Nearly 700 participants gathered in Copenhagen for the European Society of Clinical Pharmacy Symposium. Topics included antibiotic resistance, person-centred risk management plans and medication safety for housebound patients
Christine Clark PhD FRPharmS FCPP(Hon)
A 2014 World Health Organisation report emphasised that the post-antibiotic era – in which common infections and minor injuries can kill – is not an apocalyptic fantasy but a very real possibility in the 21st century, Gian Maria Rossolini (Professor of Microbiology and Clinical Microbiology, University of Siena Medical School, Italy) told the audience. Antibiotics are essential to some advanced medical practices such as abdominal (‘contaminated’) surgery, implantation of prosthetic devices and cancer chemotherapy. “If we lose antibiotics, then we lose these”, he continued.
The situation regarding methicillin-resistant Staphylococcus aureus (MRSA) has improved since 2005 with 10–25% resistance in most of Europe, although levels remain higher in Spain, Romania and Poland. Drugs for the treatment of MRSA are now limited to vancomycin and teicoplanin. Newer drugs with anti-MRSA activity include linezolid, daptomycin, tigecycline and ceftaroline and further products are in the pipeline, said Professor Rossolini.
Vancomycin-resistant enterococci (VREs) are an important cause of healthcare-associated infections (HAIs) and can be particularly problematic for neutropenic onco-haematology patients. Currently the main anti-VRE agents are linezolid and tigecycline. A combination product containing quinupristin and dalfopristin is active against VREs but is difficult to obtain and daptomycin is not approved for this indication, he said.
While the crisis for Gram-positive organisms is “largely under control”, the situation is much worse for Gram-negative organisms, he explained. There are high levels of infection with Klebsiella pneumoniae and E. coli and these are increasing. Many strains are resistant to third generation cephalosporins. Enterobacter species now cause one third of HAIs. Moreover, increasing carbapenem use has led to a growing number of carbapenem-resistant strains (CREs). One recent survey of Acinetobacter strains in Italy showed that there was 80% resistance to carbapenems and the only agent that was active against all strains was colistin. The only other option would be tigecycline, which is not approved for treatment of Acinetobacter, he noted. European prevalence studies show high levels of HAIs due to carbapenem-resistant K. pneumoniae in Italy and Poland. This is a real problem, he emphasised, for example there is 70% mortality amongst stem cell transplant patients infected with K. pneumoniae in Italy.
When there are no suitable antibiotics available clinicians are driven to use non-approved agents, large doses or combinations of products, which lead to further resistance problems. One consequence of this is increasing prevalence of combined colistin and carbapenem resistance in Klebsiella species (so-called CCRE – colistin, carbapenem-resistant enterobacter). Between 2011 and 2013–14, the prevalence of CCRE increased from 20% to 40%. New drugs, such as plazomicin, are in development but it will be several years before they reach the marketplace, said Professor Rossolini. Whereas antibiotic resistance with Gram-positive pathogens is largely under control the situation with Gram-negative pathogens is a crisis that is rapidly spinning out of control, he warned.
What is needed now is aggressive infection control measures, coupled with antibiotic stewardship and rapid diagnosis. Further exploration of vaccines and immunoglobulins is also required. Finally, the remaining antibiotics must be used in the most effective ways. Colistin was under-dosed in the early days and this encouraged the development of resistance, he explained.
Two factors have driven the current situation, namely, overuse of antibiotics and poor infection control. Unfortunately, there was a common feeling that where MRSA is concerned, infection control is expensive and not worth the effort. However, different strategies are needed for different pathogens. For MRSA, the nose should be the target, and for enterobacteria, the intestine should be the target. Aggressive infection control in Israel, for example, has been very successful, he noted.
Intelligent decision support
Only 50% of patients benefit from drug treatment and some are actually made worse by their treatment, according to Walter Haefeli (Professor of Clinical Pharmacology and Pharmaco-epidemiology, University of Heidelberg, Germany). For this reason it makes sense to examine the medication use process, he argued. About 50% of prescribing errors occur on the day of admission to hospital and 80% occur within the first three days, he added.
