signed Antibiotic Guardian poster as well as general AMS posters and videos in practice, as patients find them useful and noticeable.

Evaluation of the impact of the Accelerate Pheno\u2122 system on time to result for differing antimicrobial stewardship intervention models in patients with gram-negative bloodstream infections

BackgroundInitiating early effective antimicrobial therapy is the most important intervention demonstrated to decrease mortality in patients with gram-negative bacteremia with sepsis. Rapid MIC-based susceptibility results make it possible to optimize antimicrobial use through both escalation and de-escalation.MethodWe prospectively evaluated the performance of the Accelerate Pheno™ system (AXDX) for identification and susceptibility testing of gram-negative species and compared the time to result between AXDX and routine standard of care (SOC) using 82 patient samples and 18 challenge organisms with various confirmed resistance mechanisms. The potential impact of AXDX on time to antimicrobial optimization was investigated with various simulated antimicrobial stewardship (ASTEW) intervention models.ResultsThe overall positive and negative percent agreement of AXDX for identification were 100 and 99.9%, respectively. Compared to VITEK® 2, the overall essential agreement was 96.1% and categorical agreement was 95.4%. No very major or major errors were detected. AXDX reduced the time to identification by an average of 11.8 h and time to susceptibility by an average of 36.7 h. In 27 patients evaluated for potential clinical impact of AXDX on antimicrobial optimization, 18 (67%) patients could potentially have had therapy optimized sooner with an average of 18.1 h reduction in time to optimal therapy.ConclusionUtilization of AXDX coupled with simulated ASTEW intervention notification substantially shortened the time to potential antimicrobial optimization in this cohort of patients with gram-negative bacteremia. This improvement in time occurred when ASTEW support was limited to an 8-h coverage model.