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The coronavirus 19 disease (COVID-19) pandemic has led to a renewed focus on end-of-life care. The majority of COVID-19 deaths occur in hospital, with patients cared for by generalists and hospital specialist palliative care teams (HSPCTs). This project aims at exploring the potential influences of HSPCTs on end-of-life care in COVID-19.A retrospective observational study was carried out by exploring four end-of-life care themes in a Scottish hospital population who died from COVID-19. Comparison was made between cohorts seen by HSPCTs versus generalist clinicians.Analysis of 119 patients across NHS Greater Glasgow and Clyde (NHSGGC) health board demonstrated that COVID-19 patients seen by HSPCTs were more likely to be younger (median 77 vs. 81 years;Consistencies in end-of-life care observed across NHSGGC cohorts draw attention to the potential wider impact of HSPCT roles, including education, guideline development, and mentoring. Understanding such diverse effects is important to support funding and development of HSPCTs. Further research is required to better quantify the impact and heterogenous influences of HSPCTs in general.

Background Dental practitioners are the largest prescribers of metronidazole. Antibiotics should only be prescribed when systemic involvement is clear and should be limited to monotherapy with β-lactams in the first instance. Objectives To determine whether metronidazole used as monotherapy or in addition to a β-lactam antibiotic offers any additional benefit over β-lactam monotherapy in non-periodontal dental infections. Methods Searches of Ovid Medline, Ovid Embase, Cochrane library and trials registries, forward and backward citations, for studies published between database inception and 2 August 2021. All randomized clinical trials (RCTs) and non-randomized trials comparing either systemic metronidazole monotherapy or metronidazole combined with a β-lactam with β-lactam monotherapy for the treatment of non-periodontal dental infections in adults or children in outpatient settings were included. Results Four publications reporting three RCTs comparing metronidazole with a β-lactam antibiotic were recovered. Studies were conducted in the 1970s–80s and aimed to demonstrate metronidazole was as effective as penicillin for the treatment of acute pericoronitis or acute apical infections with systemic involvement. Meta-analysis of results was not possible due to differences in measurement of infection signs. All studies concluded that metronidazole and penicillin are equally effective for the treatment of non-periodontal dental infections with systemic involvement. Conclusions Metronidazole does not provide superior clinical outcomes (alone or in combination with a β-lactam) when compared with a β-lactam antibiotic alone for the treatment of non-periodontal dental infections in general dental practice. Guidelines should reinforce the importance of surgical interventions and if appropriate the use of a single agent narrow-spectrum β-lactam.

Objectives To investigate the effect of pH control through the use of a citrate-buffered saline diluent pH 7 on the degradation rate of piperacillin/tazobactam solutions for infusion and to determine if an extended shelf-life of up to 13 days fridge 2°C–8°C plus 24 hours ‘in-use’ at 32°C in two elastomeric devices: FOLFusor LV10 (Baxter Healthcare, Thetford, UK) and Easypump II (B. Braun Medical Ltd, Sheffield, UK) can be achieved. Methods Testing was as per the latest National Health Service (NHS) Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of the solutions of piperacillin/tazobactam at a combined concentration of 25 mg/mL and 90 mg/mL respectively. Solutions were tested in two batches in replicate (n=3) at five time points according to the requirements of the YCD. Results Piperacillin/tazobactam stability was significantly improved when 0.3% w/v citrate-buffered saline pH 7 was used as the diluent, compared with using 0.9% w/v saline as diluent. Greater than 95% of the zero-time concentration of both actives remained following storage at 2°C–8°C for up to 13 days plus 24 hours at 32°C in both devices. The data support extended storage of up to 13 days 2°C–8°C plus 24 hours at 32°C ‘in-use’ when using FOLFusor LV10 (Baxter) or Easypump II (B. Braun) pump devices. Conclusions The enhanced stability complies with UK national standards as stated in the YCD for stability testing of aseptically produced small molecules and supports the storage of piperacillin/tazobactam for up to 13 days 2°C–8°C plus 24 hours at 32°C ‘in-use’ within two elastomeric pump devices. The extended shelf-life provides a significant advantage over the stability of piperacillin/tazobactam solutions for infusion when reconstituted and diluted in 0.9% w/v saline as diluent. The data open up the possibility of a continuous infusion of piperacillin/tazobactam delivered by elastomeric pump devices over 24 hours in an outpatient parenteral antimicrobial therapy setting.

Objectives To evaluate the effect of general practice-level prescribing feedback on antibiotic prescribing in a real-world pragmatic cluster randomized controlled trial Methods Three hundred and forty general practices in four territorial Health Boards in NHS Scotland were randomized in Quarter 1, 2016 to receive four quarterly antibiotic-prescribing feedback reports or not, from Quarter 2, 2016 to Quarter 1, 2017. Reports included different clinical topics, benchmarking against national and health board rates, and behavioural messaging with improvement actions. The primary outcome was total antibiotic prescribing rate. There were 16 secondary prescribing outcomes and 5 hospital admission outcomes (potential adverse effects of reduced prescribing). The main evaluation timepoint was 1 year after the final report (Quarter 1, 2018), with an additional evaluation in the quarter after the final report (Quarter 2, 2017). Routine administrative NHS data were used to generate the feedback reports and analyse the effects. Results Total antibiotic prescribing rates were lower at the main evaluation timepoint in both intervention (1.83 versus baseline 1.93 prescriptions/1000 patients/day) and control (1.90 versus baseline 1.98) practices, with no evidence of intervention effect [adjusted rate ratio (ARR) 0.98 (95% CI 0.94–1.02; P = 0.35)]. At the additional timepoint, adjusted total antibiotic prescribing rates were 1.67 and 1.73 prescriptions/1000 patients/day, with evidence of a small intervention effect, ARR 0.99 (0.98–1.00; P = 0.03). Conclusions This well-designed, practice-level antibiotic-prescribing feedback had limited evidence of additional effects in the context of decreasing antibiotic prescribing and an established national stewardship programme.

