Christine Clark, BSc, MSc, PhD, FRPharmS, FCPP(Hon)
Effective antimicrobial stewardship, combined with a comprehensive infection control program, can limit the emergence and transmission of antimicrobial-resistant bacteria. A secondary goal of antimicrobial stewardship is to reduce healthcare costs without adversely affecting the quality of care, Ron Polk (Research Professor, Virginia Commonwealth University, USA) told the audience at the United Kingdom Clinical Pharmacy Association Autumn Symposium held at the Barceló Hotel, Hinckley Island, Leicestershire, in November 2011.
Historically, antibiotic management programs had been introduced to contain costs but this had placed pharmacists in the role of ‘antibiotic police’, often in conflict with infectious disease physicians. Eventually the benefits of cooperation were recognised and antimicrobial stewardship positions were established.
Antimicrobial stewardship is an ongoing process to optimise antimicrobial use in order to improve patient outcomes, ensure cost-effective therapy and reduce adverse sequelae of antimicrobial use, including antimicrobial resistance, emphasised Professor Polk. It includes appropriate selection of drugs, dosing, route of administration and duration of therapy. Guidelines for the development of antimicrobial stewardship programs (ASPs) have recently been published in the USA and these recommend that a clinical pharmacist with training in infectious diseases should be a core member of the team. Implementation advice has also been published in Europe, he added. (see Resources)
There are two core strategies in antimicrobial stewardship. The first is formulary restriction and pre-authorisation measures that restrict the drugs that can be used and the way in which they can be prescribed. The second involves review, feedback and, if necessary, IV-to-oral switching and discontinuation of treatment. Interest in ASPs is continuing to grow and is driven by continuing problems with resistance to antimicrobial agents. Training programs are being developed and the need for ‘better science’ to support antimicrobial stewardship activities has been recognised. In particular, better measures of drug use are needed and this could involve the use of days of therapy (DOTs) in preference to defined daily doses (DDDs), explained Professor Polk. In addition, outcome measures need to be clarified and these could include patient care and drug safety, resistance and economic measures.
Potential quality measures for antimicrobial use could include:
- Requiring an indication with every antibiotic order
- Reviewing each antibiotic order within 72 hours
- Obtaining cultures before new antibiotics are administered for sepsis or systemic inflammatory response syndrome (SIRS)
- Reviewing all positive blood cultures to check that appropriate action has been taken if therapy was incorrect, for example, because of a mismatch between organism and drug
- Switching of appropriate patients from IV to oral antibiotics.
The importance of saving money in ASPs depends on the perspective of the audience, said Professor Polk. In general, cost-saving arguments were useful to convince administrators of the value of ASPs but arguments about reductions in resistance, adverse drug reactions and reductions in the level of Clostridium difficile infections were more persuasive with clinicians.
Benchmarking of antibiotic use is a useful process because measuring what is done is the key to improving, said Professor Polk. For example, one study had examined outpatient antibiotic use in Europe and had shown a threefold variation in overall antibiotic usage (as DDDs per 1000 inhabitants per day) across 15 European countries. Inter-hospital comparisons of antibiotic use allow the organisations to compare their performance with the leaders in the field, he explained. “DDDs brought order from chaos” but, as a measure, it has some shortcomings, for example, paediatric use cannot be measured, and so alternative measures are being explored, said Professor Polk. Days of therapy and length of therapy (LOTs) are now gaining credence as useful measures of antibiotic usage. When DOTs and LOTs are displayed for each clinical service line (CSL) (groupings of related clinical conditions), a meaningful profile of hospital activity can be constructed.
In conclusion, Professor Polk said that local ASPs were the key to implementation of these ideas and that the need for more pharmacists trained in infectious disease represents a major opportunity for clinical pharmacists.
“Junior doctors relied on nurses and pharmacists to identify prescribing errors and put things right”, was the conclusion from research into the frequency, nature and causes of prescribing errors in hospitals, said Darren Ashcroft (Professor of Pharmacoepidemiology, Manchester University, United Kingdom). Problems with medicines were often not related to the product but to the medicines management system that failed to ensure that the right drug and dose reached the right patient, he noted.
