Antibiotic resistance is a global problem of increasing importance. With the antibiotic pipeline nearly empty and new drug development years from fruition, antimicrobial stewardship policies and practices are going to play a big role in ensuring patient safety. From implementation strategies to optimizing antibiotic usage, Prof. Nathwani, a global leader in the field, will outline key issues involved in antimicrobial stewardship.
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Consultant Physician & Honorary Professor of Infection, Ninewells Hospital & Medical School, Dundee, UK; Chairman of Scottish Government Funded Scottish Antimicrobial Prescribing Group (SAPG); Chair of the European Study Group on Antibiotic Policies; President-Elect British Society for Antimicrobial Chemotherapy (BSAC); National Specialty Adviser for Infectious Disease to the Scottish Government Health Department; Chair of BSAC UK OPAT group.
Professor Nathwani answers your questions
Q: It says stewardship is a fairly new concept. So if this is to be implemented into the tertiary hospital, who should be the noted person for that purpose?
Prof. NATHWANI: I think that really could be where the clinical leadership in your organization in relation to expertise for infection management, so that could be an infection disease physician with an antimicrobial pharmacist, it could be a physician with an interest in infection, provided that he is supported with the expertise of infection management, or in some organizations there are surgeons and physicians who are very interested in infection leading the antimicrobial stewardship program. So I think that we mustn’t get fixated on it being a particular person. I think it’s very much dependent on what resource you have in your organization. But traditionally, it’s usually an infection specialist that is the main person responsible for antimicrobial stewardship, normally supported by a pharmacist and others.
Q: How can we implement a stewardship program in a community setting?
Prof. NATHWANI: I think that the data is emerging that the role of stewardship is as important in community hospitals as tertiary hospitals. Here I think you’ve got to identify what the key drivers for stewardship are, what is the available expertise? For example, many community hospitals in my country have primarily elderly patients, and we work very closely with our medicine for the elderly physicians to support them and agree upon the key intervention. So I think that there are ways and means of ensuring stewardship within a tertiary program by using what you have in terms of infection-related expertise and resource.
Q: How can we implement a stewardship program in a tertiary hospital when the hospital administrator is not buying into the program?
Prof. NATHWANI: I don’t think you are unique, and I think that you have to articulate to them that if they do not have an antimicrobial stewardship program, their patients will come to harm. And I think that I really titled this presentation because this would become a patient safety issue. And when patients will come to harm, the reputation of the hospital, the medical/legal consequences of that hospital will be severely dented. And I think that that would also lead to quite a significant increase in cost. Certainly when you go back many years and you look for the argument for preventing healthcare acquired infections, the economic argument was profoundly strong in the terms of if you allow this to happen, then not only will it be costly, but your patients will come to harm and people will be reluctant to be admitted to your organization for healthcare intervention because your program is unsafe. And I think that’s the kind of argument that I would embark upon.
Q: It says in terms of choosing based on a quick improvement potential, if you were to focus on a single unit in a hospital, which one would that be, or does it really depend on the particular hospital?
Prof. NATHWANI: It depends on the particular hospital. I think the use of certain specific high risk agents, depending on the kind of problem that you have and whether it can be a quick win, and I think surgical prophylaxis is universally badly done, and I think that is something that you can do in a relatively short timeframe with good results that will allow further organizational engagement with your future program.
Q: I am from a developing country and most antimicrobial prescriptions are done without lab results. What can be done to reduce antimicrobial resistance in developing countries, given that most of the time lab facilities are not available?
Prof. NATHWANI: I think, and here lies the problem, it’s a chicken and an egg problem. I was in India and Southeast Asia listening to the concerns about stewardship, and I think one of the solutions is really getting down to the education level of the importance of taking a specimen, because without that, gauging the appropriateness of therapy is very difficult. In the situations when they haven’t taken a culture, what we need to maybe convince clinicians is that shorter periods of therapy are as effective as long periods of therapy, and there’s no doubt in my mind that if the patient is getting better and you haven’t got positive microbiology, encourage and persuade them, unless there’s obviously a deep seeded infection or so on, to use a shorter course of therapy, as that is much less of a driver for resistance.
Q: Combating antimicrobial resistance encompasses the whole of the healthcare system everywhere. What are the minimum resources that should be available in a resource-limited setting to follow the stewardship guidelines?
Prof. NATHWANI: It’s a difficult question to answer, but I think that that resource should be locally determined. I think the minimum requirement should be with a team, a relatively small team that has somebody who’s a credible leader and an expert in infection management, supported by a nurse interested or a pharmacist interested in that area would, to me, be a minimum resource required. But I think you do need that expertise and leadership, as demonstrated in one of the slides that I showed you around the core components of stewardship.
Q: What biomarkers and rapid diagnostic tests should be used regularly in the routine pallet in hospitals to best support a stewardship program?
Prof. NATHWANI: Again, that is a challenging question, depending on what resources you have available. The data to support the use of procalcitonin is very powerful in the critical care setting, particularly for respiratory tract infections, so I would tend to favor the use of procalcitonin in that particular arena. The value of C-reactive protein is less sure across the range of infections, so I think that in terms of a biomarker, if you have the resource to be able to support the use of biomarkers, I’ll tend to prefer the use of procalcitonin, particularly in the therapeutics area that I’ve just outlined.
Q: Is antimicrobial stewardship with H. pylori important or not?
Prof. NATHWANI: I’ve been intrigued in this area because there is a large amount of antimicrobial use for the management of peptic ulcer disease. There is some emerging evidence that for resistance, for example to materialize in certain healthcare settings, that it may be driven by the use of eradication therapy. Whether I can show you some powerful evidence of cause and effect, I can’t, and I think that data remains to be seen. But you would think that, wouldn’t you, that if there was excessive pressure on the use of these antibiotics, then resistance may occur.