Background To assess the feasibility of its use in OPAT via continuous infusion, the stability of temocillin solutions at clinically relevant concentrations in two elastomeric infusion devices (B. Braun Medical Ltd Easypump® II LT 270-27- S and Spirit Ltd Medical Dosi-Fuser® L25915-250D1) was evaluated during 14 days of (2°C–8°C) fridge storage followed by 24 h exposure in-use temperature at 32°C, when reconstituted with 0.3% citrate buffer at pH 7. Methods Stability testing was conducted in accordance with the standard protocols for deriving and assessment of stability of small molecule aseptic preparation as per the latest UK National Health Service Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A stability indicating assay method was developed with an ultra-HPLC (UHPLC) system using photodiode array detector. Temocillin concentrations corresponding to low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) dose in triplicate devices were tested with duplicate samples at 11 timepoints during 14 days of fridge storage followed by 24 h in-use temperature exposure at 32°C. Results A total of 396 samples were collected and assayed. The percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During in-use temperature, 95% stability limit was achieved for 12 h for all doses and devices tested except for the high concentration in the Dosi-Fuser® device, which met this criterion for only 10 h of in-use temperature exposure. Conclusions Temocillin reconstituted with 0.3% citrate buffer at pH 7 in elastomeric infusion devices can be stored in a fridge (2°C–8°C) for 2 weeks, meeting the YCD acceptance criteria of

Background Reporting of outpatient parenteral antimicrobial therapy (OPAT) outcomes with national benchmarking is key to informing service development and supporting quality improvement. Objectives To analyse and report on data collected by the BSAC OPAT National Outcomes Registry from 2015 to 2019. Methods Quarterly data to 2020 was extracted from the BSAC National Outcomes Registry and analysed. Results 57 organizations submitted data on 27 841 patient episodes and 442 280 OPAT treatment days. A diverse range of infections and antimicrobials were reported with a mean OPAT treatment duration of 16.7 days (adults) and 7.7 days (paediatrics). In adults, the top five conditions treated were skin and soft tissue (27.6%), bronchiectasis (11.4%), urinary tract infections (7.6%), and diabetic foot infections (5.5%). Ceftriaxone followed by teicoplanin, ertapenem and piperacillin/tazobactam were the most-used antimicrobials. A median of 1.4 vascular-device-related complications were observed per 1000 OPAT treatment days (range 0.11 to 10.4) with device infections in 0.3 per 1000 OPAT days (range 0.1 to 1.7). Other adverse events (rash, blood dyscrasias, antibiotic-associated diarrhoea) were observed in a median of 1.9 per 1000 OPAT days. OPAT infection outcome (cured/improved) was 92.4% and OPAT outcome (success/partial success) was 90.7%. Conclusions This report demonstrates the safety, breadth, and complexity of modern UK OPAT practice. Future analyses of OPAT data should focus on infection- and service-specific quality indicators. OPAT registries remain central to planning and assessing safe, effective, and efficient delivery of patient-centred care and should be an important focus for UK and global OPAT practice.

Objectives To investigate the stability of ceftolozane/tazobactam 5 mg/mL and 20 mg/mL solutions for infusion in two elastomeric devices: FOLFusor LV10 (Baxter Healthcare) and Easypump® II (B. Braun Medical Ltd) and determine if an extended shelf life of up to 8 days storage at 2–8°C plus 24 h ‘in use’ at 32°C was achievable. Methods Testing was as per the latest NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A stability-indicating LC method was used for assessing the stability of solutions of ceftolozane/tazobactam at 5 mg/mL and 20 mg/mL (combined concentration of both actives) respectively, tested in two batches in triplicate (n = 3) at five timepoints according to the requirements of the YCD. Results Ceftolozane/tazobactam, diluted in 0.9% w/v sodium chloride at 5 mg/mL and 20 mg/mL, degraded during in-use storage at 32°C with Conclusions Solutions of ceftolozane/tazobactam can be administered in outpatient parenteral antimicrobial therapy (OPAT) services following refrigerated storage for up to 8 days, when limited to a 12 h infusion at in-use temperature of 32°C. For UK OPAT services where twice daily dosing is feasible, our data provides another treatment option for challenging infections. In countries where a 10% loss of ceftolozane/tazobactam is acceptable, a 24 h infusion is supported by the data.

Background: Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19. Methods: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded. Findings: We analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli and S aureus. Among patients with available data, 13 390 (37·0%) of 36 145 had received antimicrobials in the community for this illness episode before hospital admission and 39 258 (85·2%) of 46 061 patients with inpatient antimicrobial data received one or more antimicrobials at some point during their admission (highest for patients in critical care). We identified frequent use of broad-spectrum agents and use of carbapenems rather than carbapenem-sparing alternatives. Interpretation: In patients admitted to hospital with COVID-19, microbiologically confirmed bacterial infections are rare, and more likely to be secondary infections. Gram-negative organisms and S aureus are the predominant pathogens. The frequency and nature of antimicrobial use are concerning, but tractable targets for stewardship interventions exist. Funding: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, UK Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, and NIHR HPRU in Respiratory Infections at Imperial College London.

