The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of antimicrobial use and misuse. Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs.

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Antibacterial resistance worldwide: causes, challenges and responses.

The 2008 crash has left all the established economic doctrines - equilibrium models, real business cycles, disequilibria models - in disarray. Part of the problem is due to Smith’s "veil of ignorance": individuals unknowingly pursue society’s interest and, as a result, have no clue as to the macroeconomic effects of their actions: witness the Keynes and Leontief multipliers, the concept of value added, fiat money, Engel’s law and technical progress, to name but a few of the macrofoundations of microeconomics. A good viewpoint to take bearings anew lies in comparing the post-Great Depression institutions with those emerging from Thatcher and Reagan’s economic policies: deregulation, exogenous vs. endoge- nous money, shadow banking vs. Volcker’s Rule. Very simply, the banks, whose lending determined deposits after Roosevelt, and were a public service became private enterprises whose deposits determine lending. These underlay the great moderation preceding 2006, and the subsequent crash.

The Economic Institutions of Capitalism

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

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Antibiotic resistance—the need for global solutions

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

Alice K. Jacobs, MD, FACC, FAHA, Chair 

Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect 

Nancy Albert, PhD, CCNS, CCRN, FAHA

Mark A. Creager, MD, FACC, FAHA

Steven M. Ettinger, MD, FACC

Robert A. Guyton, MD, FACC

Jonathan L. Halperin, MD, FACC, FAHA

Judith S. Hochman, MD, FACC, FAHA

2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions

The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed

Objective To evaluate the evidence for the effectiveness of isolation measures in reducing the incidence of methicillin resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital inpatients. Design Systematic review of published articles. Data sources Medline, Embase, CINAHL, Cochrane Library, System for Information on Grey Literature in Europe (SIGLE), and citation lists (1966-2000). Review methods Articles reporting MRSA related outcomes and describing an isolation policy were selected. No quality restrictions were imposed on studies using isolation wards or nurse cohorting. Other studies were included if they were prospective or employed planned comparisons of retrospective data. Results 46 studies were accepted; 18 used isolation wards, nine used nurse cohorting, and 19 used other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with a reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures including patient isolation were effective in controlling MRSA. In two others, isolation wards failed to prevent endemic MRSA. Conclusion Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well designed studies exist that allow the role of isolation measures alone to be assessed. None the less, there is evidence that concerted efforts that include isolation can reduce MRSA even in endemic settings. Current isolation measures recommended in national guidelines should continue to be applied until further research establishes otherwise.

https://www.bmj.com/content/bmj/329/7465/533.full.pdf

Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to the health of hospitalized patients. Attempts to reduce the spread of MRSA have largely depended on hospital hygiene and patient isolation. These measures have met with mixed success: although some countries have almost eliminated MRSA or remained largely free of the organism, others have seen substantial increases despite rigorous control policies. We use a mathematical model to show how these increases can be explained by considering both hospital and community reservoirs of MRSA colonization. We show how the timing of the intervention, the level of resource provision, and chance combine to determine whether control measures succeed or fail. We find that even control measures able to repeatedly prevent sustained outbreaks in the short-term can result in long-term control failure resulting from gradual increases in the community reservoir. If resources do not scale with MRSA prevalence, isolation policies can fail “catastrophically.”

https://www.pnas.org/content/pnas/101/27/10223.full.pdf

Methicillin-resistant Staphylococcus aureus in hospitals and the community: Stealth dynamics and control catastrophes

Objectives: To test the hypotheses that virtual outreach would reduce offers of hospital follow-up appointments and reduce numbers of medical interventions and investigations, reduce numbers of contacts with the health care system, have a positive impact on patient satisfaction and enablement, and lead to improvements in patient health status. To perform an economic evaluation of virtual outreach.Design: A randomised controlled trial comparing joint teleconsultations between GPs, specialists and patients with standard outpatient referral. It was accompanied by an economic evaluation.Setting: The trial was centred on the Royal Free Hampstead NHS Trust, London, and the Royal Shrewsbury Hospital Trust in Shropshire. The project teams recruited and trained a total of 134 GPs from 29 practices and 20 consultant specialists.Participants: In total, 3170 patients were referred, of whom 2094 consented to participate in the study and were eligible for inclusion. In all, 1051 patients were randomised to the virtual outreach group and 1043 to standard outpatient appointments. The patients were followed 6 months after their index consultation.Interventions: Patients randomised to virtual outreach underwent a joint teleconsultation, in which they attended the general practice surgery where they and their GP consulted with a hospital specialist via a videolink between the hospital and the practice.Main outcome measures: Outcome measures included offers of follow-up outpatient appointments, numbers of tests, investigations, procedures, treatments and contacts with primary and secondary care, patient satisfaction ( Ware Specific Visit Questionnaire), enablement ( Patient Enablement Instrument) and quality of life ( Short Form-12 and Child Health Questionnaire). An economic evaluation of the costs and consequences of the intervention was undertaken. Sensitivity analysis was used to test the robustness of the results.Results: Patients in the virtual outreach group were more likely to be offered a follow-up appointment. Significant differences in effects were observed between the two sites and across different specialities. Virtual outreach increased the offers of follow-up appointments more in Shrewsbury than in London, and more in ENT and orthopaedics than in the other specialities. Fewer tests and investigations were ordered in the virtual outreach group, by an average of 0.79 per patient. In the 6-month period following the index consultation, there were no significant differences overall in number of contacts with general practice, outpatient visits, accident and emergency contacts, inpatient stays, day surgery and inpatient procedures or prescriptions between the randomised groups. Tests of interaction indicated that virtual outreach decreased the number of tests and investigations, particularly in patients referred to gastroenterology, and increased the number of outpatient visits, particularly in those referred to orthopaedics. Patient satisfaction was greater after a virtual outreach consultation than after a standard outpatient consultation, with no heterogeneity between specialities or sites. However, patient enablement after the index consultation, and the physical and psychological scores of the Short Form- 12 for adults and the scores on the Child Health Questionnaire for children under 16, did not differ between the randomised groups at 6 months' follow-up. NHS costs over 6 months were greater for the virtual outreach consultations than for conventional outpatients, pound724 and pound625 per patient, respectively. The index consultation accounted for this excess. Cost and time savings to patients were found. Estimated productivity losses were also less in the virtual outreach group.Conclusions: Virtual outreach consultations result in significantly higher levels of patient satisfaction than standard outpatient appointments and lead to substantial reductions in numbers of tests and investigations, but they are variably associated with increased rates of offer of follow-up according to speciality and site. Changes in costs and technological advances may improve the relative position of virtual consultations in future. The extent to which virtual outreach is implemented will probably be dependent on factors such as patient demand, costs, and the attitudes of staff working in general practice and hospital settings. Further research could involve long-term follow-up of patients in the virtual outreach trial to determine downstream outcomes and costs; further study into the effectiveness and costs of virtual outreach used for follow-up appointments, rather than first-time referrals; and whether the costs of virtual outreach could be substantially reduced without adversely affecting the quality of the consultation if nurses or other members of the primary care team were to undertake the hosting of the joint teleconsultations in place of the GP. Qualitative work into the attitudes of the patients, GPs and hospital specialists would also be valuable.

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Jennifer A. Roberts

Papers

The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed

Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature.

Methicillin-resistant Staphylococcus aureus in hospitals and the community: Stealth dynamics and control catastrophes

Virtual outreach: a randomised controlled trial and economic evaluation of joint teleconferenced medical consultations.

Socio-economic burden of hospital acquired infection