Past, present & future

Following on from Professor Oxford’s reflections, the GRIP meeting set out to look at achievements to date, activities that are happening now and those that will deliver results in the future. To begin, long-term members were asked to give an update, reflecting on progress and forthcoming activities.

Setting the scene, Mr Adrian Shephard, from RB, said GRIP was based around an era where a number of antibiotics are useless in clinical practice, primarily because of their inappropriate usage. GRIP has consistently shown its commitment to sustainable, evidence-based interventions for the rational use of antibiotics and antibiotics stewardship.

Focus on an area where antibiotics really shouldn’t play much of a role – upper respiratory tract infections – has paid dividends through the multi-stakeholder group that is GRIP. Partnerships between policy makers, prescribers, pharmacists and patients has achieved much, but the rise in resistance continues.

The stark headlines around operations that won’t be possible in the future, the needless deaths caused by resistance and continual spread of infectious disease point continuously to the need for more action. “Progress has been made,” Mr Shephard concluded, “But there is still much more that can be done. Challenges exist around resistance, mass availability and animal usage. Education of professionals and patients is vital. There remains much to be done.”

Australia, John Bell

Australia still has quite a high use of antibiotics and this is not something we are proud of, said John Bell. One group, NPS Medicinewise, has had a concerted effort to encourage the appropriate use of antibiotics in Australia. The program had some notable successes, said Mr Bell, encouraging consumers to become ‘Resistance Fighters’.

While this initiative has come to a close, Mr Bell said he would continue to be lobby for investment in educating consumers.

As part of the Australian Government’s National Antimicrobial Resistance Strategy 2015–2019, the Australian Commission on Safety and Quality in Health Care was funded by the Department of Health to establish and coordinate a national surveillance system for Antimicrobial Use and Resistance in Australia (AURA).

Published this year, the Second Australian Report on Antimicrobial Use and Resistance in Human Health found that, while antibiotic usage declined 9.2% between 2010 and 2015 in hospitals, challenges remained.

Some 23.3% of prescribing did not comply with guidelines; 21.9% of prescriptions were assessed as inappropriate. Of surgical prophylaxis prescriptions, 27.4% were continued for longer than 24 hours (less than 5% is considered best practice).
The most common reasons that hospital prescriptions were deemed to be inappropriate were:

An antimicrobial was not needed (19.6%)
The antimicrobial chosen was incorrect (spectrum too broad: 25.2%)
The duration of treatment (17.7%) or the dose was incorrect (19.5%).

Looking at community-based healthcare, the report also found that there had been little reduction in the 30 million antimicrobial prescriptions dispensed through the Pharmaceutical Benefits Scheme/Repatriation Pharmaceutical Benefits Scheme since 2008.

In particular, prescribing antimicrobials to treat respiratory tract infections remains common, with more than 60% of patients prescribed an antimicrobial, despite the fact that antimicrobials are usually not recommended for these conditions.

As a result, the report authors have called for an intensification of community-efforts to control prescribing.

"More than 60% of patients were prescribed an antimicrobial to treat respiratory tract infections, despite the fact that antimicrobials are usually not recommended for these conditions."

Italy, Dr Aurelia Sessa

Annually 1 in every 4 people in Italy has a respiratory tract infection. In total, 85% of antibiotic prescriptions come from primary care, said Dr Sessa. This is the reason why education and interventions on antibiotic management are so important in Italy. Fuelled by historical data, the initiative, called Progetto G.A.I.A. (Gestione Appropriatezza In Antibioticoterapia), looked to:

Improve prescribing appropriateness (efficiency, efficacy and safe) of treatment of the URTI and LRTI
Adopt logical and rational empiric therapy in out-patients
Choose the appropriate medication for that RT infection, in that patient, with the right dosage and in the right duration to optimize outcomes
Identify appropriateness and inappropriateness indicators for correct or incorrect use of antibiotics.

"We are adopting a logical and rational, empirical approach to the patient for the therapy."

To date the team have created a scientific board, defined the content of educational material, and are sharing this with over 100 GPs. The group have also looked to retrospectively collect prescription data to look at indicators of appropriate prescribing in this area.