Physicians make dosing errors and need information at the point of prescribing, especially regarding dosage adjustment for renal impairment. It is widely believed that computerised prescribing (or computerised physician order entry (CPOE)) coupled with decision-support systems (DSS) can improve the quality of prescribing and therefore improve patient safety. However, so far only two studies have shown positive clinical benefit. This may be because many other factors influence clinical outcomes, commented Professor Haefeli. Furthermore, alerting systems are still relatively clumsy and often cause ‘alert fatigue’ where 95% of alerts are simply ignored. One study examined the effects of the interaction between itraconazole and simvastatin.
Itraconazole causes in sharp increase in the absorption of simvastatin but not pravastatin, so a dose-reduction alert was built into the CPOE system. When the prescribing of the combination was examined, only 50% of patients were prescribed an overdose and therefore 50% of alerts were inappropriate. A different situation arose with ciprofloxacin and multivalent cations such as aluminium and magnesium, found in antacids. A ‘simple’ system would produce an alert every time ciprofloxacin was prescribed with an antacid but an intelligent electronic decision support system has been devised that is only triggered by oral doses of ciprofloxacin and antacid prescribed at the same time, but not for doses given at different times or for intravenous ciprofloxacin and oral antacid.
Professor Haefeli concluded that single step modifications are unlikely to have a big impact on outcomes. CPOE with DSS remains an indispensable part of drug treatment but decision support systems must become more specific to become useful and widely accepted.
Medicines reconciliation is critical each time a patient transfers from one care setting to another, according to Gordon Thomson (Head of Clinical Pharmacy Development, NHS Tayside, Scotland). Medicines reconciliation has been defined as, “the process of obtaining an up-to-date and accurate medication list that has been compared with the most recently available information and has documented any discrepancies, changes, deletions or additions resulting in a complete list of medications accurately communicated”. Two case examples illustrated how badly things can go wrong without this process. A patient with well-controlled Parkinson’s disease was admitted for a chest infection but the administration times of the anti-parkinsonian treatment were not recorded. The patient lost the ability to swallow and required extra hospital days and unnecessary antibiotics. An anticoagulated patient was admitted for elective surgery but discharged without warfarin and suffered an ischaemic stroke four weeks later.
Over the past few years a rigorous programme has been implemented as part of the Scottish Patient Safety Programme (SPSP) to ensure that medicines reconciliation is embedded into the patient care process. In addition, it has become a core part of training for all doctors, pharmacists, nurses and pharmacy technicians.
Risk management plans
The number of oral or self-injectable, expensive biologic drugs is increasing. If patients taking these products experience side effects or problems in use then these will occur in the home and this represents an opportunity for community pharmacists, argued Olivier Bugnon (Professor of Pharmacy, University of Lausanne, Switzerland). Many of these medicines carry a black triangle on the label indicating the need for additional post-marketing monitoring. What is needed is risk management plans implemented by community pharmacists, said Professor Bugnon. He gave the example of a service to monitor patients who had been prescribed fingolimod (Gilenya) for relapsing and remitting multiple sclerosis. These patients have complex treatment plans commonly involving input from several different specialties.
Pharmacists conducted motivational interviews with patients, monitored adherence to treatment using electronic pill-boxes and then had face-to-face feedback consultations. During these sessions both patient and pharmacist were able to review the web-based treatment plan and graphic representation of adherence results. It was more like coaching a patient than anything else, said Professor Bugnon. So far, 43 patients have been enrolled and more than 5000 days of treatment have been logged. A higher incidence of headache and fatigue than reported in clinical trials has been found and one severe arrhythmia was identified. A similar project involving patients who self-administer subcutaneous immunoglobulins is now underway. These services are recognised and paid for by the Swiss health insurance companies.
