Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies

Objectives: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. Methods: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results: The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.Junta de Andalucía PI 0185/201

Tackling Extended Hospital Stays in Patients with Acute Bacterial Skin and Skin Structure Infections

Hospitalisation rates for acute bacterial skin and skin structure infection (ABSSSI) are rising and represent a large pharmacoeconomic burden as treatment may involve an extended number of days of antibiotic therapy. This article first aims to provide a review of treatment challenges associated with ABSSSIs in both hospital and outpatient settings, and shows that while more traditionally treatment has been conducted in a hospital setting, for a number of patients, a variety of considerations, including pharmacoeconomics, infection control, and patient preference, has led to the development of recommendations to assess the eligibility of patients for early discharge from hospital to complete their antibiotic regimen in the outpatient setting. However, such patients require monitoring for drug adherence to oral regimens or complications associated with daily intravenous administration, such as injection site reactions and infection. This review also focuses on one of a number of new antibiotics for ABSSSI, dalbavancin, as the long-acting glycopeptide with the most clinical experience to date. This antibiotic has been shown to be as effective as a daily/twice daily regimen with similar safety profiles. Health economic analysis of dalbavancin is also presented. It has shown that in some, though not all, clinical settings a reduction in the overall treatment cost is evident as, despite a higher medication cost, the lower hospitalisation time can lead to greater cost savings. In conclusion, while the burden of ABSSSI is rising, new treatment options provide additional therapeutic choice, although pharmacoeconomic considerations might limit use in some cases

Case-series Evaluating a Transdiagnostic Cognitive-behavioral Treatment For Co-occurring Anxiety Disorders.

Background. Patients with anxiety disorder diagnoses commonly have more than one anxiety diagnosis. While cognitive-behavioral interventions have proven efficacy in treating single anxiety disorder diagnoses, there has been little investigation of their efficacy in treating cooccurring anxiety disorders. Aims. To evaluate the efficacy of a transdiagnostic cognitive-behavioral intervention for treating co-occurring anxiety disorders. Methods. An A-B single case study design (N = 6) was used to evaluate the efficacy of a 12 to 13 session modular transdiagnostic cognitive-behavioral intervention for treating co-occurring anxiety disorders across patients with at least two of the following diagnoses: GAD, Social Phobia, Panic Disorder and/or OCD. Results. Five of the six participants completed treatment. At post-treatment assessment the five treatment completers achieved diagnostic and symptomatic change with three participants being diagnosis free. All participants who completed treatment no longer met criteria for any DSM-IV-TR Axis-I diagnosis at the three-month follow-up assessment, and demonstrated reliable and clinically-significant improvements in symptoms. Across the participants, statistically significant improvements from pre- to post-intervention were found on measures of anxiety, depression and general well-being, and all improvements were maintained at three-month follow-up. Conclusions. Results suggest that transdiagnostic cognitive behavioral interventions can be of benefit to patients with co-occurring anxiety disorders

Prevalence of Child Malnutrition in North Kivu, DRC: Evidence from Bunyuka Parish

Sub-Saharan Africa is the second most undernourished region in the world, with an estimated 265 million people in 2009. The Democratic Republic of the Congo (DRC) has the highest percentage of undernourished people in the region, 75% from 2004 to 2006. The Kivu region in Eastern DRC, in particular, has suffered through decades of conflict and lack of security and infrastructure obstruct data collection in this region. The main contribution of this paper is to present primary survey evidence on the prevalence of malnutrition in the village of Bunyuka in North Kivu. From a sample of over 700 mothers and 1400 children, we find significant prevalence of malnutrition and high dependence on nutritionally deficient food sources

Evaluation of in vitro activity of fosfomycin, and synergy in combination, in Gram-negative bloodstream infection isolates in a UK teaching hospital

Introduction. Fosfomycin has retained activity against many multi-drug resistant (MDR) Gram-negatives, and may be useful against extended spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacterales to improve clinical outcomes.Hypothesis/Gap Statement. There are few data from the UK on the susceptibility of invasive Gram-negative isolates to fosfomycin, especially in the era of increasing use of oral fosfomycin for urinary tract infections (UTIs).Aim. We evaluated fosfomycin susceptibility against 100 consecutive Gram-negative bloodstream isolates, both individually, and in combination with other mechanistically similar and differing antibiotics. The aim was to investigate the synergy between antibiotic combinations against several E. coli, K. pneumoniae and P. aeruginosa isolates with variable levels of resistance.Methodology. Disc diffusion and MIC test strip methods applying revised EUCAST guidelines for Fosfomycin were used, followed by the MTS™ 'cross synergy' method for 'resistant' isolates as defined below: (a) Fosfomycin resistant by MIC test strip; (b) MDR isolates defined as being resistant to ≥3 classes of antibiotics (based on routine sensitivity testing; beta lactams were considered as a single class), and/or (c) AMP C or ESBL or carbapenemase producers (or carbapenem resistant). FIC Index (Fractional Inhibitory Concentration Index) calculations were used to interpret findings, whereby: FIC = (MICA combination A+B/ MIC agent A) + (MICB combination A+B/ MIC agent B). A result of ≤0.5 was taken to indicate 'synergy', >0.5 and ≤1.0 to indicate 'additive' effect, >1.0 and ≤4.0 to indicate 'indifference', and >4.0 to indicate 'antagonism'.Results. We found that 95/100 isolates were susceptible to fosfomycin by MIC test strip, with 88/100 isolates susceptible to fosfomycin by disc, based on EUCAST guideline breakpoints. A total of 30/100 isolates (the more 'resistant' of the 100) were eligible for synergy testing according to our definitions (see Methodology), with the remaining 70 isolates not tested further. Seventeen out of 30 were MDR, 2/30 were AMP C producers and 9/30 were ESBL producers. Overall, 34/300 (11 %) of all combination tests showed synergy and 161/300 (54 %) were additive. Synergy was most commonly detected between fosfomycin and beta-lactam antibiotics, including piperacillin/tazobactam (10/30; 33 %), ceftazidime/avibactam (10/30; 30 %), and temocillin (8/30; 27 %). An additive effect was most commonly detected with aztreonam (25/30; 83 %) and meropenem (25/30; 83 %), but 100 % indifference was found with tigecycline (30/30). No antagonism was identified with any antibiotic combination.Conclusion. Fosfomycin non-susceptibility by MIC test strip was unusual. Synergy was variable when combining fosfomycin with other antibiotics against the more 'resistant' isolates. Synergistic/additive effects were detected for beta-lactam/fosfomycin combinations in >80 % of all such combinations, suggesting beta-lactams may be the preferred partner for fosfomycin. Agents with a discordant site of action were more likely to result in indifference. Antagonism was not detected

