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21 May 2009

Breaking the vicious cycle of antibiotic resistant bacteria

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More people die of hospital germs than of HIV every year. The reason is that antibiotics are becoming useless against an ever bigger number of multi-resistant bacteria that are spreading throughout the world. Today, this is not just an issue in hospitals, but throughout society at large

Bacteria and other microorganisms that cause infections are remarkably resilient and can develop ways to survive drugs meant to kill or weaken them. This antibiotic resistance, also known as antimicrobial resistance or drug resistance, is due largely to the increasing use of antibiotics. Disease-causing microbes that have become resistant to drug therapy are an increasing public health problem. About 70 percent of bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used to treat infections. And some organisms are resistant to all approved antibiotics and must be treated with experimental and potentially toxic drugs. Some research has shown that antibiotics are given to patients more often than officialy recommend. For example, patients sometimes ask their doctors for antibiotics for a cold, cough, or the flu, all of which are viral and don't respond to antibiotics. Also, patients who are prescribed antibiotics but don't take the full dosing regimen can contribute to resistance. The promiscuous use of antibiotics to treatment of community-acquired lower respiratory tract infections (CA-LRTI) accounts for a major part of the community burden of antibiotic use and contributes dramatically to the rising prevalence of resistance among major human pathogens.

GRACE (Genomics to combat Resistance against Antibiotics Community-acquired LRTI in Europe; is a Network of Excellence focusing on the complex and controversial field of CA-LRTI, which is one of the leading reasons for seeking medical care. The overall objective of GRACE is to combat antimicrobial resistance through integrating centres of research excellence and exploiting genomics in the investigation of CA-LRTI. Microbial and human genomics will be integrated with health sciences research consisting of clinical observational and intervention studies, health economics and health education to specifically change practice in managing CA-LRTI.

GRACE is exceptional as it brings together 28 academic groups with a wide spectrum of expertise, spread widely across 13 EU Member States, and 4 SMEs. GRACE organise professional education, through two leading European scientific societies (European Society of Clinical Microbiology and Infectious Diseases and European Respiratory Society). A high level of co-ordination is obtained through a professionally IT-supported and rigorous management structure. The consortium is a virtual “European LRTI Research Centre” potentially leading to a forum promoting research and good practice in the field of CA-LRTI. This research programme has been divided into 4 platforms: GRACE-COMIT, GRACETECH, GRACE-PAT, GRACE-EDUT and 12 work packages.

Some of the potential applications that will be possible by the joined forces of the GRACE network are a novel rapid genome based diagnostic tests for the detection of pathogens implicated in CA-LRTI, a European repository of specimens and strains linked to a database including microbial and patient information, risk factors for infection with resistant S. pneumoniae and H. influenzae in patients with CA-LRTI, pneumococcal genes important for virulence and for antibiotic resistance development, optimal pneumococcal treatment and prevention strategy linked to severity of CA-LRTI, human susceptibility genes affecting severe CA-LRTI, potential human target pathways for new immunomodulatory approaches, potential genetic risk profiles for various presentations and outcomes of CA-LRTI in several European populations, evidence-based definitions of the major CA-LRTI, clinical outcome measures for evaluating interventions, clinical models to differentiate viral from bacterial infections and identify pneumonia, clinical models to identify patients at risk for adverse outcomes including severe and prolonged illness, subgroups of patients with CA-LRTI which benefit and which do not from antibiotic treatment, practice based intervention in reducing inappropriate antibiotic use and resistance in patients with CA-LRTI, cost-effectiveness of the management strategies developed in the observational and intervention studies, a model for the macroeconomic impact of antibiotic resistance and policies to contain resistance, economic evaluations of molecular diagnostics, educational packages to inform postgraduate lifelong learning
needs of prescribing professionals.

3402 patients with acute cough/lower respiratory tract infection (LRTI) were included by 14 primary care research networks in 12 countries during the first clinical study within GRACE, making this the largest prospective study of LRTI ever undertaken in primary medical care. Variation in antibiotic prescribing between networks was not associated with variation in outcome for patients. The choice of antibiotics differed widely between countries. There was wide variation in use of investigations. Patients appeared to understand the potential harms of antibiotics, but clinicians and patients in high antibiotic prescribing networks believed more in the benefits of antibiotics for acute cough.

Acute cough /lower respiratory tract infection (LRTI) is one of the commonest reasons why people seek health care and take antibiotics. The implications for use of precious health care resources and antibiotic resistance are considerable. There is wide variation in antibiotic prescription in, but little is known about how comparable patients are investigated and treated in different European countries, and how this affects patient recovery. Health care resources and campaigns directed at clinicians and patients to improve the management of acute cough could be more appropriately targeted if there is a better understanding of current presentation, management and outcomes of acute cough in the community across a wide range of European countries.

The GRACE Network of Excellence therefore studied the issue. 14 primary care research networks (based in the cities of Cardiff, Southampton, Utrecht, Barcelona, Mataro, Rotenberg, Balantonfured, Antwerpen, Lodz, Milano, Jonkoping, Tromso, Helsinki and Bratislava) in 12 countries (UK, The Netherlands, Spain, Germany, Hungary, Belgium, Poland, Italy, Norway, Sweden Finland and Slovakia) collected observational data during two data collection periods (October – November 2006, January – March 2007). Adult patients with a new or worsening cough or clinically suspected LRTI as the main presenting symptom were eligible and clinicians recorded aspects of the patients’ history, symptoms, clinical findings, and their management including whether or not antibiotics were prescribed, and other treatment and investigations. Patients then kept a symptom diary for up to one month. Also included in the patient follow up diary were questions about patient’s demographics, their expectations about treatment, their satisfaction with their care, re-consultation (including at hospitals and out of hours care) and additional management, and health economics data.

The main conclusions of this study are that patients appear to understand potential harms of antibiotics, but clinicians and patients from high antibiotic prescribing networks believe more in the benefits of antibiotics for acute cough. Variations in antibiotic prescribing in this well described sample of patients with acute cough from 14 primary care research networks in 12 European countries are only partially explained by differences case mix. For example, after adjusting for age, co-morbidity and illness severity, the prescribing decisions made for recruited patients by participating clinicians were similar for networks in Spain and the Netherlands. Clinicians from networks based in Eastern Europe and Italy were more likely to prescribe antibiotics. The choice of antibiotics differed widely between countries. Crucially, antibiotic prescribing was not associated with meaningful differences in recovery, variation in antibiotic prescribing between networks is not associated with variation in outcome for patients. The next step in the study is to explore health care system level factors to explain more variation in prescribing and outcomes and to model patient symptom scores across whole to explore possible impact of antibiotics in more depth.

So what’s the bottom line? There is a huge opportunity for improvement in healthcare delivery for acute cough across Europe. Reducing unnecessary and unhelpful variation in care could save a lot of clinician and patient time, reduce antibiotic use, and help contain antibiotics resistance. These outputs are already influencing policy and practice.

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