Education and management of antimicrobials amongst nurses in Africa-a situation analysis: an Infection Control Africa Network (ICAN)/BSAC online survey.

Objectives: To assess the current involvement of nurses in the use and management of antimicrobials and their training in antimicrobial stewardship (AMS) across Africa. Methods: After a pilot study, an online questionnaire (SurveyMonkey) in both French and English was circulated via the Infection Control Africa Network (ICAN) mailing list to both members and non-members in Africa. The study was conducted from 26 May to 19 August 2016. Data were summarized in proportions and bar charts; proportions were compared using the χ2 test. A multivariate logistic regression model was built to identify independent factors associated with the practice of AMS. Results: While 96% of the 173 respondents were aware of the term 'AMS', 88.5% (146/165) undertook AMS tasks as part of their job; 91.9% (158/172) wanted to be more involved in AMS but 44.9% (71/158) reported there were barriers in doing so. AMS training was delivered to 36.7% (62/169) and 53.6% (90/168), respectively, during their undergraduate and postgraduate education. AMS training for healthcare workers in their institutions was reported by 50.3% (86/171), including training aimed at doctors (56.9%), pharmacists (76.7%), microbiologists (31.4%) and nurses (95.3%). However, 95.4% (164/172) of respondents asked for further education on AMS and the majority preferred AMS training to be part of the infection prevention curriculum (IPC) education. Three-quarters of institutions had an AMS initiative, but only ∼41% reported having seen a national AMS guideline. Conclusions: For Africa, we recommend AMS education at undergraduate level, AMS policies at institution and national levels and incorporating AMS training into the IPC for nurses.

Extended stability of antimicrobial agents in administration devices.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is an established approach to patient care. A lack of data on antimicrobial stability within administration devices is a barrier to service expansion, and poses an antimicrobial stewardship dilemma. Often broad-spectrum, long half-life agents are used instead of narrow-spectrum agents, which need more frequent administration, but could possibly be used if stability data were available. Objectives: To complete a comprehensive literature review of published antimicrobial stability data, and assess these against a nationally recognized minimum dataset for medicines compounded into administration devices. Methods: Medline, EMBASE, Global Health, International Pharmaceutical Abstracts and Biomedical Research Database were interrogated in April 2014 and updated in November 2015. Results: A total of 420 citations were reviewed with 121 selected for full text review. None of these papers met the inclusion criteria stipulated in the national standards. The most frequent reason for study exclusion was the tolerance limit for the level of the active pharmaceutical ingredient being wider than 95%-105% and absence of 'in-use' testing at 37 °C. Conclusions: This review found no published studies that comply with UK national standards for stability testing. We recommend further research and publication of antimicrobial stability data to support OPAT within the antimicrobial stewardship agenda.

Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.

OBJECTIVES: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. METHODS: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion. RESULTS: Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies. CONCLUSIONS: This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.

Testing two screening instruments for autism spectrum disorder in UK community child health services.

AIM: The aim of this study was to test the accuracy of two screening instruments in UK Community health services: Modified Checklist for Autism in Toddlers (M-CHAT) and Social Communication Questionnaire (SCQ) for autism spectrum disorder (ASD). A two-stage screening and in-depth assessment procedure, combined with sampling stratification and statistical weighting, allowed the accuracy of the screens to be estimated in the entire population of referred children. METHOD: The study included all referrals of children aged 18 to 48 months to community paediatric and speech and language therapy services in two London districts over a 12-month period between September 2004 and September 2005. Parents of 808 children were approached; screen data were obtained on 543 children (67.2%). A stratified subsample of 120 children received an in-depth assessment for ASD as defined by the International Statistical Classification of Diseases and Related Health Problems, 10th edition. Community clinician judgement of likely ASD was available for 98 out of the 120 children. RESULTS: The sensitivity and specificity were 64% (95% confidence intervals; range 51-80%) and 75% (63-85%) for the SCQ, and 82% (72-92%) and 50% (33-64%) for M-CHAT. There was no evidence that the area under the curve differed between the two screening instruments. There was also no evidence that clinician judgement of likely ASD differed from either of the screening tests. The screening tests did not perform well to confirm preliminary clinical judgement to refer (in series), nor as an alternative indicator for referral (in parallel). INTERPRETATION: While screening tests may provide useful information, their accuracy is moderate. Screening information in isolation should not be used to make referral decisions regarding specialized ASD assessment.