Misdiagnoses in the Context of Suspected Pandemic Influenza or Coronavirus Disease 2019 : A Systematic Review

There have been numerous reports of patients initially misdiagnosed in the 2009 H1N1 influenza and coronavirus disease 2019 (COVID-19) pandemics within the literature. A systematic review was undertaken to collate misdiagnoses during the H1N1 and COVID-19 pandemics and identify which cognitive biases may contribute to this. MEDLINE, Embase, Cochrane and MedRxiv databases were searched for misdiagnoses or cognitive biases resulting in misdiagnosis, occurring during the H1N1 or COVID-19 virus pandemics. Eligible studies were assessed for quality using JBI criteria; primary outcome was the final diagnosis. Sixty-nine studies involving 2551 participants were included. We identified 686 cases of misdiagnosis, categorized as viral respiratory infection, other respiratory infection, non-respiratory infection, and non-infective. Misdiagnoses are listed and relevant investigations are offered. No article described prospective assessment of decision making in the pandemic setting or debiasing diagnostic thinking. Further research is required to understand why misdiagnoses occur and harm arises and how clinicians can be assisted in their decision making in a pandemic context

Surgical debridement in long bone chronic osteomyelitis : is wide tumour-like resection necessary?

AIMS: The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit. METHODS: We analyzed the retrospective record review from 2014 to 2020 of patients with long bone COM. All were managed by multidisciplinary infection team (MDT) protocol. Adequate debridement was employed for all cases, and no case of wide resection was included. RESULTS: A total of 53 patients (54 bones) with median age of 45.5 years (interquartile range 31 to 55) and mean follow-up of 29 months (12 to 59) were included. In all, ten bones were Cierny-Mader type I, 39 were type III, and five were type IV. All patients were treated with single-staged management, except for one (planned two-stage stabilization). Positive microbial cultures grew in 75%. Overall, 46 cases (85%) had resolution of COM after index procedure, and 49 (90.7%) had resolution on last follow-up. Four patients (7%) underwent second surgical procedure and six patients (11%) had complications. CONCLUSION: We challenge the need for wide tumour-like resection in all cases of COM. Through detailed preoperative evaluation and planning with MDT approach, adequate debridement and local delivery of high concentration of antibiotic appears to provide comparable outcomes versus radical debridement

Molecular antimicrobial susceptibility testing in sepsis.

Rapidly detecting and identifying pathogens is crucial for appropriate antimicrobial therapy in patients with sepsis. Conventional diagnostic methods have been a great asset to medicine, though they are time consuming and labor intensive. This work will enable healthcare professionals to understand the bacterial community better and enhance their diagnostic capacity by using novel molecular methods that make obtaining quicker, more precise results possible. The authors discuss and critically assess the merits and drawbacks of molecular testing and the added value of these tests, including the shift turnaround time, the implication for clinicians' decisions, gaps in knowledge, future research directions and novel insights or innovations. The field of antimicrobial molecular testing has seen several novel insights and innovations to improve the diagnosis and management of infectious diseases

System-wide approaches to antimicrobial therapy and antimicrobial resistance in the UK: the AMR-X framework

Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR action-focused research beyond the confines of an isolated biomedical paradigm. An AMR learning system, AMR-X, envisions a national network of health systems creating and applying optimal use of antimicrobials on the basis of their data collected from the delivery of routine clinical care. AMR-X integrates traditional AMR discovery, experimental research, and applied research with continuous analysis of pathogens, antimicrobial uses, and clinical outcomes that are routinely disseminated to practitioners, policy makers, patients, and the public to drive changes in practice and outcomes. AMR-X uses connected data-to-action systems to underpin an evaluation framework embedded in routine care, continuously driving implementation of improvements in patient and population health, targeting investment, and incentivising innovation. All stakeholders co-create AMR-X, protecting the public from AMR by adapting to continuously evolving AMR threats and generating the information needed for precision patient and population care

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

BACKGROUND: Staphylococcus 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. METHODS: We 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 (600-900 mg/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. DISCUSSION: This 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.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are