Laurence A Goldberg
The European Union Conference on the Microbial Threat, held in Copenhagen in 1998, was the turning point for surveillance and control of antimicrobial resistance in Europe, said Dr Dominique Monnet (Statens Serum Institut, Copenhagen). During this meeting, scientific experts, public health officials and representatives from national and international organisations formulated a series of recommendations that were to have a profound influence throughout Europe over the next few years. Amongst other developments, the European Commission funded Europe-wide surveillance systems for antimicrobial resistance (European Antibiotic Resistance Surveillance System: EARSS) and for antimicrobial consumption (European Surveillance of Antibiotic Consumption: ESAC). Research projects have also been funded, and an educational film for television broadcast is planned for later in 2004.
Optimising the use of anti-infectives
Until recently, most projects have focused on outpatients; however, antibiotic resistance remains high in most European hospitals as a result of poor infection control and uncontrolled use of antibiotics. One study has shown that the level of resistance to macrolides and lincosamides was directly correlated with the consumption of these antibiotics in primary healthcare. The prevalence of resistance was highest in France, Italy, Spain and Belgium and lowest in Sweden, Denmark, Luxembourg and Germany. Data from the EARSS have shown that the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was highest in the Mediterranean countries and the UK and lowest in Scandinavia.
A number of national and international initiatives to combat antimicrobial resistance are now underway. However, the recommendations cannot be enforced, and the level of implementation is variable. From 2004 onwards, no specific financing will be provided by EARSS and ESAC to participating countries for surveillance activities. In some countries, practical tools such as systems for auditing prescriptions are missing and strategies for infection control are still weak. Dr Monnet recommended that the European Centre for Disease Prevention and Control (ECDC) should take up drug resistance and hospital infection issues as soon as possible.
Pharmacists must play a key role in the implementation of a policy on the prudent use of antibiotics in European hospitals, said Dr Monnet. At the hospital level, they should be involved in the multidisciplinary team that decides and implements the local antibiotic policy, and they should also be responsible for the provision of quantitative and qualitative information about antimicrobial use in their hospitals. At the European level, hospital pharmacists are essential to multicentre studies on antimicrobial consumption and should, therefore, get useful feedback in return for providing data.
Antibiotics are the most likely target for successful interventions in quality and cost of prescribing, according to Dr Robert Vander Stichele (GP and member of the ESAC management team). He suggested that one important role of the hospital pharmacist is the collection, transformation and analysis of data on antibiotic utilisation. All consumption of antibiotics should be tracked, by volume and expenditure, using unique identifiers for each unit of issue. The next step is to create a database of antibiotic consumption, he said. It is essential to be able to link units of issue with drug classifications to permit meaningful analysis, and this is best achieved using the ATC/DDD methodology. The anatomical therapeutic chemical classification (ATC) is a hierarchical coding system that allows identification of an antibiotic as a chemical substance or as part of a larger group. The defined daily dose (DDD) is the assumed average maintenance dose per day for a drug used for its main indication in adults. The DDD is a unit of measurement and does not necessarily reflect the recommended or prescribed daily dose. The use of the DDD means that packages of different brands with the same active ingredient but with different strength and pack size can be aggregated. Dr Vander Stichele recommended the use of the ABC Calc – free software (available on the ESCMID website – see Resources) developed to convert drug issue data into antibiotic utilisation data, usually expressed as DDD per 100 bed-days.
The ESAC retrospective study of consumption of antibiotics in hospitals in Europe has shown wide variations in the amounts of antibiotic used. Valid data have been collected from Belgium, France, Greece, Luxembourg, the Netherlands, Denmark, Finland, Sweden Hungary, Malta, Poland, Slovakia, Slovenia, Croatia and Norway. The results show that, in 2001, Finland and France used about three times as many antibiotics (in DDD per 1,000 inhabitants) as Norway. Furthermore, there are considerable differences in the patterns of usage within countries. The researchers concluded that there are large differences in the use of antibiotics in hospitals and no regional clusters. Interpretation of national data seems to be hampered by the wide variations in antibiotic use in the different hospitals within a country. Data from individual hospitals were more likely to be interpretable, suggested Dr Vander Stichele.
A continuous, multidisciplinary effort is needed to manage antibiotic usage effectively, said Hege Salvesen Blix (Lovisenberg Hospital Pharmacy and the Norwegian Institute of Public Health, Oslo). In her hospital, there is an infection control (hygiene) committee and an active antibiotic team comprising a specialist in infectious diseases, a pharmacist and an infection control nurse. The infection control committee is responsible for assessing resistance patterns, surveillance of nosocomial infections and quantitative and qualitative monitoring of antibiotic utilisation. Pharmacists follow up antibiotic prescribing on a daily basis.
Quantitative and qualitative analyses of antibiotic utilisation are prepared by the pharmacy staff. Annual antibiotic use (in packages sold) is converted to DDDs using ABC Calc and aggregated to the ATC 5th level, which corresponds to chemical substances. The data are then presented by hospital, by department and by ward. With regard to qualitative utilisation, work in Ms Blix’s hospital has shown that a 1-day, point-prevalence study of antibiotic use provides sufficient information to determine how well the antibiotic guidelines are being followed. This is now undertaken three times per year. On each occasion, each patient in the hospital who is receiving an antibiotic is identified and full details of the treatment, the indication and the patient are recorded.