Introduction Guidelines on the length of treatment of dental infections with systemic antibiotics vary across different countries. We aimed to determine if short-duration (3-5 days) courses of systemic antibiotics were as effective as longer-duration courses (≥7 days) for the treatment of dental infections in adults in outpatient settings.Methods We searched Ovid Medline, Ovid Embase, Cochrane, trials registries, Google Scholar and forward and backward citations for studies published between database inception and 30 March 2021. All randomised clinical trials (RCT) and non-randomised trials which compared length of treatment with systemic antibiotics for dental infections in adults in outpatient settings published in English were included.Results One small RCT met our defined inclusion criteria. The trial compared three-day versus seven-day courses of amoxicillin in adults with odontogenic infection requiring tooth extraction. There was no significant difference between groups in terms of participant-reported pain or clinical assessment of wound healing.Discussion While a number of observational studies were supportive of shorter-course therapy, only one small RCT concluded that a three-day course of amoxicillin was clinically non-inferior versus seven days for the treatment of odontogenic infection requiring tooth extraction. Limited conclusions on shorter-course therapy can be drawn from this study as all participants commenced amoxicillin two days before tooth extraction which is not common clinical practice. The variability in guidelines for use of antimicrobials in dental infections suggests that guidelines are based on local or national historical practice and indicates the need for further research to determine the optimum length of treatment. RCTs are required to investigate if short-duration courses of antibiotics are effective and to provide evidence to support consistent guidance for dental professionals.

Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.

Background Bacterial co-infection is infrequently observed with SARS-CoV-2/COVID-19 infection outside of critical care, however, antibiotics are commonly prescribed. Objectives To examine factors associated with antibiotic prescribing for suspected respiratory tract infection (RTI) and evaluate the nature and dynamics of prescribing in hospitalized patients with suspected and proven COVID-19 infection. Methods An antibiotic point prevalence survey in hospitalized adult patients was conducted in designated COVID-19 clinical areas (including critical care) in 15 Scottish hospitals. Antibiotics prescribed for RTI and factors associated with prescribing were investigated. Results Of 820 surveyed patients, 272 (prevalence 33.3%) received antibiotics for suspected RTI on the survey day and 58.8% were SARS-CoV-2 positive. Antibiotics were empirical in 91.9% and amoxicillin (24.6%), doxycycline (20.5%) and co-amoxiclav (15%) were most frequently prescribed. Oral antibiotics were prescribed in 54.5% and duration was recorded in 76.7% on wards for a median of 5 days. IV to oral switch occurred after a median of 2 days. Prescribing for RTI was independently and positively associated with COPD/chronic lung disease, purulent/bloody sputum, abnormal chest X-ray, and CRP ≥ 100 mg/L. Probable and definite hospital-acquired COVID-19 and diabetes were associated with a lower odds of receiving an antibiotic for RTI. Conclusions Antibiotic prescribing for suspected RTI was commonly observed and predominantly empirical in suspected or proven COVID-19. Initiatives to reinforce stewardship principles including clinical review, effective use of microbiological diagnostics and better understanding of the role of biomarkers are central to further limit unnecessary antibiotic therapy in COVID-19.

Item does not contain fulltext Delivery of parenteral antimicrobials in non-inpatient settings (DPANS) may be through a dedicated outpatient parenteral antimicrobial therapy (OPAT) service, co-ordinated by hospital- or community-based specialised teams, or via an infusion service involving community-based health professionals (nurses, general practitioners) without centralised hospital oversight, or through ad hoc arrangements. DPANS varies among countries. Our objective was to describe how DPANS is organised at a national level in European countries. A survey (65-item self-administered questionnaire) was conducted from February-June 2019 among infection specialists in 34 European countries on behalf of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) and the British Society for Antimicrobial Chemotherapy (BSAC) OPAT initiative. Most countries (28/34; 82.4%) participated in the survey. DPANS was available in almost all (27/28; 96.4%) responding countries. DPANS was predominantly provided either via specialised OPAT services (17/28; 60.7%) or via infusion services (16/28; 57.1%), with 11 countries (39.3%) providing both services. A formal OPAT team structure with specifically trained staff was reported in only six countries (6/17; 35.3%). Some countries (4/28; 14.3%) had no structured services but practiced DPANS via ad hoc arrangements. The costs of all stages of the process were covered for patients managed by specialised OPAT/infusion services, either completely, partially or for specific patient groups in the majority (20/28; 71.4%) of countries. The main barriers to implement OPAT/infusion services were lack of organisational structure or guidelines. In conclusion, DPANS with respect to availability and organisation is highly heterogeneous in Europe. National/European guidelines may help improve and standardise DPANS.

Background A 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. Methods A 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. Results Comparison 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. Conclusions The 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.

Background Approximately 10% of people have an unverified penicillin allergy, with multiple personal and public health consequences. Objectives To assess the efficacy and safety of direct oral challenge, without prior skin testing, in this population. Methods MEDLINE, 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. Results Thirteen 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. Conclusions Direct 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.

