In September 2012 a novel coronavirus (CoV) caused severe respiratory tract infections in patients from The Arabian Peninsula. It was named Middle East respiratory syndrome (MERS)-CoV. Here, a small ...series of case stories illustrates how simultaneous analyses for MERS-CoV and other agents of infections at the loca l laboratory resulted in rapid rejection of suspicion of MERS and establishment of the true cause of disease. Relevant treatment was initiated and the patients were discharged from hospital.
BACKGROUND: Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed ...genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly respond to selection pressures, such as those imposed by the immunological host response and antiviral therapy. We have applied deep sequencing to characterize influenza intra-host variation in a transmission chain consisting of three cases due to oseltamivir-sensitive viruses, and one derived oseltamivir-resistant case. METHODS: Following detection of the A(H1N1)pdm09 infections, we deep-sequenced the complete NA gene from two of the oseltamivir-sensitive virus-infected cases, and all eight gene segments of the viruses causing the remaining two cases. RESULTS: No evidence for the resistance-causing mutation (resulting in NA H275Y substitution) was observed in the oseltamivir-sensitive cases. Furthermore, deep sequencing revealed a subpopulation of oseltamivir-sensitive viruses in the case carrying resistant viruses. We detected higher levels of intra-host variation in the case carrying oseltamivir-resistant viruses than in those infected with oseltamivir-sensitive viruses. CONCLUSIONS: Oseltamivir-resistance was only detected after prophylaxis with oseltamivir, suggesting that the mutation was selected for as a result of antiviral intervention. The persisting oseltamivir-sensitive virus population in the case carrying resistant viruses suggests either that a small proportion survive the treatment, or that the oseltamivir-sensitive virus rapidly re-establishes itself in the virus population after the bottleneck. Moreover, the increased intra-host variation in the oseltamivir-resistant case is consistent with the hypothesis that the population diversity of a RNA virus can increase rapidly following a population bottleneck.
Excessive and inappropriate use of antibiotics is considered to be the most important reason for development of bacterial resistance to antibiotics. As antibiotic resistance may spread across ...borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. The majority of respiratory tract infections (RTIs) are treated in general practice. Most infections are caused by virus and antibiotics are therefore unlikely to have any clinical benefit. Several intervention initiatives have been taken to reduce the inappropriate use of antibiotics in primary health care, but the effectiveness of these interventions is only modest. Only few studies have been designed to determine the effectiveness of multifaceted strategies in countries with different practice setting. The aim of this study is to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different prevalence of antibiotic resistance: Two Nordic countries (Denmark and Sweden), two Baltic Countries (Lithuania and Kaliningrad-Russia) and two Hispano-American countries (Spain and Argentina).
HAPPY AUDIT was initiated in 2008 and the project is still ongoing. The project includes 15 partners from 9 countries. GPs participating in HAPPY AUDIT will be audited by the Audit Project Odense (APO) method. The APO method will be used at a multinational level involving GPs from six countries with different cultural background and different organisation of primary health care. Research on the effect of the intervention will be performed by analysing audit registrations carried out before and after the intervention. The intervention includes training courses on management of RTIs, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting room, brochures to patients and implementation of point of care tests (Strep A and CRP) to be used in the GPs'surgeries. To ensure public awareness of the risk of resistant bacteria, media campaigns targeting both professionals and the public will be developed and the results will be published and widely disseminated at a Working Conference hosted by the World Association of Family Doctors (WONCA-Europe) at the end of the project period.
HAPPY AUDIT is an EU-financed project with the aim of contributing to the battle against antibiotic resistance through quality improvement of GPs' diagnosis and treatment of RTIs through development of intervention programmes targeting GPs, parents of young children and healthy adults. It is hypothesized that the use of multifaceted strategies combining active intervention by GPs will be effective in reducing prescribing of unnecessary antibiotics for RTIs and improving the use of appropriate antibiotics in suspected bacterial infections.
A prerequisite for rational antibiotic treatment is the suspicion that the disease is caused by bacteria and that treatment will reduce symptoms and complications. In primary health care most ...infections are caused by bacteria. The European project HAPPY AUDIT found that an intervention targeting doctors and patients in primary care led to a considerable decrease in antibiotic prescribing. Teaching of hospital doctors, combined with a restriction in the choice of antibiotics, resulted in a decrease in multidrug-resistant strains. A concerted effort is needed to curb the growing resistance problem.
The prevalence of antibiotic resistance in a country reflects the local consumption of antibiotics. The majority of antibiotics are prescribed in general practice and most prescriptions are ...attributable to treatment of respiratory tract infections (RTIs). The aim of this study was to compare general practitioners' (GPs') prescribing of antibiotics for respiratory tract infections in a country with a high prevalence of antibiotic resistance (Spain) with a country with a low prevalence of antibiotic resistance (Denmark).
A group of GPs in Copenhagen and Barcelona registered all contacts ( n=2833) with patients with RTIs during a 3-week period between 1 November 2001 and 31 January 2002.
Overall, Spanish GPs treated a higher proportion of patients than Danish GPs. After adjusting for unequal distribution of age and sex, we found that Spanish GPs prescribed significantly more antibiotics to patients with focus of infection in tonsils and bronchi/lungs. Narrow-spectrum penicillin was the most used antibiotic in Denmark, representing 58% of all prescriptions issued, followed by macrolide and broad-spectrum penicillin. In Spain, prescriptions were distributed among a great number of compounds, with broad-spectrum penicillins and combinations of amoxicillin plus beta-lactamase inhibitors most frequently used.
The substantial difference in the way GPs manage respiratory tract infections in Denmark and Spain cannot be explained by different patterns of RTIs in general practice. The discrepancies indicate variations in national recommendations, different treatment traditions or different impact of pharmaceutical marketing.
Antibiotic consumption has increased by around 50% in Danish hospitals over the last 7 years. In percentages, the highest increase has been among broad spectrum antibiotics such as cephalosporins, ...crabapenems and fluoroquinolones. The consequence of this is selection of resistant bacteria and fungi. Control of antibiotic resistance requires implementation of different strategies: better and more rapid diagnosis of infectious origin, restriction on antibiotic use, e.g. through re-evaluation every 2-3 days of patients receiving antibiotics, optimization of dosing and duration of treatment, preferred use of narrow spectrum antibiotics and optimization of hospital hygiene.
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