Sedation modality in acute respiratory distress syndrome: does method of sedation affect length of stay, outcomes, or adverse events? A systematic review.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening, diffuse inflammatory pulmonary condition characterised by the Berlin criteria. Incidence of ARDS is estimated at 2.5-19% globally with high mortality and morbidity. Interest has been increasing in the use of inhaled sedatives because of a more rapid awakening and fewer adverse effects compared with intravenous propofol. The primary aim of this systematic review protocol is to investigate the length of critical care stay between ARDS patients who have been mechanically ventilated with inhaled anaesthetic sedatives (ie, sevoflurane and isoflurane) compared with those patients who are prescribed conventional sedatives (ie, propofol). METHODS AND ANALYSIS: Cochrane Central Register of Controlled Trials, Ovid (Embase, MEDLINE), PubMed, EBSCO (CINAHL Plus), Google Scholar will be searched and stratified by the reviewers. The literature search will be limited to English articles. Published full text peer-reviewed articles will be included.The International Prospective Register of Systematic Reviews (PROSPERO) Registration number is: CRD42023390988. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. The results will be presented at local/regional meetings and dissemination will occur through peer-reviewed publication.

Antifungal prophylaxis against invasive Candida and Aspergillus infection in adult heart transplant recipients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Invasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on how effective antifungal prophylaxis is against Candida spp infections and limited guidance on the prevention of Aspergillus spp infections. This systematic review and meta-analysis will assess the literature to see if antifungal prophylaxis reduces the incidence of IFI after heart transplant in adults. METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic reviews and Meta Analysis guidelines. A systematic search of the Cochrane Library, Web of Science, Scopus, Embase, MEDLINE, and Proquest databases will be undertaken. Reference lists of retrieved publications and conference abstracts will also be searched. Title, abstract and full-text screening will be undertaken by two reviewers. Discrepancies will be resolved by a third reviewer. Studies with paediatric patients, multi-organ transplants, or patients with a second heart transplant will be excluded, along with those who do not have clear definitions and diagnostic criteria for IFI. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool and the Risk of Bias in Non-randomised Studies of Interventions tool. A meta-analysis will be carried out, but if studies are not deemed to be sufficiently similar, only a narrative synthesis will be undertaken. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as primary data will not be collected. The results of the review will be disseminated through publication in an academic journal and scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42024516588.

Systematic review of room temperature stability of key beta-lactam antibiotics for extended infusions in inpatient settings.

BACKGROUND: Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world. METHODS: Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022. RESULTS: We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.

Widening the net: a literature review of antimicrobial agents with potential suitability for outpatient parenteral antimicrobial therapy services-the importance of storage and stability.

OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) services using continuous infusions (CIs) of antimicrobial agents in elastomeric devices require evidence of acceptable stability of the agent over the infusion period. A period of refrigerated storage of filled devices, followed by the CI period, is useful for OPAT services but can present a significant challenge to the stability of drugs. The aims of this study were to review fresh-filled stability data on antimicrobials which would be useful for OPAT services and to identify suitable candidates for further assessment. METHODS: Searches identified papers relating to stability assessments of antimicrobials for immediate use tested above 31°C using a stability-indicating method. RESULTS: We identified 18 stability studies published in 12 papers between 2015 and 2020, assessing the stability of 10 agents. Aminopenicillins like ampicillin and amoxicillin appear too unstable for CI, while benzylpenicillin may benefit from buffering to improve its stability. Cephalosporins vary in their stability and CI periods of 24 hours may not be achievable. Of the carbapenems, there are insufficient data for doripenem but meropenem has been extensively studied and is unsuitable for CI longer than 6 hours. Voriconazole may be suitable for CI but needs further investigation. CONCLUSIONS: Some drugs identified in our review are unlikely to be suitable for continuous infusion in OPAT services due to instability. Using a 'fresh-fill' approach, without refrigerated storage, may make some drugs useful while other agents should be considered for further assessment to Yellow Cover Document standards. The impact of buffering for penicillins should be assessed further.

