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Published on 29 April 2009

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Pharmacists at the forefront in the fight against disease

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Cutting-edge developments in medicines management, improved therapeutic use of medicines and new approaches to patient safety were all headline topics at the recent UKCPA symposium

Laurence A Goldberg
FRharmS
Editorial Consultant
HPE

The UKCPA Autumn Symposium was held in Hinckley, Leicestershire, in November 2008

The use of the multivariate time-series analysis model has enabled researchers in Northern Ireland to identify the antibiotics most likely to increase the incidence of hospital-acquired MRSA and the factors that are most helpful in decreasing the incidence of infection, Mamoon Aldeyab (Postdoctoral research fellow, Queen’s University, Belfast) told the audience.

Infection control for MRSA
Presenting the Novartis Antimicrobial Management Award lecture, Dr Aldeyab explained that both infection control practices and antibiotic prescribing policies have been advocated as influencing the spread of MRSA. Time-series analysis is said to be the strongest quasiexperimental method to study the impact of a number of healthcare interventions. It can take into account the lag times between interventions and effects and can describe rising level of resistance. Without such an approach significant relationships could be missed, he said.

A retrospective analysis of hospital infection surveillance data over a five-year time period was performed. The results showed that use of antibiotics, especially third-generation ephalosporins, was associated with increasing incidence of hospital-acquired MRSA (HAMRSA). Just five extra patients treated with a third-generation cephalosporin would result in the occurrence of one extra HA-MRSA case after an average delay of two months. In contrast, an additional 67 patients would have to be treated with a macrolide antibiotic to cause one extra case of HA-MRSA, the effect being seen after an average delay of four months. Two factors that reduced the frequency of infection were bulk orders for alcohol-based hand-rubs and screening of patients for MRSA. Both were associated with delays of three to four months.

“Screening is considered to be an essential strategy to identify reservoirs of infection,” explained Dr Aldeyab. However, it can take 48-80 hours to identify MRSA, and faster tests such as those based on polymerase chain reaction methods are important.

Measuring the delay required to observe an effect following the restriction or introduction of an antibiotic using the time-series analysis technique could be a possible way forward in determining the optimal time required for an antibiotic restriction policy, concluded Dr Aldeyab. In practice, fluoroquinolones and third-generation cephalosporins had been restricted at Antrim Hospital where the study was carried out. The use of antibiotics should be restricted cyclically, based on the lag times for effect, said Dr Aldeyab.

Intensive insulin therapy
Intensive insulin therapy can achieve tight glycaemic control in critically ill patients and is associated with improved 28-day survival, according to Rob Shulman (lead pharmacist, Critical Care, University College London Hospitals, and honorary senior lecturer, School of Pharmacy, University of London).

Intensive insulin therapy (IIT) is associated with reduction in mortality, but aiming for blood glucose levels of 4.4-6.1 mmol/l can cause hypoglycaemia, and some studies have been terminated early for this reason. A new IIT protocol had been devised, building on some of the findings from earlier studies, explained Dr Shulman.

A retrospective study compared blood glucose control and mortality in three groups of critically ill, ventilated and nonventilated patients – those given conventional insulin therapy (CIT), those given IIT according to the original protocol (IIT1) and those given IIT by the revised protocol (IIT2).

The results showed that patients in the CIT and IIT1 groups spent about 20% of their time in the target blood glucose range, whereas IIT2 patients were in the target range for 35% of the time. There was no increase in hypoglycaemia, and no more blood glucose readings were required in the IIT2 group than in the CIT group. Survival at 28 days was 75%, 68% and 48% in the IIT2, IIT1 and CIT groups.

The improvement in mortality might be due to metabolic effects of insulin other than blood glucose control, and changes in practice over time might also have accounted for some of the improvements, noted Dr Shulman.

Dr Shulman received the Lilly Critical Care Award 2008 for this piece of work.