Background Scottish Antimicrobial Prescribing Group (SAPG) recommendations to reduce broad-spectrum antimicrobial use led to an increase in gentamicin and vancomycin prescribing. In 2009, SAPG introduced national guidance to standardize dosage regimens, reduce calculation errors and improve the monitoring of these antibiotics. Studies conducted in 2010 and 2011 identified limitations in guideline implementation. Objectives To develop, implement and assess the long-term impact of quality improvement (QI) resources to support gentamicin and vancomycin prescribing, administration and monitoring. Methods New resources, comprising revised guidelines, online and mobile app dose calculators, educational material and specialized prescribing and monitoring charts were developed in collaboration with antimicrobial specialists and implemented throughout Scotland during 2013–16. An online survey in 2017 evaluated the use of these resources and a before (2011) and after (2018) point prevalence study assessed their impact. Results All 12 boards who responded to the survey (80%) were using the guidance, electronic calculators and gentamicin prescription chart; 8 used a vancomycin chart. The percentage of patients who received the recommended gentamicin dose increased from 44% to 89% (OR 10.99, 95% CI = 6.37–18.95) between 2011 and 2018. For vancomycin, the correct loading dose increased from 50% to 85% (OR = 5.69, CI = 2.76–11.71) and the correct maintenance dose from 55% to 90% (OR = 7.17, CI = 3.01–17.07). Conclusions This study demonstrated improvements in the national prescribing of gentamicin and vancomycin through the development and coordinated implementation of a range of QI resources and engagement with local and national multidisciplinary teams.

ObjectiveTo examine antibiotic use in patients approaching end of life, in terms of frequency of prescription, aim of treatment, beneficial and adverse effects and contribution to the development of antimicrobial resistance.DesignScoping reviewData sourcesAn information scientist searched Ovid MEDLINE, Ovid EMBASE, The Cochrane library, PubMed Clinical Queries, NHS Evidence, Epistemonikos, SIGN, NICE, Google Scholar from inception to February 2019 for any study design including, but not limited to, randomised clinical trials, prospective interventional or observational studies, retrospective studies and qualitative studies. The search of Ovid MEDLINE was updated on the 10 June 2020.Study selectionStudies reporting antibiotic use in patients approaching end of life in any setting and clinicians’ attitudes and behaviour in relation to antibiotic prescribing in this populationData extractionTwo reviewers screened studies for eligibility; two reviewers extracted data from included studies. Data were analysed to describe antibiotic prescribing patterns across different patient populations, the benefits and adverse effects (for individual patients and wider society), the rationale for decision making and clinicians behaviours and attitudes to treatment with antibiotics in this patient group.ResultsEighty-eight studies were included. Definition of the end of life is highly variable as is use of antibiotics in patients approaching end of life. Prescribing decisions are influenced by patient age, primary diagnosis, care setting and therapy goals, although patients’ preferences are not always documented or adhered to. Urinary and lower respiratory tract infections are the most commonly reported indications with outcomes in terms of symptom control and survival variably reported. Small numbers of studies reported on adverse events and antimicrobial resistance. Clinicians sometimes feel uncomfortable discussing antibiotic treatment at end of life and would benefit from guidelines to direct care.ConclusionsUse of antibiotics in patients approaching the end of life is common although there is significant variation in practice. There are a myriad of intertwined biological, ethical, social, medicolegal and clinical issues associated with the topic.

BackgroundThe Scottish Antimicrobial Prescribing Group is supporting two hospitals in Ghana to develop antimicrobial stewardship. Early intelligence gathering suggested that surgical prophylaxis was suboptimal. We reviewed the evidence for use of surgical prophylaxis to prevent surgical site infections (SSIs) in low- and middle-income countries (LMICs) to inform this work.MethodsMEDLINE, Embase, Cochrane, CINAHL and Google Scholar were searched from inception to 17 February 2020 for trials, audits, guidelines and systematic reviews in English. Grey literature, websites and reference lists of included studies were searched. Randomized clinical trials reporting incidence of SSI following Caesarean section were included in two meta-analyses. Narrative analysis of studies that explored behaviours and attitudes was conducted.ResultsThis review included 51 studies related to SSI and timing of antibiotic prophylaxis in LMICs. Incidence of SSI is higher in LMICs, infection surveillance data are poor and there is a lack of local guidelines for antibiotic prophylaxis. Education to improve appropriate antibiotic prophylaxis is associated with reduction of SSI in LMICs. The random-effects pooled mean risk ratio of SSI in Caesarean section was 0.77 (95% CI: 0.51–1.17) for pre-incision versus post-incision prophylaxis and 0.89 (95% CI: 0.55–1.14) for short versus long duration. Reduction in cost and nurse time was reported in shorter-duration surgical antibiotic prophylaxis.ConclusionsThere is scope for improvement, but interventions must include local context and address strongly held beliefs. Establishment of local multidisciplinary teams will promote ownership and sustainability of change.

