Gavin Barlow

Guidelines for the diagnosis, prevention and management of implantable cardiac electronic device infection. Report of a joint Working Party project on behalf of the British Society for Antimicrobial Chemotherapy (BSAC, host organization), British Heart Rhythm Society (BHRS), British Cardiovascular Society (BCS), British Heart Valve Society (BHVS) and British Society for Echocardiography (BSE)

Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.

The CURB65 pneumonia severity score outperforms generic sepsis and early warning scores in predicting mortality in community-acquired pneumonia

Background: The performance of CURB65 in predicting mortality in community-acquired pneumonia (CAP) has been tested in two large observational studies. However, it has not been tested against generic sepsis and early warning scores, which are increasingly being advocated for identification of high-risk patients in acute medical wards. Method: A retrospective analysis was performed of data prospectively collected for a CAP quality improvement study. The ability to stratify mortality and performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating curve) were calculated for stratifications of CURB65, CRB65, the systemic inflammatory response syndrome (SIRS) criteria and the standardised early warning score (SEWS). Results: 419 patients were included in the main analysis with a median age of 74 years (men = 47%). CURB65 and CRB65 stratified mortality in a more clinically useful way and had more favourable operating characteristics than SIRS or SEWS; for example, mortality in low-risk patients was 2% when defined by CURB65, but 9% when defined by SEWS and 11–17% when defined by variations of the SIRS criteria. The sensitivity, specificity, positive predictive value and negative predictive value of CURB65 was 71%, 69%, 35% and 91%, respectively, compared with 62%, 73%, 35% and 89% for the best performing version of SIRS and 52%, 67%, 27% and 86% for SEWS. CURB65 had the greatest area under the receiver operating curve (0.78 v 0.73 for CRB65, 0.68 for SIRS and 0.64 for SEWS). Conclusions: CURB65 should not be supplanted by SIRS or SEWS for initial prognostic assessment in CAP. Further research to identify better generic prognostic tools is required.

Evaluation of outcomes in community-acquired pneumonia: a guide for patients, physicians, and policy-makers

Community-acquired pneumonia (CAP) is a key target for research and quality improvement in acute medicine. However, many of the outcome measures used in prognostic and antibiotic studies are not validated and do not capture features of outcome that are important to patients. Substitutes for traditional outcome measures include a recently validated patient-based symptom questionnaire (the CAP-Sym) and process-of-care measures. The interpretation of outcomes also depends on the quality of the study design and methods used. This paper discusses the advantages and disadvantages of outcome, process-of-care, and economic measures in CAP and the interpretation of these measures in randomised and observational studies. A core set of measures for use in clinical CAP research and performance measurement is proposed.

Community-associated MRSA in the United Kingdom

Community-associated MRSA (CA-MRSA) strains have rapidly emerged worldwide as a cause of skin and soft tissue infections and occasionally severe disease. Although there have been relatively few reports from the UK, it is clear that the incidence of CA-MRSA infections is rising. Several distinct clonal CA-MRSA lineages have been identified causing infections in individuals both in the community and in UK hospitals. Their prevalence is likely to be considerably higher than reported. In this review article we clarify the terminology and definitions used for CA-MRSA, detail their emergence, and summarise the available information regarding their current epidemiology and clinical impact in the UK. We discuss management and preventative strategies, highlight limitations in existing surveillance and the future challenges posed by CA-MRSA in the UK.

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

BackgroundStaphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation.MethodsWe will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively.DiscussionThis pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.Trial registrationCurrent Controlled Trial ISRCTN 37666216

Evaluation of the performance of CURB-65 with increasing age

There has been concern about the performance of CURB-65 in older patients with community-acquired pneumonia (CAP) and that younger patients who subsequently die are initially misclassified as having non-severe CAP. The purpose of this study was to evaluate the effect of age on the performance of CURB-65. We analysed data prospectively, collected in two UK hospitals. Patients were stratified into four age cohorts. Mortality in each cohort was then stratified by CURB-65 score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating curve (AUROC) were calculated. Four hundred and twenty-eight patients were included. Misclassification of patients who subsequently died as non-severe CAP patients (CURB-65 score of < or =2) increased with increasing age (from 3% in the <65-year cohort to 27% in those aged >85 years). There were no deaths (0/105) in those aged <65 years who had a CURB-65 score of 0 or 1. At the British Thoracic Society cut-off for severe CAP (CURB-65 score of > or =3), CURB-65 performed best in 16-64-year-olds (PPV 0.4, NPV 0.97). The AUROC was significantly higher for the <65-year cohort in comparison with older patients (0.93 vs. 0.7, p <0.05). Clinicians should interpret the CURB-65 score with care in older patients referred to hospital with CAP. In those aged <65 years, however, CURB-65 appears to be able to identify a cohort of patients (CURB-65 score of 0 or 1) with very low mortality.