To date some 20 indicators of inappropriate prescribing have been identified including:

Number of patients who received an antibiotic prescription (numerator) of the total of patients of diagnosis of URTI (denominator)
Number of patients who received a prescription of quinolones, cephalosporins or macrolides (numerator) in bacteria URTI in patients with no asthma, chronic obstructive pulmonary disease (COPD) or penicillin allergy (denominator)
Number of patients who received a prescription of quinolones, cephalosporins or macrolides (numerator) in acute bronchitis in patients with no asthma or COPD (denominator)
Number of patients who received a first-line prescription of quinolones (numerator) in patients with exacerbation of COPD age <65 year and with no comorbidity without a prescription of penicillin or cephalosporin in the previous 30 days for another COPD exacerbation (denominator)

Appropriate indicators included:

Number of patients with exacerbation of COPD (GOLD 1 and 2) without comorbidity (asthma, heart failure, CHD/stroke, diabetes), age ≤ 65, who received a prescription of penicillins or oral cephalosporin (numerator) of the total of patients with exacerbation of COPD who received any antibiotic prescription (denominator)
Number of patients with exacerbation of COPD (GOLD 3 and 4) age > 65, with any comorbidity (heart diseases, stroke, diabetes) who received a prescription of protected penicillin, cephalosporin, macrolides, parenteral antibiotic or quinolones (numerator) of the total of patients with exacerbation of COPD who received any antibiotic prescription (denominator)
Number of patients with community acquired pneumonia (CAP) without comorbidity (asthma, COPD, heart failure, CHD/stroke, diabetes) who received a prescription of penicillins or macrolides or tetracyclins (numerator) of the total of patients with CAP who received any antibiotic prescription (denominator)

When the project ends in 2018, Dr Sessa says the team hope to be able to:

Collect the data of RTI of all GPs participants, including therapies, investigations and other related prescriptions and compare appropriateness and inappropriate indicators over time
Show how this innovative model is capable of impacting on professional performances of the GPs of the network
Drive adoption among other GPs
Influence health authority policies

USA, Doug Burgoyne

The USA has been approving a host of new anti-infectives, said Mr Burgoyne, with nine in 2015 and four so far this year in 2017.

While the majority of these are antivirals, they have received a lot of publicity in the USA, often due to their high cost. Access to these products, including the new antibiotics, is controlled through the managed care plans, meaning that the insurance companies and the pharmacy benefit management companies are putting restrictions into place on usage.

There are two reasons for this, Dr Burgoyne said: firstly an attempt to control resistance to these new products, and secondly, and probably more influential, cost. “When there’s an antibiotic that’s $5, for example, compared to one that’s $500, then it’s in the payer’s best interest to use the lower cost one.” As a result, while the resistance message is shared within the United States community, it is generally ignored by the managed care industry.

Finding the right place to start campaigns around appropriate usage is difficult, Dr Burgoyne said. If you start an antibiotic resistance campaign with an employer group, you can influence 500 or 5,000 or 50,000 people, however if you start with an insurance company, you can influence a couple of million people. But, he continued, if people change jobs and subsequently insurance schemes, then those efforts may be lost, and people stop hearing the message about antibiotic resistance. So managed care has generally taken a step back away from doing too much.

"There’s this strange world where we talk about antibiotic resistance, we know it’s a problem, the community knows it’s a problem, physicians recognise there are issues, but nobody is really putting enough effort into doing anything about it outside of the hospital."

One growing trend that may also have an impact on antibiotic resistance is a change in how consumers engage with retail pharmacy. Large chains like CVS which are attempting to be a ‘one stop shop’, replacing the GP office. Services offered include drop in clinics, where patients can go to the pharmacy, see a nurse practitioner, and be diagnosed for one of about 25 different conditions, including respiratory tract infections.

“While we haven’t analysed the data yet, our hypothesis is that nine times out of ten, someone with a respiratory infection will walk out with an antibiotic,” said Dr Burgoyne. Customer satisfaction is the number one driver of care, he continued, and every pharmacy will want to have a good score on Google or on some other type of consumer website, and this may lead to inappropriate demands.

On the positive, every pharmacy offers a wide arrange of products that offer effective symptom relief. Consumers may also be more willing to listen to pharmacists telling them they don’t need an antibiotic because “there’s a different level of trust with a pharmacist; in fact, when a pharmacist tells a patient you don’t need something, it generally improves the trust relationship between patient and pharmacist,” Dr Burgoyne concluded.

India, Dr Ashok Mahashur

Within India, the responsibility for antimicrobial prescriptions lies firmly with physicians, said Dr Mahashur. This situation is complicated however by the different types of practitioners in India, from qualified practitioners, to an equal number of unqualified practitioners who remain outside of the regulatory authorities’ control, yet may still dispense antibiotics if requested by patients.