Background Improved knowledge regarding antimicrobial use in Ghana is needed to reduce antimicrobial resistance (AMR). This includes point prevalence studies (PPSs) in hospitals. Objectives were to: (i) provide baseline data in two hospitals [Keta Municipal Hospital (KMH) and Ghana Police Hospital (GPH)] and identify priorities for improvement; (ii) assess the feasibility of conducting PPSs; and (iii) compare results with other studies. Methods Standard PPS design using the Global PPS paper forms, subsequently transferred to their template. Training undertaken by the Scottish team. Quality indicators included: rationale for use; stop/review dates; and guideline compliance. Results Prevalence of antibiotic use was 65.0% in GPH and 82.0% in KMH. Penicillins and other β-lactam antibiotics were the most frequently prescribed in both hospitals, with third-generation cephalosporins mainly used in GPH. Antibiotic treatment was mainly empirical and commonly administered intravenously, duration was generally short with timely oral switching and infections were mainly community acquired. Encouragingly, there was good documentation of the indications for antibiotic use in both hospitals and 50.0%–66.7% guideline compliance (although for many indications no guideline existed). In addition, almost all prescribed antibiotics had stop dates and there were no missed doses. The duration of use for surgical prophylaxis was generally more than 1 day (69.0% in GPH and 77.0% in KMH). Conclusions These two hospitals were the first in Ghana to use the Global PPS system. We found the PPS was feasible, relatively rapid and achieved with limited training. Targets for improvement identified included reduction of broad-spectrum antibiotics and duration of treatment.

Background The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. Objective Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. Our approach Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. Ongoing activities Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. Conclusion There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

Background: Antimicrobial resistance (AMR) is a serious global public health threat and rationale antimicrobial use through surveillance and monitoring is crucial to address AMR. To date, no study has been undertaken in Iraq using validated methodologies to document current antimicrobial use and areas for improvement given high AMR rates. Methods: Point prevalence survey (PPS), using the Global PPS methodology, conducted among the three major public hospitals in the largest city in Kurdistan Regional Government (KRG) in northern Iraq from September and December 2019. Adult inpatients receiving antibiotics on the day of the survey were included. Antibiotic prescribing quality was evaluated using agreed indicators. Findings: Prevalence of antibiotic use was high (93.7%; n=192/205) and prescribed, third generation cephalosporins were most commonly prescribed (52.6%; n=140/266). Of the 166 prescriptions with diagnosis recorded, respiratory tract infections (RTI) accounted for the majority (44%, n=73/166). Reasons for treatment was recorded for only 61.7% (n=164/266) of antibiotics and high use (89.9%) of parenteral therapy was observed. All therapy was empirical, no stop/review dates were recorded and no treatment guidelines were available. Majority of the prescribed antibiotics (62%; n=165/266) were from the WHO Watch list. Interpretation: Prevalence of antibiotic use was the highest not only in the region but globally including Africa and there was significant evidence of sub-optimal prescribing practice. Swift, action is needed to develop ASPs to improve future prescribing and reduce AMR. One-two areas should initially be targeted for quality improvement including development of local clinical guidelines, documentation of antibiotic indication and stop/review dates. Funding Statement: This study was self-funded. Declaration of Interests: Nothing to declare. Ethics Approval Statement: No unique patient identifiers were recorded and all study data were anonymised completely. The study did not involve any direct contact with patients; consequently, patient consent was not required. The study protocol was approved by the Research and Ethic Committee of Sulaymaniyah General Health Directorate.

Outpatient parenteral antimicrobial therapy (OPAT) offers safe, effective and patient-centred care for adults and children. The OPAT UK good practice recommendations for adults and children have recently been updated through a process of literature review, expert consensus and extensive stakeholder consultation. Here we discuss the key changes in the updated recommendations in the context of recent developments, including novel antimicrobial agents and delivery devices, the place of oral antimicrobials as an alternative to intravenous therapy, new OPAT service models and the broader antimicrobial stewardship agenda.

UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) were published in 2012 and 2015 for adult and paediatric patients, respectively. Here we update the initial good practice recommendations in a combined document based on a further review of the OPAT literature and an extensive consultation process. As with the previous good practice recommendations, these updated recommendations are intended to provide pragmatic guidance for new and established OPAT services across a range of settings and to act as a set of quality indicators for service evaluation and quality improvement.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality and has resultant important economic and societal costs underscoring the need for accurate surveillance. In recent years, prevalence rates reported in East Africa have been inconsistent, sparking controversy and raising concern. Methods We described antimicrobial susceptibility patterns of Staphylococcus aureus isolates cultured from patients within the Internal Medicine department of the largest public healthcare facility in East and Central Africa- the Kenyatta National Hospital (KNH) in Nairobi, Kenya. Routine antimicrobial susceptibility data from non-duplicate Staphylococcus aureus isolates cultured between the years 2014–2016 from the medical wards in KNH were reviewed. Results Antimicrobial susceptibility data from a total of 187 Staphylococcus aureus isolates revealed an overall MRSA prevalence of 53.4%. Isolates remained highly susceptible to linezolid, tigecycline, teicoplanin and vancomycin. Conclusions The prevalence of MRSA was found to be much higher than that reported in private tertiary facilities in the same region. Careful interrogation of antimicrobial susceptibility results is important to uproot any red herrings and reserve genuine cause for alarm, as this has a critical bearing on health and economic outcomes for a population. Electronic supplementary material The online version of this article (10.1186/s12879-019-4245-3) contains supplementary material, which is available to authorized users.

