Antibiotics
Our Study and Understanding the Risks
Given that we are currently only recruiting for arms of the study that include the use of antibiotics, I want to address some potential questions and concerns. Here, I’ll give some of my thoughts on the risks involved with antibiotic use, as well as the reasoning behind our study design. What I say here is merely the start of what could be many different and more in-depth discussions. Please feel free to contact us with any questions that are not addressed here, or that arise from reading through this information!
Let me start by saying that antibiotic use is something that should not be done lightly and that I have thought carefully about how and when to utilize antibiotics in my research. Additionally, if you have ever experienced an adverse reaction to ciprofloxacin (or another fluoroquinolone antibiotic) in the past, you shouldn't be signing up for our study. That said, let me expand on some different aspects of antibiotic use.
First, there are possible public health effects from antibiotics. Any use increases the potential to spread antibiotic resistance within the broader community. In designing this study, we faced the tradeoff of this risk with the benefit of understanding the dynamics of the gut microbiota in response to common, medically-relevant perturbations (which includes antibiotic use). This is a troubling problem to tackle. It would be ideal to limit unnecessary antibiotic usage and only sample participants who are going to use them anyway (due to a medical need). However, there are several complicating factors that make it difficult to get adequate data from that sort of study. It can be hard to get sufficient pre-treatment samples to characterize the gut microbiota from before the antibiotic effect. Additionally, the underlying need for the antibiotics (whether a disease, infection, or medical procedure) can have its own impact on the microbiota; it can be difficult or impossible to disentangle this impact from that of the antibiotic. For these reasons, a study that examines the use of an antibiotic as an isolated variable has a lot of scientific value and, hopefully, the results could lead to more informed and judicious use of antibiotics in the future. In light of all this, in our judgement and that of the Institutional Review Board that approved this study, the tradeoff is worth making.
Aside from public health concerns, there are also personal risks for anyone taking antibiotics. There is the same resistance-related concern on an individual scale -- that taking an antibiotic could cause microbial resistance and prevent treatment of an infection with that antibiotic later on. From my perspective, this risk is not very large; there are few conditions for which ciprofloxacin is a first choice treatment (urinary tract infections are the main one). Moreover, cipro-resistant organisms are frequently still susceptible to other fluoroquinolones (e.g. levaquin).
Separate (as far as we know) from the antibiotic action of the drug, there are also be direct effects of ciprofloxacin on human physiology. There are potentially serious side effects to taking ciprofloxacin or other fluoroquinolones. The phrase “potentially serious side effects” can sound a bit clinical and distant, especially when it could include cases of death, debilitating and painful conditions, or conditions that are permanent or long-lasting. It is good to take these possibilities seriously, but to assess the real danger of antibiotics, it becomes a question of likelihoods and relative risks to benefits. Somewhat like driving a car, there are incredibly serious risks involved, but the usefulness and careful practice of antibiotic use can be weighed against the frequency of a negative outcomes.
Finding reliable data on the frequency of antibiotic side effects can be another slippery issue. The official (e.g. FDA, Bayer) line is that the serious side effects of fluoroquinolones are real, but very rare -- to the point where good statistics are difficult. These cite incidences in the range of one per every 100,000-500,000 doses. Other sources, for example alternative medicine proponents (Mercola, etc.), often focus instead on collecting bad outcomes, but without much detail on the rates at which they occur. With the financial incentives and other biases of different sources of information in mind, I feel reasonably comfortable making some generalizations based on my reading of the scientific literature: serious side effects certainly can occur following fluoroquinolone use and it's not just unfortunate, random coincidences; however, the rates are low enough they aren't generally measurable in clinical studies involving hundreds or thousands of people. To me, this indicates that the rates are probably less than ~0.1%; Rates appear to be higher with levaquin and other, newer fluoroquinolones than they are with ciprofloxacin. Finally, many of the most serious events (with permanent/long-term consequences) have occurred when people took long courses of the antibiotic, and/or continued use despite mild side effects early on.
The single most important scientific study on this subject, in my mind, is one that followed ~60,000 postal workers, who took antibiotics for about 2 months following the anthrax events of 2001. I like this study for a number of reasons -- both because it followed a large number of subjects and because it was done independent of any drug company. Unfortunately for us, either ciprofloxacin or doxycycline were acceptable antibiotics in the anthrax exposure protocol, so researchers don’t have records for ciprofloxacin exclusively. At the time most people wanted ciprofloxacin because it was believed to be more effective against anthrax. So the true number of people taking ciprofloxacin was possibly less than 60,000, but, I believe, almost certainly well over 10,000. From my memory, 7 potentially serious events were reported among the 60,000 people, with 3 or 4 deemed likely to be related to the antibiotic, and all issues resolved once the antibiotic was stopped. In my mind, even without exact rates, those numbers give me the confidence that I'm unlikely to see any serious side effects within the scope of this study, especially since we use a very short time course of antibiotics.
As might be becoming clear from this page, one of my goals in designing this study was to limit any antibiotic-associated risks as much as possible. Beyond having a short course, we are also asking participants to immediately stop use if they have any side effects, even mild ones, involving the central or peripheral nervous system or the musculoskeletal system. As I mentioned at the outset of this discussion, we are also excluding people who have had any cipro-related adverse events in the past from participating at all. While this does not eliminate the possibility of negative side effects, my hope is that these precautions limit unnecessary risk.