To address this, a pilot project involving some 992 patients was run in India in three localities:

A slum area because this is often where the number of non-qualified doctors exceeds the number of qualified doctors, but also because this population experience poor hygiene conditions and are very prone to infections
A mid-class locality because these populations are often very concerned about their health and visit doctors frequently
And a wealthy locality with five star hospitals

The pilot placed interns or final year students in the Pharmacy to review doctors’ prescriptions. Patients were also questioned around their symptoms to check the diagnosis of upper respiratory tract infection. In many cases on reviewing prescriptions it was difficult to determine what the prescription was for. While the highest number of prescriptions for antibiotics came from the non-qualified doctor group (21%), some 17% came from the middle group populated by qualified doctors. Quinolones and macrolides topped the prescribing list.

"What makes this most worrying, said Dr Mahashur, was the use of these drugs in respiratory tract infections given a background of rampant tuberculosis in India and resistance to these valuable drugs."

Summarising the study, Dr Mahashur said evidence suggests that acute, uncomplicated upper respiratory tract infections frequently are treated with antibiotics in the Indian settings.

The question then remains why do the doctors prescribe these antibiotics indiscriminately? There could be financial considerations, doctors are keen not to lose the patient to another doctor; there could be diagnostic uncertainty, due to a lack of facilities to diagnose viral infections; and there is pressure on a doctors time.

In conclusion, Dr Mahashur said the development of guidelines and doctor and patient education were critical in preventing antimicrobial resistance.

Brazil, Professor Antonio Carlos Pignatari

prescribing remains an issue among clinical specialists, said Professor Pignatari.

Initiatives in hospitals are delivering some results, supported by those with an interest in antimicrobial stewardship, with a focus on “giving the right antibiotic at the right dose for individual patients”. Part of this has been ensuring that doctors understand prescribing mistakes are happening in hospital and the implications of errors.

Looking at the pharmacy environment in Brazil, legislative challenges have had a major impact. Previously, pharmacists were able to dispense products such as antibiotics without a prescription. This means that in terms of pure inappropriate supply challenges, this issue has been resolved in the pharmacy setting. However there is still much work to be done to ensure other healthcare provider settings continue to be educated, said Professor Pignatari.

"Policy change has had a major impact on inappropriate prescribing"

Netherlands, Dr Alike van der Velden

The Netherlands has done a lot to control inappropriate prescribing. However in a drive to improve efficiencies, online training has become a new focus areas for educating GPs, said Dr van der Velden. The RAAK project (Rational Antibiotic Use in Kids) is an online training programme for GPs with material for parents to enhance proper antibiotic use for children with respiratory tract infection (http://www.rationeelantibiotica.nl - http://www.rationeelantibiotica.nl/public/raak-informatiebrochure.pdf).

The team set out to understand the effectiveness of these interventions and how they impacted consultations.

Antibiotic prescribing rates were 21% in those that had had an intervention vs 33% in the control group. So this concise online training appeared to be effective in reducing antibiotic prescribing.

Separately in the Netherlands, the team have also been looking at out of hours service, trying to establish whether there was a pattern to these consultations and if they impacted in quality of care or inappropriate prescribing.

Results showed that the quality of antibiotic prescribing during out-of-hours care was comparable to office-hours. Tied to this was the investigation of an app called ‘Should I see a doctor?’, which was designed to help patients decide if they really needed physician care for acute symptoms.

“The app was meant as a self-triaging system for acute symptoms and to empower patients to make informed decisions about the need to consult,” said Dr van der Velden.

It encouraged patients with problematic symptoms to consult, but for others offered reassurance, on self-care advice and guidance on when to see a doctor.

Using a built-in questionnaire, it appeared that the app was used by patients of all ages and the majority of patients received the advice to call their own GP (the same day, or when app was used in the evening or weekend, the next day or Monday), or to call the out-of-hours clinic. Overall, 65% of patients intended to follow the advice.

One of the most important questions was the diagnostic accuracy of the app - did the app provide the correct advice?
Overall in 81% of cases, the app advice corresponded to the results of the triage call done by a nurse.

"I think a number of countries are looking for alternative ways to communicate with patients, importantly, patients do like these kinds of apps, so long as they are evidence-based and endorsed by GPs"

South Africa, Prof Sabiha Essack

Professor Essack focused her presentation on the GRIP ambassador work conducted over 2016 and 2017. Since the GRIP initiation, Professor Essack has been appointed as an expert consultant to the World Health Organisation Regional Office for Africa.