There have been 65 studies of prescribing errors in hospitals between 1985 and 2007, most of which were conducted in single hospitals. These studies gave a median error rate of 52 errors per 100 admissions (7% of medication orders). However, there was marked variation in the definitions of error and the methods used to collect the data.
The EQUIP study was designed to examine prescribing errors and the underlying causes in 20 hospitals in the UK. In the study all newly-prescribed or newly-written inpatient medication orders were checked for errors by hospital pharmacists for a seven-day period. More than 124,000 prescriptions were checked, corresponding to approximately 26,000 patients. The mean error rate was 8.8% and error rates were highest among the most junior grades of doctors. About 2% of the errors were classified as ‘potentially lethal’, involving failures to check on allergies or prescribing medicines that were contraindicated. Some 5% of errors were serious and 53% were potentially significant. Errors occurred most commonly at admission and typically involved unintentional omission of medicines. Errors occurred less frequently during the hospital stay and at discharge. The causes of prescribing errors were investigated by in-depth interviews of foundation year 1 trainee doctors. Both critical incident analysis and questioning about prescribing education and training were used in the interviews. Of the 85 critical incidents analysed, slips, lapses and rule-based mistakes accounted for the majority and knowledge-based errors accounted for about a quarter. A number of contributory factors were identified, including high workload, tiredness, lack of support and advice, unfamiliar drug charts and, sometimes, unfamiliar patients. Commenting on a knowledge-based error, one junior doctor said that he knew he should have looked it up but he was afraid of looking stupid in front of others.
Turning to the way in which prescribing skills are learned, Professor Ashcroft said that most junior doctors “picked it up as they went along”, with little formal training. Interviewees commented that there were few opportunities to practise prescribing in advance and that little of their training was concerned with the practical aspects of prescribing. Pharmacology teaching helped them to know about medicines but not about how to prescribe them, they said. It was also apparent to the researchers that many errors were made but junior doctors received little feedback to help them improve their performance. Junior doctors thought that errors were probably identified and rectified by someone else and that they were only told about errors that caused serious problems. This situation meant that opportunities for learning were missed, he said.
Professor Ashcroft concluded that the risks of prescribing errors remain high and he emphasised the importance of continuing education and feedback both in medical schools and in the workplace. He underlined the multifactorial nature of prescribing errors and emphasised that improved understanding of medication prescribing errors would be helpful in the design of error prevention strategies.
Pharmacists should help to shorten patients’ length of stay in hospital by using staff resources efficiently and this could involve, for example, reducing the frequency of readmissions by educating patients and making follow-up phone calls. Speaking at a session devoted to demonstrating the value of pharmacy services, Mark Tomlin (Consultant pharmacist: Critical Care, University Hospital Southampton NHS Foundation Trust), suggested a number of ways in which this might be done.
Making the patient’s stay in hospital short and safe is critical and several measures could help here, such as the use of pre-operative assessment clinics and enhanced recovery programs. The use of pre-packed medicines, advanced dispensing of take-home medicines and re-engineering of dispensing processes could also help.
A number of ‘quality-enhancing’ processes have been developed in recent years and these deserve to be widely implemented. For example, the treatment of myocardial infarction has now been transformed from thrombolytic therapy to angioplasty and stenting. Falls prevention initiatives based on avoidance of inappropriate drugs and medicines’ reconciliation at the beginning of a hospital stay are other examples. The introduction of pharmacist prescribing clinics is a major advance –”Have the drugs expert make the decisions and prescribe rather than advise the trainee diagnostician”, said Mr Tomlin. “At Southampton [University Hospital] 20% of the pharmacists are now qualified prescribers”, he added.
The key to reducing length of stay is often ‘getting it right first time’, he concluded.