Outpatient antibiotic therapy (OPAT)
Outpatient antibiotic therapy (OPAT) offers benefits in patient care, infection control and healthcare costs, according to Mark Gilchrist (lead pharmacist, Infectious Diseases, Charing Cross Hospital, London). Describing the service at his hospital, he said that suitable patients were medically stable, with infections that were not life-threatening and were responding to treatment. They should also be willing to return to hospital for treatment and have good home environments and family support. The UK OPAT registry shows that the infections most commonly treated in this way are cellulitis, osteomyelitis and postoperative wound infections. A total of 95 patients received OPAT in his hospital during 2007-08, and 2467 bed-days were saved as a result. Critically, 45% of these were for MRSA-colonised patients, which are potentially costly for the trust.

Trigger factors to identify ADEs
The use of trigger tools to identify adverse drug events (ADEs) in hospital inpatients may not be the most efficient method for ongoing detection of these episodes, concluded Gillian Cavell (King’s College Hospital NHS Foundation Trust, London). The exact incidence of ADEs in hospital inpatients in the UK is unknown because measurement relies on voluntary reporting. The use of a trigger tool – an approach that involves retrospective searches of records for selected indicators of ADEs – has been advocated by the Institute of Health Improvement
in the USA as a means of identifying and monitoring the incidence of ADEs.

An ADE trigger list was drawn up based on previous work. The list included medication triggers, such as antiemetics or plasma expanders, general care triggers, such as oversedation or falls, and laboratory triggers, such as a fall in haemoglobin of more than 25%. A total of 56 triggers were identified in 50 patients. Of these, eight patients were judged to have experienced an ADE categorised as group E: “temporary harm not requiring or prolonging hospitalisation”. The most serious event was a collapse following a dose of tamsulosin, a recognised side-effect of alpha-blockers, noted Ms Cavell.

More than 23 hours was spent reviewing notes for this study and no serious ADEs were identified, although between two and four could have been expected, based on published estimates. The review process also duplicates some of the work that is done routinely by pharmacists as part of the care process, commented Ms Cavell.

Avoiding penicillin allergy
Storing penicillins in separate medicine cupboards prompts nurses to make allergy checks, but the system falls down if the cupboard contents get mixed up, explained Alice Oborne (Guy’s and St Thomas’ NHS Foundation Trust, London).

Allergy to penicillins is the most frequent cause of drug-induced immunological conditions, but nurses are not always able to identify penicillins accurately. A study was performed to assess the impact of separate storage on allergy-checking practices and knowledge about penicillins. In the study hospital, patients’ allergy status is shown on their identity wristbands. The penicillin cupboard was labelled with a notice saying “Stop – check allergies. Do not give to patients allergic to penicillins”.

The results showed that checks of allergy status were made on 89% of occasions when a separate cupboard was used, compared with 47% when storage was not separated. However, during 17 routine cupboard checks non-beta-lactams were found in the cupboard on seven occasions and beta-lactams were found in the main medicines cupboards on six occasions. Clearly, the benefits of the cupboard would be lost in these circumstances, said Dr Oborne.

Patient-inspired research
Pharmacists are uniquely placed to connect early research with the end-user because they understand the medicine, patient, GP, surgeon and practical elements of procurement and distribution, argued Steve Brocchini (School of Pharmacy, University of London). Patientinspired research is about keeping your eye on the ball and spotting opportunities and needs. Moreover, making the effort to translate research can further refine our ability to teach with a more critical eye, he continued.

An example of the kind of thinking that is needed is provided by proteins and poorly soluble drugs. Proteins are quickly cleared from the body so that it is impossible to determine dose-response relationships, and frequent dosing is necessary. In fact, rapid clearance of proteins from the body is a undamental problem that is limiting the widespread development of protein-based medicines, he said. New approaches are now needed to make better protein products with longer half-lives. New methods of PEGylation, exploiting disulphide bonds, might be one way forward.

Another example is a polymer-linked amphotericin B (PolyAmB) that is used to treat leishmaniasis in India, where AmBisome (liposomal amphotericin) is too expensive.

Schools of pharmacy straddle both the basic science and the application endpoints of research. Furthermore, pharmacy is a profession that understands goals and milestones, and this means that it is well positioned from a business perspective.

Pharmacists will continue to become even greater stakeholders in helping to influence the development of new treatments, predicted Dr Brocchini.



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