Systematic review of high-dose amikacin regimens for the treatment of Gram-negative infections based on EUCAST dosing recommendations.

BACKGROUND: Updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) amikacin breakpoints for Enterobacterales and Pseudomonas aeruginosa included revised dosing recommendations of 25-30 mg/kg to achieve key pharmacokinetic/pharmacodynamic parameters, higher than recommended in the British National Formulary. The objectives of this review were to identify clinical evidence for high-dose amikacin regimens and to determine drug exposures that are related to adverse events and toxicity. METHODS: The literature search was conducted in October 2021 and updated in May 2022 using electronic databases for any study reporting adult participants treated with amikacin at doses ≥20 mg/kg/day. Reference lists of included papers were also screened for potential papers. Data were extracted for pharmacokinetic parameters and clinical outcomes, presented in a summary table and consolidated narratively. Meta-analysis was not possible. Each study was assessed for bias before, during and after the intervention using the ROBINS-I tool. RESULTS: Nine studies (total 501 participants in 10 reports) were identified and included, eight of which were observational studies. Assessment of bias showed substantial flaws. Dosing regimens ranged from 25 to 30 mg/kg/day. Six studies adjusted the dose in obesity when participants had a body mass index of ≥30 kg/m2. Target peak serum concentrations ranged from 60 mg/L to 80 mg/L and 59.6-81.8% of patients achieved these targets, but there was no information on clinical outcomes. Two studies reported the impact of high-dose amikacin on renal function. No studies reporting auditory or vestibular toxicity were identified. CONCLUSION: All included papers were limited by a significant risk of bias, while methodological and reporting heterogeneity made drawing conclusions challenging. Lack of information on the impact on renal function or ototoxicity means high-dose regimens should be used cautiously in older people. There is a need for a consensus guideline for high-dose amikacin to be written. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42021250022).

The journey of 'Living with Pain': A feasibility study of the development and running of a collective narrative group.

INTRODUCTION: Chronic Pain is increasingly affecting young people, their quality of life and wellbeing including education, social life and mental health. Current Western approaches to psychological support for Chronic Pain often focus on 'pain management' and learning skills and strategies from professionals, making use of Cognitive Behavioural Therapy (CBT), Acceptance and Commitment Therapy (ACT) and psychoeducation approaches in individual and group interventions. As a Paediatric Psychology service, we have trialled groups running over multiple weeks informed by these approaches and experienced low attendance rates. METHOD: This paper describes a feasibility study of an alternative group intervention; the 'Living with Pain group', which combines the 'Journey of Life' (Denborough, 2014) with collective narrative and liberation psychology approaches. RESULTS: Thirty three young people and eight parents / carers attended the intervention. Attendance rates, quantitative and qualitative feedback from one face-to-face group for young people and parents and two online groups for young people showed increased access and acceptability of the group. CONCLUSION: The findings from this study have shown that a 1-day collective narrative group intervention is feasible, suitable and acceptable and has increased access to our group intervention. Future directions include co-creation with young people and families, community engagement to increase accessibility of our groups and developing partnerships to respond to young people's hopes to raise awareness.

Systematic review of the stability of antimicrobial agents in elastomeric devices for outpatient parenteral antimicrobial therapy services based on NHS Yellow Cover Document standards.