Swine flu and antibiotics

Health services worldwide are likely to be hard-pressed by swine flu-related illness in the months ahead. Secondary infections with Streptococcus pneumoniae, other streptococci (e.g. Streptococcus pyogenes), Haemophilus influenzae and Staphylococcus aureus are likely to be important causes of morbidity and mortality. The UK Department of Health recently published clinical pathways for the management of swine flu. Suggested severity criteria have not been validated in respiratory infection and are different from those previously published. Antibiotics are recommended for all patients assessed at hospital, regardless of severity of illness; cephalosporins or quinolones are suggested for inpatients with pneumonia. These recommendations will jeopardize recent decreases in Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant S. aureus (MRSA) in UK hospitals. This article, written on behalf of the BSAC Council, considers these recommendations and provides alternative antibiotic regimens for a range of clinical scenarios.

Long-term mortality following bloodstream infection

Bloodstream infection is associated with significant short-term mortality, but less is known about long-term outcome. We describe factors affecting mortality up to 3 years after bloodstream infection in a cohort of patients reviewed at the bedside by an infection specialist. Patients seen by the bacteraemia service of our infectious diseases department between June 2005 and November 2008 were included in analyses. Routine clinical data collected at the time of consultation, together with laboratory, demographic and outcome data were analysed to identify factors predicting death at 30 days and 3 years after bloodstream infection. Cox regression models for both time-points were constructed, together with Kaplan-Meier survival curves. In all, 322 bloodstream infections were recorded in 304 patients. The 30-day mortality was 15%, with a 3-year mortality of 49%. At 30 days after bacteraemia, in the Cox regression model, increasing age (p 0.003) and lower serum albumin (p 0.014) were predictive of death. At 3 years, age (p <0.0001) and albumin (p 0.004) remained significant predictors of death, with the presence of vascular disease (p 0.05) also significantly associated with mortality. If temperature was treated as a continuous variable then urea was significant (p 0.044); however, if temperature was categorized into hypothermia and non-hypothermia, then the presence of hypothermia (p 0.008) and chronic renal disease (p 0.034) became significant. There is an appreciable and gradual increase in mortality after an episode of bloodstream infection. Although many factors may not be amenable to intervention, patients at high risk of long-term mortality might require further follow up and assessment for potentially modifiable factors.

Investigation of suspected urinary tract infection in older people

#### Learning points An 84 year old woman, who lived in a residential home, was referred to the acute medical assessment unit with a two day history of increasing confusion of unclear cause. She was unable to provide a clear history, but her daughter mentioned that she was not usually confused. On examination, her temperature was 36.8°C, her heart rate was 67 beats per minute, and her blood pressure was 135/70 mm Hg. She looked dehydrated and was noted to be incontinent of dark, offensive smelling urine. Urinary tract infection was suspected. Suspected urinary tract infection is a common scenario when evaluating ill older adults. The diagnosis may be challenging, as patients are often unable to provide a history of acute urinary symptoms (for example, owing to delirium or dementia), and asymptomatic bacteriuria (see table 1⇓ for definitions) is common in older people. The prevalence of …

Sequential antibiotic therapy.

Antimicrobials are an important source of hospital expenditure. Traditionally, severe bacterial infections have been treated initially with intravenous antibiotics, followed by physician-directed switch to oral therapy. Unfortunately this approach results in unnecessary prolongation of intravenous treatment, with all its inherent disadvantages. Sequential antibiotic therapy, however, ensures an early switch to the oral route when the patient is clinically stable. This increasingly employed strategy is safe and results in improved quality and cost-effectiveness of health care. To ensure timely and appropriate switch, such programmes need to be underpinned by clear guidelines and supported by a multidisciplinary team. In the future, key questions, such as what is the optimal time of switch for specific infections, and can conditions such as osteomyelitis and endocarditis be efficaciously treated with oral therapy, need to be answered. Only then will clinicians be able to practise evidence-based infection management incorporating sequential antimicrobial therapy.