The global public health threat of antibiotic-resistant infections as well as the lack of new treatments in clinical development is a critical issue. Reasons for this include diminished commercial incentives for pharmaceutical companies to develop new antibiotics, which part-reflects a shift in antibiotic marketing paradigm from broad deployment to targeted therapy in relatively small patient populations. Such changes are encouraged by antimicrobial stewardship (AMS). Other factors include a lack of recognition in the traditional assessment of new antibiotics by regulators, health technology assessors and payers of the broad range of benefits of new agents, particularly their value to health care, economies and society. Recognising the seriousness of the situation, there have been recent changes and proposals by regulators for modification of the assessment process to accommodate a broader range of acceptable data supporting new drug applications. There is also increasing recognition by some payers of the societal benefit of new antibiotics and the need for financial incentives for those developing high-priority antibiotics. However, progress is slow, with recent publications focusing on industry and strategic perspectives rather than clinical implications. In this opinion piece, we therefore focus on clinicians and the practical steps they can take to drive and contribute to increasing awareness and understanding of the value of antibiotics. This includes identifying and gathering appropriate alternative data sources, educating on AMS and prescribing habits, and contributing to international antibiotic susceptibility surveillance models.

ObjectivesDevelopment of evidence-based good practice recommendations for clinicians considering the use of antibiotics in patients towards the end of life.DesignA multiprofessional group of experts in end-of-life care and antimicrobial stewardship was convened. Findings from a scoping review of the literature and a consultation of clinicians were triangulated. Expert discussion was used to generate consensus on how to approach decision-making.SettingRepresentatives from hospital and a range of community health and care settings.ParticipantsMedical, pharmacy and nursing professionals.Main outcome measuresGood practice recommendations based on published evidence and the experience of prescribers in Scotland.ResultsThe findings of 88 uncontrolled, observational studies of variable quality were considered alongside a survey of over 200 prescribers. No national or international guidelines were identified. Antibiotic use towards the end of life was common but practice was highly variable. The potential harms associated with giving antibiotics tended to be less well considered than the potential benefits. Antibiotics often extended the length of time to death but this was sometimes at the cost of higher symptom burden. There was strong consensus around the importance of effective communication with patients and their families and making treatment decisions aligned to a patient’s goals and priorities.ConclusionsGood practice recommendations were agreed with focus on three areas: making shared decisions about future care; agreeing clear goals and limits of therapy; reviewing all antibiotic prescribing decisions regularly. These will be disseminated widely to support optimal care for patients towards the end of life. A patient version of the recommendations has also been produced to support implementation.

Introduction Daptomycin, a rapid concentration-dependent bactericidal antibiotic, is approved at a dose of 4 mg/kg/day for the treatment of complicated skin and soft tissue infections (cSSTI) and at a dose of 6 mg/kg/day for the treatment of Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE. Studies have reported the successful use of high-dose daptomycin (>6 mg/kg/day) in patients with difficult-to-treat infections. The present analysis evaluated the effectiveness and safety of high doses (>6 mg/kg/day) of daptomycin for the treatment of different Gram-positive infections. Methods European Cubicin® Outcomes Registry and Experience (EU-CORE) is a non-interventional, multicenter, retrospective, patient registry designed to collect real-world data from patients treated with daptomycin between 2006 and 2012. Clinical outcomes were assessed at the end of daptomycin treatment for three dose groups: ≤6, >6 to 6 mg/kg/day). The primary infections with the largest proportion of patients treated with a high dose (>6 mg/kg/day) were osteomyelitis (37.1%), foreign body/prosthetic infection (31.6%), and endocarditis (27.6%). S. aureus was identified in 42.9% of patients with positive cultures treated with either ≤6 or >6 mg/kg/day. The overall clinical success rate was 82.0% (899/1097) with high doses (>6 mg/kg/day) and 80.3% (3928/4890) with doses ≤6 mg/kg/day. Numerically higher clinical success rate was observed for endocarditis and foreign body/prosthetic infection, as well as for coagulase-negative staphylococcal and enterococcal infections, with high-dose daptomycin treatment. There were no new or unexpected safety findings at doses >6 mg/kg/day. Conclusion These results suggested that daptomycin at doses >6 mg/kg/day was effective and well tolerated. High-dose daptomycin is a potential therapeutic option in patients with difficult-to-treat Gram-positive infections. Funding This study was funded by Novartis Pharma AG. Electronic supplementary material The online version of this article (doi:10.1007/s12325-015-0267-4) contains supplementary material, which is available to authorized users.

BACKGROUND: Osteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated. CONCLUSIONS: This analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.

Background Pooled data from two large registries, Cubicin® Outcomes Registry and Experience (CORE; USA) and European Cubicin® Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions. Methods Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of ‘cured’ or ‘improved’. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment. Results In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1–103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively. Conclusions The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.

Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010.Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery.Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed.In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

In 2008, the Scottish Management of Antimicrobial Resistance Action Plan (ScotMARAP) was published by the Scottish Government. One of the key actions was initiation of the Scottish Antimicrobial Prescribing Group (SAPG), hosted within the Scottish Medicines Consortium, to take forward national implementation of the key recommendations of this action plan. The primary objective of SAPG is to co-ordinate and deliver a national framework or programme of work for antimicrobial stewardship. This programme, led by SAPG, is delivered by NHS National Services Scotland (Health Protection Scotland and Information Services Division), NHS Quality Improvement Scotland, and NHS National Education Scotland as well as NHS board Antimicrobial Management Teams. Between 2008 and 2010, SAPG has achieved a number of early successes, which are the subject of this review: (i) through measures to optimise prescribing in hospital and primary care, combined with infection prevention measures, SAPG has contributed significantly to reducing Clostridium difficile infection rates in Scotland; (ii) there has been engagement of all key stakeholders at local and national levels to ensure an integrated approach to antimicrobial stewardship within the wider healthcare-associated infection agenda; (iii) development and implementation of data management systems to support quality improvement; (iv) development of training materials on antimicrobial stewardship for healthcare professionals; and (v) improving clinical management of infections (e.g. community-acquired pneumonia) through quality improvement methodology. The early successes achieved by SAPG demonstrate that this delivery model is effective and provides the leadership and focus required to implement antimicrobial stewardship to improve antimicrobial prescribing and infection management across NHS Scotland.