BACKGROUND: In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial agents to assign a product shelf-life. In the UK, the relevant standards for stability testing and shelf-life assignment are published in 'A Standard Protocol for Deriving and Assessment of Stability-Part 1 (Aseptic Preparations-Small Molecules), commonly called the Yellow Covered Document (YCD). A previous systematic review published in 2017 failed to identify data on the stability of antimicrobials in elastomeric devices for OPAT services that met YCD requirements in force at the time. The aim of this review was to update that search, following a subsequent change to YCD requirements in 2017 and 2019 and expand that dataset to identify progress made in providing assurance about the stability of antimicrobial agents for OPAT services. METHODS: Searches were undertaken for papers relating to extended stability of antimicrobials. Citations were included when antimicrobial shelf-life was assessed using a stability-indicating method and considered a period of storage, either refrigerated or at room temperature, followed by in-use testing at a temperature at or above 32°C. RESULTS: Of 267 initial citations, six met the inclusion criteria and underwent full text review for data extraction. Included antimicrobials were cefazolin, ceftazidime, piperacillin/tazobactam, flucloxacillin and ceftolozane/tazobactam. Of these, only flucloxacillin and piperacillin demonstrated YCD compliant stability over the 24-hour infusion period while cefazolin, ceftazidime and ceftolozane/tazobactam could be infused over 12-hour period. CONCLUSIONS: Contrary to the position found in 2017 review, high-quality data are now available to support the use of a number of antimicrobial agents in extended infusion in elastomeric devices for OPAT services. There is a need to expand the dataset, as well as developing international consensus on the ideal parameters for stability assessment of such infusions in elastomeric devices.

Treatment of methicillin-resistant Staphylococcus aureus (MRSA): updated guidelines from the UK.

These evidence-based guidelines are an updated version of those issued in 2008. They have been produced following a review of the published literature (2007-18) pertaining to the treatment of infections caused by MRSA. The guidelines update, where appropriate, previous recommendations, taking into account changes in the UK epidemiology of MRSA, ongoing national surveillance data and the efficacy of novel anti-staphylococcal agents licensed for use in the UK. Emerging therapies that have not been licensed for use in the UK at the time of the review have also been assessed.

The State of Education and Training for Antimicrobial Stewardship Programs in Indian Hospitals-A Qualitative and Quantitative Assessment.

Background: To understand the role of infrastructure, manpower, and education and training (E&T) in relation to Antimicrobial Stewardship (AMS) in Indian healthcare organizations. Methods: Mixed method approach using quantitative survey and qualitative interviews was applied. Through key informants, healthcare professionals from 69 hospitals (public & private) were invited to participate in online survey and follow up qualitative interviews. Thematic analysis was applied to identify the key emerging themes from the interviews. The survey data were analyzed using descriptive statistics. Results: 60 healthcare professionals from 51 hospitals responded to the survey. Eight doctors participated in semi-structured telephone interviews. 69% (27/39) of the respondents received E&T on AMS during undergraduate or postgraduate training. 88% (15/17) had not received any E&T at induction or during employment. In the qualitative interviews three key areas of concern were identified: (1) need for government level endorsement of AMS activities; (2) lack of AMS programs in hospitals; and, (3) lack of postgraduate E&T in AMS for staff. Conclusion: No structured provision of E&T for AMS currently exists in India. Stakeholder engagement is essential to the sustainable design and implementation of bespoke E&T for hospital AMS in India.

A case of phenytoin toxicity in a patient with advanced lung cancer.

Phenytoin is an anti-convulsant drug commonly used to prevent seizures in patients with cerebral metastases. Phenytoin has complicated non-linear kinetics, is highly protein bound and has a small window between its therapeutic and toxic dose. This combination of factors means that small increases in dosage can all too quickly result in high plasma levels and toxic symptoms. Symptoms of phenytoin toxicity include: confusion, nystagmus, agitation, abnormal gait and hallucinations. This case report describes phenytoin toxicity in a patient receiving phenytoin 300 mg three times a day for a number of weeks. The patient was admitted to the unit for terminal care, where his phenytoin levels were found to be very high. Phenytoin was withheld until levels returned to within the normal range. During this time the patient became orientated and many of his symptoms resolved.