Q: In one of your slides, it said when the 4C reduced C. diff. Was there any increase in serious infections and/or mortality?
Prof. NATHWANI: I’m really glad you asked that question because one of the key concerns my colleagues and clinicians expressed to me by restricting the use of the range of antibiotics as a 4C, as you refer in this case, that they would see more infection, they will see more complications, they would see more admissions to the critical care settings, and we have very eloquent data to show you that there was no increase in 30 day or cause mortality, there was no increase in admissions to surgical and medical as a high dependency unit or intensive care unit, so we certainly have segregate markers to suggest that patient outcomes were not compromised as a result of reduction in the 4C’s.
Q: Do you know if using probiotics for patients who have been started on antibiotics has shown any promise in decreasing CDI’s [Clostridium difficile infections]?
Prof. NATHWANI: There is some very peripheral early data to suggest that, but the jury is very equivocal and I’m not sure I can provide you with enough data to suggest that that should be an encouraging direction. But there is certainly some data to support that.
Q: Any antibiotic use has micro evolutionary consequences in an individual, and mass overuse may negatively impact future treatment of populations. So is the current stewardship initiative sufficient to convince local hospitals and physicians of this evolutionary reality and that antibiotic administration must be greatly reduced? I guess that’s an opinion question.
Prof. NATHWANI: Yes, I think that – again, that’s a very perceptive question. So after a fairly intensive six-year stewardship program focusing on a range of antibiotics, we’re very aware of the squeezing balloon effect, and we perhaps are now beginning to think that we need to practice a broader diversity in our strategic direction of what we suggest. So we’re beginning to see that some of the antibiotics that we’re particularly restrictive about, we’re now, in a sense, loosening the strings to allow people to use not only those, but a range of other antibiotics that perhaps give that particular hospital setting or tertiary or community center broader diversity. So, in a sense you don’t allow the squeezing the balloon effect and you get the physicians to stop using the antibiotics that you’ve overused. I think this is interesting work and we’re about to publish some interesting early data about our experience in doing so. Again, a very good question, but I’m not sure if I can give you a clear-cut answer except the experience that I’ve just shared with you.
Q: What is the evidence for appropriate empiric antibiotic use, for example, in septic patients?
Prof. NATHWANI: I think there is very powerful evidence that if you get your treatment in terms of choice and root and timeliness, particularly in those with serious infections, then your outcomes will be better. There have been a couple of systematic reviews in the critical care setting, and reviews in patients with only sepsis as compared to severe sepsis. I think there is not only existing evidence but a powerful range of emerging evidence to show that appropriateness is important in terms of outcomes, particularly in relation to serious infections. The evidence for less serious infections is perhaps less dominant.
Q: Could you please comment on penicillin allergy? I am from a low resistance country and penicillins are still widely used, but patient-reported penicillin allergies very often results in a change to broad spectrum quinolones. What do you do in an emergency setting?
Prof. NATHWANI: We have the same problem, and we have some data to suggest that most patient-reported allergic reactions are not true allergic reactions but rather intolerance. So in my view, unless they present – and this is – they have to be unwell and they’re in the hospital where it’s a supervised setting-- we take a very stringent view that unless they have history of anaphylaxis or one of the related symptoms of anaphylaxis, or a clear cut rash, we would endeavor to give penicillin, and only in other situations would we use an alternative like a quinolone or something else. I think you have to be very clear in what you understand by true penicillin allergy or intolerance.
Q: What role does the microbiology lab play in the stewardship team effort?
Prof. NATHWANI: I think the microbiology lab plays a pivotal role. They play a role not only in ensuring that the laboratory investigations are returned in a timely and appropriate manner, but also in certain situations, we provide selective reporting, so we do not give all sensitivities in the hope that they will stop using these antibiotics to treat what often is the case is asymptomatic bacteria. And I think in the next decade with the new evolving rapid diagnostics, the microbiology laboratories will play an even more critical role as long as, as I’ve shown in one of my slides, they’re very strongly aligned to the implementation arm, which is the antimicrobial stewardship. So I think that is an important partnership over the next five to ten years if we’re going to really make stewardship effective.
Q: What is the role of a pharmacist in the antimicrobial stewardship program?
Prof. NATHWANI: Pivotal. To me, antimicrobial stewardship in my country, and I suspect in many other countries, would not be possible without the pharmacist, and we have at great lengths in this presentation talked about the role of the antimicrobial pharmacist, they are a part of the antimicrobial management team. But to me, the ward-based clinical pharmacists are the eyes, the ears and the intelligence on the antimicrobial management team telling us where the inappropriate or poor prescribing is happening so that we can actually then go and review the patient and provide, hopefully, an effective positive intervention. So I think they are absolutely critical, and I implore any countries that do not have clinical pharmacists or the role of the clinical pharmacist has not evolved in a kind of clinical way, I think that it is high time they did, because without them, and also nurses, we cannot have an effective stewardship program across the whole organization.
Q: And what role do nurses play in this kind of program?
Prof. NATHWANI: I think they need to play a much more pivotal role than they currently do. Australia is one of the first countries that are really evolving and developing the skillset of the nurses - they have done infection control for 20 to 25 years. Why can they not support antimicrobial stewardship, and join the agenda? So we are now developing skills and competencies for ward-based nurses around leadership, as well as around basic knowledge for stewardship, and I think they will have a very crucial role in our stewardship programs as we go into the next five to ten years, and I would encourage you across the world to consider that particular resource also.