Objectives: To describe the patient populations and infections being treated with daptomycin, as well as the efficacy and safety outcomes. Patients and methods: Data from the European Cubicin Outcomes Registry and Experience (EU-CORE ™ ), retrospectively collected at 118 institutions between January 2006 and August 2008, were analysed. Results: Daptomycin treatment was documented in 1127 patients with diverse infections, including complicated skin and soft tissue infections (33%), bacteraemia (22%), endocarditis (12%) and osteomyelitis (6%). It was used empirically, before microbiological results became available, in 53% of patients. Staphylococcus aureus was the most common pathogen (34%), with 52% of isolates resistant to methicillin; coagulase-negative staphylococci and enterococci were also frequent, with 22% of Enterococcus faecium isolates resistant to vancomycin. Daptomycin was used as first-line therapy in 302 (27%) patients. When used second line, the most common reasons for discontinuation of previous antibiotic were treatment failure and toxicity or intolerance. The use of concomitant antibiotics was reported in 65% of patients. Most frequent doses were 6 mg/kg (47%) and 4 mg/kg (32%). The median duration of daptomycin therapy was 10 days (range 1-246 days) in the inpatient setting and 13 days (range 2-189 days) in the outpatient setting. The overall clinical success rate was 79%, with a clinical failure rate of

The long elimination half-life of teicoplanin facilitates outpatient parenteral antibiotic therapy (OPAT) with thrice-weekly dosing. This study aimed to develop teicoplanin dosage guidelines for OPAT use from routine clinical data.Patients received 15-25 mg/kg/day for 3 days, then 15-25 mg/kg thrice weekly. Trough concentrations were measured weekly and doses adjusted to maintain 20-30 or 10-20 mg/L according to clinical condition. Concentration-time data were analysed using the pharmacokinetic package NONMEM and the final model was used to develop new dosage guidelines.Data from 94 and 36 patients were used for model development and validation, respectively. Patient ages ranged from 15 to 94 years, weights from 43 to 146 kg and estimated CL(CR) from 9 to 195 mL/min. Teicoplanin concentrations (n = 670) ranged from 6.7 to 66.9 mg/L and a one-compartment model adequately described the data. The typical estimate of CL was 0.542 L/h and changed by 10.6% for every 10 mL/min difference from a CL(CR) of 66 mL/min. V was 1.62 L/kg. Dosage guidelines based on body weight and CL(CR) can be expected to lead to a significant improvement in the proportion of concentrations in the range 20-30 mg/L. Alternative doses aimed at lower target concentrations have also been developed.New dosage guidelines have been developed to support thrice-weekly administration of teicoplanin in an OPAT setting.

Acute bacterial meningitis (ABM) is a potentially life-threatening neurological emergency. An agreed protocol for early, evidence-based and effective management of community-acquired ABM is essential for best possible outcome. A literature search of peer-reviewed articles on ABM was used to collect data on the management of ABM in older children and adults. Based on the strength of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community-acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast-track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after first contact of patient with health service. In every case, blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and whenever possible, the choice of antibiotics, and the duration of therapy, should be guided by the microbiological diagnosis. Parenteral therapy with a third-generation cephalosporin is the initial antibiotics of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis because of Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin-resistant pneumococcal meningitis. Dexamethasone should be administered both in adults and in children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. Influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of known history of penicillin allergy.

Objectives and methods: A management protocol for specialist nurses was developed for ambulatory management of uncomplicated cellulitis requiring initial intravenous (iv) antibiotic therapy. Patients were all managed through an outpatient parenteral antibiotic therapy (OPAT) service. Those with cellulitis were compared pre- and post-intervention. Results: One hundred and fourteen patients were compared with 230 retrospective controls all managed through the OPAT service. Protocol management was associated with reduced duration of outpatient iv therapy from 4 to 3 days, P 5 0.02, and reduced need for physician review (100% to 19%). Outcomes, complications and readmissions were similar. Conclusions: Specialist nurse-led management is safe and effective in the management of uncomplicated cellulitis in the context of an OPAT service and reduces the need for regular medical review without compromising clinical care.

Objectives To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.