Antibiotics – missed doses
A point prevalence audit of missed doses of antimicrobials in 45 hospitals showed that doses were omitted in 13.2% of patients, according to Jane Hough and Jane Nicholls (East and South East England Specialist Pharmacy services). A recent publication from the National Patient Safety Agency about reducing harm from omitted and delayed doses had identified antimicrobials as critical drugs. In this study, antimicrobial prescriptions for a 24-hour period were reviewed in 45 acute hospitals. More than 80% of the prescribed antimicrobials were stocked on the wards, and many of the doses recorded as ‘not available’ on administration charts were subsequently shown to be available. Antibiotics that were not stocked on wards were twice as likely to be omitted. Of particular concern was the high number of first doses omitted on intermediate care wards (27.6%) and surgical admission wards (21.1%).
An incident involving the administration of morphine to a paediatric patient had prompted the introduction of a dosage calculation confirmation chart at King’s College Hospital NHS Foundation Trust (London). Gillian Cavell and Lydia Marsh described how the chart had been evaluated. Nurses from five paediatric wards were asked to calculate doses for five scenarios. One required calculation of the concentration of morphine sulphate infusion and the remainder required calculation of volumes of naloxone (two different doses and indications), cyclizine and ondansetron injections. The first assessment was done in the usual way – with calculators and product information available. For the second assessment nurses were provided with a dosage calculation confirmation chart and an explanation of how to use it. The results showed that correct calculation increased from 86% to 95%. “Current strategies for confirming accuracy [of calculations] are not sufficiently reliable”, commented Ms Cavell. At King’s College Hospital, modified charts are to be introduced for paediatric analgesia, although Ms Cavell emphasised that the charts should be seen as an adjunct and not a substitute for arithmetic skills.
Acute renal toxicity
It is estimated that 50–70% of adverse drug reactions (ADR) are avoidable. Acute renal toxicity due to medicines is a common cause of reversible acute renal failure and it is regarded as a serious ADR, said Katherine Davidson (NHS Lothian Pharmacy Service, Scotland). Ms Davidson and colleagues had analysed ADR reports of acute renal failure to identify the groups of drugs implicated most frequently. The results showed that non-steroidal anti-inflammatory drugs (NSAIDs), drugs affecting the renin-angiotensin system and lipid-lowering agents were the top three categories reported. The first two groups of drugs had been expected but the finding of lipid-lowering agents as the third most frequently reported group was an unexpected result, commented Ms Davidson. Overall the results confirmed the need for vigilant monitoring of renal function in elderly patients who are prescribed nephrotoxic medicines, she said.
A dispensing process in which one person both dispenses medicines and generates labels is the quickest and least prone to errors, according to a study presented by Nigel Brinklow (King’s College Hospital NHS Foundation Trust, London). A comparison of three styles of dispensing was undertaken. The ‘production’ approach involved one person generating labels and another dispensing medicines; the ‘mixed’ approach involved one person dispensing items from a dispensing robot (including labels) and another person dispensing other items on a prescription. These two approaches were compared with the ‘own’ dispensing process in which one person both dispenses medicines and generates labels. The results showed that the ‘own’ process was much faster – the time taken to dispense one item was 2.7 minutes compared with 5.7 minutes (production) and 4.0 minutes (mixed). It was also less likely to produce dispensing errors with an error rate of 1.75% compared with 2.51% (production) and 3.37% (mixed). There is a popular assumption that if two people are involved in a dispensing process then errors are more likely to be detected and prevented, but this is not borne out by this study, commented Mr Brinklow.
Dellit TH et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin Infect Dis 2007;44:159–77. www.premierinc.com/informatics/tools-services/safety/topics/guidelines/downloads/CID-Guideline-Antibiotic-Stewardship_b.pdf
Allerberger F et al. Antibiotic stewardship implementation in the EU: the way forward. Exp Rev Anti Infect Ther 2009;7(10):1175-83. http://www.stophetzout.be/internet2Prd/groups/public/@public/@mixednews/documents/ie2faq/19064967.pdf