What I’ve said here is certainly not all that there is to say about antibiotic use, but I hope to have touched on some common questions. Please let us know about any further questions or concerns!
Let me start by saying that antibiotic use is something that should not be done lightly and that I have thought carefully about how and when to utilize antibiotics in my research. Additionally, if you have ever experienced an adverse reaction to ciprofloxacin (or another fluoroquinolone antibiotic) in the past, you shouldn't be signing up for our study. That said, let me expand on some different aspects of antibiotic use.
First, there are possible public health effects from antibiotics. Any use increases the potential to spread antibiotic resistance within the broader community. In designing this study, we faced the tradeoff of this risk with the benefit of understanding the dynamics of the gut microbiota in response to common, medically-relevant perturbations (which includes antibiotic use). This is a troubling problem to tackle. It would be ideal to limit unnecessary antibiotic usage and only sample participants who are going to use them anyway (due to a medical need). However, there are several complicating factors that make it difficult to get adequate data from that sort of study. It can be hard to get sufficient pre-treatment samples to characterize the gut microbiota from before the antibiotic effect. Additionally, the underlying need for the antibiotics (whether a disease, infection, or medical procedure) can have its own impact on the microbiota; it can be difficult or impossible to disentangle this impact from that of the antibiotic. For these reasons, a study that examines the use of an antibiotic as an isolated variable has a lot of scientific value and, hopefully, the results could lead to more informed and judicious use of antibiotics in the future. In light of all this, in our judgement and that of the Institutional Review Board that approved this study, the tradeoff is worth making.
Aside from public health concerns, there are also personal risks for anyone taking antibiotics. There is the same resistance-related concern on an individual scale -- that taking an antibiotic could cause microbial resistance and prevent treatment of an infection with that antibiotic later on. From my perspective, this risk is not very large; there are few conditions for which ciprofloxacin is a first choice treatment (urinary tract infections are the main one). Moreover, cipro-resistant organisms are frequently still susceptible to other fluoroquinolones (e.g. levaquin).
Separate (as far as we know) from the antibiotic action of the drug, there are also be direct effects of ciprofloxacin on human physiology. There are potentially serious side effects to taking ciprofloxacin or other fluoroquinolones. The phrase “potentially serious side effects” can sound a bit clinical and distant, especially when it could include cases of death, debilitating and painful conditions, or conditions that are permanent or long-lasting. It is good to take these possibilities seriously, but to assess the real danger of antibiotics, it becomes a question of likelihoods and relative risks to benefits. Somewhat like driving a car, there are incredibly serious risks involved, but the usefulness and careful practice of antibiotic use can be weighed against the frequency of a negative outcomes.
Finding reliable data on the frequency of antibiotic side effects can be another slippery issue. The official (e.g. FDA, Bayer) line is that the serious side effects of fluoroquinolones are real, but very rare -- to the point where good statistics are difficult. These cite incidences in the range of one per every 100,000-500,000 doses. Other sources, for example alternative medicine proponents (Mercola, etc.), often focus instead on collecting bad outcomes, but without much detail on the rates at which they occur. With the financial incentives and other biases of different sources of information in mind, I feel reasonably comfortable making some generalizations based on my reading of the scientific literature: serious side effects certainly can occur following fluoroquinolone use and it's not just unfortunate, random coincidences; however, the rates are low enough they aren't generally measurable in clinical studies involving hundreds or thousands of people. To me, this indicates that the rates are probably less than ~0.1%; Rates appear to be higher with levaquin and other, newer fluoroquinolones than they are with ciprofloxacin. Finally, many of the most serious events (with permanent/long-term consequences) have occurred when people took long courses of the antibiotic, and/or continued use despite mild side effects early on.
The single most important scientific study on this subject, in my mind, is one that followed ~60,000 postal workers, who took antibiotics for about 2 months following the anthrax events of 2001. I like this study for a number of reasons -- both because it followed a large number of subjects and because it was done independent of any drug company. Unfortunately for us, either ciprofloxacin or doxycycline were acceptable antibiotics in the anthrax exposure protocol, so researchers don’t have records for ciprofloxacin exclusively. At the time most people wanted ciprofloxacin because it was believed to be more effective against anthrax. So the true number of people taking ciprofloxacin was possibly less than 60,000, but, I believe, almost certainly well over 10,000. From my memory, 7 potentially serious events were reported among the 60,000 people, with 3 or 4 deemed likely to be related to the antibiotic, and all issues resolved once the antibiotic was stopped. In my mind, even without exact rates, those numbers give me the confidence that I'm unlikely to see any serious side effects within the scope of this study, especially since we use a very short time course of antibiotics.
As might be becoming clear from this page, one of my goals in designing this study was to limit any antibiotic-associated risks as much as possible. Beyond having a short course, we are also asking participants to immediately stop use if they have any side effects, even mild ones, involving the central or peripheral nervous system or the musculoskeletal system. As I mentioned at the outset of this discussion, we are also excluding people who have had any cipro-related adverse events in the past from participating at all. While this does not eliminate the possibility of negative side effects, my hope is that these precautions limit unnecessary risk.
What I’ve said here is certainly not all that there is to say about antibiotic use, but I hope to have touched on some common questions. Please let us know about any further questions or concerns!