Antimicrobial Resistance: Challenges and Potential Solutions

Stephen Tyring, MD, PhD, MBA, spoke with Dermatology Times on the growing concern of antimicrobial resistance, emphasizing the need for judicious use of antibiotics and alternative treatments.

Transcript:

Stephen Tyring, MD, PhD, MBA: I'm Stephen Tyring, MD, PhD. My PhD being in virology and my dermatology training has brought me together with my background in virology to be quite interested in infectious diseases, particularly of the skin. As the world has seen, the treatment we have for various infectious diseases globally and specifically for the skin, has been limited by antimicrobial resistance.

Dermatology Times: Can you tell us about your session at the 2024 Society of Dermatology Physician Assistants (SDPA) Summer Conference?

Tyring: I'm going to be talking about something that is of hopeful interest to all PAs, nurse practitioners, physicians, anybody who takes care of patients, and should be of interest to the patients themselves. Antimicrobial resistance is an increasing problem that we don't have great solutions to, but we have potential solutions. I'm not just going to talk about the problem, I'm hopefully going to talk about potential solutions that are being discovered and being tested. 

DT: What should clinicians keep in mind when prescribing medications considering this increase in antimicrobial resistance?

Tyring: Anybody who cares for a patient should be aware that antibiotics should be used only where they're needed. I intend to talk about something a little more broadly than just antibacterial drugs, because antimicrobial resistance is a problem against all infectious agents. Of course, it's antibiotics that we vastly overuse, and we should think every time we're going to prescribe antibiotic, does the patient need it? Beyond dermatology, antibiotics are widely prescribed for viral diseases. General practitioners will give antibiotics for viral colds and viral sore throats and all kinds of things that have nothing to do directly to a bacterial cause.

In dermatology, of course, we sometimes use antibiotics too long and too actively for conditions such as acne and rosacea that we hope we can find better and safer treatments that will not involve eventual resistance. It goes beyond just where we most commonly use it, and I mentioned some of the conditions;, but beyond acne and rosacea, we use it to treat inflamed cysts and other conditions where we're not sure of the infection or just if it's inflammation. We use it to treat a multitude of other inflammatory conditions. Until the approval of the first 2 drugs for hidradenitis suppurativa, a lot of antibiotics were given, and still are. But outside of dermatology, people prescribe antibiotics for hidradenitis suppurativa quite commonly. We could go on and on about the various conditions that antibiotics are used and overused. It's a matter of outright, not just the dosage, but also the duration and the indication where these antibiotics can be used. The problem has been recognized for some time.

As I'll mention, the person that we think about the beginning of the era of antibiotics for the general population was Fleming when he got the Nobel Prize in 1954 for his discovery that led to widespread use of antibiotics World War II, but only for the general public after World War II.He said in the Nobel Prize speech that we know bacteria can develop resistance in the petri dish, so it's going to happen in humans, and we have to be aware of it.He was absolutely right. We had a potential solution throughout the end of the 20th century and into the early 21st by developing new antibiotics that work through different mechanisms. We kind of ran low on new antibiotics. We do have some, but they're kind of limited, and the newer ones are much more expensive and sometimes don't work as well.

There are bacteria that certainly develop resistance to everything. There are instances in dermatology where a bacteria that causes skin problems could be resistant to everything that's in the pharmacy and even experimentally, and we have to think beyond antibiotics. But then again, those that take care of HIV positive individuals have thought about this ever since the first antiretroviral drug in 1987. You can't control HIV very well with just 1 class of drugs, because the virus will develop resistance. You have to add the second class, which in the 90s was the protease inhibitors.Even the reverse transcriptase inhibitors, starting in 1987, and the protease inhibitors of the 90s didn't always stop the virus from developing resistance, and so they had to add new classes. We recognized 7 areas of the replication cycle of HIV that drugs can intervene, but to which the virus can develop resistance. Multiple drugs, 2 or 3 have to be used together to hold HIV intact, or else there will be resistance. The more mechanisms that are added in, the lower the rate of resistance to all 3 and beyond the development of antiretrovirals. Even the HIV positive individuals that we see in dermatology sometimes have acyclovir resistant herpes. So no matter how much acyclovir, valacyclovir, and famciclovir you give them, then they're still not going to respond. We have to think beyond the use of those class of drugs and use not only the officially recommended drugs that involve the hospitalization, IV, expense, and potential kidney damage, but think about recommendations that come from the Centers for Disease Control but are not officially FDA approved, such as topical sanofiber. Other infectious agents, or the general class of agents, or fungi that we deal with every day, and we think, “Well, if one antifungal doesn't work, we can just get the other one off the shelf and it will work.”That was true of the most common fungi that we see, the tinea that causes the tinea corpus or pedis or other areas of the body, until a new strain was described. First in India and then in the United States, it was resistant to most of the common antifungal drugs. We have to think about even resistance there.

The biggest worry for the medical community in general is a new fungus that came out of basically nowhere. It was unknown until a decade ago, and that is candida auris, a very evil cousin of the common candida albicans that we deal with every day. Auris likes to pick on people in the intensive care unit. Usually, the first antifungal systemically used doesn't work, and sometimes the second, third, and beyond that doesn't work. The only thing that's worked in a lot of these patients has been the experimental antifungal drugs. Even then, there is a high rate of deaths, meaning a lot of morbidity and mortality among this species of candida auris, and so this goes even beyond areas that we don't commonly deal with. In dermatology, there's a major killer of people in the world, namely malaria, that doesn't have a lot of cutaneous manifestations and often develops resistance to common anti-malarial drugs. These other areas, we have to think about what we can do beyond just a new drug to treat the bacteria, the virus, the fungus, or in the case of malaria, the parasite. Another major killer in the world is tuberculosis, and tuberculosis is notorious for developing resistance to antibiotics and the need for new antibiotics is pressing. That brings us beyond the antibiotics into thinking beyond the box. That's what I think is most exciting.

In 2024, we have several examples of people thinking beyond the box for antibiotic resistant bacteria. We have a classic example that brings us back to the beginning of the 20th century, when something called bacteriophages was being used the Soviet Union, and people in the Western world didn't believe it, because it was coming out of the Soviet Union. It was hard to believe. Then it was sort of revived a few years ago, and it came from 2 doctors here in San Diego. One was dying of a very deadly bacteria and would have been dead had the wife of that doctor not intervened and got the head of infectious diseases interested in reviving the interest in bacteriophages. Now there's hundreds of millions of dollars of research into bacteriophages. That brings us to the question of, can the enemy of our enemy be our friend? In other words, can a bacteriophage that's the enemy of our enemy bacteria be our friend? Yes, I would sayviruses can be domesticated or tamed to do what we want in some cases, and I'll give several other examples where viruses can be used to either deliver a drug or a vaccine. There are many uses of viruses beyond just the classic example of bacteriophages. It's all thinking beyond the box.

Where we all should be thinking beyond the box is the fact that it's better to prevent than lament. Public health measures are of immense importance, and that is always the first line of defense against any infectious agent. But then, came the vaccines. Vaccines have been around for over 200 years, but for the first time in those 200 plus years, people have been leading the charge against vaccines, thinking that vaccines cause more harm than they do good. My personal opinion, based upon my review of the literature and recommendation of vaccines, is that any vaccine is about a million-fold safer than the virus or bacteria it's designed to prevent against. Everything in life has a risk, but if it's a case of get the vaccine or have the infection, well, you're a million times better off going for the vaccine. I want to emphasize that as well; it's all under the umbrella of it's better to prevent than lament.

[Transcript has been edited for clarity.]