“Now that income from traditional dispensing activities is falling, pharmacists should seize this opportunity”, said Professor Bugnon.
Training home care employees, such as nurse aids and helpers, to recognise ‘red flags’, such as bruising in an anticoagulated patient, can alert healthcare professionals to drug-related problems in house-bound elderly patients, explained Marieke Schuurmans (Professor of Nursing, Utrecht University Medical Centre, The Netherlands). The over-75s take five times more medicines than young people and are therefore at greater risk of drug-related problems. While many studies have focused on prescribing and dispensing, the question of how medicines are taken in the home receives little attention. The fact that 3–10% of acute admissions are drug-related suggests that there are problems, said Professor Schuurmans. User-related problems with medicines have been identified in 26% of community-dwelling older people, she said. “Look behind the front door – there is often evidence of medicines not taken as intended”, she advised.
Professor Schuurmans and her colleagues realised that healthcare employees who visit elderly patients at home could identify the ‘red flags’ that suggest drug-related problems if they knew what to look for. Pharmacists and nurses then collaborated to develop the Home care Observation of Medication related problems by home care Employees (HOME) instrument – a simple questionnaire that allows home care personnel to identify ‘red flags’. The information can then be passed to a doctor, specialist nurse or pharmacist for action. In a pilot study, 234 red flags were recorded in 92 patients. Of these, 116 (50%) were considered to be potentially drug-related. Sensitivity ranged from 0.1 to 0.75 and specificity ranged from 0.70 to 0.97. The HOME instrument has now been built into an app for electronic use.
People with intellectual disability (also known as learning difficulties in the UK) are often prescribed combinations of psychotropic drugs, said Martin Henman (Associate Professor, Department of Pharmacy,Trinity College, Dublin, Ireland). The factors that contribute to psychotropic polypharmacy include the level of intellectual disability, sleep disturbance, living in residential care and the number of mental health diagnoses. Age is not a factor, he emphasised.
One important result of psychotropic polypharmacy can be a high anticholinergic burden as many of these drugs have anticholinergic effects. A study of elderly patients with intellectual disability conducted in Ireland showed that 70% were exposed to anticholinergic activity and nearly 30% had an anticholinergic burden (ACB) score of 5 or more (a score of 3 or more is considered to be clinically relevant). Further investigations had shown that the higher the ACB score, the greater the likelihood of central and peripheral anticholinergic effects, such as dozing during the day and suffering from constipation that required laxative treatment. A high ACB also predisposes patients to the risk of cognitive slowing and falls, added Professor Henman. In addition, combinations of psychotropic drug use could contribute to the high levels of obesity, metabolic syndrome and diabetes in this population, and may predispose to premature mortality, he said.
In conclusion, Professor Henman commented that this is a group of patients that needs the safeguards that pharmacists can offer because they are unable to argue the case for themselves.
Antipsychotics in dementia
Describing pharmacy care for people with dementia, Ian Maidment (Senior lecturer, University of Aston, Birmingham, UK) said that in 2009 in the UK, some 1800 excess deaths were attributed to the use of antipsychotics in dementia patients. Since then, there have been a number of projects to reduce the level prescribing of antipsychotic drugs in dementia patients. In one study, medication reviews were performed for 86 patients and 162 medicines for potential discontinuation were identified. One case involved a patient who was prescribed lorazepam in the afternoon and zopiclone at night. Seven medicines were discontinued for a patient with end-stage dementia; one of these was a salbutamol inhaler which the patient could not use but staff said they “sprayed it around and hoped for the best”.
Other studies have shown that many older people with dementia were receiving inappropriate medication. Demented patients cannot self-advocate or complain and so much of the burden for medicines management falls on carers, explained Dr Maidment. He concluded that there are significant medicines management issues in dementia and an urgent need for further research in this area.
The ESCP congress, Patient safety: bridging the gaps, was held in Copenhagen, 22–24 October 2014