Fungal infections update
Intravenous drug users are particularly at risk of developing systemic Candida infections as a result of dissolving heroin in lemon juice, which is commonly contaminated with Candida, said Dr Werner Zimmerli (Basel University Medical Clinic). He explained that the most common fungal infections in Europe were those due to Candida, Aspergillus and Cryptococcus species. People with compromised immune systems or impaired nonimmune barriers were most at risk. Airborne Aspergillus conidia are often released during construction work and can pose a particular risk to immunocompromised patients. In most hospitals, this is a daily hazard. Dr Zimmerli said that it was important for the infection control team to be in contact with those responsible for construction work.
There are problems with amphotericin B, the gold standard drug for systemic fungal infections, reported Dr William Hope (Wythenshawe Hospital, Manchester). Amphotericin B is associated with infusional toxicity and nephrotoxicity. Lipid-based formulations are generally less toxic but are no more efficacious than conventional amphotericin B, he explained. Voriconazole is now the treatment of choice for invasive aspergillosis. It is formulated with cyclodextrin, and the intravenous form should not be given in renal failure due to risk of accumulation of cyclodextrin. In the treatment of invasive Candida infections, caspofungin is equivalent in efficacy to amphotericin B but has fewer side-effects. It is also active against azole-resistant Candida species.
Integrating professional and organisational quality
Healthcare is a high-risk industry, but we are not managing it as such, according to Professor Dr Marc Berg (Professor of Socio-Medical Sciences at the Institute of Health Policy and Management, Erasmus University Medical Centre, Rotterdam). Up to 3.7% of all hospital admissions in the USA are due to medical errors or omissions, and up to 13.6% of these end in the death of the patient. This means that errors or omissions are the third to eighth leading cause of death, he said. Similar rates have been observed in Australia, Canada and the UK. A graph of mortality rate against expenditure shows that there is no relationship between the amount of money spent and the death rate.
Part of the problem is that no single professional has “routine, integrated access to the medication record”, explained Professor Berg.
Research in Western countries has shown that 5–15% medication orders contain mistakes and that 10–15% of these cause adverse drug events. Moreover, there is typically only 30% agreement between medication histories taken from the GP, the patient and the community pharmacist. Healthcare systems are not currently equipped to deliver standard quality, but factors such as the ageing population, empowered patients and demands for accountability will increase the pressure for high-quality services, he predicted. Several critical features of the present system account for the lack of quality (see Panel).
The four elements that are fundamental to the delivery of top-quality care are: optimally patient-centred services; effective and safe services; efficiency; and a learning organisation. In addition, the system should provide a pleasurable working environment for staff. The current step-by-step approach is “utterly dysfunctional”, said Professor Berg, and leads to a lot of waiting, unnecessary steps and continuous battles on the shop floor. Overall, it increases the risks of errors or omissions. A fundamental redesign of the healthcare system is now required to ensure integration between professional and organisational aspects of care. This could be achieved through the development of standardised care trajectories (SCTs). It is possible to predict a care pathway for specific groups of patients and, therefore, to plan at an aggregated level. He added that 80% of activities can be standardised for 80% of patient flows. SCTs should not be “straightjackets” – as standardisation should be applied only to activities that bring direct benefit. SCTs should not be written as guidelines (that tend to stay on shelves) but should be embedded in standardised operating procedures (SOPs).
A basic step in designing SCTs is to identify all individual tasks, decision points and procedures so that care becomes predictable and can be planned. The introduction of SCTs makes integrated planning possible because patient trajectories rather than departmental capacity become the central ordering principle. In the current situation every department is geared to maximise use of its own capacity. This works well when capacity is abundant, but if it is limited then waiting is inevitable. When capacity is >75% saturated, waiting time increases dramatically. If capacity were to be planned on the basis of SCTs (and therefore a predictable workload), there would be enormous gains in productivity and reduction of work stress. Furthermore, capacity problems can then be addressed as a joint problem.
Potassium chloride errors
Potassium chloride (KCl) misadministration events should not be underestimated, said Professor David Cousins (Head of Safe Medication Practice of the National Patient Safety Agency, NPSA). Hospitals should increase safety controls for KCl before and during administration and, whenever possible, make ready-to-use (RTU) KCl solutions available.
Medication errors involving concentrated KCl are not perceived as a serious problem outside the UK and, consequently, the measures adopted by hospitals to prevent errors are not as drastic as those in the UK. In most hospitals, concentrated KCl ampoules are available on wards. The absence of a harmonised European medication error reporting system means that it is difficult to obtain an accurate picture of adverse events involving concentrated KCl. Methods to raise awareness of the dangers of concentrated KCl could include lectures and workshops run by hospital pharmacists’ associations, training sessions for doctors and nurses and the creation of a hospital pharmacists’ information network on a national or Europe-wide basis.
The UK Safety Alert document led to improvements in hospital policies, training and the use of RTU KCl infusions and, thereby, it contributed to a reduction in the numbers of medication errors related to KCl dilution and administration in UK. To achieve the same results in other European countries, there needs to be wider awareness of the problem and effective methods to manage the risks.
European Antibiotic Resistance Surveillance System (EARSS)
European Surveillance of Antibiotic Consumption (ESAC)
Report from the Invitational EU Conference on the Microbial Threat. Copenhagen Denmark, 9-10 September 1998
European Centre for Disease Prevention and Control (ECDC) W:europa.eu.int/comm/health/ph_overview/strategy/ecdc
European Surveillance of Antimicrobial Consumption (ESAC)
European Society of Clinical Microbiology and Infectious Diseases (ESCMID)