Infections caused by Gram-positive pathogens remain a major public health burden and are associated with high morbidity and mortality. Increasing rates of infection with Gram-positive bacteria and the emergence of resistance to commonly used antibiotics have led to the need for novel antibiotics. Daptomycin, a cyclic lipopeptide with rapid bactericidal activity against a wide range of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, has been shown to be effective and has a good safety profile for the approved indications of complicated skin and soft tissue infections (4 mg/kg/day), right-sided infective endocarditis caused by S. aureus, and bacteremia associated with complicated skin and soft tissue infections or right-sided infective endocarditis (6 mg/kg/day). Based on its pharmacokinetic profile and concentration-dependent bactericidal activity, high-dose (>6 mg/kg/day) daptomycin is considered an important treatment option in the management of various difficult-to-treat Gram-positive infections. Although daptomycin resistance has been documented, it remains uncommon despite the increasing use of daptomycin. To enhance activity and to minimize resistance, daptomycin in combination with other antibiotics has also been explored and found to be beneficial in certain severe infections. The availability of daptomycin via a 2-minute intravenous bolus facilitates its outpatient administration, providing an opportunity to reduce risk of health care-associated infections, improve patient satisfaction, and minimize health care costs. Daptomycin, not currently approved for use in the pediatric population, has been shown to be widely used for treating Gram-positive infections in children.

A retrospective analysis of data from patients receiving daptomycin as outpatient parenteral antimicrobial therapy (OPAT) within the European Cubicin Outcomes Registry and Experience (EU-CORE(SM)) was performed. Of 4592 enrolled patients in 15 countries, 550 (12%) received daptomycin OPAT. Of these, 149 (27%) received daptomycin without hospital admission, 84% had significant underlying diseases and 44% were ≥65 years of age. Most frequently treated infections were complicated skin and soft-tissue infections (28%), osteomyelitis (17%), foreign body/prosthetic infections (15%) and endocarditis (14%). In patients with culture results available, Staphylococcus aureus and coagulase-negative staphylococci were the most commonly isolated primary pathogens [n = 218 (46%) and n = 102 (21%), respectively]. Daptomycin was typically used at doses of 6 mg/kg (n = 210; 38%) and 4 mg/kg (n = 160; 29%), with concomitant antibiotics used in 41%. The median treatment duration was 22 days (range 1-300 days), with a median of 13 OPAT days (range 1-290 days). Overall clinical success was observed in 89%, with high success rates across the wide range of infections, including those caused by meticillin-resistant and meticillin-susceptible S. aureus (88% and 90%, respectively). Daptomycin exhibited a favourable safety profile; 3.1% of patients discontinued treatment owing to an adverse event. These data demonstrate that daptomycin is effective and well tolerated in the treatment of a wide range of Gram-positive infections in the outpatient setting. Ease of administration of daptomycin, via a daily 2-min injection, and its efficacy and safety combine to make it an attractive treatment option for OPAT.

These good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) are an update to a previous consensus statement on OPAT in the UK published in 1998. They are based on previous national and international guidelines, but have been further developed through an extensive consultation process, and are underpinned by evidence from published literature on OPAT. They provide pragmatic guidance on the development and delivery of OPAT services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high-quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services.

Background More than 30 years since it was developed for clinical use, the third-generation cephalosporin ceftriaxone remains the most commonly used agent for outpatient parental antimicrobial therapy (OPAT). Recent antimicrobial stewardship programmes have tended to restrict ceftriaxone use in hospitals to control antibiotic resistance and outbreaks of Clostridium difficle infection (CDI). Considering the expansion of OPAT programmes both in the UK and worldwide, revisiting the role of ceftriaxone in OPAT in the context of changing antimicrobial prescribing practices is timely. Aim of the review To identify the evidence base for OPAT, review current and historical data on indications for, and safety of ceftriaxone within the OPAT setting, and to provide some perspectives on the future role of ceftriaxone. Method We searched PubMed and Scopus for articles published in English, and hand searched reference lists. We also conducted a complementary descriptive analysis of prospectively acquired data on the use of ceftriaxone in more than 1,300 OPAT episodes over a 10-year period in our UK centre. Results Ceftriaxone has an excellent safety profile in the OPAT setting, and its broad spectrum of activity makes it an established agent in a wide range of clinical infection syndromes, such as skin and soft-tissue infection, bone and joint infection, streptococcal endocarditis and several others. Intriguingly, in contrast to the inpatient setting, liberal use of ceftriaxone in OPAT has not been strongly linked to CDI, suggesting additional patient and environmental factors may be important in mediating CDI risk.

Acute bacterial meningitis (ABM) is a potentially life-threatening neurological emergency. An agreed protocol for early, evidence-based and effective management of community-acquired ABM is essential for best possible outcome. A literature search of peer-reviewed articles on ABM was employed to collect data on the management of ABM in older children and adults. Based on the robustness of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community-acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast-track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after the first contact of the patient with health services. In every case, a blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and, whenever possible, the choice of antibiotics and the duration of therapy should be guided by the microbiological diagnosis. Parenteral therapy with a third-generation cephalosporin is the initial antibiotic of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis due to Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin-resistant pneumococcal meningitis. Dexamethasone should be administered in both adults and children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of a known history of penicillin allergy.

Acute bacterial meningitis (ABM) is a potentially life-threatening neurological emergency. An agreed protocol for early, evidence-based and effective management of community-acquired ABM is essential for best possible outcome. A literature search of peer-reviewed articles on ABM was used to collect data on the management of ABM in older children and adults. Based on the strength of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community-acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast-track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after first contact of patient with health service. In every case, blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and whenever possible, the choice of antibiotics, and the duration of therapy, should be guided by the microbiological diagnosis. Parenteral therapy with a third-generation cephalosporin is the initial antibiotics of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis because of Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin-resistant pneumococcal meningitis. Dexamethasone should be administered both in adults and in children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. Influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of known history of penicillin allergy.