A critical enabler of local action plans is education and awareness. To date, as part of this, 5 workshops have been held covering almost all of the 47 countries in the WHO AFRO region.

In the context of global pharmacy, Professor Essack participated in a stakeholder roundtable on the responsibility with antimicrobial medicines, prior to the FIP meeting in Argentina 2016. GRIP’s Pentagonal Framework featured here.

Interviews were also held with Eduardo Savio, chairperson of the AMR working group of FIP. In exploring a potential partnership with FIP, Professor Essack was able to present the pharmacy practice and pharmacy resources, the need for pharmacy optimisation and communications. A key challenge to GRIP as a result of these meetings was proving the impact of these resources and improved outcomes to drive adoption more widely.

Separately, Professor Essack reflected on the keynote presentation she gave on the on the appropriate use of antibiotics at the 2nd National Pharmacy Conference in Durban, South Africa. This webinar went out live to 1,769 pharmacists in 12 African countries.

"I was able to showcase GRIP resources in all of my presentations nationally, regionally in Africa and internationally"

Looking closer to home, Professor Essack acknowledged that the pharmacy advisory group was formalised in South Africa in 2017 to discuss ways in which pharmacy could be advanced.
Leveraging existing resources, such as those of GRIP, has already been acknowledged as an important step forward.

Russia, Professor Roman Kozlov

Russia is making substantive steps in surveillance and research, said Professor Roman Kozlov, greatly influenced by support from the Russian Minister of Health (who has been elected chairman of the World Health Assembly for the coming year).

A pilot project that ran from February 2017 to June 2017 looked at reducing systemic antimicrobial use in outpatients linked to respiratory tract infections, concentrating on educating healthcare teams who engage patients at a primary care level, as well as public education. A number of channels were used to deliver the educational activities including a website for physicians, pharmacists and the general public, and social media channels, as well as colouring books for children. Information was provided on the classical pathway for a diagnosis of sore throat, how to use diagnostic aids like throat cultures as well as lectures from experts, such as clinical microbiologists, together with advice on how to manage patients.

Learnings from this pilot, supported by the Minister of Health, have applicability elsewhere, said Professor Kozlov. Pharmacists also remain an important target, he said, with opportunities to train through the pharmacy chains. The chains have also agreed to put posters in their pharmacies to help educate consumers.

However, messaging has also gained support from other channels including the Russian Post Office and the Russian Tax agency who have been displaying information to help educate the public as well.

Students were also particularly interested, especially military and physical education students, through lectures and ‘flash mobs’ activations.

Measuring the impact of these initiatives is challenging, Professor Koslov concluded because there are many variables that may impact on overall reduction in antimicrobial prescribing, however there is a high degree of transferability of these initiatives and government support will aid future uptake.

"The Russian Ministry of Health is very motivated by antimicrobial stewardship"

United Kingdom, Dr Martin Duerden

Barely a week goes by in the UK without some mention of the challenges caused by antibiotic resistance in the media, said Dr Duerden. In part this is triggered by the focus of Dame Sally Davis, the UK Chief Medical Officer, who has made the issue her life’s ambition to tackle.

Nonetheless, in the UK 60% of all antibiotic usage is for respiratory tract infections, said Dr Duerden, the vast majority of all those prescriptions come from the primary care setting.

To tackle this, guidelines have been established which try to address prescribing behaviours, as well as other initiatives such as comparative prescribing information within an area, and comparative resistance information within areas.

Public Health England (PHE) has been highly active, said Dr Duerden, helping to deliver a consistent message and encouraging everyone to work together in this field. In collaboration with PHE, the Royal College of General Practitioners has issued a set of TARGET resources designed to provide education and advice on the use of antibiotics, including a website, and training resources, feeding into the personal development plans that now guide GPs fitness to practice. Resources also target patients, encouraging self-care, and include posters and leaflets for patients as well as online advice around whether antimicrobials are required, and other treatment options.

The role of the community pharmacist has also been highlighted, not least because of an emerging issue with a shortage of doctors in primary care. Pharmacists could play an increasing role here, said Dr Duerden, helping to manage patients with symptoms and avoiding them unnecessarily presenting to GPs with upper respiratory tract infections.

In terms of impact, to date there has been a 7% reduction in prescribing between 2014 and 2015, but Dr Duerden questioned, is this real and will it be sustained?

"The problem is there is such a wide variation on the use of antibiotics and, it very much depends how bad the winter is. So, if we have a mild winter, you will get the 7% reduction in antibiotic usage. If we have a hard winter, I think that we’ll lose that benefit."